Diagnostic Imaging: Brain

DIAGNOSTIC IMAGING

BRAIN

11

DIAGNOSTIC IMAGING

BRAIN Anne G. Osborn, MD, FACR

Gary L. Hedlund, DO

Distinguished Professor of Radiology William H. and Patricia W. Child Presidential Endowed chair in radiology University of Utah School of Medicine

Clinical Associate Professor of Radiology University of Utah Pediatric Neuroradiologist Department of Medical Imaging Primary Children's Medical Center

Amersham Visiting Professor in Diagnostic Imaging Armed Forces Institute of Pathology

Anna Illner, MD

Susan I. Blaser, MD, FRCPC

Assistant Professor of Radiology Division of Pediatric Neuroradiology Riley Children's Hospital Indiana University School of Medicine

Staff Neuroradiologist Hospital for Sick Children Associate Professor of Diagnostic Imaging University of Toronto, Canada

H. Ric Harnsberger, MD Karen L. Salzman, MD

Professor of Radiology R.C. Willey Chair in Neuroradiology University of Utah School of Medicine

Assistant Professor of Radiology Division of Neuroradiology University of Utah School of Medicine

james A. Cooper, MD Gregory L. Katzman, MD

Diagnostic Radiology and Neuroradiolgy Radiology Medical Group, Inc

Associate Professor, Radiology and Medical Informatics Chief, Radiology Clinical Research University of Utah School of Medicine

james Provenzale, MD Professor of Radiology Chief, Neuroradiology Department of Radiology Duke University Medical Center

Blaise V. jones, MD Associate Professor, Radiology & Pediatrics Director, Division of Neuroradiology Department of Radiology Cincinnati Children's Hospital Medical Center

Bronwyn E. Hamilton, MD

Mauricio Castillo, MD, FACR

Assistant Professor of Radiology Oregon Health & Science University

Professor of Radiology Chief of Neuroradiology University of North Carolina School of Medicine

AMI RSYS® A medical reference publishing

company 111

AMIRSYS® A medical reference publishing

company

First Edition Text - Copyright

Anne G Osborn MD 2004

Drawings - Copyright Amirsys Inc 2004 Compilation

- Copyright Amirsys Inc 2004

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or media or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from Amirsys Ine.

Composition

by Amirsys Inc, Salt Lake City, Utah

Printed by Friesens, Altona, Manitoba,

Canada

ISBN: 0-7216-2905-9

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In the cases where drugs or other chemicals arc prescribed! readers are advised to check the Product information currently provided by the manufacturer of each drug to be administered to verify the recommended dose! the method and duration of administration, and contraindications. It is the responsibility of the treating physician relying on experience and knowledge of the patient to determine dosages and the best treatment for the patient. To the maximum extent permitted by applicable law, Amirsys provides the Product AS is AND WITH ALL FAULTS,AND HEREBY DISCLAiMS ALL WARRANTIES AND CONDITIONS, WHETHER EXPRESS. IMPLIED OR STATUTORY,INCLUDING BUT NOT LIMITED TO, ANY (IF ANY) IMPLIED WARRANTIES OR CONDITIONS OF MERCHANTABILITY. OF FiTNESS FOR A PARTICULAR PURPOSE, OF LACK OF VIRUSES, OR ACCURACY OR COMPLETENESS OF RESPONSES, OR RESULTS,AND OF LACK OF NEGLIGENCE OR LACK OF WORKMANLIKE EFFORT. ALSO, THERE IS NO WARRANTY OR CONDITION OF TITLE, QUIET ENJOYMENT~QUIET POSSESSION. CORRESPONDENCE TO DESCRIPTION OR NON-INFRINGEMENT, WITH REGARD TO THE PRODUCT. THE ENTIRE RISK AS TO THE QUALITY OF OR ARISING OUT OF USE OR PERFORMANCE OF THE PRODUCT REMAINS WITH THE READER. Arnirsys disclaims all warranties of any kind if the Product was customized, repackaged or altered in any way by any third party.

Library of Congress Cataloging-in-Publication

Data

Diagnostic imaging. Brain / Anne 0. Osborn ... let al.]. p. ;cm.

Includes bibliographical references and index. ISBN 0-7216-2905-9 l. Brain--Imaging--Handbooks, manuals, etc. r. Title: Brain. II. Osborn, Anne G., 1943[DNLM: l. Brainnradiography. 2. Central Nervous System Diseases--diagnosis. 3. Diagnosis, Differential. 4. Neuroradiography--methods. WL 141 053472004] RC386.6.D52D53 2004 616.8'04757ndc22 2004047735

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To my beloved husband and eternal sweetheart Ron Now and forever together. Thanks for your unfailing patience, support and humor. You make me laugh every day.

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DIAGNOSTIC IMAGING: BRAIN

The neuroimaging, neurology, neurosurgery, neuropathology communities have been waiting a long time for a new "Osborn". We at Amirsys and Elsevier are proud to present a precedent-setting, image- and graphics-packed series that debuts with a brand-new work by Anne G. Osborn and colleagues. This splendid work represents the textbook of the twenty-first century: Not your old-fashioned, dense prose exposition with comparatively few images. The unique bulleted format of the Diagnostic Imaging books allows our authors to present approximately twice the information and four times the images per diagnosis, compared to the old-fashioned traditional prose textbook. These richly illustrated books will cover all major body areas and follow a similar format. The same information is in the same place: Every time! A welcome innovation is the new visual differential diagnosis "thumbnail" that provides at-a-glance looks at entities that can mimic the diagnosis in question. "Key Pacts" boxes provide a succinct summary for quick, easy review. In short, this is a product designed with you, the reader, in mind. Today's typical practice settings demand efficiency in both image interpretation and learning. We think you'll find the Diagnostic Imaging format a highly efficient and wonderfully rich resource. Enjoy!

H. Ric Harnsberger, MD Chairman and CEO, Amirsys Inc

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It looks like Anne Osborn has done it again! After several years of taking the pulse of the medical community, lecturing far and wide, and hearing the "pros" and "cons" of her earlier books (mostly "pros") she has decided to abandon the usual conventions of medical textbooks. In this volume, she and her co-authors (a cadre of neuroradiological household names), and Dr. James Cooper, a medical illustrator in the tradition of Frank Netter, deliver diagnostic neuroradiology in its most concise and user-friendly format to date. Building on the experience and success of the series of "Top 100 Diagnoses", this is now the one volume that makes the radiologist conversant with his or her clinical constituency, not only in arriving at a diagnosis, but in discussing the pathology, anatomy, clinical manifestations, and treatment rationales. As radiology has become the cornerstone of medical diagnosis, the radiologist is often the first physician with whom a patient interacts. This book assumes that there are many instances in which the radiologist is thrust into the role of primary physician, and it provides a concise package of facts about a given disease or radiological sign that can be quickly and easily accessed and included in a written report or a discussion, adding value for the patient and referring physician. It would be difficult to find a wasted word in this book. The authors have studied the economics of verbiage and concluded that 50% of the words in a standard medical textbook could be eliminated and it would still deliver the same bolus of information to today's physicians, most of whom have been weaned on reading e-mail. As a result, hordes of words have been reduced to a small arsenal of bullets and bulleted statements. This conservation of linguistic space allows profuse inclusion of illustrations. The quality of photographs is superb and there is ample use of color for the pathologic and anatomic photos, many of which are positioned adjacent to Dr. Cooper's near in-vivo drawings. Illustrations of major anatomy, pathology, and radiological findings are uniformly 6x6 cm (a size which most readers are accustomed to seeing on a PACSstation) and the illustrations of differential diagnoses, being of less importance, are 3x3 cm. Figures are well spaced and are not cluttered with overuse of arrows and other notation. Diagnostic Imaging: Brain, in a single volume, is the "internet" of neuroradiology and diseases of the central nervous system: complete, accessible, concise, and up to date. The only thing that seems to be missing is a chain and lock to keep it from being stolen from the table next to the PACSstation. Perhaps that will be an option with the next edition.

Michael S. Huckman, MD Professor of Radiology Rush Medical College Director of Neuroradiology Rush University Medical Center

IX

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PREFACE

Just about every place I go, I'm asked, "Are you writing a second edition of The Red Book (Diagnostic Neuroradiology)?" The answer has been-and remains-an emphatic "No!" Now you know why. The proverbial cat is out of the bag, and you literally see it in front of your eyes: An exciting, brand-new approach to teaching textbooks in diagnostic radiology. Ric Harnsberger and I had a vision when we started Amirsys. We wanted to found an author-centric company that would be both market-facing and database-driven, specializing in highly innovative yet simple ways of presenting complex content. The changes we've all experienced in our practice patterns over the last decade necessitate-even dictate-new approaches. We've become victims of our own success: We are getting better and better at imaging more and more stuff. This translates into an ever-increasing case load. Time is a luxury most of us don't have. We need our information in easily accessible format. The closer to the "point-of-care" the better! We began with the highly successful PocketRadiologist® concept. The available PRs-iS in all-now cover all parts of the body and are available in both print and PDA. The Diagnostic Imaging series has just started with David Stoller's spectacular book on Orthopaedics (he likes the British-style spelling!). We love the graphics and high information density that is the result of using bulleted text (rather than traditional prose). You don't have time to read extra words that don't carry essential information-so we don't write them! We added Key Facts boxes to each diagnosis for quick review and have chosen selected references for your further delectation and delight. You will note that there are many 2004 references included-the references were updated to include key articles published within a month of the book going to press. For example when the March 2004 issue of A]NR appeared with an important new (to neuroradiologists) entity-Susac syndrome-on the cover, we were able to include it both in the text and the references. Diagnostic Imaging: Brain is divided into two parts: The first part organizes diagnoses according to general pathology category (congenital malformations, trauma, neoplasms, etc). The second, shorter part is organized according to anatomy. Here we present diagnoses for which location is key to the diagnosis. Where appropriate, we have included some special introductory overviews of general anatomy or embryology and pathology to assist the reader in thinking about the diagnoses that follow. Finally, we couldn't have produced such a monumental book in less than a year without the stellar author team listed on the book cover. As Michael Huckman noted in his Forward, many are literally household names in neuroradiology-and the others are all promising new young academics. The templated approach we took and the use of bulleted information eliminates nearly all the stylistic differences that have plagued multi-author textbooks in the past. Without looking at the Table of Contents, you probably can't tell who wrote what. We feel the sacrifice of individual creativity for the sake of uniformity is a plus. So sit down, fasten your seat belt, and dig in. Have fun reading-and know that we had fun putting this project together. Enjoy!

Anne G. Osborn, MD, FACR Distinguished Professor of Radiology William H. and Patricia W. Child Presidential Endowed Chair in Radiology University of Utah School of Medicine Amersham Visiting Professor in Diagnostic Imaging Armed Forces Institute of Pathology Washington, D.C.

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ACKNOWLEDGMENTS Illustrations James A. Cooper, MD

Art Direction and Design Lane R. Bennion, MS Richard Coombs, MS

Image/Text Editing Angie D. Mascarenaz Cassie L. Dearth Kaerli Main

Medical Text Editing Gregory L. Katzman, MD Karen L. Salzman, MD Richard H. Wiggins III, MD Andre Macdonald, MD Mingqian Huang, MD A. Roxana Gafton, MD

Case Management David Harnsberger Roth LaFleur

Production Lead Melissa A. Morris

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XIV

SECTIONS

PART I Pathology-Based

Diagnoses

Congenital Malformations

[I]

Trauma ~ Subarachnoid

Hemorrhage and Aneurysms Stroke

[!J

ffiJ

Vascular Malformations

ffiJ

Neoplasms and Tumorlike lesions Primary Non-Neoplastic

[ZJ

Cysts

Infection and Demyelinating Disease Metabolic/Degenerative Toxic/Metabolic/Degenerative

ru

[ID

Disorders, Inherited Disorders, Acquired

[2]

[ill

PART II Anatomy-Based

Diagnoses

rn rn

Ventricles and Cisterns Sella and Pituitary CPA-lAC [l]

Skull, Scalp, and Meninges

@] xv

TABLE OF CONTENTS Malformations of Cortical Development

PART I Pathology-Based

Diagnoses

1-1-50

Microcephaly Gary 1. Hedlund, DO

Congenital Muscular Dystrophy

SECTION 1 Congenital Malformations Introduction Congenital

Heterotopic

1-1-62

Pachygyria -Polymicrogyria 1-1-4

Anne G. Osborn, MD, FACR

Hindbrain

1-1-58

Gray Matter

Susan I. Blaser, MD, FRCP(C)

and Overview

Malformations

1-1-54

Susan I. Blaser, MD, FRCP(C)

Gary 1. Hedlund, DO

1-1-66

Lissencephaly Type 1 Susan I. Blaser, MD, FRCP(C)

Herniations, Miscellaneous Malformations 1-1-8

Chiari 1

1-1-70

Schizencephaly Susan I. Blaser, MD, FRCP(C)

1-1-74

Hemimegalencephaly Susan I. Blaser, MD, FRCP(C)

Susan I. Blaser, MD, FRCP(C)

1-1-12

Chiari 2 Susan I. Blaser, MD, FRCP(C)

1-1-16

Chiari 3 Mauricio Castillo, MD, FACR Susan I. Blaser, MD, FRCP(C)

1-1-22

Lipoma Anne G. Osborn, MD

1-1-26

Type 2

1-1-82

Blaise V. Jones, MD

1-1-86

von Hippel Lindau

Vermian Hypoplasia

1-1-30 1-1-34

1-1-100

Basal Cell Nevus Syndrome Mauricio Castillo, MD, FACR

1-1-104

HHT

Holoprosencephaly

Encephalocraniocutaneous

1-1-38

Susan I. Blaser, MD, FRCP(C)

Anne G. Osborn, MD, FACR

Lipomatosis

1-1-108

Anna Illner, MD

1-1-42

Anna Illner, MD Mauricio Castillo, MD, FACR

1-1-98

Meningioangiomatosis

Disorders of Diverticulation/Cleavage

Septooptic Dysplasia

1-1-94

Sturge- Weber Syndrome

Mauricio Castillo, MD, FACR

Susan I. Blaser, MD, FRCP(C)

Variants

1-1-90

Susan I. Blaser, MD, FRCP(C)

Susan I. Blaser, MD, FRCP(C)

XVI

Neurofibromatosis

Susan I. Blaser, MD, FRCP(C)

FRCP(C)

Rhombencephalosynapsis

Holoprosencephaly

1-1-78

Tuberous Sclerosis Complex

Malformations

Dandy Walker Spectrum

Congenital

Type 1

Anne G. Osborn, MD, FACR

Hindbrain Susan I. Blaser, MD,

Neurofibromatosis

Susan I. Blaser, MD, FRCP(C)

1-1-18

Callosal Dysgenesis

Familial Tumor/Neurocutaneous Syndromes

Cowden Syndrome

1-1-112

Mauricio Castillo, MD, FACR

1-1-46

Neurocutaneous Anna Illner, MD

Melanosis

1-1-116

Superficial Siderosis

1-3-8

H. Ric Harnsberger, MD

Aneurysms Primary Effects of CNS Trauma

Saccular Aneurysm

1-3-12

Anne G. Osborn, MD, FACR

Missile and Penetrating

1-2-4

Injury

1-2-6

Epidural Hematoma Gregory L. Katzman,

Bronwyn E. Hamilton,

1-2-10

Bronwyn E. Hamilton,

1-2-14

Bronwyn E. Hamilton,

Blood Blister-like Aneurysm

1-2-20 1-2-22

Hemorrhage

Introduction and Overview

MD

1-2-26

Cerebral Contusion MD

Stroke Anatomy and Imaging Issues

1-2-30

Nontraumatic Intracranial Hemorrhage

MD

1-2-34

Subcortical Injury MD

1-2-38

Trauma

Susan 1. Blaser, MD, FRCP(C)

Intracerebral Hematoma Gregory L. Katzman,

Spontaneous

Herniation

Hypertensive

MD

MD

Castillo,

1-2-54 MD

1-2-56

Dissection

MD, FACR

Atherosclerosis,

1-4-20

MD

Intracranial

Atherosclerosis,

1-4-24

MD

Extracranial

Arteriolosclerosis Bronwyn E. Hamilton,

1-4-28 1-4-32

MD

1-2-58

James Provenza Ie, MD

Nonatheromatous Vasculopathy

Traumatic Carotid-Cavernous Castillo,

1-4-16

James A. Cooper, MD

Traumatic Extracranial Dissection

Mauricio

Hemorrhage

Remote Cerebellar Hemorrhage

Bronwyn E. Hamilton,

Brain Death

Mauricio

1-4-12

Atherosclerosis and Carotid Stenosis 1-2-50

Traumatic Cerebral Ischemia

Traumatic Intracranial

Hemorrhage

1-2-46

Susan I. Blaser, MD, FRCP(C)

Bronwyn E. Hamilton,

Intracranial

Bronwyn E. Hamilton,

Traumatic Cerebral Edema

Gregory L. Katzman,

Intracranial

James A. Cooper, MD

1-2-42

Syndromes

1-4-8

MD

James A. Cooper, MD

Secondary/Vascular Effects of CNS Trauma Bronwyn E. Hamilton,

1-4-4

Anne G. Osborn, MD, FACR

Diffuse Axonal Injury (DAI)

Intracranial

1-3-22

MD

Traumatic Subarachnoid

Gregory L. Katzman,

1-3-20

MD

Mixed Subdural Hematoma

Nonaccidental

Fusiform Aneurysm, Non-ASVD

1-2-16

Chronic Subdural Hematoma

Gregory L. Katzman,

1-3-18

Anne G. Osborn, MD, FACR

MD

Bronwyn E. Hamilton,

Fusiform Aneurysm, ASVD

Anne G. Osborn, MD, FACR

MD

Subacute Subdural Hematoma

Gregory L. Katzman,

1-3-16

Anne G. Osborn, MD, FACR

MD

Acute Subdural Hematoma

Gregory L. Katzman,

Pseudoaneurysm Anne G. Osborn, MD, FACR

James A. Cooper, MD

1-2-62

Fistula

MD, FACR

Persistent Trigeminal Artery Mauricio

1-4-38

Sickle Cell Disease

SECTION 3 Subarachnoid Hemorrhage Aneurysms

Mauricio

and

1-4-36

Castillo, MD, FACR

Castillo, MD, FACR

1-4-42

Moyamoya Susan 1. Blaser, MD, FRCP(C)

Primary Arteritis of the CNS

1-4-46

James A. Cooper, MD

Subarachnoid Aneurysmal Subarachnoid

Hemorrhage

Hemorrhage

Anne G. Osborn, MD, FACR

Nonaneurysmal

Perimesencephalic

Anne G. Osborn, MD, FACR

1-4-50

Vasculitis 1-3-4

James A. Cooper, MD

Systemic Lupus Erythematosus SAH

1-3-6

1-4-54

James Provenza Ie, MD

Cerebral Amyloid Disease Bronwyn E. Hamilton,

1-4-58

MD XVll

1-4-62

CADASIL James Provenza Ie, MD

Astrocytic Tumors-Infiltrating Diffuse Astrocytoma, Low Grade

Cerebral Ischemia and Infarction 1-4-66

Hydranencephaly Anna Illner, MD

1-4-68

HIE, Preterm Gary L. Hedlund, DO

1-4-72

HIE, Term Susan I. Blaser, MD, FRCP(C)

1-4-76

Acute Cerebral Ischemia-Infarction MD

Bronwyn E. Hamilton,

1-4-80

Subacute Cerebral Infarction

1-6-8

Karen L. Salzman, MD

Pediatric Brainstem Glioma

1-6-12

Susan 1. Blaser, MD, FRCP(C)

Anaplastic Astrocytoma

1-6-16

Karen L. Salzman, MD

Glioblastoma Multiforme

1-6-20

Karen L. Salzman, MD

1-6-24

Gliosarcoma Karen L. Salzman, MD

Gliomatosis Cerebri

1-6-26

Karen L. Salzman, MD

James A. Cooper, MD

1-4-84

Chronic Cerebral Infarction

Astrocytic Tumors-localized

James A. Cooper, MD

1-4-88

Lacunar Infarction James A. Cooper, MD

1-4-92

Hypotensive Cerebral Infarction Bronwyn E. Hamilton,

MD

1-4-96

Dural Sinus Thrombosis Bronwyn E. Hamilton,

MD

1-4-100

Cortical Venous Thrombosis Bronwyn E. Hamilton,

MD

1-4-104

Deep Cerebral Venous Thrombosis Bronwyn E. Hamilton,

MD

Pilocytic Astrocytoma

1-6-30

Blaise V. Jones, MD

Pleomorphic Xanthoastrocytoma

1-6-34

Karen L. Salzman, MD

Subependymal Giant Cell Astrocytoma

1-6-38

Gary L. Hedlund, DO

Oligodendroglial and Miscellaneous Tumors Oligodendroglioma

1-6-42

Karen L. Salzman, MD

Anaplastic Oligodendroglioma

SECTION 5

Vascular Malformations >

i'."··.·"·.··"·"·.'··' ..'.'·.·..·"."·"·'"

1-6-46

Karen L. Salzman, MD

.

1-6-50

Astroblastoma Karen L. Salzman, MD

CVMs With A-V Shunting Arteriovenous Malformation

Ependymal Tumors

1-5-4 Ependymoma

Anne G. Osborn, MD, FACR

Dural A-V Fistula

1-5-8

Subependymoma

Anne G. Osborn, MD, FACR

Vein of Galen Malformation

1-5-12

1-6-52

Blaise V. Jones, MD

1-6-56

Karen L. Salzman, MD

Anna Illner, MD

Choroid Plexus Tumors CVMs Without A-V Shunting Developmental Venous Anomaly

Choroid Plexus Papilloma 1-5-16

Choroid Plexus Carcinoma

Anne G. Osborn, MD, FACR

Sinus Pericranii

1-5-20

1-6-60

Gary L. Hedlund, DO

1-6-64

Gary L. Hedlund, DO

Anna Illner, MD

Cavernous Malformation

1-5-24

Anne G. Osborn, MD, FACR

Capillary Telangiectasia

1-5-28

Anne G. Osborn, MD, FACR

Neuronal, Mixed Neuronal-Glial Tumors Ganglioglioma

1-6-66

Karen L. Salzman, MD

Dysplastic Cerebellar Gangliocytoma

1-6-70

Blaise V. Jones, MD

Desmoplastic Infantile Ganglioglioma Mauricio

DNET

Introduction

and Overview

Neoplasms Pathology and Imaging Issues Anne G. Osborn, MD, FACR

XV111

1-6-74

Castillo, MD, FACR

1-6-76

Susan 1. Blaser, MD, FRCP(C)

1-6-4

Central Neurocytoma Karen L. Salzman, MD

1-6-80

Anne G. Osborn, MD, FACR

Pineoblastoma

1-6-84

Anna I/lner, MD

1-7-12

Dermoid Cyst Gregory L. Katzman, MD

Pineocytoma

1-6-88

Karen L. Salzman, MD

Embryonal and Medulloblastoma

Neuroblastic Tumors

(PNET-MB)

1-6-92 1-6-96

PNET

Atypical Teratoid-Rhabdoid

1-7-20

Neuroglial Cyst Anne G. Osborn, MD, FACR

1-7-22

Enlarged Perivascular Spaces Anne G. Osborn, MD, FACR

Gary L. Hedlund, DO

1-7-26

Pineal Cyst Anne G. Osborn, MD, FACR

Tumor

1-6-100

Blaise V. Jones, MD

Neuroblastoma,

1-7-16

Epidermoid Cyst Gregory L. Katzman, MD

Blaise V. Jones, MD

Supratentorial

1-7-8

Colloid Cyst

Pineal Parenchymal Tumors

Metastatic

Anne G. Osborn, MD, FACR

1-6-104

Blaise V. Jones, MD

Tumors of Cranial/Peripheral Schwannoma

1-7-34

Ependymal Cyst Karen L. Salzman, MD

Nerves 1-6-108

Anne G. Osborn, MD, FACR

Neurofibroma

1-7-30

Choroid Plexus Cyst

Porencephalic

1-7-36

Cyst

Anne G. Osborn, MD, FACR

Neurenteric

1-7-40

Cyst

Anne G. Osborn, MD, FACR

1-6-112

Anne G. Osborn, MD, FACR

Blood Vessel and Hemopoietic Tumors Hemangioblastoma

1-6-114

Congenital/Neonatal

Anne G. Osborn, MD, FACR

Hemangiopericytoma

1-6-118

Karen L. Salzman, MD

Primary CNS Lymphoma (Angiocentric) Lymphoma

1-6-122

1-8-4

Congenital

HIV

1-8-8

Mauricio Castillo, MD, FACR

1-6-126

Karen L. Salzman, MD

Congenital

Herpes

1-8-10

Mauricio Castillo, MD, FACR

1-6-128

Leukemia

Acquired Infections

Blaise V. Jones, MD

Group B Streptococcal Meningitis

Germ Cell Tumors Gary L. Hedlund, DO Gary L. Hedlund, DO

Carcinoma

1-6-138

Syndromes

1-8-20

Meningitis

1-8-24

Abscess

1-8-28

Ventriculitis Karen L. Salzman, MD

1-8-30

Empyema

1-6-140

Karen L. Salzman, MD

Herpes Encephalitis

Anne G. Osborn, MD, FACR

Paraneoplastic

1-8-16

Karen L. Salzman, MD

Metastatic Tumors and Remote Effects of Cancer Metastases

Meningitis

Karen L. Salzman, MD

Gary L. Hedlund, DO

Parenchymal

Citrobacter

Gary L. Hedlund, DO

1-6-136

Teratoma

1-8-12

Anna I/lner, MD

1-6-132

Germinoma

Embryonal

Infections

CMV

Gary L. Hedlund, DO

Karen L. Salzman, MD

Intravascular

Congenital

1-6-144

Encephalitis

Karen L. Salzman, MD

1-8-34

Karen L. Salzman, MD

(Miscellaneous)

1-8-38

Karen L. Salzman, MD

Rasmussen Encephalitis

1-8-42

Mauricio Castillo, MD, FACR

Tuberculosis

1-8-46

Karen L. Salzman, MD

Neurocysticercosis Arachnoid

Cyst

1-7-4

1-8-50

Karen L. Salzman, MD

Anne G. Osborn, MD, FACR XIX

1-8-54

Parasites, Miscellaneous

1-9-46

Urea Cycle Disorders Mauricio Castillo, MD, FACR

Karen L. Salzman, MD

1-8-58

Fungal Diseases

1-9-48

Glutaric Aciduria Type 1 Mauricio Castillo, MD, FACR

Mauricio Castillo, MD, FACR

1-8-62

Rickettsial Diseases

1-9-52

Canavan Disease Gary L. Hedlund, DO

Mauricio Castillo, MD, FACR

1-8-64

Lyme Disease

1-9-54

Alexander Disease Anna Illner, MD

Mauricio Castillo, MD, FACR

1-8-66

HIV Encephalitis

Miscellaneous

James Provenza Ie, MD

1-8-70

Opportunistic Infection, AIDS James Provenza Ie, MD

1-9-58

van der Knaap Leukoencephalopathies Susan I. Blaser, MD, FRCP(C)

Demyelinating

Anna Illner, MD

1-8-74

Multiple Sclerosis

1-9-62

Hallervorden-Spatz Syndrome

Disease

1-9-66

Huntington Disease James Provenza Ie, MD

Gregory L. Katzman, MD

ADEM

1-8-78

1-9-70

Wilson Disease James Provenzale, MD

Gregory L. Katzman, MD

Subacute Sclerosing Panencephalitis

1-8-82

Mauricio Castillo, MD, FACR

SECTION.10

Toxi.c/MetaboUc/Degenerative

SECTION 9

Disorders, Acquired

Metabolic/Degenerative Disorders, Inherited Normal/Variant Normal Myelination

1-9-4

Toxic, Metabolic, Nutritional, Systemic Diseases with eNS Manifestations 1-10-4

Hypoglycemia

Blaise V. Jones, MD

Hypomyelination

1-9-8

Mauricio Castillo, MD, FACR

1-10-6

Kernicterus

Blaise V. Jones, MD

Mauricio Castillo, MD, FACR

Mitochondrial Leigh Syndrome

James Provenza Ie, MD

1-9-12

Anna Illner, MD

MELAS

1-9-16

Anne G. Osborn, MD, FACR

1-9-20 1-9-24 1-9-28

1-10-28 1-10-32

Idiopathic Intracranial Hypertension

1-10-36 1-10-38

James Provenza Ie, MD

1-9-36

Osmotic Demyelination Syndrome

1-10-42

Anne G. Osborn, MD, FACR

1-9-38

Susan I. Blaser, MD, FRCP(C)

Radiation and Chemotherapy

1-10-46

Karen L. Salzman, MD

Organic and Aminoacidopathies

xx

Chronic Hypertensive Encephalopathy

CO Poisoning

Gary L. Hedlund, DO

Susan I. Blaser, MD, FRCP(C)

PRES

Mauricio Castillo, MD, FACR

Peroxisomal Disorders

Maple Syrup Urine Disease

Acute Hypertensive Encephalopathy,

James Provenza Ie, MD

1-9-32

X-Linked Adrenoleukodystrophy

1-10-24

Hepatic Encephalopathy

Anne G. Osborn, MD, FACR

Gregory L. Katzman, MD

Zellweger

1-10-20

James Provenza Ie, MD

Gary L. Hedlund, DO

Krabbe

1-10-16

Fahr Disease

Anne G. Osborn, MD, FACR

Anna Illner, MD

Metachromatic Leukodystrophy (MLD)

James Provenza Ie, MD

Alcoholic Encephalopathy

Susan I. Blaser, MD, FRCP(C)

Gangliosidosis (GM2)

1-10-12

Hypothyroidism

James Provenza Ie, MD

Lysosomal Disorders Mucopol ysaccharidoses

1-10-8

Drug Abuse

Disorders

1-9-42

Mesial Temporal Sclerosis

1-10-50

Karen L. Salzman, MD

Status Epilepticus Karen L. Salzman, MD

1-10-54

Dementias and Degenerative Disorders 1-10-58

Aging Brain, Normal James Provenza Ie, MD

Introduction 1-10-62

Alzheimer Dementia James Provenza Ie, MD

Sella, Para sellar Anatomy-Imaging

Congenital

1-10-70

Dementia

1-10-74

Disease (C1D)

James Provenza Ie, MD

1-10-78

Parkinson Disease

Susan I. Blaser, MD, FRCP(C)

11-2-12

Tuber Cinereum Hamartoma Mauricio Castillo, MD, FACR

11-2-16

Rathke Cleft Cyst

James Provenza Ie, MD

1-10-82

Multiple System Atrophy

Anne G. Osborn, MD, FACR

James Provenza Ie, MD

Neoplasms

1-10-86

Lateral Sclerosis (ALS)

11-2-20

Pituitary Microadenoma

James Provenza Ie, MD

1-10-90

Wallerian Degeneration

Anne G. Osborn, MD, FACR

11-2-24

Pituitary Macroadenoma

James Provenzale, MD

Hypertrophic

11-2-8

Pituitary Stalk Anomalies

James Provenza Ie, MD

Amyotrophic

11-2-4

1-10-66

James Provenza Ie, MD

Creutzfeldt-lakob

Issues

Anne G. Osborn, MD, FACR

Multi-infarct Dementia Frontotemporal

and Overview

1-10-94

Olivary Degeneration

Anne G. Osborn, MD, FACR

11-2-28

Pituitary Apoplexy

James Provenza Ie, MD

Anne G. Osborn, MD, FACR

11-2-32

Craniopharyngioma Gary L. Hedlund, DO

PART II Anatomy-Based

11-2-36

Pituicytoma Karen L. Salzman, MD

Diagnoses

Miscellaneous 11-2-38

Pituitary Hyperplasia

SECTION 1 Ventricles and Cisterns

Karen L. Salzman,

Lymphocytic

MD

11-2-40

Hypophysitis

Anne G. Osborn, MD, FACR

Introduction

and Overview

Ventricles, Cisterns Anatomy-Imaging

Issues

11-1-4

SECTION 3 CPA-lAC

Anne G. Osborn, MD, FACR

Normal Variants 11-1-8

Cavum Septi Pellucidi (CSP) Anne G. Osborn, MD, FACR

Cavum Velum Interpositum

Introduction

and Overview

CPA-lAC Anatomy and Imaging Issues (CVI)

11-1-10

11-3-4

H. Ric Harnsberger, MD

Anne G. Osborn, MD, FACR

Enlarged Subarachnoid

Spaces

Congenital

11-1-12

Susan I. Blaser, MD, FRCP(C)

Lipoma, CPA-lAC

11-3-8

H. Ric Harnsberger, MD

Hydrocephalus Obstructive

Hydrocephalus

Epidermoid Cyst, CPA-lAC 11-1-16

James A. Cooper, MD

Aqueductal Stenosis

11-3-12

H. Ric Harnsberger, MD

Arachnoid Cyst, CPA-lAC 11-1-20

11-3-16

H. Ric Harnsberger, MD

James A. Cooper,MD

Normal Pressure Hydrocephalus

11-1-24

James Provenza Ie, MD

CSF Shunts and Complications

Inflammatory Ramsay Hunt Syndrome

11-1-28

11-3-20

H. Ric Harnsberger, MD

Susan I. Blaser, MD, FRCP(C)

Vascular Vascular Loop Compression,

CPA-lAC

11-3-24

H. Ric Harnsberger, MD XXI

Malignant Nonmeningothelial

Neoplasms Acoustic Schwannoma

11-3-28

H. Ric Harnsberger, MD

Meningioma,

CPA-lAC

11-3-32 11-3-36

H. Ric Harnsberger, MD

Introduction

and Overview Issues

11-4-4

Anne G. Osborn, MD, FACR

Congenital Craniostenoses

11-4-8

Susan 1. Blaser, MD, FRCP(C)

Atretic Cephalocele

11-4-12

Gary 1. Hedlund, DO

Trauma Calvarium Fracture

11-4-14

Gregory 1. Katzman, MD

Pneumocephalus

11-4-18

Gregory 1. Katzman, MD

Hypotension

11-4-22

Anne G. Osborn, MD, FACR

Nonneoplastic and Tumorlike Disorders Pseudotumors

11-4-26

H. Ric Harnsberger, MD

Pachymeningitis

11-4-30

Anne G. Osborn, MD, FACR

Fibrous Dysplasia

11-4-34

Susan 1. Blaser, MD, FRCP(C)

Paget Disease

11-4-38

Gregory 1. Katzman, MD

Extramedullary

Hematopoiesis

11-4-42

Gregory 1. Katzman, MD

Thick Skull

11-4-44

Gregory 1. Katzman, MD

Histiocytosis

11-4-48

Gary 1. Hedlund, DO

Neurosarcoid

11-4-52

Gregory 1. Katzman, MD

Neoplasms Meningioma

11-4-56

Gregory 1. Katzman, MD

Atypical and Malignant Meningioma

11-4-60

Gregory 1. Katzman, MD

Benign Nonmeningothelial Gregory 1. Katzman, MD XXll

Myeloma Skull and Meningeal Metastases Gregory 1. Katzman, MD

Skull, Scalp, Meninges Anatomy-Imaging

Hypertrophic

Hemangioma

11-4-72 11-4-76

Gregory 1. Katzman, MD

Metastases, CPA-lAC

Intracranial

11-4-68

Gregory 1. Katzman, MD

H. Ric Harnsberger, MD

Intracranial

Tumors

Gregory 1. Katzman, MD

Tumors

11-4-64

11-4-80

XXlll

XXiV

ABBREVIATIONS IH: Proton 3T (imaging):

CST: Cavernous sinus thrombosis 3 Tesla

CVD: Collagen vascular disease

AC: Arnold Chiari

CVT: Cerebral venous thrombosis

ACA: Anterior cerebral artery

DSA: Digital subtraction angiography

AcoA: Anterior communicating ACTH: Adrenocorticotrophic

artery

hormone

ECA: External carotid artery EMA: External maxillary artery

ADC: Apparent diffusion coefficient

EpC: Epidermoid cyst

ADHP: Autosomal dominant

FlU: Follow-up

holoprosencephaly

AICA: Anterior inferior cerebellar artery

FDG: Fluordeoxygluose

ApoE: Apolipoprotein

E

GAl: Glutaric academia type 1

ASVD: Atherosclerotic

vascular disease

GFAP: Glial fibrillary acidic protein

BIT:

Between

GM1/2:

BA: Basilar artery BCKD: Branched-chain

Gangliosidosis

1/2

GSW: Gunshot wound Alpha-keto dehydrogenase

HA:. Headache

BFGF: Basic fibroblast growth factor

HGBL(s): Hemangioblastoma(s)

BaS fx: Base of skull fracture

HHT: Hereditary hemorrhagic

CBLL: Cerebellar

HMPAO: Hexamethylopropyleneamine

Cele: Encephalocele

HU: Hounsfield unit

Cf: Compare

HUS: Hemolytic-uremic

CHARGE: Coloboma; Heart defects; Atresia of choanae; Retardation of growth; Genitourinary abnormalities; Ear abnormalities

ICA: Internal carotid artery

Cho:

Choline

CN(s): Cranial nerve(s) CNS: Central nervous system COHb:

Carboxyhemoglobin

COP: Carbon monoxide poisoning COW: Circle of Willis CPA-lAC: Cerebellopontine angle-internal auditory canal

ICH: Intracranial

telangiectasia oxime

syndrome

hemorrhage

IC-PCoA: Internal carotid-posterior artery junction

communicating

IEL: Internal elastic lamina INO: Internuclear Ino:

ophthalmopligia

Inositol

ION: Inferior olivary nucleus ISF: Interstitial fluid

Cr: Creatine

ISUIA: International Aneurysms

CSF: Cerebrospinal fluid

IVH: Intraventricular

Study on Unruptured

Intracranial

hemorrhage

LHX3: 11M homeobox 3 gene

xxv

LHX4: LIM homeobox 4 gene

TOF: Time of flight

LV: Lateral ventricle

TPIT: Treponema pallidum immobilization

MCA: Middle cerebral artery

TS: Transverse sinus

MEN1: Multiple endocrine neoplasia 1

TIP: Thrombotic thromocytopenic

MIB-1: Histiologic marker of cell proliferation

VA: Vertebral artery

MIH: Melanotropin

VACTERL: Vertebral Anal Cardiac Tracheal Esophageal Renal Limb

release-inhibiting

hormone

MIP: Maximum intensity projection

VEGF: Vascular endothelial growth factor

MSH: Melanotropin

stimulating hormone

VHL: von Hippel Lindau

NAT: Nonaccidental

trauma

WaD: Wallerian degeneration

NF: Neurofibromatosis

WM: White matter

NIH: National Institutes of Health (USA)

WWS: Walker- Warburg syndrome

NSE: Neural-specific enolase NTD(s): Neural tube defect(s) OMIM: Online Mendelian Inheritance

in Man

PAS: Periodic acid schiff PCA: Posterior cerebral artery PCoA: Posterior communicating PcomA:

artery

Posterior communicating

artery

PnSAH: Perimesencephalic non aneurysmal subarachnoid hemorrhage PICA: Posterior inferior cerebellar artery PPm: Mean ocular perfusion pressure PRL: Prolactin PVSs: Perivascular space(s) rCBF: Relative cerebral blood flow rCBV: Relative cerebral blood volume SIP:

Following (status post)

SAH: Subarachnoid hemorrhage SOY: Superior ophthalmic

vein

SPECT: Single photon emission computed tomography SPGR: Spoiled gradient refocused SPS: Superior petrosal sinus SS: Straight sinus SSAC(s): Suprasellar arachnoid cyst(s) SSS: Superior sagittal sinus SVC: Superior vena cava TBI: Traumatic brain injury TCE: T-cell TIAs: Transient ischemic attack(s)

XXVI

purpura

test

XXVll

XXVlll

DIAGNOSTIC IMAGING

BRAIN

XXIX

xxx

PART I PathololY-Based Dlaposes

Congenital Malformations Trauma

[I]

rn

Subarachnoid Hemorrhage and Aneurysms

rn

Stroke @] Vascular Malformations

rn

Neoplasms and Tumorlike Lesions

lliJ

Primary Non-Neoplastic Cysts [l] Infection and Demyelinating Disease Metabolic/Degenerative

[ID

Disorders, Inherited

~

Toxic/Metabolic/Degenerative Disorders, Acquired [1Q]

10

PART I SECTION 1 Consenltal Malformations The human brain is subject to a variety of developmental anomalies that vary from mild to so evere that they are incompatible with life. Formation of the S is a tunningly complex proce with many cycles of development, mod ling and remod ling that b gins in early fetal life and continues into th third postnatal decade. Mor than 2000 different malformations have been described in the clinical and imaging literature. n exhau tive (even comprehensive) discus i n of S anomalies is far beyond the cope of this text. We have att mpted to select for discussi n those malformations that are either stati tically among the most c mmon ncountered in g n ral imaging practice or tho e that are e pecially important to rec gnize. It should be empha ized that our understanding of the genetic and in uter environmental influences on brain devel pment and malformati n continu t evolve. Imaging is only a part of the larger puzzl . Knowledge of th basic principl underlying S development is the foundation for approaching c ngenital malformations f the brain. While an ind pth discu sion of neuroembryology i al 0 beyond th scope of thi book, we present a bri f review of "embr ology in a nutshell" that is helpful as a starting point in und rstanding the specific diagnoses in thi s ction. We begin the discussion of ongenital malformations f the brain with hindbrain herniati n and malformations. Included in this group are the hiari malf rmations, a 'r up of mostly embryolo 'i ally unrelated hindbrain anomalies in which cereb liar tissue i di placed into the cervi al canal. Also included in hindbrain malformations are the posterior fo a cystic malf rmations (DandyWalk r "com pi XU including the Dandy-Walker malformation and variant ). Oth r cerebellar malformations such as rhombencephalo ynapsis are discus ed here. Di erticulation and cleavage disorder of the developing brain include the sp ctrum of h I prosen ephalies and their variants. Malf rmations of cortical development are a large and diverse group. The major ones are discu sed in this s ction. The ection concludes with a group of disorders that no one knows quite what to call: eurocutaneous syndromes? ot all have cutaneous manifestation. Phakomat ses? ot all have spots. Inherited tumor yndromes? ot all hav associated neoplasms. Inherited genetic syndrom ? ot all are kn wn, and some (such as Sturge-Weber malformation) are not inherited. Whatever you want to call them, here they ar !

SECTION 1: Congenital Malformations

Introduction and Overview Congenital Malformations

1-1-4

Hindbrain Herniations, Miscellaneous Malformations Chiari 1 Chiari 2 Chiari 3 Callosal Dysgenesis Lipoma

1-1-8 1-1-12 1-1-16 1-1-18 1-1-22

Hindbrain Malformations Dandy Walker Spectrum Rhombencephalosynapsis Congenital Vermian Hypoplasia

1-1-26 1-1-30 1-1-34

Disorders of Diverticulation/Cleavage Holoprosencephaly Holoprosencephaly Variants Septooptic Dysplasia

1-1-38 1-1-42 1-1-46

Malformations of Cortical Development Microcephaly Congenital Muscular Dystrophy Heterotopic Gray Matter Pachygyria -Polymicrogyria Lissencephaly Type 1 Schizencephaly Hemimegalencephaly

1-1-50 1-1-54 1-1-58 1-1-62 1-1-66 1-1-70 1-1-74

Familial Tumor/Neurocutaneous Syndromes Neurofibromatosis Type 1 Neurofibromatosis Type 2 von Hippel Lindau Tuberous Sclerosis Complex Sturge- Weber Syndrome Meningioangiomatosis Basal Cell Nevus Syndrome HHT Encephalocraniocutaneous Lipomatosis Cowden Syndrome Neurocutaneous Melanosis

1-1-78 1-1-82 1-1-86 1-1-90 1-1-94 1-1-98 1-1-100 1-1-104 1-1-108 1-1-112 1-1-116

CONGENITAL MALFORMATIONS

1 4

Graphic shows neural plate (red, upper left). Upper right: NT folds. Lower left: NT closes. Lower right: Cutaneous, neuroectoderm separate; neural crest (blue) migrates laterally

Clinical photograph shows NTDS with MMC. The protruding raw red mass is the dorsal surface of the unclosed neural tube that remains open, everted (Courtesy C. Hedlund, MO).

ITERMINOLOGY Abbreviations

•

and Synonyms

• Neural tube defects (NTDs) • Malformations of cortical development

(MCD)

Definitions • Congenital malformations are primary disorders resulting from disturbed embryonic/fetal development • Encephaloclastic defects are secondary disorders that result from in utero insults to otherwise normally-developed brain (e.g., vascular, infectious, toxic, etc) and are considered acquired disorders

I PATHOLOGY

ISSUES

•

Classification • Many classifications proposed; none universally accepted • Neural tube defects/dysraphic disorders o Exencephaly, anencephaly o Myelomeningocele with Chiari II malformation o Herniations through cranial defects (covered in Part II) • Cephalocele (named for bone through which they pass) • Meningocele • Disorders of forebrain induction o Holoprosencephaly (HPE) (no absolute distinction between categories; overlap common) • Alobar • Semilobar • Lobar • Kallman syndrome and HPE variants (e.g., central incisor syndrome) o Septo-optic dysplasia (+/- hypothalamic-pituitary dysfunction) o Arrhinencephaly o Callosal dysgenesis • Partial

•

•

• Agenesis • With or without lipoma Malformations of cortical development (proliferation, migration, organization) o Lissencephalies (classic, cobblestone types) o Pachygyria (incomplete lissencephaly) o Polymicrogyria o Schizencephaly ("open" or "closed" lip) o Hemimegalencephaly o Gray matter heterotopias • Subependymal heterotopia • Focal subcortical ("masslike") heterotopia • Band heterotopia ("double cortex") o Focal cortical dysplasias Cerebellar malformations o Cerebellar agenesis (sometimes termed "Chiari IV") o Joubert syndrome (congenital vermian aplasia/hypoplasia) o Tectocerebellar dysraphia o Rhombencephalosynapsis o Dandy-Walker malformation Miscellaneous malformations o Lipoma (maldifferentiation of primitive developing meninges) Familial tumor/neurocutaneous syndromes o With CNS neoplasm (major CNS listed) • Nfl (plexiform neurofibroma, MPNST, optic glioma, astrocytoma) .' NF2 (schwan noma, meningioma, ependymoma) • von Hippel-Lindau (hemangioblastoma) • Tuberous sclerosis (subependymal giant cell astrocytoma) • Li-Fraumeni (astrocytoma, PNET) • Cowden (dysplastic cerebellar gangliocytoma) • Turcot (medulloblastoma, GBM) • Nevoid basal cell carcinoma (Gorlin) syndrome (medulloblastoma) o Without CNS neoplasm • Sturge- Weber syndrome • Wyburn-Mason syndrome

CONGENITAL MALFORMATIONS

1 DIFFERENTIALDIAGNOSIS Chromosomal anomalies with CNS manifestations • Trisomies (21, 18, 13)

Neural tube defects (NTDs) • Anencephaly • Cephaloceles • Myelomeningocele

(with Chiari II)

Abnormalities of brain cleavage, diverticulation • Holoprosencephaly • Septooptic dysplasia • Kallman syndrome

• Hereditary hemorrhagic telangectasia (HHT or Rendu-Osler- Weber syndrome) • Ataxia-telangiectasia • Neurocutaneous melanosis (can have intracranial malignant melanoma) • Meningioangiomatosis (can be locally invasive) • Encephalo-craniocutaneous lipomatosis

IClINICAllMPlICATIONS Clinical Importance • Approximately 3% of newborns have major malformations o Approximately 60% of congenital malformations remain of unknown etiology o Approximately 20% are multifactorial (combination of hereditary tendencies, nongenetic influences) o 7.5% are monogenic o 6% have major chromosomal anomalies o 12-15% acquired encephaloclastic disorders (e.g., toxins, drugs, infection, nutrition) • > 75% of fetal deaths have cerebral malformations o More than 2,000 different congenital cerebral malformations have been described o One-third of all major malformations involve the CNS

IEMBRYOLOGY Embryologic Events • Primary neurulation o Notochordal process, prechordal plate induce development of neural plate o Lateral portions of neural plate thicken, fold o Neural folds bend medially towards each other o Neural folds fuse, neural crest cells detach from lateral lips of neural folds and migrate laterally o Neural tube closes bidirectionally in "zipper-like" fashion o Surface ectoderm fuses, neural tube separates and sinks into mesenchyme of posterior body wall

5

Hindbrain malformations • • • • • •

Chiari I Chiari II Chiari III Dandy-Walker spectrum Cerebellar, vermian hypoplasias Rhombencephalosynapsis

Malformations • • • • • • •

of cortical development

Microcephaly Congenital muscular dystrophy Heterotopic gray matter Pachygyria-polymicrogyria Lissencephaly type 1 Hemimegalencephaly Schizencephaly

o Neural tube bends, forms primary, then secondary vesicles • Prosencephalon (forebrain) gives rise to telencephalon, diencephalon • Mesencephalon gives rise to midbrain • Rhombencephalon (hindbrain) gives rise to developing pons, cerebellum, medulla o Cerebral hemispheres, ventricles develop as diverticulae from lateral walls of forebrain, expand rapidly to cover diencephalon • "H"-shaped central monoventricle formed with developing lateral ventricles communicating with central3rd V through an interventricular foramen (of Monro) • Choroid fissure runs length of lateral ventricles, contains choroid plexus that elaborates CSF • Proliferating cells around ventricles form germinal zones of neuroblasts • Neuroblasts migrate peripherally in waves, creating cortex in an "inside-out" sequence (Le., from deep to superficial layer • Commissural tracts (anterior, hippocampal, corpus callosum) form at cranial end of telencephalon • Corpus callosum undergoes bidirectional thickening; anterior portion of genu, posterior callosal body form"'! same time; rostrum forms last (after splenium) o Diencephalic alar plate forms thalamus, hypothalamus; roof plate and ependyma form choroid plexus, circumventricular organs o Primitive mesenchymal tissue ("leptomeninx") differentiates into arachnoid, pia; arachnoid space is created as mesenchumal tissue between arachnoid, pia is resorbed leaving scattered arachnoidal trabeculae or struts • Secondary neurulation o Mesodermal cells in caudal eminence (tail mass) fuse o Vacuoles in tail mass form, fuse ~ hollow tube o Lumen of caudal eminence fuses/becomes continuous with neural tube o Caudalmost part of neural tube eventually regresses, forming filum terminale

CONGENITAL MALFORMATIONS 1 6

NTOS with Chiari II. Elongated 4th V (open arrow), tissue "cascade" (vermian nodulus, choroid plexus) (curved arrow), medullary spur (white arrow) and kink (black arrow) (Courtesy S. VandenBerg and Rubinstein collection).

• Failure of part of neural neural tube closure ~ neural tube defects (NTDS) that range from mild, simple spina bifida to myelomeningocele • Defective development of ventromedial forebrain ~ defects ranging from mild anomalies of olfactory bulbs to alobar holoprosencephaly • Faulty neuronal migration ~ lissencephaly, subcordical band heterotopia, etc • Failure of normal commissural development ~ corpus callosum anomalies • Maldifferentiation of primitive leptomeninix ~ lipoma

DIFFERENTIAL

DIAGNOSIS

Small head (2 S D below mean for age) • Primary microcephaly o Familial and autosomal dominant microcephaly o Trisomy 21, 13 o Rubinstein-Taybi syndrome • Secondary microcephaly o Severe intrauterine hypoxic-ischemic injury o Fetal alcohol syndrome o Congenital infection ("TORCH" syndromes)

Large head (> 2 S D above mean or percentile by at least 0.5 cm)

Small posterior fossa • • • •

Chiari II malformation Occipital cephalocele Achondroplasia Chiari I malformation (variable)

Large posterior fossa • Dandy-Walker syndrome • Large bulky congenital infratentorial neoplasm (rare; e.g., atypical teratoid/rhabdoid tumor)

I

Prominent sutures • "Pseudosplit" sutures o Normally seen in infants up to 2-4 mos (due to underossification) ! • Increased intracranial pressure • NFl with sutural defects • Metastases (leukemia, neuroblastoma) • Hypothyroidism, hypophosphatasia • Osteogenesis imperfecta

I SELECTED 1.

> 97th

• Hydrocephalus o Aqueductal stenosis o Dandy-Walker, other malformations • Chronic subdural fluid collections • Enlarged subarachnoid spaces (benign macrocrania infancy) • Neurocutaneous syndrome (Nfl, TSC) • Metabolic storage diseases (e.g., mucopolysaccharidoses) • Dysmyelinating disorders (Alexander, Canavan) • Achondroplasia

MO).

• Megalencephaly, cerebral gigantism (Sotos syndrome), etc • Neoplasm (large, bulky mass; prior to sutural closure)

Practical Implications

ICUSTOM

Sagittal gross pathology shows Chiari II malformation with callosal dysgenesis. Note high-riding 3rd V, small posterior fossa contents (arrows) (Courtesy R. Hewlett,

2.

3.

of

4.

5. 6.

REFERENCES

Glass RB] et al: The infant skull: A vault of information. RadioGraphies 24: 507-22, 2004 Kurul S et al: Agyria-pachygyria complex: MR findings and correlation with clinical features. Pediatr Neurol. 30(1):16-23,2004 Garcia-Cazorla A et al: White matter alterations associated with chromosomal disorders. Dev Med Child Neural. 46(3):148-53,2004 Sisodiya SM: Malformations of cortical development: burdens and insights fram important causes of human epilepsy. Lancet Neural. 3(1):29-38, 2004 Larsen W]: Human Embryology (3rd ed), Churchill Livingstone, 2001 Barkovich A]: Pediatric Neuraimaging (3rd ed), Lippincott Williams and Wilkins, 2000

CONGENITAL MALFORMATIONS

1

I IMAGE GAllERY

7

Normal vs. Pathology (Left) Lateralgross pathology

shows normal early fetal brain development. Note shallow, open sylvian fissure (arrow) and virtually complete lack of sulcation/gyration (Courtesy S. Stensaas, PhO). (Right) Lateralgross pathology shows brain of infant born with near-complete agyria (lissencephaly). Minimal sulcation/gyration is seen. Compare with normal fetal brain on left (Courtesy R. Hewlett, MO).

Normal vs. Pathology (Left) Axial gross pathology of a normally developing

fetal brain (same case as above) shows completely smooth hemispheres. (Right) Coronal gross pathology, section through posterior ventricles (same case as above) shows essentially agyric brain with smooth, thin cortex. Note subependymal gray matter (arrows) in germinal matrix.

Normal vs. Pathology (Left) Submentovertex gross pathology of normal fetal brain shows lobulation but little evidence for significant sulcation or gyration. Note shallow, open Sylvian fissures (arrows). (Right) Coronal gross pathology, section through thalami again shows agyric brain. Compare to normal fetal brain on left. Periventricular germinal hemorrhage is present (arrows).

CHIARI1

1 8

Sagittal T7WI M R shows sliver of tonsils (curved arrow) protruding through the foramen magnum posteriorly compressing the upper cervical cord. There is mild ventriculomegaly (arrow).

Sagittal graphic shows caudal descent of nucleus gracilis (curved arrow) marking obex. The tonsils (arrow) protrude through foramen magnum and the cisterna magna is obliterated.

• Morphology o Tonsils can normally lie below FM (:::;5 mm in adults, slightly more in children < 4 y) o Unless tonsils ~ 5 mm and/or pointed, probably not Ch 1 o Tonsillar impaction in FM without caudal herniation can also be symptomatic • Look for absent cisterna magna, posteriorly angled odontoid with compressed brainstem, short posterior arch C1, short supra occiput, syrinx

ITERMINOlOGY Abbreviations

and Synonyms

• Chiari type I malformation tonsil ectopia

(Ch 1); cerebellar (CBLL)

Definitions • Caudal protrusion foramen magnum

of "peg-shaped" CBLL tonsils below (FM)

Radiographic Findings

!IMAGING FINDINGS

• Radiography o 4th occipital sclerotome syndromes> 50% • Short clivus, craniovertebral segmentation/fusion anomalies, pro-atlas remnants, atlas assimilation, odontoid retroflexion • Small occipital enchondral skull: Basiocciput, exocciput, supra occiput • 1 Angulation of posteriorly tilted odontoid process (more common in females) => 1 symptoms o Suspect Ch 1 if • Cervical lordoses > 0 degrees • Thoracic kyphosis> 40 degrees o Suspect syrinx if enlarged cervical spinal canal on lateral film

General Features • Best diagnostic clue o Low-lying, pointed (not rounded) "peg-like" CBLL tonsils o Tonsillar sulci have vertical (not horizontal) orientation o Compressed/absent cisterna magna • Size o Age-related tonsil descent below "opisthion-basion line" • 1st decade (6 mm) (most pronounced at"" 4 y, then tonsils "retreat") • 2nd/3rd decades (5 mm) • 4th to 8th decades (4 mm) • 9th decade (3 mm)

CT Findings • NECT

DDx: Protrusion of Cerebellar Tonsils

Ch I at .f Yrs

Resolution

by (, Yrs

Congenital

Shunt /\cquirpcl

Malformations

Ch I

Epcnclym( )fna

CHIARI1 1

Key Facts Terminology • Chiari type I malformation (Ch 1); cerebellar (CBLL) tonsil ectopia • Caudal protrusion of "peg-shaped" CBLL tonsils below foramen magnum (FM)

• I::=asymptomatic: 14-50%, treatment • II::=brainstem compression • III::=hydrosyringomyelia

Clinical Issues • Treatment aim ::=restore normal CSF flow at FM

Imaging Findings • Tonsils can normally lie below FM (::; 5 mm in adults, slightly more in children < 4 y) • Unless tonsils 2: 5 mm and/or pointed, probably not Ch 1 • Small bony PF ::>low torcular, effaced PF cisterns • "Crowded" FM

controversial

Diagnostic Checklist • Low tonsils with normal rounded shape are usually asymptomatic • Tonsils with peg/triangular shape + obliteration of surrounding CSP are abnormal at any level below opisthion-basion line

Pathology • "Mismatch" between posterior fossa size (small), CBLL (normal) ::>tonsillar "ectopia"

o Small bony PF ::>low torcular, effaced PF cisterns o "Crowded" FM o Lateral/3rd ventricles usually normal (89%)

MR Findings • TlWI o Sagittal: Pointed, triangular-shaped ("peg-like") tonsils 2: 5 mm below FM o Surrounding CSF in PM effaced o Short clivus::> apparent descent 4th ventricle, medulla • T2WI: Look for upper cervical cord edema, syrinx (15-75%) • Phase-contrast cine MR shows pulsatile systolic tonsillar descent, obstructed CSF flow through FM

Ultrasonographic

Findings

• Color Doppler: Loss of bidirectional CSF flow, peak velocity of 3-5 cm/s, and waveform that exhibits vascular and respiratory variations

Nuclear Medicine

Findings

• Radionuclide cisternography: Patients with demonstrable FM block have more predictable relief of symptoms following posterior fossa decompression and duraplasty than those with syrinx and free tracer flow across foramen magnum

Imaging Recommendations • Best imaging tool: MR brain with thin sagittal views of the craniocervical junction • Protocol advice o MR brain +/- CSF flow studies o Spine MRI to detect syrinx, low/tethered cord, +/fatty filum

I DIFFERENTIAL DIAGNOSIS Acquired tonsillar ectopia/herniation • Basilar invagination • "Pull from below" o Lumbar puncture hypotension

or (LP) shunt::> intracranial

• "Sagging" brain stem, acquired tonsillar herniation o Spontaneous intracranial hypotension • "Push from above" o Chronic ventriculo-peritoneal shunt (thick skull, premature sutural fusion, lumbar arachnoidal adhesions) o Tonsillar herniation 2° 1 ICP, mass effect or tumor

I

PATHOLOGY

General Features • General path comments o Embryology • Underdeveloped occipital enchondrium ::>small posterior fossa (PF) vault ::>crowded PF ::> downward herniated hindbrain::> obstructed FM ::>lack of communication between cranial/spinal CSF compartments • Genetics o Syndromic/familial • Craniosynostoses; midline anomalies • Mutated LHX4 gene (Chr 1q25): Posterior pituitary ectopia, Ch 1 • Etiology o "Mismatch" between posterior fossa size (small), CBLL (normal) ::>tonsillar "ectopia" o Hydrodynamic theory of symptomatic Chiari 1 • Systolic piston-like descent of impacted tonsils/medulla::> abnormal intraspinal CSF pressure-wave • Hydrosyringomyelia develops as secondary phenomenon • Epidemiology: 0.01 % of population • Associated abnormalities o Craniocervical junction bony anomalies frequent • 4th occipital sclerotome anomalies, underdeveloped basichondrocranium, Klippel-Feil, Sprengel deformity, platybasia o NFl patients comprise approximately 5% of symptomatic Chiari 1 o FG syndrome

Congenital Malformations

9

Gross Pathologic & Surgical Features 10

• • • •

Herniated, sclerotic tonsillar pegs Tonsils grooved by impaction against opisthion Arachnoid adhesions between CBLLtonsils, medulla Thickened leptomeninges and/or thickened dura mater at CVJ

Microscopic

Features

• Purkinje/granular

cell loss

Staging, Grading or Classification Criteria • I = asymptomatic: 14-50%, treatment controversial • II = brainstem compression • III = hydrosyringomyelia

Syrinx shunted only if syrinx persists or progresses post suboccipital decompression • Treatment aim = restore normal CSF flow at FM o Suboccipital decompression/resect posterior arch Cl; +/- duraplasty, CBLLtonsil resection • > 90% ~ !brainstem signs • > 80% ~ ! syringohydromyelia • Scoliosis arrests (improves in youngest) • Progression of spinal deformity post suboccipital decompression 1 with older age, severity of initial symptoms, double scoliosis curve, thoracic kyphosis, rotation, large curve o

1·.[)IA{jN4QSl"I(iCEHECEl{~.ISI Consider

I.C~lNICA.l-ISSl,lES Presentation • Most common signs/symptoms o Up to 50% asymptomatic • Prevalence of symptoms 1 if canal diam < 19 mm o "Chiari 1 spells": Cough or sneezing ~ acute 1 intrathecal pressure due to obstructed CSF flow ~ headache or syncope o Symptomatic brainstem compression • Hypersomnolence/central apnea/sudden death (infant) • Bulbar signs (e,g" lower CN palsies) • Neck or back pain, torticollis, ataxia o Symptomatic syringohydromyelia • Paroxysmal dystonia, unsteady gait, incontinence • Atypical scoliosis (progressive, painful, atypical curve) • Dissociated sensory loss/neuropathy (hand muscle wasting) o Other: Hiccoughs, trigeminal facial pain, may mimic multiple sclerosis • Clinical profile o Infant/very young child: Impaired oropharyngeal function common o Child: Headache, neck pain, syrinx and scoliosis o Adult: Neck pain, and drop attacks

• Etiologies other than Ch 1 when tonsillar descent seen on spine MRI first (hydrocephalus and brain tumors "push" tonsils down)

Image Interpretation

1,

2,

3,

4.

S,

6,

Demographics • Age o Very young child: Mean 3.3 years o Pediatric: Mean 11 years (range in one series 2 months to 20 years) o Adult: Mean age 34 years • Gender: M:F = 1:1.3

Natural History & Prognosis • Increasing ectopia + 1 time ~ 1 likelihood symptoms • Children respond better than adults; treat early • Postoperative complications o Cerebellar ptosis o Regrowth/ossification of resected bone

Pearls

• Low tonsils with normal rounded shape are usually asymptomatic • Tonsils with peg/triangular shape + obliteration of surrounding CSF are abnormal at any level below opisthion-basion line

7.

8,

9,

Flynn JM et al: Predictors of progression of scoliosis after decompression of an Arnold Chiari 1 malformation, Spine 29(3):286-92, 2004 Arora P et al: Chiari 1 malformation related syringomyelia: Radionuclide cisternography as a predictor of outcome, Acta Neurochir 146(2)119-30, 2004 Schijman E, Steinbok P: International survey on the management of Chiari 1 malformation and syringomyelia, Childs Nerv Syst, 2004 Tubbs RSet al: Inclination of the odontoid process in the pediatric Chiari 1 malformation. J Neurosurg 98(lSuppl):43-9, 2003 Venureyra EC et al: The role of cine flow MRI in children with Chiari 1 malformation, Childs Nerv Syst 19(2):109-13, 2003 Tubbs RSet al: Surgical experience in 130 pediatric patients with Chiari 1 malformations, J Neurosurg 99(2):291-6, 2003 Loder RT et al: Sagittal profiles of the spine in scoliosis associated with an Arnold-Chiari malformation [type 11 with or without syringomyelia, J Pediatr Orthop 22(4):483-91,2002 Kyoshima K et al: Syringomyelia without hindbrain herniation: Tight cisterna magna, J Neurosurg 96(2Suppl):239-49,2002 Greenlee JD et al: Chiari 1 malformation in the very young child: The spectrum of presentations and experience in 31 children under age 6 years, Pediatrics 110(6):1212-9, 2002

Treatment • Controversial: International consensus states "no intervention for asymptomatic Chiari 1 unless syrinx" o Most will also intervene if scoliosis, even in absence of syringohydromyelia

Congenital Malformations

1 11 (Left) Sagittal T2WI MR shows posteriorly tilted odontoid (curved arrow) indenting the junction of the medulla and upper cervical cord. There is abnormal cervical cord signal (arrow) and Ch 7 (open arrow). (Right) Sagittal NECT 30 reconstruction shows a short, flat clivus and a posteriorly angled, bulbous odontoid tip (curved arrow).

(Left) Sagittal T7WI MR shows an "impacted" foramen magnum in Proteus syndrome and megalencephaly. The cisterna magna is effaced and the pointed tonsils (arrow) protrude slightly through foramen magnum. (Right) Sagittal T2WI MR shows marked protrusion of cerebellar tonsils through foramen magnum. The odontoid is posteriorly angled; medulla is indented (arrow). The tonsils are round and surrounded by CSF.

(Left) Axial T2WI MR shows cerebellar tonsils (open arrow) protrude through the foramen magnum to surround and compress the cervical cord. Posterior fossa cisterns are obliterated. (Right) Coronal T2WI MR shows moderate unilateral protrusion of the right cerebellar tonsil (arrow). The left cerebellar tonsil remains in normal position.

Congenital Malformations

12

Sagittal graphic shows small PF, large massa intermedia, beaked tectum, callosal dysgenesis, elongated 4th Vand (in order) herniating nodulus, choroid plexus, and medullary spur (arrows).

Sagittal TlWI MR shows beaked tectum (arrow), large massa intermedia (curved arrow), dysgenetic corpus callosum, small 4th ventricle, and protrusion of tissue through foramen magnum.

Radiographic Findings Abbreviations • Arnold-Chiari

and Synonyms malformation

(AC2), Chiari type II

Definitions • Complex malformation of hindbrain virtually 100% associated with neural tube closure defect (NTD), usually lumbar myelomeningocele (MMC)

r·IMAGINYFINOlNG$ General Features • Best diagnostic clue o Presence of MMC o Small posterior fossa o Elongated, "straw-like" 4th ventricle • Location: Hindbrain • Size: Small posterior fossa • Morphology o "Cascade" of tissue herniates through foramen magnum behind upper cervical cord • Vermis (nodulus) • Choroid plexus of 4th V • Medullary "spur"

• Radiography o "Lacunar" (Lucken shadel) skull • Universal at birth, largely resolves by 6 months • Craniolacunia involves inner, outer tables (squamous bones) • Caused by mesenchymal defect (not i ICP!) o Incorporation of accessory frontal bone ~ transient "bifrontal foramina" o Widened upper cervical canal (Chiari malformation +/- syrinx) • Myelography o Tethered cord o Nerve roots pass horizontal or even upwards

CT Findings • NECT o Small posterior fossa (PF) • Low lying tentorium/torcular inserts near foramen magnum • Large, funnel-shaped foramen magnum • "Scalloped" petrous pyramid, "notched" clivus o Dural abnormalities • Fenestrated/hypoplastic falx ~ interdigitated gyri • "Heart-shaped" incisura • Absent falx cerebelli

DDx: The Chiari Malformations

Chiari 7

Chiari 2

Chiari 3

Congenital Malformations

Chiari 4

CHIARI2 1

Key Facts • Other Chiari malformations

Terminology • Arnold-Chiari malformation (AC2), Chiari type II • Complex malformation of hindbrain virtually 100% associated with neural tube closure defect (NTD), usually lumbar myelomeningocele (MMC)

Imaging Findings • Presence of MMC • Small posterior fossa • "Cascade" of tissue herniates through foramen magnum behind upper cervical cord • "Lacunar" (Lucken shadel) skull • Universal at birth, largely resolves by 6 months • Caused by mesenchymal defect (not 1 ICPl)

Top Differential

Diagnoses

• Severe, chronic shunted congenital

Diagnostic Checklist • Imaging features due to long term effects of mechanical distortion • "Too small" PF • Cerebellar contents herniate!, 1

hydrocephalus

• Reported""

MR Findings • T1WI o Small PF ~ contents shift! into cervical canal, herniate upward through incisura • Cerebellar (CBLL) hemispheres/tonsils "wrap" anteriorly around medulla • Pons, cranial nerve roots often elongated • Compressed, elongated, low-lying 4th V often lacks fastigium, may pouch into cervical canal • "Towering" cerebellum protrudes up through incisura, compresses tectum o Associated abnormalities: Dysgenetic corpus callosum (CC) 90% • T2WI o Ventricles • Lateral: Pointed anterior horns, colpocephaly • 3rd: Large massa intermedia, high-riding (if CC agenesis present) • 4th: Elongated, "straw-like" without posterior point (fastigium) o Small PF • Concave clivus, temporal bones • Low-lying torcular, TSs • Obliterated basal cisterns • "Cascade" or "waterfall" of tissue down, behind medulla • MRV: Torcular, transverse sinuses extremely low • MR spine o Open dysraphism, MMC almost 100% (lumbar> > cervical) o Hydrosyringomyelia 20-90% o Posterior arch Cl anomalies 66% o Diastematomyelia 5%

Ultrasonographic

Pathology • MTHFR mutations + folate deficiency ~ 1 risk NTD • Decreases in serum folate are seen with anti-epileptic drugs, oral contraceptives, and smoking • Abnormal neurulation ~ CSF escapes through NTD ~ failure to maintain 4th ventricular distention ~ hypoplastic PF chondrocranium ~ displaced/distorted PF contents

Findings

• Real Time o Fetal ultrasound (US) • MMC defined as early as 10 weeks on on US • AC2 ("lemon," "banana" signs) recognized as early as 12 weeks gestation • Lacunar skull identified by irregular echogenicity of skull

to fetal MRI for assessing spinal level

Imaging Recommendations • Best imaging tool: MRI brain + spine • Protocol advice o Initial screening MR (brain, spine) o Follow-up for • Symptoms of brainstem compression • Increasing ventricular size • Increasing spinal symptoms

I DIFFERENTI~[DI~GN0$1$ Severe, chronic shunted congenital hydrocephalus • May cause collapsed brain, upward herniated cerebellum, but no spina bifida

Other Chiari malformations • Chiari 1: Herniated CBLL tonsils • Chiari 2: Vermis may be impacted, rather than herniated or may "disappear" due to compressive injury • Chiari 3: Chiari 2 PLUS encephalocele • Chiari 4: Controversial, not just hypoplastic cerebellum o Some reserve term for severe hypoplasia of cerebellum in association with Chiari 2

I P~TI-I0[0G¥ General Features • General path comments: Neurogenic, renal, & orthopedic complications are the norm • Genetics o 4-8% risk recurrence if have one affected child o Menthylene-Tetra-Hydrofolate-Reductase (MTHFR) mutations (esp C677T) associated with abnormal folate metabolism o MTHFR mutations + folate deficiency ~ 1 risk NTD

Congenital Malformations

13

14

o Decreases in serum folate are seen with anti-epileptic drugs, oral contraceptives, and smoking • Etiology o Embryology • Origins during 4th fetal week • Abnormal neurulation =} CSF escapes through NTD =} failure to maintain 4th ventricular distention =} hypoplastic PF chondrocranium =} displaced/distorted PF contents o New studies demonstrate that vimentin is focally upregulated in the ependyma in dysgenetic regi0foLs • Theory that genetic defect may also playa role III etiology of Ch 2 brain malformation • Epidemiology: 0.44:1000 births, decreasing with folate replacement and elective termination of affected fetus • Associated abnormalities o 4th ventricular glial or arachnoidal cysts, choroidal nodules and subependymoma • Situated in the roof of 4th ventricle, closely associated with choroid plexus • Rarely identified on imaging

Gross Pathologic & Surgical Features • Basic abnormality = small PF with herniated hindbrain, hydrocephalus • Associated abnormalities o "Polygyria" (too many small crowded gyri) with normal 6 layer lamination o +/- Absent septum pellucidum/fused forniceal columns o Heterotopias o Aqueduct stenosis

Microscopic

Features

• Purkinje cell loss • Variable sclerosis of herniated

tissues

Staging, Grading or Classification Criteria • Hydrocephalus, brain malformation o Size of PF o Degree of hindbrain descent

relate to

Presentation • Most common signs/symptoms: Neonate: MMC • Clinical profile oMMC o Enlarging head o Lower extremity paralysis, sphincter dysfunction o Bulbar signs

Demographics • Age o Identified in utero or at birth • Fetal screening: i lX-feto protein • Gender: Slight female predominance • Ethnicity o I Incidence in Mexico o Probably associated with high prevalence of MTHFR mutation

Natural History & Prognosis • AC2 most common cause of death in MMC o Brainstem compression/hydrocephalus o Intrinsic brain stem "wiring" defects

Treatment • Folate supplements given to mothers o From pre-conception to 6 weeks post conception !! (but doesn't eradicate) risk of MMC • Chiari decompression • CSF diversion/shunting • Fetal repair MMC in selected patients may ameliorate severity AC2

Consider • Brainstem compression anesthesia risks

Image Interpretation

may cause sedation and

Pearls

• Imaging features due to long term effects of mechanical distortion o "Too small" PF o Cerebellar contents herniate!, i

1.

Sarnat HB: Regional Ependymal Upregulation of Vimentin in Chiari II Malformation, Aqueductal Stenosis, and Hydromyelia.Pediatr Dev Pathol. 7(1), 2004 . 2. Reimao R et al: Frontal foramina, Chiari II malformatIOn, and hydrocephalus in a female. Pediatr Neurol 29(4):341-4, 2003 3. Tulipan N et al: Intrauterine myelomeningocele repair. Clin Perinatol. 30(3):521-30, 2003 4. McLone DG et al: The Chiari II malformation: cause and impact. Childs Nerv Syst. 19(7-8):540-50, 2003 5. Aaronson OS et al: Myelomeningocele: prenatal evaluationncomparison between transabdominal US and MR imaging. Radiology 227(3):839-43, 2003 6. Tubbs RSet al: Absence of the falx cerebelli in a Chiari II malformation. Clin Anat 15(3):193-5, 2002 7. Northrup H et al: Spina bifida & other neural tube defects. CUff Probl Pediatr 30:313-32, 2000 8. Coley BD: Ultrasound diagnosis of luckenschadel (lacunar skull). Pediatr Radiol. 30(2):82-4, 2000 9. Mutchinick OM et al: High prevalence of the thermolabile methylenetetrahydrofolate reductase variant in Mexico: a country with a very high prevalence of neural tube defects. Mol Genet Metab 68(4):461-7, 1999 10. Rollins N et al: Coexistent holoprosencephaly and Chiari II malformation. AJNRAm J Neuroradio120(9):1678-81, 1999 11. Lewis DP et al: Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother 32(7-8):802-17, 1998

Congenital Malformations

1 15

Typical (Left) Axial T2WI MR shows heart-shaped tectum. Shape is due to fusion of collicular bodies (arrow). There is abnormal orientation of the folia of the hypoplastic cerebellum (open arrow). (Right) Axial T2WI MR shows colpocephaly (open arrows), enlarged massa intermedia (arrow), typical pointed anterior horns.

Typical (Left) Axial T2WI MR shows interdigitating gyri along the posterior interhemispheric fissure (open arrow), polygyria (arrow). (Right) Axial T2WI MR shows interdigitation (arrow) of gyri due to dehiscent falx (open arrow). Multiple subcortical heterotopias (curved arrow) are seen. Note too many small, short gyri (" stenogyria").

Typical (Left) Sagittal T7 WI MR shows "cascade" (open arrow) of vermis and medullary kink and spur. Pons and 4th ventricle (arrow) are caudally displaced and elongated. Clivus (curved arrow) is scalloped. (Right) Coronal T2WI MR shows "towering" cerebellum due to upward herniation (open arrows) through dehiscent incisural leaves. Deficiency of medial occipital tissue in region of calcar avis (arrow).

Congenital Malformations

1 16

Sagittal T7WI MR shows occipital encephalocele, beaked tectum (arrow) and large massa intermedia.

Abbreviations

• Cisterns, 4th ventricle, dural sinuses (50%) o Hydrocephalus; occasionally absent ventricles o Chiari 2 features • T2WI: Tissues in sac may be bright (gliosis) • MRV: ± Veins in cephalocele

and Synonyms

• Chiari III, Ch 3

Definitions • High cervical/occipital meningoencephalocele intracranial Chiari 2 malformation

+

General Features • Best diagnostic clue: Low occipital, high cervical meningoencephalocele • Size: Variable

CT Findings • NECT o Occipital squama defect ~ may involve high cervical vertebrae o Bony features of Chiari 2 • Small posterior cranial fossa, scalloped clivus, lacunar skull

MR Findings • TIWI o Sac contents • Meninges, cerebellum,

Axial T7WI MR shows dysplastic cerebellum and occipital encephalocele. Note that the venous sinuses (arrows) lie intracranially

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Sag Tl WI and MR venogram

Isolated occipital encephalocele • Lack intracranial

findings of Chiari 2

Other occipital encephaloceles • Iniencephaly: Occipital defect, ectatic foramen magnum +/- encephalocele, dorsal medullary cleft, cervical dysraphism/Klippel-Feil, severe cervicothoracic lordosis, fixed retroflexion of head • Syndromic occipital encephalocele o Meckel-Gruber: Occipital encephalocele, multicystic kidney, polydactyly o Dandy-Walker malformation, Goldenhar-Gorlin, MURCS (Mullerian, renal, cervical-spine), Walker-Warburg, amniotic band

± brain stem

DDx: Occipital Encephaloceles

Occ Cephalocele

C-O-Parietal Cele

o Walker + Cele

Congenital Malformations

Parietal Cele

CHIARI3 1

Key Facts Terminology

Top Differential

• Chiari III, Ch 3 • High cervical/occipital meningoencephalocele intracranial Chiari 2 malformation

• Isolated occipital encephalocele +

Imaging Findings • • • •

Sac contents Cisterns, 4th ventricle, dural sinuses (50%) Hydrocephalus; occasionally absent ventricles Chiari 2 features

Diagnoses

Pathology • Rare form of Chiari malformations

Clinical Issues • Cerebrospinal fluid diversion • Resect or repair sac (most structures in sac are non-functioning) • Mechanical traction brainstem, respiratory deterioration, lower cranial nerve dysfunction

IPATHOI..O~¥ General Features • General path comments o High cervical-occipital meningoencephalocele with herniated cerebellar tissue and caudal displacement of brainstem o Embryology-anatomy • Failure of enchondral bone induction by incomplete closure neural tube • Failure of fusion of ossification centers • Parietal extension: Faulty induction or pressure erosion by sac • Genetics o Nearly half NTD cases have 677C ~ T mutation on methylene-tetra-hydrofolate reductase (MTHFR) gene • Especially occipital encephalocele or extensive spina bifida • Leads to t amniotic homocysteine levels • Etiology o Etiologies NTD • Maternal dietary folate deficiency; folate antagonists (anti epileptics) • Toxins: Tripterygium wilfordii (Chinese herbs), arsenic • Maternal hyperthermia • Epidemiology o Rare form of Chiari malformations o 1.5-1/150 of all Chiari cases

Demographics • Age: Newborns • Gender: Girls over represented (as in all NTDs)

Natural History & Prognosis • Proportional to amount and type of herniated tissue

Treatment • Cerebrospinal fluid diversion o Diversion pre-resection sac may allow decreased tension on brain stem • Resect or repair sac (most structures in sac are non-functioning) o Beware venous structures and brainstem!

I DIA~NOSTIC

CHIECKI..IST

Consider • Chiari 3 in newborn with occipital encephalocele

I SIEI..IECTIEDRIEFIERIENCIES 1.

2. 3.

Caldarelli M et al: Chiari type III malformation. Childs Nerv Syst 18(5):207-10, 2002 Castillo M et al: Chiari III malformation: Imaging features. A]NR 13:107-13, 1992 Cohen MM et al: Syndromes with cephaloceles. Teratology 25(2):161-72, 1982

Gross Pathologic & Surgical Features • Sac contents: Disorganized cerebellum, occasionally occipital/parietal brain tissues

Microscopic

IIMA~IE ~AI..I..IERY

Features

• Tissues in sac o Disorganized (neuronal migration anomalies, cortical dysplasias) • Lining of sac may show gray matter heterotopias

I CI..INIGAI..

ISSI.JIES

Presentation • Most common signs/symptoms: Occipital encephaloceles, microcephaly • Discovered by fetal sonography/MRI or at birth • Developmental delay, spasticity, hypotonia, seizures

(Left) 3D CT of midline occipital squama and upper cervical defect (arrows). (Right) Axial T1WI MR shows brainstem!cerebellum protruding through defect (white arrow) (Courtesy S. Blaser, MO).

Congenital Malformations

17

CALLOSAL DYSGENESIS 18

Coronal graphic shows corpus callosal agenesis with widely spaced lateral ventricles (arrows), high riding 3rd ventricle and "Probst bundles" (open arrows) along the lateral ventricles.

Abbreviations

• Genu • Body, isthmus • Splenium

and Synonyms

• Agenesis/dysgenesis ACC

corpus callosum (CC), agen CC,

Definitions • One or all segments of CC absent (if partial, body remains)

General Features • Best diagnostic clue o Axial: Parallel lateral ventricles o Coronal: "Trident" anterior horns resemble "viking helmet" or "moose head" • Location: Midline anomaly • Size o CC remnants vary in size, shape • Remnant may be paper thin or bulbous • Prior to myelin maturation, may be difficult to define • Morphology o CC segments front to back • Lamina rostralis (unmyelinated) • Rostrum (myelinated)

DDx: Incomplete

Partial Absence

Coronal T2WI MR in fetus shows trident shaped lateral ventricles, agenesis of Cc, age appropriate smooth cortex, "Probst bundle" (curved arrow) and vertical hippocampus (arrow).

Radiographic Findings • Radiography o Orbital hypertelorism o Rim calcified lipoma (if present)

CT Findings • NECT o Lateral ventricles are key to diagnosis • Parallel (non-converging) • Widely separated o Persistent fetal shape • Occipital horns often dilated (colpocephaly) • Pointed frontal horns o Variable findings • Midline cyst, calcified lipoma, high-riding 3rd ventricle • CTA o "Meandering" anterior cerebral arteries (ACAs) o ACAs course directly upwards in interhemispheric fissure

MR Findings • TlWI o Sagittal • Radially arrayed gyri "point to" 3rd ventricle

Visualization of the Corpus Callosum

Callosotomy

Callosotomy

Congenital Malformations

Stretched

CALLOSAL DYSGENESIS

1

Key Facts Terminology

Top Differential

• Agenesis/dysgenesis corpus callosum (CC), agen CC, ACC • One or all segments of CC absent (if partial, body remains)

• Destruction of CC • Stretched CC (e.g., hydrocephalus)

Imaging Findings

• •

•

Pathology • Most common anomaly seen with other central nervous system (CNS) malformations

• Axial: Parallel lateral ventricles • Coronal: "Trident" anterior horns resemble "viking helmet" or "moose head" • Occipital horns often dilated (colpocephaly) • Radially arrayed gyri "point to" 3rd ventricle • Probst bundles: Compact longitudinally oriented white matter tracts, brighter than other myelin on TlWI

•

Diagnoses

• Absent cingulate gyrus • Exquisite demonstration of lipoma if present o Coronal • "Trident-shaped" anterior horns • Elongated foramina of Monro • "Keyhole" temporal horns & vertical hippocampi • Probst bundles: Compact longitudinally oriented white matter tracts, brighter than other myelin on TlWI T2WI o Probst bundles • Represent non-crossing commissural fibers that would have formed CC • Darker than other myelin on T2WI • Indent medial ventricular walls • Course front to back, not side to side (across midline) o Heterotopias and cortical dysplasias not uncommon T2* GRE: Calcified rim of lipoma DWI: DTI: Fiber tracts from all brain regions converge on remnant of CC if partial, form Probst bundles if complete agen MRA o ACAs "meander", no CC genu to curve around o +/- Azygous ACA

Clinical Issues • Gender: If isolated finding M > F • Sporadic/isolated ACC: 75% normal or near normal at 3 years • Subtle cognitive defects become apparent with increasing complexity of school tasks

Imaging Recommendations • Best imaging tool: MR • Protocol advice o Multiplanar MR (look for additional malformations) o If MR unavailable, multiplanar US or CT will diagnose ACC

I DIFFERENTIAL DIAGNOSIS Destruction of CC • Surgery (callosotomy), trauma o Acquired =} interhemispheric disconnection syndrome • Hypoxic ischemic encephalopathy (HIE), infarcts • Metabolic (Machiafavi-Bignami with necrosis, longitudinal splitting of cc

Stretched CC (e.g., hydrocephalus) • Thinned CC but all parts present • Severe hydrocephalus often present

Immature CC • Pre-myelinated CC may be difficult to confirm, look for cingulate gyrus

• MRV

o Occasional midline venous anomalies • Persistent falcine sinus common

Ultrasonographic

I Pr\THOlOG¥

Findings

General Features

• Real Time o Coronal • Absent CC • Trident lateral ventricles • Widely spaced lateral ventricles, colpocephaly o Sagittal • Radially arranged gyri "point to" 3rd ventricle • Color Doppler: ACAs wander between frontal lobes

Angiographic

Findings

• Conventional o ACAs don't conform to normal CC shape o +/- Azygous ACA

• General path comments o Associated syndromes/malformations common (50-80%) • Midline anomalies: Lipoma, dorsal/interhemispheric cysts, inferior vermian hypoplasia • Ocular/spinal/facial anomalies • Cortical maldevelopment: Heterotopias, schizencephaly, lissencephaly o Embryology • CC forms in midline lamina between 8-20 fetal weeks

Congenital Malformations

19

CALLOSAL DYSGENESIS

1 20

• Genetics o Genetics of associated/syndromic CC anomalies • Mendelian syndromes, chromosomal anomalies (trisomy 13) • Midline anomalies (Dandy Walker, Arnold-Chiari) • Malformations of embryonic forebrain occurring prior to CC formation (holoprosencephaly, frontal encephaloceles) • Syndromes/anomalies with mutations in neural adhesion molecules (11CAM) guiding axonal outgrowth and pathfinding • Etiology o Axons fail to form (rare, seen only in severe cortical malformations like cobblestone lissencephaly) o Axons not guided to midline (mutations in adhesion molecules) o Axons reach midline but fail to cross (absence or malfunction of midsagittal guiding "substrate") o Axons turn back, form large aberrant, longitudinal fiber bundles (Probst bundles) o Miscellaneous • Toxic: Fetal alcohol exposure may affect 11 neuronal cell adhesion molecules • Infection: In-utero cytomegalovirus (CMV) • Inborn errors of metabolism: Non-ketotic hyperglycinemia, PDH deficiency, maternal phenylketonuria (PKU), Zellwegers • Epidemiology o 0.5-70 per 10,000 live births o 4% of CNS malformations o Can be isolated (often males), or associated with other CNS malformations • Associated abnormalities o Most common anomaly seen with other central nervous system (CNS) malformations • Too many syndromes to count!

Gross Pathologic & Surgical Features • Leaves of septum pellucidum laterally displaced to form membranous roof of lateral ventricles o Project between fornices, Probst bundles • Probst bundles formed by longitudinal callosal bundle o Only form if callosal neurons present o Variable sized bundles smaller than normal CC o Covered with leptomeninges

Microscopic

Features

• Variability of signal ( !T1WI over time) and size (i over time) due to maturation of axonal cytoskeleton

Staging, Grading or Classification Criteria • Complete (agenesis) vs partial/variable

(dysgenesis)

I CI.IN ICA.I.ISSl..JES

• Gender: If isolated finding M > F

Natural History & Prognosis • Sporadic/isolated ACC: 75% normal or near normal at 3 years o Subtle cognitive defects become apparent with increasing complexity of school tasks • ACC + associated/syndromic anomalies = worst

Treatment • Treat associated endocrine deficiencies, seizures

Consider • Syndromic associations common • Presence of congenital malformation inherited disorder of metabolism

Image Interpretation

does not exclude

Pearls

• Don't stop with the obvious • Look for additional lesions (they are commonly present)

I SELECTED REFERENCES Lee SK et al: Diffusion tensor MR imaging visualizes the altered hemispheric fiber connection in callosal dysgenesis. AJNR Am J Neuroradiol. 25(1): 25-28, 2004 2. Moutard M-L et al: Agenesis of corpus callosum: Prenatal diagnosis and prognosis. Childs Nerv Syst 19:471-476, 2003 3. Kuker W et al: Malformations of the midline commissures: MRI findings in different forms of callosal dysgenesis. Eur Radiol. 2003 13(3): 598-604. Epub, 2002 Sato N et al: MR evaluation of the hippocampus in patients 4. with congenital malformations of the brain. AJNR Am J Neuroradiol. 22(2): 389-93, 2001 5. Giedd IN et al: Development of the human corpus callosum during childhood and adolescence: a longitudinal MRI study. Prog Neuropsychopharmacol BioI Psychiatry. 23(4): 571-88, 1999 6. Pirola B et al: Agenesis of the corpus callosum with Probst bundles owing to haploinsufficiency for a gene in an 8 cM region of 6q25. J Med Genet. 35(12): 1031-3, 1998 7. Kier EL et al: The lamina rostralis: modification of concepts concerning the anatomy, embryology, and MR appearance of the rostrum of the corpus callosum. AJNR Am J Neuroradiol. 18(4): 715-22, 1997 8. Dobyns WB: Absence makes the search grow longer. (Editorial) AmJ Hum Genet 58:7-16,1996 9. Kier EL et al: The normal and abnormal genu of the corpus callosum: An evolutionary, embryologic, anatomic, and MR analysis. AJNR 17:1631-41,1996 10. Pujol J et al: When does human brain development end? Evidence of corpus callosum growth up to adulthood. Ann Neurol. 34(1): 71-5, 1993 1.

Presentation • Most common signs/symptoms o Seizures, developmental delay, microcephaly o Hypopituitarism hypothalamic malfunction • Clinical profile: Hypertelorism

Demographics • Age: Any age, usually identified early childhood

Congenital Malformations

1 21

Typical (Left) Sagittal T2WI MR

shows complete agenesis of the corpus callosum and a radial array (arrow) of gyri "pointing" to the 3rd ventricle. (Right) Sagittal sonography shows radially arranged gyri "pointing" (arrow) to the third ventricle.

Typical (Left) Coronal T2WI MR shows agenesis of the corpus callosum, trident shaped lateral ventricles, vertical hippocampi (open arrow), enlarged, "keyhole" shaped temporal horns and Probst bundles (curved arrow). (Right) Axial T2WI MR shows parallel, widely spaced lateral ventricles. Note adjacent Probst bundle (open arrow).

Typical (Left) Axial NECT with

widened "windows" shows colpocephaly, calcified (arrow) midline lipoma that extends through choroid fissures into lateral ventricles (open arrows). (Right) Axial TlWI MR shows parallel ventricles, colpocephaly, and a midline lipoma. Note lipoma (arrow) protruding into the lateral ventricles.

Congenital Malformations

22

Coronal graphic shows CC agenesis with a bulky tubonodular-type interhemispheric lipoma (open arrow) that extends into lateral ventricles (arrows), encasing ACAs (curved arrow).

Abbreviations • Intracranial

and Synonyms

lipoma (lCL); lipomatous

hamartoma

Definitions • Mass of mature non-neoplastic adipose tissue o CNS lipomas are congenital malformations, not true neoplasm o Lipoma variants in the CNS include: Angiolipoma, hibernoma, osteolipoma

General Features • Best diagnostic clue: Well-delineated lobulated extra-axial mass with fat attenuation/intensity • Location o Midline location common o 80% supratentorial • 40-50% interhemispheric fissure (over corpus callosum; may extend into lateral ventricles, choroid plexus) • 15-20% suprasellar (attached to infundibulum, hypothalamus) • 10-15% pineal region (usually attached to tectum)

DDx: lipoma

Ossified Falx

Sagittal TlWI MR shows a classic curvilinear interhemispheric lipoma (arrows). Other than mild hypoplasia of the splenium, the CC appears normal.

• Uncommon: Meckel cave, lateral cerebral fissures, middle cranial fossa o 20% infratentorial • Cerebellopontine angle (may extend into lAC, vestibule) • Uncommon: Jugular foramen, foramen magnum • Size: Varies from tiny to very large • Morphology o Lobulated pial-based fatty mass that may encase vessels & cranial nerves o Two kinds of interhemispheric lipoma • Curvilinear type (thin ICL curves around CC body, splenium) • Tubulonodular type (bulky mass; frequent CaH, usually associated with CC agenesis)

Radiographic Findings • Radiography o Usually normal o Very large interhemispheric lipomas may show low density o Tubulonodular lipomas may show rim Ca++

CT Findings • NECT o -50 to -100 H (fat density) o Ca++ varies from none to extensive • Present in 65% of bulky tubulonodular lipomas

(T1 Shortening)

Pineal Teratoma

Ruptured Dermoid

Congenital Malformations

Thrombosed Aneurysm

CC

LIPOMA 1

Key Facts Terminology

Top Differential

• Mass of mature non-neoplastic adipose tissue • CNS lipomas are congenital malformations, not true neoplasm

• • • •

Imaging Findings • Best diagnostic clue: Well-delineated lobulated extra-axial mass with fat attenuation/intensity • 40-50% interhemispheric fissure (over corpus callosum; may extend into lateral ventricles, choroid plexus) • -50 to -100 H (fat density) • Ca++ varies from none to extensive • Standard SE: Hyperintense on TlWI • Becomes hypointense with fat suppression • Standard SE: Hypointense with striking chemical shift artifact (CSA) on T2WI • Rare in posterior fossa, para sellar lesions • CECT: Doesn't enhance • CTA: May demonstrate aberrant ACA course in interhemispheric CC lipoma associated with callosal dysgenesis

Diagnoses

Dural dysplasia Dermoid Teratoma Lipomatous differentiation/transformation neoplasm • Subacute hemorrhage

23

of

Pathology • Cranial, spinal intradural fat is a congenital anomaly (not a true neoplasm) • Persistence, maldevelopment of embryonic meninx primitiva

I DIFFERENTIAl.. DIAGN0818 Dural dysplasia • Fat not normally found inside dura • Metaplastic ossified dura may contain fat

MR Findings

Dermoid

• TlWI o Standard SE: Hyperintense on Tl WI o Becomes hypo intense with fat suppression • T2WI o Standard SE: Hypointense with striking chemical shift artifact (CSA) on T2WI • Round/linear "filling defects" present where vessels, cranial nerves pass through lipoma • May show low signal intensity foci (Ca++) o FSE: Iso- to hyperintense (j-coupling) • PD/lntermediate o Standard SE: Iso- to hyperintense (depending on TR/TE) • Striking CSA • STIR: Hypointense • FLAIR: Hyperintense • DWI: Diffusion tensor imaging visualizes altered fiber connections if associated callosal dysgenesis present • Tl C+: Doesn't enhance • MRA: May show aberrant ACA in callosal agenesis

• Density usually 20 to 40 H • Signal intensity usually more heterogeneous than lipoma • Rupture with cisternal fat droplets common • Usually no associated malformations (common with lipoma) • Dermoids often calcify, lipomas in locations other than interhemispheric don't

Ultrasonographic

Findings

• Real Time o Generally hyperechoic o May show other fetal anomalies (CC agenesis, etc)

Angiographic

Findings

• Conventional o ACA courses directly superiorly if CC agenesis present o Arteries & veins often embedded within lipoma

Imaging Recommendations • Best imaging tool: MR • Protocol advice: Add fat suppression confirmation

sequence for

Teratoma • Locations similar to lipoma • Tissue from all 3 embryonic germ layers o May have prominent adipose component o Other: Mucous cysts, chondroid nodules, bony spicules o Teeth, well-formed hairs rarely present • Imaging appearance usually more heterogeneous o May show foci of contrast-enhancement

Lipomatous differentiation/transformation neoplasm • May occur occasionally in neuroectodermal tumors (PNETs, ependymoma, gliomas) • Cerebellar liponeurocytoma o Newly-recognized mixed mesenchymal/neuroectodermal posterior fossa neoplasm o Primarily hypointense on Tl WI, mixed with hyperintense foci o Patchy, irregular enhancement • Other neoplasms with prominent lipomatous elements o Meningioma (lipomatous transformation uncommon) o Metastases tumor (rare)

Congen ital Malformations

of

1 24

Subacute hemorrhage

Demographics

• Tl shortening can be confused with lipoma • Use T2* (hemorrhage blooms), fat-saturation (hemorrhage doesn't suppress)

• Age: Any age • Gender: M = F • Ethnicity: None known

Natural History & Prognosis General Features • General path comments o Fat not normally present in CNS o Cranial, spinal intradural fat is a congenital anomaly (not a true neoplasm) • Genetics o No known defects in sporadic ICL o Occurs in encephalocraniocutaneous lipomatosis, a congenital neurocutaneous syndrome • Etiology o Persistence, maldevelopment of embryonic meninx primitiva • Normally differentiates into leptomeninges, cisterns • Maldifferentiates into fat instead o Developing pia-arachnoid invaginates through embryonic choroid fissure • Explains frequent intraventricular extension of interhemispheric lipomas • Epidemiology: < 0.5% of all intracranial tumors (not true neoplasm) • Associated abnormalities o Most common: Interhemispheric lipoma + corpus callosum anomalies o Other congenital malformations • Cephaloceles • Closed spinal dysraphism o Encephalocraniocutaneous lipomatosis => Fishman syndrome o Pai syndrome => facial clefts, skin lipomas; occasional ICLs, usually interhemispheric

Gross Pathologic & Surgical Features • Yellow lobulated fatty mass attached to leptomeninges, sometimes adherent to brain • Cranial nerves, arteries/veins pass through lipoma

Microscopic

Features

• Identical to adipose tissue elsewhere • Cells vary slightly in shape/size, measure up to 200 microns • Occasional nuclear hyperchromasia • Mitoses rare/absent • Liposarcoma = extremely rare malignant intracranial adipose tumor

Presentation • Most common signs/symptoms o Usually found incidentally at imaging, autopsy o Rare: Cranial neuropathy (vestibulocochlear dysfunction, facial pain), seizures (associated with other congenital anomalies)

• Benign, usually stable • May expand with corticosteroids o High-dose, long-term administration neural compressive symptoms

may result in

Treatment • Generally not a surgical lesion; high morbidity/mortality • Reduce/eliminate steroids

I DIAGNOSTIC

CHECKLIST

Consider • Could high signal on T1WI be due to other substances with short T1 (e.g., subacute hemorrhage)?

Image Interpretation

Pearls

• When in doubt, use fat-saturation I SELECTED

sequence

REFERENCES

1. Lee SKet al: Diffusion tensor MR imaging visualizes the altered hemispheric fiber connection in callosal dysgenesis. AJNR25: 25-8, 2004 2. Gaskin CM et al: Lipomas, lipoma variants, and well-differentiated liposarcomas (atypical lipomas). AJR 182: 733-9, 2004 3. Tankere F et al: Cerebellopontine angle lipomas: report of four cases and review of the literature. Neurosurg 50: 626-31, 2002 4. Fitoz S et al: Intracranial lipoma with extracranial extension through foramen ovale in a patient with encephalocraniocutaneous lipomatosis syndrome. Neuroradiol44: 175-8, 2002 5. Kiymaz N et al: Central nervous system lipomas. Tohoku J Exp Med. 198: 203-6, 2002 6. Kurt G et al: Hypothalamic lipoma adjacent to mammillary bodies. Childs Nerv Syst 18: 732-4, 2002 Ickowitz V et al: Prenatal diagnosis and postnatal follow-up 7. of peri callosal lipoma: Report of seven new cases. AJNR 22: 767-72,2001 8. Feldman RP et al: Intracranial lipoma of the sylvian fissure. Case report and review of the literature. J Neurosurg. 94(3):515-9,2001 9. Alafaci C et al: Trigeminal pain caused by a cerebellopontine-angle lipoma. Case report and review of the literature. J Neurosurg Sci. 45(2):110-3, 2001 10. Kieslich M et al: Midline developmental anomalies with lipomas in the corpus callosum region. J Child Neurol. 15(2):85-9, 2000 11. Ichikawa T et al: Intracranial lipomas: demonstration by computed tomography and magnetic resonance imaging. J Nippon Med Sch. 67(5):388-91, 2000 12. Amor DJ et al: Encephalocraniocutaneous lipomatosis (Fishman syndrome): a rare neurocutaneous syndrome. J Paediatr Child Health. 36(6):603-5, 2000

Congenital Malformations

1 25

Typical (Left) Sagittal Tl WI MR shows a small interhemispheric lipoma (arrows) above the corpus callosum, found incidentally at MR imaging in this patient with headache. (Right) Sagittal Tl WI MR with fat-saturation shows complete signal suppression (open arrows), confirming the diagnosis of intracranial lipoma.

(Left) Sagittal TlWI MR shows a well-circumscribed high signal lesion in the pineal region (arrow). The patient was asymptomatic. (Right) Axial gross pathology shows a quadrigeminal lipoma (arrow) with classic yellowish, slightly lobulated appearance. The lesion was found incidentally at autopsy (Courtesy E.T. Hedley-Whyte, MO).

Variant (Left) Sagittal Tl WI MR shows a small hypothalamic

lipoma (arrow), found incidentally in this patient with headache and normal neurologic examination. Also note the "empty sella". (Right) Sagittal TlWI MR shows an enormous lipoma occupying most of the posterior fossa and cervical spine (open arrows). Note large cutaneous lipoma (arrow). Encephalocraniocutaneous lipomatosis.

Congenital Malformations

DANDY WALKER SPECTRUM 26

Sagittal graphic shows enlarged posterior fossa, elevated torcular Herophili (arrow), superior rotation of small vermian remnant (open arrow) over large cyst with thin wall (curved arrow).

Abbreviations

General Features

and Synonyms

• Dandy Walker (DW) spectrum (DWS); DW complex (DWC); "classic" DW malformation (DWM); DW variant (DWV) • Persistent Blake pouch cyst (BPC), mega cisterna magna (MCM)

Definitions • DWS represents a broad spectrum of cystic posterior fossa (PF) malformations o 4th ventriculocele variant of DWM • DWM in which large cyst erodes occipital bone =} "encephalocele" OR encysted 4th ventricle (4th V) herniates into occipital encephalocele o "Classic" DWM • Cystic dilatation of 4th V =} enlarged PF, superiorly rotated vermian remnant o DW "variant" • Vermian hypoplasia + partial obstruction 4th V o BPC • Failure of regression of BPC + compression/obliteration of basal cisterns may explain appearance of "open 4th ventricle" oMCM • Enlarged cisterna magna communicates freely with 4th V, basal subarachnoid spaces

Classic OWS

Sagittal T2WI MR shows large rotated vermian remnant. There is a hypoplasdc fastigial crease (curved arrow). The cyst wall is visible (arrow) and the posterior fossa is expanded.

OW Variant

• Best diagnostic clue o DWM: Large PF + big cerebrospinal fluid (CSF) cyst, normal 4th ventricle (V) absent o DWV, BPC: Failure of "closure" of 4th V • Location: Posterior fossa • Size: Varies from slightly enlarged cisterna magna to huge PF cyst • Morphology o DWS (from most to least severe) • 4th ventriculocele (10-15% of cases): DWM plus posterior outpouching • "Classic" DWM: Small hypoplastic vermis superiorly rotated by cyst, torcular arrested in fetal position (cyst mechanically hinders caudal migration) • DWV (mild form of DW complex): Variable vermian hypoplasia, no or small cyst, normal sized PF/brainstem, "keyhole" vallecula • BPC: "Open" 4th ventricle communicates with cyst, basal cisterns +/- completely effaced • MCM: Large PF, normal vermis/4th ventricle, cistern crossed by falx cerebelli, tiny veins

Radiographic Findings • Radiography

Open 4th Ventricle

Congenital Malformations

Retro CBLL Cyst

DANDY WALKER SPECTRUM ,-----------------------------------------------,

1

Key Facts

Terminology

Top Differential

• Dandy Walker (DW) spectrum (DWS); DW complex (DWC); "classic" DW malformation (DWM); DW variant (DWV) • Persistent Blake pouch cyst (BPC), mega cisterna magna (MCM) • DWS represents a broad spectrum of cystic posterior fossa (PF) malformations • 4th ventriculoceIe variant of DWM

• PF arachnoid cyst (retrocerebellar, supravermian or in cerebellopontine angle) • Congenital vermian hypoplasia (prototype = Joubert anomaly) • Isolated 4th ventricle • 2/3 have associated CNS/extracranial

Imaging Findings

Clinical Issues

• DWM: Large PF + big cerebrospinal fluid (CSF) cyst, normal 4th ventricle (V) absent • DWV, BPC: Failure of "closure" of 4th V

• DWM: Macrocephaly, bulging fontanel, etc • Classic DWM: Early death common (up to 44%)

o Enlarged calvarium, particularly posterior fossa o DWM: Lambdoid-torcular inversion (transverse sinus grooves elevated above lambda) • Sinuses are originally above lambda in fetus, cyst mechanically hinders descent

Diagnoses

27

Pathology anomalies

• FLAIR: Very slight differentiation between cyst, compressed basal cisterns may be present • DWI: Very slight diffusion restriction in cyst may be seen • MRV: Elevated torcular Herophili (DWM)

CT Findings

Ultrasonographic

• NECT o DWM: Large posterior fossa • Variable-sized cyst communicates with 4th V • Torcular-lambdoid inversion (torcular above lambdoid suture) o Occipital bone may appear scalloped, remodeled with all DWS types, including MCM

• Real Time: Fetal diagnosis of DWM and DWV possible

Findings

Imaging Recommendations • Best imaging tool: MR best characterizes severity, associated anomalies • Protocol advice: Routine MR imaging (thin sagittal views crucial)

MR Findings • TIWI o Sagittal DWM • Floor 4th V present • 4th v opens dorsally to variable-sized CSF cyst • Cyst wall difficult to discern • Vermian remnant (variable presence of fastigium, fissures) rotated up, over cyst • +/- Remnant fused to tentorium • Elevated torcular with high/steeply sloping tentorium (classic) o Sagittal DWV • Smaller PF +/- cyst • 4th V "open" with partial rotation vermis, presence of fastigium and fissures variable o Sagittal BPC • Rotated but normal-appearing vermis • Free communication of 4th V with prominent inferior CSF space • Basal cisterns compressed posteriorly or effaced o Sagittal MCM • Normal vermis (not rotated/hypoplastic) • 4th V is "closed" • T2WI o Associated anomalies • Cortical dysplasia, heterotopias, myelination delays (syndromic DWS)

I DIFFERENTIAL DIAGNOSIS DW spectrum • "In-between" cases common

PF arachnoid cyst (retrocerebellar, supravermian or in cerebellopontine • • • •

angle)

Included in DW spectrum by some authors Normal 4th V compressed or displaced AC not traversed by falx cerebelli, tiny veins ACs lined by arachnoid cells/collagen

Congenital vermian hypoplasia (prototype Joubert anomaly)

=

• Episodic hyperpnea, oculomotor apraxia, retinal dystrophy; +/- renal cysts, hepatic fibrosis • Split vermis, "bat-wing" 4th V, mesencephalon shaped like "molar-tooth"

Isolated 4th ventricle • Inferior 4th ventricle "closed" versus "open" in DWM/DWV on sagittal view • May be normal or 1 size

Congenital Malformations

DANDY WALKER SPECTRUM 1 28

Demographics • Age: DWM: 80% diagnosed by 1 Y • Gender: M ::0; F

General Features • General path comments o Embryology • Common association DWM/DWV with facial, cardiovascular anomalies suggests onset between formation, migration of neural crest cells (3rd-4th post-ovulatory week) • Genetics o Majority sporadic, X-linked DWM reported o Many, many syndromes with DWS • Chromosomal or midline anomalies; PHACE (facial hemangiomas, coarctation, DW in 81 %) • Etiology o Rhombencephalic roof divides into cephalic (anterior membranous area AMA) and caudal (posterior membranous area PMA) • AMA invaded by neural cells =}becomes CBLL • PMA expands then disappears to form outlet foramina of 4th V o Hindbrain development arrest • Defective formation AMA and PMA =} DWM and DWV • Defective PMA only =} BPC and MCM • Epidemiology o 1:25,000-100,000 births o Accounts for 1-4% of all hydrocephalus cases • Associated abnormalities o 2/3 have associated CNS/extracranial anomalies • Craniofacial, cardiac/urinary tract anomalies, polydactyly, orthopedic and respiratory problems

Gross Pathologic & Surgical Features • DWM: Large posterior fossa with big CSF-containing cyst o Inferior margin vermian remnant continuous with cyst wall o 4th V choroid plexus absent or displaced into lateral recesses

Microscopic

Natural History & Prognosis • Classic DWM: Early death common (up to 44%) • Cognitive outcome dependent upon associated syndromes or supratentorial anomalies/hydrocephalus and completeness of residual vermis o Intelligence normal in 35 to 50% of classic DWM • If small remnant without fissures or fastigium: Seizures, developmental delay, poor motor skills/balance • If large remnant with normal lobulation and fastigium and normal supratentorial brain: Good outcome even if classic DWM

Treatment • CSF diversion IF hydrocephalus: shunt/marsupialization

I.D1AGNt)SIl(J(Jt-(E()ls:lIS-r Consider • Many associated syndromes,

Image Interpretation

• DWM: Outer cyst wall layer continuous with leptomeninges o Intermediate stretched neuroglial layer is continuous with vermis o Inner layer of glial tissue lined with ependyma/ependymal nests o Anomalies of inferior olivary nuclei/corticospinal tract crossings

Staging, Grading or Classification Criteria

1.

2.

4. 5.

6.

7.

8. 9.

• Most common signs/symptoms o DWM: Macrocephaly, bulging fontanel, etc o MCM: Incidental finding • Clinical profile: Marked heterogeneity in genetic, clinical findings

Pearls

I SELECTED REFERENCES

• Spectrum: DWM with 4th ventriculocele (most severe) =} classic DWM=} DWV =} BPC =} MCM (mildest)

Presentation

"look-alikes"

• Presence of fastigium/vermian lobulation predicts good outcome • Thin sagittal views in Tl-, T2WI crucial for delineation, diagnosis

3.

Features

VP shunt (+/-) cyst

ten Donkelaar HJ et al: Development and developmental disorders of the human cerebellum. J Neurol 250(9):1025-36, 2003 Klein 0 et al: Dandy-Walker malformation: Prenatal diagnosis and prognosis. Childs Nerv Syst 19(7-8):484-9, 2003 Boddaert N et al: Intellectual prognosis of the Dandy-Walker malformation in children: The importance of vermian lobulation. Neuroradiology 45(5):320-4, 2003 Patel S et al: Analysis and classification of cerebellar malformations. AJNR 23(7):1074-87,2002 Calabro F et al: Blake's pouch cyst: An entity within the Dandy-Walker continuum. Neuroradiology 42(4):290-5, 2000 Kalidasan V et al: The Dandy-Walker syndrome--a lO-year experience of its management and outcome. Eur J Pediatr Surg 5 Suppll:16-8, 1998 Tortori-Donati P et al: Cystic malformations of the posterior cranial fossa originating from a defect of the posterior membranous area. Mega cisterna magna and persisting Blake's pouch: Two separate entities. Childs Nerv Syst 12:303-8, 1996 Pascual-Castroviejo I et al: Dandy-Walker malformation: analysis of 38 cases. Childs Nerv Syst 7(2):88-97, 1991 Barkovich AJ et al: Revised classification of posterior fossa cysts and cyst-like malformations based on the results of multiplanar MR imaging. AJR 153:1289-300, 1989

Congenital Malformations

1 29

Typical (Left) Coronal oblique 3D

MR SPCR reconstruction with removal of the cyst wall shows tentorial elevation and hypoplastic cerebellar hemispheres. The small vermian remnant (arrow) is superiorly rotated. (Right) Axial T2WI MR shows enlarged posterior fossa and hypoplastic cerebellar hemispheres. The vermis is absent.

(Left) Coronal T2WI MR shows "keyhole" configuration formed by large 4th ventricle communicating with large vallecula (arrows). There are hypoplastic cerebellar hemispheres. (Right) Coronal T2WI MR in another child shows Inverted "Y" of elevated tentorium (arrows) and torcular (open arrow).

(Left) Sagittal T2WI MR

shows elevation of the torcular Herophili (arrow). There is expansion of the posterior fossa and formation of a 4th ventriculocele (curved arrow). The vermian remnant is small. (Right) Lateral MR venogram demonstrates angled "transverse" sinuses (curved arrows) rising to the elevated torcular Herophili (arrow) in the same child.

Congenital Malformations

RHOMBENCEPHALOSYNAPSIS 30

Axial graphic shows absence of vermis. There is fusion of folia, interfoliate sulci, dentate nuclei (arrow) and cerebellar white matter (open arrow) across the midline.

Axial T2WI MR in a neonate shows similar features. There is fusion of the dentate nuclei (arrow) and of the folia across the midline (open arrows).

o Narrow diamond or "keyhole" shaped 4th ventricle o Narrowed transverse diameter of cerebellum

Abbreviations

and Synonyms

• Rhombencephalosynapsis

MR Findings

(RES)

Definitions • Congenital fusion of cerebellar hemispheres, dentate nuclei, and superior cerebellar peduncles; vermian agenesis

I.INf;\(jlN(jfINDtNG;~ General Features • Best diagnostic clue: Hypoplastic, single lobed cerebellum • Location: Midline posterior fossa • Size: Narrowed transverse diameter of cerebellum • Morphology: One hemisphere, not two

Radiographic Findings • Radiography o Bilateral lambdoid synostosis => "flattened" occiput o Occasionally associated with holoprosencephaly => hypotelorism or midline facial anomalies/clefts

CT Findings • NECT o Cerebellar hemispheric

• TlWI o Coronal • Fused cerebellar hemispheres: Total or partial • Absent or severely hypoplastic vermis • +/- Septo-optie-dysplasia or holoprosencephaly o Sagittal • Absent primary fissure (usually easy to find in normal cerebellum) • +/- Fastigial recess of 4th ventricle appears upwardly rounded • +/- Aqueductal stenosis => hydrocephalus • +/- Corpus callosum dysgenesis (especially posterior) o Axial • Narrow diamond or "keyhole" shaped 4th ventricle • +/- Holoprosencephaly • T2WI o Transverse folia o Absent posterior cerebellar notch and vallecula o Fused horseshoe-shaped dentate nuclei • May be "apposed, not fused" in mild cases o +/- Cortical dysplasias • FLAIR: No gliosis

fusion

DDx: Transverse Folia

Deformed

Post-shunt

Post-shunt

Partial RES

Congenital Malformations

Partial RES

RHOMBENCEPHALOSYNAPSIS Key Facts Terminology

Pathology

• Rhombencephalosynapsis (RES) • Congenital fusion of cerebellar hemispheres, dentate nuclei, and superior cerebellar peduncles; vermian agenesis

• Likely genetic defect "isthmic organizer" ::} abnormal dorsal patterning • Extremely rare but increasingly recognized on MR • Prosencephalic and midline facial anomalies common

Imaging Findings

Clinical Issues

• Best diagnostic clue: Hypoplastic, single lobed cerebellum • Size: Narrowed transverse diameter of cerebellum • Morphology: One hemisphere, not two • Narrow diamond or "keyhole" shaped 4th ventricle

Top Differential

• Short lifespan usual

Diagnostic Checklist • Remember to define associated supratentorial anomalies

Diagnoses

• Chronic shunting • Congenital vermian hypoplasia

(prototype

==

Joubert)

• T2* GRE: Occasional TORCH-related or dystrophic Ca++ of supratentorial white matter • MRA o Azygous anterior cerebral artery (if holoprosencephaly present) o No posterior circulation arterial anomalies described

Ultrasonographic

•

Findings

• Real Time: Has been reported in fetal sonography (rare)

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Multiplanar

MRI

•

I DIFFERENTIAL DIAGNOSIS Chronic shunting • Distortions especially in Chiari 2 malformation rotation or unilateral herniation

with

Congenital vermian hypoplasia (prototype Joubert) • Vermian agenesis or hypogenesis, hemispheres not fused

=

but cerebellar

Syndromic vs non-syndromic rhombencephalosynapsis • Complicated midline anomaly syndromes • Gomez-Lopez-Hernandez (cerebellotrigeminal dysplasia) o Rhombencephalosynapsis o Trigeminal anesthesia o Midface hypoplasia o Scalp: Bilateral bands of alopecia

I PATHOLOGY General Features • General path comments o Embryology-Anatomy

dermal

•

•

• Failure of induction/differentiation of normal midline structures • Lateral structures relatively preserved Genetics o Likely genetic defect "isthmic organizer" ::} abnormal dorsal patterning • FGF8 and Lmxla genes being considered o Gomez-Lopez-Hernandez syndrome • Likely under-recognized • Inheritance unknown o Anecdotal reports • Interstitial deletion chromosome 2q • Parental consanguinity Etiology o Disturbed early cerebellar development (genetic or acquired): 33-34 days gestation o Maternal environment • Hyperpyrexia • Diabetes • Phencyclidine or alcohol Epidemiology o Extremely rare but increasingly recognized on MR o Approximately SO cases reported Associated abnormalities o Prosencephalic and midline facial anomalies common o Occasional associated extracranial anomalies • Segmentation and fusion anomalies in spine • Cardiovascular (conotruncal) anomalies reported • Variable respiratory, GU anomalies reported • Musculoskeletal anomalies common: Phalangeal and radial-ray

Gross Pathologic & Surgical Features • Usual o Fused cerebellar hemispheres o Fused cerebellar white matter::} large corpus medullare o Absent posterior cerebellar incisura, vallecula o Horseshoe-shaped dentate nuclei o Agenesis or hypogenesis anterior vermis, velum medullare anterior and nuclei fastigii o Hypoplastic posterior vermis: Nodulus may form

Congen ital Malformations

1 31

RHOMBENCEPHALOSYNAPSIS 32

• Often o Supratentorial midline anomalies • Commissural (corpus callosum, anterior commissure) dysgenesis/hypoplasia • Holoprosencephaly or septo-optic dysplasia • Fused inferior colliculij absent dorsal olivary nuclei o Aqueductal stenosis-related hydrocephalus o Craniosynostosis (especially lambdoid) • Rare o Aventriculy (also called synencephaly or telencephalosynapsis)j encysted 4th ventricle

Staging, Grading or Classification Criteria • Isolated or involves supratentorial • Fusion can be partial or total

midline structures

ICtINIC)\l.\IS$lJES Presentation • Most common signs/symptoms o Variable neurological signs • Ataxia, gait abnormalities • Involuntary head movement • Developmental delay • Seizures • Cerebral palsy • Compulsive self-injurious behavior common • Rare: Near normal patients have been discovered at autopsy • Clinical profile o Ataxia o Developmental delay o Variable growth hormone deficiency (depends on supratentorial midline anomalies)

• Remember to define associated supratentorial anomalies

Image Interpretation

Pearls

• Can be simulated by mechanically induced cerebellar deformation in chronically shunted patients

1.

Demaerel P et al: Partial rhombencephalosynapsis. AJNR 25(1):29-31,2004 2. Toelle SP et al: Rhombencephalosynapsis: Clinical findings and neuroimaging in 9 children. Neuropediatrics 33:209-14,2002 3. Patel S et al: Analysis and classification of cerebellar malformations. AJNR23:1074-87,2002 4. Yachnis AT:Rhombencephalosynapsis with massive hydrocephalus: Case report and pathogenetic considerations. Acta Neuropathol103(3):305-6, 2002 5. Brocks D et al: Gomez-Lopez-Hernandez syndrome: Expansion of the phenotype. Am J Med Genet 94(5):405-8, 2000 6. Takanashi J et al: Partial midline fusion of the cerebellar hemispheres with vertical folia: A new cerebellar malformation. AJNR20(6):1151-3, 1999 7. Utsonomiya H et al: Rhombencephalosynapsis: Cerebellar embryogenesis. AJNR 19(3):547-9, 1998 8. Romanengo M et al: Rhombencephalosynapsis with facial anomalies and probable autosomal recessive inheritance: A case report. Clin Genet 52(3):184-6, 1997 9. Isaac M et al: Two cases of agenesis of the vermis of cerebellum, with fusion of the dentate nuclei and cerebellar hemnipheres. Acta Neuropathol 74(3):278-80, 1987 10. Lopez-Hernandez A. craniosynostosis, ataxia, trigeminal anaesthesia and parietal alopecia with pons-vermis fusion anomaly (atresia of the fourth ventricle). Report of two cases. Neuropediatrics 13(2):99-102, 1982

Demographics • Age o Usually found during early infancy or childhood o Rare incidental finding • Gender: No gender or ethnic predilection

Natural History & Prognosis • Short lifespan usual • Occasional survival to early adult life o Developmental delay o Psychiatric disorders (self-injurious, bipolar, hyperactive) • Additional midline supratentorial anomalies and hydrocephalus ~ worse prognosis

Treatment • Treat related hydrocephalus, monitor hypothalamic-pituitary axis

IOIAGNgSTIGGI--iECKEIST Consider • Isolated rhombencephalosynapsis is less common than rhombencephalosynapsis with supratentorial anomalies

Congenital Malformations

RHOMBENCEPHALOSYNAPSIS

1 33

Typical (Left) Axial T2WI MR shows fusion of the interfoliate sulci and of the gray and white matter (arrow) of the folia across the midline. (Right) Coronal T2WI MR shows typical transverse folia (arrow) and sulci.

(Left) Axial NECT shows a "keyhole" shaped 4th ventricle. There is a narrow transverse cerebellar diameter, midline fusion of the cerebellar white matter (arrow) and faint frontal Ca++ (curved arrow). (Right) Axial T2WI MR shows "keyhole" shaped 4th ventricle (arrow) and midline fusion of cerebellar white matter. Note lack of normal vermian tissue and lack of hemispheric separation.

(Left) Sagittal T2WI MR shows slight rounding of the fastigial recess (arrow) and absence of the primary fissure in a child with isolated rhombencephalosynapsis. (Right) Sagittal TlWI MR in a patient with atrophy of an otherwise normal cerebellum shows a sharp fastigial recess (arrow) and a well defined primary fissure (open arrow).

Congenital Malformations

CONGENITAL VERMIAN HYPOPLASIA 34

Sagittal T1WI MR shows vermian remnant (arrows). 4th ventricle and cisterna magna are large. Fastigial point and primary fissure are lacking. The brainstem and pituitary axis are small.

Axial T2WI MR shows the typical "molar tooth" (arrow) appearance of the brainstem. There is clefting of the vermis (curved arrow).

o +/- Pre and postaxial polydactyly o Syndactyly

Abbreviations

and Synonyms

CT Findings

• Congenital vermian hypoplasia (CVH) o Prototype = Joubert syndrome, Joubert-Boltshauser syndrome • Cerebelloparenchymal disorder IV (CPD IV)

Definitions • Inherited hypoplasia or aplasia of vermis characterized by transient episodic hyperpnea, oculomotor abnormalities, ataxia, variable mental retardation

• NECT o Enlarged, "bat-wing" or "open umbrella" 4th ventricle o "Molar-tooth" pons/midbrain • Deficient anterior vermis • Thin or thick superior cerebellar (CBLL) peduncles o "Buttocks sign" • Only narrow cleft separates CBLL hemispheres

MR Findings

General Features • Best diagnostic clue o "Molar tooth" brainstem o "Bat-wing" or " umbrella" shaped 4th ventricle o Cleft vermis • Location: Vermis of cerebellum • Size: Vermian remnant variable size • Morphology: Complex brainstem malformation ~ "molar-tooth" brainstem appearance

Radiographic Findings • Radiography

• TlWI o Above PLUS • +/- Small vermian remnant (if residual, often cleft) • +/- Variable brainstem hypoplasia • Abnormally deep interpeduncular fossa • Midline anomalies common (holoprosencephaly, frontonasal dysplasia, facial clefting) • Pituitary hypoplasia • Enlarged superior ampulla of aqueduct • T2WI o +/- t Signal periventricular white matter o +/- t Signal in decussation of superior CBLL peduncles . o +/- Persistent embryonic vessels along CBLL folIa o +/- Hamartomas or heterotopias

Congenital Malformations

CONGENITAL VERMIAN HYPOPLASIA Key Facts Terminology

• Rhombencephalosynapsis

• Congenital vermian hypoplasia (CVH) • Prototype = Joubert syndrome, Joubert-Boltshauser syndrome • Inherited hypoplasia or aplasia of vermis characterized by transient episodic hyperpnea, oculomotor abnormalities, ataxia, variable mental retardation

Imaging Findings • • • •

"Molar tooth" brainstem "Bat-wing" or " umbrella" shaped 4th ventricle Cleft vermis Size: Vermian remnant variable size

Top Differential • Dandy-Walker

Ultrasonographic

Diagnoses

I PATHOLOGY

Findings

Imaging Recommendations • Best imaging tool: MRI brain • Protocol advice o MRI brain o Abdominal sonogram

I DIFFERENTIAL DIAGNOSIS Dandy-Walker

spectrum (DWS)

Anterior vermian remnant present in DWS Posterior vermian remnant usually remains in CVH Cyst in classic DWS Widely separated CBLL hemispheres in DWV and classic DWS

"CVH-plus" (numerous)

Diagnostic Checklist • Special care in sedation or anesthesia for neuroimaging examinations • Look for fastigial point of 4th ventricle, primary fissure on sagittal views as first clues to diagnosis

spectrum (DWS)

• Real Time o Posterior anomalies difficult to confirm on head ultrasound o Non-cranial ultrasound • Renal anomalies (often cysts) • +/- Hepatic fibrosis • +/- Cardiac anomalies

• • • •

Pathology • Many syndromes with congenital vermian hypoplasia • Joubert syndrome is prototype: Only brain findings on imaging • If more than brain findings = one of many "CVH plus" syndromes: (+ Renal cysts/hepatic fibrosis/ocular abnormalities)

eponymous syndromes

• Mohr; Rischer-Schinzel; Varadi (soft tissue tumors in tongue) • Meckel-Gruber; Dekaban; ectodermal dysplasia/brain cysts; Arima • Senior-Loken: Leber congenital amaurosis plus juvenile nephronophthisis • Coach (includes hepatic fibrosis); cerebello-oculo-hepa to- renal • Look for extra cranial features in all of above

Rhombencephalosynapsis • No vermis, but cerebellar hemispheres

are fused

General Features • General path comments o If Joubert: CVH only o If cerebello-oculo-renal = CVH + some of the following • Renal: Congenital renal cysts; cystic dysplastic kidney, juvenile nephronophthisis NH1; renal cystic disease unlikely in patients without retinal dystrophy • Oculo: Retinal dystrophy similar to Leber congenital amaurosis, chorioretinal colobomata • Other: Congenital hepatic fibrosis; poly- or syn-dactyly; nail hypoplasia; cardiac; cleft palate/bifid uvula; short neck o Embryology-anatomy • Abnormal patterning of midbrain-hindbrain by homeotic genes • Genetics o Autosomal recessive, clinically and genetically heterogeneous o Loci mapping to Chr 9q34.3 OBTS1) and 17p11.2 do not explain all cases in Joubert syndrome o llp12-q13.3 (CORS2) mutation: Cerebello-oculo-renal syndrome • Etiology o Anomaly of mesencephalic/rhombomere 1 development o Possible malposition of isthmic organizer • Epidemiology: 1 in 30,000 - 100,000 (likely under reported) • Associated abnormalities o Many syndromes with congenital vermian hypoplasia • Joubert syndrome is prototype: Only brain findings on imaging • If more than brain findings = one of many "CVH plus" syndromes: (+ Renal cysts/hepatic fibrosis/ocular abnormalities)

Congen ital Malformations

1 35

CONGENITAL VERMIAN HYPOPLASIA 1 36

Gross Pathologic & Surgical Features

I DIAGNOSTIC

CHECKLIST

• CBLL vermian deficiency • +/- Other midline CNS anomalies o Callosal dysgenesis o Posterior pituitary ectopia o Occasional encephalocele

Consider

Microscopic

• Look for fastigial point of 4th ventricle, primary fissure on sagittal views as first clues to diagnosis

• Special care in sedation or anesthesia for neuroimaging examinations

Image Interpretation

Features

• • • • •

Elongated locus coeruleus Lack of decussation of superior CBLL peduncles Dysplastic dentate nuclei Hypoplasia or fragmentation of brainstem nuclei Absent posterior sulcus of medulla with fused fasciculi gracilis and cuneatus • Hypoplasia of middle CBLL peduncles • CBLL heterotopias • Occasional cortical dysplasias

Staging, Grading or Classification Criteria • CVH or "CVH plus"

I SELECTED REFERENCES 1.

2.

3. 4.

I ClINliCAL ••IS5l.JE·S

5.

Presentation • Most common signs/symptoms o Classic: Episodic hyperpnea plus abnormal eye movements (70%+) o Rhythmic tongue protrusion o Triangular shaped mouth stays open o "Cerebellar speech": Hoarse voice/dysarthria o Early hypotonia, ataxia o Maxillary recession, mandibular protuberance with age • Clinical profile o Mental retardation may be severe (majority), autistic-like, or near normal • If near normal, have typical poor judgment o Variable phenotype even within sibships

6.

7.

8.

Gleeson JG et al: Molar tooth sign of the midbrain-hindbrain junction: Occurrence in multiple distinct syndromes. Am J Med Genet. 125A(2):125-34, 2004 Padgett KR et al: Ex vivo high-resolution magnetic resonance imaging of the brain in Joubert syndrome. J Child NeuroI17(12):911-3, 2002 Yachnis AT et al: Neuropathology of Joubert syndrome. J Child NeuroI14(10):655-9, 1999 Quisling RG et al: MRI features and classification of CNS malformations in Joubert syndrome. J Child Neurol 14:628-36, 1999 Satran D et al: Cerebello-oculo-renal syndromes including Arima, Senior-Loken and Coach syndromes: More than just variants of Joubert syndrome. Am J Med Genet 86(5):459-69, 1999 Maria BL et al: Clinical features and revised diagnostic criteria in Joubert syndrome. J Child NeuroI14(9):583-90, 1999 Yachnis AT et al: Cerebellar and brainstem development: An overview in relation to Joubert syndrome. J Child NeuroI14(9):570-3, 1999 Maria BL et al: Molar tooth sign in Joubert syndrome: Clinical, radiologic, and pathologic significance. J Child NeuroI14(6):368-76, 1999

Demographics • Age: Presentation in infancy • Gender: M:F = 2:1 • Ethnicity: Increased in population

Pearls

isolates

Natural History & Prognosis • Neonatal hyperpnea usually (not always) intermitten t/transien t • Hypotonia improves over time o 75% learn to sit o 50% learn to walk • CVH alone Goubert): Poor, significant mental retardation is usual o Likely under-reporting of milder cases • "CVH plus" syndromes: Renal disease may progress to renal failure • Both: Prone to apnea in early life

Treatment • Care in sedation/anesthesia o t Sensitivity to respiratory depressant effects of anesthesia/opioids

Congenital Malformations

CONGENITAL VERMIAN HYPOPLASIA 1 37

Typical (Left) Axial T2WI MR shows small vermian remnant (arrow). The superior cerebellar peduncles (curved arrow) are well seen due to hypoplasia of the usually intervening anterior vermian lobules. (Right) Axial Tl WI MR shows prominent vermian clefting (arrow).

Typical

(Left) Axial T2WI MR shows hypertelorism and frontonasal dysplasia. Note large aqueduct of Sylvius with disturbed flow (curved arrow). Superior CBLL peduncles (arrow) are well seen. CBLL is dysplastic. (Right) Axial TlWI MR shows typical cleft (arrow) leading into the deformed 4th ventricle. The combination gives the appearance of an open "umbrella".

Typical

(Left) Coronal T2WI MR shows apposed cerebellar hemispheres and heterotopic nodule (arrow) embedded within the white matter. (Right) Coronal T2WI MR shows small remnant (open arrow) of the vermis. Abnormal axis due to central up-tilting of the hemispheres. Prominent cisterna magna (curved arrow).

Congenital Malformations

HOLOPROSENCEPHALY 38

Coronal oblique 30 SPCR surface reconstruction shows absence of interhemispheric fissure and fusion of the gyri across the midline.

• Lines drawn tangentially through Sylvian fissures = Sylvian angle (SA) • Anteriorly displaced Sylvian fissures ~ 1 SA • 1 SA ~ 1 severity frontal lobe hypoplasia

ITERMINOl.OGY Abbreviations

and Synonyms

• Holoprosencephaly (HPE) • Formerly called arrhinencephaly

Radiographic Findings

Definitions • Spectrum of congenital structural forebrain anomalies defined by degree of frontal lobe fusion • Most common "brain plus face" malformation o "Face predicts brain": Severe midline anomaly ~ severe HPE o Function predicted by degree of non-separation of brain structures

I IMAGING .FlN.[J1NGS General Features • Best diagnostic clue o Monoventricle + fused (uncleaved) frontal lobes ~ absent anterior midline falx/fissures o Fusion (non-cleavage) diencephalon> basal ganglia (BG) > thalami (THAL) • Location: Predominantly anterior brain process • Morphology o Anomaly defined by degree of frontal lobe fusion

DDx: Holoprosencephaly

MIH Variant

Axial T2WI MR shows fusion of basal ganglia (arrow). The frontal lobe is hypoplastic and cortex and white matter are fused across the midline (open arrow).

• Radiography: Hypotelorism, fused metopic suture or single frontal "plate" of bone, variable degree of microcephaly

CT Findings • NECT o Uncleaved basal nuclei/ventricles; variable absence interhemispheric fissure (IHF) o Ventricles • Lobar: Absent septum pellucidum; formed lateral ventricles including temporal and occipital horns (anterior may be deficient) • Semilobar: Absent septum pellucidum; anterior horns absent, partial occipital and temporal horns • Alobar: Monoventricle, often incompletely covered posteriorly by brain ~ dorsal "cyst" o Skull base/vault • Cleft palate; variable optic canal hypoplasia • Absent or hypoplastic ethmoid sinus, anterior falx (and superior sagittal sinus), crista galli

Variants

MIH, CC-GM Fusion

Lobar HPE, Note Genu

Congenital Malformations

SOD, Note Chiasm

HOLOPROSENCEPHALY

1

Key Facts Terminology

• Marked hydrocephalus

• Holoprosencephaly (HPE) • Spectrum of congenital structural forebrain anomalies defined by degree of frontal lobe fusion • Most common "brain plus face" malformation • "Face predicts brain": Severe midline anomaly => severe HPE

Clinical Issues

Imaging Findings • Monoventricle + fused (uncleaved) frontal lobes

=>

absent anterior midline falx/fissures • Fusion (non-cleavage) diencephalon> basal ganglia (BG) > thalami (THAL) • Location: Predominantly anterior brain process

Top Differential

=

Diagnostic Checklist • HPE variants (lobar, septooptic dysplasia, single central midline incisor) may still present with hypothalamic/pituitary crisis • Sylvian angle (of Barkovich) key to understanding neuroanatomic anomalies

variant (MIH): ZIC2

MR Findings • Tl WI: Corpus callosum (CC) "replaced" by fused anterior brain • T2WI o Delayed myelin maturation in classical HPE, but normal in middle hemispheric variant (MIH) o Following are variable • Degree of frontal lobe hypoplasia, basal nuclei fusion • Presence of dorsal cyst (suprapineal recess) • Degree of hypoplasia or absence olfactory nerves (best seen on coronal views) • Subcortical heterotopia anterior to IHF and subjacent to shallow frontal sulci • DWI: DTI (alobar) demonstrates absence of corticospinal tracts • MRA o Azygous or absent anterior cerebral artery (ACA) o Single midline anterior arterial trunk with fan-like array of arteries over surface of frontal lobe • MRV o Absent superior sagittal, inferior sagittal and straight sinuses o Cortical veins and deep veins drain directly to torcular

Findings

• Real Time: Diagnosable on fetal ultrasound (and fetal MRI) • Color Doppler: Absent superior sagittal sinus, variable absence deep and midline venous structures

Angiographic

• Clinical profile: Mentally retarded microcephalic infant with midline facial anomalies, disturbed endocrine function • Clinical severity relates to degree of hemispheric and deep gray nuclei non-separation (alobar HPE worst)

Diagnoses

• Middle interhemispheric

Ultrasonographic

+ ruptured septum pellucidum

Findings

• Conventional o (+1-) Azygous (unpaired) or absent ACA o Fan-like array of arteries over surface of "pancake" hemisphere o If ACA absent, middle cerebral arteries have more medial course

Imaging Recommendations • Best imaging tool: MRI

• Protocol advice: Multiplanar MR imaging with special attention to midline structures

I DIFFER.ENTIAI. DIAGNOSIS Middle interhemispheric

variant (MIH): ZIC2

• Sylvian fissures connected across midline over vertex (86%) • Non-cleavage THAL > BG • Heterotopias and dysplastic cortex common (86%) • Thought to reflect abnormal induction of embryonic roof plate (classic HPE = abnormal induction of embryonic floor plate)

Other holoprosencephaly disorders

spectrum

• Septo-optic dysplasia • Central incisor syndrome • Non-specific midline dysplasias & frontonasal dysplasia, agnathia-otocephaly, anencephaly

Marked hydrocephalus + ruptured septum pellucidum • Macrocephalic

(HPE usually microcephalic)

I PATHOI.OGY General Features • General path comments o Embryology-anatomy • Normal prosencephalic cleavage occurs 4-6 wks • Genetics o Cytogenetic abnormality in 50%: Especially trisomy 13; also 18q-, 18p-, 3p, 7-, trisomy 9, lq15q, llq12-q13 (DHCR7 gene mutation = Smith-Lemli-Opitz) o Classic HPE: Sonic hedgehog (SSH: Chr 7q36), SIX3 (2p21), TGIF (18pl1.3) all => ventrodorsal gradient => non-cleavage midline, disorganized neocortex (anterior), formation dorsal cyst

Congenital Malformations

39

HOLOPROSENCEPHALY

1 40

o Middle interhemispheric (MIH) variant: ZIC2 (13q32) =>dorsoventral gradient • Etiology o Mutations affecting signaling genes (e.g., Sonic hedgehog) which regulate neural tube patterning o Disruption in dorsoventral axis patterning of secondary prosencephalon • Epidemiology: 1 to 1.4 per 10,000 live births (more common in early embryogenesis with high spontaneous miscarriage rates) • Associated abnormalities o Non-facial/non-CNS anomalies 65% • Developmental field defects: Extensive midline, schisis anomalies o Maternal factors • ETOH, diabetes, retinoic acid o 80% Correlation severity facial anomalies with severity HPE • +/- Midline facial clefting; premaxillary agenesis if severe; absent superior lingual frenulum • +/- Central incisor; proboscis; single nare; single nasal bone/absent internasal suture and caudal metopic suture • Infants of diabetic mothers: Alobar HPE with normal facies

Gross Pathologic

& Surgical Features

• Extreme hypoplasia of neocortex • Variable degree of fusion of diencephalon and THAL/BG with incorporation into upper brain stem • Dorsal cyst (especially in association of noncleaved thalamus) felt to represent expansion of partially blocked posterodorsal 3rd ventricle • Variable attenuation of anterior recess 3rd ventricle

Microscopic

Features

• Fused diencephalon structures

and variable fusion of deep gray

Staging, Grading or Classification

Criteria

• 1 SA => 1 frontal lobe deficiency and clinical severity • Lobar: Formed lateral ventricles; j or no dorsal cyst; fused diencephalon or fornices, (+/-) partial fusion BG > THAL; near normal IHF; small or normal olfactory nerves • Semilobar: Partial occipital/temporal horns; 1 moderate dorsal cyst; fused diencephalon, partial fusion BG > THAL; posterior IHF; (-) or small olfactory nerves • Alobar: "pancake brain" or "horseshoe" brain; monoventricle; 11 dorsal cyst; fused diencephalon, BG and THAL=> may form gray matter fusion mass, no IHF; (-) olfactory nerves

o Severity of pituitary/hypothalamic malfunction (75%, esp diabetes insipidus) and disturbed body temperature regulation correlates with degree of hypothalamic non-separation o Seizures (50%) and mental retardation: Most severe with cortical malformations o Dystonia and hypotonia: Severity correlates with degree of BG non-separation • Clinical profile: Mentally retarded microcephalic infant with midline facial anomalies, disturbed endocrine function

Demographics • Age: Presentation in infancy (can be diagnosed with fetal US or MRI) • Gender: M:F = 1.4:1

Natural History & Prognosis • Over-represented in fetal demise, stillbirths • Clinical severity relates to degree of hemispheric and deep gray nuclei non-separation (alobar HPE = worst)

Treatment • Treat seizures and endocrine

dysfunction

IDIt\GN()s-rtci(SI-I~<Sf(1..1ST Consider • HPE variants (lobar, septooptic dysplasia, single central midline incisor) may still present with hypothalamic/pituitary crisis

Image Interpretation

Pearls

• Sylvian angle (of Barkovich) key to understanding neuroanatomic anomalies

ISELECTED 1.

2.

3. 4.

5.

REFERENCES

Hayashi M et al: Neuropatholigcal evaluation of the diencephalon, basal ganglia and upper brainstem in alobar holoprosencephaly. Acta Neuropathol107(3):190-6, 2004 Blaas HG et al: Brains and faces in holoprosencephaly: Preand postnatal description of 30 cases. Ultrasound Obstet GynecoI19(1):24-38, 2002 Simon EM et al: The middle interhemispheric variant of holoprosencephaly. AJNR23(1):151-6,2002 Barkovich AJ et al: Analysis of the cerebral cortex in HPE with attention to the Sylvian fissures. AJNR23:143-50, 2002 Simon EM et al: The dorsal cyst in holoprosencephaly and the role of the thalamus in its formation. Neuroradiology 43(9):787-91,2002

I CUN1CAL1SSUES Presentation • Most common signs/symptoms o Worst (classic alobar HPE) = cyclopia, proboscis, midline facial clefting, microcephaly

Congenital Malformations

1 41

Tvpical (Left) Axial T2WI MR shows arteries wandering over brain surface (open arrow), fused anterior lobes and basal ganglia (arrow), and dorsal cyst. Note the partially fused thalami (curved arrow). (Right) Axial TlWI MR in the same child shows a "pancake" hemisphere and monoventricle. Small posterior tissue band (arrows) represents hippocampal formation.

Typical (Left) Sagittal T2WI MR shows "shield"-like hemisphere, hippocampal band (open arrow) and monoventricle/dorsal cyst. Cyst wall (arrows) is comprised of telencephalic roof plate and tela choroidea remnants. (Right) Sagittal oblique NECT (30) shows "pancake brain" "wrapped" around space occupied by dorsal cyst.

(Left) Axial T2WI MR shows venous structure draining to midline venous trunk (arrow). Be and thalami form midline fusion mass (open arrow). (Right) Axial MRA shows azygous (unpaired) anterior cerebral artery (arrow).

Congenital Malformations

HOLOPROSENCEPHALY VARIANTS 42

SMMCI. Coronal NECT shows a single median maxillary central incisor (SMMCI) (arrow). Note the precise midline location.

Abbreviations and Synonyms • Solitary median maxillary central incisor (SMMCI); solitary central maxillary incisor • Middle interhemispheric variant of holoprosencephaly (MIH); syntelencephaly

Definitions • SMMCI: One of several "microforms" of autosomal dominant holoprosencephaly (HPE) • MIH: Variant of HPE characterized by mid-interhemispheric fusion

I IMAGING

I

FIN DING $

General Features • Best diagnostic clue o SMMCI: Single, midline central maxillary incisor o MIH: Interhemispheric fusion of posterior frontal/parietal lobes + normal separation of frontal/occipital poles • Location o SMMCI: Midline, superior alveolar ridge o MIH: Posterior frontal and parietal lobes • Size: SMMCI: Equivalent to normal central incisor • Morphology: SMMCI: Normal central incisor

DDx: Holoprosencephaly

MIH. Axial 3D SPCR shows interhemispheric fusion of the sylvian fissure (SF), posterior frontal and parietal lobes. Note branches of the middle cerebral artery in the SF (arrows).

·MIH o Distinguishing features compared with classic HPE • Fusion sylvian fissures (SF)/posterior frontal and parietal lobes across midline • Normal separation frontal poles with present anterior interhemispheric fissure (IHF)/falx • Callosal (CC) dysgenesis characterized by presence of genu and splenium with absent body • Normal separation hypothalamus & basal ganglia o Frequent features MIH • Incomplete thalamic separation 33% • Cortical dysplasia/heterotopia o Occasional features MIH • Cerebellar abnormalities 20%: Cerebellar hypoplasia, Chiari 1 & 2, cephalocele o Features in common with classic HPE • Absent septum pellucidum • Azygous anterior cerebral artery

CT Findings • NECT o SMMCI • Single, midline central maxillary incisor • Midpalatal vomerine ridge • V-shaped palate oMIH • Interhemispheric isodense band of brain + sylvian fissure (SF)

Variants

.-

It f .

Mesiodens

Lobar HPE

Congen ital Malformations

Semi/obar HPE

HOLOPROSENCEPHALY

VARIANTS

1

Key Facts Terminology

Top Differential

• Solitary median maxillary central incisor (SMMCI); solitary central maxillary incisor • Middle interhemispheric variant of holoprosencephaly (MIH); syntelencephaly • SMMCI: One of several"microforms" of autosomal dominant holoprosencephaly (HPE) • MIH: Variant of HPE characterized by mid-interhemispheric fusion

• SMMCI vs hypodontia • SMMCI vs mesiodens • MIH vs classic holoprosencephaly

Imaging Findings

Clinical Issues

• SMMCI: Single, midline central maxillary incisor • MIH: Interhemispheric fusion of posterior frontal/parietal lobes + normal separation of frontal/occipital poles

• Isolated SMMCI: Eruption deciduous SMMCI; absent upper labial frenulum • MIH: Spasticity, hypotonia, seizures, developmental delay (DD)

Pathology • Several genetic mutations linked to SMMCI; sonic hedgehog (SHH) mutation, 7q36, most common • MIH: Linked to ZIC2 mutation at 13q32

o MIH: MR with 3D SPGR sequence • Protocol advice: SMMCI: Thin section axial/coronals

• CTA oMIH • Azygous ACA • MCA branches in abnormal SF

I DIFFERENTIAL DIAGNOSIS

MR Findings • TIWI o SMMCI: Dental abnormality more difficult to identify compared with CT • Occasional pituitary/stalk hypoplasia oMIH • Abnormal SF spans both hemispheres • Fused posterior frontal, parietal lobes isointense on all pulse sequences • Normal myelin maturation (in contrast to classic HPE) • Dysgenetic CC (genu present more often than splenium) • T2WI o MIH: 25% hyperintense dorsal cyst • Occurs with thalamic non-cleavage ~ obstructs third ventricle • MRA oMIH • Azygous ACA • MCA branches identified in abnormal SF

Ultrasonographic

Diagnoses

Findings

SMMCI vs hypodontia • Congenital absence of teeth • Permanent dentition> deciduous • Second premolars, third molars, and maxillary lateral incisors most commonly affected

SMMCI vs mesiodens • Supernumary permanent tooth between central maxillary incisors • Conical, slightly off midline

MIH vs classic holoprosencephaly • Failure of cleavage of basal forebrain structures • Severity of malformation related to degree of anterior development of brain o Alobar (least differentiated): Lack of IHF, falx and CC with pancake-like mass of brain o Semilobar (moderate differentiation): Partially formed IHF/falx posteriorly; splenium CC present o Lobar (most differentiated): IHF/falx extend into frontal region; genu CC aplastic/hypoplastic; frequent minimal frontal lobe fusion

• Prenatal US o MIH identified on 2nd trimester US o Often initially identified as lobar HPE

I PATH0 LOG¥

Angiographic

General Features

Findings

• Conventional oMIH • Azygous ACA • MCA branches identified in abnormal SF

Imaging Recommendations • Best imaging tool o SMMCI: CT (brain), include bone alga (face/jaw) • Supplemental MR for neurological, endocrine abnormalities

• General path comments o SMMCI: Deciduous & permanent teeth affected o Embryology-anatomy • SMMCI: Odontogenic maxillary epithelium forms along inferolateral frontalnasal prominence day 35 gestation • SMMCI: Central incisors formed by division midline 'epithelial dental lamina and lateral growth day 37-38 gestation

Congenital Malformations

43

HOLOPROSENCEPHALY VARIANTS

1 44

•

•

•

•

• MIH: Mitosis/apoptosis of embryonic roof plate form IHF after neural tube closure (fetal weeks 3-4) Genetics o SMMCI: Microform of autosomal dominant HPE (ADHPE); fewer sporadic cases • Variable expression ADHPE accounts for wide range of craniofacial and CNS phenotypes (cyclopia/alobar HPE to microforms/normal intelligence) • 70% penetrance ADHPE =} risk SMMCI, or other microform in offspring of obligate carrier = 13-14% • Risk of severe (semilobar/alobar) HPE in offspring obligate carrier ADHPE = 16-21% o Several genetic mutations linked to SMMCI; sonic hedgehog (SHH) mutation, 7q36, most common • SHH expressed in large number fetal tissues; responsible for induction ventral patterning in neuraxis • Less common mutations: SIX3 at 2p21, TGIF at 18pl1.3, 22qll deletion and ring chromosome 18 o MIH: Linked to ZIC2 mutation at 13q32 • In mice, ZIC2 plays role in differentiation of embryonic roof plate; mutations cause neural tube defects, HPE • In contrast to genes linked to classic HPE (SHH, for eg), ZIC2 not involved in ventral patterning of neuraxis =} accounts for lack of severe midline facial dysmorphisms in MIH Etiology o SMMCI: Theory: Lack of midline cell division and lateral growth of dental lamina creates single, midline "fused" central incisor o MIH: Impaired expression of roof plate properties alters mitosis and apoptosis leading to faulty IHF formation and fusion of the cerebral hemispheres Epidemiology o SMMCI: 1:50,000 o MIH: Rare Associated abnormalities o SMMCI: Rare reports VACTERL, CHARGE, velocardiofacial syndrome, vertebral anomalies o MIH: Report of 5 patients with ZIC2 mutations with limb, renal, genital anomalies

Gross Pathologic & Surgical Features • MIH: IHF present frontal, occipital poles; hemispheric fusion posterior frontal and parietal lobes; fused SF • MIH: Foci of undifferentiated cortex, subependymal gray matter heterotopia

Microscopic

Features

• +/- Other microforms ADHPE: Cleft lip, mid-face hypoplasia, microcephaly, coloboma, choanal atresia, midnasal stenosis, pyriform aperture stenosis, developmental delay, learning difficulties • Presence of SMMCI with severe manifestations ADHPE (cyclopia/alobar HPE) uncommon o MIH: Spasticity, hypotonia, seizures, developmental delay (DD) • Dx frequently known at birth (prenatal US) • Mild facial dysmorphisms frequent: Hypertelorism, cleft lip/palate, SMMCI • Severe facial dysmorphisms (as seen with classic HPE) do not occur • Clinical profile o SMMCI • Infant with SMMCI, short stature, hypotelorism • Isolated SMMCI in mother with offspring with classic HPE o MIH: Infant/young child with spasticity, DD

Demographics • Age: SMMCI: 1-2 yrs of age (eruption deciduous teeth) • Gender: Isolated SMMCI more common in females

Natural History & Prognosis • Prognosis o SMMCI: Determined by CNS involvement; isolated SMMCI or other microforms, good to excellent o MIH: Mild/moderate psychomotor delay, seizures • Clinical profile MIH most similar to lobar HPE

Treatment • SMMCI: No treatment for isolated dental abnormality o Hormone replacement, corrective surgery for other microforms ADHPE • MIH: Anti-epileptics

I DIAGNOSTIC

Image Interpretation

Pearls

• SMMCI: Careful scrutinization additional anomalies

of brain and face for

I SELECTED REFERENCES 1.

2.

3.

• MIH: Callosal fibers identified anteriorly, posteriorly 4.

Presentation • Most common signs/symptoms o Isolated SMMCI: Eruption deciduous SMMCI; absent upper labial frenulum • Short stature (50%) and hypotelorism frequent (33% short stature 2° to growth hormone deficiency)

CHECKLIST

5.

Simon EM et al: The middle interhemispheric variant of holoprosencephaly. AJNR Am J Neuroradiol. 23(1): 151-6, 2002 Heussler HS et al: Extreme variability of expression of a Sonic Hedgehog mutation: attention difficulties and holoprosencephaly. Arch Dis Child. 86(4): 293-6, 2002 Lewis AJ et al: Middle interhemispheric variant of holoprosencephaly: a distinct cliniconeuroradiologic subtype. Neurology. 59(12): 1860-5, 2002 Nanni L et al: SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature. Am J Med Genet. 102(1): 1-10, 2001 Hall RK et al: Solitary median maxillary central incisor, short stature, choanal atresia/midnasal stenosis (SMMCI) syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 84(6): 651-62, 1997

Congenital Malformations

HOLOPROSENCEPHALY VARIANTS 1 45

Typical (Left) SMMCI. Axial NECT shows an unerupted single median maxillary central incisor (SMMCI). Note normal incisor morphology. The prominent vomerine ridge is seen in the mid palate (arrow). (Right) SMMCI. Axial NECT in a patient with SMMCI shows overgrowth of the nasal process of maxilla (arrows) consistent with nasal pyriform aperture stenosis (NPAS). SMMCI is seen in 60% NPAS.

Typical (Left) MIH. Sagittal T1WI MR shows a dysgenetic corpus callosum (CC) with only a normal genu (arrow) identified. In classic forms HPE, the genu is the least well formed portion of the cc. Note Chiari 7. (Right) MIH. Axial T2WI MR shows fusion of posterior ventricles, absent septum pellucidum, findings also seen in classic HPE. However, note normal cleavage of the basal ganglia, findings typical of MIH.

Typical

/~

\, \

,

,

i

.

.

~~ ~

Congenital

Malformations

(Left) MIH. Axial T1WI MR shows clear separation of the frontal and occipital poles with the interhemispheric fissure (lHF) identified anteriorly and posteriorly (arrows). (Right) MIH. Axial 30 SPCR through the rostral brain shows interhemispheric fusion of posterior frontal and parietal lobes with focal absence of IH F (arrow). Note right frontal lobe pachygyria (open arrow).

SEPTOOPTIC DYSPLASIA

1 46

Coronal graphic depicts flat-roofed anterior horns & absence of midline septum pellucidum. Anterior horns are draped inferiorly around fornices (open arrow). Optic chiasm (arrow) small.

Abbreviations • • • • • •

Coronal T1WI MR shows absent septum pellucidum, flat roof of lateral ventricles, frontal horns "pointing" down and hypoplastic pituitary stalk (arrow).

• Location: Optic nerves, pituitary gland, septum pellucidum • Size o Small optic nerves o Small pituitary gland with ectopic posterior lobe o Absent septum pellucidum • Morphology o Coronal imaging shows • Flat-roofed ventricles • Downward pointing anterior horns

and Synonyms

Septooptic dysplasia (SOD) De Morsier syndrome Kaplan-Grumbach-Hoyt syndrome Suprasellar dysgenesis Septo-optic-pituitary dysgenesis SOD plus: Abnormal optic nerves/chiasm, septum pellucidum, pituitary gland, + cortical dysplasias

Definitions

CT Findings

• SOD = heterogeneous disorder characterized by hypoplasia of optic nerves/tract, absent septum pellucidum, hypothalamic-pituitary dysfunction • De Morsier (1956): Described 7 patients with SOD • Hoyt (1978): Described the association of SOD with hypopituitarism • Some authors consider SOD, lobar holoprosencephaly same disorder

• NECT o Absent septum pellucidum o Large lateral ventricles o Small bony optic foramina on axial and coronal imaging

MR Findings

I·IMAClN(j··.·.· ••FlN[)lNG~ General Features • Best diagnostic clue: Absent septum pellucidum, optic chiasm

small

DDx: Small Optic Nerves/Posterior

DID

DID

• TlWI o Three planes crucial to identify all findings • Absent septum pellucidum (remnants may be present) • Flat roof of frontal horns, inferior aspect of frontal horns "point down" • Small optic chiasm/nerves (fat-sat aides visualization of optic nerves) • +/- Thin pituitary stalk • Posterior pituitary ectopia

Ectopic Pituitary lobe

Ectopic Lobe

Congen ital Malformations

Ectopic Lobe

SEPTOOPTIC DYSPLASIA Key Facts Terminology • De Morsier syndrome • SOD = heterogeneous disorder characterized by hypoplasia of optic nerves/tract, absent septu~ pellucidum, hypothalamic-pituitary dysfunctIOn

Imaging Findings • Absent septum pellucidum (remnants may be present) • Flat roof of frontal horns, inferior aspect of frontal horns "point down" • Small optic chiasm/nerves (fat-sat aides visualization of optic nerves) • +/- Thin pituitary stalk

Top Differential

• Lobar holoprosencephaly • Isolated ectopic posterior pituitary lobe

Pathology • Optic nerve hypoplasia (ONH) • 60% have brain abnormalities (not just schizencephaly) • 62-88% have pituitary insufficiency • Frequently associated with other cerebral anomalies • Most common = schizencephaly • Midline malformations (callosal dysgenesis, etc) • Ocular anomalies (coloboma, anophthalmia, microphthalmia) • Olfactory tract/bulb hypoplasia

Diagnoses

• Kallman syndrome

• Callosal-forniceal continuation or fused midline fornices • Thin corpus callosum • Vertical hippocampi • +/- Hypoplastic/absent olfactory nerves • +/- Schizencephaly • +/- Heterotopias, cortical dysplasias • T2WI: Deficient falx (esp anteriorly); +/hypomyelination • Tl C+ o Enhancement of infundibulum, ectopic posterior pituitary lobe o Delayed enhancement of anterior pituitary lobe on dynamic MRI

Imaging Recommendations • Best imaging tool: MRI • Protocol advice o Coronal, sagittal thin sections through sella/orbits o Use fat-sat to better visualize optic nerves

I DIFFERENTIAL DIAGNOSIS Syndromes overlapping with septooptic dysplasia • Optic-infundibular dysplasia (OlD), normal septum • Schizencephaly: EMX 2 gene mutations reported in some severe cases

Kallman syndrome • Absent olfactory nerves • +/- Visual, septal, pituitary abnormalities

Lobar holoprosencephaly • Similar to SOD • Many consider it same disorder

Isolated ectopic posterior pituitary lobe • Normal chiasm/nerves,

septum pellucidum

IPATHOlOG¥ General Features • General path comments o Sudden death reported from hypothalamic-pituitary axis malfunction o Embryology-Anatomy • Disorder of midline prosencephalic development (6th wk gestation): Pituitary gland, forebrain, eyes, olfactory bulbs • HESXl (homeobox gene): Needed for pituitary/forebrain development • Genetics o Most are sporadic o Some are autosomal dominant or recessive o Some cases have mutations in Hesxl/HESXl genes • Homozygous mutations = full syndrome • Heterozygous mutations = milder pituitary phenotypes o Inactivation of Hesxl (3p21.2-3p21.2) by an Arg53Cys substitution leads to deficient anterior pituitary lobe (doesn't occur in sporadic SOD) • Etiology o Theories • Midline heritable defect (mild holoprosencephaly variant) • Or secondary degeneration of optic nerve fibers due to cerebral lesion • Or vascular disruption (field defect) during brain development • Epidemiology olin 50,000 o Optic nerve hypoplasia (ONH) • 60% have brain abnormalities (not just schizencephaly) • 62-88% have pituitary insufficiency • 30% have both of the above • 25-50% have absent septum pellucidum o Septooptic dysplasia (SOD) • 75-90% have brain abnormalities; 45% have pituitary insufficiency • Bilateral optic nerve hypoplasia 70%

Congenital Malformations

1 47

1 48

• Associated abnormalities o Frequently associated with other cerebral anomalies • Most common ::= schizencephaly • Peri-Sylvian cortical dysplasias • Midline malformations (callosal dysgenesis, etc) • Ocular anomalies (coloboma, anophthalmia, microphthalmia) • Olfactory tract/bulb hypoplasia o Overlapping syndromes with optic, septal, frontal lobe, midline, olfactory deficiencies

Natural History & Prognosis • Hypothalamic and pituitary crises; sudden death (hypocortisolism) • Depends upon severity of associated brain and pituitary malformations

Treatment • Hormonal replacement therapy

Gross Pathologic & Surgical Features • • • •

Small optic chiasm/nerves Small or absent geniculate nucleus Deficient/absent septum pellucidum Forniceal columns (+/- fused) =:> run along roof of 3rd ventricle • Common: Hypoplasia pituitary, olfactory lobes

Microscopic Features • Optic nerves, chiasm have sparse or absent myelinated fibers • Geniculate nucleus (if found): Disorganized layering of small neurons

Staging, Grading or Classification Criteria • Isolated ONH: Visual defect only; intelligence and growth normal • ONH and septal deficiency: Same as isolated • ONH and septal and pituitary deficiency: May have developmental delay • Above plus hemispheric migrational anomaly: Plus seizures • Intrauterine or perinatal insult (especially meningitis) as cause of optic nerve, chiasmatic, and hypothalamic deficiency

I.Gll .•NJ.GAliISSUES Presentation • Most common signs/symptoms o Newborns: Hypoglycemic seizures, apnea, cyanosis, hypotonia, prolonged conjugated jaundice, (and microphallus in boys) o Abnormal endocrine function (60%): Look for multiple pituitary deficiencies o Normal endocrine function (40%): Usually have schizencephaly, seizures • Clinical profile o Child with short stature, endocrine dysfunction o Normal or color blindness, visual loss, nystagmus, strabismus o +/- Mental retardation, spasticity, microcephaly, anosmia

Consider • SOD in small stature pediatric patient with absent septum pellucidum

Image Interpretation

I SELECTED REFERENCES Gasparetto EL et al: Septo-optic dysplasia plus: case report. Arq Neuropsiquiatr. 61(3A):671-6, 2003 2. Campbell CL: Septo-optic dysplasia: a literature review. Optometry. 74(7):417-26,2003 3. Wakeling EL et al: Septo-optic dysplasia, subglottic stenosis and skeletal abnormalities: a case report. Clin Dysmorphol. 12(2):105-7,2003 4. Camino R et al: Septo-optic dysplasia plus. Lancet Neurol. 2(7):436, 2003 5. Tajima T et al: Sporadic heterozygous frameshift mutation of HESXl causing pituitary and optic nerve hypoplasia and combined pituitary hormone deficiency in a Japanese patient. J Clin Endocrinol Metab. 88(1):45-50, 2003 6. Dattani M: Structural hypothalamic defects. J Pediatr Endocrinol Metab. 15 SuppI5:1423-4, 2002 7. Antonini SR et al: Cerebral midline developmental anomalies: endocrine, neuroradiographic and ophthalmological features. J Pediatr Endocrinol Metab. 15(9):1525-30, 2002 8. Orrico A et al: Septo-optic dysplasia with digital anomalies associated with maternal multi drug abuse during pregnancy. Eur J Neurol. 9(6):679-82, 2002 9. Miller SP et al: Septo-optic dysplasia Plus: A spectrum of malformations of cortical development. Neurology 54:1701-3,2000 10. Dattani MT et al: Molecular genetics of septo-optic dysplasia. Horm Res 53(S): 26-33, 2000 11. Barkovich AJ et al: Septo-optic dysplasia: MR imaging. Radiology 171:189-92, 1989 1.

Demographics • Age o Generally detected in infants o More common among younger mothers & first-born • Gender: M ::= F

Congenital

Pearls

• Small optic nerves, + ectopic posterior pituitary lobe, + absent septum pellucidum ::= SOD

Malformations

1 49

Typical (Left) Sagittal Tl WI M R

shows calloso-forniceal continuation and large lateral ventricles in SOD. (Right) Coronal Tl WI M R shows tiny optic nerves (arrows).

Typical (Left) Coronal TlWI MR

shows absent septum pellucidum (arrow) and a right open lip schizencephaly. (Right) Coronal TlWI MR in same patient shows absent septum pellucidum, frontal horns "pointing down ", thin pituitary stalk and small pituitary gland (arrow).

Typical (Left) Axial FLAIRMR shows

large lateral ventricles and absent septum pellucidum (arrow). (Right) Coronal T2WI MR in same patient confirms absent septum pellucidum, typical shape of frontal horns (arrows) and small stalk and pituitary gland.

Congenital Malformations

50

Sagittal T2WI MR shows profound microcephaly (microlissencephaly), thinning of the corpus callosum and dysplasia of the cerebellum (arrow).

Abbreviations

and Synonyms

• Primary (genetic) microcephaly, secondary (nongenetic) microcephaly, micrencephaly, microencephaly

Definitions • Microcephaly: Small head size o Primary (genetic): Mendelian inheritance OR associated with a specific genetic syndrome o Secondary (nongenetic): Results from noxious agent that affects fetal/infant brain growth • Micrencephaly: Brain reduced in size as a result of genetic or noxious insult

IIMAOINO •• ·FINOINCS General Features • Best diagnostic clue o !Craniofacial proportions o Sutural apposition or overlap o Simplified cortical gyral pattern • Imaging findings: Dictated by the cause of microcephaly o Primary (genetic) microcephaly

Coronal T2WI MR of microlissencephaly shows: Simplified gyral pattern, reduced white matter volume, and indistinct gray-white differentiation (impaired neuronal migration) (arrows).

• Small, but grossly normal brain ~ gyral simplification • OR ± pachygyric, lissencephalic, holoprosencephalic • OR ± hypoplastic cerebellum, hypomyelination o Secondary (nongenetic) microcephaly • Hypoxic ischemic encephalopathy: ± Cortical, white matter, or basal ganglia volume loss • (S)TORCH infection: Ca++, abnormal WM , neuronal migration anomalies • Fetal alcohol syndrome (FAS): Callosal abnormalities, ventriculomegaly • Nonaccidental head injury (NAHI); Encephalomalacia, chronic subdurals, ± parenchymal lacerations • Lateral radiograph, CT topogram, or sagittal MRI o ! Craniofacial proportions (skull: Face ratio) • Normal craniofacial ratios: Premature (5:1), term (4:1),2 yrs (3:1), 3 yrs (2.5:1), 12 yrs (2:1), adult (1.5:1) • Fetal Sonography or FMRI Findings o Difficult to confirm microcephaly until late 2nd or early 3rd trimester

Radiographic Findings • Radiography: !Craniofacial ratio, slanted forehead, closely apposed or overlapping calvarial sutures

DDx: Microcephaly

Congenital CMV

HIE

NAHI Chronic

Congen ital Malformations

Fetal Alcohol

MICROCEPHALY

1

Key Facts Terminology • Microcephaly: Small head size • Primary (genetic): Mendelian inheritance OR associated with a specific genetic syndrome • Secondary (nongenetic): Results from noxious agent that affects fetal/infant brain growth

Imaging Findings • 1 Craniofacial proportions • Imaging findings: Dictated by the cause of microcephaly • Normal craniofacial ratios: Premature (5:1), term (4:1),2 yrs (3:1), 3 yrs (2.5:1), 12 yrs (2:1), adult (1.5:1)

• Small yet normal brain ~ simplified gyral pattern (oligogyria) ~ microlissencephaly

CT Findings • NECT o Small cranial vault: Sutures closely apposed, overlapping or with secondary craniosynostosis o Ca++ in (S)TORCH and heredito-genetic (S)TORCH look-alikes (pseudo-TORCH syndromes) o Cortical surface: Normal ~ simplified ~ migrational abnormalities ~ micro lissencephaly o White matter attenuation: Normal ~ diminished (secondary to hypomyelination or demyelination)

• ± Various telencephalic anomalies: Callosal absence or dysgenesis, holoprosencephaly

Pathology • Primary (genetic) microcephaly is typically autosomal recessive (example: Familial form - 1/40,000 births) • Primary microcephaly is associated with many syndromes

Clinical Issues • Criteria for the diagnosis of microcephaly: Head circumference> 3 SD below the mean for age and sex

Diagnostic Checklist • Presence of cerebellar hypoplasia more common primary (genetic) microcephaly • If midline anomalies accompany microcephaly, consider fetal alcohol syndrome (FAS)

• FLAIR: Periventricular: Cavitation (1 signal), gliosis (1 signal), ± hyperintense chronic subdural collections • T2* GRE: Sequelae to non accidental trauma: Hypointensities from hemorrhagic parenchymal shear injury • DWI: T2 shine-through in states associated with gliosis or demyelination • MRS: 1 NAA, myoinositol and choline may be 1 in states of ongoing demyelination and neurodegeneration

Ultrasonographic

MR Findings • TlWI o Primary (genetic) microcephaly • Small yet normal brain ~ simplified gyral pattern (oligogyria) ~ microlissencephaly • Normal myelination ~ hypomyelination ~ demyelination • ± Various telencephalic anomalies: Callosal absence or dysgenesis, holoprosencephaly • ± Cerebellar hypoplasia (more common in genetic causes of microcephaly) o Secondary (nongenetic) microcephaly • Destructive changes: Encephalomalacia, ± Ca++ (S)TORCH infections, ± subdural collections • T2WI o Primary (genetic) microcephaly • Sulci (%-Vz normal depth), cortex simplified ~ pachygyric~ heterotopic ~ microlissencephalic • 1 Commisural fiber tracts, normal basal ganglia volume, ± cerebellar hypoplasia • White matter maturation: Normal ~ hypomyelinated ~ demyelinated o Secondary (nongenetic) microcephaly • White matter: Gliosis, cavitation, demyelination, diminished volume, ± hypointensity (Ca++) • Cortex: Normal ~ simplified ~ polymicrogyria (TORCH) • Possible midline anomalies: Absent corpus callosum, holoprosencephaly • PD/Intermediate: Gliosis (1 signal) and Ca++ (! signal) more common in secondary microcephaly (infection)

in

Findings

• Real Time o Small fontanel due to sutural overlap, sulcal and ventricular expansion o ± Basal ganglia or thalamic Ca++ (TORCH or HIE), ± periventricular volume loss (TORCH or HIE)

Imaging Recommendations • Best imaging tool o NECT detects: Ca++ (TORCH, pseudo-TORCH, HIE), encephalomalacia, and subdural collections o MR depicts: Gyral pattern, cortical organization/migration, myelination, midline anomalies, gliosis, hemorrhage • Protocol advice o Consider liberal us of NECT to detect Ca++ o MR brain: GRE T2* (blood and Ca++), 3D SPGR to evaluate brain convolutions, FLAIR for detecting subdurals

I DIFFERENTIAl.. DIAGNOSIS Secondary (nongenetic)

microcephaly

• Antenatal causes: Pre-eclampsia, maternal infection (TORCH), maternal diabetes, FAS, hyperphenylalaninemia • Perinatal causes: Hypoxic ischemic encephalopathy (HIE), infection • Postnatal: Prolonged status epilepticus, HIE, hypoglycemia, meningo-encephalitis, neurodegenerative, NAT

Congenital Malformations

51

MICROCEPHALY 1 52

• Noxious insult: Prenatal irradiation, maternal ingestion of anticonvulsants, ETOH, cocaine, excessive vitamin A

[PATHOL()GY

Demographics

General Features • General path comments o Skull changes: Sloping forehead, flattened vault, prominent ears, up-slanting palpebral fissures o Embryology-anatomy • Pathways in which genes affect neuronal progenitor cells & brain size • Genetics o Primary (genetic) microcephaly is typically autosomal recessive (example: Familial form ~ 1/40,000 births) • MCPH genetic heterogeneity: Mutations MCPHS (1q31) most prevalent • Primary microcephaly is associated with many syndromes • Etiology: Heterogeneous: Inherited or acquired • Epidemiology o Incidence of microcephaly in the general population: 0.6-1.6% o Incidence of genetically determined microcephaly: Familiall/40,OOO, Down synd 1/800 • Associated abnormalities: Frequently seen as a component of other severe malformations

Gross Pathologic & Surgical Features • Skull capacity < 1300 ml, brain weight < 900 grams • Extreme microcephaly (as low as 300 gms, HC = S-10 SD below mean) • General reduction in cerebral hemisphere size • Simple gyral pattern (oligogyria) • Short central sulcus, sulci (shallow, narrow or wide) • Sulcus parieto-occipitalis may be enlarged - simian fissure • Island of Reil remains uncovered (incomplete operculization) • ± Lissencephaly, oligogyria, heterotopias, holoprosencephaly, cerebellar hypoplasia • Acquired microcephaly: ± Cystic degeneration of white matter, infarcts, Ca++, hemorrhagic products

Microscopic

• Clinical profile: Slanted forehead, prominent nose and ears, up-slanting palpebral fissures, conical head, ± overlapping sutures • Criteria for the diagnosis of microcephaly: Head circumference> 3 SD below the mean for age and sex

• Age o Primary (genetic) microcephaly often reveals itself either in utero or shortly after birth o Secondary (nongenetic) microcephaly usually results from insults within the first two years of life • Gender: Variable based upon type: Primary (autosomal recessive inheritance) vs secondary (nongenetic) • Ethnicity: The common genetic forms;::; pan-ethnic, certain syndromic causes of microcephaly may show ethnicity

Natural History & Prognosis • Dictated by the cause of microcephaly

Treatment • Supportive, genetic testing available for some microcephalic disorders • Variable degree of mental retardation and motor handicap

I DIAGNOSIICctI-lE<:I<.LIST Consider • Presence of cerebellar hypoplasia more common in primary (genetic) microcephaly • If midline anomalies accompany microcephaly, consider fetal alcohol syndrome (FAS)

Image Interpretation

I SELECTED REFERENCES 1.

2.

3.

Features

• MCPHS: No evidence of abnormal neuronal migration or architecture • Other forms may occur with 4 layer cortex (lissencephalic)

Staging, Grading or Classification Criteria • Grouped by: Myelination, neuronal organization migration, and associated congenital anomalies

and

Pearls

• MR provides the most sensitive tool for investigating the simplified cortex in microcephaly

4.

5.

Bond J et al: ASPM is a major determinant of cerebral cortical size. Nat Genet 32:316-20,2002 Jackson AP: Identification of microcephalin, a protein implicated in determining the size of the human brain. Am J Hum Genet 71(1):136-42, 2002 Custer DA et al: Neurodevelopmental and neuroimaging correlates in nonsyndromal microcephalic children. J Dev Behav Pediatr 21(1): 12-18,2000 Barkovich AJ et al: Microlissencephaly: A heterogeneous malformation of cortical development. Neuropediatrics 29(3):113-19, 1998 Swayze VW et al: Magnetic resonance imaging of brain anomalies in fetal alcohol syndrome. Pediatrics 99(2):232-40, 1997

I CLiN ICALlSSLJES Presentation • Most common signs/symptoms: Severe mental retardation, ± seizures, developmental delay

Congenital Malformations

1 53

Typical (Left) Sagittal T7WI MR in a patient with familial microcephaly (autosomal recessive), shows a diminished craniofacial ratio. (Right) Axial T2WI MR in a patient with familial microcephaly shows simplified gyral pattern, mild ventriculomegaly, and subarachnoid space enlargement.

Variant (Left) Axial T2WI MR in a child with periventricular leukomalacia (PVL), shows profound 1055 of white matter volume. Note the gyral indentation against the ventricular margins (arrows). (Right) Axial NECT in a microcephalic infant who experienced chronic profound hypoxia, shows diffuse cerebral hemispheric atrophy, calcification of the thalami, and marked sutural overlap (arrows).

Variant (Left) Axial FLAIR MR in a microcephalic infant with PEHO syndrome (progressive encephalopathy, hypsarrhythmia, and optic atrophy) shows periventricular bright signal (gliosis) mimicking PVL (arrows). (Right) Axial NECT in a child with Aicardi-Coutieres syndrome (Pseudo-TORCH), shows extensive periventricular calcification (arrows), and moderate ventriculomegaly secondary to white matter volume 1055.

Congenital Malformations

CONGENITAL MUSCULAR DYSTROPHY 54

Axial T2WI MR in Walker-Warburg; the most severe of the CMOs. Showing cobblestone lissencephaly (arrows), hypomyelination, absence of septum pellucidum and ventriculomegaly.

Sagittal T2WI MR shows a flexed or "Z-shaped", hypoplastic brainstem. The belly of the pons is notched (arrow). The cerebellum is severely hypoplastic and rotated. There is hydrocephalus.

o Example: Merosin (-) CMD with brain malformations

Abbreviations

and Synonyms

• Congenital muscular dystrophy (CMD 1): Merosin positive (+) or merosin negative (-) CMD • CMD 2-4: Cobblestone lissencephaly (LIS); type 2 LIS; CMD with severe CNS malformations

General Features • Best diagnostic clue: "Z-shaped" brainstem in a hypotonic infant • Morphology o CMDs with major brain malformations (WWS most severe) • Cortical dysplasia, cobblestone LIS or pachygyria • Varying degrees agenesis or hypogenesis of corpus callosum, septum pellucidum, vermis • Flat or "Z-shaped" brain stem or "notched" pons • +/- Hydrocephalus or encephalocele

Definitions • CMDs = heterogeneous group of autosomal recessive myopathies presenting at birth with hypotonia • CMDs without major brain malformations are either me rosin positive or merosin negative o CMD 1 Merosin (-): Significant dys-/hypomyelination of white matter (WM) o CMD 1 Merosin (+): Normal/very mild imaging findings (cerebellar CBLL hypoplasia, non-specific WM changes, focal polymicrogyria PMG) • "" 50% of children with CMD (CMD 2-4) have major brain abnormalities with a spectrum of overlapping findings including abnormal signal of WM & ocular, cortical (cobblestone LIS), and CBLL anomalies o CMD 2: Fukuyama (FCMD) = least severe o CMD 3: Santavuori muscle-eye-brain or Finnish type (MEB) o CMD 4: Walker-Warburg syndrome (WWS) = most severe • Mixed patterns occur

CT Findings • NECT o All imaging findings most severe in WWS • I Attenuation WM, vermian dysgenesis (looks like Dandy Walker spectrum) • +/- Occipital cephalocele, +/- hydrocephalus, shallow or absent sulci

MR Findings • TlWI

DDx: Cerebellar Cysts and Brainstem Hypoplasia

Cystic CBLL Mets

Non CMD CBLL Cysts

Congenital

DWM Normal Pons

Malformations

HGPS

CONGENITAL MUSCULAR DYSTROPHY Key Facts • All imaging findings most severe in WWS

Terminology • CMDs:::: heterogeneous group of autosomal recessive myopathies presenting at birth with hypotonia • CMD 1 Merosin (-): Significant dys-/hypomyelination of white matter (WM) • CMD 1 Merosin (+): Normal/very mild imaging findings (cerebellar CBLL hypoplasia, non-specific WM changes, focal polymicrogyria PMG) • '" 50% of children with CMD (CMD 2-4) have major brain abnormalities with a spectrum of overlapping findings including abnormal signal of WM & ocular, cortical (cobblestone LIS), and CBLL anomalies • Mixed patterns occur

Pathology • Marked phenotypic overlap amongst FCMD, Walker- Warburg, and MEB • Muscle biopsy: Mild to moderate dystrophic changes, +1- inflammatory infiltrate, +1- absent staining laminin-lX2

Clinical Issues • Clinical profile: Floppy newborn • No treatment other than supportive: Major respiratory and cardiovascular concerns

Imaging Findings • Best diagnostic clue: "Z-shaped" brainstem hypotonic infant

in a

o Thin, dysplastic, polymicrogyria (PMG) or "pebbled" supratentorial cortex, +1- hydrocephalus o +1- Callosal, vermian, or septal hypogenesis o Flat, deeply clef ted, notched or "Z-shaped" brain stem • T2WI o Polymicrogyria of cerebellar cortex, +1- cysts o CMD merosin (-): Dysmyelination of centrum semiovale, +1- subcortical U-fibers o FCMD, MEB: WM abnormalities in half o WWS: Severe WM hypomyelination

Ultrasonographic

•

Findings

• Real Time: Fetal US or fetal MRI may be diagnostic

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Multiplanar T2/FLAIR of posterior fossa to define CBLL cysts and brain stem malformation

I DIFFERENTIAl.. DIAGNOSIS Dandy Walker malformation • Small vermian remnant rotated superiorly by cyst; pons usually normal in size and not clefted or notched

Multiple

disorders with brainstem c1efting

• Joubert (mesencephalon and vermian hypoplasia); midline clefting syndromes

•

Horizontal gaze palsy associated with progressive scoliosis (HGPS): Chr 11q23 • Horizontal gaze palsy, progressive scoliosis, brainstem hypoplasia/clefting, mild CBLL volume loss •

IPATHOI..OGY •

General Features • General path comments o Marked phenotypic overlap amongst FCMD, Walker-Warburg, and MEB

o Muscle biopsy: Mild to moderate dystrophic changes, +1- inflammatory infiltrate, +1- absent staining laminin-lX2 Genetics o CMD 1 Merosin (+): Genetic defect(s) unknown o CMD 1 Merosin (-): Mutation in gene for laminin-lX2 on Chr 6 o CMDs with brain anomalies have hypoglycosylation of lX-dystroglycan allowing neuronal overmigration through gaps in external lamina ~ "pebbled" surface of brain • FCMD: Mutation in gene encoding fukutin (FCMD at 9q31) • MEB: O-Mannoside N-acetyl-glucosaminyl-transversae (POMGnT1 at 1p32-p34) • WWS: O-Mannosyltransferase gene (POMT1) o Mutations in FKRP (fukutin-related protein gene) may cause congenital or late onset phenotypes o Other CMD variants with known defects • CMD with mutation integrin-lX7 gene on Chr 12 • CMD with familial junctional epidermolysis bullosa (plectin gene on Chr 8) • CMD with spine rigidity (linked to Chr 1 in some) o Mixed patterns and intermediate forms occur • CMD Merosin (-) with brain anomalies, cerebellar cysts, vermis hypoplasia, mental retardation Etiology o Mutations in molecules with roles in cell migration and connection • Merosin (laminin-lX2) utilized in migration of oligodendrocyte precursors • Merosin is a skeletal muscle extracellular matrix protein that binds dystrophin associated glycoprotein complex Epidemiology: 7-12 per 100,000 children in Japan; incidence elsewhere uncertain Associated abnormalities: Some associated features in CMD variants with "not yet found" mutations are occipito-temporal polymicrogyria, occipital agyria, calf-hypertrophy, arthrogryposis, ptosis, adducted thumbs

Congenital Malformations

1 55

CONGENITAL MUSCULAR DYSTROPHY 1 56

Gross Pathologic & Surgical Features

Natural History & Prognosis

• CMDs with brain malformations o Supratentorial: Disorganized cortex: Coarse gyri, agyric regions, +/- hydrocephalus and focal interhemispheric fusion o Brainstem: Variable degrees of pontine hypoplasia and fused colliculi ~ flat, cleft or "Z-shaped" brainstem o Infratentorial: CBLL hypoplasia, PMG and cysts related to PMG, +/- encephalocele o Ocular anomalies: Retinal/optic nerve dysplasias, microphthalmia, buphthalmos, glaucoma, anterior chamber dysplasias, cataracts

• CMD 1 with normallaminin-oc.2 expression (merosoin +): Decreased fetal movement, hypotonia, proximal weakness, contractures, mild or nonprogressive course, most can sit, some can walk, intellect usually normal • CMD 1 with deficient laminin-<x2 expression (merosoin -): More severe than above, intellect usually normal, but some have Sz • FCMD: Severely hypotonia, Sz, MR, contractures early, rarely learn to walk, death before 20 yrs • MEB: Severe hypotonia, Sz, MR, may survive to 20 yrs, but develop spasticity and contractures • WWS: Most severely affected, lethal in infancy, little spontaneous movement, no motor/cognitive skills, usually die in first year of life

Microscopic Features • Cerebral and CBLL PMG • Fibroglial proliferation of leptomeninges (leads to pebbled surface and trapped CSF "cysts") • Hypoplasia of corticospinal tracts

Treatment • No treatment other than supportive: Major respiratory and cardiovascular concerns

Staging, Grading or Classification Criteria • CMD IA: Congenital merosin-deficient muscular dystrophy (abnormal WM) • CMD 2: FCMD (moderate dysplasia of neocortex, CBLL cortex and abnormal WM) o Frontal polymicrogyria, occipital cobblestone cortex, delayed myelin with "peripheral first" myelination pattern • CMD 3: Finnish type MEB (less severe than CDM 4) o Hydrocephalus, vermian hypogenesis, dysplastic cortex, patchy abnormal WM, +/- callosal dysgenesis • CMD 4: Walker-Warburg (most severe) o Hydrocephalus, vermian hypogenesis, kinked pons-midbrain, cobblestone cortex, no myelin, +/cephalocele, +/- callosal dysgenesis

Consider • Typical brainstem and cerebellar findings should prompt the diagnosis of CMD, even if eyes and supratentorial cortex radiographically normal

Image Interpretation

1.

Presentation

2.

• Most common signs/symptoms: Hypotonia, mentally retarded, delayed motor, poor vision, elevated serum creatine kinase • Clinical profile: Floppy newborn

3.

4.

Demographics • Age o CMD with brain malformations can be diagnosed in utero via US and MRI, otherwise in early infancy o FCMD: High percentage spontaneous abortions • Gender: Autosomal recessive: M = F usual (some M > F or F > M variants) • Ethnicity o FCMD most common in Japan (carrier state 1:88) o MEB more prevalent in Finland o WWS has worldwide distribution o Other country and population-isolate specific variants are known

Congenital

Pearls

• Not all "Z-shaped" brainstems are CMD, clinical and laboratory features are crucial for the diagnosis • Not all CMD have "Z-shaped" brainstems, remember merosin (-) CMD

5.

6.

7.

8.

Zolkipli Z et al: Occipito-temporal polymicrogyria and subclinical muscular dystrophy. Neuropediatrics 34(20):92-5, 2003 Lopate G et al: Congenital muscular dystrophy. eMedicine (topic 549), 2003 Triki C et al: Merosin-deficient CMD with mental retardation and cerebellar cysts. Neuromuscul Disord 13(1):4-12,2003 Olson EC et al: Smooth, rough and upside-down neocortical development. Curr Opin Genet Dev 12(3):320-7, 2002 Mercuri E et al: Early white matter changes on brain magnetic resonance imaging in a newborn affected by merosin-deficient congenital muscular dystrophy. Neuromuscul Disord 11(3):297-9, 2001 Philpot] et al: Brain magnetic resonance imaging abnormalities in merosin-positive congenital muscular dystrophy. Eur] Paediatr NeuroI4(3):109-14, 2000 Barkovich A]: Neuroimaging manifestations and classification of congenital muscular dystrophies. A]NR 19:1389-96, 1998 Santavuori P et al: Muscle-eye-brain disease: Clinical features, visual evoked potentials and brain imaging in 20 patients. Eur] Paediatr Neurol 2(1):41-7, 1998

Malformations

CONGENITAL MUSCULAR DYSTROPHY 1 57

Typical (Left) Sagittal T2WI MR

shows flexed brainstem, unusual tectum (open arrow), hypoplastic pons, vermian dysgenesis, tiny cerebellar cysts (arrow) and hydrocephalus. (Right) Coronal T2WI MR shows occipital cobblestone lissencephaly (arrow), dysplastic cerebellum with cysts (curved arrow) and ventriculomegaly.

Typical (Left) Axial T2WI MR shows

disorganized cerebellar folia with cysts (arrow) and a hypoplastic pons. (Right) Axial FLAIRMR in another child shows notched pons (arrow) and multiple cerebellar cysts (curved arrow).

Typical (Left) Axial T2WI MR in a

child with CMD and brain malformations shows abnormal frontal white matter and pachygyria/polygyria of the frontal lobes (open arrow). (Right) Axial T2WI MR in a child with merosin negative CMD shows diffusely abnormal periventricular, lobar, and subcortical WM (arrows).

Congenital Malformations

58

Axial graphic shows extensive bilateral subependymal heterotopia (arrow) lining the lateral ventricles. Gray matter cortical ribbon is thin and the sulci are shallow.

Abbreviations • Heterotopic

and Synonyms

gray matter (HGM)

Definitions • Arrested/disrupted neurons along migration path from periventricular germinal zone to cortex o Can be inherited o Can be acquired (maternal trauma, infection, or toxin)

General Features • Best diagnostic clue: Nodule or ribbon, isointense with gray matter (GM), "stuck" in wrong place (+/- thin overlying cortex) • Location: Can leave "heterotopic" neuronal deposits along migration path • Size: Diffuse or focal • Morphology o Subependymal heterotopia (most common) • GM nodules + focal/multifocal indentation of ventricle o Band heterotopia ("double cortex")

Coronal T7 WI MR 3D cutaway reconstruction shows bilateral subependymal HGM (arrow) lining ventricles. Small linear HGM bands (curved arrow) traverse between ventricular surface and cortex.

• Thick inner GM band + thin, abnormal cortex (seizure risk) • Thin/partial inner band + normal cortex = normal function o Lissencephaly type 1 • Part of agyria, agyria/pachygyria spectrum • Thick inner band GM, cell sparse WM zone, thin outer layer GM • Shallow Sylvian fissure with "hour-glass" cerebral configuration o Lissencephaly type 2 ("cobblestone") • Usually occurs with congenital muscular dystrophies • Neurons "overmigrate" through gaps in external layer of cortex =:> "pebbled" surface of brain • Associated ocular, cerebellar anomalies common o Subcortical heterotopia: Large foci have thinned and dysplastic overlying cortex, small foci don't • Focal HGM nodules • Large nodular HGM (can mimic neoplasm!) • Swirling, curvilinear GM mass continuous both with cortex, underlying ventricular surface

CT Findings • NECT: Always isodense with GM (extremely rare dysplastic Ca++) • CECT: No enhancement

DDx: Nodules and lines

TS SEN and Tubers

CMV Calcification

White Lines of TS

Congenital Malformations

Migrating Neurons

HETEROTOPIC GRAY MATTER 1

Key Facts Imaging Findings

Pathology

• • • • •

• Genetic: Mutations alter molecular reactions at multiple migration points => migrational arrest => HGM • Acquired: Toxins/infections => reactive gliosis/macrophage infiltration => disturbed neuronal migration/cortical positioning

Sub ependymal heterotopia (most common) Band heterotopia ("double cortex") Lissencephaly type 1 Lissencephaly type 2 ("cobblestone") Subcortical heterotopia: Large foci have thinned and dysplastic overlying cortex, smalHoci don't • Imaging characteristics match gray matter (GM) • Margins may be distinct • If subcortical, look for continuity with cortex and ventricular surface

Top Differential

(peroxisomal

disorder)

• Xenon-CT: 1 Regional cerebral blood flow (rCBF) during functional testing suggests HGM is functional

MR Findings • TIWI o Imaging characteristics match gray matter (GM) o Margins may be distinct • T2WI o Imaging characteristics of GM o If subcortical, look for continuity with cortex and ventricular surface • FLAIR: No abnormal signal • DWI: Eigenvectors (DTI) pass through band heterotopia, connectivity patterns may explain absence of focal neurologic deficits • MRS: Choline and NAA are variable

Findings

• Real Time: Fetal US and fetal MRI have documented subependymal heterotopia

Nuclear Medicine

Findings

• PET: Band heterotopia: Glucose uptake similar to or > than normal cortex • Brain Scan (HMPAO-SPECT): Perfusion similar to normal cortex

Imaging Recommendations • MRI + thin slice SPGR (surface coil/3D reconstruction) for subtle lesions

I DIFFERENTIAL DIAGNOSIS Tuberous sclerosis • SENs of tuberous sclerosis may resemble heterotopias • SENs often calcify, may enhance

Zellweger

syndrome (peroxisomal disorder)

• Abnormal neuronal

Diagnostic Checklist • HGM is common and commonly associated with other anomalies • HGM doesn't enhance and doesn't calcify

Diagnoses

• Tuberous sclerosis • Zellweger syndrome • Cytomegalovirus

Ultrasonographic

59

migration,

hypomyelination

Many syndromes and complicated brain malformations include HGM amongst findings • Agenesis CC, Chiari 2 are the most common of these

Cytomegalovirus • Periventricular

calcifications

I PATHOLOGY General Features • General path comments o GM nodules/masses in wrong location o Embryology complicated, process dependent upon multiple molecular mechanisms • Cell cycle control, cell-cell adhesion, growth factor, neurotransmitter release, interaction with matrix proteins o Specific (normal) orderly pattern of development • Subependymal germinal zones proliferate, form neuroblasts & glia • Neuroblasts leave ventricular surface by "leading edge" extension/growth cone formation (requires filamen) • Neuroblasts attach to radially arranged glial fibers (RGFs) • Neuroblasts migrate along RGFs to mantle (requires cell-adhesion, ligand-receptor interactions) • RGFs guide/nourish migrating neuroblasts • Neuroblasts disengage from RGFs (requires "reelin" secreted by layer 1 pioneer neurons) • Earliest neuroblasts disengage in cortical subplate • Later waves pass through initial layer, form 6 layered cortex • Genetics o Genetics = complete/partial deletion/mutation of genes that govern specific stages of neuronal migration

Congenital Malformations

60

• Type 1 (classic or Miller-Dieker) lissencephaly: Large deletion LIS1 gene located on 17p13.3 • Isolated lissencephaly/posterior band heterotopia: Smaller deletion LIS1 • Isolated lissencephaly/anterior band heterotopia: XLIS gene on Xq22.3-q23 • Bilateral, diffuse subependymal heterotopia: Filamin-1 gene (required for cell migration to cortex) on Xq28 • Isolated foci (large masses or single small foci) of HGM occur with many, many other syndromes and malformations • There are additional (newly described) periventricular heterotopic mutations localizing to ChrSp • Etiology o Genetic: Mutations alter molecular reactions at multiple migration points =;> migrational arrest =;> HGM o Acquired: Toxins/infections =;> reactive gliosis/macrophage infiltration =;> disturbed neuronal migration/cortical positioning • CMV-infected cells can fail to migrate =;> lissencephaly • Toxins (alcohol, XRT) =;> slow/abnormal migration • Epidemiology o 17% of neonatal CNS anomalies at autopsy o Found in up to 40% of patients with intractable epilepsy

Gross Pathologic & Surgical Features • Spectrum: Agyria to normal cortex + small ectopic nodules GM • Persistent fetal leptomeningeal vascularization if severe

Microscopic Features • Multiple neuronal cell types, immature/dysplastic neurons o Excess of excitatory over inhibitory neuronal circuitry • Neuronal numbers, positioning abnormal

Staging, Grading or Classification Criteria • Classification by specific location, type, and size of HGM may predict specific gene mutation o Nodular/band/curvilinear, anterior/posterior, subcortical, subependymal

I CLINICAL. ISSUES Presentation • Most common signs/symptoms: Cognitive function, age of seizure (Sz) onset/severity depend on location/amount of abnormally positioned GM • Clinical profile: Young child with developmental delay and Sz

o Mild cases or simple subcortical nodules can be asymptomatic and only incidental findings on imaging or autopsy • Gender: Males with X-linked disorders have significantly worse brain malformation and outcome

Natural History & Prognosis • Variable life span dependent upon extent of malformation o Type 2 lissencephaly: Months o Focal heterotopias: Can be normal (depends on Sz control)

Treatment • Surgery reserved for intractable Sz o Resect small accessible epileptogenic nodules o Corpus callosotomy if bilateral or diffuse unresectable lesions

I

DIAGNOSTIC

CHECKLIST

Consider • HGM is common and commonly other anomalies

Image Interpretation

associated with

Pearls

• HGM doesn't enhance and doesn't calcify • Subcortical HGM can appear mass-like, mimic tumor

I SELECTED

REFERENCES

Sheen VLet al: Periventricular heterotopia associated with chromosome 5p anomalies. Neurology 60:(6):1033-6,2003 2. Eriksson SH et al: Exploring white matter tracts in band heterotopia using diffusion tractography. Ann Neurol 52(3):327-34, 2002 3. Barkovich AJet al: Classification system for malformations of cortical development update 2001. Neurology 57(12):2168-78,2001 4. Barkovich AJ,Kuzniecky RI: Gray matter heterotopia. Neurology 55: 1603-8,2000 5. Gressens P: Mechanisms and disturbances of neuronal migration. Pediatric Research 48: 725-30, 2000 6. Barkovich AJ:Morphologic characteristics of subcortical heterotopia: MR imaging study. AJNR21(2):290-5,2000 7. Morioka T et al: Functional imaging in periventricular nodular heterotopia with the use of FDG-PETand HMPAO-SPECT. Neurosurg Rev 22(1):41-4, 1999 8. Hannan AJet al: Characterization of nodular neuronal heterotopia in children. Brain 122(Pt 2): 219-38, 1999 9. Marsh L et al: Proton magnetic resonance spectroscopy of a grey matter heterotopia. Neurology 47(6):1571-4, 1996 10. Shimodozono M et al: Functioning hetertopic grey matter? Increased blood flow with voluntary movement and sensory stimulation. Neuroradiology 37(6):440-2, 1995 11. De Voider AG et al: Brain glucose utilization in band heterotopia: Synaptic activity of "double cortex". Pediatr Neurolll(4):290-4, 1994 1.

Demographics • Age o Severe cases present in infancy with Sz & associated malformations

Congen ital Malformations

HETEROTOPIC GRAY MATTER 1 61

Typical (Left) Axial T2WI MR shows symmetrical subependymal nodular heterotopia (open arrow) lining ventricles. Note thin HeM line (arrows) paralleling ventricle and nodules of HeM between ventricles and cortex. (Right) Axial T2WI MR shows unusual linear array of subcortical nodules of HeM. Overlying cortex is thinned (open arrow) and has abnormal gyri (arrow).

Typical

(Left) Axial T7WI MR shows

mass like collection of nodules and sworls of HeM enlarging the left parietal lobe. The ipsilateral cortex (arrows) and the body of caudate nucleus (curved arrow) are abnormal. (Right) Axial TlWI MR in child with agenesis of the CC shows fused left basal ganglia (arrow).Subependymal HeM lines anterior horn (open arrow) and extends to the ipsilateral abnormal overlying cortex.

(Left) Coronal TlWI MR shows thinned left frontal white matter and hazy HeM (arrow) between ventricle and overlying cortex. The left and right frontal cortex are asymmetric. (Right) Axial MEe in same patient shows multiple EEe spikes overlying the same region and the overlying cortex.

Congenital Malformations

62

Coronal oblique graphic shows the thickened "pebbly" gyri of polymicrogyria involving the opercular cortex (arrow). Note the irregular cortical - white matter interface (curved arrow).

Abbreviations

and Synonyms

• Pachygyria = term that is interchangeable with incomplete lissencephaly • Polymicrogyria (PMG) sometimes referred to as cortical dysplasia

Definitions • Pachygyria or incomplete lissencephaly o Malformation due to abnormal neuronal migration, sparse, broad, flat gyri o Two major classifications: Cobblestone complex and lissencephaly/subcortical band heterotopia spectrum • Polymicrogyria o Malformation due to abnormality in late neuronal migration and cortical organization o Neurons reach the cortex but distribute abnormally forming multiple small undulating gyri

General Features • Best diagnostic clue o Incomplete lissencephaly (pachygyria): "Figure-of-eight" morphology of cerebrum, smooth brain

Coronal T2WI MR shows the excessive small convolutions of polymicrogyria (arrow). Also note left frontal subcortical heterotopias (curved arrow), absence of the corpus callosum.

o PMG: Excessively small and prominent convolutions • Location o Incomplete lissencephaly (pachygyria): When focal, nearly always bilateral, often parietooccipital o Polymicrogyria: Predilection for perisylvian regions, when bilateral often syndromic • Morphology o Incomplete lissencephaly (pachygyria): Smooth thick cortex, sparse flat gyri, sharp gray-white junction o Polymicrogyria: Small irregular gyri ,normal or thick cortex, indistinct cortical-white matter junction

Radiographic Findings • Radiography: Polymicrogyric microcephalic

newborns, infants often

CT Findings • NECT o Incomplete lissencephaly (pachygyria) • Lissencephaly/subcortical band heterotopia spectrum: Thick, smooth cortex with shallow sulci, flat gyri • Cobblestone complex: Pebbled cortex, shallow sulci, ~ WM attenuation, ± other brain malformations o Polymicrogyria: Excessive small convolutions, periventricular Ca++ if secondary to CMV

DDx: Cortical Malformations

Zellweger Syndrome

Microlissencephaly

Hemimegalencephaly

Congenital Malformations

Congenital CMV

PACHYGYRIA-POLYMICROGYRIA 1

Key Facts Terminology • Pachygyria = term that is interchangeable with incomplete lissencephaly • Polymicrogyria (PMG) sometimes referred to as cortical dysplasia

Imaging Findings • Incomplete lissencephaly (pachygyria): "Figure-of-eight" morphology of cerebrum, smooth brain • PMG: Excessively small and prominent convolutions • Incomplete lissencephaly (lissencephaly/subcortical band heterotopia) • Arrested neurons ~ thick inner subcortical GM band, lateral to this ~ hyperintense cell sparse zone • Polymicrogyria (two imaging patterns)

• < 12 months: Small, fine undulating cortex with normal thickness (3-4 mm) • > 18 months: Thick, bumpy cortex (6-8 mm), ± hypomyelination, ± cortical infolding

Clinical Issues • Incomplete lissencephalies cobblestone complex (CMDs) ~ hypotonia, weakness, ± seizures • Polymicrogyria ~ faciopharyngoglossomasticatory diplegia, developmental delay, seizure, hemiparesis

Diagnostic Checklist • Polymicrogyria ~ always seen with schizencephaly • Incomplete lissencephaly (pachygyria) ~ smooth "figure-of-eight brain"

• MRS: !NAA at seizure-precipitating, hypomyelinated sites

MR Findings • TlWI o Incomplete lissencephaly (lissencephaly/subcortical band heterotopia) • Figure of eight brain morphology, vertical shallow sylvian fissures, smooth brain with thick cortex • Thin outer GM mantle ~ cell sparse zone (isointense to WM) ~ thick inner GM band o Incomplete lissencephaly (cobblestone complex) • Neurons overmigrate creating a pebbled contour of the brain surface o Polymicrogyria • Irregular cortical surface, cortex isointense to gray matter, indistinct cortical-white matter interface • T2WI o Incomplete lissencephaly (lissencephaly/subcortical band heterotopia) • Thickened cortex, sparse large gyri, shallow vertical sylvian fissures • Arrested neurons ~ thick inner subcortical GM band, lateral to this ~ hyperintense cell sparse zone • Location: Typically parietooccipital (exception: X-linked lissencephaly ~ involves the frontal lobes) o Incomplete lissencephaly (cobblestone complex) • Irregular cortical projections into white matter, hypomyelination common • Ocular and cerebral anomalies, and hydrocephalus secondary to aqueductal stenosis o Polymicrogyria (two imaging patterns) • < 12 months: Small, fine undulating cortex with normal thickness (3-4 mm) • > 18 months: Thick, bumpy cortex (6-8 mm), ± hypomyelination, ± cortical infolding • T2* GRE: Hypointense foci at sites of periventricular Ca++ ~ CMV • Tl C+: Amplifies dysplastic leptomeningeal veins overlying regions of polymicrogyria • MRV: Demonstrates persistent embryonic veins overlying abnormal cortex

Congenital

63

Ultrasonographic

atrophic and/or

Findings

• Subcortical band heterotopia may show disorganized parenchymal echogenicity, mimic edema

Nuclear Medicine

Findings

• PET o Increased metabolism during ictus o Hypometabolic interictally

Other Modality

Findings

• Fetal MR and US: Agyric cortex normal up to 26 weeks • Prenatal MR can defect PMG other anomalies of cortical development as early as 24 weeks

Imaging Recommendations • Best imaging tool: MRI comprehensively assesses malformation, NCCT for suspected Ca++ (TORCH) • Protocol advice: Techniques that accentuate cortical-white matter interface: Volume 3D SPGR (Tl weighted)

I DIFFERENTIAL

DIAGNOSIS

Malformations of cortical development otherwise classified

not

• Malformations secondary to inborn errors of metabolism o Mitochondrial and pyruvate metabolism disorders o Zellweger syndrome: Deficiency of peroxisomes, severe hypomyelination, cortical malformations • Microlissencephaly: Disorder of stem cell proliferation, HC < 3 SDs below the mean • Hemimegalencephaly: Disorder of neuronal proliferation, migration, and differentiation • Congenital CMV: Association with polymicrogyria, NCCT for detection of periventricular Ca++

Malformations

PACHYGYRIA-POLYMICROGYRIA 1 64

General Features

Presentation

• General path comments o Incomplete lissencephaly/subcortical band heterotopia complex ~ arrest of neuronal migration o Incomplete lissencephaly cobblestone complex ~ neuronal overmigration o Polymicrogyria ~ disorder of late neuronal migration and cortical organization • Genetics o Incomplete lissencephaly/subcortical band heterotopia spectrum • Chromosome 17 gene deletions (ARX & LISl) ~ parietooccipitallocation ~ Miller-Dieker syndrome • X-linked mutations: Xq22.3-23 deletion associated with frontal lobe involvement o Incomplete lissencephaly/cobblestone complex ~ congenital muscular dystrophies (CMD) • Fukuyama CMD ~ mutation of 9q31-33 o Polymicrogyria: Deletions of: 22q 11.2 (DiGeorge critical region), Xq28 and 16qI2.2-21 • Etiology: Polymicrogyria ~ intrauterine infection, ischemia, toxins or gene mutations • Epidemiology: Malformations of cortical development found in - 40% of children with intractable epilepsy • Associated abnormalities o Incomplete lissencephaly/cobblestone complex ~ ocular, cerebellar, white matter, hydrocephalus • Walker-Warburg syndrome, Fukuyama CMD, muscle-eye-brain disease o Polymicrogyria ~ congenital bilateral perisylvian syndrome (Foix-Chavany-Marie) • Aicardi, Zellweger, and Peliziaeus-Merzbacher disease

• Most common signs/symptoms o Incomplete lissencephalies cobblestone complex (CMDs) ~ hypotonia, weakness, ± seizures o Polymicrogyria ~ faciopharyngoglossomasticatory diplegia, developmental delay, seizure, hemiparesis • Clinical profile: Onset and severity of seizures relates to extent of malformation

Gross Pathologic & Surgical Features • Incomplete lissencephaly/subcortical band heterotopia spectrum ~ smooth cortex with cell-sparse zone • Incomplete lissencephaly/cobblestone complex ~ pebbled surface of the brain • Polymicrogyria ~ multiple small gyri, gyri lie in haphazard orientation

Microscopic

Features

• Polymicrogyria ~ range of histology reflecting derangement of the six layered lamination of the cortex o Cortical layers 4 and 5 most involved o Leptomeningeal embryonic vasculature overlies malformation o Myelination within the subcortical or intracortical fibers changes the cortical appearance on T2 weighted images

Staging, Grading or Classification Criteria • Polymicrogyria ~ unlayered or four layered cytoarchitecture

Demographics • Age: Signs and symptoms vary with severity of gene mutation, and resultant phenotypic expression • Gender: X-linked lissencephalies ~ boys • Ethnicity: Fukuyama muscular dystrophy seen primarily in children of Japanese ancestry

Natural History & Prognosis • Variable life span based on: Severity of genetic mutation, resultant malformation and associated anomalies

Treatment • Options, risks, complications o Medical management of seizures and supportive o Corpus callosotomy if bilateral or diffuse unresectable lesions and intractable epilepsy

care

IDIAGNOST1CiCHE
Image Interpretation

Pearls

• Fetal appearance of the newborn brain (lissencephaly), primitive sylvian fissures with thick cortex (polymicrogyria)

I SELECTED REFERENCES 1. 2.

3.

4. 5.

6.

Righini A et al: Early prenatal MR imaging diagnosis of polymicrogyria. AJNR 25: 343-6, 2004 Takanashi J et al: The changing MR imaging appearance of polymicrogyria: A consequence of myelination. AJNR 24: 788-93, 2003 Barkovich AJ et al: Classification system for malformations of cortical development Update 2001. Neurology 57: 2168-78, 2001 Barkovich AJ et al: Syndromes of bilateral symmetrical polymicrogyria. AJNR 20: 1814-21, 1999 Barkovich AJ et at. Neuroimaging manifestations and classification of congenital muscular dystrophies. AJNR 19: 1389-96, 1998 Kuzniecky R et at. The congenital bilateral perisylvian syndrome: imaging findings in a multicenter study. AJNR 15: 139-44, 1994

Congenital Malformations

PACHYGYRIA-POLYMICROGYRIA 1 65

Tvnir>ll (Left) Axial NECT shows "figure-of eight" configuration of the brain. Note the smooth, thick cortex with sparse flat gyri (arrow). Pachygyria, (incomplete lissencephaly). (Right) Axial T2WI MR shows hour-glass configuration of the brain, smooth cortex, and sub-cortical band heterotopia (arrows). Incomplete lissencephaly/subcortical band heterotopia spectrum.

(Left) Axial T2WI MR shows absence of the corpus callosum and bi-frontal shallow sulci and flat gyri (arrow). X-linked pachygyria (incomplete lissencephaly). (Right) Axial PO/Intermediate MR shows closed lip schizencephaly lined by polymicrogyric cortex (arrow).

Typical (Left) Sagittal T7 WI MR shows polymicrogyria involving the opercular cortex. Note the loss of normal gyral architecture, thickened cortex and indistinct cortical-white matter interface (arrow). (Right) Axial T2WI MR shows diffuse small irregular gyri with indistinct gray-white interface indicative of polymicrogyria (arrows). Congenital bilateral perisylvian syndrome.

Congenital Malformations

LISSENCEPHALY TYPE 1 66

Axial graphic depicts band heterotopia (arrow) in right hemisphere. Left hemispheric lissencephaly has thick subcortical GM band, thin outer cortex (open arrow).

ITER.MINOLOGY Abbreviations

and Synonyms

• Classical lissencephaly (LIS); type llissencephaly (LISl); pachygyria-agyria complex; X-linked lissencephaly (XLIS) • Band heterotopia (BH), double cortex (DCX)

Definitions • Classical type 1 lissencephaly is a congenital developmental disorder characterized by arrested neuronal migration, a 4-layer cortex, and a smooth (or relatively smooth) brain surface o Spectrum of lissencephaly phenotypes caused by gene alterations, most commonly LISl and DCX (also called XLIS)

!IMAGING. FIND.INGS General Features • Best diagnostic clue o LIS: Hour-glass configuration of brain; often somewhat incomplete (pachygyria-agyria) o BH: Thinner, symmetric subcortical ribbons of GM, paralleling cortex and embedded in white matter • Location o LISl: More severe parietal/occipital

Axial TlWI MR in band heterotopia shows thin cortex (open arrow), adjacent white matter layer (white arrow) and thick subcortical GM band (black arrow) paralleling the cortex.

o XLIS (DCX): More severe sub frontal/temporal • Size o Thickness of band of GM predicts configuration/thickness of overlying cortex AND underlying white matter (WM) • Thin band predicts near normal cortical thickness/ appearance • Thick band predicts thin, abnormally convoluted overlying cortex • Morphology o LIS • Thick inner band GM, cell sparse WM zone, thin outer layer GM • Shallow Sylvian fissure ~ brain with "hour-glass" configuration • Usually some gyral formation (pachygyria-agyria complex) o BH • Thick inner GM band + thin, abnormal cortex OR • Thin/partial inner band + normal cortex

CT Findings • NECT o Always isodense with GM o +/- Small midline septal Ca++ (Miller-Dieker) • CECT: No enhancement

DDx: Lissencephaly

CMV Lissencephaly

Type 2 Lissencephaly

LCH Microcephaly

Congenital Malformations

LCH Microcephaly

LISSENCEPHALY TYPE 1

1 67

to

MR Findings • TIWI: Distinct GM-WM layers; cell-sparse WM layer may have !signal • T2WI: Distinct layering; 1 signal cell sparse WM layer • T2* GRE o Midline calcification in Miller-Dieker o Periventricular and subcortical white matter calcifications in CMV related lissencephaly • MRS: !N-acetylaspartate (NAA) in affected cortex

Ultrasonographic Findings • Real Time: Late intrauterine

o Severe cerebellar and hippocampal involvement suggests RELN mutation (7q22) o +/- Microcephaly, hydrocephalus, micro calcification, axonal swelling, agenesis of corpus callosum, hypoplastic brain stem, stippled epiphyses, loose skin, lymphedema, arthrogryposis

Cobblestone or type 2 lissencephalies • "Pebbly" surface of brain, cerebellar and ocular abnormalities, congenital muscular dystrophy

Bilateral, diffuse subependymal

documentation

possible

Angiographic Findings • Conventional o Lateral placement of middle cerebral artery branches due to shallow Sylvian fissures o Wavy vessels on surface of brain o Lack of formed gyral blush

heterotopia

• Mutation Filamin-l gene (required for cell migration to cortex) on Xq28 • Nodular heterotopia lines ventricles, simulates tuberous sclerosis, no enhancement, no Ca++

I PATHOLOGY General Features

Nuclear Medicine Findings • PET: Inner cellular layer has higher glucose utilization than outer layer (fetal pattern)

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: MRI + thin slice SPGR (surface coil/3D reconstruction) for subtle, focal band heterotopia and adjunctive surface reconstruction (gyral array)

I DIFFERENTIALDIAGNOSIS lissencephaly syndromes and variants • Miller-Dieker syndrome: LISI plus deficiency of 14-3-3epsilon => Miller-Dieker syndrome (severe LIS plus facial features) • ARX mutations: XLIS with abnormal genitalia (XLAG) o Males have XLAG, females have agenesis of corpus callosum • Lissencephaly with cerebellar hypoplasia (LCH) o Can be seen with LISI and XLIS mutations

• General path comments o Surface gyral pattern predicts associated chromosomal deficiency o Embryology • Subependymal germinal zones proliferate, form neuroblasts, glia • Neuroblasts leave ventricular surface by "leading edge" extension/growth cone formation (requires "filamen") • Neuroblasts attach to radially arranged glial fibers (RGFs) • Neuroblasts migrate along RGFs to mantle (via cell-adhesion, ligand-receptor interactions) • RGFs guide/nourish migrating neuroblasts • Neuroblasts disengage from RGFs (requires "reelin" secreted by layer 1 pioneer neurons) • Earliest neuroblasts disengage in cortical subplate • Later waves pass through initial layer, form 6-layered cortex • Genetics o Deletion of genes that govern specific stages of neuronal migration

Congenital Malformations

LISSENCEPHALY TYPE 1

1 68

• Large deletion LIS1 gene located on 17p13.3 plus deficiency of 14-3-3epsilon ~ Miller-Dieker • Smaller deletion LIS1gene (also called PAFAH1B1 gene) ~ isolated LIS1/BH • DCX (found in the leading edge of migrating neurons and growth cone of migrating neurons) mutated in XLIS • XLIS/BH: XLIS gene on Xq22.3-q23, mothers (focal band heterotopia), sons (lissencephaly) • Etiology o Genetic: Mutations alter molecular reactions at any/multiple migration points ~ migrational arrest • LIS is one of most common neuronal migrational disorders associated with consanguinity o Acquired: Toxins/infections ~ reactive gliosis/macrophage infiltration disturbs neuronal migration/cortical positioning • CMV-infected cells can fail to migrate or arrest • Toxins (alcohol/irradiation) ~ abnormal migration • Epidemiology: 1-4:100,000 live births • Associated abnormalities: +/- Cardiac or facial anomalies

Gross Pathologic

& Surgical Features

• Variable cortical, gyral thickness and maturity of gyral array • Variable thickness of subcortical WM

Microscopic

Features

• 4-layer cortex o Superficial molecular or marginal layer o Thin outer cortical layer of neurons (large, abnormal position) o "Cell-sparse" WM zone o Thick deep cortical layer of neurons (lack orderly arrangement) • Sparse underlying WM • Hypoplastic corticospinal tracts, heterotopia of olives

Staging, Grading or Classification • Graded by location (frontal/posterior), cortex/inner band GM o Agyria with limited frontotemporal common

Criteria thickness of pachygyria most

I CLlN1CAlJSSUES Presentation • Most common signs/symptoms o LIS: Developmental delay and seizures o BH: Seizures may be late onset & cognitive function may be normal if well developed cortex • Clinical profile: Cognitive function, age of seizure onset/severity depends on location/amount of abnormally positioned GM

Demographics • Age: Severe forms LIS identified in infancy, milder BH forms identified in older child or adult • Gender o LIS1: Full mutations ~ severe posterior lissencephaly, mosaic mutations ~ posterior BH

o XLIS/DCX (anterior): Responsible for most familial BH, 80% sporadic female cases, 25% sporadic males • Mothers (focal band heterotopia), sons (lissencephaly) • Missense mutations account for less severe brain malformations (BH or pachygyria-BH) in some males

Natural History & Prognosis • Variable life span dependent upon extent of malformation o Focal subcortical BH often lead normal life o LIS, thick complete band/thin cortical ribbon: Significant mental retardation, motor deficits, seizures, early demise

Treatment • Treat seizures (corpus callosotomy intractable epilepsy)

an option for

IOlAGNQST1C··CHECKEIST Consider • Gyral pattern predicts inheritance

Image Interpretation

pattern

Pearls

• Fetal MR, US: Agyric (smooth) cortex is normal up to 26 weeks! • Look for specific signs on fetal studies: Presence or absence of parieto-occipital fissure; poor development of Sylvian fissure

I SELECTED REFERENCES Sicca F et al: Mosaic mutations of the LISI gene cause subcortical band heterotopia. Neurology 61(8):1042-6, 2003 2. Toyo-oka K et al: 14-3-3epsilon is important for neuronal migration by binding to NUDEL: A molecular explanation for Miller-Dieder syndrome. Nat Genet 34(3):274-85, 2003 3. Barkovich AJ et al: Classification system for malformations of cortical development: Update 2001. Neurology 26;57(12):2168-78,2001 Ross ME et al: Lissencephaly with cerebellar hypoplasia 4. (LCH): A heterogeneous group of cortical malformations. Neuropediatrics 32(5):256-63, 2001 5. Kaminaga T et al: Proton magnetic resonance spectroscopy in disturbances of cortical development. Neuroradiology 43(7):575-80,2001 Pfund Z et al: Lissencephaly: Fetal pattern of glucose 6. metabolism on positron emission tomography. Neurology 55(11):1683-8, 2000 Gressens P: Mechanisms and disturbances of neuronal 7. migration. Pediatr Res 48:725-30,2000 8. Pilz DT et al: Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1. Hum Mol Genet 8(9):1757-60,1999 9. al-Qudah AA. Clinical patterns of neuronal migrational disorders and parental consanguinity. J Trop Pediatr 44(6):351-4, 1998 10. Pilz DT et al: LISI and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. Hum Mol Genet 7(13):2029-37, 1998 1.

Congenital Malformations

1 69

Typical (Left) Axial T2WI MR in lissencephaly shows thin, smooth cortical ribbon (arrow) and thick inner band of gray matter (curved arrow). Primitive Sylvian fissures give the brain an "hour-glass" configuration. (Right) Axial T2WI MR in pachygyria-agyria complex shows posterior agyria, anterior pachygyria, thin cortical ribbon (open arrow), cell sparse white matter (arrow) and thick inner neuron band (curved arrow).

(Left) Coronal T2WI MR of a fetus with lissencephaly. Note the lack of gyral formation (open arrow) and the vertical hippocampal formations (arrow). (Right) Coronal T2WI MR in a child with lissencephaly shows thin outer cortex (open arrow), cell-sparse layer (white arrow), thick inner gray matter band (black arrow) and slight gyral formation.

Typical (Left) Coronal TlWI MR shows a thick inner band of grey matter (arrow) and a primitive appearing cortical ribbon (open arrow) with shallow sulci in this child with band heterotopia. (Right) Coronal TlWI MR in another child shows a thin inner gray matter band (arrow) and a near normal outer cortical ribbon (open arrow) with well developed gyri and sulci.

Congenital Malformations

SCHIZENCEPHALY 1 70

Coronal graphic shows right closed-lip (arrow) and left open-lip (open arrow) schizencephaly, both lined by gray matter. Note absence of septum pellucidum (curved arrow).

Coronal oblique 3D CT shows bilateral open-lip schizencephaly. Note gyri radially arranged around cleft (arrows). They give the appearance of "diving" into the cleft.

[TERMINOLOGY

Radiographic Findings

Abbreviations

• Myelography: Cisternography may define ruptured membrane in "collapsed" open-lip Schiz

and Synonyms

• Schizencephaly (Schiz); formerly called "absence of the septum pellucidum with porencephalies"

Definitions • Schizencephaly is a congenital brain malformation characterized by clefts extending from pial surface of cerebral mantle to ventricle and are lined by polymicrogyric cortex

CT Findings • NECT: Relatively dense gray matter lines CSF clefts • CECT o Large, primitive appearing veins near cleft o +/- Hydrocephalus (especially open-lip Schiz with ruptured membrane)

MR Findings

I IMAGING

FINDINGS

General Features • Best diagnostic clue: Trans-mantle gray matter lined clefts • Location: Usually involving insula/adjoining pre/postcentral gyri • Size: "Closed-lip" (small defect) or "open-lip" (large defect) • Morphology o Bilateral or unilateral full surface clefts of cortical mantle o Gyri and sulci radiate into cleft or furrow, aiding differentiation from late intra-uterine or early postnatal MCA infarction

• TlWI o Deformity of ventricle at site of closed-lip Schiz "points" to cleft o Septum pellucidum absent, partially deficient, or present • Usually present if temporal or occipital clefts • T2WI o Infolding of gray matter along transmantle clefts • Gray matter is nodular, pachy-polygyric • Abnormally arrayed gyri "dive" into cleft • +/- Arachnoid membrane covers cleft, easily ruptured • Heterotopias, incomplete heterotopia-lined clefts, and peri-opercular dysplasias commonly associated o Additional related anomalies (in some patients)

DDx: Cortical Defects

Perinatal Stroke

Perinatal Stroke

Fetal Insult

Congenital Malformations

Fetal Insult

SCHIZENCEPHALY Key Facts Imaging Findings

Pathology

• Location: Usually involving insula/adjoining pre/postcentral gyri • Bilateral or unilateral full surface clefts of cortical mantle • Gyri and sulci radiate into cleft or furrow, aiding differentiation from late intra-uterine or early postnatal MCA infarction • Deformity of ventricle at site of closed-lip Schiz "points" to cleft

• Genetic: EMX2 is first mutation to be identified • Early prenatal insult: Affecting germinal zone prior to neuronal migration • Type I (closed-lip): Fused pial-ependymal seam lined by gray matter forms "furrow" in cortex • Type II (open-lip): Large, gray matter lined, fluid-filled cerebrospinal fluid clefts

Top Differential

• Type I: May be near normal or have congenital hemiparesis and seizures • Type II: Mental retardation, spasticity, seizures, severely compromised

Diagnoses

• "Clastic schizencephaly" • Porencephaly • Hydranencephaly

• • • • •

•

• Pituitary/optic pathway hypoplasias • Anomalous hippocampus and enlarged temporal horn (50%) • If septum pellucidum absent, forniceal columns may be fused in midline • Truncated corpus callosum (may be deficient anteriorly) • Anomalies of basal ganglia and thalami FLAIR: Gliotic foci present in later insults T2* GRE: Rare Ca++ (more common in intrauterine injury or infection) DWI: In utero demonstration of hypoperfusion injury and stroke possible MRV: Prominant embryonic venous elements overlying cleft 3D Surface Rendered MRI o Best defines relationship of gyri/sulci to cleft in cerebral mantle fMRI: Functional reorganization of the undamaged hemisphere reported

Ultrasonographic

Findings

Findings

• Conventional: Middle cerebral artery deficiencies occur, may be difficult to confirm when bilaterally symmetrical

Nuclear Medicine

Findings

• PET: Normal or t glucose metabolism and perfusion of wall of cleft (normal gray matter activity)

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Multiplanar reconstruction)

MRI (+/- 3D

I DIFFERENTIAl. DIAGNOSIS "Clastic schizencephaly" • Insult after neuronal migration complete (may still be late intrauterine) • Cortex maintains normal array of atrophied gyri

Porencephaly • Caused by trauma vascular insult etc • Lined by gliotic WM, not dysplastic GM! • High signal run on FLAIR

Hydranencephaly • Destruction of tissue in middle and anterior cerebral artery territory • Difficult to differentiate if severe schizencephaly plus hydrocephalus

I PATHO[OGY General Features

• Real Time: Diagnosable by fetal ultrasound and fetal MRI; progressive changes have been reported

Angiographic

Clinical Issues

• General path comments o Insult or inherited mutation lead to same pathologic/imaging features, typically in MCA distribution • Intrauterine insults include: Infection (CMV), maternal trauma or toxin exposure • Reported with alloimmune thrombocytopenia (acquired, but subsequent pregnancies have same risk of intrauterine damage) o Experimental schizencephaly induced by mumps virus • Antigen detected in ventricular zone neuroepithelial cells & radial glial fibers ~ destruction & disordered migration o Embryology-anatomy • Emx2 (gene locus 10q26.1) is a regulatory gene with a role in structural patterning of developing forebrain • Emx2 is expressed in proliferating neuroblasts of ventricular zone & postmitotic Cajal-Retzius cells (control neuronal migration)

Congenital Malformations

1 71

1 72

• Genetics: Mutations in the homeobox gene Emx2 in some (not all) cases; particularly type II Schiz (bilateral) • Etiology o Genetic: EMX2 is first mutation to be identified o Early prenatal insult: Affecting germinal zone prior to neuronal migration • Epidemiology o Bilateral clefts are more commonly reported in neuropathologic series o Unilateral = bilateral or unilateral> bilateral in live patient series o Exact incidence unknown (changing terminology to describe Schiz) • Associated abnormalities o Frontal lobe dysplasia or inferior fusion, partial clefts, loss of WM, ventricular diverticula o Hippocampal and callosal anomalies, septal, optic, and pituitary anomalies

Gross Pathologic & Surgical Features • Transmantle clefts with separated or apposed gray matter lining • Abnormal cortical array of pachy, poly, or near normal-sized gyri "dive" into cleft • Thalami, corticospinal tracts may be atrophied or not formed

Microscopic

• Size and magnitude of clefts, as well as number of associated malformative lesions, govern severity of motor deficits, developmental delays, and epilepsies • Single closed-lip defects may be asymptomatic or diagnosed in adult • Bilateral clefts usually associated with severe disabilities

Treatment • Treat seizures and hydrocephalus; motor deficits

• Little if any glial scarring • Loss of normal laminar architecture • Pachygyria, polymicrogyria, or heterotopic

Consider • Image to confirm etiology of "congenital hemiparesis": Perinatal stroke versus unilateral schizencephaly

Image Interpretation

I SELECTED REFERENCES 2.

Staging, Grading or Classification Criteria

3.

• Type I (closed-lip): Fused pial-ependymal seam lined by gray matter forms "furrow" in cortex • Type II (open-lip): Large, gray matter lined, fluid-filled cerebrospinal fluid clefts

4.

5.

Presentation

6.

• Most common signs/symptoms o Unilateral: May present with seizures or motor deficit "congenital" hemiparesis o Bilateral: Hemi or quadriparesis, microcephaly or hydrocephalus, spasticity, severe developmental delays, mental retardation; seizures are not universal • Clinical profile o Type I: May be near normal or have congenital hemiparesis and seizures o Type II: Mental retardation, spasticity, seizures, severely compromised

7.

8.

Vandermeeren Y et al: Functional relevance of abnormal fMRI activation pattern after unilateral schizencephaly. Neuroreport 13(14):1821-4, 2002 Dale ST et al: Neonatal alloimmune thrombocytopenia: Antenatal and postnatal imaging findings in the pediatric brain. AJNR 23(9):1457-65,2002 Cecchi C: Emx2, a gene responsible for cortical development, regionalization and area specification. Gene 29;291(1-2):1-9, 2002 Hayashi N et al: Morphological features and associated anomalies of schizencephaly in the clinical population: Detailed analyis of MR images. Neuroradiology 44(5):418-427, 2002 Raybaud C et al: Schizencephaly: Correlation between the lobar topography of the cleft(s) and absence of the septum pellucidum. Childs Nerv Syst 17:217-22, 2001 Sato N et al: MR evaluation of the hippocampus in patients with congenital malformations of the brain. AJNR 22(2):389-93, 2001 Takano T et al: Experimental schizencephaly induced by Kilham strain of mumps virus: Pathogenesis of cleft formation. Neuroreport 10(15):3149-54, 1999 Morioka T et al: Functional imaging in schizencephaly using [18F] fluoro-2-deoxy D-glucose positron emission tomography (FDG-PET) and single photon emission computed tomography with technetium -99m -hexamethyl- propyleneamine oxime (HMPAO-SPECT).Neurosurg Rev 22(2-3):99-101, 1999

Demographics • Age: Diagnosed at onset of seizures or when motor deficit noticed

Natural History & Prognosis • Malformation common

is stable, development

of epilepsy

Congenital

Pearls

• Clefts formed before neuronal migration have "diving gyri" • Gyri around defects formed after neuronal migration have a normal array, but are shrunken

gray matter

ICtlN IQAtlSStJES

for

~.[)IAG·.NO$TIC~•• •• I-1.E¢~~ls-r

1.

Features

physiotherapy

Malformations

1 73

Tvoical (Left) Axial TlWI MR shows a unilateral closed-lip schizencephaly. Thickened gray matter (arrows) lines the cleft. There is deficiency of the right caudate body. The septum pellucidum is present. (Right) Axial TI WI MR in another child with seizures and hemiparesis shows similar findings. Thickened gray matter lines the cleft (arrow). The septum pellucidum is absent (open arrow).

(Left) Axial TI WI MR shows focal calcifications (arrow) lining the ventricles in this infant with early intrauterine CMV infection leading to schizencephaly. Periventricular cysts (open arrow) are noted. (Right) Axial T2WI MR in the same infant shows ventriculomegaly and widely open left schizencephalic cleft. The thin cortical ribbon (arrow) extends along the surface of the cleft.

(Left) Axial T2WI MR in a fetus shows huge bilateral open-lip schizencephalic clefts (arrows). (Right) Coronal T2WI MR in another child shows similar findings. Gray matter (arrows) lines the clefts. The forniceal columns (curved arrow) are fused in the midline. Left temporal GW junction is abnormal.

Congenital Malformations

HEMIMEGALENCEPHALY 74

Coronal graphic shows overgrowth of the left cerebral hemisphere. Note shift of midline structures, excess of white matter, flattened gyri and abnormal ipsilateral anterior horn (arrow).

I

!TERMINOlOGY Abbreviations

Coronal NECT with 3D skin surface reconstruction in a child with hemimegalencephaly shows overgrowth of facial tissues. There is also hypertrophy of the underlying bony structures.

Radiographic Findings • Radiography o Asymmetric calvarium o +/- Hemimandibular, or hemimaxillary

and Synonyms

• Unilateral megalencephaly • Focal megalencephaly

overgrowth

CT Findings

Definitions • Hamartomatous overgrowth of part/all of a hemisphere • Defect of cellular organization, neuronal migration

I IMAGING F1NDING§ General Features • Best diagnostic clue o Mild, moderate, or markedly enlarged dysplastic hemisphere o Dysplastic cortex, abnormal gyri o Displaced posterior falx o Large lateral ventricle with abnormally shaped frontal horn • Location: Occipital common (any lobe may be involved) • Size: Subtle or grossly enlarged • Morphology: Normal sulci or pachygyria,or polygyria

DDx: Asymmetric

Megalencephaly

• NECT o Large cerebral hemisphere, hemicranium o Posterior falx and occipital pole "swing" to contralateral side o Lateral ventricle is large with abnormally shaped frontal horn o Dystrophic Ca++ of white matter (WM) or of thickened cortex • CECT: Large vessels common • CTA: May show enlarged ipsilateral vessels which are tortuous or bizarre

MR Findings • TlWI o Thick cortex: Pachygyria, polygyria, fused gyri and shallow sulci o Neuronal heterotopias, subependymal, +/- scattered throughout hemisphere o Lateral ventricle is usually large, frontal horn is straight, pointed o Cerebellum, brainstem may be dysplastic

Hemispheres

Megalencephaly

Rasmussen

Congenital Malformations

Rasmussen

HEMIMEGALENCEPHALY 1

Key Facts Terminology

Top Differential

• Unilateral megalencephaly • Hamartomatous overgrowth of part/all of a hemisphere • Defect of cellular organization, neuronal migration

• Megalencephaly (both hemispheres) • Hemiatrophy • Hemimegalencephaly of tuberous sclerosis (TS)

Imaging Findings

• Variable patterns of overgrowth, gliosis reflect variability in timing of precipitating insult

• Mild, moderate, or markedly enlarged dysplastic hemisphere • Dysplastic cortex, abnormal gyri • Large lateral ventricle with abnormally shaped frontal horn • Location: Occipital common (any lobe may be involved) • +/- Small brainstem, crossed cerebellar diaschisis • +/- Cerebellar hemiovergrowth, heterotopias

•

• • • • • •

o +/- Chiari 1 (bulky supratentorial brain tissue displaces tonsils) T2WI o Variable WM signal (advanced myelination, gliosis, Ca++) o Size, signal intensity of affected hemisphere changes over time o Margins between gray/white matter often blurred (from cortical dysplasia) o +/- Small brain stem, crossed cerebellar diaschisis o +/- Cerebellar hemiovergrowth, heterotopias T2* GRE: Dystrophic calcification Tl C+: None OR bizarre MRA o May show t flow o Enlarged vessels supply dysplastic hemisphere MRV: Primitive venous pattern MRS: With seizures, progressive ! NAA and t creatine, choline, and myoinositol ~ reflects glial proliferation Magnetoencephalography (MEG) o Somatosensory maps predict severity of cortical lamination defects

Ultrasonographic

Findings

• Real Time o Displaced midline and hemispheric overgrowth • Diagnosis can be made in fetus and neonate • Color Doppler o +/- Enlarged ipsilateral arteries o Frequent dysplastic, primitive venous system

Angiographic

Findings

• Conventional:

+/- High flow shunting

Nuclear Medicine

to involved side

Findings

• PET: Glucose hypometabolism in 50% • SPECT o Increased or decreased tracer uptake in affected side

Imaging Recommendations • Best imaging tool: Multiplanar • Protocol advice o Multiplanar MRI

MRI

Diagnoses

Pathology

Diagnostic Checklist • Hemiovergrowth syndromes: Remember potential airway compromise, sedation risk • Involved hemisphere may atrophy (effect of chronic seizures)

• Serial imaging may be required to document full extent • Image before seizures lead to significant atrophy of involved hemisphere

I DIFFERENTIAL DIAGNOSIS Megalencephaly

(both hemispheres)

• Most syndromic, enlargement of both hemispheres, may be asymmetricj heterotopias & dysplasias common

Hemiatrophy • Rasmussen syndrome: Chronic focal encephalitis o Unilateral fronto-temporal atrophy o Progressive atrophy, signal change of caudate & putamen

Hemimegalencephaly

of tuberous sclerosis

(TS) • Some overlap as both are disorders of cellular proliferation • Imaging markers and cutaneous stigmata TS • Superficial resemblance of balloon cells in hemimegalencephaly and TS o But immunohistochemistry and electron microscopic profiles different

Mild hemimegalencephaly • May be familial and isolated

I PATHOLOGY General Features • General path comments o Variable patterns of overgrowth, gliosis reflect variability in timing of precipitating insult o Hemiovergrowth syndromes may have visceral (and airway) involvement o Embryology: Theories

Congenital Malformations

75

1 76

•

•

• •

• Insult (for example CMV) to developing brain: Brain plasticity allows development of new (too many) synapses, persistence of supernumerary axons and potential for white matter overgrowth • Localized epidermal growth factor EGF in cortical neurons and glial cells may lead to excessive proliferation Genetics o Overgrowth/hemiovergrowth syndromes plus hemimegalencephaly • Possibly related to survival autosomal lethal gene by somatic mosaicism o Syndromic hemimegalencephaly with somatic hemihypertrophy (30%) • Proteus, Hypomelanosis of Ito, ]adassohn linear nevus sebaceous, epidermal nevus, Adams-Oliver, Klippel-Trenaunay-Weber congenital infiltrating lipomatosis, in continentia pigmenti Etiology o Disturbed cellular lineage o Disturbed cellular differentiation, proliferation and migration Epidemiology: Approximately 3% of cortical dysplasias diagnosed by imaging Associated abnormalities o Isolated o Associated with neurocutaneous and overgrowth syndromes

Gross Pathologic & Surgical Features • Large hemisphere, shallow sulci, fused & disorganized gyri • Regional polymicrogyria, pachygyria and heterotopias

Microscopic

Features

• Giant neurons, loss of horizontal layering of neurons • Balloon cells, hypertrophic/atypical cells have variable reactivity for neuronal and glial proteins o Contain few lysosomes, microfilaments, microtubules o Have abundant lipofuscin granules • White matter hypertrophy & gliosis • Dystrophic Ca++ • Contralateral hemisphere may harbor occult heterotopias and cortical dysplasia • Platelet-activating factor (role in neuronal migration) reported absent in hemimegalencephaly specimens

Staging, Grading or Classification Criteria • Variable patterns of cortical and white matter involvement may allow estimation of timing of precipitating insult

o Severe developmental hemiparesis common o Systemic involvement common

Presentation

syndromes

Demographics Natural History & Prognosis • Intractable seizures • Progressive hemiparesis • Poor outcome =? intractable seizures, developmental delay • Early surgery allows brain plasticity to take over function of resected areas (if remainder of brain is normal!)

Treatment • Anticonvulsants often ineffective • Occasional shunting to control head size and cerebellar displacement • Surgical resection or embolic hemispherectomy of seizure focus o Confirm normal contralateral hemisphere first!

1.[)IAGN()S~I<:(EI-JE<:KLls-r Consider • Hemiovergrowth syndromes: Remember potential airway compromise, sedation risk

Image Interpretation

Pearls

• Serial imaging shows remarkable signal transformation with myelin maturation • Involved hemisphere may atrophy (effect of chronic seizures)

I SELECTED REFERENCES 1.

2.

3.

4.

5.

7.

8.

• Most common signs/symptoms o Seizures o Macrocrania • Clinical profile o Early seizures (infantile spasms, focal and later generalized)

with overgrowth

• Age: Usually diagnosed during first year of life

6.

l CLINICALISSU~S

delay and contralateral

9.

Malinger G et al: Assessment of fetal intracranial pathologies first demonstrated late in pregnanacy: Cell proliferation disorders. Reprod BioI Endocrinol1(1):1l0, 2003 Flores-Sarnat L et al: Hemimegalencephaly: Part 2. Neuropathology suggests a disorder of cellular lineage. J Child Neurol18(1l):776-785, 2003 Ishibashi H et al: Somatosensory evoked magnetic fields in hemimegalencephaly. Neurol Res 24(5):459-62,2002 Flores-Sarnat L: Hemimegalencephaly: Part 1. Genetic, clinical, and imaging aspects. J Child Neurol, 17(5):373-84, 2002 DiRocco F et a1. Hemimegalencephaly involving the cerebellum. Pediatr Neurosurg 35(5):274-6,2001 Barkovich AJ: Pediatric Neuroimaging, 3rd ed. Lippincott Williams & Wilkins, pp 291-6, 2000 Hoffmann KT et al: MRI and 18F-flourodeoxyglucose PET in hemimegalencephaly 42(10):749-752,2000 Arai Y et al: A comparison of cell phenotypes in hemimegalencephaly and tuberous sclerosis. Acta Neuropatho198(4):407-13, 1999 Hanefeld F et al: Hemimegalencephaly: Localized proton magnetic resonance spectroscopy in vivo. Epilepsia 36(12):1215-1224, 1995

Congenital Malformations

1 77

Typical (Left) Axial NECT shows extensive dystrophic calcification of left hemispheric white matter. There are prominent primitive veins in the primitive Sylvian fissure (arrow). (Right) Axial T7 WI MRshows "pseudo-accelerated" myelin maturation (arrow) in the affected left hemisphere. There is a blurred gray-white junction from cortical dysplasia. There are shallow sulci.

Typical (Left) Axial T2WI MR shows primitive veins (arrows) in the enlarged Sylvian fissure. The gyri are fused (open arrow) and there is focal cortical dysplasia and "pseudo-accelerated" myelin maturation. (Right) Axial T2WI MR in the same child after myelin maturation of the remainder of the brain shows increased signal in the periventricular region (arrows), likely due to gliosis.

... /

,. .'

.~~~

--

[' ,

Congenital Malformations

-. .

(Left) Axial T2WI MR in an infant with macrocrania and seizures shows mild right hemispheric hemimegalencephaly with diffuse thickening of the cortex (arrows). (Right) Axial MRA in another child with hemimegalencephaly shows enlargement of the left middle cerebral artery (arrow) and branches on the involved side.

NEUROFIBROMATOSIS TYPE 1 78

Axial graphic shows enlarged right middle cranial fossa, sphenoid wing dysplasia, and a large peri-orbital PNF. There is exophthalmos and buphthalmos of the involved globe (arrow).

Abbreviations

and Synonyms

• Neurofibromatosis type 1 (Nfl), von Recklinghausen disease • Neurofibroma (NF); plexiform neurofibroma (PNF)

Definitions • Neurocutaneous disorder, phakomatosis • Inherited tumor disorder characterized by diffuse neurofibromas, intracranial hamartomas, benign & malignant tumors

Axial T1 C+ MR shows enlargement of the right bony orbit. Note the enlarged tortuous optic nerves, right sided buphthalmos, and right orbital PNF (arrows).

o PNF: Orbit/scalp/skull base; paraspinal; other body locations o ONG: Can involve any or all portions of visual pathway • Size o FASI:Variable sized o PNF: Localized or diffuse • Morphology o FASI: Small discrete or large, subtle, hazy foci of t signal intensity o PNF: Snake-like ropes of variable signal/enhancement; "target" sign characteristic

Radiographic Findings

I IMAGING. FlNDINOS General Features • Best diagnostic clue o Classic imaging appearance: Focal areas of signal intensity (FASI) in white matter (WM) & deep gray matter (GM) o Plexiform neurofibroma (PNF) and optic nerve gliomas (ONGs) • Location o Foci of abnormal signal intensity (FASI), minimal or no mass effect • Globus pallidi, WM, thalami, hippocampi, brain stem

• Radiography o Scoliosis (often acute angle) 30%, worse prognosis if appears at younger age o Hypoplastic posterior elements, scalloped vertebrae (dural ectasia/lateral meningoceles > underlying NFs) o Dysplastic sphenoid wing, ribbon ribs, multiple pseudarthroses o Enlarged superior orbital fissure with ONG • Myelography: Dural ectasia; lateral meningoceles

CT Findings • NECT o Enlarged optic foramina and fissures (ONG) or foramen ovale (PNF)

DDx: Foci of Abnormal Signal Intensity

Gliomatosis Cerebri

Demyelination MS

Moderate ADEM

Congenital Malformations

Flagrant ADEM

NEUROFIBROMATOSIS TYPE 1

1

Key Facts Terminology

Pathology

• Neurofibromatosis type 1 (Nfl), von Recklinghausen disease • Neurocutaneous disorder, phakomatosis • Inherited tumor disorder characterized by diffuse neurofibromas, intracranial hamartomas, benign & malignant tumors

• Gene locus = 17q11.2; autosomal dominant; 50% new mutations • NF gene product "neurofibromin" is tumor suppressor; inactivation allows cell proliferation & tumor development • Etiology: NFl tumor suppressor gene "turned off" in Nfl patients • One of most common inherited CNS disorders • Most common autosomal dominant disorder • Most common inherited tumor syndrome • 1:2,500 live births • Cutaneous lesions: Cafe-au-Iait spots appear early childhood; axillary or inguinal freckling childhood and adolescence; subcutaneous or cutaneous NF when older

Imaging Findings • Classic imaging appearance: Focal areas of signal intensity (FASI) in white matter (WM) & deep gray matter (GM) • Plexiform neurofibroma (PNF) and optic nerve gliomas (ONGs)

o Progressive sphenoid wing dysplasia (associated with PNF) o Lambdoid suture defect; dural Ca++ (at vertex) • CTA: NFl plus suprasellar glioma plus radiation therapy => i risk moyamoya

MR Findings • TlWI o FASI: Variable, i signal with age o Macrocephaly due to i white matter volume o Cortical dysplasias occur • T2WI o FASI: Hyperintense, margins sharp or hazy • Typically not tumefactive o PFN: "Target" sign (bright with central collagen dot) o PFN, NF and ONG have variable T2 signal which may i or i over time • FLAIR o Best sequence for FASI: Present in 60-85% of NFl • Pattern: Wax for 2-10 yrs, wane by 20 yrs • 11% proliferate: Predictors = enhancement, mass effect; i numbers, brainstem/splenium/cerebellum involvement • DWI: i ADC values for FASI, possibly due to i myelin vacuole size or number

79

Imaging Recommendations • Baseline MR brain and orbits; +/- spine • Follow-up if ONG or i i FASIs or FASls with brainstem swelling o If new symptoms: Headaches, visual change, precocious puberty

I DIFFERENTIAL DIAGNOSIS Other disorders of the NF spectrum • • • • • •

NF2; multiple schwannomatosis syndrome Mosaic (segmental) NFl or NF2 Hereditary spinal NF Familial intestinal NF Autosomal dominant cafe-au-Iait spots Autosomal dominant neurofibromas alone

Demyelination • WM lesions predominate, although may occur, especially in ADEM

deep GM lesions

Gliomatosis cerebri • If FASI are extensive

• T1 C+

o FASI: Enhancement of lesions worrisome, although rare transient enhancement of FASI reported o PNF, NF, and ONG have variable enhancement patterns which change over time • MRS: FASI & tumor both i Cho: Cr ratio (tumors higher) but FASI have near normal NAA; tumors show ii NAA

Angiographic

Findings

• Conventional o MRA/DSA: Vascular intimal proliferation => stenoses => moyamoya o Other: Aneurysms/AVMs, renal artery stenoses, coarctation aorta

Nuclear Medicine

Findings

• PET: i Glucose metabolism

in large areas of FASI

I PATHOLOGY General Features • General path comments: Embryology: Disorder of histogenesis • Genetics o Gene locus = 17q11.2; autosomal dominant; 50% new mutations o Variable expression, but virtually 100% penetrance by 5 yr o NF gene product "neurofibromin" is tumor suppressor; inactivation allows cell proliferation & tumor development • Etiology: Nfl tumor suppressor gene "turned off" in Nfl patients • Epidemiology

Congenital Malformations

NEUROFIBROMATOSIS TYPE 1 80

o One of most common inherited CNS disorders o Most common autosomal dominant disorder o Most common inherited tumor syndrome o 1:2,500 live births • Associated abnormalities: Associated pheochromocytomas, neurofibrosarcomas, malignant nerve sheath tumors

Demographics • Age: Cutaneous markers noted during 1st year, later progressive i conspicuity & i number • Gender: M = F • Ethnicity: Risk for ONG lower in African-Americans than in Caucasians or Hispanics

Gross Pathologic & Surgical Features

Natural History & Prognosis

• Visual pathway glioma 15-20%; dilated optic nerve sheath common (+/- ONG): Symptoms/progression 5% o Can be isolated (common) to one region or involve entire visual pathway • Opti nerve/chiasm> extension to geniculate bodies & postgeniculate tracts o Hamartoma, usually low grade o Frank malignancy < 20% o Peri-chiasmatic infiltration subarachnoid space • More likely to act aggressively • i Frequency precocious puberty 30% • PNF degeneration to neurofibrosarcoma 2-12% • Slight i incidence medulloblastoma/ependymoma • Definite i incidence astrocytomas o 1-3% of NFl cases o Earlier presentation, more frequent, more likely multi-centric o Brainstem/cerebellum, splenium CC common sites • Often less aggressive than sporadic brainstem gliomas • Anaplastic astrocytoma, GBM also occur • Cutaneous lesions: Cafe-au-Iait spots appear early childhood; axillary or inguinal freckling childhood and adolescence; subcutaneous or cutaneous NF when older • Other ocular findings: Lisch nodules (iris hamartomas) in 85% > 10 years old; buphthalmos; pthisis bulbi

• NFl related learning disability 30-60%, significant association with FASI, especially hippocampal; mental retardation 8% • Risk of other CNS tumors i with presence of ONG • i Risk sarcomatous degeneration PNF • i Incidence MS: Thought due to mutations in oligodendrocyte-myelin glycoprotein gene which is embedded in NFl gene • Vascular stenoses: Intra- and extracranial • Life expectancy shortened in NF due to hypertension, malignancy, and spinal cord lesions

Microscopic

Treatment • Clinical observation

I DIAGNOSTIC Consider

• Disorder of histogenesis;

systemic disorder

Image Interpretation

Pearls

• FASI are transient, usually nonenhancing lesions of childhood, beware of persistent, tumefactive, or enhancing lesions

I SELECTED REFERENCES 1.

Features

• FASI: Foci of myelin vacuolization • PNF: Schwann cells, perineural fibroblasts, grow along nerve fascicles

Staging, Grading or Classification Criteria • NFl if two or more of following o ~ 6 cafe-au-Iait spots (evident during yr 1) o ~ 2 NF(puberty) or 1 PNF o Axillary/inguinal freckling o ONG o Typical bone lesion o 1 relative with NFl

2.

3.

4.

0

I CLINICALilSSUES

CHECKLIST

5.

Geldmann R et al: Neurofibromatosis type 1: Motor and cognitive function and T2W MRI hyperintensities. Neurology 61(12):1725-8,2003 Wilkinson ID et al: Proton MRS of brain lesions in children with neurofibromatosis type 1. Magn Reson Imaging 19(8):1081-9,2001 Raininko R et al: Atypical focal non-neoplastic brain changes in neurofibromatosis type 1: Mass effect and contrast enhancement. Neuroradiology 43(7):586-590, 2001 Steen RG et al: Prospective evaluation of the brain in asymptomatic children with NF 1: Relationship of macrocephaly to T1 relaxation changes and structural brain anomalies. AJNR 22(5):810-7, 2001 Eastwood JD et al: Increased brain apparent diffusion coefficient in children with neurofibromatosis type 1. Radiology 2192):354-8,2001

Presentation • Most common signs/symptoms: Cafe-au-Iait spots are earliest finding • Clinical profile o Short stature; early OR delayed puberty; learning disabilities (+/- ADHD) in 30-60% o Clinical manifestations appear slowly throughout life

Congenital Malformations

1 81

Typical (Left) Axial T2W/ MR shows

typical bilateral FAS/ (arrow) of the globus pallidus. (Right) Axial T2W/ MR shows posterior extension of abnormal signal in the retrochiasmatic visual pathway of a child with NFl, this case represents visual pathway gliomas (arrows).

Typical (Left) Sagittal oblique T1 C+

MR shows tortuosity of the intraorbital optic nerve and enhancement of the enlarged optic chiasm (arrow) in a patient with visual pathway glioma. (Right) Anteroposterior NECT with 3D reformat shows enlarged right right orbit and enlarged superior orbital fissure (arrow) in a patient with both orbital plexiform neurofibroma and an optic nerve glioma.

Typical (Left) Lateralselective

catheter angiography shows fusiform aneurysmal dilatation (arrow) of the internal carotid artery. (Right) Coronal T2W/ MR shows extensive plexiform neurofibroma of the scalp and neck (black arrows). Note extensive typical "target" signs (white arrow) throughout the lesion.

Congenital Malformations

NEUROFIBROMATOSIS TYPE 2 82

Axial graphic shows bilateral CPA schwannomas pathognomonic of NF2. Tumor on the right (open arrow) is large; several small schwannomas are seen on left vestibulocochlear nerves (arrow).

Abbreviations

and Synonyms

• Neurofibromatosis type 2 (NF2) • MISME o Multiple intracranial schwannomas, meningiomas, and ependymomas • Acoustic neurofibromatosis, central neurofibromatosis, bilateral acoustic neurofibromatosis

Definitions • Hereditary syndrome causing multiple cranial nerve schwannomas, meningiomas, and spinal tumors

IIMAGING.FINDINGS General Features • Best diagnostic clue: Bilateral vestibular schwannomas • Location o Multiple extra-axial tumors • Schwannomas on cranial nerves and spinal nerve roots • Meningiomas on dural surfaces o Intra-axial tumors • Ependymomas in spinal cord and brainstem • Size: Cranial nerve tumors typically symptomatic while still small, but can achieve great size

Axial T1 C+ MR shows bilateral enhancing vestibular schwannomas bulging from lACs into CPA cisterns in a young adult with NF 2. CN 5 schwannoma enlarges left cavernous sinus (arrow).

• Morphology: Tumors grow spherically, but accommodate to bony canals, e.g., internal auditory canal (lAC) • Multiplicity of lesions o Schwannomas of other cranial nerves o Schwannoma "tumorlets" of spinal nerves o Meningiomas (often multiple) o Intramedullary ependymomas (spinal cord) o Cerebral calcifications o Posterior lens opacities o Meningioangiomatosis o Glial microhamartomas

Radiographic Findings • Radiography o Scoliosis o Widened neural foramina o Widened lAC • Myelography o Will demonstrate multiple spinal tumorlets • Replaced by contrast-enhanced MR

CT Findings • NECT o Vestibular schwannoma • Cerebello-pontine angle (CPA) mass +/- widened lAC • Isodense to hyperdense • Rarely cystic/necrotic

DDx: CPA Mass

Epidermoid

Arachnoid Cyst

Aneurysm

Congenital Malformations

Ependymoma

NEUROFIBROMATOSIS TYPE 2

1 83

•

o Meningioma • High density focal/diffuse dural-based mass(es) o Nonneoplastic cerebral Ca++ (uncommon) • Extensive choroid plexus Ca++ • Cortical surface • Ventricular lining • CECT o Cranial nerve tumor enhancement o Meningioma enhancement

MR Findings • TlWl o Schwannomas • Hypointense to isointense • Rare cystic change o Meningiomas • lsointense to hypointense • Occasional hyperintense foci from Ca++ • T2Wl o Schwannomas • Small intra canalicular lesions can be shown on high resolution T2Wl o Meningiomas • May incite significant adjacent edema • T2* GRE: Shows nonneoplastic Ca++ to best advantage • DWl o Meningiomas • Usually show restricted diffusion, bright on DWl • ADC = 0.5 to 1.1 • Tl C+ o Schwannomas • Diffuse enhancement • Usually homogeneous • T1 C+ with fat saturation and thin slice profile essential for identification of small CN tumors • Vestibular schwannomas typically "bulge" into CPA cistern from lAC o Meningiomas • Diffuse enhancement of tumor, may be plaque-like • MRS o Meningioma • Absent NAA peak, +/-lactate

o Schwannoma • Absent NAA peak, usually no lactate

Angiographic Findings • Conventional o Meningioma • Prolonged tumor blush • Up to 40% have A-V shunting, early veins • Pre-operative embolization may reduce blood loss in selected cases o Schwannoma • Usually hypovascular, displace AlCA loop from porus acusticus

Imaging Recommendations • Contrast-enhanced MR screening of entire neuraxis (brain, spine) • High resolution T1 C+ through basal cisterns to evaluate cranial nerves

I DI.FFERENTIALDIAGNQSIS Schwan nomatosis • Multiple schwannomas without vestibular tumors • No cutaneous stigmata or meningiomas

Cerebellopontine

angle (CPA) masses

• Arachnoid cyst o Follows CSF on all sequences • Epidermoid o DWl and MRS easily distinguish from arachnoid cyst • Aneurysm o Vertebral or petrous aneurysms may project into CPA o Pulsation artifact in phase-encoding direction • Ependymoma o Extends into CPA from fourth ventricle

Multiple meningiomas • Recurrent or metastatic • Secondary to radiation therapy

Congenital Malformations

NEUROFIBROMATOSIS TYPE 2 1 84

Metastases

Demographics

• CNS primary o Glioblastoma, PNET-MB, germinoma • Non-CNS primary

• Age o Patients typically become symptomatic in 3rd decade o Screening of children of NF2 parents can identify asymptomatic tumors • Gender o No predilection o Pregnancy may exacerbate symptoms • Ethnicity: No predilection

Granulomatous

disease

• Sarcoidosis • Tuberculosis

Natural History & Prognosis General Features • General path comments: Multiple schwannomas, meningiomas, ependymomas • Genetics o Autosomal dominant o All NF2 families have chromosome 22q12 abnormalities o Germline, somatic NF2 gene mutations • NF2 gene functions as tumor suppressor gene • Encodes for merlin protein • Links cytoskeleton and cell membranes • Etiology o 50% known family history of NF2; 50% new mutations o Mutations cause truncated, inactivated merlin protein o Loss of both alleles predisposes to tumor formation • Epidemiology: 1 in 40,000-100,000

Gross Pathologic & Surgical Features • Multiple schwannomas

Microscopic

and meningiomas

• NF2-associated schwannomas occur earlier in life than sporadic tumors o Often multiple o Can affect any cranial/peripheral nerve (sensory> motor)

Treatment • Complete resection of CN 8 schwannoma if feasible • Subtotal microsurgical resection with functional cochlear nerve preservation in the last hearing ear

IDIAGNQST1C:CPiE.CKI..JS-r Consider • Carefully evaluate other cranial nerves in any new diagnosis of vestibular schwannoma o Be highly suspicious if < 30 yrs • Study entire neuraxis in suspected cases (multiple small, asymptomatic schwannomas on cauda equina common)

Image Interpretation

Features

Pearls

• NF2-related schwannomas have higher proliferative activity than sporadic tumors but not necessarily more aggressive course

• Coronal thin slice T1 C+ with fat saturation cranial nerves

Staging, Grading or Classification Criteria

I SELECTED

• NF2-associated

schwannomas

are WHO grade I

IG~If'nCAE·••. lS.StJES

1.

2.

Presentation • Most common signs/symptoms o Hearing loss, vertigo (CN 8 schwannoma) • Vestibular schwannomas may be minimally symptomatic in younger patients o Multiple cranial neuropathies o Scoliosis, paraplegia or neck pain from spinal lesions • Clinical profile: Young adult with multiple cranial neuropathies, cataracts, and extremity weakness • Clinical diagnosis o Bilateral vestibular schwannomas; or o 1st degree relative with NF2 and 1 vestibular schwannoma; or o 1st degree relative with NF2 and 2 of the following • Neurofibroma • Meningioma • Glioma • Schwannoma • Posterior subcapsular lenticular opacity

Congenital

3.

4.

5.

6. 7.

8.

to assess

REFERENCES

Kluwe L et al: Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas.] Med Genet. 40(2):109-14, 2003 Leverkus M et al: Multiple unilateral schwannomas: segmental neurofibromatosis type 2 or schwannomatosis? Br] Dermatol. 148(4):804-9,2003 Mautner VF et al: The neuroimaging and clinical spectrum of neurofibromatosis 2. Neurosurgery. 38(5):880-5; discussion 885-6, 1996 Mautner VF et al: Neurofibromatosis 2 in the pediatric age group. Neurosurgery. 33(1):92-6, 1993 Pont MS et al: Lesions of skin and brain: modern imaging of the neurocutaneous syndromes. A]R Am ] Roentgenol. 158(6):1193-203, 1992 Egelhoff]C et al: Spinal MR findings in neurofibromatosis types 1 and 2. A]NR Am] Neuroradiol. 13(4):1071-7, 1992 Mayfrank L et al: Intracranial calcified deposits in neurofibromatosis type 2. A CT study of 11 cases. Neuroradiology. 32(1):33-7, 1990 Aoki S et al: Neurofibromatosis types 1 and 2: cranial MR findings. Radiology. 172(2):527-34, 1989

Malformations

1 85

Typical (Left) Axial T7 C+ MR shows schwannomas of CN 5 (white arrow), CN 6 (black arrow), CN 8 (open arrow), and posterior meningioma (curvedarrow). (Right) Axial T7 C+ MR shows enhancing CN 12 schwan noma filling the hypoglossal canal on the left (arrow). Solitary tumors of uncommonly affected cranial nerves (3, 4, 6, 9-12) can be presenting sign of NF2.

(Left) Coronal Tl C+ MR shows bilateral enhancing schwannomas of CN 5 (arrows), and residual deformity of pons after resection of left CPA schwannoma. This patient had multiple other cranial nerve tumors. (Right) Coronal T7 C+ MR shows meningiomas over the cerebral convexity on right (curved arrow) and inferior cerebellar convexity on left (open arrow).

Typical (Left) Sagittal T7 C+ MR of cranial-cervical junction shows enhancing ependymomas in medulla and cervical cord (arrows). Enhancement over pons (curved arrow) is from large CPAschwannoma. (R~h0 Sagittal T7 C+ MR in same patient shows multiple enhancing nodules "studding" cauda equina. Spinal tumors are present in virtually all cases of NF2, and are a major cause of morbidity.

Congen ital Malformations

VON HIPPEL LINDAU 86

Sagittal graphic shows two HGBLs in VHL. In this case, the spinal cord tumor has an associated cyst (arrows) and would cause myelopathy. The small cerebellar HGBL is asymptomatic.

o Ocular angiomas • Found in 75% of VHL gene carriers • Cause retinal detachment, hemorrhage • Size: HGBLs vary from tiny to very large lesions with even larger associated cyst • Morphology: Symptomatic HGBLs more often cystic than solid

ITERMl~QtOGY Abbreviations

Lateral OSA in a patient with VHL shows intense, prolonged vascular stain characteristic of multiple cerebellar (arrows) and spinal cord (open arrow) HGBLs (Courtesy G. Katzman, MO).

and Synonyms

• von Hippel Lindau (VHL) syndrome (OMIM 19330)

Definitions • Autosomal dominant familial tumor syndrome with hemangioblastomas (HGBLs), clear cell renal carcinoma, cystadenomas, pheochromocytomas o Affects six different organ systems, including eye, ear, CNS o Involved tissues often have multiple lesions o Lesions = benign cysts, vascular tumors, carcinomas

CT Findings • NECT o 2/3 have well-delineated cerebellar cyst + nodule • Nodule typically abuts pial surface o 1/3 solid, without cyst o +/- Obstructive hydrocephalus • CECT: Intense enhancement of tumor nodule

I IMAGING FINDINGS

MR Findings

General Features

• TlWI o HGBL: Mixed iso ~ hypointense nodule, +/- "flow voids" o Associated cyst slightly hyperintense to CSF • T2WI: Hyperintense nodule, cyst • FLAIR o Cyst typically very hyperintense o Variable high signal edema around lesion • T2* GRE: Blooms if hemorrhage present • Tl C+ o Tumor nodule enhances strongly

• Best diagnostic clue: 2 or more CNS HGBL or 1 HGBL + retinal hemorrhage • Location o HGBLs in VHL • Typically multiple • 50% in spinal cord (posterior half) • 35-40% cerebellum • 10% brainstem (posterior medulla) • 1% supratentorial (along optic pathways, in cerebral hemispheres)

DDx: VHl

Br"-'~ r.· .::». -~~~ ;7' ..).:.~

L~·.<, .

..

Solitary HGBL

"

'

..

AVM in HHT

Congenital Malformations

Vascular Metastasis

VON HIPPEL LINDAU

1

Key Facts Terminology

Pathology

• Autosomal dominant familial tumor syndrome with hemangioblastomas (HGBLs), clear cell renal carcinoma, cystadenomas, pheochromocytomas

• Both alleles of VHL tumor suppressor gene on chromosome 3 inactivated

Clinical Issues

Imaging Findings

• Earliest symptom in VHL often visual • Phenotypes based on absence or presence of pheochromocytoma • HGBLs often have multiple periods of tumor growth (usually associated with increasing cyst size) separated by periods of arrested growth • On average, new lesion develops every 2 yrs in VHL

• Best diagnostic clue: 2 or more CNS HGBL or 1 HGBL + retinal hemorrhage

Top Differential • • • • •

Diagnoses

Vascular metastasis Solitary hemangioblastoma Pilocytic astrocytoma Disseminated HGBLs without VHL Multiple AVMs in vascular neurocutaneous

Diagnostic Checklist syndrome

o Associated cyst wall usually nonneoplastic, doesn't enhance o May detect tiny asymptomatic enhancing nodules

Angiographic

Findings

• Conventional o DSA shows intensely vascular mass, prolonged o A-V shunting (early draining vein) common

stain

Imaging Recommendations • Best imaging tool: Brain: MR without & with contrast • Protocol advice: Scan entire spine • NIH recommendations o Contrast-enhanced MR of brain/spinal cord from age 11 y, every 2 years o US of abdomen from 11 y, yearly o Abdominal CT from 20 y, yearly or every other year o MRI of temporal bone if hearing loss, tinnitus/vertigo

I DIFFERENTIAL DIAGNOSIS Vascular metastasis • Usually solid, not cyst + nodule • Some tumors (e.g., renal clear cell carcinoma) can resemble hemangioblastoma histopathologically • GLUT 1 immunoreactivity, inhibin A expression distinguish HGBL from clear cell RCC metastasis • Rare: RCC metastasis to an HGBL reported

Solitary hemangioblastoma • 25-40% of HGBLs occur in VHL • No family history, other tumors or cysts • No VHL gene alterations

Pilocytic astrocytoma • • • •

87

Common in cerebellum, brain stem Different age (usually younger than VHL patients) No family history, lacks retinal angioma/hemorrhages Tumor nodule often lacks large flow voids (more characteristic of HGBL) • Tumor nodule often does not abut pial or ependymal surface

• Solitary HGBL in a young patient may indicate VHL

Disseminated

HGBls without VHl

• Rare; occurrence recently reported • Multiple sites of subarachnoid dissemination 1-8 yrs after initial complete resection of solitary HGBL • Somatic deletion of one copy of the VHL gene in tumors (derive from single clone)

Multiple AVMs in vascular neurocutaneous syndrome • HHT, Wyburn-Mason, etc • Small AVMs may resemble HGBL at angiography

I

PATHOLOGY

General Features • General path comments o VHL characterized by development of • Capillary hemangioblastomas of the CNS and retina • Cysts, renal clear cell carcinoma • Pheochromocytoma • Pancreatic cysts, islet cell tumors • Endolymphatic sac (ELS) tumors • Epididymal cysts, cystadenomas • Genetics o Autosomal dominant inheritance with high penetrance, variable expression o Germline mutations of VHL tumor suppressor gene • Chromosome 3p25-26 • Involved in cell cycle regulation, angiogenesis • Different mutations scattered throughout gene • Disease features vary depending on specific VHL mutations • Inactivating mutations (nonsense mutations/deletions) predispose to VHL type 1 • Missense mutations predispose to VHL types 2A, 2B

• Etiology o Both alleles of VHL tumor suppressor gene on chromosome 3 inactivated o Suppressor gene product = VHL protein (pVHL)

Congenital Malformations

1 88

o Mechanism by which neoplasia is induced unclear • Epidemiology: 1 in 35-50,000

Gross Pathologic & Surgical Features • HGBL seen as well-circumscribed, very vascular, reddish nodule o 75% at least partially cystic, contain amber-colored fluid • Rare: Leptomeningeal hemangioblastomatosis

Microscopic Features • Two components in HGBL o Rich capillary network o Large vacuolated stromal cells with clear cytoplasm • Immunohistochemistry + for cytokeratins, Lu-5

• HGBLs often have multiple periods of tumor growth (usually associated with increasing cyst size) separated by periods of arrested growth • On average, new lesion develops every 2 yrs in VHL

Treatment • Ophthalmoscopy yearly from infancy • Physical/neurological examination, from 2 yrs, then yearly • Surgical resection of symptomatic cerebellar/spinal hemangioblastoma • Stereotactic radiosurgery may control smaller lesions • Laser treatment of retinal angiomata

Staging, Grading or Classification Criteria • Capillary hemangioblastoma

=

WHO grade I

Consider • Follow NIH screening rules • Look for ELS tumors in VHL patients with dysequilibrium, hearing loss or aural fullness

Presentation

Image Interpretation

• Most common signs/symptoms o VHL is clinically very heterogeneous; phenotypic penetrance = 97% at 65 y o Retinal angiomas • Earliest symptom in VHL often visual • Retinal detachment, vitreous hemorrhages o Cerebellar HBGLs • H/ A (obstructive hydrocephalus) • Nearly 75% of symptom-producing tumors have associated cyst o Spinal cord HBGLs • Progressive myelopathy • 95% associated syrinx • Clinical profile o Phenotypes based on absence or presence of pheochromocytoma • Type 1 = without pheochromocytoma • Type 2A = with both pheochromocytoma, renal cell carcinoma • Type 2B = with pheochromocytoma, without renal cell carcinoma o Diagnosis of VHL = capillary hemangioblastoma in CNS/retina and one of typical VHL-associated tumors or previous family history

• Solitary HGBL in a young patient may indicate VHL

Demographics • Age o VHL presents in young adults • Retinal angioma: Mean age = 25 Y • Cerebellar: Mean age = 30 Y o Mean age of presentation with other VHL-associated tumors • Pheochromocytoma (30 y) • Renal carcinoma (33 y) • Endolymphatic duct tumor • Gender: M = F • Ethnicity: None

Natural History & Prognosis

1.

Pearls

Choo D et al: Endolymphatic sac tumors in von Hippel-Lindau disease. J Neurosurg 100:480-7, 2004 2. Weil RJ et al: Surgical management of brainstem hemangioblastomas in patients with von Hippel-Lindau disease. J Neurosurg. 98(1):95-105, 2003 3. Wanebo JE et al: The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease. J Neurosurg. 98(1):82-94, 2003 4. Weil RJ et al: Clinical and molecular analysis of disseminated hemangioblastomatosis of the central nervous system in patients without von Hippel-Lindau disease. Report of four cases. J Neurosurg. 96(4):775-87, 2002 5. Sims KB:Von Hippel-Lindau disease: gene to bedside. CUff Opin Neurol. 14(6):695-703,2001 6. Allen RC et al: Molecular characterization and ophthalmic investigation of a large family with type 2A Von Hippel-Lindau Disease. Arch Ophthalmol. 119(11):1659-65,2001 7. Sora S et al: Incidence of von Hippel-Lindau disease in hemangioblastoma patients: the University of Tokyo Hospital experience from 1954-1998. Acta Neurochir (Wien). 143(9):893-6, 2001 8. Friedrich CA: Genotype-phenotype correlation in von Hippel-Lindau syndrome. Hum Mol Genet. 10(7):763-7, 2001 9. Conway JE et al: Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurg 48:55-63, 2001 10. North PE et al: GLUTI immunoreaction patterns reliably distinguish hemangioblastoma from metastatic renal cell carcinoma. Clin Neuropathol. 19(3):131-7,2000 11. Bohling T et al: Von Hippel-Lindau disease and capillary hemangioblastoma. In Kleihues P, Cavanee WK (eds): Tumours of the Central Nervous System, 223-6, IARC Press, 2000

• Renal carcinoma proximal cause of death in 15-50%

Congenital Malformations

1 89

Typical (Left) Axial T1 C+ MR in a patient with VHL shows two intensely enhancing solid HGBLs (arrows). (Right) Axial T1 C+ MR in the same patient shows a tiny enhancing lesion in the left globe characteristic of a retinal angioma (arrow).

Variant (Left) Axial CECT shows

bilateral mixed cystic, solid enhancing masses in both CPA cisterns (arrows). The patient has a family history of VHL. (Right) Axial T2WI MR shows the lesions involving both temporal bones (heterogeneously hyperintense). Note the bilateral endolymphatic duct tumors (arrows) (Courtesy R. Ramakantan, MO).

Variant (Left) Axial T1 C+ MR in an a patient with VHL with visual problems shows a tiny, strongly enhancing solid tumor nodule in the posterior fossa (arrow). Presumed HGBL. (Right) Coronal T1 C+ MR shows a strongly enhancing mass (arrow) adjacent to the infundibulum and optic chiasm. Proven HGBL (Courtesy G. Katzman, MO).

Congenital Malformations

TUBEROUS SCLEROSIS COMPLEX 90

Axial graphic shows a giant cell astrocytoma in the left foramen of Monro, subependymal nodules (open arrow), radial lines (curved arrow) and cortical/subcortical tubers (arrow).

I TER.MI~()tQG¥ Abbreviations

and Synonyms

• Tuberous sclerosis complex (TSC); Bourneville-Pringle syndrome

Definitions • Inherited tumor disorder with multi-organ hamartomas o Spectrum of CNS hamartomas, all contain giant balloon cells

Axial T2WI MR show cortical/subcortical tubers (arrows) expanding the gyri, one is calcified. There are calcified subependymal nodules in the foramina of Monro (open arrow) and trigones.

o Cyst-like white matter lesions (cystoid brain degeneration) • Size: Thickened cortex, enlarged gyri associated with cortical/subcortical tubers • Morphology o Pyramidal-shaped gyral expansion o 20% have "eye-of-potato" central depression

Radiographic Findings • Radiography o Bone islands (skull) o Undulating periosteal new bone

CT Findings

IIMAGI NGFINDIN.GS General Features • Best diagnostic clue o Classic imaging appearance: Calcified (Ca++) subependymal nodules • 98% have subependymal nodules (SENs) • Location o Subependymal giant cell astrocytoma (SGCA) 15% o Cortical/subcortical tubers, WM lesions 70-95% • Frontal> parietal> occipital> temporal> cerebellum • 1 Number tubers ~ 1 neurologic symptoms o White matter lesions along lines of neuronal migration

• NECT o SENs • Along caudothalamic groove> atrial> > temporal • 50% Ca++ (progressive after 1 yr) o Tubers • Early: Low density/Ca++ cortical/subcortical mass • Later: Isodense/Ca++ (50% by 10 yr) o Ventriculomegaly common even without SGCA • CECT: Enhancing/enlarging SEN suspicious for SGCA

MR Findings • TlWI o Cortical/subcortical tubers: Early Tl I, but variable after myelin maturation o Focallacune-like cysts WM (vascular etiology)

DDx: Tubers and Calcifications

Heterotopia

Heterotopia

Cytomegalovirus

Congenital Malformations

Taylors Dysplasia

TUBEROUS SCLEROSIS COMPLEX

1

Key Facts Terminology • Tuberous sclerosis complex (TSC)j Bourneville-Pringle syndrome • Inherited tumor disorder with multi-organ hamartomas

Imaging Findings • Classic imaging appearance: Calcified (Ca++) subependymal nodules • Subependymal giant cell astrocytoma (SGCA) 15% • Cortical/subcortical tubers, WM lesions 70-95% • White matter lesions along lines of neuronal migration • Cyst-like white matter lesions (cystoid brain degeneration) • Cortical/subcortical tubers: Early T1 t, but variable after myelin maturation • T2WI: Variable signal (relative to myelin maturation) • FLAIR o White matter (WM) lesions • Streaky linear or wedge-shaped hyperintensities (along radial migration lines from ventricle to cortex) o FLAIR becomes more positive with age • T2* GRE: Ca++ SEN more readily discerned • DWI: t ADC values in epileptogenic tubers • T1 C+

• Streaky linear or wedge-shaped hyperintensities (along radial migration lines from ventricle to cortex) • SEN enhancement more visible on MRI than on CT • 30-80% enhance (enlarging SEN at foramen of Monro = SGCA) • Fetal documentation of rhabdomyoma: TSC confirmed in 96%

Top Differential

Pathology

• Look for rapid growth, +/- ventricular

X-linked subependymal

(SnORCH • Cytomegalovirus (CMV) o Periventricular Ca++ o White matter lesions o Cortical dysplasia

I PATHOLOGY

Findings

• Conventional: DSA/MRA: Vascular dysplasia (rare moyamoya, aneurysm)

Nuclear Medicine

=

Findings

• PET: !Glucose metabolism in lateral temporal gyri in TSC plus autism • Brain SPECT: ! Uptake quiescent tubersj ictal SPECT t uptake tubers with active seizure focus o Helps localize for surgery

Imaging Recommendations • Best imaging tool: MR with contrast • Protocol advice o MR with contrastj +/- NECT (document Ca++ SENs) o Yearly surveillance imaging if: Incompletely calcified SGCA or enhancing SGCA

heterotopia

• Isointense to GM T1/T2j don't enhance or Ca++

Ultrasonographic

Angiographic

obstruction

I DIFFERENTIAL DIAGNOSIS

Taylors dysplasia

• Real Time o Fetal documentation of rhabdomyoma: TSC confirmed in 96% • Rhabdomyomas identifiable as early as 20 wks gestation

heterotopia

• Mutations in TSC tumor suppressor genes cause abnormal cellular differentiation, proliferation

o SEN enhancement more visible on MRI than on CT • 30-80% enhance (enlarging SEN at foramen of Monro = SGCA) • Other enhancing lesions followed (unless growing, or obstructing CSF) o 12% cortical/subependymal tubers enhance • MRA: Rare aneurysms and dysplasias • MRS: ! NAA/Cr, t ml/Cr in subcortical tubers, SENs

Findings

Diagnoses

• X-linked subependymal • (S)TORCH • Taylors dysplasia

• Considered forme fruste TSC (single cortical lesion can mimic neoplasm)

General Features • General path comments o Inherited tumor disorder with multi-organ hamartomas o Occasionally seen in association with other cortical dysplasias (hemimegalencephaly, focal cortical dysplasia) • Genetics o Approximately 50% of TSC cases inherited • De novo = spontaneous mutation/germ-line mosaicism • Autosomal dominant, high but variable penetrance o Mutations in TSC tumor suppressor genes cause abnormal cellular differentiation, proliferation • Two distinct loci: TSC1 (9q34.3) encodes "hamartin"j TSC2 (16p13.3) encodes "tuberin" • Etiology o Abnormal differentiation/proliferation of germinal matrix cells o Migrational arrest of dysgenetic neurons • Epidemiology: 1:10,000-20,000

Congenital Malformations

91

1 92

• Associated abnormalities o Renal: Angiomyolipoma and cysts 40-80% o Cardiac: Rhabdomyomas 50-65%; majority involute over time o Lung: Cystic lymphangiomyomatosis/fibrosis o Solid organs: Adenomas; leiomyomas o Skin: Ash-leaf spots (majority) including scalp/hair; facial angiofibromas; shagreen patches 20-35% post pubertal o Extremities: Subungual fibromas 15-20%; cystic bone lesions; undulating periosteal newbone formation o Ocular: "Giant drusen" (50%) o Dental pitting permanent teeth in most adults with TSC

• First year of life if: Infantile spasms or surveillance for positive family history • Child: Autistic-like behavior, mental retardation, seizures, or skin lesions • Adult diagnoses reported with demonstration of symptomatic SGCA on brain imaging

Natural History & Prognosis • CNS: SCGAs 10-15%

Treatment • Treat seizures; resect isolated tubers if seizure focus or if able to identify seizure focus among many tubers • SGCAs resected if obstructing foramen of Monro

Gross Pathologic & Surgical Features • Firm cortical masses ("tubers") with dimpling ("potato eye") • Cortical dysplasias, hemimegalencephaly, transmantle dysplasia described

Consider

Microscopic

• T1WI readily documents early white matter abnormalities (pre-myelin maturation)

Features

• Balloon cells • Myelin loss, vacuolation • Ectopic neurons =

Image Interpretation

common

Pearls

and gliosis

Staging, Grading or Classification Criteria • SGCA

• Systemic involvement

WHO grade I

lCLINICi\lISSIJES Presentation • Most common signs/symptoms o Classic clinical triad • Facial angiofibromas 90%; mental retardation (MR) 50-80%; seizures (Sz) 80-90% • All three ("epiloia") = 30% • Clinical profile o Seizures (infantile type spasms in very young), facial angiofibroma, hypopigmented skin lesions, MR o Infant/toddler: Infantile spasms (65%), autism (50%) => bad prognosis • Infantile spasms occur before development of facial lesions, shagreen patches o Diagnostic criteria: Two major or one major + one minor • Major: Facial angiofibroma/forehead plaque, sub-/periungual fibroma, ~ 3 hypomelanotic macules, shagreen patch, multiple retinal nodular hamartomas, cortical tuber, SEN, SGCA, cardiac rhabdomyoma, lymphangiomyomatosis, renal angiomyolipoma • Minor: Dental enamel pits, hamartomatous rectal polyps, bone cysts, cerebral WM radial migration lines (> 3 = major sign), gingival fibromas, non-renal hamartoma, retinal achromic patch, confetti skin lesions, multiple renal cysts

1.

Narayanan V: Tuberous sclerosis complex: Genetics to pathogenesis. Pediatr Neurol 29(5):404-9, 2003 2. Jansen FE et al: Diffusion-weighted MRI and identification of the epileptogenic tuber in patients with tuberous sclerosis. Arch Neurol 60(11):1580-4, 2003 3. Bader RS et al: Fetal rhabdomyoma: Prenatal diagnosis, clinical outcome, and incidence of associated tuberous sclerosis complex. J Pediatr 143(5):620-4, 2003 4. Rott HD et al: Cyst-like cerebral lesions in tuberous sclerosis. Am J Med Genet 111(4):435-9, 2002 5. Asano E et al: Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction. Neurology 57(7):1269-77, 2001 6. Cristophe C et al: MRI spectrum of cortical malformations in tuberous sclerosis complex. Brain Dev 22(8):487-493, 2000 7. Varon Y et al: MR imaging of tuberous sclerosis in neonates and young infants. AJNR20(5):907-16, 1999 8. Roach ES et al: Tuberous sclerosis complex consensus conference: Revised clinical diagnostic criteria. J Child Neurol13:624-28, 1998 9. Jay V et al: Cerebellar pathology in tuberous sclerosis. Ultrastruct PathoI22(4):331-9, 1998 10. Griffiths PD et al: White matter abnormalities in tuberous sclerosis complex. Acta RadioI39(5):482-6, 1998

Demographics • Age o Diagnosed at any age

Congenital Malformations

TUBEROUS SCLEROSIS COMPLEX 1 93

Typical (Left) Axial T2WI MR in newborn shows low signal cortical tubers (arrows) and subependymalnodules (open arrows). There is right Sylvian dysplasia. (Right) Axial T2WI MR in the same infant at 10 months of age shows change in signal intensity of the lesions. Some of the tubers now are increased in signal intensity. More lesions are apparent (arrows).

(Left) Axial NECT in same infant shows bilateral subependymal nodules at the foramina of Monro, subtle calcification in the left frontal tuber (arrow) and marked calcification of the large opercular tuber. (Right) Axial Tl C+ MR in another child shows bilateral, asymmetric, enhancing subependymal giant cell astrocytomas (arrows), enhancing trigonal SEN, and low signal subcortical tuber (open arrow).

Typical

(Left) Axial FLAIRMR shows increased signal of cortical/subcortical nodules, expanded and flattened gyri (open arrow) and multiple small cystic lesions of white matter (arrows). Tiny SENs are also present. (Right) Axial TlWI MR shows extensive and diffuse radial white matter bands (arrows) in both hemispheres. These bands were noted to become less prominent with age and advancing myelin maturation.

Congenital Malformations

STURGE-WEBER SYNDROME

1 94

Coronal graphic shows extensive pial angiomatosis (white arrow), prominent medullary collaterals (black arrow), enlarged ipsilateral choroid plexus (open arrow), & righthemisphere atrophy.

Coronal T1 C+ MR shows right hemisphere atrophy, extensive pial enhancement and involvement of the prominent overlying subarachnoid space by pial angiomatosis (arrows).

ITERMINOLOGY

CT Findings

Abbreviations

• NECT o Gyrallsubcortical white matter (WM) Ca++ • Ca++ not in leptomeningeal angioma • Progressive, generally posterior to anterior (2-20 yrs) o Late • Atrophy • Hyperpneumatization of paranasal sinuses • Thick diploe • CECT o Serpentine leptomeningeal enhancement o Ipsilateral choroid plexus enlargement almost universal • Choroidal fissure if frontal involvement • Glomus in trigone if posterior involvement (most common)

and Synonyms

• Sturge-Weber syndrome (SWS); Sturge-Weber-Dimitri; encephalotrigeminal angiomatosis

Definitions • Usually a sporadic congenital (but not inherited) malformation in which fetal cortical veins fail to develop normally o Imaging features are sequelae of progressive venous occlusion and chronic venous ischemia

I IMAGING FINDINGS General Features • Best diagnostic clue: Cortical Ca++, atrophy, and enlarged ipsilateral choroid plexus • Location o Pial angiomatosis unilateral 80%, bilateral 20% o Occipital> parietal> frontalltemporallobes > diencephalon/midbrain> cerebellum • Size: Small focal or bilateral multi-lobar involvement

Radiographic Findings • Radiography:

Tram-track calcification

MR Findings • TlWI o Atrophy over time o t WM volume subjacent to pial angiomatosis (early); atrophy of WM and GM (late) • T2WI o Early: Transient hyperperfusion ~ "accelerated" myelin maturation o Late: t Signal in region of gliosis & ~cortical signal in regions of calcification

DDx: Abnormal Vessels and Enhancement Patterns

Venous Anomalies

Venous Anomalies

TB Meningitis

Congenital Malformations

TB Follow-up

STURGE-WEBER SYNDROME 1

Key Facts Terminology • Sturge-Weber syndrome (SWS); Sturge-Weber-Dimitri; encephalotrigeminal angiomatosis • Usually a sporadic congenital (but not inherited) malformation in which fetal cortical veins fail to develop normally • Imaging features are sequelae of progressive venous occlusion and chronic venous ischemia

• Late: t Signal in region of gliosis & ! cortical signal in regions of calcification • Early: Serpentine leptomeningeal enhancement, pial angiomatosis of subarachnoid space • Late: "Burnt-out" ~ !pial enhancement, t cortical/subcortical Ca++; atrophy • Progressive sinovenous occlusion

Pathology

Imaging Findings

• Epidemiology:

• Best diagnostic clue: Cortical Ca++, atrophy, and enlarged ipsilateral choroid plexus • Pial angiomatosis unilateral 80%, bilateral 20% • Radiography: Tram-track calcification • Early: Transient hyperperfusion ~ "accelerated" myelin maturation

Clinical Issues

• FLAIR o Late: Gliois in involved lobes o FLAIR C+: Improved visualization of leptomeningeal enhancement • T2* GRE: Tram-track gyral calcifications • DWI: Restricted diffusion in acute ischemia • Tl C+ o Early: Serpentine leptomeningeal enhancement, pial angiomatosis of subarachnoid space o Late: "Burnt-out" ~ !pial enhancement, t cortical/subcortical Ca++; atrophy o Engorged, enhancing choroid plexus • MRA: Rare high-flow arteriovenous malformations • MRV o Progressive sinovenous occlusion • Lack of superficial cortical veins • ! Flow transverse sinuses/jugular veins • t t Prominence deep collateral (medullary/subependymal) veins • MRS: t Choline; !NAA in affected areas • Fat-saturation: Orbital enhancement> 50%, best seen with T1 C+ fat-saturation o Choroidal angioma, periorbital soft tissues, bony orbit and frontal bone

Ultrasonographic

Findings

• Pulsed Doppler: ! Middle cerebral artery velocity

Angiographic

Findings

• Conventional o Pial blush, rare arteriovenous malformation o Findings mostly venous: Paucity of normal cortical veins, extensive medullary and deep cOllaterals

Nuclear Medicine

Findings

• Bone Scan o Hypertrophied ipsilateral cortex, diploic involvement o Intracranial dystrophic gyral calcification • PET: Progressive hypoperfusion; progressive glucose hypometabolism • SPECT: Transient hyperperfusion (early); hypoperfusion (late)

Rare: 1:50,000

• Clinical profile: "Port-wine stain", seizures, hemiparesis

o Pattern inconsistent, may be smaller or larger than abnormality detected on CT/MRI

Imaging Recommendations • Best imaging tool: Enhanced MRI • Protocol advice o NECT to evaluate for calcification (may be more extensive than recognized on MRI) o MR with contrast (assess extent, uni-/bilaterality, orbital involvement) • FLAIR + contrast improves conspicuity of leptomeningeal angiomatosis

I DIFFERENTIAL DIAGNOSIS Other vascular phakomatoses (neurocutaneous syndromes) • Blue-rubber-bleb nevus syndrome o Multiple small cutaneous venous malformations plus intracranial developmental venous anomalies • Wyburn-Mason syndrome o Facial vascular nevus; visual pathway and/or brain arteriovenous malformation (AVM) • Klippel-Trenaunay-Weber syndrome o Osseous/soft tissue hypertrophy, extremity vascular malformations o May be combined with some features of SWS • PHACE o Posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta, cardiac and eye anomalies • Meningioangiomatosis o Ca++ common; variable leptomeningeal enhancement o May invade brain through Virchow-Robin perivascular spaces o Atrophy usually absent

Celiac disease • Bilateral occipital Ca++; no angiomatous of brain/face

Congenital Malformations

involvement

95

STURGE-WEBER SYNDROME

1

Leptomeningeal

96

• Meningitis; leptomeningeal

enhancement metastases, & leukemia

o Stroke-like episodes; neurological deficit 65%; migraines • Clinical profile: "Port-wine stain", seizures, hemiparesis

Demographics General Features • General path comments o Cutaneous nevus flammeus CN VI & V2; +/- visceral angiomatosis o Embryology • 4-8 week stage: Embryonic cortical veins fail to coalesce & develop ~ persistence of primordial vessels • Visual cortex adjacent to optic vesicle and upper fetal face • Genetics o Usually sporadic: Probable somatic mutation or cutaneous mosaicism • Fibronectin (found in SWS port-wine-derived fibroblasts and SWS surgical brain samples) regulates angiogenesis and vasculogenesis o Very rarely familial, but occasionally with other vascular phakomatosis • Etiology: Persistent fetal vasculature ~ deep venous occlusion/stasis ~ anoxic cortex • Epidemiology: Rare: 1:50,000 • Associated abnormalities: 50% have extracranial port-wine stains (torso or extremities), so evaluate for other vascular phakomatoses

Gross Pathologic & Surgical Features • Meningeal hypervascularity & angiomatosis • Subjacent cortical & subcortical Ca++

Microscopic

Features

• Pial angioma = multiple thin-walled vessels in enlarged sulci • Cortical atrophy, Ca++ • Occasional underlying cortical dysplasia

Staging, Grading or Classification Criteria • Roach Scale o Type I: Leptomeningeal plus facial; +/- glaucoma o Type 2: Facial only; +/- glaucoma o Type 3: Leptomeningeal only

ICLlNJCAllSSU ES

• Age o Facial lesion visible at birth • Pial angiomatosis may be occult if no facial lesion and no seizures to prompt imaging o Seizures (Sz) develop first year of life • Infantile spasms ~ tonic/clonic, myoclonic • Gender: M = F • Ethnicity: No ethnic predilection

Natural History & Prognosis • 1 Extent of lobar involvement and atrophy ~ 1 likelihood Sz • If Sz ~ developmental delay 43%, emotional/behavioral problems 85%, special education 70%, employability 46% • Progressive hemiparesis 30%, homonymous hemianopsia 2%

Treatment • Treat seizures; resection affected lobes (hemisphere) may be required • Laser skin lesions (cosmetic)

I DIAGNOSTIC Consider

• In "Sturge-Weber-like" syndromes, look for extracranial manifestations

Image Interpretation

Pearls

• Choroid plexus nearly always enlarged on involved side o May be only finding in first 6 months of life o If both sides enlarged, look for bilateral involvement (may be subtle)

I SELECTED REFERENCES 1. 2.

3.

Presentation • Most common signs/symptoms o CN VI facial nevus flammeus ("port-wine stain") 98%; (+/- V2, V3) • Need to look at mucous membranes for occult lesions o Eye findings especially with upper and lower lid nevus flammeus • Choroidal angioma 70% ~ 1 intraocular pressure/congenital glaucoma ~ buphthalmos • Retinal telangiectatic vessels; scleral angioma; iris heterochromia o Seizures 90%; hemiparesis 30-66%

CHECKLIST

4.

5.

6.

7.

Comi AM et al: Increased fibronectin expression SWS fibroblasts and brain tissue. Pediatr Res 53(5):762-9, 2003 Pfund Z et al. Quantitative analysis of gray-and white-matter volumes and glucose metabolism in Sturge-Weber syndrome. J Child NeuroI18(2):119-26, 2003 Lin DD et al: Early characteristics of Sturge-Weber syndrome shown by perfusion MRI and proton MRS imaging. AJNR 24(9):1912-5,2003 Portilla P: SW disease with repercussion on the prenatal development of the cerebral hemisphere. AJNR 23(3):490-2, 2002 Cohen MM: Asymmetry: Molecular, biologic, embryopathic, and clinical perspectives. Am J Med Genet 101(4):292-314,2001 Maria BL et al: CNS structure and function in Sturge-Weber syndrome: Evidence of neurologic and radiologic progression. J Child Neurol13:606-18, 1998 Griffiths PD et al: 99m Technetium HMPAO imaging in children with the Sturge-Weber syndrome: A study of nine cases with CT and MRI correlation. Neuroradiology 39(3):219-224, 1997

Congenital Malformations

1 97

Typical (Left) Axial T1 C+ MR in a

70 month old with SWS shows bilateral disease with frontal pial angiomatosis (arrows), contralateral Sylvian angiomatosis (open arrow) and engorged choroid plexus (black arrow). (Right) Axial T2WI MR shows "accelerated" myelin maturation (arrow) of involved right frontal lobe. There is contralateral Sylvian CSFprominence associated with pial angiomatosis as shown in previous image.

Typical (Left) Axial NECT shows

"tram-track" calcification (arrow), parallel calcified lines in cortical gyri at the vertex. Significant ipsilateral volume loss is identified. (Right) Axial OWl MR in another patient with Sturge-Weber shows restricted diffusion in an area of cortical involvement (open arrow). Patient presented with a stroke-like episode.

(Left) Lateral view, catheter

angiogram (venous phase) shows extensive medullary venous collateral drainage and lack of superficial drainage in a child with Sturge-Weber syndrome. (Right) Axial T1 C+ MR fat-saturated view of orbit shows choroidal angioma (arrow), periorbital enhancement (curved arrow) and enhancement of the enlarged ipsilateral, greater wing of sphenoid (open arrow).

Congenital Malformations

MENINGIOANGIOMATOSIS 98

Axial CECT in a patient with menmgloangiomatosis shows peripherally located mass on the surface of the right cerebellar hemisphere containing calcifications (arrow) and a cyst.

Axial CECT in the same patient clearly shows cerebellar calcifications (arrow). Note enlarged optic chiasm (open arrow) in this patient with NFl.

•

Definitions • Rare, hamartomatous malformation

cortical/leptomeningeal • • •

General Features • Best diagnostic clue: Cortical mass with Ca++ • Location o Cortex (frontal and temporal lobes), right> left o Rarely in: 3rd ventricle, thalami, brainstem, cerebellum • Size: Generally small lesions (1-3 cm)

CT Findings • NECT o Solitary or multiple cortical mass(es) & Ca++ • Ca++: Nodular, linear, or gyriform o Occasional: hemorrhage & cysts o No or little mass effect • CECT: Homogeneous enhancement • CT Perfusion

MR Findings • TlWI

o Isointense with areas of signal void (Ca++) o Hypointense cysts T2WI o Hyperintense with areas of signal void (Ca++) o Target-like lesions, central hyperintensity o Hyperintense cysts PD/lntermediate: Slightly hyperintense, areas of signal void (Ca++) T2* GRE: Accentuates Ca++ T1 C+: Homogeneous enhancement

Angiographic Findings • Conventional:

Generally normal

Imaging Recommendations • Best imaging tool: MRI and CT • Protocol advice: Noncontrast CT to look for calcium, contrast enhanced MRI to look at cysts, edema and parenchymal enhancement

lesions with Ca++ and cysts • • • • •

Meningioma Oligodendroglioma Granulomatous meningitis (sarcoid, tuberculosis) Parasitic diseases (Cysticercosis) Ganglioglioma

DDx: lesions with Ca++ and Cysts

Meningioma

Oligodendroglioma

Cysticercosis

Congenital Malformations

Canglioglioma

MENINGIOANGIOMATOSIS

1

Key Facts Terminology

Pathology

• Rare, hamartomatous malformation

cortical/leptomeningeal

99

• Neurofibromatosis found in Vz of patients (particularly NF2)

Imaging Findings

Diagnostic Checklist

• Best diagnostic clue: Cortical mass with Ca++ • Hyperintense cysts

• Calcified cortical mass (with or without cysts)

• Sturge- Weber disease • DNET

• Clinical profile: Young patients with long-standing history of seizures

I PATHOlOGY

• Age: Children, young adults • Gender: M > F

Demographics General Features • General path comments o Cortical meningovascular proliferation with Ca++ o Generally solitary but may be multiple • Diffuse lesions are very rare o Often extends into cortex via perivascular spaces o No malignant degeneration • Etiology o Uncertain • Hamartoma? Meningioma invading brain? Vascular malformation? • Epidemiology: Children, young adults • Associated abnormalities o Neurofibromatosis found in Vz of patients (particularly NF2) o Meningioma o Oligodendroglioma o Arteriovenous malformation o Encephalocele o Meningeal hemangiopericytoma

Gross Pathologic & Surgical Features • • • •

Features of meningioma and angioma Slow-growing tumor Psammomatous Ca++ or dense osteoid Serpentine blood vessels overlying lesion

Microscopic

Natural History & Prognosis • Prognosis is excellent with excision

Treatment • Options, risks, complications:

Surgery

I DIAGNOSTIC CHECKUST Image Interpretation

Pearls

• Calcified cortical mass (with or without cysts)

I SElECTED REFERENCES 1.

2.

3. 4.

Kim NR et al: Childhood meningiomas associated with meningioangiomatosis: report of five cases and literature review. Neuropath Applied Neurobiol, 28: 48-56, 2002 de Felipe MA et al. Neuronal and mixed neuroglial tumors associated to epilepsy. A heterogeneous and related group oftumors. Histol Histopathol16: 613-22, 2001 Scroop R et al: Meningioangiomatosis. Australian Radiology, 44: 460-63, 2000 Park MS et al: Multifocal meningioangiomatosis: a report of two cases. A]NR, 20: 677-80, 1999

I IMAGE GAllERY

Features

• Leptomeningeal proliferation of meningoendothelial cells exhibiting degenerative reactions • Ca++, fibrocartilage and/or bone formation • Cortical plaques of proliferating small blood vessels • Perivascular cuffs of spindle-shaped fibroblast-like cells • Occasional neuro-fibrillary tangles • Gliotic cortex

I CUNICAl

ISSUES

Presentation • Most common signs/symptoms o Intractable seizures, headaches o Can be found incidentally (particularly NF2)

Axial FLAIR MR shows hyperintense meningiomatosis with central hypointensity (Ca++) (arrow). (Right) Coronal T1 C+ MR shows homogeneous enhancement of tumor. Also note perivascular extension (arrow).

(Left)

Congenital Malformations

1 100

Axial NECT shows expansile cysts (arrows) containing unerupted molars in the area of the retromolar triangles.

ItERMINOLOc;Y Abbreviations

Radiographic Findings

and Synonyms

• Basal cell nevus syndrome (BCNS), Gorlin syndrome, Gorlin-Goltz syndrome, nevoid basal cell carcinoma syndrome

Definitions • BCNS = hereditary tumor syndrome characterized by multiple basal cell epitheliomas (BCE)/basal cell carcinomas (BCC), odontogenic keratocysts, palmoplantar pits, dural Ca++, +/- medulloblastoma

11MAGtNG••FIN[)I~GS General Features • Best diagnostic clue o Multiple jaw cysts, prominent dural Ca++, abnormal ribs o Other generic features: Macrocephaly, hyperaerated paranasal sinuses, splayed/fused/bifid ribs, . kyphoscoliosis, platybasia, Sprengel deformIty of scapulae • Location o Cysts: Mandible, maxilla o Ca++: Intracranial dura • Size: Variable enlargement of mandible, maxilla

DDx: Cystic Mandible

Ameloblastoma

Axial NECT shows expansile odontogenic keratocysts in the region of the maxillary sinuses. Note unerupted teeth (arrows).

• Radiography o Diffuse, tiny, lytic (kerato) cysts of bones (35%), esp jaws o Other • Thick calvarium with platybasia • Rib anomalies • Short 4th metacarpals • Spina bifida occulta; vertebral segmentation anomalies

CT Findings • NECT o Odontogenic keratocysts (OKC) in 80-90% • Large, uni- or multilocular cysts, containing unerupted teeth • Mandible> maxilla o Ca++ of falx (eventually 100%), tentorium, peri-clinoid ligaments (dural bridging), dura, pia, choroid plexus & basal ganglia o Ca++ occurs late, is are progressive o +/- Ventriculomegaly o +/- Callosal dysgenesis o Cysts of all kinds common • CECT o Look for • Desmoplastic medulloblastoma • Meningioma

lesions

ABC

Mucocele

Congenital Malformations

Rep Granuloma

BASAL CELL NEVUS SYNDROME 1

Key Facts Terminology • Basal cell nevus syndrome (BCNS), Gorlin syndrome, Gorlin-Goltz syndrome, nevoid basal cell carcinoma syndrome • BCNS = hereditary tumor syndrome characterized by multiple basal cell epitheliomas (BCE)/basal cell carcinomas (BCC), odontogenic keratocysts, palmoplantar pits, dural Ca++, +/- medulloblastoma

Imaging Findings • Multiple jaw cysts, prominent dural Ca++, abnormal ribs • Odontogenic keratocysts (OKC) in 80-90% • Large, uni- or multilocular cysts, containing unerupted teeth

• Colloid cyst

Top Differential • • • • •

Diagnoses

Ameloblastoma Dentigerous cyst Cherubism Aneurysmal bone cyst Giant reparative granuloma

Clinical Issues • Usually diagnosed during the 1st decade of life

Aneurysmal bone cyst

MR Findings • T1WI o OKC are hypointense to isointense, contain a hypointensity representing the unerupted tooth o Dural Ca++ may be MR "occult" or only seen on MPGR sequence • T2WI: OKC are hyperintense, contain a hypointensity representing the unerupted tooth • T1 C+: Cysts may show thin peripheral enhancing rim

Nuclear Medicine

Findings

• Multilocular, muti-septated mass in mandible • Enhancing soft tissues inside and outside of bony rim

Miscellaneous

maxillary masses

• Maxillary sinus mucocele: Contains no cyst or septae, smooth expansion of sinus walls • Incisor canal cyst: Found in midline anterior maxilla, posterior to incisors, water density/intensity, small • Globulomaxillary cyst: Located between lateral incisor and canine, small

Giant reparative granuloma

• Bone Scan: May show 1 uptake

Other Modality

• Ca++ of falx (eventually 100%), tentorium, peri-clinoid ligaments (dural bridging), dura, pia, choroid plexus &;basal ganglia

• Solitary mass, generally solid, does not contain unerupted tooth

Findings

• Dural Ca++: Possibly associated with 1 Alk Phos noted in patients with growing odontogenic keratocysts; seen earlier on CT than PF

I PATHOL.OGY

Imaging Recommendations

General Features

• Best imaging tool: CT mandible for oral surgery planning • Protocol advice o 3 mm axial and coronal CT of the face including mandible o Pelvic sonography to detect ovarian tumors

• General path comments o 3x more common in mandible than in maxilla • Mainly in premolar and retromolar triangle area o May be small, single, multiple, large, unilocular or multilocular o May cross the midline • Genetics o Autosomal dominant: Complete penetrance, variable expression o New mutations 1 with advanced paternal age o Mutation inactivated tumor suppressor genes PTCH1&;2 (9q22.3-q31) • Etiology: The PATCHED (PTC) gene encodes a Sonic hedgehog (SHH) receptor and a tumor suppressor protein that is defective in BCNS • Epidemiology olin 57,000 (1 in 200 with BCC have syndrome, 1 in 5 if < 19 yrs) o Most BCNS have odontogenic keratocysts (OKC); 5% of patients with OKC have BCNS • Associated abnormalities

I DIFFERENTIAL. DIAGNOSIS Ameloblastoma • Bubbly-appearing, solitary lesion may contain unerupted tooth • When large, associated enhancing soft tissue mass nearly always present • May have enhancing solid mural nodule

Dentigerous

cyst

• Unilocular cyst surrounding tooth crown • No enhancing intra- or extra-cyst soft tissue

Cherubism • Symmetrical

cystic fibrous dysplasia of mandible

Congenital Malformations

101

BASAL CELL NEVUS SYNDROME

1 102

o Associated neoplasms (mutation inactivated tumor suppressor genes) • Rare ameloblastoma & squamous cell cancer • Desmoplastic medulloblastoma (5% medulloblastoma have BCNS) • Cardiac, abdominal and pelvic mesenchymal tumors

Gross Pathologic & Surgical Features • OKC: Expansile mandible and/or maxillary cysts with unerupted tooth o Satellite cyst formation is common; may involve coronoid process o Maxillary canine/premolar area> retromolar

Microscopic

o Especially fair skin, sun exposure, irradiation o Darkly pigmented skin protective, has smaller numbers BCC • Normal life expectancy if no medulloblastoma

Treatment • Options, risks, complications: After surgery, recurrence is very high (up to 60%) • Skin lesions: Lifelong monitoring; topical tretinoin/5-fluorouracil, photodynamic therapy; early surgical removal • Surgery/chemotherapy, avoid radiotherapy for medulloblastoma

Features

• OKC: Parakeratinized factor receptor

lining and 1 epithelial growth

Consider

Staging, Grading or Classification Criteria • Need 2 major or 1 major and 2 minor criteria for diagnosis • Major criteria: > 2 (or 1 under 30 yrs) basal cell carcinomas; > 10 basal cell nevi; odontogenic keratocyst or polyostotic bone cyst; ~ 3 palmar/plantar pits; lamellar or (under 20 yrs) falx Ca++; family history • Minor criteria: Rib or vertebral anomalies, macrocrania/frontal bossing; cardiac or ovarian fibromas; mesenteric cysts; facial clefting (5-13%), hand (long fingers, short 4th metacarpal, polydactyly) or ocular anomalies

• BCNS when precocious dural Ca++ and OKC are detected

Image Interpretation • Multiple mandibular teeth I SELECTED 1. 2.

3.

I CLlN.ICALISSl.JES

4.

Presentation • Most common signs/symptoms: Jaw and maxilla deformity with pain • Clinical profile: Desmoplastic medulloblastoma in boys 2 years and younger (before syndrome apparent), beware, irradiation induced 11 number BCC • BCE (75%) onset puberty, resemble nevi or skin tags; BCC by 40yrs • Skin (other): Epidermal (kerato) cysts (55%), milia, fibromas, lipomas • Palmar and plantar pits (> 85%): Usually noticed after childhood • Multiple OKC that may fracture or become infected • Dysmorphic facies; large head/large brow, everted mandibular angle, hypertelorism, lip clefts common, macrosomia, tall stature • Cognition normal if no malformations/tumors and no prior irradiation

5.

6.

7.

8.

teeth or parts of

REFERENCES

Kahn]L et al: [Imaging of mandibular malformations and deformities]] Radiol. 84(9):975-81, 2003 Ozturk A et al: Neuroradiological findings in a mother and daughter with Godin syndrome. Clin Dysmorphol. 12(2):145-6,2003 Su CW et al: Spontaneous recovery from a medulloblastoma by a female with Godin-Goltz syndrome. Pediatr Neurol. 28(3):231-4, 2003 Leonardi R et al: Bilateral hyperplasia of the mandibular coronoid processes in patients with nevoid basal cell carcinoma syndrome: an undescribed sign. Am] Med Genet 110:400-403. Am] Med Genet. 120A(3):446, 2002 Rozylo-Kalinowska I et al: Odontogenic keratocyst in Godin-Goltz syndrome. Ann Univ Mariae Curie Sklodowska [Med]. 57(2):79-85, 2002 Iwanaga S et al: Godin syndrome: Unusual manifestations in the sella turcica and the sphenoidal sinus. A]NR 19:956-8, 1998 Wicking C et al: De novo mutations of the PATCHED gene in nevoid BCC syndrome help to define the clinical phenotype. Am] Med Genet 73(3):304-7,1997 Mosskin M et al: Nevoid basal cell carcinoma syndrome. Int] Neuroradiol 2(5):480-8, 1996

Demographics • Age o Usually diagnosed during the 1st decade of life • OKC usually form before 7 years of age • Gender: No predilection • Ethnicity: No predilection

Natural History & Prognosis • Develop enormous

Pearls

cysts containing

numbers BCCs

Congenital Malformations

BASAL CELL NEVUS SYNDROME

1

IIMAGE GALLERY

103

Typical (Left) Coronal NECT shows odontogenic keratocysts in right maxillary sinus (arrow) containing an unerupted tooth and in the midline mandible (curved arrow). (Right) Coronal NECT shows cyst in left maxillary sinus containing unerupted tooth (arrow).

Typical (Left) Axial NECT shows calcified falx cerebri (arrows) in a child with Gorlin syndrome. (Right) Anteroposterior chest radiograph shows multiple right sided rib anomalies (arrow).

Typical (Left) Axial T2WI MR shows multiple hyperintense mandibular cysts (arrows). (Right) Axial T2WI MR shows a fourth ventricular medulloblastoma in a child with Gorlin syndrome.

Congenital Malformations

HHT

1 104

Frontal clinical photograph shows a patient with HHT. Note purplish discolorations of scalp and cheek (open arrows), plus small mucosal telangiectasias of the nose and lip (curved arrows).

Frontal OSA in an asymptomatic patient with HHT shows a classic small cAVM (arrow). Priorscreening MR detected the lesion.

ITERMINOLOGY Abbreviations

CT Findings • NECT o Brain • AVM = isodense serpentine vessels • Abscess = low density mass with iso-/hyperdense rim o Lung: High-resolution NON CONTRAST multi slice CT shows well-delineated vascular mass(es), usually in lower lobes • CECT o Brain • Strong, uniform, well-delineated enhancement of cAVMs • Ring-enhancement of abscesses (late cerebritis, early capsule stage) o Liver: Multi-detector row helical contrast-enhanced CT demonstrates abnormalities in 75% of HHT patients • Arterioportal, arteriosystemic shunts (100%) • Intraparenchymal telangiectases (60-65%) • Large confluent vascular masses (25%) • CTA: May demonstrate visceral, CNS high-flow vascular malformations (AVMs, AVFs)

and Synonyms

• Hereditary hemorrhagic telangiectasia Osler-Weber-Rendu (OWR) syndrome

(HHT)i

Definitions • Autosomal dominant disorder with widely distributed, multisystem angiodysplastic lesions o Mucocutaneous, visceral telangiectasias o AVMs/AVFs (lungs, brain, GI tract, liver)

I IMAGING

FINDINGS

General Features • Best diagnostic clue: Multiple pulmonary (pAVM) or cerebral (cAVM) arteriovenous malformations in patient with recurrent epistaxis • Location o Capillary telangiectasias in scalp, nasopharynx, orbit o Intracranial vascular malformations (AVM, DVA) may be multiple, occur anywhere • Size: Intracranial vascular malformations in HHT are usually small, often incidental • Morphology: Mottled, purplish skin, scalp, mucosal lesions

MR Findings • TlWI o AVM: "Flow voids" common, +/- hemorrhage o Small DVAs, telangiectasias often not visualized

DDx: HHT

Normal Nasal Blush

VHL

Congenital Malformations

Giant OVA

HHT

1

Key Facts Terminology • Hereditary hemorrhagic telangiectasia (HHT)i Osler-Weber-Rendu (OWR) syndrome • Autosomal dominant disorder with widely distributed, multisystem angiodysplastic lesions

Imaging Findings • Best diagnostic clue: Multiple pulmonary (pAVM) or cerebral (cAVM) arteriovenous malformations in patient with recurrent epistaxis • Capillary telangiectasias in scalp, nasopharynx, orbit • Intracranial vascular malformations (AVM, DVA) may be multiple, occur anywhere • Liver: Multi-detector row helical contrast-enhanced CT demonstrates abnormalities in 75% of HHT patients

• T2WI o cAVM: "Flow voids" o Usually no hemorrhage, edema, mass effect • FLAIR: Nest of flow voids • T2* GRE o May show flow in cAVMs o Capillary telangiectasias become mildly hypointense o Useful in detecting micro hemorrhages • Tl C+: Slow-flow vascular malformations (e.g., DVAs, telangiectasias) enhance ·MRA o Demonstrates intermediate to large cAVMs o "Micro" AVMs may not be visualized without contrast-enhanced MRA • MRV: May demonstrate DVA

Angiographic

Top Differential

Diagnoses

• Nasal mucosal "blush" • Multiple intracranial AVMs without HHT

Pathology • Autosomal dominant mutations

inheritancei

two known

Clinical Issues • Epistaxis typically begins by age 10, most HHT patients are symptomatic by age 21 y

Multiple

intracranial DVAs

• Rarely associated with HHTi seen in bean and blue rubber bleb nevus syndromes

Multiple capillary telangiectasias • Can be found incidentally without HHT • Capillary telangiectasias in HHT are much more common outside brain than in it!

Multiple cavernous malformations • More common in multiple cavernoma

syndrome

I PATHOl.OGY General Features

Findings

• Conventional o Varies with findings (AVM, AVF,DVA) o cAVMs can be micro-, small, or macro-AVM • Only 10-12% of cAVMs in HHT patients are> 10 mm

Imaging Recommendations • Best imaging tool o Brain: MR with contrast • Baseline screening of brain in all patients with HHT highly recommended (cAVMs can have devastating neurologic sequelae) o Lungs, liver: Multislice CT/CTA • Protocol advice: Brain: Include: Contrast, T2* GRE, MRA

I DIFFERENTIAl. DIAGNOSIS Nasal mucosal "blush" • Prominent but normal nasal mucosal blush can mimic capillary telangiectasia

Multiple

• Baseline screening of brain in all patients with HHT highly recommended (cAVMs can have devastating neurologic sequelae)

intracranial AVMs without HHT

• Rare in absence of vascular neurocutaneous syndrome • 50% not associated with HHT (Wyburn-Mason, etc)

Congenital

• General path comments: Abnormalities of vascular structures account for all recognized phenotypic manifestations of HHT • Genetics o Autosomal dominant inheritancei two known mutations o Type 1 HHT: Endoglin gene (chromosome 9q33-q34) mutation • Earlier onset of epistaxis, telangiectasis • pAVMs o Type 2 HHT: ALK-l gene mutation • Lower penetrance, milder disease • GI bleeds • Etiology o Abnormal intracellular signal transduction during angiogenesis o Abnormalities of transforming growth factor-beta (TGF-b) receptors • Epidemiology: Rarei 10-20 cases/lOO,OOO individuals • Associated abnormalities o 70% of patients with pAVMs have HHT o At least 50% of patients with multiple cAVMs have HHT o 5-15% of people with HHT have pAVMs o 5-13% of patients with HHT have cAVMs o 2- 17% have hepatic AVMs (depends on kindred)

Malformations

105

106

Gross Pathologic & Surgical Features

Treatment

• Multiple telangiectasias of mucosa, dermis almost universal • AVMs, AVFs appear in only certain forms of HHT o Most pAVMs are actually AVFs (direct connection between pulmonary artery and vein through thin-walled aneurysm) o Hepatic AV shunts less common, often numerous

• pAVMs: Surgery no longer indicated because of excellent results with embolization for pAVMs • cAVMs: Varies with lesion size, location o Options: Embolotherapy, stereotaxic radiosurgery • Mucosal telangiectasias (nose, GI tract) can be treated with laser coagulation • Prophylactic antibiotics prior to all dental work if pAVM present • IV iron useful when oral iron fails to keep stores at satisfactory level

Microscopic

Features

• Smallest telangiectasias = focal dilatations of post-capillary venules • Larger lesions extend through entire dermis, often connect directly to dilated arterioles

IDIAGNQSTIC.CI--lE(:KLIST

Staging, Grading or Classification Criteria • Most cAVMs in HHT are low grade (Spetzler-Martin

I

or II)

Consider • Screening brain MRI in family members of HHT patients

Image Interpretation

I CliNICAL1SSUES Presentation • Most common signs/symptoms: Recurrent epistaxis from nasal mucosal telangiectasias • Clinical profile o HHT diagnosis based on combination of findings • Mucocutaneous telangiectasias • Spontaneous/recurrent episodes of epistaxis • Presence of visceral involvement • Family history • Neurologic symptoms common o Parenchymal or SAH with brain AVM o TIA, stroke, abscess as complications of pulmonary AVMs • Pulmonary AVMs cause o R/L shunts o Dyspnea, cyanosis o Fatigue o Polycythemia o Serious complication = cerebral emboli/abscess

Demographics • Age o Epistaxis typically begins by age 10, most HHT patients are symptomatic by age 21 y • Can be severe, exsanguinating o Skin lesions appear later (most by 40 y)

Natural History & Prognosis • Epistaxis increases in frequency, severity • Unless large, cAVMs in HHT have lower bleeding risk than sporadic AVMs; rare cases may regress spontaneously • Significant lifetime risk of brain abscess or stroke if pAVM present • Heart failure a poor prognoses in patients with hepatic AVM • GI bleeding also limits lifespan when occurs under age 50; many require multiple transfusions and endoscopies

Pearls

• The most common intracranial vascular malformation in HHT patients is AVM, not capillary telangiectasia • Brain abscess is uncommon but serious complication in HHT patients with pAVMs

I SELECTED

REFERENCES

1. Ianora AAS et al: Hereditary hemorrhagic telangiectasia: Multi-detector row helical CT assessment of hepatic involvement. Radiol230: 250-9, 2004 2. Kuwayama K et al: Central nervous system lesions associated with hereditary hemorrhagic telangiectasia--three case reports. Neurol Med Chir (Tokyo). 43(9):447-51,2003 3. Berg J et al: Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALKI mutations. J Med Genet. 40(8):585-90, 2003 4. Abdalla SA et al: Visceral manifestations in hereditary haemorrhagic telangiectasia type 2. J Med Genet. 40(7):494-502, 2003 5. Marchuk DA et al: Vascular morphogenesis: tales of two syndromes. Hum Mol Genet. 12 Spec No I:R97-112, 2003 6. Larson AM: Liver disease in hereditary hemorrhagic telangiectasia. J Clin Gastroenterol. 36(2):149-58, 2003 Sabba C et al: Hereditary hemorrhagic teleangiectasia 7. (Rendu-Osler-Weber disease). Minerva Cardioangiol. 50(3):221-38,2002 8. Shah RK et al: Hereditary hemorrhagic telangiectasia: a review of 76 cases. Laryngoscope. 112(5):767-73, 2002 9. Arnold SM et al: Acute hepatic encephalopathy with diffuse cortical lesions. Neuroradiology. 43(7):551-4, 2001 10. Byard RW et al: Osler-Weber-Rendu syndrome--pathological manifestations and autopsy considerations. J Forensic Sci. 46(3):698-701, 2001 11. Dong SL et al: Brain abscess in patients with hereditary hemorrhagic telangiectasia: case report and literature review. J Emerg Med. 20(3):247-51, 2001 12. Willemse RB et al: Bleeding risk of cerebrovascular malformations in hereditary hemorrhagic telangiectasia. J Neurosurg. 92(5):779-84, 2000

Congenital Malformations

HHT 1

I IMAGE GALLERY

107

Typical (Left) Axial T2WI MR obtained for screening purposes in an asymptomatic patient with HHT shows a nest of "flow voids" suggesting a small AVM (arrow). (Right) Lateral OSA in the same patient shows a classic AVM with nidus (open arrow) and early draining vein (arrow). Note absence of mass effect.

Typical (Left) Lateral OSA of the right internal carotid artery late arterial phase, in a patient with HHT and epilepsy shows a small frontal AVM (arrow). (Right) Lateral OSA of the left vertebral artery in the same case shows another small AVM (arrow).

Typical (Left) Lateral OSA of the internal maxillary artery in a patient with HHT and recurrent epistaxis shows multiple small scalp and mucosal vascular telangiectasias (arrows). (Right) Lateral OSA of the ipsilateral internal carotid artery in the same patient shows enlarged branches of the ophthalmic artery supply a small asymptomatic telangiectasia in the orbital mucosa (arrow).

Congenital Malformations

ENCEPHALOCRANIOCUTANEOUS

LIPOMATOSIS

1 108

Photo shows the typical appearance of "nevus psiloliparus", a well-circumscribed area of scalp alopecia. The nevus overlies a lipoma and is the hallmark of encephalocutaneous lipomatosis.

I TERMINOLOGY Abbreviations

and Synonyms

• Encephalocraniocutaneous lipomatosis (ECCL), Haberland syndrome, Fishman syndrome

Definitions • Rare congenital neurocutaneous syndrome characterized by ipsilateral cranial, facial, ocular and CNS anomalies • First described by Catherine Haberland in 1970

I IMAGING

FINDINGS

General Features • Best diagnostic clue o Unilateral hemispheric cerebral atrophy and ventriculomegaly in a child with ipsilateral alopecia overlying a scalp lipoma • Although ventriculomegaly primarily 2° parenchymal volume loss, hydrocephalus is frequently present • Location o Except intracranial (Ie) lipomas, CNS imaging findings ipsilateral to cranial, ocular abnormalities o Focal occipital lobe atrophy and occipital horn enlargement characteristic

DDx: Neurocutaneous

Sturge-Weber

Sagittal T1WI MR shows an ipsilateral scalp (arrow) and orbital (open arrow) lipoma. The globe is buphthalmic with a sclerallipodermoid.

• Other frequent hemispheric abnormalities: Middle cranial fossa arachnoid cyst, cortical dysplasia and Ca++ • CNS lipomas occur inconsistently o IC lipomas usually ipsilateral; occasionally contra- or bilateral • Location: Cerebellopontine angle, Meckel cave/CN 5, foramen magnum o Spinal lipomas occur in 15%; cervicothoracic > lumbar

CT Findings • NECT o Unilateral hemispheric atrophy, ventriculomegaly, +/- cortical Ca++ • Cortical Ca++ progressive; identified as early as 1st month of life o +/- Focal calvarial enlargement o Scalp/IC lipoma: Low density • CECT: +/- Diffuse, unilateral leptomeningeal (LM) enhancement • CTA: Arterial ectasias, pouches, and aneurysms described in older patients

MR Findings • TlWI o Scalp/intracranial lipomas hyperintense o Unilateral polymicro- > pachygyria of temporal, parietal, and/or occipital lobes

Syndromes with Hemispheric Abnormalities

Epidermal Nevus

Epidermal Nevus

Congenital Malformations

Proteus

ENCEPHALOCRANIOCUTANEOUS

LIPOMATOSIS 1

Key Facts Pathology

• Rare congenital neurocutaneous syndrome characterized by ipsilateral cranial, facial, ocular and CNS anomalies

• Sporadic • Epidemiology: Rarei - 40 reported cases (likely under-reported)

Imaging Findings

Clinical Issues

• Unilateral hemispheric cerebral atrophy and ventriculomegaly in a child with ipsilateral alopecia overlying a scalp lipoma • CNS lipomas occur inconsistently

• Nevus psiloliparus: Sharply demarcated, hairless scalp lesion (overlies scalp lipoma) • Newborn> infant presentation most common • Variable degrees of psychomotor impairment and dependency

Top Differential • • • •

•

•

• • • •

109

Terminology

Diagnoses

Sturge- Weber syndrome (SWS) Oculocerebrocutaneous syndrome (OCCS) Epidermal nevus syndrome (ENS) Proteus syndrome

o Sclerallipodermoids occasionally identified on imaging (better evaluated clinically) • Heterogeneous with focal areas of hyperintensity T2WI o Cortical Ca++ hypointense o Lipomas hyperintense on FSE T2 o Temporal lobe hypoplasia adjacent to middle cranial fossa arachnoid cyst o Prominent subarachnoid space adjacent to atrophic hemisphere FLAIR o Occasional unilateral subdural hematoma o Nulling of signal from arachnoid cyst T2* GRE: Blooming of cortical Ca++ DWI: No diffusion restriction of arachnoid cyst Tl C+: +/- Diffuse, unilateral LM enhancement MRA: Arterial ectasias, pouches, and aneurysms described in older patients

Ultrasonographic

Findings

• Prenatal US: Ventriculomegaly trimester US

Angiographic

reported on 3rd

Findings

• Conventional: Arterial ectasias, pouches, and aneurysms described in older patients

Imaging Recommendations • Best imaging tool: MR C+/MRA • Protocol advice: Coronal/sagittal T1 C+ with fat-saturation useful for identification scalp lipoma

I DIFFERENTIAL DIAGNOSIS Sturge-Weber

syndrome (SWS)

• Imaging: Unilateral hemispheric cerebral atrophy, cortical Ca++, LM and choroid plexus (glomus) enhancement o CNS anomalies frequently confined to temporal/parietal/occipital lobes • Clinical appearance: Port wine nevus of forehead ipsilateral to CNS anomalies

Diagnostic Checklist • IC and scalp lipoma differentiate imaging)

Oculocerebrocutaneous

ECCL from SWS (on

syndrome (OCeS)

• Imaging: Ventriculomegaly, callosal agenesis, and cystic microphthalmia o Cortical dysplasia, Dandy-Walker malformation occasionally present • Clinical appearance: Unilateral> bilateral skin appendages and focal dermal hypoplastic defects o Cutaneous anomalies usually ipsilateral to microphthalmic eye

Epidermal nevus syndrome (ENS) • Imaging: Hemimegalencephaly, rare IC lipoma • Clinical appearance: Unilateral facial lipoma, epidermal nevus, and hemi-hypertrophy ipsilateral to CNS anomalies o Occasional sclerallipodermoid

Proteus syndrome • Imaging: CNS anomalies uncommoni hemimegencephaly most common • Clinical appearance: Progressive asymmetric, bilateral trunk/limb hypertrophy, osteomas, lipomas, and pigmented nevi

I PATHOLOGY General Features • General path comments o ECCL considered distinct entityi however, some clinical/imaging overlap with SWS, OCCS, ENS, and Proteus syndrome o Few reports heart, limb involvementi cafe-au-lait spots, maxillary/mandibular odontomas o Embryology-anatomy • 3rd week gestation: Embryonic disc consists of ectoderm, mesoderm, entoderm • Neural tube develops from ectoderm during 3rd week gestation • 4th & 5th week gestation: Mesoderm forms mesenchymal sheath over brain and spinal cord ~ precursor blood vessels, bone, cartilage and fat

Congen ital Malformations

ENCEPHALOCRANIOCUTANEOUS

1 110

• Genetics o Sporadic o Best theory: Survival autosomal lethal gene by somatic mosaicism • Etiology o Theory: Primary mesodermal dysgenesis of unknown etiology • Neuroectoderm secondarily involved • Epidemiology: Rare; - 40 reported cases (likely under-reported)

Gross Pathologic & Surgical Features • Brain: Cortical atrophy, white matter hypoplasia, ventriculomegaly, polymicro- > pachygyria, wallerian degeneration brains tern o Arterial ectasias, pouches, aneurysms described in older patients • Leptomeninges: Thick, gray, gelatinous with excess underlying arteries, veins, and varicose capillaries • Skull: Macrocranium with focal hyperostosis • Scalp: Focal lipomatous thickening with overlying circumscribed alopecia • Face: Multiple tiny white/purple/yellow periocular> perinasal papules • Eye: Yellowish scleral/limbal mass o Other ocular abnormalities: Persistent hyaloid vasculature, coloboma, cloudy cornea, lens dislocation, ectopic pupils

Microscopic

Features

• Brain: Abnormal, four-layered cytoarchitecture; mineral concretions outer cortical lamina; scattered glial nodules • Leptomeninges: Lipoangiomatosis • Skull: Diploic replacement with mature fat cells • Scalp: Benign lipoma> fibrolipoma expanding into dermis; absent hair follicles with preserved erector pili muscles • Skin: Subcutaneous angiofibroma, fibrolipoma, or lipoma • Eye: Corneallimbus/sclerallipodermoid, choristoma

o Newborn> infant presentation most common o Rare presentation teen/adult with cutaneous, ocular lesions • Gender: M = F • Ethnicity: No racial or geographic predilection

Natural History & Prognosis • Natural History o Growth sclerallipodermoids and lipomas has been reported; remaining congenital abnormalities static o Reports of abnormal vasculature, aneurysms later in life • Prognosis o Variable degrees of psychomotor impairment and dependency • Majority patients with moderate impairment o Rare functional, independent teens/adults described

Treatment • Anti-epileptics • Shunt placement

Consider • Could cerebral atrophy, Ca++, and leptomeningeal enhancement represent SWS • Could cerebral hemisphere be megencephalic rather than atrophic

Image Interpretation

Presentation

Pearls

• Low density IC lipoma may be difficult to distinguish from CSF on CT • IC and scalp lipoma differentiate ECCL from SWS (on imaging) • Clinical information (esp appearance of patient) indispensable

I SELECTED REFERENCES 2.

• Most common signs/symptoms o Nevus psiloliparus: Sharply demarcated, hairless scalp lesion (overlies scalp lipoma) o Other signs/symptoms • Other external lesions: Periocular> perinasal papules, yellow scleral mass • Seizures, psychomotor delay, spastic hemiparesis, macrocranium • Scoliosis, foot deformities, sensorimotor deficits (2° to spinal lipoma) • Clinical profile o Newborn with nevus psiloliparus, periocular papules, and scleral mass o Infant with seizures, nevus psiloliparus, periocular papules and scleral mass

for macrocranium

I DIAGNOSTICCHECKLJS"f

1.

I CLINICAL ISSUES

LIPOMATOSIS

3.

4.

5.

6.

Gawel J et al: Encephalocraniocutaneous lipomatosis. J Cutan Med Surg. 7(1):61-5,2003 Parazzini C et al: Encephalocraniocutaneous Lipomatosis: Complete Neuroradiologic Evaluation and Follow-up of Two Cases. AJNR 20:173-6, 1999 Rizzo R et al: Encephalocraniocutaneous lipomatosis, Proteus syndrome, and somatic mosaicism. Am J Med Genet. 47(5):653-5, 1993 Fishman MA. Related Articles et al: Encephalocraniocutaneous lipomatosis. J Child Neurol. 2(3):186-93, 1987 Alfonso I et al: Spinal Cord Involvement in Encephalocraniocutaneous Lipomatosis. Pediatr Neurol 2:380-4, 1986 Haberland C et al: Encephalocraniocutaneous Lipomatosis. Arch Neuro122:144-55, 1970

Demographics • Age

Congenital Malformations

ENCEPHALOCRANIOCUTANEOUS

LIPOMATOSIS 1 111

Typical (Left) Axial T2WI MR shows

marked left ventriculomegaly and hemispheric volume loss. The enlarged ventricle compresses and distorts the right hemisphere. (Right) Sagittal TlWI MR shows ipsilateral orbital and intracranial lipomas (open arrows). Note pachygyric cortex (arrows) and intracranial cyst (curved arrow).

(Left) Axial NfCT shows left

hemispheric atrophy and ventriculomegaly in a patient with fCCL. Cortical calcifications are absent. The scalp lipoma (nevus psiloliparus) is more obvious clinically than by CT. (Right) Axial NfCT shows a middle cranial fossa arachnoid cyst in a patient with fCCL. The cyst is ipsilateral to hemispheric atrophy and a scalp lipoma.

Variant

(Left) Sagittal TI WI M R

shows craniocervical and cerebellopontine angle (arrows) lipomas. Severe ventriculomegaly is likely secondary to CSF obstruction at foramen magnum and cerebral atrophy. (Right) Axial TI WI MR shows an intra- and extracraniallipoma. There is no hemispheric atrophy or ventriculomegaly. The patient is clinically normal. The findings may represent a forme fruste of fCCL.

Congenital Malformations

1 112

Axial T2WI MR shows a hyperintense lesion in right cerebellum (arrows) with striations ("corduroy" sign). Despite its size, the mass results in little mass effect.

Axial T1 WI M R shows the striated internal pattern of the mass (arrows).

1···"fE:RMI·NC)~(j(3Y Abbreviations

and Synonyms

General Features

• Cowden syndrome (CS) ~ multiple hamartoma syndrome, multiple hamartoma-neoplasia syndrome • Lhermitte-Duclos disease (LD) o Hamartoma of cerebellum o Hamartoblastoma o Granule cell hypertrophy, granulomolecular hypertrophy o Diffuse ganglioneuroma of cerebellar cortex o Neurocytic blastoma o Myelinated neurocytoma o Purkingeoma

Definitions • Hereditary hamartoma-tumor syndrome ("phakomatosis") characterized by o Mucocutaneous lesions o Multiple hamartomas/neoplasias in breast/thyroid o Gastrointestinal tract polyps o Genitourinary malignancies oLD

• Best diagnostic clue: Lhermitte-Duclos disease • Location: LD always in cerebellum • Size o Dysplastic cerebellar gangliocytoma varies in size/extent o May be large ~ mass effect • Morphology: LD: Relatively well-defined mass containing a "gyriform" pattern

CT Findings • NECT o Hypodense cerebellar mass with/striations density o Relatively well-demarcated, no edema o Usually little mass effect o Variable hydrocephalus • CECT: Enhancement ~ very rare • CT Perfusion

of t

MR Findings • TlWI o Hypointense mass with striations ("corduroy" or "tiger-striped" pattern) o Signal similar to gray matter

DDx: Cerebellar Tumors

Gang/iog/ioma

Gang/iog/ioma

Pi/oeytie G/ioma

Congenital Malformations

Medullob/astoma

COWDEN SYNDROME Key Facts Terminology

Pathology

• Cowden syndrome (CS) ~ multiple hamartoma syndrome, multiple hamartoma-neoplasia syndrome • Lhermitte-Duclos disease (LD)

• Patients w/CS • > 1h of patients w/LD have CS

Imaging Findings • Hypointense mass with striations ("corduroy" or "tiger-striped" pattern) • t Signal, striations are iso to hypointense • May have a very bizarre gyriform appearance • Tl C+: Enhancement very rare (if + may reflect cerebellar venous drainage)

Top Differential

Clinical Issues • Vague neurological findings related to i intracranial pressure, brain stem and cerebellar findings (cranial nerve palsies, ataxia) • LD ~ very rare, all patients must by screened for CS; in patients w/CS LD must be excluded • Surgical resection in symptomatic patients

Diagnoses

• Ganglioglioma • Astrocytoma • Medulloblastoma

•

• • •

• •

o Generally affects one hemisphere but commonly extends to vermis T2WI o t Signal, striations are iso to hypointense o May have a very bizarre gyriform appearance o Rarely the tumor may extend to the brain stem PD/Intermediate: Similar to T2WI FLAIR: Similar to T2WI DWI o Generally bright on trace images o ADC not restricted Tl C+: Enhancement very rare (if + may reflect cerebellar venous drainage) MRS o ~ Levels of NAA o ~-To-normallevels of choline o t Lactate

Angiographic

Findings

• Conventional o Avascular o Mass effect varies

Nuclear Medicine

Findings

• PET: Some areas of t FDG uptake

Other Modality

Findings

• Perfusion MRI may show areas of t rCBV • SPECT may show t levels of 201-TI uptake

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Routine MRI (include Tl C+)

I DIFFERENTIAl..

DIAGNOSIS

Ganglioglioma • Ganglioglioma may have bizarre appearance simulating Lhermitte-Duclos disease o 50% have cysts o 50% enhance o 50% have Ca++

Astrocytoma • Pilocytic o 50-80% cystic o Almost all have nodules that enhance

Medulloblastoma • Lateral "desmoplastic" type may have somewhat striated appearance • Nearly all show moderate enhancement

I PATHOI..OGY General Features • General path comments o Very rare, benign mass-like lesion of cerebellum o May produce mass-effect, cause hydrocephalus • Genetics o CS ~ autosomal dominant o Some patients: Mutations of PTEN/MMAC 1 gene at lOq23.3 (phosphatase/tensin homologue, a tumor suppressor gene) • Etiology o Unclear if origin is hamartomatous or neoplastic o Evidence of non-proliferation/absence of malignant transformation ~ favors hamartomatous nature • Epidemiology o Generally M = F but in some series M < F o t Degree of penetrance in family members • Associated abnormalities o Patients w/CS • Macrocephaly • Benign breast, skin lesions • Oral papillomas • Benign thyroid lesions (adenomas) • Gastrointestinal tract polyps/hamartomas • Cataracts • Genitourinary neoplasias o Patients w/CS also have l,OOOx risk of developing meningiomas o > 1h of patients w/LD have CS

Congenital Malformations

1 113

COWDEN SYNDROME 114

o CS ~ associated to other hamartoma syndromes such as the Bannayan-Zonana syndrome o Associated systemic AVMs and retinal angiomas are rare

Gross Pathologic & Surgical Features • Markedly enlarged cerebellar hemisphere/vermis thick folia • Pale appearing mass

Microscopic

with

Features

• Widening of molecular cell layer ~ occupied by abnormal ganglion cells • Absence of Purkinje cell layer • Hypertrophy of granule cell layer • I Volume of white matter • Histologically may be confused with ganglion cell tumor

Staging, Grading or Classification Criteria • WHO grade 1

I CLINICAL ISSUES Presentation • Most common signs/symptoms o Vague neurological findings related to t intracranial pressure, brainstem and cerebellar findings (cranial nerve palsies, ataxia) o Chronic hydrocephalus o CS may have • Multiple facial trichilemmomas • Oral mucosa papillomatosis • Palmoplantar keratosis • Gastrointestinal polyposis • Clinical profile o Onset of symptoms most common during 3rd-4th decades of life o LD ~ very rare, all patients must by screened for CS; in patients w/CS LD must be excluded

I DltXG\Nds"lC(SFlE~K.tIS1" Consider • Lhermitte-Duclos when a cerebellar lesion is diagnosed in a patient with Cowdens syndrome phenotype

Image Interpretation

Pearls

• Solitary mass in the cerebellum containing striations of intensity similar to gray matter ~ Lhermitte-Duclos disease

I·SELECTEOREfErtEN¢ES 1.

Buhl R et a1. Dysplastic gangliocytoma of the cerebellum: rare differential diagnosis of space occupying lesions of the posterior fossa. Acta Neurochir (Wien) 145: 509-12, 2003 2. Okunaga T et la. A case report of Lhermitte-Duclos disease with systematic AVM's. No To Shinkei 55: 251-55, 2003 3. Capone AM et a1. Lhermitte-Duclos disease in 3 children: a clinical long-term observation. Neuropediatrics 34: 30-35, 2003 4. Gicquel JJ et la. Retinal angioma in a patient with Cowden disease. Am J Ophthalmol135: 400-2, 2003 5. Spaargaren L et a1. Contrast enhancement in Lhermitte-Duclos disease of the cerebellum: correlation of imaging with neuropathology in two cases. Neuroradiology 45: 381-85, 2003 6. Nowak DA, Trost HA: Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma): a malformation, hamartoma or neoplasm? Acta Neurol Scand 105: 137-45,2002 7. Klisch Jet al: Lhermitte-Duclos disease: assessment wit MR imaging, positron emission tomography, single-photon emission CT, and MR spectroscopy. AJNR 22; 824-30, 2001 8. Robinson S: Cowden disease and Lhermitte-Duclos disease: characterization of a new phakomatosis. Neurosurgery 46: 371-83, 2000 9. Murate J et al: Dysplastic gangliocytoma (Lhermitte- Duclos disease) associated with Cowden disease: report of a case and review of the literature for the genetic relationship between the two diseases. J Neuro-Oncol 41; 129-36, 1999 10. Awad EE et al: Atypical appearance of Lhermitte-Duclos disease with contrast enhancement. AJNR 16; 1719-20, 1995

Demographics • Age o Any age, birth-60 years o > Between 30-40 years o Congenital lesions have been reported • Gender: M :S: F • Ethnicity: No predilection

Natural History & Prognosis • Many lesions do not grow or grow slowly • If mass effect is not relieved ~ prognosis is poor • Post surgery recurrences are rare but occur

Treatment • Options, risks, complications o Surgical resection in symptomatic patients o Borders of lesion blend into normal surrounding cerebellum ~ total resection is difficult

Congenital Malformations

COWDEN SYNDROME

1 115

Typical (Left) Axial OWl MR shows a

Lhermitte-Ouclos lesion with high signal intensity. (Right) Axial TlWI MR shows thick intralesional striations (arrows).

(Left) Axial TlWI MR shows

Lhermitte-Ouclos disease involving the cortex of the left cerebellar hemisphere. Note that mass is isointense to normal cerebellum (arrow). (Right) Axial T2WI MR shows the mass to be slightly hypointense to gray matter (arrows).

Variant (Left) Axial Tl C+ MR shows

an unusual histologically proven Lhermitte-Ouclos in the midline cerebellum that shows contrast-enhancement (arrows). (Right) Axial T2WI MR shows hyperintensity of this atypical lesion (arrow).

Congenital Malformations

NEUROCUTANEOUS

MELANOSIS

1 116

Graphic shows dark (melanouc) pigmentation of the leptomeninges. Inset demonstrates extension into the brain substance along the Virchow-Robin spaces (arrow).

Abbreviations

and Synonyms

• Neurocutaneous

melanosis (NCM)

T7WI MR shows foci of hyperintensity in the cerebellar hemispheres (arrows) without mass effect, consistent with parenchymal melanosis. Note mild hypoplasia of the cerebellarhemispheres.

•

Definitions • Congenital phakomatosis characterized by giant or multiple cutaneous melanocytic nevi (GCMN) and benign and malignant melanotic lesions of the CNS o CNS disease: Parenchymal • Melanosis: Focal collection of benign melanotic cells • Malignant melanoma (MM) o CNS disease: Leptomeningeal • Leptomeningeal melanosis (LMs): Excess of benign melanotic cells in the leptomeninges • Leptomeningeal melanoma (LMm): Malignant melanoma of the leptomeninges

•

• • •

CT Findings

t··IN\AG.I.·Ny ••·•·Ff~[)~NCS • General Features • Best diagnostic clue o GCMN + foci of T1 hyperintensity (parenchymal melanosis) in amygdala or cerebellum o GCMN + diffuse leptomeningeal (LM) enhancement • Location

DDx: Diffuse leptomeningeal

TB Meningitis

•

o Parenchymal melanosis: Amygdala, cerebellum, basis pontis, thalami, base of frontal lobes o LMs or LMm: Diffuse LM involvement; rarely focal o MM: Temporal lobe most common Size o Parenchymal melanosis: < 1 em o MM: Typically several ems Morphology o Parenchymal melanosis: Round or oval lesions o LMs/LMm: Linear or nodular (bulky) o MM: Large, round mass 64% symptomatic (sx), patients with NCM (MM, LMm, +/- LMs) have hydrocephalus o Communicating> non-communicating Arachnoid cysts occasionally identified Spinal involvement (LM enhancement, syrinx, arachnoiditis) in 20% Stable free radicals in melanin responsible for MR appearance

• NECT o Parenchymal melanosis: Normal or hyperdense o MM: Hyperdense mass with edema, mass effect; frequent necrosis/hemorrhage • CECT o Parenchymal melanosis: No enhancement o LMs: Normal or diffuse LM enhancement

Enhancement

Sarcoidosis

PNET-MB Mets

Congenital Malformations

CP Carcinoma Mets

NEUROCUTANEOUS

MELANOSIS

1

Key Facts

117

Terminology

Pathology

• Neurocutaneous melanosis (NCM) • Congenital phakomatosis characterized by giant or multiple cutaneous melanocytic nevi (GCMN) and benign and malignant melanotic lesions of the CNS

• Sporadic; theory: Survival autosomal lethal gene by somatic mosaicism • NCM: Rare; 100+ reported cases • GCMN: 1:20,000 live births • Strong association Dandy-Walker spectrum (10%) • Patients with nevi;::: SO cm at highest risk NCM

Imaging Findings • GCMN + foci of Tl hyperintensity (parenchymal melanosis) in amygdala or cerebellum • GCMN + diffuse leptomeningeal (LM) enhancement

Top Differential

Diagnoses

• Tl hyperintense mass • Diffuse leptomeningeal

Diagnostic Checklist enhancement

MR Findings • TlWI o Parenchymal melanosis: Hyperintense o LMs/LMm: Sulci/cisterns normal, iso-, or hyperintense o MM: Mixed signal intensity; frequently hyperintense • T2WI o Parenchymal melanosis: Mixed signal intensity, frequently hypointense; no edema, mass effect o LMs/LMm: Sulci/cisterns normal, iso-, or hypointense o MM: Mixed signal intensity with edema, mass effect; frequent necrosis, hemorrhage • FLAIR: LMm/LMs: Variable leptomeningeal hyperintensity • T2* GRE: "Blooming" of hemorrhage and melanin • T1 C+

Parenchymal melanosis: No enhancement LMs: Normal or diffuse LM enhancement LMm: Diffuse LM enhancement MM: Avid enhancement, often heterogeneous

Imaging Recommendations • Best imaging tool: MR C+ brain and spine • Protocol advice: MR screen for asymptomatic infants with GCMN

(asx)

I DIFFERENTIAl.. DIAGNOSIS T1 hyperintense

• 1 Intracranial pressure (seizures, vomiting, headache, macrocranium, CN6 palsy, irritability, lethargy) • MR appearance diagnostic in appropriate clinical setting • Normal MR does not exclude diagnosis NCM

o LMm: Diffuse LM enhancement o MM: Avid enhancement, often heterogeneous

o o o o

Clinical Issues

mass

• Lipoma: Chemical shift artifact; extra-axial (subarachnoid) location • Dermoid: Chemical shift artifact; extra-axial location; sharply demarcated; exerts mass effect • Acute/subacute hemorrhage: Marked T2 hypointensity; mass effect/edema; neurological deficit • Hemorrhagic, non-melanotic neoplasms: Areas of marked T2 hypointensity; mass effect/edema

Congenital

Diffuse leptomeningeal

enhancement

• Carcinomatous meningitis/CSF seeding: History 10 malignancy; linear/nodular LM enhancement • Infectious meningitis (routine bacterial, TB, coccidiomycosis): Basal cisterns, linear enhancement; signs/symptoms meningitis; (+) CSF cultures • Non-infectious inflammation (sarcoidosis, Wegener granulomatosis): Linear/nodular enhancement

I PAIHOI..OG~ General Features • General path comments o Embryology • Neural crest derived primordial cells migrate, differentiate into melanocytes in pia mater and basal layer epidermis • Melanocytes in epidermis at 8-10 wks gestation • Melanocytes in pia mater at - 23 wks gestation o Anatomy • Melanocytes normally present in pia mater over convexities, base of brain, ventral brainstem, upper cervical and lumbosacral spinal cord • Melanocytes normally surround blood vessels, but do not extend into Virchow-Robin (VR) spaces • Genetics o Sporadic; theory: Survival autosomal lethal gene by somatic mosaicism o Deregulation hepatocyte growth factor/scatter factor and receptor (Met) may play role • Etiology o Increased number melanotic cells in pia mater o Pathological presence melanotic cells in VR spaces o Hypotheses • Abnormal migration melanocyte precursor cells • Abnormal expression melanin producing genes in cells within LM • Proliferation normal melanin-producing LM cells o LMm/MM: Degeneration (anaplasia) melanotic cells o Hydrocephalus: Obstruction of CSF flow at basal cisterns and arachnoid granulations

Malformations

NEUROCUTANEOUS MELANOSIS 1 118

• Epidemiology o NCM: Rare; 100+ reported cases • 64% patients with pathologically proven NCM haveLMm o GCMN: 1:20,000 live births • Sx NCM: < 3% patients with GCMN • - 30% patients with GCMN have parenchymal melanosis (asx NCM) • Associated abnormalities o Strong association Dandy-Walker spectrum (10%) • Abnormal meningeal cells causally related to hindbrain malformation

• Clinical profile o Asx infant with GCMN (parenchymal melanosis) • Parenchymal melanosis may causes seizures o Infant/child with GCMN + signs/symptoms 1 intracranial pressure (LMm, +/- LMs, MM) • Histologically benign disease (LMs) may be sx • CSF (Sx NCM): 1 Protein, t glucose, +/benign/malignant melanotic cells

Demographics • Age: Sx NCM manifests by 2-3 years of age • Gender: M = F

Gross Pathologic & Surgical Features

Natural History & Prognosis

• Parenchymal melanosis: Focal, abnormal pigmentation within the brain • LMs/LMm: Darkly pigmented, thickened pia mater • MM: Pigmented mass, +/- necrosis, hemorrhage • GCMN: Giant or multiple pigmented, hairy nevi o Giant nevi comprise 66% (in NCM) • Lumbosacral> occipital, upper back • Involvement of head & neck occurs in 94% • Patients with nevi::::: 50 cm at highest risk NCM o Multiple nevi comprise 34%

• Natural History o Asx NCM: Parenchymal melanosis often stable • Few reports regression, and degeneration into MM o GCMN (isolated or NCM): 5-15% lifetime risk of malignant degeneration (melanoma) • Prognosis o Asx NCM: Unknown; at risk developing sx NCM o Sx NCM: Dismal; median survival 6.5 months after symptom onset • Prognosis equally poor for histologically benign (LMs) or malignant (LMm, MM) sx NCM

Microscopic

Features

• Parenchymal melanosis: Melanotic cells & melanin laden macrophages in VR spaces, parenchyma • Benign LMs difficult to differentiate from LMm histologically o Cellular pleomorphism, nests of cells, appearance of parenchymal invasion seen in LMs and LMm o Indicators of malignancy: Necrosis, hemorrhage, basal lamina invasion, cellular atypia, frequent mitoses, presence of annulate lamellae • Immunohistochemistry: (+) Vimentin, S100, HMB45 o Amelanotic lesions lack melanin pigment, identified by immunohistochemistry • GCMN: Melanocytic nevi> compound nevi o Cells in reticular dermis, occasionally subcutis o Nevus cells present between collagen bundles, around appendages, nerves and blood vessels

Staging, Grading or Classification Criteria • Criteria for diagnosis o Giant or multiple (:::::3) cutaneous melanocytic nevi • Child: 6 cm body, 9 cm head maximal diameter • Adult: 20 cm maximal diameter o Cutaneous melanoma only in patients with benign meningeal lesions o Leptomeningeal melanoma only in patients with benign cutaneous lesions

Treatment • Asx NCM: Screening MR beginning 6 months of age • Sx NCM: Shunt hydrocephalus (filter prevents peritoneal seeding) o Surgery, XRT, systemic/intrathecal chemotherapy • Palliative; no significant alteration course of NCM

I D.IAGNOSTlcCI-IECKI..IST Consider • Clinical hx in child with diffuse LM enhancement or T1 hyperintense foci amygdala, cerebellum o MR appearance diagnostic in appropriate clinical setting

Image Interpretation

I SELECTED REFERENCES 1.

2.

I CUNICALISSUES Presentation

3.

• Most common signs/symptoms o 1 Intracranial pressure (seizures, vomiting, headache, macro cranium, CN6 palsy, irritability, lethargy) o Other signs/symptoms • Focal neurological deficit, psychiatric disturbance in rare older child/young adult presentation

Congenital

Pearls

• Normal MR does not exclude diagnosis NCM • LMs cannot be distinguished from LMm by imaging o Clinically irrelevant since sx LMs and LMm have equally poor prognosis

4.

Hayashi M et al: Diffuse leptomeningeal hyperintensity on FLAIR MR images in neurocutaneous melanosis. AJNR 25: 138-41,2004 Mena-Cedillos CA et al: Neurocutaneous melanosis in association with the Dandy-Walker complex, complicated by melanoma: report of a case and literature review. Pediatr Dermatol. 19(3):237-42, 2002 Peters R et al: Neurocutaneous melanosis with hydrocephalus, intraspinal arachnoid collections and syringomyelia: case report and literature review. Pediatr Radiol. 30(4):284-8, 2000 Byrd SE et al: MR imaging of symptomatic neurocutaneous melanosis in children. Pediatr Radiol 27:39-44, 1997

Malformations

NEUROCUTANEOUS MELANOSIS

I IMAGE

1

GALLERY

119

Typical (Left) Axial T1WI MR shows characteristic amygdala (arrows) hyperintensity seen in parenchymal melanosis. A more mass-like, hyperintense lesion is present in the ambient cistern (open arrow). (Right) Axial FLAIR MR shows mixed signal intensity of lesions in the amygdala and ambient cistern. Both hyperintense (arrows) and hypointense (open arrows) foci are identified. Note the lack of edema.

Typical

(Left) Axial T1WI MR shows multiple areas of hyperintensity within the cerebellar hemispheres. Note involvement of the dentate nuclei (arrows). (Right) Sagittal T1WI MR shows focal hyperintensity in the basis pontis (arrow) without mass effect or edema in this asymptomatic patient with parenchymal melanosis.

Typical

(Left) Axial T1WI MR in a symptomatic patient shows loss of CSF signal intensity in the cerebellar sulci and prepontine cistern (arrows). Note focal hyperintensity in the amygdala (open arrow). (Right) Axial T1WI MR in a symptomatic patient shows diffuse leptomeningeal (LM) enhancement consistent with LM melanosis or LM melanoma. Note bulky LM enhancement in the pre-pontine cistern (arrows).

Congenital

Malformations

PART I SECTION 2 Trauma Trauma i the leading cau e of death in children and young adults. In traumatized patients, head injury and its sequelae are the major cause of mortality in well over half of all cases and a significant cause of morbidity in many survivors. High-speed, high-impact accidents are not the only contributor to the e dismaying tatistics. Ground-level falls in anticoagulated older adults, nonaccidental injury in infants and young children, and penetrating injuries from high energy projectiles contribute their share to the overall trauma picture. euroimaging is fundamental to the rapid, accurate diagnosis and assessment of traumatized patients. With the advent of multidetector row CT canner and their immediate availability in-and close proximity to-Level One trauma centers, imaging has become an essential part of patient managaement. Because it's quick and relatively easy to do, rapid skull/brain/cervical spine imaging with multiplanar reconstructions is increasingly more common. Poly trauma cases often get what our residents call "The Grand Slam" (brain, C/T/ Lspine, chest, abdomen and pelvis). Imaging as triage is here to stay. In this section we review both the direct and indirect effects of trauma on the brain (skull fractures are covered in Part 1/ of this book). Specific diagnoses are organized as follows: Primary effects of craniocerebral trauma Mi sile and penetrating injury Epidural hematoma Acute subdural hematoma Subacute ubdural hematoma Chronic ubdural hematoma Mixed subdural hematoma Traumatic subarachnoid hemorrhage (yes, trauma IS the most common cause of subarachnoid hemorrhage!) Cerebral contusion Diffuse axonal injury Subcortical injury onaccidental trauma Secondary and vascular effects of trauma Intracranial herniations Traumatic cerebral edema Traumatic cerebral ischemia Brain death Traumatic intracranial dissection Traumatic extracranial dissection Traumatic carotid-cavernous fistula

SECTION 2: Trauma

Primary Effects of CNS Trauma Missile and Penetrating Injury Epidural Hematoma Acute Subdural Hematoma Subacute Subdural Hematoma Chronic Subdural Hematoma Mixed Subdural Hematoma Traumatic Subarachnoid Hemorrhage Cerebral Contusion Diffuse Axonal Injury (DAI) Subcortical Injury Nonaccidental Trauma

1-2-4 1-2-6 1-2-10 1-2-14 1-2-16 1"2-20 1-2-22 1-2-26 1-2-30 1-2-34 1-2-38

Secondary/Vascular Effects of CNS Trauma Intracranial Herniation Syndromes Traumatic Cerebral Edema Traumatic Cerebral Ischemia Brain Death Traumatic Intracranial Dissection Traumatic Extracranial Dissection Traumatic Carotid-Cavernous Fistula

1-2-42 1-2-46 1-2-50 1-2-54 1-2-56 1-2-58 1-2-62

MISSILE AND PENETRATING

INJURY

2 4

CT topogram on patient who sustained CSW to head. Bullet fragments (arrows) are dispersed from region of suprasellar cistern to parieto-occipital lobe. Patient intubated.

Axial NECT shows acute CSW with right frontal entry site (arrow). Note bullet & bone fragments along tract, extensive SAH, intraparenchymal & intraventricular blood & pneumocephalus.

• Hemorrhagic tract through brain • Intracerebral, intraventricular hemorrhage o Secondary effects • Ischemia & infarction • Brain herniation

ITERMINOLOGY Abbreviations

and Synonyms

• Gun shot wound (GSW)

Definitions • Cranial trauma from high-velocity GSW)

projectile (typically

IIMAGING FINDINGS

• Tl WI: Variable signal from hemorrhage, foreign bodies & air • T2WI: Edema from pressure wave • T2* GRE: Hemosiderin deposition as well as susceptibility artifact from foreign bodies • MRV o Venous injury or thrombosis if missile tract crosses or tears interdural veins or lacerates sinus o Dural sinus thrombosis ~ reported incidence < S% with penetrating trauma

• Best diagnostic clue: Single or multiple intracranial foreign bodies, missile tract, pneumocephalus, entry +/- exit wound • Location: Supra or infra tentorial, affecting cerebral/cerebellar hemispheres or brain stem • Morphology o Extremely variable depending on • Size, shape & number of projectiles • Projectile velocities • Entry/exit site(s) & course through brain o Skull fracture(s) • Entry site ~ embedded bullet & bone fragments • Pneumocephalus o Intracranial hemorrhage • Epidural, subdural, subarachnoid hemorrhage

Intracranial

DDx: Non-projectile

I

Angiographic Findings • Conventional o Traumatic intracranial aneurysms occur in atypical locations ~ proximal to or beyond COW & major arterial bifurcations

Injury \

/

\

I

\" Trauma

• NECT o Best assessment of extent of soft tissue injury o Identify entrance & exit wounds

MR Findings

General Features

Intracranial

CT Findings

Axonal

1~

) Injury

Hemorrhagic

Trauma

OAI

Cerebral

Contusion

MISSILE AND PENETRATING INJURY Key Facts • • • •

Terminology • Gun shot wound (GSW)

Imaging Findings • Best diagnostic clue: Single or multiple intracranial foreign bodies, missile tract, pneumocephalus, entry +1- exit wound • Entry site ...•embedded bullet &: bone fragments • Epidural, subdural, subarachnoid hemorrhage • Hemorrhagic tract through brain o Extracranial pseudo aneurysms vary from small saccular lesions &: fusiform dilatations to large collections with huge cavitating hematomas o Other possible injuries: Traumatic direct CCFs, dural AVFs involving meningeal vessels, extracranial AVFs, arterial dissection o Vascular spasm from projectile velocity or SAH

Nuclear Medicine

Findings

• Nuclear Medicine brain death scanning with cerebral perfusion agents can be a confirmatory test

Imaging Recommendations • Best imaging tool: NECT • Protocol advice o NECT +1- MRI/MRA o Conventional cerebral angiography type of trauma &: degree of injury

Intracerebral, intraventricular hemorrhage Ischemia &: infarction Brain herniation Nuclear Medicine brain death scanning with cerebral perfusion agents can be a confirmatory test

Diagnostic Checklist • Post-traumatic pseudoaneurysm may be overlooked on CT ...•often obscured by hemorrhagic contusion

Natural History & Prognosis • Prognosis ranges from brain death to full recovery

Treatment • Options, risks, complications: degree of injury

I DIAeJNOSTIC

Dependent

upon type &:

CHECKliST

Consider • Could there be associated vascular injury &: aneurysm formation? • Post-traumatic pseudo aneurysm may be overlooked on CT ...•often obscured by hemorrhagic contusion

depending

on

I SEI..ECTED REFERENCES 1.

I PATHOI..OeJ¥

General Features

2.

• General path comments o Appearance &: degree of injury highly variable o Traumatic aneurysms account for < 1% of all intracranial aneurysms • Etiology: Pressure wave in front of missile crushes/stretches/disintegrates tissue, creates temporary cavitation • Epidemiology: Highly variable ...•incidence higher in inner cities &: combat situations

3.

Thiex R et al: Delayed oedema in the pyramidal tracts remote fram intracerebral missile path following gunshot injury. Neuroradiology 46:140-3,2004 Cruz J et al: Cerebral extraction of oxygen and intracranial hypertension in severe, acute, pediatric brain trauma: preliminary novel management strategies. Neurosurgery. 50(4):774-9; discussion 779-80, 2002 Nathoo N et al: Civilian infratentorial gunshot injuries: outcome analysis of 26 patients. Surg Neural. 58(3-4):225-32; discussion 232-3, 2002

IIMAeJE eJAI..I..ER¥

Gross Pathologic & Surgical Features • Highly variable depending

Microscopic

on severity of trauma

Features

• Highly variable ranging from axonal transection to axonal edema; vascular transection to luminal injury

I CliNICAl..

ISSlJES

Presentation • Most common signs/symptoms: Highly variable depending on type &: degree of traumatic injury

Demographics • Age: Any age can be affected • Gender: No gender predilection

(Left) Axial NECT shows left temporal scalp hematoma from self-inflicted CSW Intracranial hemorrhage & pneumocephalus are present. Diffuse cerebral edema is also present. (Right) Axial NECT with bone windowing demonstrates right temporal CSW with calvarial fragments displaced intracranially. Smaller entry site outer table & larger opening inner table, indicating trajectory.

Trauma

2 5

6

Coronal graphic illustrates swirling acute hemorrhage from middle meningeal artery, lacerated by an overlying skull fracture. Epidural hematoma displaces dura inward as it expands.

Abbreviations

Axial NECT shows a hyperdense, biconvex epidural hematoma with compression of brain. Note internal hypodense "swirl sign" (arrow) implying active bleeding with unretracted semiliquid clot.

• Biconvex or lentiform extra-axial collection at impact ("coup") site • Does not cross sutures unless sutural diastasis/fracture present • Can cross falx & tentorium • Compresses & displaces underlying brain & subarachnoid space o Venous EDH • EDH adjacent to venous sinus • Sinus transgressed by fracture line o 1/3-1/2 have other significant lesions • Skull fracture in 85-95% • "Contrecoup" subdural hematoma • Cerebral contusions • Mass effect with secondary herniations common (subfalcine, descending transtentorial)

and Synonyms

• Epidural hematoma

(EDH)

Definitions • Blood collection within potential inner table & dura mater

space between skull

General Features • Best diagnostic clue: Hyperdense biconvex extra-axial mass on NECT in acute phase • Location o Epidural space between skull & dura o Nearly all EDH occur at impact ("coup") site o > 95% unilateral o 90-95% supratentorial • 66% temporoparietal • 29% frontal, parietooccipital o 5-10% posterior fossa o Rarely at the vertex • Size: Variable, although most attain final size quickly • Morphology o EDH

Radiographic Findings • Radiography: Skull fracture if present

CT Findings • NECT o Acute EDH: 2/3 hyperdense, 1/3 mixed hyper/hypodense • Low density "swirl sign" = actively/rapidly bleeding hematoma with unretracted semiliquid clot • Acutely extravasated = 30-50 HUi coagulated = 50-80 HU

DDx: Epidural Hematoma

~\\

f.. I '

I

l ~

\ Extramed Hemato

\'"

Meningioma

JJ Trauma

Metastases

Subdural Hematoma

EPIDURAL HEMATOMA Key Facts Top Differential Diagnoses

Terminology • Blood collection within potential inner table & dura mater

space between skull

Imaging Findings • Best diagnostic clue: Hyperdense biconvex extra-axial mass on NECT in acute phase • Does not cross sutures unless sutural diastasis/fracture present • Can cross falx & tentorium • Compresses & displaces underlying brain & subarachnoid space • Low density "swirl sign" = actively/rapidly bleeding hematoma with unretracted semiliquid clot • If MRI unavailable, consider coronal CT reconstructions to evaluate vertex EDH

• Subdural hematoma • Neoplasm • Extramedullary hematopoiesis

Pathology • Arterial = 90%, venous = 100/0 • Arterial EDH with fracture nearly always secondary to MMA groove fracture

Clinical Issues • Classic "lucid interval" • Generally good outcome if promptly recognized & treated • Posterior fossa EDH have 1 mortality (26%)

o Air within EDH (20%) suggests sinus or mastoid fracture o Can easily miss vertex EDH • If MRI unavailable, consider coronal CT reconstructions to evaluate vertex EDH • CECT o Acute: Rarely contrast extravasation o Chronic: Peripheral enhancement due to neovascularization & granulation

• Best imaging tool o Traumatic: NECT o Nontraumatic: MRI • Protocol advice o Traumatic: Consider coronal MRI for vertex EDH o Nontraumatic: Enhanced MRI + MRA

MR Findings

I DIFFERENTIAL

Imaging Recommendations

• TlWI o Acute: Isointense o Subacute/early chronic: Hyperintense o Black line between EDH & brain = displaced dura • T2WI o Acute: Variable hyper- to hypo intense o Early subacute: Hypointense o Late subacute/early chronic: Hyperintense o Black line between EDH & brain = displaced dura • Tl C+ o May be able to confirm venous origin of EDH • Demonstrates displaced venous sinus by hematoma • Occlusion of venous sinus seen as as absence of local luminal enhancement • Proximity of sinus/EDH to skull fracture • MRA: For evaluation of nontraumatic EDH (e.g., AVM) • MRV o May be able to confirm venous origin of EDH • Direct involvement with/without occlusion • Proximity of sinus flow/EDH to skull fracture o Displaced venous sinus flow by hematoma

Angiographic Findings • Conventional o Avascular mass effect • Cortical arteries displaced away from skull • May displace dural venous sinus o Middle meningeal artery (MMA) laceration (rare) o "Tram-track" sign (contrast extravasates from MMA into paired middle meningeal veins) o Arteriovenous fistula

DIAGNOSIS

Subdural hematoma • Usually crescentic, but may also be biconvex • Crosses sutures, does not cross falx • No displaced dura

Neoplasm • Meningioma, metastasis, bone primary • Dural based, enhancing mass • ± Skull involved

Extramedullary hematopoiesis • History of blood dyscrasia

I PATIrtfOlOG~ General Features • Etiology o Trauma most common • Arterial = 90%, venous = 10% • Arterial EDH with fracture nearly always secondary to MMA groove fracture • Venous EDH usually related to occipital, parietal, or sphenoid fractures o Nontraumatic • Coagulopathy, thrombolysis, vascular malformation, neoplasm, epidural anesthesia, Paget disease of skull • Epidemiology o 1-4% of imaged head trauma patients o 5-15% of patients with fatal head injuries

Trauma

2 7

8

• Associated abnormalities o Skull fracture in 85-95%, usually across MMA groove • However only minority of MMA groove fractures actually result in EDH o Subdural hemorrhage, contusion

• Posterior fossa EDH have 1 mortality (26%) o Can have delayed symptom onset secondary to slower expansion from lower venous pressures • Epidural abscess may develop if bacteria colonize EDH via fracture site

Gross Pathologic & Surgical Features

Treatment

• Hematoma collects between calvarium, outer dura o May cross midline, dural attachments o Rarely crosses sutures (exception = large hematoma with diastatic fx) • "Vertex" EDH is rare o Usually venous: Linear or diastatic fracture crosses superior sagittal sinus • At surgery or autopsy, 20% have blood in both epidural & subdural spaces

• Prompt recognition, appropriate treatment essential o Poor outcome often related to delayed referral, diagnosis, or operation • Nearly always requires surgical evacuation o EDH elsewhere may be unmasked after procedure • Small EDH sometimes followed without surgery o Need repeat CT over 36 hrs to monitor for change o EDH 1 during conservative management (23%) • Occurs within 36 hrs • Mean enlargement = 7 mm • Complications are usually secondary to EDH mass effect causing brain herniations

Microscopic Features • Tearing/laceration

of adjacent vessel

Staging, Grading or Classification Criteria • Type I: Acute EDH, arterial bleeding (58%) • Type II: Subacute EDH (31%) • Type III: Chronic EDH, venous bleeding (11%)

Image Interpretation

Pearls

• NECT highly sensitive & widely available • If MRI unavailable, consider coronal CT reconstructions to evaluate vertex EDH

Presentation • Most common signs/symptoms o Classic "lucid interval" • Initial brief loss of consciousness (LOC) • Subsequent asymptomatic time between LOC & symptom/coma onset • Occurs "" 50% o Headache, nausea, vomiting, seizures, focal neurological deficits (e.g., field cuts, aphasia, weakness) o Signs of mass effect/herniation common • Pupil-involving CN3 palsy, somnolence, consciousness, coma • Clinical profile: Alcohol & other intoxications associated with 1 incidence of EDH

Demographics • Age o More common in younger patients: 20-40 years o EDH without fracture particularly common in children o Uncommon in infants • Gender: M:F = 4:1

Natural History & Prognosis • Factors affecting rate of EDH growth o Arterial vs venous flow rate, arterial spasm o Decompression through fracture into scalp o Tamponade • Delayed development or enlargement common o 10-25% of cases o Usually occurs within first 36 hours • Generally good outcome if promptly recognized & treated o Overall mortality"" 5% o Bilateral EDH has 15-20% mortality rate

1.

Rochat P et al: Sequentially evolved bilateral epidural haematomas. Clin Neurol Neurosurg. 105(1):39-41,2002 2. Server A et al: Vertex epidural hematoma neuroradiological findings and management. Acta Radiol. 43(5):483-5, 2002 3. Messori A et al: Acute posttraumatic paraplegia caused by epidural hematoma at the vertex. A]NR Am] Neuroradiol. 22(9):1748-9,2001 4. Al-Nakshabandi NA: The swirl sign. Radiology. 218(2):433, 2001 5. Singleton SD et al: Lenticular lesions: not always an epidural hematoma. Pediatr Emerg Care. 17(4):252-4,2001 6. Khwaja HA et al: Posterior cranial fossa venous extradural haem atom a: an uncommon form of intracranial injury. Emerg Med]. 18(6):496-7,2001 7. Harbury OL et al: Vertex epidural hematomas: imaging findings and diagnostic pitfalls. Eur] Radiol. 36(3):150-7, 2000 8. Sullivan TP et al: Follow-up of conservatively managed epidural hematomas: implications for timing of repeat CT. A]NR Am] Neuroradiol. 20(1):107-13,1999 9. Bozbuga M et al: Posterior fossa epidural hematomas: observations on a series of 73 cases. Neurosurg Rev. 22(1):34-40, 1999 10. Paterniti S et al: Is the size of an epidural hematoma related to outcome? Acta Neurochir 140: 953-5,1998 11. Servadei F: Prognostic factors in severely head injured adult patients with epidural haematoma's. Acta Neurochir (Wien). 139(4):273-8, 1997

Trauma

Typical (Left) Axial NECT demonstrates bilateral fractures (white arrows). The right fracture has caused an epidural hematoma (black arrows), barely visible with bone reconstruction algorithm. (Right) Axial T2WI MR demonstrates linear hypointense dura (arrow) interposed between an epidural hematoma & underlying brain. This distinguishes EDH from subdural hematoma.

Tvnical (Left) Axial NECT demonstrates an epidural hematoma crossing falx attachment site (black arrow), distinguishing it from a subdural hematoma. A hemorrhagic cerebral contusion is also present (white arrow). (Right) Axial NECT shows a large biconcave hyperdense epidural hematoma containing air from frontal sinus fracture. Note "swirl" sign (arrow). Significant midline shift as well as pneumocephalus are present.

Typical (Left) Coronal T2WI MR shows venous epidural hematoma from lacerated superior sagittal sinus (555). Dura (arrow) & 555 (open arrow) are displaced. Skull fracture is barely visible (curved arrow). (Right) Sagittal MRV demonstrates mass effect from vertex venous epidural hematoma displacing the superior sagittal sinus.

Trauma

9

10

Axial graphic shows acute subdural hematoma (curved white arrows) compressing left hemisphere & lateral ventricle. Note contusions (black arrows) & axonal injuries (curved black arrows)

Axial NEeT shows a crescentic, homogenously hyperdense extraaxial collection (white arrows) with compression & displacement of underlying brain typical of acute subdural hematoma.

o CT density & MR signal intensity vary with age & organization of hemorrhage

Abbreviations

and Synonyms

• Acute subdural hematoma

CT Findings

(aSDH)

Definitions • Acute (± 6 hrs-3 days) hemorrhagic subdural space

collection in

General Features • Best diagnostic clue: Crescent-shaped, homogenously hyperdense on CT, extra-axial collection that spreads diffusely over affected hemisphere • Location o Between arachnoid & inner layer of dura o Supratentorial convexity most common • Morphology o Crescent-shaped extra-axial fluid collection o May cross sutures, not dural attachments o May extend along falx & tentorium o Compresses & displaces underlying brain o Other lesions (e.g., traumatic SAH) in> 70% o Recurrent, mixed-age hemorrhage common ~ in a child raises suspicion of non accidental trauma!

DDx: Acute Subdural Hematoma

Dural Thickening

• NECT o Hyperacute SDH (± < 6 hrs) mostly hypodense (un clotted) o aSDH (± 6 hrs-3 days) • 60% aSDH typically homogenously hyperdense • 40% mixed hyper-, hypodense ~ active bleeding ("swirl" sign), torn arachnoid with CSF accumulation, clot retraction • Rarely isodense ~ coagulopathy, anemia (Hgb < 8-10 g/dl) • Density decreases ± 1.5 HU/day as SDH evolves • CECT o Inward displacement of cortical vessels o Dura & membranes enhance when subacute, useful to visualize loculations

MR Findings • TlWI o Hyperacute: Isointense o Acute: Iso- to moderately hypointense • T2WI o Hyperacute: Iso- to hyperintense o Acute: Hypointense • FLAIR o Hyperintense to CSF

Mimics

Epidural Hematoma

Trauma

PICA Infarct

Sarcoma Met

ACUTE SUBDURAL HEMATOMA Key Facts Terminology

Top Differential

• Acute (± 6 hrs-3 days) hemorrhagic subdural space

collection in

Imaging Findings • Best diagnostic clue: Crescent-shaped, homogenously hyperdense on CT, extra-axial collection that spreads diffusely over affected hemisphere • May cross sutures, not dural attachments • May extend along .falx &: tentorium • Compresses &: displaces underlying brain • Recurrent, mixed-age hemorrhage common - in a child raises suspicion of nonaccidental trauma! • CT density &: MR signal intensity vary with age &: organization of hemorrhage • Protocol advice: Use wide window settings (150-200 HU) to identify small SDH

• •

•

•

o Acute hematomas most conspicuous on FLAIR imaging T2* GRE: Hypointense signal in most cases DWI o Heterogenous signal (non-specific) o May differentiate extra-axial empyema (marked hyperintensity) from hemorrhage o Demonstrates areas of secondary ischemic injury vascular compromise secondary to herniation Tl C+ o Enhancement of bridging veins o Enhancement of subdural collection predictive of subsequent growth Signal of SDH quite variable on MR o Generally evolve in pattern similar to intracerebral hemorrhage

Angiographic

Findings

• • • • • •

Diagnoses

Other subdural collections Acute epidural hematoma Pachymeningopathies (thickened Tumor Peripheral infarct Chemical shift artifact

dura)

Pathology • Stretching &: tearing of bridging cortical veins as they cross subdural space to drain into dural sinus • Associated abnormalities: > 70% of aSDH have other significant associated traumatic lesions

Clinical Issues • Prognosis in aSDH poor (35-90% mortality)

Acute epidural hematoma • Biconvex extra-axial collection • Often associated with fracture • May cross dural attachments, limited by sutures

Pachymeningopathies

(thickened dura)

• Chronic meningitis (may be indistinguishable) • Post-surgical (shunt, etc) • Intracranial hypotension ("slumping" midbrain, tonsillar herniation) • Sarcoid (nodular, "lumpy-bumpy")

Tumor • Meningioma, lymphoma, leukemia, metastases • Dural based, enhancing mass • ± Skull involved

Peripheral infarct

• Conventional o Displacement, mass effect from extra-axial mass o Useful to exclude vascular malformation in non-traumatic cases

• Cortex involved, not displaced • DWI hyperintense

Chemical shift artifact

Imaging Recommendations • Best imaging tool o NECT initial screen for aSDH o MRI more sensitive for SDH &: additional findings of traumatic brain injury; most appropriate in subacute phase • Protocol advice: Use wide window settings (150-200 HU) to identify small SDH

I DIFFERENTIAL DIAGNOSIS Other subdural collections • Hygroma (clear CSF, no encapsulating membranes) • Effusion (xanthochromic fluid from extravasation of plasma from outer membrane; 20% evolve into chronic SDH) • Empyema (peripheral enhancement, restricted diffusion centrally)

• Marrow or subcutaneous fat may "shift" - can appear intracranial, mimic Tl hyperintense SDH • Seen with 1 field of view or I bandwidth

I PATHOLOGY General Features • Etiology o Trauma most common • Stretching & tearing of bridging cortical veins as they cross subdural space to drain into dural sinus • Both nonimpact as well as direct injury • Trauma may be minor, particularly in elderly o Less common etiologies include • Dissection of intraparenchymal hematoma into subarachnoid, then subdural space • Aneurysm rupture • Vascular malformations: Dural AVF,AVM, cavernoma • Coagulopathy

Trauma

2 11

• FLAIR, T2* most sensitive sequences for SDH when isointense on standard sequences

o Predisposing factors • Atrophy • Shunting (leads to increased traction on superior cortical veins) • Arachnoid cyst (middle fossa most common site) • Epidemiology: SDH found in 10-20% imaged & 30% autopsy cases following craniocerebral trauma • Associated abnormalities: > 70% of aSDH have other significant associated traumatic lesions 12

1.

2.

Gross Pathologic & Surgical Features • Hematoma • Delayed development tissue

Microscopic

3.

of membranes/granulation 4.

Features

• Outer membrane formed by proliferating fibroblasts & capillaries • Fragile capillaries hypothesized as source of recurrent hemorrhage in chronic SDH • Inner membrane formed by dural fibroblasts or border cells, forms fibrocollagenous sheet

5.

6. 7.

8.

Presentation • Most common signs/symptoms o Most commonly following trauma o Varies from asymptomatic to loss of consciousness • "Lucid" interval in aSDH: Initially awake, alert patient who loses consciousness a few hours after trauma o Other symptoms from mass effect, diffuse brain injury, secondary ischemia

9. 10.

11.

12.

Demographics • Age: Any age, more common in elderly • Gender: No gender predilection

13. 14.

Natural History & Prognosis • Can grow slowly over time, with increasing mass effect if untreated

15.

Treatment • Prognosis in aSDH poor (35-90% mortality) o Emergency preoperative high dose mannitol may improve outcome • Hematoma thickness, midline shift> 20 mm correlate with poor outcome • Lethal if hematoma volume> 8-10% of intracranial volume

16.

17. 18. 19. 20. 21.

Consider • NECT initial screen • Consider MRI in first 2 weeks post-trauma to identify extent of traumatic brain injury when patient is stable

Image Interpretation

Pearls

• Wide window settings for CT increases conspicuity subtle SDH

of

Trauma

Cruz J et al: Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial. J Neurosurg. 100:376-83,2004 Abe M et al: Analysis of ischemic brain damage in cases of acute subdural hematomas. Surg Neurol 59:464-72, 2003 Tseng H et al: Dural metastasis in patients with malignant neoplasm & chronic subdural hematoma. Acta Neurol Scand 108:43-6, 2003 Burger, Peter C. et al: Surgical Pathology of the Nervous System & Its Coverings, 4th ed. Churchill Livingstone, NY, 2002 Nakaguchi H et al: Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg 95:256-62, 2001 Matano S et al: Primary leptomeningeal lymphoma. J Neurooncol 52:81-3, 2001 Lin DM et al: Detection of intracranial hemorrhage: comparison between gradient-echo images and bO images obtained from diffusion-weighted echo-planar sequences. AJNR22:1275-81,2001 Mori K et al: Delayed magnetic resonance imaging with Gd-DTPA differentiates subdural hygroma and subdural effusion. Surg Neurol 53:303-11, 2000 Ibarra R et al: Role of MR imaging in the diagnosis of complicated arachnoid cyst. Pediatr Radiol 30:329-31, 2000 Kaminogo M et al: Characteristics of symptomatic chronic subdural haematomas on high-field MRI. Neuroradiol 41:109-16, 1999 Abdulrauf SI et al: A comparison of the clinical profile of cavernous malformations without associated venous malformations. Neurosurg 44:41-46, 1999 Campbell BG et al: Emergency magnetic resonance resonance of the brain. Top Magn Reson Imaging 9:208-27, 1998 Ashikaga R et al: MRI of head injury using FLAIR. Neuroradiology 39:239-42, 1997 Massaro F et al: One hundred and twenty-seven cases of acute subdural haematoma operated on. Acta Neurochir 138:185-91, 1996 Zumkeller M et al: Computed tomography criteria and survival rate for patients with acute subdural hematoma. Neurosurg 39:708-12,1996 Cho SJ et al: Assumption of the age of subdural hematomas based on computed tomographic findings. Neurol Med Chir 24:607-14, 1995 Oikawa A et al: Arteriovenous malformation presenting as acute subdural haematoma. Neurol Res 15:353-5, 1993 Wilms G et al: CT and MR in infants with pericerebral collections and macrocephaly. AJNR 14:855-60, 1993 Wilms G et al: Isodense subdural haematomas on CT: MRI findings. Neuroradiology 34:497-9, 1992 Fobben ES et al: MR characteristics of subdural hematomas and hygromas at 1.5 T. AJR 153:589-95, 1989 Kelly AB et al: Head trauma: comparison of MR and CT. AJNR9:699-708, 1988

(Left) Coronal T1WI MR shows a crescentic nearly isointense (to brain) extra-axial collection, compatible with acute subdural hematoma (arrows). (Right) Axial NEeT shows hypodense areas ("swirl" sign) indicative of active extravasation in an anticoagulated patient with acute subdural hematoma (arrows).

Typical (Left) Axial FLAIRMR shows acute subdural hematoma with hyperintense signal, indicative of proteinaceous content &/or blood. (Right) Axial T2WI MR shows heterogeneous signal, largely iso- to hyperintense in bilateral acute subdural hematoma (arrows).

Typical (Left) Sagittal T1WI MR shows isointense subdural over the hemisphere (arrows). Note secondary hemorrhage into an arachnoid cyst, an infrequent complication (open arrow). (Right) Axial NECT shows right tentorial, parafalcine, & hemispheric acute hyperdense subdural hematoma (arrows).

Trauma

2 · 13

14

Axial graphic shows subacute subdural hematoma (white arrows). Inset shows traversing "bridging" vein (black arrow), & developing membranes (curved arrow).

Sagittal TlWI MR shows a hyperintense extra-axial collection compressing adjacent brain parenchyma consistent with subacute blood (methemoglobin).

CT Findings Abbreviations

and Synonyms

• Subacute subdural hematoma

(sSDH)

Definitions • Subacute (± 3 days-3 weeks) hemorrhagic subdural space

collection in

General Features • Best diagnostic clue: Crescent-shaped, iso- to hypodense on CT, extra-axial collection that spreads diffusely over affected hemisphere • Location: Between arachnoid & inner layer of dura • Morphology o Crescent-shaped extra-axial fluid collection o May cross sutures, not dural attachments o May extend along falx & tentorium o Compresses & displaces underlying brain o Recurrent, mixed-age hemorrhage common ~ in a child raises suspicion of non accidental trauma! o CT density & MR signal intensity vary with age & organization of hemorrhage

• NECT o Iso- to hypodense ~ may be same density as underlying cortex o Gray-white junction displaced medially o Surface sulci do not reach inner calvarial table o May see line of displaced/compressed sulci as "dots" of CSF • CECT o Dura & membranes enhance o Inward displacement of enhancing cortical vessels

MR Findings • • • •

T1WI: Typically hyperintense (methemoglobin) T2WI: Variable, usually hyperintense FLAIR: Hyperintense (most conspicuous sequence) Tl C+: May see enhancing membranes on post-contrast imaging

Imaging Recommendations • Best imaging tool o NECT initial screen, consider CECT for membranes/loculations o MRI more sensitive for SDH & additional traumatic brain injury

DDx: Imaging Mimics of Subacute Subdural Hematoma ~ . .t-

~"

.

-

,

,

'".

'"

,

'.

](

l

t"~ ~.~

/ J

Meningioma (+ SOH)

Sinus Thrombosis

Leukemia

Trauma

Dural Thickening

findings of

SUBACUTE SUBDURAL HEMATOMA Key Facts • Inward displacement

Terminology • Subacute (± 3 days-3 weeks) hemorrhagic in subdural space

collection

Top Differential

Imaging Findings • Best diagnostic due: Crescent-shaped, iso- to dense on CT, extra-axial collection that spreads ly over affected hemisphere • Gray-white junction displaced medially • Surface sulci do not reach inner calvarial table

IDIFFERENTIAL

• • • • •

Diagnoses

CHECKLIST

Other subdural collections

Consider

• Effusion, empyema,

• Contrast-enhancement to look for membrane

hygroma

Pachymeningopathies • • • •

(thickened dura)

Chronic meningitis (may be indistinguishable) Post-surgical (shunt, etc) Intracranial hypotension Sarcoid (nodular, "lumpy-bumpy")

if suspected isodense subdural formation/loculations

I SELECTED REFERENCES 1.

Chronic dural sinus thrombosis • Diffuse dural thickening

cortical vessels

Other subdural collections Pachymeningopathies (thickened dura) Chronic dural sinus thrombosis Tumor Chemical shift artifact

IDIAGNOSTIC

DIAGNOSIS

of enhancing

2.

& enhancement

Tumor

3.

• Meningioma, lymphoma, leukemia, metastases • Dural based, enhancing mass • ± Skull involved

4.

5.

Chemical shift artifact • Marrow or subcutaneous fat may "shift" - can appear intracranial, mimic Tl hyperintense SDH

6. 7.

IPATHOlOG¥

8.

General Features

9.

• Etiology o Traumatic stretching & tearing of bridging cortical veins as they cross subdural space o Trauma may be minor, particularly in elderly • Epidemiology: SDH found in 10-20% imaged & 30% autopsy cases following craniocerebral trauma

Mori K et al: Delayed magnetic resonance imaging with Gd-DTPA differentiates subdural hygroma and subdural effusion. Surg Neurol 53: 303-11, 2000 Kaminogo M et al: Characteristics of symptomatic chronic subdural haematomas on high-field MRI. Neuroradiol 41: 109-16, 1999 Okuno S et al: Falx meningioma presenting as acute subdural hematoma. Surg Neurol 52:180-4, 1999 Fujisawa H et al: Serum protein exudation in chronic subdural haematomas. Acta Neurochir 140:161-5,1998 Park CK et al: Spontaneous evolution of posttraumatic subdural hygroma into chronic subdural haematoma. Acta Neurochir 127:41-7, 1994 Wilms G et al: CT and MR in infants with peri cerebral collections and macrocephaly. AJNR 14:855-60, 1993 Smith AS et al: Intracranial chemical-shift artifacts on MR images of the brain. AJR 154:1275-83, 1990 Fobben ES et al: MR characteristics of subdural hematomas and hygromas at 1.5 T. AJR 153:589-95, 1989 Destian S et al: Differentiation between meningeal fibrosis and chronic subdural hematoma after ventricular shunting. AJNR 10:1021-6, 1989

I IMAGE

GAllER¥

Gross Pathologic & Surgical Features • Membranes products

=

granulation

tissue, with resorbing blood

I Cli N I€AlISSl.J ES Presentation • Most common signs/symptoms: Varies asymptomatic to loss of consciousness

Natural History & Prognosis • Can spontaneously

resolve or enlarge

Treatment • Surgical drainage if growing/symptomatic

Coronal TlWI MR shows bilateral subdural hematomas of differing ages: Older right hematoma, with methemoglobin (black arrow), & acute-early subacute left subdural (white arrows). (Right) Axial NECT shows mixed density subacute subdural hematoma with a blood/hematocrit level (black arrow). Note displaced cortical vessels, or "dot" sign (white arrows). (Left)

Trauma

2 15

16

Axial graphic shows chronic subdural hematoma, with formation of internal membranes (white arrows). Note intact "bridging" veins, normally traversing subdural space (black arrows).

Abbreviations

Axial NEeT shows chronic subdural hematoma with enhancing membranes (arrows) & internal septae (open arrows).

o Enhancement of encapsulating membranes o Recurrent, mixed-age hemorrhage common ~ in a child raises suspicion of nonaccidental trauma! o CT density & MR signal intensity vary with age & organization of hemorrhage

and Synonyms

• Chronic subdural hematoma

(cSDH)

Definitions

CT Findings

• Chronic (± > 3 wks) collection of blood products in subdural space

General Features • Best diagnostic clue: Crescent-shaped, multi septated, extra-axial collection with enhancing surrounding membranes, that spreads diffusely over affected hemisphere • Location o Potential space between inner layer of dura mater & arachnoid o Supratentorial convexity most common • Morphology o Crescent-shaped extra-axial fluid collection o May cross sutures, not dural attachments o May extend along falx & tentorium o Compresses & displaces underlying brain o Often septated, with internal membranes o Calcification in 1-2%

• NECT o Density varies, depending on stage of evolution • Progresses from hyperdense acute SDH to iso(subacute) to hypodense cSDH over ± 3 week period • Progressive increase in density &/or size of cSDH from 3 weeks to 3 months, likely from re-bleed of fragile neocapillaries in outer membrane • Eventual resorption in most cSDH > 3 months (outer membrane "stabilizes" & thus not prone to re-bleed) • CECT o Inward displacement of enhancing cortical vessels o Enhancement of dura & membranes

MR Findings • TlWI o Variable depending on stage of evolution • Isointense to CSF if stable/chronic • Hyperintense with re-bleed or t protein • T2WI o Variable depending of stage of evolution

DDx: Mimics of Chronic Subdural Hematoma

Dural Mets

Chemical Shift

Meningeal Sarcoid

Trauma

Enlarged SAS

CHRONIC SUBDURAL HEMATOMA Key Facts Terminology • Chronic (± > 3 wks) collection of blood products in subdural space

Imaging Findings • Best diagnostic clue: Crescent-shaped, multiseptated, extra-axial collection with enhancing surrounding membranes, that spreads diffusely over affected hemisphere • May cross sutures, not dural attachments • May extend along falx & tentorium • Often septated, with internal membranes • Calcification in 1-2% • Enhancement of encapsulating membranes

Top Differential

• • • • •

Subdural effusion Subdural empyema Pachymeningopathies (thickened dura) Tumors Chemical shift artifacts

Pathology • SDH most commonly results from traumatic stretching & tearing of bridgi cortical veins as they cross subdural space to drain dural sinus • Encapsulated by granulation tissue: "Neomembranes" with fragile capillaries

Diagnoses

• Subdural hygroma

• • • •

• Isointense to CSF if stable/chronic • Hypointense with re-bleed o T2 hypointense signal seen in majority of cSDH (73%) ~ related to repeat hemorrhage o Membranes usually hypointense PD/lntermediate: Iso- to hyperintense, depending on protein content or re-bleed into collection FLAIR o Hyperintense to CSF o Most sensitive sequence for detection of SDH T2* GRE: Hypointense signal from subacute-chronic blood products DWI: Variable signal

• T1 C+

o Peripheral &/or dural enhancement o Delayed scans show contrast diffusion into SDH • Signal of SDH quite variable on MR o Generally evolve in pattern similar to intracerebral hemorrhage

Imaging Recommendations • Best imaging tool o NECT good initial screen o MRI better demonstrates ~ cSDH frequently hyperintense (due to methemoglobin) on Tl, T2, PD, FLAIR o MRI uniquely suited to evaluate nonaccidental trauma cases, since differing ages of blood products are better characterized • Protocol advice: Use wide window settings (150-200 HU) to identify small SDH

I DIFFERENTIAL DIAGNOSIS Subdural hygroma • Clear CSF • No encapsulating

membranes

Subdural effusion • Xanthochromic fluid from extravasation from outer membrane • 20% evolve into cSDH

of plasma

Subdural empyema • Peripheral enhancement • Restricted diffusion (hyperintense)

Pachymeningopathies

centrally

(thickened dura)

• Chronic meningitis (may be indistinguishable) • Post-surgical (shunt, etc) • Intracranial hypotension ("slumping" midbrain, tonsillar herniation) • Sarcoid (nodular, "lumpy-bumpy")

Tumors • Meningioma, lymphoma, leukemia, metastases • May also result in hemorrhagic SDH, particularly breast cancer metastasis • Dural based, enhancing mass • ± Skull involved

Chemical shift artifacts • Marrow or subcutaneous fat may "shift" ~ can appear intracranial, mimic T1 hyperintense SDH • Seen with t field of view or ~ bandwidth

IPATfJOlOG¥ General Features • General path comments: Blood in subdural space incites tissue reaction resulting in organization & resorption of hematoma • Etiology o SDH most commonly results from traumatic stretching & tearing of bridging cortical veins as they cross subdural space to drain into dural sinus o cSDH • Develops over 2-3 weeks • May continue to enlarge • May resolve spontaneously if membrane stabilizes o Mechanisms for SDH enlargement • Re-hemorrhage • Serum protein exudation • Epidemiology: SDH found in 10-20% imaged & 30% autopsy cases following craniocerebral trauma

Trauma

2 17

• Associated abnormalities: > 70% of acute SDH have other significant associated traumatic lesions

18

Gross Pathologic & Surgical Features

Image Interpretation

• Serosanguineous fluid • Encapsulated by granulation tissue: "Neomembranes" with fragile capillaries • S% multiloculated with fluid-blood density levels • Cycle of recurrent bleeding-coagulation-fibrinolysis

• Enhancement helpful to differentiate from pachymeningopathies

Microscopic

1.

Features

• Outer membrane formed by proliferating fibroblasts & capillaries; fragile capillaries hypothesized as source of recurrent hemorrhage in cSDH • Inner membrane formed by dural fibroblasts or border cells, forms fibrocollagenous sheet

2.

3. 4.

Staging, Grading or Classification Criteria • cSDH may be classified by internal architecture o Homogeneous/laminar • Homogeneous content • Can be laminar (thin, layer of fresh blood along inner membrane) o Separated • Hematocrit level • Sometimes content gradually changes ("gradated") o Trabecular • Inhomogeneous with internal septae • Thickened or calcified capsule

5.

6.

7.

8.

9. 10.

Presentation • Most common signs/symptoms o Most commonly following trauma o Varies from asymptomatic to loss of consciousness • "Lucid" interval in aSDH: Initially awake, alert patient who loses consciousness a few hours after trauma o Other symptoms from mass effect, diffuse brain injury, secondary ischemia

11.

12.

13.

Demographics

14.

• Age: Any age, more common in elderly • Gender: No gender predilection

15.

Natural History & Prognosis

16.

• Older age & brain atrophy are contributory factors in conversion of traumatic SDH into cSDH • Recurrence rate higher for skull base location SDH compared to convexity SDH • Recurrence high for separated SDH, low for trabeculated SDH • Extent of primary brain injury most important factor overall affecting outcome

Treatment

17.

18.

19.

20.

• Surgical drainage with resection of membranes • Recurrence risk of cSDH varies with type ("separated" is highest; thickened or calcified membrane almost never re- hemorrhages)

Trauma

Pearls chronic SDH

Tseng H et al: Dural metastasis in patients with malignant neoplasm and chronic subdural hematoma. Acta Neurol Scand 108:43-6, 2003 Alimehmeti R et al: Epidural B cell non-Hodgkin's lymphoma associated with chronic subdural hematoma. Surg Neurol 57:179-82,2002 Burger P et al: Surgical Pathology of the Nervous System and Its Coverings, 4th ed. Churchill Livingstone, NY, 2002 Nakaguchi H et al: Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg 95: 256-62, 2001 Mori K et al: Surgical treatment of chronic subdural hematoma in 500 consecutive cases. Neurol Med Chir 41:371-81, 2001 Tanikawa M et al: Surgical treatment of chronic subdural hematoma based on intrahematomal membrane structure on MRI. Acta Neurochir 143:613-618, 2001 Mori K et al: Delayed magnetic resonance imaging with Gd-DTPA differentiates subdural hygroma and subdural effusion. Surg Neurol 53: 303-11, 2000 Kaminogo M et al: Characteristics of symptomatic chronic subdural haematomas on high-field MRI. Neuroradiol41: 109-16, 1999 Fujisawa H et al: Serum protein exudation in chronic subdural haematomas. Acta Neurochir 140:161-5, 1998 Lee KSet al: The computed tomographic attenuation and the age of subdural hematomas. J Korean Med Sci 12:353-9, 1997 Massaro F et al: One hundred and twenty-seven cases of acute subdural haematoma operated on. Acta Neurochir 138:185-91, 1996 Cho SJ et al: Assumption of the age of subdural hematomas based on computed tomographic findings. Neurol Med Chir 24:607-14,1995 Park CK et al: Spontaneous evolution of posttraumatic subdural hygroma into chronic subdural haematoma. Acta Neurochir 127:41-7, 1994 Wilms G et al: CT and MR in infants with pericerebral collections and macrocephaly. AJNR 14:855-60, 1993 Smith AS et al: Intracranial chemical-shift artifacts on MR images of the brain. AJR 154:1275-83, 1990 Fobben ES et al: MR characteristics of subdural hematomas and hygromas at 1.5 T. AJR 153:589-95, 1989 Destian S et al: Differentiation between meningeal fibrosis and chronic subdural hematoma after ventricular shunting. AJNR 10:1021-6, 1989 Gentry LR et al: Prospective comparison study of intermediate-field MR and CT in the evaluation of closed head trauma. AJNR9:91-100, 1988 Yamashima T et al: The origin of inner membranes in chronic subdural hematomas. Acta Neuropath 67:219-225, 1985 Cameron MM et al: Chronic subdural hematoma: a review of 114 cases. J Neurol Neurosurg Psychiatry 41:834-39, 1978

(Left) Axial NECT shows

chronic CSF-isodense subdural hematoma. Note inward displacement of cortical vessels (arrows) by the collection. (Right) Coronal T1 C+ MR shows chronic subdural hematoma (white arrows) & extensive dural thickening & enhancement (black arrows) (Courtesy M. Fruin, MO).

Typical (Left) Axial NECT shows hemispheric chronic subdural hematoma, largely CSF density, with interval re-bleed (arrow) producing a "separated" appearance or hematocrit level. (Right) Axial CECTshows numerous enhancing septae (arrows) traversing a chronic subdural hematoma.

Typical (Left) Axial NECT shows chronic ossified subdural hematomas (arrows). (Right) Axial NECT shows bilateral cSOHs (arrows). Note foci of acute hemorrhage into periphery of loculated right-sided collection, which itself is more recent than the underlying very hypodense cSOH.

Trauma

19

2 20

Axial graphic shows hemorrhage of multiple ages in subdural hematoma, with numerous loculations from membranes (white arrows) & multiple fluid levels (black arrows).

Abbreviations

Axial NECT shows mixed density subdural hematoma, with multiple loculations (arrows) & differing ages of blood products.

• Often septated, with internal membranes • Enhancement of encapsulating membranes • Recurrent, mixed-age hemorrhages common; in a child should raise suspicion of nonaccidental trauma! o Mixed SDH may also be acute • When acute, higher mortality than homogenous high density acute SDH • Low density foci ("swirl" sign) reflect unclotted blood, serum extrusion, or CSF leak due to arachnoid tear

and Synonyms

• Subdural hematoma (SDH)

Definitions • Hemorrhage of differing ages/evolution in subdural space

General Features

CT Findings

• Best diagnostic clue: Crescent-shaped, mixed density/signal intensity, extra-axial collection with enhancing membranes, that spreads diffusely over affected hemisphere • Location o Potential space between inner layer of dura mater & arachnoid o Supratentorial convexity location most common • Morphology o Mixed SDH usually 2 days to 2 weeks after formation • Crescent-shaped extra-axial fluid collection • May cross sutures, not dural attachments • May extend along falx & tentorium • Compresses & displaces underlying brain

• NECT o Variable density • Isodense to underlying cortex ~ heterogenous density • CECT o Inward displacement of enhancing cortical vessels o Enhancement of dura & membranes

MR Findings • • • • •

T1WI: Mixed signal, usually Tl hyperintense T2WI: Mixed signal, hypo- to hyperintense FLAIR:Mixed signal, hyperintense to CSF Tl C+: Membrane enhancement in chronic SDH Mixed signal usually reflects re-bleed into chronic SDH

DDx: Mixed Subdural Hematoma /'" ....••..

;' "f"~ . \ ,

,

•..

\

,

t~~.

l~~ ) Leukemia + Bleed

Meningeal Sarcoid

Trauma

Melanoma Mets

En Plaque Mening

MIXED SUBDURAL HEMATOMA Key Facts Terminology • Hemorrhage space

of differing ages/evolution

in subdural

• • • •

Imaging Findings • Best diagnostic due: Crescent-shaped, mixed density/signal intensity, extra-axial collection with enhancing membranes, that spreads diffusely over affected hemisphere • Mixed SOH usually 2 days to 2 weeks after formation

May cross sutures, not dural attachments May extend along falx & tentorium Mixed SOH may also be acute Low density foci ("swirl" sign) reflect undotted serum extrusion, or CSF leak due to arachnoid

Pathology • Associated abnormalities: > 70% of SOH have other significant associated traumatic lesions

Imaging Recommendations

11D1~(ljNOBTICCHECKUBT

• Best imaging tool o NECT initial screen o MRI more sensitive for SDH, better detection of extent of intracranial injuries • Protocol advice: Use wide window settings (lS0-200 HU) to identify small SDH

Consider • IV contrast to demonstrate membranes/loculations

1.

• Effusion, empyema,

2.

hygroma

Acute epidural hematoma

3.

• Biconvex extra-axial collection • May cross dural attachments, limited by sutures

4.

Pachymeningopathies • • • •

(thickened dura)

Chronic meningitis (may be indistinguishable) Post-surgical (shunt, etc) Intracranial hypotension Sarcoid (nodular, "lumpy-bumpy")

• Meningioma,

5. 6. 7.

Tumor lymphoma,

leukemia, metastases 8.

I P~TH()l.:()(ljY

enhancement

of

I BEl.:ECTEID REFERENCEB

IIDIFFERENl'l~l.:1D1~(ljNOBIB Other subdural collections

blood, tear

9.

Nakaguchi H et al: Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg 95:256-62, 2001 Nakaguchi H et al: Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg 95: 256-62, 2001 Mori K et al: Delayed magnetic resonance imaging with Gd-DTPA differentiates subdural hygroma and subdural effusion. Surg Neurol 53: 303-11, 2000 Kaminogo M et al: Characteristics of symptomatic chronic subdural hematomas on high-field MRI. Neuroradiol41: 109-16, 1999 Fujisawa H et al: Serum protein exudation in chronic subdural haem atom as. Acta Neurochir 140:161-5, 1998 Wilms G et al: CT and MR in infants with pericerebral collections and macrocephaly. AJNR 14:855-60, 1993 Destian S et al: Differentiation between meningeal fibrosis and chronic subdural hematoma after ventricular shunting. A]NR 10:1021-6, 1989 Fobben ES et al: MR characteristics of subdural hematomas and hygromas at 1.5 T. AJR 153:589-95, 1989 Reed D et al: Acute subdural hematomas: atypical CT findings. AJNR 7:417-21,1986

General Features • Etiology: Usually re-hemorrhage into chronic SDH • Epidemiology: SDH found in 10-20% imaged & 30% autopsy cases following craniocerebral trauma • Associated abnormalities: > 70% of SDH have other significant associated traumatic lesions

IIM~(ljE (lj~l.:l.:ERY

I CUNIC~l.: IBB0EB Presentation • Most common signs/symptoms: Varies from asymptomatic to headaches or loss of consciousness

Natural History & Prognosis • Can spontaneously

resolve or enlarge

Treatment • Surgical evacuation

if symptomatic

or growing

(Left) Axial NEeT shows bilateral SOH of differing ages, right more acute. (Right) Axial T7WI MR shows differing ages of subdural hematomas; late subacute-chronic right (arrows), & acute-early subacute (curved arrows).

Trauma

2 21

22

Axial NECT shows diffuse hyperdense traumatic subarachnoid hemorrhage within sulci near the vertex.

Abbreviations

Axial FLAIR MR demonstrates traumatic subarachnoid hemorrhage as hyperintense sulci; hemoglobin presence prevents normal CSF nulling.

o Identical to aneurysmal SAH except for location • Adjacent to contusions, subdural hematomas • Convexity sulci> basal cisterns o Cortical vein sign = cortical veins evident crossing through hyperdense SAH

and Synonyms

• Traumatic subarachnoid

hemorrhage

(tSAH)

Definitions • Blood within subarachnoid arachnoid membranes

MR Findings

spaces between pial &

• • • •

General Features • Best diagnostic clue: High density on CT, hyperintensity on FLAIR within sulci/cisterns in setting of trauma • Location o Focally, adjacent to contusion, SDH, fracture, laceration o Diffusely throughout subarachnoid space &/or basal cisterns o Layering upon tentorium

T1WI: Isointense with brain on Tl WI ("dirty" CSF) T2WI: Isointense with brain on T2WI ("dirty" CSF) FLAIR: Hyperintense sulci/cisterns DWI o Useful for evaluation of tSAH-induced spasm • Hyperintense restricted diffusion in areas of ischemia • MRS: t Choline & creatine found in SAH patients suggest t cell-wall turnover

Angiographic Findings • Conventional o DSA • Useful for evaluation of tSAH-induced spasm • "Beaded appearance" of spasm-involved vessels

Imaging Recommendations

CT Findings

• Best imaging tool: CT > MRI given its accessibility • Protocol advice o NECT o FLAIR> CT in detection of small amounts of SAH

• NECT o High density in subarachnoid space(s)/cisterns o Hyperdense blood in interpeduncular cistern • May be only manifestation of subtle SAH

DDx: Traumatic Subarachnoid

Hemorrhage ~

...

~

..

~ AneurysmalSAH

Meningitis

Carcinomatosis

Trauma

j Pseudo-SAH

TRAUMATIC SUBARACHNOID HEMORRHAGE Key Facts Pathology

Terminology spaces between pial &

• Blood within subarachnoid arachnoid membranes

• tSAH-associated vasospasm 2-41% of cases • Expected evolutionary hemoglobin changes different than described for intracerebral hematoma

Imaging Findings

Top Differential • • • •

• Most common signs/symptoms: Headache, emesis, ~ consciousness • Clinical profile: Trauma is most common cause of SAH, not ruptured aneurysm • Amount of tSAH on initial CT correlates with delayed ischemia, poor outcome • Requires supportive therapy

Diagnoses

Non-traumatic SAH (ntSAH) Meningitis Carcinomatosis High inspired oxygen

Diagnostic Checklist • Hyperdense blood in interpeduncular only manifestation of subtle SAH

I [)IFFItRIt~~I~l:[)1~uf';J(])SIS Non-traumatic

Gadolinium

SAH (ntSAH)

• Ruptured aneurysm o 80-90% ntSAH in North America o Aneurysm identified on DSA, CTA, MRA in > 85% • Arterio-venous malformation o 15% ntSAH o Identified on DSA, CTA, MRA • Perimesencephalic venous hemorrhage o Often limited cisternal SAH o Negative initial & repeat DSA • Ruptured dissecting aneurysm o Aneurysmal dissection with rupture • Hypertensive hemorrhage o Longstanding hypertension o Negative initial & repeat DSA • Cerebral infarction with reperfusion hemorrhage o Presence of known infarct • Anticoagulation therapy o Often long-term Coumadin therapy o Usually unrecognized mild head trauma • Blood dyscrasia o Pre-existing entity, usually known • Eclampsia (aka pregnancy-induced hypertension) o Reported complication o Eclampsia symptomatology • Spinal vascular malformation o Spontaneous rupture o Diagnosis of exclusion with negative initial & repeat cerebral DSA

Meningitis • Proteinaceous

CSF prevents FLAIR CSF nulling

Carcinomatosis • Cellular CSF prevents FLAIR CSF nulling

Pseudo-subarachnoid

hemorrhage

• Severe, diffuse cerebral edema ~ brain becomes diffusely hypodense • Dura & circulating blood appear "hyperdense" compared to adjacent brain

2

Clinical Issues

• Best diagnostic clue: High density on CT, hyperintensity on FLAIR within sulci/cisterns in setting of trauma • FLAIR: Hyperintense sulci/cisterns • FLAIR> CT in detection of small amounts of SAH

cistern may be

administration

• Administered intravenously for routine enhanced-MRI • Can cause FLAIR hyperintensity o Seen in patients with stroke, high-grade gliomas (whose neoplasms surface contacted subarachnoid spaces or ventricles), & meningiomas o CSF changes more evident close to pathology &/or hemisphere involved

High inspired oxygen • Administration of 100% 02 during general anesthesia may cause incomplete nulling of CSF on FLAIR • Incomplete nulling of CSF FLAIR signal 2° to propofol has been described

I P~~f'i(])l:(])u¥ General Features • Genetics: Less favorable outcome in SAH patients who possess APO,£4 allele • Etiology: Most likely arises from tearing of veins in subarachnoid space • Epidemiology o 33% with moderate brain injury; nearly 100% at autopsy o tSAH-associated vasospasm 2-41 % of cases • Associated abnormalities: Contusions, subdural/epidural hematoma, diffuse axonal injury

Gross Pathologic & Surgical Features • Acute blood within sulci/cisterns

Microscopic

Features

• Expected evolutionary hemoglobin changes different than described for intracerebral hematoma o Progression occurs much slower o Most likely because high ambient oxygen tension of subarachnoid CSF delays degradation

Staging, Grading or Classification Criteria • tSAH Grading Scale o Grade 1: Thin tSAH :s;5 mm

Trauma

23

o o o o

Grade 2: Thick tSAH > 5 mm Grade 3: Thin tSAH with mass lesion(s) Grade 4: Thick tSAH with mass lesion(s) Patients with lower grades have better admission Glasgow coma scale values & discharge Glasgow outcome scale scores

Image Interpretation

Pearls

• Hyperdense blood in interpeduncular cistern may be only manifestation of subtle SAH • tSAH often accompanied by additional injuries

24

Presentation

1.

• Most common signs/symptoms: Headache, emesis, ! consciousness • Clinical profile: Trauma is most common cause of SAH, not ruptured aneurysm

2.

3.

Demographics • Age: Median age = 43 years (SD = 21.1 years) • Gender: Men"'" 2x more likely than women to sustain traumatic brain injury (TBI) • Populations at increased risk of sustaining TBI o Young people o Low-income individuals o Unmarried individuals o Members of ethnic minority groups o Residents of inner cities o Individuals with previous history of substance abuse o Individuals with previous TBI

4.

5.

6.

7.

8.

Natural History & Prognosis • Natural history = breakdown & resorption from CSF • Acute hydrocephalus o Rare ~ usually obstruction of aqueduct or 4th ventricular outlet by clotted SAH o Obstructive, non-communicating hydrocephalus • Asymmetric ventricular dilatation • Delayed hydrocephalus o Arachnoid granulation defect in CSF resorption o Obstructive, communicating hydrocephalus • Symmetric ventricular dilatation • Vasospasm o May develop quickly (2-3 days post-injury) o Peaks 7-10 days after injury o Threat remains up to 2 weeks o Uncommon cause of post traumatic infarct • tSAH associated with TBI has poor prognosis o Amount of tSAH on initial CT correlates with delayed ischemia, poor outcome o 46-78% of TBI involving tSAH result in severe disability, vegetative state, or death

9.

10. 11.

12. 13.

14.

Treatment • Requires supportive therapy o Intubation, supplemental oxygen, IV fluids, therapy of altered vital signs o Sedatives & medications for pain, nausea, & vomiting as needed o Anticonvulsants for seizures • Nimodipine, a calcium channel blocker, may prevent vasospasm & its complications

15.

16.

Trauma

Parasad K et al: Traumatic subarachnoid hemorrhage. J Neurosurg 100:739-41, 2004 Given CA 2nd et al: Pseudo-subarachnoid hemorrhage: a potential imaging pitfall associated with diffuse cerebral edema. AJNRAm J Neuroradiol. 24(2):254-6, 2003 Rumboldt Z et al: Hyperacute subarachnoid hemorrhage on T2-weighted MR images. AJNRAm J Neuroradiol. 24(3):472-5,2003 Kay A et al: Temporal alterations in cerebrospinal fluid amyloid beta-protein and apolipoprotein E after subarachnoid hemorrhage. Stroke. 34(12):e240-3, 2003 Shah AK:Non-aneurysmal primary subarachnoid hemorrhage in pregnancy-induced hypertension and eclampsia. Neurology. 61(1):117-20, 2003 Bozzao A et al: Cerebrospinal fluid changes after intravenous injection of gadolinium chelate: assessment by FLAIRMR imaging. Eur Radiol. 13(3):592-7, 2003 Mattoli C et al: Traumatic subarachnoid hemorrhage on the CT scan obtained at admission. J Neurosurg 98:37-42, 2003 Macmillan CS et al: Traumatic brain injury and subarachnoid hemorrhage: in vivo occult pathology demonstrated by magnetic resonance spectroscopy may not be "ischaemic". A primary study and review of the literature. Acta Neurochir (Wien). 144(9):853-62; discussion 862, 2002 Servadei F et al: Traumatic subarachnoid hemorrhage: demographic and clinical study of 750 patients from the European brain injury consortium survey of head injuries. Neurosurgery. 50(2):261-7; discussion 267-9, 2002 Boto GR et al: Basal ganglia hematomas in severely head injured patients. J Neurosurg 94: 224-32, 2001 Taoka T et al: Sulcal hyperintensity on fluid-attenuated inversion recovery mr images in patients without apparent cerebrospinal fluid abnormality. AJRAm J Roentgenol. 176(2):519-24,2001 Server A et al: Post-traumatic cerebral infarction. Acta Radiol 42: 254-60, 2001 Filippi CG et al: Hyperintense signal abnormality in subarachnoid spaces and basal cisterns on MR images of children anesthetized with propofol: new fluid-attenuated inversion recovery finding. AJNRAm J Neuroradiol. 22(2):394-9,2001 Noguchi K et al: Comparison of fluid-attenuated inversion-recovery MR imaging with CT in a simulated model of acute subarachnoid hemorrhage. AJNRAm J Neuroradiol. 21(5):923-7, 2000 Noguchi K et al: Subacute and chronic subarachnoid hemorrhage: diagnosis with fluid-attenuated inversion-recovery MR imaging. Radiology. 203(1):257-62, 1997 Greene KAet al: Impact of traumatic subarachnoid hemorrhage on outcome in non penetrating head injury. Part I: A proposed computerized tomography grading scale. J Neurosurg. 83(3):445-52, 1995

Typical (Left) Axial NECT

demonstrates a small collection of hyperdense traumatic subarachnoid hemorrhage within the interpeduncular cistern (arrow). (Right) Axial NECT shows hyperdense traumatic subarachnoid hemorrhage throughout the basilar cisterns.

Typical (Left) Axial NECT shows

subtle hyperdense traumatic subarachnoid hemorrhage within the left Sylvian fissure (arrows). (Right) Axial NECT demonstrates a very small hyperdense focus of traumatic subarachnoid hemorrhage (arrow). Volumes vary from tiny to massive amounts.

Typical (Left) Axial FLAIRMR

demonstrates hyperintense subarachnoid blood within cisterns (white arrow) & supratentorial sulci (black arrow) as well as between cerebellar folia (open arrow). (Right) Axial FLAIR MR shows hyperintense SAH in interpeduncular cistern (white arrow), sulci (black arrows) & between cerebellar folia (open black arrow). Note left epidural hematoma (open white arrow).

Trauma

2... 25

26

Coronal graphic illustrates hemorrhagic foci involving gray matter of several gyri as well as deeper white matter & gray nuclei. Mass effect is causing left to right shift.

Abbreviations

• Size: Barely discernible to large • Morphology o CC evolve with time • Early: Patchy, ill-defined superficial foci of punctate or linear hemorrhages along gyral crests • 24-48 hrs: New lesions appeari size/shape of existing lesions may enlarge • Chronic: Encephalomalacia with parenchymal volume loss o Multiple, bilateral lesions in 90%

and Synonyms

• Cerebral contusion

Axial FLAIRMR shows cerebral contusion hyperintensity involving temporal cortices & frontal lobe rectus gyri (white arrows). The left uncus is beginning to herniate (black arrow).

(CC)

Definitions • Injury to brain surfaces involving superficial gray matter

Radiographic Findings General Features

• Radiography: Scalp hematomas

• Best diagnostic clue: Patchy superficial hemorrhages within edematous background • Location o Occur in characteristic locations where brain is adjacent to bony protuberance or dural fold • Nearly 50% involve temporal lobes: Temporal pole, inferior surface, perisylvian cortex • 33% involve frontal lobe surfaces: Frontal pole, inferior surface (inferior frontal & rectus gyri) • 25% parasagittal = "gliding" contusions o Less common locations • Inferior cerebellar surfaces, parietal/occipital lobes, vermis, cerebellar tonsils o Focal contusions may also occur at site of depressed skull fracture

CT Findings

or skull fractures

• NECT o Early: May be normal • Poorly defined hypodensity & swelling • Patchy, ill-defined low-density lesion with small hyperdense foci of petechial hemorrhage o 24-48 hrs • Multiple new hypodense lesions appear • Lesions often t edema & size ~ worsening mass effect • Delayed hyperdense hemorrhages develop in 20% • Petechial hemorrhage may become hematomas o Chronic • Become isodense ~ hypodense • Brain parenchymal volume loss

"\ I, ~,::~)'

DDx: Cerebral Contusion

,\

.

, .•• ~.t, •• , "~.r \ I

',COllI

.

,.v

I

'.

.

..

.

.., .

,:

"

~ Cerebritis

Infarct

Low grade Neoplasm

Trauma

Post-ictal Changes

CEREBRAL CONTUSION Key Facts Terminology

Top Differential

• Injury to brain surfaces involving superficial gray matter

• • • •

Imaging Findings • Best diagnostic clue: Patchy superficial hemorrhages within edematous background • Occur in characteristic locations where brain is adjacent to bony protuberance or dural fold • Focal contusions may also occur at site of depressed skull fracture • FLAIR best demonstrates hyperintense cortical edema • FLAIR may show hyperintense SAH • Acute: Hypointense hemorrhagic foci "bloom" on GRE (often not seen on other sequences) • Best imaging tool: MR > CT in detecting presence, delineating extent of lesions o Secondary lesions common • Herniations/mass effect, hyperdense subarachnoid hemorrhage (SAH), intracerebral hematoma • t Ventricles of hydrocephalus • Xenon-CT o I CBF around contusions compared to global CBF o I CBF in first 24 hrs associated with poor outcome

MR Findings • TlWI· o Acute: Inhomogeneous due to admixture of edema & hemorrhage o Chronic: Focal or diffuse atrophy • FLAIR o Acute • FLAIR best demonstrates hyperintense cortical edema • FLAIR may show hyperintense SAH o Chronic • Best to follow edema resolution • Hypointense hemosiderin, ferritin deposit "stain" in scarred residual parenchyma • Hyperintense Wallerian-type axonal degeneration, demyelination, & microglial scaring • Hypointense cavitation (cystic encephalomalacia) • T2* GRE o Acute: Hypointense hemorrhagic foci "bloom" on GRE (often not seen on other sequences) o Chronic: Hemosiderin, ferritin deposits "bloom" as hypointense "stain" in scarred residual parenchyma • DWI o Acute: Foci of restricted diffusion possible • Matches I ADC • Extends beyond visible edema • MRS o In normal-appearing occipitoparietal white & occipital gray matter • I NAA in white matter from neuronal injury • t Choline in gray matter, suggestive of inflammation

Diagnoses

Cerebritis Infarct Low-grade neoplasm Transient post-ictal changes

2

Pathology • 1994: Traumatic brain injury caused 6.5% of American deaths • "Coup" lesion(s): Ipsilateral to impact site, from main force blow, associated with calvarial fractures • "Contrecoup" lesion(s): Opposite impact site, induced by gyral crests striking fixed surface

• NAA & creatine in white & gray matter significantly associated with composite neuropsychological function & neuropsychological tests • Gray matter choline abnormality not related to neuropsychological function

Nuclear Medicine

Findings

• SPECT: Blood-flow imaging with technetium-99m HMPAO o Depict focal changes in 53% patients with mild head injury & few findings on MRI/CT o Negative SPECT in first month predicts good outcome o Positive SPECT can predict poor outcome of clinical deterioration & posttraumatic headaches o Poor outcomes correlation between MR & SPECT

Imaging Recommendations • Best imaging tool: MR > CT in detecting presence, delineating extent of lesions • Protocol advice o FLAIRto evaluate edema & SAH oGRE for hemorrhagic foci

'DIFFERENTIAL DIAGNOSIS Cerebritis • History of trauma absent • Herpes typically involves medial temporal lobe & hippocampus

Infarct • History of trauma absent • Characteristic acute stroke-like symptoms hemiplegia)

low-grade

neoplasm

• History of trauma absent • Often asymptomatic • Solitary lesion, often non-traumatic

Trauma

(e.g.,

locations

27

Transient post-ictal changes • History of trauma absent • Preceding or on-going seizure activity • Can enhance acutely

28

Presentation

General Features • Etiology o Direct & indirect trauma • Direct injury ("coup" lesion) occurs at site of initial impact • Indirect injury ("contrecoup" lesion) induced by gyral crests striking fixed surface ~ bone & dural fold o Mechanism = linear differential acceleration (e.g., boxing) or deceleration (e.g., MVA) forces o "Gliding" injury = cortex anchored to dura via arachnoid granulations ~ subcortical tissue moves ("glides") more freely than adjacent cortex • Epidemiology o 45% primary intra-axial traumatic lesions o 94% of non-missile head injuries in Glasgow postmortem series o 1994: Traumatic brain injury caused 6.5% of American deaths o About 32 per 100,000 population • Associated abnormalities o Soft tissue (scalp, subgaleal) contusions 70% o SDH, traumatic SAH, IVH common o Skull fracture, possibly depressed 35%

Gross Pathologic & Surgical Features • Contusions o "Coup" lesion(s): Ipsilateral to impact site, from main force blow, associated with calvarial fractures o "Contrecoup" lesion(s): Opposite impact site, induced by gyral crests striking fixed surface o Often evolve • Petechial hemorrhages (often more evident in 24-48 hrs), edema form along gyral crests • Small hemorrhages may coalesce • Large hematomas may occur in 30-60 min • Delayed hematomas may develop 24-48 hrs later • Lacerations o Intracerebral hematoma with "burst" lobe o SDH common; communicates with hematoma via lacerated brain, torn pia-arachnoid o SAHcommon • May ultimately undergo encephalomalacic change/atrophy o Focal encephalomalacia at site of contusion o Whole-brain atrophy after mild/moderate injury o Evident by 11 months following trauma

Microscopic

Features

• Most common signs/symptoms o Initial symptom: Confusion o Focal neurologic deficits vary: Focal cerebral dysfunction, seizures, personality changes o Loss of consciousness less common than with diffuse axonal injury (DAI) • Clinical profile o 2nd most common primary traumatic neuronal injury (44%): DAI = 1st o Present in nearly half of moderate/severe closed head injury cases

Demographics • Age: Children:Adults = 2:1 (15-24 years at highest risk) • Gender: M:F= 2:1 • Ethnicity: Occur with slightly greater frequency among minority groups

Natural History & Prognosis • Varies with extent of primary injury, associated/secondary lesions (mass effect, herniations, perfusion alterations) • Elderly population has highest mortality rate • Although 90% of patients survive injury, 25% or more have significant residual complaints

Treatment • Evacuate focal hematoma if symptoms require • Mitigate secondary effects of closed head injury o Raised intracranial pressure o Perfusion disturbances

Consider • If negative initial exam, 24-48 hrs repeat recommended

1.

2.

3. 4.

5.

6.

• Capillary disruption • Whole blood extravasation into tissue o Plasma content leads to edema o Red blood cells account for visible hemorrhage • Liquefaction & encephalomalacia may occur

Trauma

MacKenzie]D et al: Brain atrophy in mild or moderate traumatic brain injury: a longitudinal quantitative analysis. A]NR Am] Neuroradiol. 23(9): 1509-15, 2002 Hofman PA et al: MR imaging, single-photon emission CT, and neurocognitive performance after mild traumatic brain injury. A]NR Am] Neuroradiol. 22(3):441-9, 2001 Adams]H et al: The neuropathology of the vegetative state after an acute brain insult. Brain. 123 (Pt 7):1327-38, 2000 Uu AYet al: Traumatic brain injury: diffusion-weighted MR imaging findings. A]NR Am] Neuroradiol. 20(9):1636-41, 1999 Laatsch L et al: Incorporation of SPECTimaging in a longitudinal cognitive rehabilitation therapy programme. Brain Inj. 13(8):555-70, 1999 Friedman SD et al: Proton MR spectroscopic findings correspond to neuropsychological function in traumatic brain injury. A]NR Am] Neuroradiol. 19(10):1879-85, 1998

Typical (Left) Axial T2WI MR demonstrates cortical hyperintensity & early encephalomalacia of the anterior temporal lobe from evolving cerebral contusion. (Right) Axial NECT shows a large cerebral contusion that rapidly increased in size over a short imaging interval with worsening midline shift; hyperdense hemorrhage has progressed to frank hematoma.

Typical (Left) Admission axial NECT of a patient with closed head injury shows a small frontal cerebral hypodense contusion with foci of hyperdense hemorrhage (arrow). (Right) Axial NECT in the same case obtained 24 hours later shows evolution, clear demarcation of the hypodense contusion with interspersed foci of hyperdense hemorrhage (arrow).

Typical (Left) Axial NECT shows multifocal contusions involving inferior frontal & temporal lobes. Some are nonhemorrhagic (white arrows) & others have hyperdense foci of hemorrhage (black arrows). (Right) Axial NECT demonstrates contrecoup hemorrhagic cerebral contusion within a lacerated temporal lobe. Tentorial subdural (arrow) & coup scalp injury (open arrow) are also seen.

Trauma

2.... 29

30

Sagittal graphic illustrates multiple hemorrhagic foci of diffuse axonal injury within the corpus callosum & brainstem.

Abbreviations

Axial T2* eRE MR shows multifocal hypointense foci from susceptibility of hemorrhagic diffuse axonal injury Most lesions are at the gray/white interface, but some are also periventricular .

• Size: Punctate to 15 mm • Morphology o Multifocal punctate, round, ovoid, elliptical hemorrhagic foci at characteristic locations o Multiple, bilateral lesions in nearly all cases

and Synonyms

• Diffuse axonal injury (DAI) • Traumatic brain injury (TBI)

CT Findings

Definitions

• NECT o Initially often normal (50-80%) • 30% with negative CT are positive on MRI o Small hypodense foci corresponding to edema at site of shearing injury o Hyperdense foci of petechial hemorrhage(s) (20-50%) o 10-20% evolve to focal mass lesion with hemorrhagic/edema admixture o Delayed scans often reveal"new" lesions

• Traumatic axonal stretch injury

General Features • Best diagnostic clue: Multifocal punctate hemorrhages at corticomedullary junction, corpus callosum, deep gray matter & upper brainstem • Location o Common • Gray/white matter (GM/WM) interface (67%) ~ esp frontotemporal lobes • Corpus callosum (20%) ~ 3/4 of which involve splenium/undersurface of posterior body • Brainstem ~ esp dorsolateral midbrain & upper pons o Less common • Caudate, thalamus, internal/external capsule, tegmentum, fornix, corona radiata, cerebellar peduncles

MR Findings • TlWI o Often unremarkable o If hemorrhagic, may demonstrate hemoglobin products (signal dependent on age) • T2WI o Multifocal hyperintense foci at characteristic locations o If hemorrhagic, may demonstrate hemoglobin products (signal dependent on age) o Multifocal hypointense residua may remain for years

DDx: Diffuse Axonal Injury

Amyloid Angiopathy

Cav Malformations

Hypertensive Enceph

Trauma

Hemorrhagic Mets

DIFFUSE AXONAL INJURY (DAI) Key Facts Terminology

Top Differential Diagnoses

• Traumatic axonal stretch injury

• Multifocal nonhemorrhagic lesions • Multifocal hemorrhagic lesions

Imaging Findings • Best diagnostic clue: Multifocal punctate hemorrhages at corticomedullary junction, corpus callosum, deep gray matter & upper brainstem • Gray/white matter (GM/WM) interface (67%) - esp frontotemporal lobes • Corpus callosum (20%) - 3/4 of which involve splenium/undersurface of posterior body • Brainstem - esp dorsolateral midbrain & upper pons • Multifocal hypointense foci on T2* GRE secondary to susceptibility from blood products at characteristic locations

Pathology • General path comments: Overlying cortex moves at different speed in relation to underlying deep brain structures resulting in axonal stretching • 80% DAI lesions are microscopic, nonhemorrhagic • Visible lesions are "tip of the iceberg" • Stage 1: Frontal & temporal lobe gray/white interface • Stage 2: Lesions in lobar WM & s callosum • Stage 3: Lesions of dorsolateral mi rain & upper , pons

Clinical Issues • Loss of consciousness

• FLAIR: Multiple high signal foci at characteristic locations • T2* GRE o Multifocal hypointense foci on T2* GRE secondary to susceptibility from blood products at characteristic locations o Multifocal hypointense foci may remain for years oGRE may be only technique identifying DAI • DWI o Hyperintense foci of restricted diffusion o Decreased ADC & diffusion anisotropy o DTI may show severity of WM injury • MRS o In normal-appearing occipitoparietal WM & occipital GM • I NAA in WM from neuronal injury • 1 Choline in GM suggestive of inflammation • NAA & creatine in WM & GM significantly associated with composite neuropsychological function & neuropsychological tests • GM choline abnormality not related to neuropsychological function o Decreased NAA/Cr correlates with poor outcome • Susceptibility-weighted (SW) imaging o High-spatial-resolution 3D fast low-angle shot o Extremely sensitive to susceptibility o Can be performed with conventional MR imagers o Depicts significantly more DAI foci than GRE

Nuclear Medicine Findings • SPECT: Blood-flow imaging with Tc-99m HMPAO o May show focal perfusion abnormalities

Imaging Recommendations • Best imaging tool: MR » CT for detection • Protocol advice o SW best sequence, although GRE more available o Follow-up at 24 hrs as 1/6 evolve

I DIFFERENII~1:l

(LOC) at moment

of impact

DI~(jJN(}SIS

Multifocal non hemorrhagic lesions • Aging - trauma history absent; leukoariosis & lacunes • Demyelinating disease - ovoid, may enhance • Marchiafava-Bignami syndrome - splenium lesion in chronic alcoholism & poor nutrition • Non-hemorrhagic metastases - enhancing masses • Radiation therapy - may cause focal lesions of the splenium

Multifocal hemorrhagic lesions • Amyloid angiopathy - elderly, normotensive, often demented • Hypertensive microhemorrhages - longstanding chronic HTN • Cavernous malformations - often mixed age hemorrhages • Hemorrhagic metastases - enhancing masses

I P~TH(}t(}(jJ¥ General Features • General path comments: Overlying cortex moves at different speed in relation to underlying deep brain structures resulting in axonal stretching • Genetics o Significant genomic responses to brain trauma occur • Induction of "immediate early genes" • Activation of signal transduction pathways • Apolipoprotein E (apoE) genotype, amyloid deposition may influence clinical outcome • Etiology o Trauma induced forces of inertia • Differential acceleration/deceleration & rotational/angular forces • Head impact not required o Axons stretched, rarely disconnected or "sheared" (only in most severe injury) o Non-disruptively injured axons undergo

Trauma

2 31

32

• Traumatic depolarization, massive ion fluxes, spreading depression & excitatory amino acid release • Metabolic alterations with accelerated glycolysis, lactate accumulation • Cellular swelling & cytotoxic edema o Corpus callosum injury • Believed caused by rotational shear-strain forces • Falx likely indirectly contributes posteriorly by preventing transient tissue displacement thus allowing greater tensile stresses locally • Epidemiology o "" 50% of all 1° intra-axial traumatic brain lesions o 80-100% autopsy prevalence in fatal injuries • Associated abnormalities: Corpus callosal injury associated with intraventricular hemorrhage

Demographics • Age: Any, may occur in-utero if pregnant woman subjected to sufficient force • Gender: No predilection

Natural History & Prognosis • Severe DAI rarely causes death o > 90% remain in a persistent vegetative state (brain stem spared) o Prognosis worsens as number of lesions 1 • Brainstem damage (ponto medullary rent) associated with immediate or early death • 10% of patients return to normal function, do so within the 1st year o May experience post-concussion syndrome: Persistent headache, cognitive decline, personality changes

Gross Pathologic & Surgical Features • Multiple small round/ovoid/linear WM lesions • Widely distributed: Para sagittal WM, corpus callosum, brain stem tracts (e.g., medial lemnisci, corticospinal tracts)

Microscopic

Features

• 80% DAI lesions are microscopic, nonhemorrhagic o Visible lesions are "tip of the iceberg" • Impaired axoplasmic transport, axonal swelling • Axonal swelling, 2° "axotomy", "retraction" balls • Microglial clusters • Macro-, microhemorrhages (torn penetrating vessels) • Wallerian degeneration

Treatment • No real treatment for diffuse axonal injury • Supportive therapy • Treatment of associated abnormalities: Herniation, hematoma, hydrocephalus, seizures, etc

Consider • Consider DAI if patient symptoms disproportionate imaging findings

Image Interpretation

Staging, Grading or Classification Criteria

Pearls

• Lesions best detected by susceptibility

• Adams & Gennarelli staging o Stage 1: Frontal & temporal lobe gray/white interface • Mild head trauma o Stage 2: Lesions in lobar WM & corpus callosum • More severe rotational force injury o Stage 3: Lesions of dorsolateral midbrain & upper pons • Trauma of even greater severity than Stage 2 • Correlates with deeper brain involvement from increasing severity of traumatic forces

1.

2.

3.

4.

Presentation • Most common signs/symptoms o Loss of consciousness (LOC) at moment of impact o Immediate coma typical • Persistent vegetative state possible • Mild DAI can occur without coma o Disconnection & diffuse deafferentation o Greater impairment than with cerebral contusions, intracerebral hematoma, extra-axial hematomas • Clinical profile o Most common 1° traumatic neuronal injury (48%) • Usually in setting of high-velocity MVA • Admission GCS does not always correlate with outcome o Suggested in patient with clinical symptoms disproportionate to imaging findings

5. 6.

7.

8.

Trauma

to

sensitive MRI

Huisman TAGM et al: Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury. A]NR 25:370-6, 2004 Cruz] et al: Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial.] Neurosurg. 100:376-83, 2004 Tong KAet al: Hemorrhagic shearing lesions in children and adolescents with posttraumatic diffuse axonal injury: improved detection and initial results. Radiology. 227(2):332-9, 2003 Pekala]S et al: Focal lesion in the splenium of the corpus callosum on FLAIRMR images: a common finding with aging and after brain radiation therapy. A]NR Am] Neuroradiol. 24(5):855-61, 2003 Arfanakis K et al: Diffusion tensor MR imaging in diffuse axonal injury. A]NRAm] Neuroradiol. 23(5):794-802, 2002 Hofman PA et al: MR imaging, single-photon emission CT, and neurocognitive performance after mild traumatic brain injury. A]NR Am] Neuroradiol. 22(3):441-9, 2001 Sinson G et al: Magnetization transfer imaging and proton MR spectroscopy in the evaluation of axonal injury: correlation with clinical outcome after traumatic brain injury. A]NR Am] Neuroradiol. 22(1):143-51, 2001 Kuzma BB, Goodman ]M: Improved identification of axonal shear injuries with gradient echo MR technique. Surg Neurol 53: 400-2, 2000

Typical (Left) Axial T2* GRE MR shows multifocal hypointense foci from susceptibility of hemorrhagic diffuse axonal injury. Deep white matter & pericallosal tissue are involved. (Right) Axial NECT demonstrates multiple petechial hemorrhages at bifrontal gray/white interfaces (white arrows) in diffuse axonal injury. Also note the presence of subarachnoid hemorrhage (black arrows).

Typical (Left) Axial NECT shows hyperdense hemorrhage within the fornices (arrow) from diffuse axonal injury (OAI). The splenium is hypodense (open arrow) from non hemorrhagic OAI involvement. (Right) Axial OWl MR shows restricted diffusion with susceptibility within fornices (arrow) from hemorrhage. The splenium is hyperintense (open arrow) from non hemorrhagic OAI.

Typical (Left) Axial NECT demonstrates characteristic hemorrhage involving dorsolateral midbrain (white arrow) from OAI. Interpeduncular cisternal subarachnoid hemorrhage is also present (black arrow). (Right) Axial T2WI MR shows hyperintensity within the dorsolateral brainstem from evolving diffuse axonal injury (white arrow). There are also bitemporal chronic subdural hematomas (black arrows).

Trauma

33

34

Axial FLAIR MR shows hyperintense anterorostral brainstem subcortical injury from sudden craniocaudal brain displacement. Bitemporal FLAIR hyperintense contusion injuries are also seen.

Abbreviations

• Size o SCI: Limited to size of BS o IVH: Can fill/expand ventricles o CH: Limited to size of choroid involved • Morphology o SCI: Petechial, linear o IVH: Can cast ventricle o CH: Shape of choroid involved

and Synonyms

• Subcortical injury (SCI) • Intraventricular hemorrhage • Choroid hemorrhage (CH)

(IVH)

Definitions • SCI = traumatic lesions of brainstem (BS), basal ganglia, thalamus, & regions around 3rd ventricle • IVH = hemorrhage with ventricular system • CH = hemorrhage with choroidal tissues

CT Findings

General Features • Best diagnostic clue o SCI: Deep gray matter (GM), BS FLAIR signal o IVH: Hyperdense intraventricular CSF on NECT, fluid-heme level common o CH: Hyperdense, enlarged choroid on NECT • Location o SCI = BS, basal ganglia, thalamus, & regions around 3rd ventricle • Most within thalamus & putamen o IVH: Intraventricular spaces o CH: Localized within choroid tissue

DDx: Subcortical

Cav Malformation

Sagittal T2WI MR demonstrates hyperintense hemorrhagic subcortical Injury involving the anterorostral brainstem as well as fornix (arrows). Open arrow = fat in crista galli.

• NECT o SCI: Often normal; petechial hyperdense foci • Deep GM nuclei, dorsolateral BS, periaqueductal region • Rarely overt hemorrhage oIVH • Hyperdense intraventricular blood • May fill, even expand, ventricle • Fluid-heme level common o CH: Isolated dense choroidal hemorrhage without associated IVH

MR Findings • TlWI o SCI: Acutely isointense o IVH: Fluid-heme level common • T2WI o SCI: Acutely hyperintense o IVH: Fluid-heme

Injury

Cav Malformation

Acute Infarct

Trauma

Small Vessel Disease

SUBCORTICAL INJURY Key Facts • CH: Blood extravasated into choroid tissue from traumatic rent/tear/laceration

Terminology • SCI = traumatic lesions of brainstem (BS), basal ganglia, thalamus, & regions around 3rd ventricle • IVH = hemorrhage with ventricular system • CH = hemorrhage with choroidal tissues

Clinical Issues • • • • • • •

Imaging Findings • SCI: Deep gray matter (GM), BS FLAIR signal • IVH: Hyperdense intraventricular CSF on NECT, fluid-heme level common • CH: Hyperdense, enlarged choroid on NECT

Pathology • SCI: Petechial hemorrhages thalamus, & regions around • IVH: Expected evolutionary different than described for

of BS, basal ganglia, 3rd ventricle hemoglobin changes intracerebral hematoma

Diagnostic Checklist • SCI: MRI is superior to CT • IVH/CH: CT is superior to MRI

• FLAIR o SCI: Most sensitive sequence - foci of hyperintense signal o IVH: Detection comparable to CT in acute stage • T2* GRE: SCI: Susceptibility of petechial hemorrhage • DWI: SCI: Foci of restricted diffusion

Imaging Recommendations • Best imaging tool o SCI: MRI »> CT • Protocol analogous to diffuse axonal injury (DAI) o ICH/CR: NECT >>> MRI • Protocol analogous to subarachnoid hemorrhage • Protocol advice o SCI: FLAIR & GRE o ICH/CR: CT = NECT; MRI = FLAIR & GRE

I DIFFERENTIAL

DIAGNOSIS

SCI • Cavernous malformation: Symptoms w/o trauma • Lacunar infarcts: Located in central tegmentum of pons/BS • Small vessel ischemia

ICH • None

CH • Normal calcification

may mask small hemorrhages

I PATHOLOGY General Features • General path comments o SCI • Some classify as Stage 3 DAI • Less common than diffuse axonal injury or cerebral contusion • 3rd most common primary traumatic neuronal injury (5%)

SCI: Profound neurologic deficits IVH: Obtundation, seizures SCI: Severely injured patients IVH: Hydrocephalus rare manifestation CH: Can lead to IVH Supportive therapy Treatment considerations of indirect/associated abnormalities: Herniation, hematoma, hydrocephalus, seizures, etc

o ICH: Blood filling ventricular CSF space o CH: Hemorrhage within choroid tissue • Etiology o SCI: Most commonly induced by shear-strain forces that disrupt penetrating and/or choroidal vessels • Usually very small, typically nonhemorrhagic o SCI: Less commonly • Dorsolateral BS impacts tentorial incisura with violent brain motion • Anterorostral BS damaged with sudden craniocaudal brain displacement o IVH • Disruption of subependymal veins (most common) • Bleeding from choroid plexus • Shearing injuries • Basal ganglia/intracerebral hemorrhage with rupture into ventricles • Isolated IVH in absence of parenchymal hematoma is unusual o CH: Traumatic shear forces damage choroid tissue • Epidemiology o SCI: 5-10% primary traumatic brain injuries o IVH: Common in closed head injury • 60% patients with corpus callosal DAI • 12% patients without corpus callosal DAI • Associated abnormalities o SCI: All stages of DAI (without exception), cerebral contusion, extra-axial hemorrhage o IVH: DAI, deep GM/BS/intracerebral hemorrhage, SAH, cerebral contusion o CH: DAI, SAH, cerebral contusion

Gross Pathologic & Surgical Features • SCI o Usually nonhemorrhagic, yet more often hemorrhagic than other forms of primary intra-axial injury o Secondary to rich network of perforating vessels within basal ganglia & thalamus • IVH o Gross blood collected within ventricular system o Blood-CSF level common

Trauma

2 35

• High rate of layering, rather than clot formation, most likely relates to intrinsic anti thrombotic properties of CSF because of high concentrations of fibrinolytic activators o May cast/expand involved ventricle • CH: Hemorrhagic choroid tissue

Microscopic 36

Features

• SCI: Petechial hemorrhages of BS, basal ganglia, thalamus, & regions around 3rd ventricle • IVH: Expected evolutionary hemoglobin changes different than described for intracerebral hematoma o Progression occurs much slower o Most likely because high ambient oxygen tension of CSF delays degradation • CH: Blood extravasated into choroid tissue from traumatic rent/tear/laceration

Staging, Grading or Classification Criteria • SCI: BS injury (BSI) o Primary injury: Direct result of trauma; 4 categories • 1: Direct laceration/contusion; rare • 2: Diffuse axonal injury (DAI); associated with more superficial DAI; most common primary BSI • 3: Multiple primary petechial hemorrhages; not associated with more superficial DAI • 4: Ponto medullary rent or separation; may occur without widespread brain injury o Secondary injury: Indirect result of trauma, most common cause of BSI, usually herniation • SCI: When BSI ~ BS hemorrhage o Group 1: Midline rostral anterior BS, posterior to the interpeduncular cistern (69%) • Associated with anterior head and/or face impact; 71% survival o Group 2: Misc foci of acute BS hemorrhage (18%) • Associated with transtentorial herniation & BS compression; 88% survival o Group 3: Any BS hemorrhage • Associated with transtentorial herniation & BS compression, 100% mortality

• SCI: May proceed to BS hemorrhage o Associated with high mortality • IVH: Gradually clears as resorbed, although patients> 20 cc of blood do poorly • IVH: Hydrocephalus rare manifestation o Early: CSF outlet obstruction • Obstructive, non-communicating hydrocephalus • Asymmetric ventricular dilatation o Late: Arachnoid dysfunction of CSF resorption • Obstructive, communicating hydrocephalus • Symmetric ventricular dilatation • IVH: Hemorrhagic dilation of 4th ventricle is an ominous predictor with 100% reported mortality • CH: Can lead to IVH

Treatment • SCI o Supportive therapy o Treatment considerations of indirect/associated abnormalities: Herniation, hematoma, hydrocephalus, seizures, etc • IVH o Ventriculostomy o Excellent results following r-TPA thrombolytic therapy • Effective & safe, despite preexisting multiple hemorrhagic intracranial injuries o Repeat NECT to evaluate for hydrocephalus, treatment complications

Image Interpretation

1.

2.

Presentation 3.

• Most common signs/symptoms o SCI: Profound neurologic deficits • Low initial Glasgow coma scale scores; coma o IVH: Obtundation, seizures

4.

Demographics • Age o Highest incidence of traumatic brain injury (TBI) = 15-24 years & > 75 years o Additional smaller peak occurs children < 5 years • Gender: Men "" 2x > women to sustain TBI

5.

Natural History & Prognosis

7.

• SCI: Severely injured patients o Poor prognosis, often die soon after trauma o Regain consciousness very slowly, incompletely time, & retain permanent neurological im pairmen t/ disability

Pearls

• SCI: MRI is superior to CT • IVH/CH: CT is superior to MRI

6.

over

Trauma

Bakshi R et al: MRI in cerebral intraventricular hemorrhage: analysis of 50 consecutive cases. Neuroradiology. 41(6):401-9, 1999 Grabb PA:Traumatic intraventricular hemorrhage treated with intraventricular recombinant-tissue plasminogen activator: technical case report. Neurosurgery. 43(4):966-9, 1998 Rohde V et al: Intraventricular recombinant tissue plasminogen activator for lysis of intraventricular haemorrhage. J Neurol Neurosurg Psychiatry. 58(4):447-51, 1995 Shapiro SA et al: Hemorrhagic dilation of the fourth ventricle: an ominous predictor. J Neurosurg. 80(5):805-9, 1994 Meyer CA et al: Acute traumatic midbrain hemorrhage: experimental and clinical observations with CT. Radiology. 179(3):813-8, 1991 Young WB et al: Prognostic significance of ventricular blood in supratentorial hemorrhage: a volumetric study. Neurology. 40(4):616-9, 1990 Gentry LR et al: Traumatic brain stem injury: MR imaging. Radiology. 171(1):177-87, 1989

Typical

(Left) Axial FLAIR MR shows hyperintense dorsolateral brainstem subcortical injury (arrow) from tentorial incisura impact during violent brain motion. Left temporal hyperintense shear injury is also seen. (Right) Axial FLAIR MR demonstrates hyperintense right basal ganglia subcortical injury.

Typical

(Left) Axial OWl MR shows foci of hyperintense restricted diffusion within brainstem subcortical injury representing cytotoxic edema. (Right) Axial NECT shows hyperdense left basal ganglia hemorrhagic subcortical injury (white arrow). More medial and bilateral hyperdensities are senescent calcifications (black arrows).

(Left) Axial NEeT shows bilateral intraventricular hemorrhage as well as bilateral depressed skull fractures, right frontal cerebral contusion, left frontal epidural hematoma, & subarachnoid hemorrhage. (Right) Axial NECT demonstrates extensive hyperdense hemorrhage confined to the choroid plexus bilaterally.

Trauma

2 37

38

Loronal graphIc ShOWSleatures 01 /\IAI mCluamg subdurals of differing ages (arrows), SAH, cortical contusions (open arrows), depressed skull fracture (curved arrow) & scalp hematoma.

Abbreviations

and Synonyms

• Nonaccidental trauma (NAT); non accidental injury (NAI); shaken-baby syndrome; whiplash shaken infant syndrome; nonaccidental head injury (NAHI)

Definitions • Inflicted brain injury

General Features • Best diagnostic clue: Multiple brain injuries at different stages of evolution • Spectrum of findings including scalp injuries, skull fractures, intracranial hemorrhages, cerebral contusions, shear injuries, ischemic brain injury • Skull fractures o Linear ~ low specificity NAT o Compound ~ moderate specificity NAT o Multiple, depressed, diastatic (> 5 mm wide), non-parietal, growing Fxs, fractures crossing midline/sutures ~ high specificity NAT • Intracranial hemorrhage o Epidural hemorrhage (EDH) • EDH very rare in NAT

Loronal II VVI IVII< snows mU/uple suoaural interhemispheric hemorrhages of different ages.

(\0

o Subdural hemorrhage (SDH) • SDH most common manifestation in NAT • Multiple SDH in different locations, different ages • SDH over cerebral convexities or in interhemispheric fissure most common location o Subarachnoid hemorrhage (SAH) • Present in up to 50% o Intraventricular hemorrhage • Parenchymal features o Cortical contusions • Typical locations include surface of frontal & temporal lobes • Cortical hemorrhages, edema in acute phase o Shear injuries • Punctate focal hemorrhages ± cavitation • Typical locations include corticomedullary junction, sentrum semiovale, corpus callosum • Larger shearing injuries manifest as subcortical lacerations o Ischemic injury • Varies from global hypoxic brain injury to individual vascular territory infarction • Late sequelae o Subdural hygroma/chronic SDH o Hydrocephalus o Encephalomalacia o Atrophy o Leptomeningeal cyst

Birth Injury

Trauma

NONACCIDENTAL TRAUMA Key Facts Terminology

Pathology

• Inflicted brain injury

• 85% non-survivers have evidence of impact head injury at postmortem examination • Upper cervical cord stretching =;> apnea =;> ischemic brain injury • Epidural hematoma (EDH) very rare in NAT • Most common cause of traumatic death in infancy: 1,200 deaths per year in USA

Imaging Findings • Best diagnostic clue: Multiple brain injuries at different stages of evolution • Spectrum of findings including scalp injuries, skull fractures, intracranial hemorrhages, cerebral contusions, shear injuries, ischemic brain injury • Multiple, depressed, diastatic (> 5 mm wide), non-parietal, growing Fxs, fractures crossing midline/sutures ...•high specificity NAT • SDH most common manifestation in NAT • Hypoechoic "slit-like" tears from shearing injuries at corticomedullary junction • Healing fractures (Fxs) of differing ages!

Radiographic Findings • Radiography: Remains best method of evaluation skull fractures

• Notification to local Child Protection Agency mandated in US/Canada/Australia/some European countries

Diagnostic Checklist • Inborn error of metabolism or bleeding dyscrasia may RARELYsimulate non-accidental injury

Other Modality Findings of

• Skeletal survey: Skeleton is most common site of inflicted injury o Healing fractures (Fxs) of differing ages! o Metaphyseal corner, posterior rib, scapular, sternal Fxs; T-L compression Fxs; spinous process avulsion Fxs

CT Findings • NECT o Primary imaging tool in initial evaluation o High sensitivity in detecting fractures, hemorrhage, edema & hypoxic-ischemic injury • Fractures oriented in axial plane may be missed! o Aging of hemorrhage (SDH) variable! • Complex spectrum of appearances of intracranial hemorrhage on CT • General pattern: Hyperdense « 7 days), isodense to brain (7-21days), hypodense to brain (> 21 days)

Imaging Recommendations

MR Findings • MR difficult to perform in acute setting o Long procedure, sensitivity to motion, requirement for sedation ± general anaesthetic • However, overall increased sensitivity for most injuries except fractures outweigh difficulties of performing o T2* GRE most sensitive for depicting hemorrhage o DWI most sensitive for depicting early ischemic changes in unmyelinated brain o DWI/FLAIR "mismatch" may confirm multiple or previous episodes of brain injury o Optimal method of evaluation of cervical spine o MRS: ~ NAA, t Ch/Cr ratio, ~ Cr, t lactate!lipid peaks poor prognostic indicators: +/- Normal in first 24 hours

Ultrasonographic

Clinical Issues

Findings

• Hypoechoic "slit-like" tears from shearing injuries at corticomedullary junction

• Best imaging tool: NECT to start • Protocol advice o NECT o +/- MR to document age of bleed, sequelae (first day of admission useful to confirm multiple ages of hemorrhages), evaluation of cervical spine o Skeletal survey +/- scintigraphy (if> 2 yrs or if skeletal survey equivocal, clinical suspicion high) o Abdominal CT if multiple injuries, abnormal liver function test (LFT), or coma

I DIFFEREN"EIk\l. DIk\{;jNO$I$ Accidental trauma • • • •

Appropriate history for degree of injury Acute SDH 7% (70% in inflicted brain injury) Retinal hemorrhage 0-2% (50-96% in inflicted injury) Preexisting brain injury, atrophy, SDH hygroma 0% (45% in inflicted injury) • Subsequent mental deficiency 5% (45% or more in inflicted brain injury)

NAT mimics (uncommon) • Brain: Coagulopathies (hemophilia, leukemia) • Skeletal: Osteogenesis imperfecta, rickets, syphilis • Metabolic: Glutaric aciduria type I, Menkes

Nuclear Medicine Findings

Physiologic EVOH

• Bone Scan: Evidence of multiple healing fractures • PET: ~ Glucose metabolism in brain trauma, but not specific for inflicted brain injury

• Subarachnoid

Trauma

CSF prominence

with traversing veins

2 39

General Features

40

• General path comments o 85% non-survivers have evidence of impact head injury at postmortem examination o 50% significant extra cranial injuries o Cause of death in 80% is brain swelling (not hemorrhage) o Upper cervical cord stretching ~ apnea ~ ischemic brain injury • Focal axonal damage to cranio-cervical junction of cervical cord o Severe hypoxic ischemic encephalopathy (HIE) 78% > classical diffuse axonal injury (DAI) o Epidural hematoma (EDH) very rare in NAT o 20-45% evidence for prior brain injury o Retinal hemorrhage 70-96% (usually bilateral, always with SDH) • Non-ophthalmologists miss hemorrhages in 30% • Etiology o Injuries result of direct trauma, shaking injuries, strangulation, or a combination thereof o Reason infants are vulnerable • Large head:body ratio + weak neck muscles • Developing brain o Shaking/impact ~ torn bridging veins, retinal schisis o Minor falls do not typically cause rotational forces needed for spectrum of brain injuries seen in NAT!! • Epidemiology o 17-25:100,000 annual incidence o Most common cause of traumatic death in infancy: 1,200 deaths per year in USA o Risk factors • < 1 years, prematurity, twin, male, physical handicap, stepchild • Young parents, ~ socioeconomic status, 1/3 of perpetrators under influence of alcohol or drugs

Gross Pathologic & Surgical Features • Acute (immediate) o Skull fractures, extra-axial hemorrhage, disrupted brain tissue, intra-ocular hemorrhages, brainstem dysfunction • Early subacute (hours to days) o Impaired cerebral autoregulation/perfusion & chemically mediated tissue damage: Edema, HIE, infarction • Late subacute or chronic o Hydrocephalus, atrophy, chronic SDH, gliosis, microcephaly, leptomeningeal cysts, delayed myelin maturation

Presentation • Most common signs/symptoms o Discordance between stated history & injury on imaging! (history of minimal or no trauma) o Presentation with "apnea" (33-45%), unexplained seizures, "unable to rouse" o Retinal hemorrhage in up to 96%

• Clinical profile o Infants have relatively large heads, weak neck muscles o Poor feeding, vomiting, irritability, seizures, lethargy, coma, apnea

Demographics • Age: Median age 2.2-4.6 months old • Gender: Male> female (up to 2:1)

Natural History & Prognosis • High mortality 15-38% (60% if coma at presentation) • Neurologic deficits include acquired microcephaly (93%), early post-traumatic seizures (79%), late posttraumatic epilepsy (> 20%), poor visual outcome (20-65%)

Treatment • Notification to local Child Protection Agency mandated in US/Canada/Australia/some European countries • Multidisciplinary child abuse & neglect team intervention

Consider • Inborn error of metabolism or bleeding dyscrasia may RARELYsimulate non-accidental injury

Image Interpretation

Pearls

• Look for combination of hemispheric brain swelling, HIE-like edema, bilateral or interhemispheric SDH

1.

Lo TY et al: Cerebral atrophy following shaken impact syndrome and other non-accidental head injury (NAHI). Pediatr Rehabil6(1):47-55, 2003 2. ]aspan T et al: Neuroimaging for non-accidental head injury in childhood: A proposed protocol. Clin Radiol 58(1):44-53, 2003 3. Kemp AM et al: Apneoa and brain swelling in non-accidental head injury. Arch Dis Child 88(6):472-6, 2003 4. Wells RG et al: Intracranial hemorrhage in children younger than 3 years: Prediction of intent. Arch Pediatr Adolesc Med 156(3):252-7, 2002 5. Suh DY et al: Nonaccidental pediatric head injury: DWI findings. Neurosurgery 49(2):309-318, 2001 6. Geddes et al: Neuropathology of inflicted head injury in children: 1. Patterns of brain damage. 2. Microscopic brain injury in infants. Brain 124:1290-306, 2001 7. Ewing-Cobbs et al: Acute neuroradiologic findings in young children with inflicted or noninflicted traumatic brain injury. Childs Nerv System 16:25-34, 2000 8. Naidoo S et al: A profile of the oro-facial injuries in child physical abuse at a children's hospital. Child Abuse Negl 24(4):521-534,2000 9. Kivlin]D et al: Shaken baby syndrome. Ophthalmology 107(7):1246-54, 2000 10. Dashti SRet al: Current patterns of inflicted head injury in children. Pediatr Neurosurg 31(6):302-6, 1999

Trauma

Typical (Left) Axial NECT in NAT shows bifrontal (arrows) & interhemispheric (open arrow) subdural hemorrhages of different densities & ages. SOHs are most common neurologic manifestation of NAT (Right) Axial TlWI MR shows bilateral hygromas (white arrows), hemorrhage within chronic SOHs (curved arrow), acute SOHs (open arrow) & subarachnoid hemorrhages (black arrow).

Typical (Left) Axial T2WI MR in a patient with NAT shows subdural collections of different signal intensities & ages. Multiple subdural collections of differing ages is most common CNS manifestation of NAT (Right) Axial OWl MR in same patient obtained at same time as previous T2Wl shows extensive left hemispheric restricted diffusion.

Typical (Left) Axial T2* GRE MR shows multiple foci of hypointense blooming (arrows) secondary to hemosiderin staining within subdural collections. (Right) Coronal oblique radiography shows multiple rib fractures (arrows) of different stages of healing in this infant. Note endotracheal & NG tube in this critically brain injured infant.

Trauma

41

42

Sagittal graphic shows 4th ventricular mass resulting in superior transtentorial herniation (white arrows) & inferior tonsillar herniation (black arrows).

Definitions • Herniation of brain from one compartment (normally separated by calvarial &/or dural boundaries) to another

General Features • Subfalcine herniation = herniation of cingulate gyrus under falx o Secondary to unilateral frontal lobe mass effect o Cingulate gyrus displaced under falx o Ipsilateral lateral ventricle compressed o Foramen of Monro obstructs ~ opposite lateral ventricle enlarges o Anterior cerebral arteries (ACAs) displaced ~ may become occluded • Unilateral descending transtentorial herniation (DTH) = herniation of medial temporal lobe inferiorly through incisura o Secondary to unilateral mass effect on temporal lobe o Early • Uncus, parahippocampal gyrus displaced medially • Ipsilateral suprasellar cistern effaced • Ipsilateral ambient, CPA cisterns enlarge

DDx: Complications

Syrinx

Coronal graphic shows acute epidural hematoma causing subfalcine (curved arrow) & left uncal (open arrow) herniation. Note obstructed left foramen of Monro (arrow).

• Contralateral cisterns effaced due to shift/torque of brain stem • Contralateral temporal horn enlarged (trapped) o Late • Suprasellar cistern completely obliterated • Brainstem compressed & displaced by herniating temporal lobe ~ brain stem compression against opposite tentorial margin = "Kernohan notch" • Cranial nerve (CN) 3 compressed • Posterior cerebral artery (PCA) displaced inferomedially ~ may occlude (occipital infarct) o "Uncal" herniation = type of early DTH, with uncus filling ipsilateral suprasellar cistern • Bilateral DTH ("central" herniation) = bilateral downward herniation through incisura o Severe uni- or bilateral supratentorial mass effect o Both hemispheres, basal nuclei pushed downwards ~ diencephalon, midbrain displaced inferiorly o Both temporal lobes herniate into tentorial hiatus o Angle between midbrain, pons becomes more acute o Optic chiasm/hypothalamus displaced downwards, draped over sella o Penetrating basal arteries often occlude ~ basal infarcts • Ascending transtentorial herniation = cerebellum & brain stem displaced up through incisura o Secondary to posterior fossa mass effect o Quadrigeminal cistern deformed

of Herniation

Hydrocephalus

Duret Hemorrhage

Trauma

Infarcts

INTRACRANIAL HERNIATION SYNDROMES Key Facts Terminology • Herniation of brain from one compartment (normally separated by calvarial &/or dural boundaries) to another

Imaging Findings • Subfalcine herniation = herniation of cingulate gyrus under falx • Unilateral descending transtentorial herniation (DTH) = herniation of medial temporal lobe inferiorly through incisura • "Uncal" herniation = type of early DTH, with uncus filling ipsilateral suprasellar cistern • Bilateral DTH ("central" herniation) = bilateral downward herniation through incisura • Ascending transtentorial herniation = cerebellum & brainstem displaced up through incisura o Midbrain displaced anteriorly o May obstruct aqueduct - hydrocephalus • Tonsillar herniation = tonsillar herniation into spinal canal o Secondary to posterior fossa mass effect o Tonsils pushed inferiorly, impacted into foramen magnum o "Peg_like" configuration of tonsils o General rule: Displacement> 5 mm below foramen magnum abnormal, however morphology is more important o Tonsil folia usually oriented horizontally - become vertically oriented when herniated o Cisterna magna obliterated o Fourth ventricle may obstruct, cause obstructive hydrocephalus • Transalar herniation = herniation across sphenoid wing o Uncommon o Few clinical symptoms o Can be ascending (middle cranial fossa or temporal lobe mass) or descending (frontal lobe mass) o Displacement of temporal & frontal lobes, middle cerebral artery across lesser sphenoid wing • Transdural/transcranial herniation = herniation through dural &/or skull defect o Skull fracture & dural laceration (may also occur with craniotomy) o Elevated ICP o Brain extrudes through torn dura o May extend under galea

CT Findings • Variable causes of herniation demonstrated • Secondary effects of herniation demonstrated o Hydrocephalus o Vascular occlusion - infarcts o Duret hemorrhage

MR Findings • Tl WI: Low signal in subacute infarcts, edema • T2WI: High signal in subacute infarcts, edema

• Tonsillar herniation = tonsillar herniation into spinal canal • Transalar herniation = herniation across sphenoid wing • Transdural/transcranial herniation herniation through dural &/or skull defect

2

Pathology

43

=

• Secondary effects exacerbate severity of primary injuries • Herniations, i intracranial pressure (ICP), altered cerebral hemodynamics - ischemia & infarction

Clinical Issues • Decreased mental status or obtundation • Brain death if intracranial pressure continues to rise, mass effect progresses unabated

• T2* GRE: Hypointense hemorrhagic foci (e.g., Duret hemorrhages) • DWI: Hyperintensity in secondary ischemic areas, usually from vascular compression • Variable causes of herniation demonstrated • Secondary effects of herniation demonstrated o Hydrocephalus o Vascular occlusion - infarcts o Duret hemorrhage

Angiographic Findings • Conventional: Local mass effect, vascular compression, venous dilation

Imaging Recommendations • Best imaging tool o NECT best rapid screen o Multiplanar ability of MR optimally demonstrates brain shift • Protocol advice: Add DWI + GRE to imaging of post-trauma patients to identify infarcts & occult hemorrhagic foci

I DIFFERENTIAL

DIAGNOSIS

Intracranial hypotension syndrome • Caused by brain "pulled" not "pushed" down • Dural thickening, enhancement usually present

I PATIflOlOG¥ General Features • Etiology o Trauma most common clinical setting o Hemorrhage, extracellular fluid or added tissue accumulate within closed space o CSF spaces (cisterns, ventricles) initially compressed o If added intracranial volume can't be accommodated • Gross mechanical displacement of brain, vessels occurs - herniation

Trauma

44

o Secondary effects exacerbate severity of primary injuries o Herniations, i intracranial pressure (ICP), altered cerebral hemodynamics ~ ischemia & infarction • PCA occlusion ~ occipital infarct most common • ACA occlusion ~ distal (cingulate gyrus) infarcts • Perforating vessels ~ basal ganglia, capsule infarcts • Midbrain ("Duret") hemorrhage can occur from stretching or tearing of pontine perforators • Associated abnormalities: Secondary hydrocephalus, ischemia, hemorrhage, necrosis

5. 6. 7.

8. 9.

Gross Pathologic & Surgical Features

10.

• Grossly swollen, edematous brain • Gyri compressed, flattened against calvarium • Sulci effaced

11. 12.

13.

Presentation 14.

• Decreased mental status or obtundation • Focal neurologic deficit o Contralateral hemiparesis o Ipsilateral pupil-involving CN 3 palsy o Ipsilateral hemiplegia • Kernohan notch ~ compression of opposite cerebral peduncle against tentorium • "False localizing signs" • Decreased brainstem blood flow, cardiovascular collapse • Decerebrate posturing

15.

16. 17.

18. 19.

Natural History & Prognosis

20.

• Brain death if intracranial pressure continues to rise, mass effect progresses unabated

21.

Treatment • Treatment Issues o Aimed at mitigating secondary effects of trauma o Prolonged posttraumatic brain hypersensitivity • May offer potential "therapeutic window" • Possible use of neuroprotective agents

22.

Consider • DWI, GRE sequences in brain trauma or suspected herniation • Intracranial hypotension syndrome can mimic DTH, tonsillar herniation caused by supratentorial mass

1.

2.

3. 4.

Cruz J et al: Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial. J Neurosurg. 100:376-83, 2004 Stein SC et al: Association between Intravascular Microthrombosis and Cerebral Ischemia in Traumatic Brain Injury. Neurosurgery. 54(3):687-91, 2004 Derakshan I: Kernohan notch. J Neurosurg 100:741-2, 2004 Parizel PM et al: Brainstem hemorrhage in descending

Trauma

transtentorial herniation (Duret hemorrhage). Intensive Care Med 28:85-8, 2002 Server A et al: Post-traumatic cerebral infarction. Acta Radiol 42:254-60, 2001 Juul N et al: Intracranial hypertension and cerebral perfusion pressure. J Neurosurg 92: 1-6,2000 Sheehan JM et al: Resolution of tonsillar herniation and syringomyelia after supratentorial tumor resection. Neurosurg 48:702-4,2000 Fujimoto Y et al: Recovery from duret hemorrhage. Neurol Med Chir 40:508-10,2000 Mastronardi L et al: Magnetic resonance imaging findings of Kernohan-Woltman notch in acute subdural hematoma. Clin Neurol Neurosurg 101:122-4, 1999 Povlishock JT et al: Are the pathobiological changes evoked by traumatic brain injury immediate and irreversible? Brain Pathol 5: 415-26, 1995 Laine FJ et al: Acquired intracranial herniations. AJR 165: 967-73, 1995 Tachibana S et al: Syringomyelia secondary to tonsillar herniation caused by posterior fossa tumors. Surg Neurol 43:470-5, 1995 Opeskin K: Traumatic pericallosal artery aneurysm. Am J Forensic Med Path 16:11-6, 1995 Laine FJ et al: Acquired intracranial herniations. AJR 165:967-73,1995 Endo M et al: Capsular and thalamic infarction caused by tentorial herniation subsequent to head trauma. Neuroradiol 33:296-9, 1991 Osborn AG: Secondary effects of intracranial trauma. Neurosurg Clin N Amer 1:461-74, 1991 Jones KM et al: Ipsilateral motor deficit resulting from a subdural hematoma and a Kernohan's notch. AJNR 12:1238-1239, 1991 Mirvis SE et al: Post-traumatic cerebral infarction diagnosed by CT. AJNR 11:355-60, 1990 Spiegelman R et al: Upward transtentorial herniation. Neurosurg 24:284-99,1989 Rothfus WE et al: Callosomarginal infarction secondary to transfalcial herniation. AJNR 8:1073-76, 1987 Ropper AH: Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass. NEJM 314:953-8, 1986 Alexander E et al: Brainstem hemorrhages and increased intracranial pressure. Surg NeuroI17:107-1O, 1982

Typical (Left) Sagittal T1WI MR shows superior transtentorial herniation (arrows) & inferior tonsillar herniation (open arrows) due to large mass in the cerebellum (Lhermitte Duclos). Note hydrocephalus. (Right) Axial T2WI MR shows ascending transtentorial herniation due to cerebellar mass (arrows). Note anterior displacement of brainstem (open arrow) & obstructive hydrocephalus.

Typical (Left) Axial T2WI MR shows unilateral descending trans tentorial herniation secondary to left temporal lobe mass, with effacement of left suprasellar cistern (arrow) & midbrain compression (open arrow). (Right) Axial NECT shows bilateral descending transtentorial herniation through the tentorial incisura (arrows). The midbrain is compressed & deformed.

Typical (Left) Axial NECT shows parenchymal hematoma in the right temporal lobe, with resultant transalar herniation of the anterior temporal lobe across the greater sphenoid wing (arrows). (Right) Axial CECT shows multiple enhancing metastases. Right frontal mass effect results in subfalcine herniation, with left displacement of cingulate gyrus & anterior cerebral arteries under falx (arrow).

Trauma

45

46

Axial OWl MR shows left hemispheric edema involving the cortex, subcortical and periventricular white matter in a toddler with inflicted brain injury.

Abbreviations

and Synonyms

• Vasogenic edema (VE), cytotoxic edema (CTE), cerebral edema (CE), diffuse brain swelling (DBS)

Definitions • Brain, CSF and blood exist in closed intracranial compartment o To maintain normal ICP, 1 in one compartment must be balanced by I in others (Monro-Kellie) • CE (a secondary effect of trauma, ischemia) is a dynamic process involving glutamate-mediated excitotoxicity & cell damage • Two basic forms of brain edema in trauma: VE and CTE =:> often co-exist o VE: Extracellular edema, follows blood brain barrier (BBB) breakdown o CTE: Intracellular (closed barrier) edema

General Features • Best diagnostic clue: Compressed ventricles and effaced sulci due to focal or diffuse increase in brain water • Location

Axial AOC map shows extensive left hemispheric decreased AOC (arrows) in the same toddler, confirming cytotoxic edema.

o Vasogenic more prominent in WM, cytotoxic more prominent in GM o Often co-exist • Morphology o Compressed ventricles & effaced sulci o Secondary effects of CE • Herniation of brain • Vascular compression =:> infarction

Radiographic Findings • Radiography: +/- Fractures, split sutures

CT Findings • NECT o Compressed ventricles & effaced sulci o Low-attenuation brain parenchyma: WM > GM • Subcortical WM less resistant to fluid accumulation than GM • Loss of GM-WM interfaces o Vasogenic more prominent in WM, cytotoxic more prominent in GM o I Supratentorial perfusion with preservation of infratentorial perfusion =:> "white cerebellum" sign o High density hemorrhage often present in closed head injury • CECT: Usually no enhancement unless BBB disrupted • Xenon CT: Brain edema major contributor to brain swelling

DDx: Brain Edema

Newborn

HIE

Metabolic

(MELAS)

Trauma

PRES VE

PRES Normal

OWl

TRAUMATIC CEREBRAL EDEMA Key Facts • Vasogenic more prominent in WM, cytotoxic more prominent in GM • Herniation of brain • Vascular compression ~ infarction • DWI together with ADC differentiates VE from CTE • Brain edema accompanied by t ICPt t pulsatility index, ! blood flow velocity within 24 hours ~ poor prognosis • Disturbed cerebral autoregulation during first 48 hours correlates with poor outcome

Terminology • Vasogenic edema (VE), cytotoxic edema (CTE), cerebral edema (CE), diffuse brain swelling (DBS) • CE (a secondary effect of trauma, ischemia) is a dynamic process involving glutamate-mediated excitotoxicity & cell damage • Two basic forms of brain edema in trauma: VE and CTE ~ often co-exist • VE: Extracellular edemat follows blood brain barrier (BBB) breakdown • CTE: Intracellular (closed barrier) edema

Clinical Issues • Goal = maintain cerebral perfusion pressure (CPP) without inducing hydrostatic vasogenic edema

Imaging Findings • Best diagnostic clue: Compressed ventricles and effaced sulci due to focal or diffuse increase in brain water

o Cerebral blood volume actually decreases in proportion to cerebral blood flow

Angiographic Findings • Conventional:

MR Findings • Tl WI: Hypointense edema • T2WI: Hyperintense edema • FLAIR o Hyperintense edema o Less useful in newborn due to normally t water content of neonatal brain • T2* GRE: +/- Blood products • DWI o DWI together with ADC differentiates VE from CTE • VE: Increased extracellular brain water (t ADC) • CTE: Cellular swelling (I ADC) o Diffusion tensor imaging (DTI): I Diffusion anisotropy early, when MRI/DWI still normal o DTI identifies traumatic penumbra, potentially salvageable brain • Tl C+: Patchy enhancement if BBBbreakdown • MRA o +/- I Flow ("thinned" arteries) o Vascular obstruction (compression or dissection during herniation) ~ post-traumatic infarction • MRV: Sinus compression with severe edema • MRS: I NAA, elevated Cho (membrane breakdown) or lactate presence predict poor prognosis • Perfusion: I Brain perfusion with progressive t ICP

Ultrasonographic

Findings

Slow arteriovenous

Nuclear Medicine

transit if t ICP

Findings

• PET: PET/SPECT: I rCBV, hypometabolism upon timing)

(dependent

Imaging Recommendations • NECT performed due to accessibility in critically ill trauma patients • DWI with ADC maps (or DTI) important to differentiate VE and CTE • Multiplanar MR allows characterization of acquired cerebral herniations o Subfalcine (cingulate), tonsillar, uncal, transtentorial (central ascending, central descending, lateral), transalar, external

I DIFFtiRENTI,l\1;.

DI,l\{)N(ij)SIS

Anoxic encephalopathy • Hypoxic-ischemic encephalopathy, cardiopulmonary arrest

Metabolic

drowning,

encephalopathy

• Uremia, mitochondrial cycle)

disorders (e.g., MELAS, urea

Pressure related edema

• Pulsed Doppler o Brain edema accompanied by t ICP, t pulsatility index, I blood flow velocity within 24 hours ~ poor prognosis o Moving correlation index between mean arterial BP & ICP = PRx(measures cerebral vasomotor reactivity) • PRx < 0.3 = intact reactivity; PRx > 0.3 = impaired reactivity • Disturbed cerebral autoregulation during first 48 hours correlates with poor outcome • Color Doppler: Hyperemia precedes brain edema in some patients

• Posterior reversible encephalopathy syndrome (PRES) o Hypertensive encephalopathy, cyclosporin/FKS06 encephalopathy, L-asparaginase, eclampsia o Predominantly VE in subcortical WM parieto-occipital regions • Venous obstruction with t venous pressure

I P,l\TH(ij)I;.(ij)GY General Features • General path comments

Trauma

2 47

48

o 1 Brain water & astroglial swelling (not reactive astrogliosis) o CTE: Gray matter predominance, intracellular, ADC o VE: White matter, extracellular, 1 ADC o Diffuse brain swelling (DBS) more common in children • 1 Oxidative stress endangers BBB • Sustained posttraumatic cerebral hypoperfusion • Childhood transient 1 NMDA receptor expression may allow 1 intracellular Na++ accumulation in brain cells • Genetics o Differential expression of genes controlling destructive and neuroprotective cascades determine cellular response to injury • Genes govern inflammation, transcription regulation, inflammation, cell adhesion, extracellular matrix • Etiology o Vasogenic edema • 1 BBB permeability • Endothelial tight junctions disrupted ~ leakage of proteins/Na/water ~ fluid shift into extracellular spaces • Primarily WM, myelin (major association bundles, relative sparing of commissural/projection fibers) o Cytotoxic edema • Intracellular (closed barrier) edema • Energy failure ~ loss of Na++/K homeostasis • Intracellular water uptake causes cell swelling, compression of extracellular space o Other brain water disturbances • Hydrocephalic (interstitial) = 1 intraventricular volume/pressure drives CSF through ependymal lining • Hydrostatic (congestive) = 1 intravascular pressure ~ cerebrovascular resistance increase ~ flooding capillary beds • Hypo-osmotic = flooding with IV fluids, inappropriate secretion of antidiuretic hormone, multiple, bilateral lesions in 90% • Epidemiology o 1.5 million traumatic brain injury per year (USA) • Highest incidence < 5 years old

Gross Pathologic & Surgical Features • 1 Brain water, obliteration

Microscopic

o Teens and adults: MVA (especially auto without seat belts, motorcyclists/bicyclists without helmets), assaults o Over 65 years old: Falls

Demographics • Age: DBS more common in children than adults • Gender: Males over-represented 1.6-2:1 • Ethnicity: African-American, Native Americans over -represented

Natural History & Prognosis • Slowly expanding lesions can be accommodated without elevated ICP • Rapid expansion (trauma, rapid tumor growth, abscess) ~ rapid rise of ICP , o Followed by "cascade" of sequelae (e.g., excitotoxin release) ~ cell death • Post-traumatic edema generally resolves within 2 weeks, atrophy (due to cellular death) ensues

Treatment • Goal = maintain cerebral perfusion pressure (CPP) without inducing hydrostatic vasogenic edema o 1 CPP in selected patients with intact cerebral vasomotor reactivity • Osmotherapy, neuroprotective agents, steroids all controversial

Consider • Hypoxia as contributing

factor

Image Interpretation

Pearls

• Image timing crucial: VE (first hours) replaced by CTE

1.

2.

3.

of cisterns/ventricles/sulci

Features

• Extracellular fluid of cortex neuropil ~ swelling & shrinkage of pre-/post-synaptic structures, synaptic disassembly • Effects of hypoxia and cell death

4.

5. 6.

7.

Presentation • Most common signs/symptoms: Altered consciousness, coma • Clinical profile o < 2 years old: Inflicted injury 80% cases

8.

Trauma

Stein SC et al: Association between Intravascular Microthrombosis and Cerebral Ischemia in Traumatic Brain Injury. Neurosurgery. 54(3):687-91, 2004 Cruz J et al: Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial. J Neurosurg. 100:376-83, 2004 Langlois JA et al: Traumatic brain injury-related hospital discharges. Results from 14-state surveillance system, 1997. MMWR Surveill Summ. 52(4):1-20, 2003 Lang EW et al: Cerebral vasomotor reactivity testing in head injury: The link between pressure and flow. J Neurol Neurosurg Psychiatry. 74(8):1053-9, 2003 Field AS et al: Diffusion tensor imaging in an infant with traumatic brain swelling. AJNR. 24(7):1461-4, 2003 Natale JE et al: Gene expression profile changes are commonly modulated across models and species after traumatic brain injury. J Neurotrauma. 20(10):907-27, 2003 Czosnyka M et al: Continuous assessment of cerebral autoregulation - clinical verification of the method in head injured patients. Acta Neurochir Suppl. 76:483-4, 2000 Marmarou A et al: Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients. J Neurosurg. 93(2):183-93, 2000

Typical (Left) Coronal FLAIR MR shows left hemispheric brain swelling in a child with non-accidental head trauma ..•. Note sulcal effacement & diffuse signal loss (arrows) of left hemispheric cortical grey matter. (Right) Follow-up axial NECT shows volume loss of left hemicranium with compensatory enlargement of ventricular system secondary to atrophy of cortex & underlying white matter, particularly posteriorly.

Typical (Left) Sagittal T1WI MR in a child with brain swelling shows herniation of the cerebellar tonsils (arrow). Tonsils are pyramidal shaped, indicative of compression. (Right) Sagittal T2WI MR shows ventricular catheter (curved arrow), abnormal signal in impacted cervicomedullary cord (arrow) & edema of cerebellar tonsils (open arrow) following tonsillar herniation.

Typical (Left) Axial NEeT shows severe midline herniation, obstruction of contralateral and effacement of ipsilateral ventricles, subdural hemorrhage with active bleeding, and diffuse loss of grey white junction. (Right) Sagittal brain scan shows absence of cerebral perfusion in followup of same patient. Study is diagnostic of brain death.

Trauma

2 49

50

Axial T2WI MR shows bilateral PCA and right cerebellar hyperintense infarctions following massive downward transtentorial herniation from a large supratentorial lesion in a trauma patient.

Abbreviations

• "" 55%: Diffuse hypodense cerebral edema with swelling • "" 55%: Hypodense contusion, +/- hyperdense hemorrhagic foci • 50%: Calvarial fractures • "" 20%: Diffuse axonal injury • "" 20%: Epidural hematoma o Secondary infarcts from brain herniation • Downward tentorial herniation - PCA occlusion: If CT evidence of transtentorial herniation incidence of occipital lobe infarction"" 10% • Subfalcine - ACA occlusion • Central - basal perforating vessel occlusions • CT Perfusion o CT perfusion may reveal changes in CBF, CBY, & time to peak enhancement in ischemic territories o Xenon CT perfusion demonstrates abnormalities of cerebral perfusion but requires specialized hardware

and Synonyms

• Traumatic cerebral ischemia (TCI) • Synonym: Post-traumatic cerebral infarction

Definitions • Commonly seen hemodynamic alterations (local, regional, general perfusion disturbances) induced by traumatic brain injury (TBI)

General Features • Best diagnostic clue: Restricted diffusion • Location o Most commonly occur in PCA vascular distribution, o MCA, ACA, vertebrobasilar relatively common o Other: Lenticulostriate, thalamoperforating; cortical/subcortical; cerebellar

MR Findings • TlWI o Acute ischemia: Hypointense o Sagittal best to evaluate for herniation(s) • T2WI: Acute ischemia: Hyperintense • FLAIR: Acute ischemia: Hyperintense • T2* GRE: Best for imaging any hemorrhagic foci • DWI o Restricted diffusion (high signal), I ADC

CT Findings • NECT o Initial presentation NECT findings of TBI patients: • "" 70%: Hyperdense traumatic subarachnoid hemorrhage (tSAH) • "" 60%: Hyperdense subdural hematoma

DDx: Non-traumatic

Nontrauma MCA CVA

Axial T2WI MR shows cortical hyperintensity & swelling of infarction (white arrows) from an overlying subdural hematoma; note intact dura separating hematoma from cortices (black arrows).

Cerebrallschemia/lnfarction

Nontrauma ACA CVA

Vascular Dementia

Trauma

Vascular Dementia

TRAUMATIC CEREBRAL ISCHEMIA Key Facts Terminology • Commonly seen hemodynamic alterations (local, regional, general perfusion disturbances) induced by traumatic brain injury (TBI)

Imaging Findings • Best diagnostic clue: Restricted diffusion • Most commonly occur in PCA vascular distribution, • Midsagittal imaging to evaluate for herniation

Top Differential • Non-traumatic

• • • •

•

• Secondary brain injury occurs after initial trauma, defined as damage to neurons due to systemic physiologic responses to initial injury • Mechanical shift of brain with herniation across falx and/or tentorium .....•80-90% of TCI • Ischemic damage present in 9/10 fatal TBI deaths

2

Clinical Issues

51

• Most common sign: GCS s 8 • No reliable clinical findings indicate presence of traumatic cerebral ischemia • Symptoms often delayed 12-24 hrs to several weeks

Diagnoses

ischemia/infarction

Pathology

Diagnostic Checklist

• Primary brain injury is the result of direct mechanical damage that occurs at time of trauma

• Secondary brain injury can occur after negative primary radiologic evaluation

o Reflects cytotoxic edema of acute ischemia o Shows multifocal areas of ischemia in many cases T1 C+: Subacute ischemia will enhance MRA: Vessel occlusion, regional hypoperfusion MRV: Occlusion, displacement (e.g., from epidural) MRS o TBI: I NAA/Cr & 1 Lactate/Cr ratios; persistent abnormalities prognostic o NAA in white & gray matter is significantly associated with composite neuropsychological function • Early NAA concentrations in gray matter predict overall neuropsychological performance & Glasgow outcome scale • Patients with poorer outcomes have 1 mean gray matter choline 3 months post-injury MR Perfusion o T2* sensitive echo-planar MRI with first-pass gadolinium bolus for rCBV • Shows areas of hypoperfusion • With arterial input can calculate rCBF & MTT

Ultrasonographic

Imaging Recommendations • Best imaging tool: MRI + diffusion • Protocol advice o Diffusion most sensitive sequence for acute ischemia o Midsagittal imaging to evaluate for herniation

I DIFFERENTIAL Non-traumatic

Vascular (multi-infarct)

dementia

• Also focal hypoperfusion & ischemia/infarct • Elderly; atraumatic history

Atherosclerotic

occlusion

• Elderly, typical location (proximal ICA)

Subarachnoid induced vasospasm • Usually in setting of ruptured aneurysm

Findings

I PATf-IOlOG'Y General Features

Findings

• Conventional: DSA may show vasospasm • Interventional therapy of vasospasm o Verapamil: 5-10 mg (1 mg/cc pulsed per territory) o Mechanical angioplasty

Nuclear Medicine

ischemia/infarction

• Appears identical; a traumatic history

• Transcranial Doppler: o Trauma-induced vasospasm: 1 Peak MCA velocity (VMCA) & "hemispheric ratio" (VMCA/VEC-ICA)

Angiographic

DIAGNOSIS

Findings

• SPECT: 99mTc-HMPAO-SPECT is very sensitive for cortical ischemia & demonstrates high sensitivity & specificity within the first 48 hours for infarction • Oxygen-IS PET o Coexistence of ischemia and hyperemia shown in some TEl patients o Implies mismatch of perfusion to oxygen use in TCI o 1 Ischemic brain volume acutely correlates with poor Glasgow outcome score 6 months after injury

• General path comments o Primary brain injury is the result of direct mechanical damage that occurs at time of trauma o Secondary brain injury occurs after initial trauma, defined as damage to neurons due to systemic physiologic responses to initial injury • TCI may be the most common cause of secondary brain injury in the setting of severe TBI o Secondary injuries may be more devastating than those sustained from primary injuries o Most secondary injuries result from i intracranial pressure or cerebral herniations • Etiology o Motor vehicle accidents are the most common cause of closed head injuries & TCI o A variety of mechanisms account for TCI • Direct vascular compression by mass effects

Trauma

52

• Systemic hypo perfusion • Vascular injury, embolization • Cerebral vasospasm from tSAH o Two common mechanisms • Mechanical shift of brain with herniation across falx and/or tentorium ~ 80-90% of TCI • Result of intracranial space-occupying lesion • Epidemiology o TBI is a leading cause of death & disability in children and adults o There are nearly 1.6 million head injuries every year in the US, > 250,000 admitted o Each year there are"" 60,000 US deaths from TBI and another 70-90,000 have permanent neurologic disabilities o TCI occurs in 1.9-10.4% of craniocerebral trauma o Ischemic damage present in 9/10 fatal TBI deaths • Associated abnormalities: Subdural/epidural hematomas, calvarial fractures, contusions, diffuse axonal injury, direct vascular injury

o No reliable clinical findings indicate presence of traumatic cerebral ischemia o Neurological signs from brain injury obscure focal findings that may be from secondary ischemia • Clinical profile o Symptoms often delayed 12-24 hrs to several weeks o Varies greatly with type of injury

Demographics • Age: Children:Adults = 2:1 (15-24 years at highest risk) • Gender: Male:Female = 2: 1 • Ethnicity: Occur with slightly greater frequency among minority groups

Natural History & Prognosis • Poor prognosis: Presence of subdural hematoma, brain swelling/edema, tSAH • Good prognosis: Patients with none or only one of the poor prognostic factors • Outcome: 50% die or left in persistent vegetative state

Treatment

Gross Pathologic & Surgical Features • Profound global or regional cerebral blood flow occur in most patients with Glasgow coma scores (GCS) s 8 • Specific infarctions (in order) o PCA: Compression of PCA against rigid tentorial edge from medial temporal lobe herniation o ACA: Subfalcine herniation of cingulate gyrus compresses one or both ACAs and/or their branches o MCA: Occurs with gross herniation or severe cerebral edema o Lenticulostriate, thalamoperforating: Gross mass effects cause stretching and attenuation of these small perforating vessels o Cortical/subcortical: Direct compression from overlying masses; 2 mechanisms • Direct pressure effects limit arterial flow • Local venous drainage compression occurs • Both often result in hemorrhagic infarcts o Superior cerebellar artery: Ascending or descending transtentorial herniation compresses artery against tentorium o PICA: Compression of artery from tonsillar herniation • In children TBI may have intracranial and systemic effects combined ~ global cerebral ischemia

• Initial care focuses control, treatment • Cerebral perfusion secondary cerebral • Herniation and/or craniectomy

Consider • What is causing the ischemia

Image Interpretation

1.

2.

Features

• Blood-brain barrier disruption with vasogenic edema • Excitatory amino acids induce cellular swelling leading to cytotoxic edema • Intravascular microthrombosis • Over production of free radicals • Inflammation and apoptosis both occur • Auto-protective mechanisms are induced: Production of heat shock proteins, anti-inflammatory cytokines, endogenous antioxidants

Pearls

• Secondary brain injury can occur after negative primary radiologic evaluation

3.

Microscopic

on proper oxygenation, airway of arterial hypotension MUST be monitored to detect ischemia following TBI diffuse swelling may require

4.

5.

6.

7.

Presentation • Most common signs/symptoms o Most common sign: GCS s 8

Trauma

Coles JP et al: Incidence and mechanisms of cerebral ischemia in early clinical head injury. J Cereb Blood Flow Metab. 24(2):202-11, 2004 Huisman TA: Diffusion-weighted imaging: basic concepts and application in cerebral stroke and head trauma. Eur Radiol. 13(10):2283-97, 2003 Abe M et al: Analysis of ischemic brain damage in cases of acute subdural hematomas. Surg Neurol. 59(6):464-72; discussion 472, 2003 Bissonnette B: Cerebral oedema in children compared to cerebral oedema in adults. Ann Fr Anesth Reanim. 22(4):331-5,2003 Leker RR et al: Cerebral ischemia and trauma-different etiologies yet similar mechanisms: neuroprotective opportunities. Brain Res Brain Res Rev. 39(1):55-73, 2002 Server A et al: Post-traumatic cerebral infarction. Neuroimaging findings, etiology and outcome. Acta Radiol. 42(3):254-60, 2001 Brooks WM et al: Metabolic and cognitive response to human traumatic brain injury: a quantitative proton MRS study. J Neurotrauma. 17(8):629-40,2000

Typical (Left) Sagittal TlWI MR demonstrates hypointense PICA infarction secondary to tonsillar herniation. Note low-lying tonsil (open arrow) and flattening of the pons. (Right) Axial FLAIR MR reveals hyperintense PICA infarction secondary to tonsillar herniation.

Typical (Left) Axial NECT shows hypodense right ACA, MCA, PCA infarctions as well as left thalamoperforating ischemia (arrow) from massive traumatic cerebral edema and swelling. Right craniectomy has been performed. (Right) Axial NECT shows right PCA hypodense infarction after traumatic brain injury. Also note intraventricular hemorrhage and multifocal right frontoparietal hemorrhagic contusions.

Typical (Left) Axial NECT reveals bilateral ACA hypodense infarctions (arrows), right> left, with bifrontal hemorrhagic contusions & subarachnoid blood. A ventriculostomy catheter is seen on the right. (Right) Axial OWl MR demonstrates acute infarction of the entire left MCA territory following traumatic left internal carotid vascular injury.

Trauma

53

54

Anteroposterior 99mTc-HMPAO scan shows "hot nose" (arrow), "light bulb" (curved arrows) in brain death. No radionuclide seen in intracranial arteries or veins (Courtesy B. Vomocil, MO).

Abbreviations

o Complete central brain herniation • T2WI: Cortex hyperintense, gyri swollen • DWI o Hemispheric high signal, severe ADC drop o Diffusion anisotropy diminishes between 1-12 hours after BD • MRA: No intracranial flow demonstrated

and Synonyms

• Brain death (BD)

Definitions • Complete,

Lateral OSA of a left common carotid angiogram, late arterial phase, in a patient with clinical brain death shows no flow in supraclinoid (intradural) ICA (arrow), confirming the diagnosis.

irreversible cessation of brain function

Ultrasonographic

General Features • Best diagnostic clue: No flow in intracranial arteries/venous sinuses on Tc99m ECD ("neurolite") • Imaging may confirm but does not substitute for clinical criteria!

CT Findings • NECT o Diffuse cerebral edema (GM/WM borders effaced) • "Reversal sign" (density of cerebellum » hemispheres) o Gyri swollen, ventricles/cisterns compressed • CECT: No enhancement of intracranial arteries, veins • CTA: No intravascular enhancement

MR Findings • TlWI o Hypointense,

GM/WM differentiation

lost

Findings

• Orbital Doppler o Absence/reversal of end-diastolic flow in ophthalmic, central retinal arteries o Markedly increased arterial resistive indices • Transcranial Doppler o Global circulatory arrest o Oscillating "to and fro" signal o Caution: 20% have ICA flow demonstrated despite cerebral circulatory arrest

Angiographic Findings • Conventional o No intracranial flow o Contrast stasis (ECA fills, supraclinoid

Nuclear Medicine

Findings

• (99m)Tc-Iabelled exametazime scintigraphy o Absent supra-, infratentorial uptake ("light bulb" sign) o Increased extracranial activity ("hot nose" sign)

DDx: Clinical Brain Death Mimics

Near-drowning

ICA doesn't)

Some CBF

Trauma

Cocaine Overdose

BRAIN DEATH Key Facts Terminology

Top Differential

• Complete, irreversible cessation of brain function

• Diffuse cerebral edema from reversible cause (drug OD, status ticus) • Technica (not an issue with current radionuclide studies) • Massive cerebral infarction

2

Clinical Issues

55

Imaging Findings • Ima may confirm but does not substitute for clin teria! • Best imaging tool: EEG + bedside scintigraphy ("neuralite")

Diagnoses

• Remember: BD is primarily clinical diagnosis, legal criteria vary

Other Modality

o Reversible causes of coma must be excluded! • Clinical profile o Clinical diagnosis of BD highly reliable if • Examiners are experienced, use established criteria o Remember: BD is primarily clinical diagnosis, legal criteria vary

Findings

• EEG isoelectric

Imaging Recommendations • Best imaging tool: EEG + bedside scintigraphy ("neuralite")

Natural History & Prognosis

I ~IFFERIEN'J"I,l\L ~1,l\GN@SIS

• Ancillary studies (absent BAERS, "isoelectric" cortical EEG, no intracranial flow on imaging studies) help confirm clinical Dx

Diffuse cerebral edema from reversible cause (drug aD, status epilepticus) • Clinically can mimic BD

I SELEC'J"ED REFERENCES

Technical difficulty (not an issue with current radionuclide studies)

1.

• Missed bolus • Dissection, vasospasm (catheter angiography)

2.

Massive cerebral infarction • "Malignant" MCA infarct can mimic BD

3.

I P,l\'J"H@L@G¥

4.

General Features

5.

• General path comments: BD is anatomically, physiologically complex • Etiology o Severe cell swelling elevates intracranial pressure (ICP) o Markedly elevated ICP decreases cerebral blood flow o If ICP > end-diastolic pressure in cerebral arteries, diastolic reversal occurs o If ICP > systolic pressure, blood flow ceases o Complete and irreversible loss of brain function

6.

Dosemeci L et al: Utility of transcranial doppler ultrasonography for confirmatory diagnosis of brain death: two sides of the coin. Transplantation. 77(1):71-5,2004 Watanabe T et al: Serial evaluation of axonal function in patients with brain death by using anisotropic diffusion-weighted magnetic resonance imaging. J Neurosurg. 100(1):56-60, 2004 Booth CM et al: Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. 291(7):870-9, 2004 Donohoe KJ et al: Procedure guideline for brain death scintigraphy. J Nucl Med. 44(5):846-5 I, 2003 Truog RD et al: Role of brain death and the dead-donor rule in the ethics of organ transplantation. Crit Care Med. 31(9):2391-6,2003 Belber CJ: Brain death documentation: analysis and issues. Neurosurgery. 53(4):1009; author reply 1009, 2003

IIM,l\GE G,l\LlERY

Gross Pathologic & Surgical Features • Markedly swollen brain with severely compressed sulci • Bilateral descending transtentorial herniation o Downwards displacement of diencephalon o "Grooving" of temporal lobes by tentorial incisura

I CUNIC,l\L

ISSUES

Presentation • Most common signs/symptoms o Profound coma (GCS = 3) "known cause"

(Left) Axial NECT shows massive left hemisphere infarction and diffuse cerebral swelling in a patient suspected to have clinical brain death (Courtesy H. Yonas, MO). (Right) Axial xenon-CT cerebral blood flow imaging in the same case shows homogeneous low blood flow with values < 6 cel/OOg/min, which is incompatible with life, confirms clinical diagnosis of brain death.

Trauma

56

Frontal projection arterial phase OSA demonstrates a luminal dissection flap throughout the right M 7 segment (arrows).

Axial MRA shows multiple irregularities and narrowing in the left middle cerebral artery (Courtesy E. Grant, MO).

• Hyperintense crescent on axial Tl WI o Complications common • Subarachnoid hemorrhage (SAH) secondary to ruptured dissecting aneurysm • Findings of cerebral ischemia

Definitions • Expanding hematoma cervicocranial trauma

in vessel wall following

CT Findings • NECT o Subarachnoid hemorrhage may be presenting feature in rupture of dissecting aneurysm o Features of ischemia • CTA: Demonstrates vessel contour changes

General Features • Best diagnostic clue o Hyperintense crescent within vessel wall on axial, fat-saturated Tl WI o Tapered stenosis or abrupt occlusion ± intimal flap on angiography • Location o Most common sites • Vertebral arteries most common ~ 72% • Basilar, PICA, SCA, PCA • ACA (A2 segment = t common), MCA • Morphology o Vessel contour changes • Irregular vessel narrowing ± occlusion commonest • Tapered stenosis with occlusion • Fusiform aneurysmal dilatation o Intimal flap • Double lumen o Intramural hematoma

MR Findings • TlWI o Hyperintense crescentic intramural hematoma within vessel wall o Absent or !flow void • FLAIR: Hyperintense signal in CSF with SAH ·MRA o Demonstrates vessel contour changes o "Double lumen" sign ~ source images

Angiographic Findings • Conventional o Vessel contour changes • "String" sign ~ long segment stenosis • Fusiform dilatation o Intimal flap/double lumen specific ~ very rare

DDx: Intracranial Dissection

. ,•. ~

"""lOl

!J.·r·

. .

. ,'-:'.. ~ ~. .

't,

'

VB Atherosclerosis

,-,

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Sickle Cell Disease

Vasospasm

Trauma

Evans Syndrome

TRAUMATIC INTRACRANIAL DISSECTION Key Facts • n sign - long segment stenosis • dilatation • Intimal flap/double lumen specific - very rare • Conventional angiography most sensitive modality

Terminology • Expanding hematoma cervicocranial trauma

in vessel wall following

Imaging Findings • Hyperintense crescent within vessel wall on axial, fat-saturated T1 WI • Tapered stenosis or abrupt occlusion ± intimal flap on angiography • Vertebral arteries most common - 72%

Top Differential Diagnoses • Atherosclerosis • Vasospasm • Vasculitis

• Best imaging tool o Conventional angiography most sensitive modality o MRA less sensitive, but equivalent specificity • Protocol advice o NECT important to exclude subarachnoid hemorrhage o MRI/MRA o Conventional angiography indicated when clinical suspicion is high, but MRI/MRA negative

! DIFFERENTIAL

57

o Acute or delayed (days - months) effects of arterial dissection • Stroke, SAH • Painful CN 3 palsy w/o SAH - dissected PCA, PComA

Imaging Recommendations

Demographics • Age: Mean age: 48 years

Natural History & Prognosis • Spontaneous

improvement

Atherosclerosis • Multiple vessels with irregular stenoses & filling defects in older patients

• • • •

Anticoagulation - prevents progressive thrombosis Endovascular occlusion Angioplasty and stenting - controversial Surgical occlusion/wrapping/bypass

Vasospasm

I SELECTED

• Usually diffuse involving multiple vessels • 1 Severity in region of most SAH

1. 2.

Vasculitis • History/laboratory findings of inflammation, tuberculosis/syphilis • Collagen vascular disorders

3. 4.

I PATHOLOGY General Features • General path comments: Clot between media/adventitia • Etiology o Traumatic event highly variable • Minor forgotten incident - severe closed/penetrating head injury o Intimal tear vs vasa vasorum hemorrhage • Epidemiology: 1.5-10% of SAHs • Associated abnormalities o Fibromuscular dysplasia, arterial fenestrations o Collagen disorders, rheumatoid arthritis o Angiolipomatosis o Alpha-I-antitrypsin deficiency

I CLINICAL

ISSUES

Presentation • Most common

or worsening may occur

Treatment

DIAGNOSIS

signs/symptoms

REFERENCES

Benninger DH et al: Mechanism of ischemic infarct in spontaneous carotid dissection. Stroke. 35(2):482-5, 2004 Mizutani T et al: Healing process for cerebral dissecting aneurysms presenting with subarachnoid hemorrhage. Neurosurgery. 54(2):342-7; discussion 347-8,2004 Anxionnat R et al: Treatment of hemorrhagic intracranial dissections. Neurosurg 53: 289-301, 2003 Ohkuma H et a1. Neuroradiologic and clinical features of arterial dissection of the anterior cerebral artery. AJNR 24: 691-99, 2002

I IMAGE

GALLERY

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••••• , •

)

1/ ....

•

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(Left) Axial TlWI MR shows hyperintense intramural hemorrhage within M7 segment of MCA (arrow) & terminallCA (open arrow) from traumatic intracranial dissection. Also note luminal flow void irregularity. (Right) Collapsed MRA MIP image (in another case) shows complete loss of flow within left petrous & cavernous carotid extending into left MCA from dissection.

Trauma

2

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i

.. ,

58

I

~

• i' ~I

\ ..•

'1

,I

CT angiogram shows marked, tapered narrowing of the internal carotid artery (arrow) secondary to dissection in a patient following a fall from a ladder.

Axial T1WI MR in a patient with traumatic VA dissection shows crescentic hyperintense signal surrounding a narrowed left vertebral artery flow void (arrow) secondary to intramural hematoma .

• Secondary emboli, stroke common

Radiographic Findings

Abbreviations

and Synonyms

• Cervicocephalic

arterial dissection (CAD)

• Radiography: ± Fracture of skull base or cervical spine

CT Findings

Definitions • Post-traumatic hemorrhage within wall of internal carotid artery (lCA) or vertebral artery (VA)

General Features • Best diagnostic clue o Aneurysmal dilatation or tubular narrowing in sites unusual for atherosclerotic disease o Crescentic, hyperintense intramural hematoma within vessel wall on axial T1WI • Location o Between adventitia-media or between media-intima o Traumatic dissection: ICA > VA o ICA dissection: Few cm above carotid bifurcation ending at skull base o VA dissection most common at C1-C2level o 15% multiple vessels • Size: Intramural hematoma propagates variable distances ~ distally> proximally • Morphology: Pseudoaneurysm or long stenosis

• NECT o Usually no abnormality is seen in artery o Occasionally carotid space mass (dissecting aneurysm) o Brain NECT may show arterial territorial low density (post-traumatic infarction) • CECT o ± Linear lucency within enhancing vessel ~ flap separating true & false lumen o Thin rim of contrast-enhancement surrounding mural hematoma • Probably due to enhancement of vasa va sorum

MR Findings • Intramural hematoma o Curvilinear, crescentic, band-like or small focus adjacent to lumen o Usually eccentric (may be circumferential) o Widens external diameter of artery o Surrounds normal/narrow flow void o Signal characteristics • Acute: May be isointense/slightly hyperintense TlWI&T2WI

DDx: Extracranial Arterial Narrowing

Left ICA Slow Flow

ICA & VA FMD

Spont Dissection

Trauma

on

TRAUMATIC EXTRACRANIAL DISSECTION Key Facts Terminology

Top Differential

• Post-traumatic hemorrhage within wall of internal carotid artery (ICA) or vertebral artery (VA)

• • • • •

Imaging Findings • Aneurysmal dilatation or tubular narrowing in sites unusual for atherosclerotic disease • Crescentic, hyperintense intramural hematoma within vessel wall on axial T1 WI • VA dissection most common at C1-C2level • Echogenic intimal flap (most specific sign) • Segmental tapered narrowing by intramural hematoma - "string" sign • Segmental dilatation of vessel - pseudoaneurysm • Intimal flaps are rarely seen on catheter angiography • Double lumen (specific, but rare) - true lumen & intramural dissection

59

• Intimal disruption or vasa vasorum hemorrhage • CAD = common cause of stroke < 40 Y • Asymptomatic dissection of second artery (20%)

Clinical Issues • Unrelenting headache or neckache in young/middle-aged adults

Imaging Recommendations • Best imaging tool: MRA of both head & neck, with overlapping imaging volumes • Protocol advice o MR (fat-suppressed T1WI), MRA o DSA if MR/MRA negative

I DIFFERENl'lAI. ProximallCA

Findings

• • • • •

Echogenic intimal flap (most specific sign) Echogenic thrombus Abrupt smooth tapering of arterial lumen False lumen occasionally seen with color Doppler VA dissection: ± t Contralateral VA blood flow velocities • !Carotid bulb velocities (t resistance/biphasic pattern) or t velocities

Angiographic

2

Pathology

• Subacute: Initially becomes hyperintense on T1WI, later on T2WI • Chronic: Remains hyperintense for months • Intimal flap o Thin curvilinear hypointense partition separating true & false lumen • Residual lumen o Eccentrically narrowed o May have absent/diminished "flow void" o Slow flow may cause loss of flow void

Ultrasonographic

Diagnoses

Proximal ICA stenosis "Spontaneous" dissection Arterial thrombosis Atherosclerosis Vasospasm

Findings

• DSA/CTA/MRA o Segmental tapered narrowing by intramural hematoma - "string" sign o Segmental dilatation of vessel - pseudoaneurysm • Oval, parallel to artery, variable size • May have extraluminal pouch • Pearl & string sign (common) - distal margin of stenotic region • Small pouch in midportion of stenotic region o ± Intimal flap at proximal margin of dissection • Intimal flaps are rarely seen on catheter angiography o Double lumen (specific, but rare) - true lumen & intramural dissection o True lumen may completely occlude o Slow arterial filling in parent artery o Distal branch occlusions due to embolization o CTA: Independent of flow phenomena • Shows even small residual lumen & pseudo aneurysms causing slow or turbulent flow

DIA~N(i)SIS

stenosis

• Severe extracranial arterial stenosis =} slow flow in intracranial segment, simulating an intracranial dissection ("pseudodissection") o Can produce periarterial rim of abnormal signal that is not due to hematoma o T1WI isointense, T2WI hyperintense

"Spontaneous" dissection • Underlying vasculopathy common o Fibromuscular dysplasia • "String of beads" appearance> long tubular stenosis o Marfan syndrome, type IV Ehlers-Danlos syndrome • Familial ICA dissection may occur • Hypertension in 1/3 of patients • Differentiate from delayed presentation (> 1 y) of undiagnosed blunt artery injury (occult CAD)

Arterial thrombosis • Often difficult to establish whether underlying dissection is present

Atherosclerosis • Typically occurs at carotid bifurcation • Irregular> smooth tapered narrowing • Ca++ often present

or VA origin

Vasospasm • Can be seen at catheter angiography due to catheter placement • Typically lasts a few minutes, unlike dissection

Trauma

General Features

60

• General path comments o Intimal disruption or vasa vasorum hemorrhage o False lumen => luminal stenosis ± occlusion, pseudo aneurysm, thrombosis & embolism • Etiology o Penetrating injury (gunshot wound or stabbing) => may injure common carotid, ICA or VA o Blunt trauma => extracranial ICA affected • Usually sustained in motor vehicle accidents (high acceleration/hyperextension => whiplash injury) • Falls, strangulation, blows to neck area, digital carotid compression, iatrogenic (VAdissection in 5% facet joint surgeries) • Chiropractic manipulation (stretching/torsion) affects VA> ICA o Potential mechanisms of injury • Most common: Sudden, severe stretch of artery over upper cervical spine in hyperextension & lateral flexion to opposite side • Stretching of ICA over transverse processes of upper cervical vertebrae • Compression of ICA between angle of mandible & upper cervical vertebral bodies • Injury of ICA by prominent styloid process • Stretching of VA over C1-C2 vertebral bodies, primarily during head rotation o Combination of head, facial & cervical injuries • Epidemiology o Incidence of ICA dissection in blunt trauma patients = 0.08-0.4% o CAD accounts for 0.4-2.5% of all strokes o CAD = common cause of stroke < 40 Y • 20% of strokes in young patients • Associated abnormalities o Asymptomatic dissection of second artery (20%) • Usually accompanies symptomatic VAdissection o Severe trauma to cervical spine o Patients evaluated for blunt aortic trauma are lOx more likely to have blunt carotid injury

o Carotid bruits, pulsatile tinnitus • Clinical profile o Unrelenting headache or neckache in young/middle-aged adults

Demographics • Age o Spontaneous dissection => 70% between 35-50 y o Average age => 42-45 Y o Uncommon in children, adolescents (7% of cases) • Gender o ICA dissection (all causes) => M:F = 1.5:1 o VA dissection (all causes) => M:F = 1:3

Natural History & Prognosis • Delayed diagnosis of blunt carotid injury common • Traumatic CAD versus spontaneous CAD o Traumatic CAD less likely to spontaneously improve o Traumatic CAD more likely to lead to residual neurological deficits • > 2/3 of patients have complete recovery

Treatment • Anticoagulation with Heparin followed by Coumadin • Surgical intervention (balloon dilatation & stenting)

Consider • Early screening through MRI/MRA of severely injured patients => detection of occult CAD • Consider CAD in any young/middle aged patient with stroke/unrelenting headache or neckache

Image Interpretation

1.

2.

Gross Pathologic & Surgical Features • Hemorrhage between intima-media => luminal stenosis • Hemorrhage between adventitia-media => pseudoaneurysm formation

3. 4.

5.

Presentation • Most common signs/symptoms o Headache, neck pain • 60-90% of patients with cervical ICA dissection • Onset a few hours up to 3-4 weeks o Focal cerebral ischemic symptoms (TIA, stroke) • Often delayed (hours-years post-injury) o Horner syndrome • Injury of sympathetic nerves adjacent to ICA • May be incomplete (only miosis, ptosis) • Uncommon o Cranial nerve palsy (CN 12> 9, 10, 11)

Pearls

• Differentiate intramural hematoma from flow artifact from more proximal atherosclerotic narrowing

6.

7.

Trauma

Mizutani T et al: Healing process for cerebral dissecting aneurysms presenting with subarachnoid hemorrhage. Neurosurgery. 54(2):342-7; discussion 347-8, 2004 Benninger DH et al: Mechanism of ischemic infarct in spontaneous carotid dissection. Stroke. 35(2):482-5, 2004 Hughes KM et al: Traumatic carotid artery dissection: a significant incidental finding. Am Surg 66:1023-1027, 2000 Oelerich M et al: Craniocervical artery dissection: MR imaging and MR angiographic findings. Eur Radiol 9:1385-1391, 1999 Provenzale]M et al: Spontaneous vertebral dissection: clinical, conventional angiographic, CT and MR findings. ]CAT 20:185-193, 1996 Provenzale ]M: Dissection of the internal carotid and vertebral arteries: Imaging features. A]R 165:1099-1104, 1995 Heinz ER et al: Significant extracranial carotid stenosis: detection on routine cerebral MR images. Radiology 170:843-848, 1989

Typical (Left) CT angiogram shows marked narrowing of the left vertebral artery in a patient with acute neck pain after weight lifting. (Right) Axial T1 WI MR with fat-saturation in the same patient shows crescentic hyperintense signal adjacent to a narrowed left vertebral artery flow void (arrow), consistent with dissection.

Typical (Left) Catheter angiogram shows long region of narrowing (arrows) in high cervical portion of ICA, consistent with dissection. Atherosclerotic narrowing is unlikely because lesion is distal to bifurcation. (Right) Catheter angiogram of high cervical segment of internal carotid artery in a different patient shows a pseudoaneurysm (arrow) indicative of dissection.

Typical (Left) Catheter angiogram of high cervical segment of internal carotid artery shows occlusion (arrow) a few centimeters above the carotid bifurcation, indicative of dissection. (Right) Axial TOF MRA image in a different patient shows intramural hematoma (arrow) adjacent to a narrowed right ICA lumen (compare to left ICA) indicating dissection of the right ICA.

Trauma

61

TRAUMATIC CAROTID-CAVERNOUS

FISTULA

62

Axial MIP MRA shows flow-related enhancement in left cavernous sinus (arrow) & flow in left superior ophthalmic vein (open arrow).

Lateral selective ICA conventional angiogram shows contrast immediately filling the cavernous sinus and draining via a very large superior ophthalmic vein (arrow).

o Adjacent or diffuse dural enhancement

·MRA Abbreviations

o i Flow-related signal in CS o i Flow void (due to i turbulence) in CS o Flow in SOY and/or transellar collaterals

and Synonyms

• Carotid-cavernous Fistula (CCF), direct CCF, high-velocity CCF

Ultrasonographic

Definitions

Findings

• Doppler shows reversal of flow direction in SOY (P ~ A)

• High flow fistula between cavernous internal carotid artery (lCA) & cavernous sinus (CS)

Angiographic Findings • Conventional o Very rapid filling of enlarged CS after ICA injection o Common drainage pathway ~ SOY & IOV ~ facial vein o Other drainage pathways • Superior & inferior petrosal sinuses ~ internal jugular vein • Opposite CS via trans sellar or basilar plexus • Vein of Rosenthal ~ vein of Galen o Signs of danger: Filling of cortical veins, pseudoaneurysm, CS varices, thrombosis/obstruction of venous drainage

General Features • Best diagnostic clue: Proptosis, large superior ophthalmic vein (SOV) & CS

CT Findings • NECT o Proptosis, orbital edema, enlarged extra-ocular muscles o SAH secondary to reflux to cortical veins ~ rupture • CECT: Prominent SOY & CS ~ may be bilateral • CT Perfusion

Imaging Recommendations • Best imaging tool: Catheter angiography • Protocol advice o Rapid filming ~ to identify site of ICA tear

MR Findings • T1WI: Large CS with multiple flow voids • Tl C+ o Enlarged, enhancing CS & SOY

DDx: Enlarged Extraocular Muscles

Grave's Disease

Pseudotumor

Pseudotumor

Trauma

Metastasis

TRAUMATIC CAROTID-CAVERNOUS

FISTULA

Key Facts Terminology • Carotid-cavernous Fistula (CCF), direct CCF, high-velocity CCF • High flow fistula between cavernous internal carotid artery (ICA) & cavernous sinus (CS)

Imaging Findings • Best diagnostic clue: Proptosis, large superior ophthalmic vein (SOV) & CS

o Injection of a vertebral artery with compression involved ICA ....•to identify tear

• Skull base fracture commonest

o Severe/rapid vision loss, SAH ....•emergency o Focal deficits ....•CN 3-6 o Findings usually unilateral but may be bilateral

of

Demographics • Age: Average = 37 years • Gender: Male

of SOY

• CS thrombosis - no fistula on angiography • Grave's disease ....•signs of hyperthyroidism • Masses in orbital apex

Natural History & Prognosis • Spontaneous

thrombosis

is rare; progresses if untreated

Treatment

Enlargement of extraocular muscles

• ICA/jugular vein compression - only for small CCF • Embolization: Transarterial or transvenous o Liquid adhesive, particles, coils, balloon, stents • Surgery - last resort, gamma knife (?)

• Grave's & inflammatory pseudotumor • Intra-muscular masses (metastases)

IPATHOLOGM

I DIAGNOSTIC

General Features • General path comments o Blood from cavernous ICA to CS - SOY & petrosal sinuses o Reflux into cerebral cortical veins occurs when SOY/IOV & petrosal sinus cannot handle large blood volume ....•increased risk SAH • Etiology o Skull base fracture commonest o Ruptured cavernous ICA aneurysm • Epidemiology o Younger individuals (prone to trauma) o t Incidence in collagen-vascular disorders

CHECKLIST

Image Interpretation

Pearls

• Enlarged cavernous sinus and SOY ....•consider CCF

I SELECTED REFERENCES 1.

2.

Fattahi TT et al: Traumatic carotid-cavernous fistula: pathophysiology and treatment. J Craniofac Surg 14: 240-46,2003 Chuman H et al: Spontaneous direct carotid-cavernous fistula in Ehler-Danlos syndrome type IV: two case reports and a review of the literature. J Neuroophthalmol 22: 75-81,2002

Gross Pathologic & Surgical Features • Most tears involve proximal horizontal cavernous ICA

or vertical

I IMAGE

GALLERM

Staging, Grading or Classification Criteria • Classification o Type A: Direct communication between ICA & CS o Types B-D: Indirect communications between meningeal branches of ICA and CS ....•trauma?

I CLINICAL ISSUES Presentation • Most common signs/symptoms o Symptoms may develop spontaneously (ruptured aneurysm) or days-weeks after trauma o Bruit (50%), pulsating exophthalmos, orbital edema/erythema, I vision, glaucoma, headache

(Left) Axial CECT shows marked right proptosis, enlarged superior ophthalmic vein (arrow) and swelling of eyelids. (Right) Axial TlWI MR shows dilated left cavernous sinus (arrow) containing multiple flow voids.

Trauma

2 63

Pathology

I DIFFERENTIAL DIAGNOSIS Causes of enlargement

• Proptosis, orbital edema, enlarged extra-ocular muscles • Prominent SOY & CS ....•may be bilateral • Very rapid filling of enlarged CS after ICA injection • Signs of danger: Filling of cortical veins, pseudoaneurysm, CS varices, thrombosis/obstruction of venous drainage

PART I SECTION 3 Subarachnoid Hemorrhase and Aneurysms Subarachnoid hemorrhage (SAH) causes approximately SOlo of all "strokes." The most common cause of nontraumatic SAH is ruptured intracranial aneurysm. A relatively uncommon but important cause of non traumatic SAH is the entity known as nonaneurysmal peri mesencephalic subarachnoid hemorrhage (pnSAH). Both types of SAH are discussed in this section. We also discuss the pathology, clinical presentation and imaging appearance of chronic SAH, usually seen as superficial siderosis. Intracranial aneurysms are generally classified according to phenotype (gross pathologic appearance). Three general categories are recognized: (1) saccular aneurysms (also known as "berry" aneurysm; (2) fusiform aneurysms; and (3) the rare, recently-described "blood blister-like" aneurysms. Saccular aneurysms are round or lobulated focal outpouchings that typically arise from areas of high hemodynamic stress, namely major vessel bifurcations. Fusiform aneurysms are long-segment vessel elongations that can be associated either with atherosclerotic vascular disease (ASVD) or non-atherosclerotic pathology such as connective tissue disorders like Type IV Ehlers-Danlos syndrome. All true intracranial aneurysms lack one or more layers of normal arterial wall, usually the internal elastic lamina and a thinned or absent muscularis. Intracranial pseudoaneurysms lack all vessel wall layers and are typically a cavitated paravascular hematoma that mayor may not communicate directly with the true arterial lumen. The wall of the rare but dangerous "blood blister-like" aneurysm is tissue-paper thin, with sometimes only a thin layer of translucent fibrous connective tissue covering the broad-based arterial defect. This entity, now well-known to neurosurgeons but rarely discussed in the imaging literature, is often subtle on, and underdiagnosed at, cerebral angiography.

SECTION 3: Subarachnoid Hemorrhage and Aneurysms I

Subarachnoid Hemorrhage Aneurysmal Subarachnoid Hemorrhage Nonaneurysmal Perimesencephalic SAH Superficial Siderosis

1-3-4 1-3-6 1-3-8

Aneurysms Saccular Aneurysm Pseudoaneurysm Fusiform Aneurysm, ASVD Fusiform Aneurysm, Non-ASVD Blood Blister-like Aneurysm

1-3-12 1-3-16 1-3-18 1-3-20 1-3-22

ANEURYSMAL SUBARACHNOID

HEMORRHAGE

3 4 Axial graphic shows classic aSAH from rupture of a saccular aneurysm on the circle of Willis. Blood fills suprasellar, sylvian, interhemispheric cisterns.

ITERMINOlOGY Abbreviations • Aneurysmal

Angiographic Findings

and Synonyms

subarachnoid

Axial NEeT shows acute aSAH, seen as high density filling the suprasellar cistern and sylvian fissures (arrows). Note early hydrocephalus.

hemorrhage

(aSAH)

Definitions • SAH caused by rupture of intracranial

aneurysm

IIMAGING FINDINGS General Features • Best diagnostic clue: Hyperdense CSF on NECT • Location: Interhemispheric SAH suggests ACoA aneurysm, sylvian correlates with MCA

CT Findings • NECT: 95% positive in first 24 h, < 50% by 1 week • CTA: Multislice CTA 90-95% + for aneurysm ~ 2 mm

MR Findings • • • •

T1WI: "Dirty" CSF (isointense to brain) T2WI: Hyperintense CSF FLAIR: Hyperintense (not pathognomonic for SAH!) T2* GRE: Hypointense hemosiderin deposition in 70-75% of patients with prior SAH • DWI: May show multifocal restrictions • MRA: 85-95% sensitive

• Conventional o Negative in 15-20% of aSAHi repeat positive < 5% o Considered "gold standard"

Imaging Recommendations • Best imaging tool: NECT + multi slice CTA • Protocol advice: Thin slices, low pitch, arterial phase only

I DIFFERENTIAL Nonaneurysmal

DIAGNOSIS SAH

• Occult trauma, dissection • Perimesencephalic nonaneurysmal SAH • Vascular malformation, neoplasm (e.g., ependymoma)

"PseudoSAH" • Low density brain (e.g., with diffuse cerebral edema) • High density CSF (e.g., following intrathecal contrast)

NonSAH causes of high CSF signal on FLAIR • Meningitis (inflammatory, neoplastic) • High oxygen tension or gadolinium in CSF

DDx: Acute Aneurysmal SAH

Subarachnoid Hemorrhage and Aneurysms

ANEURYSMAL

SUBARACHNOID

HEMORRHAGE

Key Facts • NonSAH causes of high CSF signal on FLAIR

Imaging Findings • Best diagnostic clue: Hyperdense CSF on NECT • Location: Interhemispheric SAH suggests ACoA aneurysm, sylvian correlates with MCA • FLAIR: Hyperintense (not pathognomonic for SAH!) • Best imaging tool: NECT + multi slice CTA

Top Differential • Nonaneurysmal • "PseudoSAH"

Diagnoses

Pathology • Most common cause of SAH is trauma (not aneurysm rupture) • aSAH causes 5% of "strokes" • 85% of non traumatic SAH caused by ruptured aneurysm

SAH

o Severity related to volume, duration of perivascular clotting in subarachnoid space o 70-90% prevalence in first 2 weeks • Caused by prostacyclin release, decreased iNO • Onset 3-5 days after aSAH, maximal at 5-8 days

I PATHOLOGY General Features • Etiology o Most common cause of SAH is trauma (not aneurysm rupture) o Both saccular, dissecting intracranial aneurysms can cause aSAH o Increased risk with smoking, family history of aSAH • Epidemiology o aSAH causes 5% of "strokes" o 85% of non traumatic SAH caused by ruptured aneurysm

Treatment • Locate, clip/coil ruptured aneurysm • Prevent/treat vasospasm o Hypertensive hypervolemic therapy + nimodipine o Endovascular (balloon angioplasty) o Intrathecal urokinase

Gross Pathologic & Surgical Features

I DIAGNOSTIC

• Clotted blood in basal cisterns

Consider

Microscopic

• Nonaneurysmal SAH (pnSAH, tSAH) or "pseudoSAH" (low density brain)

Features

• Early: Arterial smooth muscle contraction, vasoconstriction • Late: Smooth muscle necrosis, endothelial desquamation, apoptosis

CHECKLIST

Image Interpretation

Pearls

• High CSF signal on FLAIR has many causes besides SAH (high protein, oxygen, artifact, etc)

Staging, Grading or Classification Criteria • Clinical: Hunt and Hess grade o 0 = unruptured aneurysm o 1 = asymptomatic or minimal HA, nuchal rigidity o 2 = moderate HA, no deficit other than CN palsy o 3 = drowsy, mild focal deficit o 4 = stuporous, hemiparesis, early decerebrate o 5 = deep coma, moribund • New grading systems correlate outcome

I SELECTED 1.

I

REFERENCES

Hasen-Schwartz]: Receptor changes in cerebral arteries after subarachnoid hemorrhage. Acta Neruol Scand 109:33-44, 2004

IMAGE GALLERY

I CLINICAL ISSUES Presentation • Most common signs/symptoms: Sudden severe ("thunderclap") headache • Clinical profile: Middle-aged patient with "worst headache of my life"

Demographics • Age: Peak = 40-60 y; 30% of women> • Gender: F > M

70 y

Natural History & Prognosis • 50% mortality, 15% rebleed within first 24 h o Hemodynamic, metabolic disturbances common 24-48 h after aSAH • Vasospasm + ischemia = delayed morbidity, mortality

(Left) Axial TlWI MR shows no obvious abnormality in this patient

with "thunderclap" headache and lumbar puncture that showed mildly bloody CSF. (Right) Axial FLAIR MR in the same case shows widespread high signal intensity within the cerebral sulci caused by aSAH.

Subarachnoid Hemorrhage and Aneurysms

3 5

NONANEURYSMAL

PERIMESENCEPHALIC

SAH

3 6 Axial graphic shows classic pnSAH. Hemorrhage is confined to the interpeduncular fossa and ambient (perimensencephalic) cisterns (arrows). Source is usually venous. Contrast with aSAH.

o No extension into distal sylvian, interhemispheric fissures o "Quadrigeminal variant" occurs without pretruncal blood • CTA: Posterior circulation aneurysm in 5-10%

ITERMINOLOGY Abbreviations

and Synonyms

• Perimesencephalic

nonaneurysmal

Axial NECT shows high density hemorrhage in the interpeduncular fossa extending into the left ambient cistern (arrow). The suprasellar cistern and sylvian fissures are normal.

SAH (pnSAH)

Definitions

MR Findings

• Clinically benign entity with SAH confined to perimesencephalic, prepontine cisterns • No identifiable source demonstrated at angiography

• • • •

T1WI: "Dirty" CSF (iso-, not hypo intense) T2WI: Acute pnSAH hyperintense (difficult to see) FLAIR: Hyperintense CSF in/around pons, midbrain T2* GRE: Hypointense

IIMAGING FINDINGS

Angiographic Findings

General Features

• Conventional o Considered "gold standard" o Saccular or blister-like aneurysm identified as cause of pnSAH in 5-10% o Vasospasm, hydrocephalus rare « < aSAH)

• Best diagnostic clue: Hyperdense prepontine, perimesencephalic CSF • Location: "Pretruncal" (anterior to pous, around midbrain) • CTA/MRA/DSA o Angiography negative in 90-95% of pnSAH o 5-10% prevalence of vertebrobasilar aneurysm in pnSAH

Imaging Recommendations • Best imaging tool: NECT scan = best screening for pnSAH • Protocol advice: If NECT scan positive, CTA +/- DSA

CT Findings • NECT o High attenuation cisterns

anterior to midbrain, in ambient

aSAH

rSAH

Subarachnoid Hemorrhage and Aneurysms

NONANEURYSMAL

PERIMESENCEPHALIC

SAH

Key Facts Terminology

Top Differential

• Clinically benign entity with SAH confined to perimesencephalic, prepontine cisterns

• • • •

Imaging Findings • Best diagnostic clue: Hyperdense prepontine, peri mesencephalic CSF • T1WI: "Dirty" CSF (iso-, not hypointense)

I DIFFERENTIAL DIAGNOSIS • More extensive hemorrhage (suprasellar cistern, sylvian/interhemispheric fissures) • 17% of posterior circular aneurysms initially have pnSAH pattern

Traumatic SAH (tSAH) pretruncal

• Gender: M

=

vein

3

F

7

• Generally benign clinical course (no vasospasm) • Rebleed rate < 1%

Treatment • No further treatment aneurysm excluded

once posterior circulation

pattern

I DIAGNOSTIC CHECKLIST

Meningitis • May cause hyperintense

CSF on FLAIR

Artifact

Consider • Occult trauma, vertebral dissection may cause SAH

• Incomplete CSF suppression CSF signal on FLAIR • > 50% oxygen concentration hyperintensity on FLAIR

I

Pathology • Most likely cause = ruptured perimesencephalic/prepontine

Natural History & Prognosis

Aneurysmal SAH (aSAH)

• Perisylvian, convexity>

Diagnoses

Aneurysmal SAH (aSAH) Traumatic SAH (tSAH) Meningitis Artifact

may cause spurious high causes CSF

Image Interpretation

I SELECTED

PATHOLOGY

1.

General Features • General path comments: Except for location, general appearance similar to aSAH • Etiology o Most likely cause = ruptured perimesencephalic/prepontine vein o Saccular or blister-like posterior circulation aneurysm in 5-10% of cases • Epidemiology o SAH causes 2-4% of "strokes" o pnSAH accounts for 20-70% of angiogram-negative aSAH

Pearls

• No NECT pattern absolutely differentiates pnSAH

aSAH,

REFERENCES

Matsumaru Y et al: Significance of a small bulge on the basilar artery in patients with perimesencephalic nonaneurysmal subarachnoid hemorrhage. Report of two cases. J Neurosurg. 98(2):426-9, 2003

I IMAGE GAllERY

[

.

,

Gross Pathologic & Surgical Features • Clotted blood in peri mesencephalic

Microscopic

cisterns

Features

~,

• Usually normal

I/

(Left) Axial NECT shows variant pnSAH. Hemorrhage extends from

I CLINICAL ISSUES Presentation • Most common signs/symptoms: Hunt/Hess grade 1 or 2)

Headache (usually

Demographics • Age: Mean age at presentation

....

=

interpeduncular/ambient cisterns into proximal sylvian fissures but does not completely fill suprasellar cistern or interhemispheric fissure. (Right) Axial TlWI MR shows "dirty" CSF in angio-negative pnSAH. Note interpeduncular, ambient cisterns (usually contain hypointense CSF) are filled with acute hemorrhage that appears isointense to brain.

55 Y

Subarachnoid Hemorrhage and Aneurysms

SUPERFICIAL

SIDEROSIS

3 8 Axial graphic shows darker brown hemosiderin staining on all surfaces of the brain, meninges and cranial nerves. Notice cranial nerves 7th & 8th in the CPA-lAC are particularly effected.

ITERMINOLOGY Abbreviations and Synonyms • Synonyms: Central nervous system siderosis, siderosis

Definitions • Recurrent subarachnoid hemorrhage (SAH) causes hemosiderin deposition on surface of brain, brain stem & cranial nerve leptomeninges

IIMAGING FINDINGS General Features • Best diagnostic clue: Contours of brain & cranial nerves outlined by hypointense rim on T2 or T2* GRE MRimages • Location: Cerebral hemispheres, cerebellum, brainstem, cranial nerves & spinal cord may all be affected • Size: Linear low signal along CNS surfaces varies in thickness but usually ::::;2 mm • Morphology: Curvilinear dark lines on CNS surfaces

CT Findings • NECT o Cerebral & cerebellar atrophy o Brain atrophy only

Axial T2* eRE MR reveals superficial siderosis as dark hemosiderin staining in folia of cerebellum (arrows). In addition, the 7th & 8th cranial nerves in the CPA-lAC are black (open arrows).

o Especially marked in posterior fossa • Cerebellar sulci often disproportionately large o Slightly hyperdense rim over brain surface • Relatively insensitive to presence of hemosiderin on CNS surfaces • CECT: No enhancement typical

MR Findings • T1WI: Hyperintense signal may be seen on CNS surfaces • T2WI o High-resolution, thin section T2 MR of CPA-lAC • Cranial nerves 7 & 8 appear darker & thicker than normal • Adjacent cerebellar structures & brain stem show low signal surfaces • Less easily seen than on T2* GRE images • FLAIR: Dark border on local surface of brain, brain stem, cerebellum & cranial nerves • T2* GRE o Most sensitive to hemosiderin deposition on CNS surfaces o "Blooms" dark signal; makes it appear more conspicuous, thicker • Tl C+: Surface of CNS does not enhance • MR findings do not correlate with severity of disease

Imaging Recommendations • Best imaging tool

DDx: low Signal on Brain Surface ~.~

I

Superficial Vein

NeuroC Melanosis

.

LJ MA

Subarachnoid Hemorrhage and Aneurysms

SUPERFICIAL SIDEROSIS Key Facts • Meningioangiomatosis

Terminology • Synonyms: Central nervous system siderosis, siderosis • Recurrent subarachnoid hemorrhage (SAH) causes hemosiderin deposition on surface of brain, brain stem & cranial nerve leptomeninges

Imaging Findings • Best diagnostic clue: Contours of brain & cranial nerves outlined by hypo in tense rim on T2 or T2* GRE MR images • Location: Cerebral hemispheres, cerebellum, brainstem, cranial nerves & spinal cord may all be affected

Top Differential

Diagnoses

• MR sequence artifact • Neurocutaneous melanosis

o Brain MR • Once diagnosis of superficial siderosis is made, search for cause of recurrent SAH must commence • Whole brain MR with contrast & MRA first • Total spine MR second if brain negative for underlying lesion • Protocol advice o Brain MR • Unenhanced MR with FLAIR initially • If suspect superficial siderosis, add T2* GRE sequences to confirm

I DIFFERENTIAL DIAGNOSIS MR sequence artifact • Variably thick & prominent low signal on surface of brain • Imaging clue is not present on all sequences

Brain surface vessels • Normal or abnormal surface veins • Linear, focal area of low signal on surface of brain

Neurocutaneous

melanosis

• Congenital syndrome • Large or multiple congenital melanocytic nevi • Benign or malignant pigment cell tumors of the leptomeninges may be low signal on surface of brain • T1 high signal diffusely in pia-arachnoid • T2 low signal diffusely in pia-arachnoid

Meningioangiomatosis

(MA)

• Hamartomatous proliferation of meningeal cells via intraparenchymal blood vessels into cerebral cortex • Leptomeninges are thick & infiltrated with fibrous tissue, may be calcified

I

PATHOLOGY

General Features • General path comments

(MA)

Pathology • Repeated SAH deposits hemosiderin on meningeal lining of CNS • Hemosiderin is cytotoxic to neurons • Causes of recurrent SAH found in - 50% • CSF cavity lesion (surgical cavity) with fragile neovascularity most common • Bleeding neoplasms (35%) • Vascular abnormalities (18%)

Clinical Issues • Classic presentation is adult patient with bilateral SNHL & ataxia • Pre-symptomatic phase averages 15 years • Treat source of bleeding

o Hemosiderin staining of meninges • Hemosiderin is cytotoxic to underlying tissues o Xanthochromic CSF • Etiology o Repeated SAH deposits hemosiderin on meningeal lining of CNS • Affects brain, brain stem, cerebellum, cranial nerves & spinal cord o Hemosiderin is cytotoxic to neurons • "Free" iron with excess production of hydroxyl radicals is best current hypothesis explaining cytotoxicity o CN 8 is extensively lined with CNS myelin which is supported by hemosiderin-sensitive microglia • Increased exposure in CPA cistern • Epidemiology o Rare chronic progressive disorder o 0.15% of patients undergoing MR imaging • Associated abnormalities o Causes of recurrent SAH pathologies include • Traumatic nerve root avulsion, bleeding CNS neoplasm, vascular malformations & aneurysms

Gross Pathologic & Surgical Features • Dark brown discoloration of leptomeninges, ependyma & subpial tissue • Causes of recurrent SAH found in - 50% o Dural pathology (47%) • CSF cavity lesion (surgical cavity) with fragile neovascularity most common • Traumatic cervical nerve root avulsion o Bleeding neoplasms (35%) • Ependymoma, oligodendroglioma & astrocytoma o Vascular abnormalities (18%) • Arteriovenous malformation (AVM) or aneurysm • Multiple cavernous malformations near brain surface o Idiopathic (46%)

Microscopic Features • Hemosiderin staining of meninges and subpial tissues to 3 mm depth • Thickened leptomeninges

Subarachnoid Hemorrhage and Aneurysms

3 9

SUPERFICIAL SIDEROSIS • Cerebellar folia: Loss of Purkinje cells and Bergmann gliosis

I SELECTED REFERENCES 1.

I CLINICAL ISSUES

2.

Presentation

3 10

• Most common signs/symptoms: Bilateral sensorineural hearing loss (SNHL) present in 95% of cases • Clinical profile o Classic presentation is adult patient with bilateral SNHL & ataxia o Seen less commonly as late complication of treated childhood cerebellar tumor • Laboratory o CSF from lumbar puncture • High protein (100%) • Xanthochromic (75%) • Other symptoms o Ataxia (88%) o Bilateral hemiparesis o Hyperreflexia, bladder disturbance, anosmia, dementia & headache • Anosmia: Olfactory nerve particularly sensitive to hemosiderin deposition o Pre-symptomatic phase averages 15 years

Demographics

3.

4.

5.

6.

7.

8.

9.

10.

• Age: Broad age range: 14-77 years • Gender: M:F ratio = 3:1 11.

Natural History & Prognosis • Profound bilateral SNHL & ataxia within 15 years of onset • Deafness almost certain if unrecognized • 25% become bed-bound in years following 1st symptom o Result of cerebellar ataxia, myelopathic syndrome or both

12.

13.

Treatment • Treat source of bleeding • Surgically remove source of bleeding (surgical cavity, tumor) • Endovascular therapy for AVM & aneurysm • Cochlear implantation for SNHL

14.

15.

16.

I

DIAGNOSTIC

CHECKLIST 17.

Consider • Remember that cause • Look for source or brain • MR findings do severity o MR diagnosis

superficial siderosis is an effect, not a 18.

of recurrent SAH somewhere in spine not correlate with patient's symptom

19.

Spengos K et al: Superficial siderosis of the brain as a late complication of subarachnoid hemorrhage. Cerebrovasc Dis 17:87, 2004 Leussink VI et al: Superficial siderosis of the central nervous system: pathogenetic heterogeneity and therapeutic approaches. Acta Neurol Scand 107(1):54-61, 2003 Kale SU et al: Superficial siderosis of the meninges and its otolaryngologic connection: a series of five patients. Otol Neurotol 24(1):90-5, 2003 Dhooge 1] et al: Cochlear implantation in a patient with superficial siderosis of the central nervous system. Otol Neuroto123(4):468-72,2002 Li KW et al: Superficial siderosis associated with multiple cavernous malformations: report of three cases. Neurosurgery 48(5):1147-50,2001 Weller M et al: Elevated CSF lactoferrin in superficial siderosis of the central nervous system. J Neurol 246(10):943-5, 1999 Manfredi M et al: Superficial siderosis of the central nervous system and anticoagulant therapy: a case report. Ital J Neurol Sci 20(4):247-9, 1999 Hsu WC et al: Superficial siderosis of the CNS associated with multiple cavernous malformations. AJNR 20(7):1245-8, 1999 Iannaccone S et al: Central nervous system superficial siderosis, headache, and epilepsy. Headache 39(9):666-9, 1999 Anderson NE et al: Superficial siderosis of the central nervous system: a late complication of cerebellar tumors. Neurology 1;52(1):163-9, 1999 Schievink WI et al: Surgical treatment of superficial siderosis associated with a spinal arteriovenous malformation. Case report. J Neurosurg 89(6):1029-31, 1998 Matsumoto S et al: Spinal meningeal melanocytoma presenting with superficial siderosis of the central nervous system. Case report and review of the literature. J Neurosurg 88(5):890-4, 1998 Lemmerling M et al: Secondary superficial siderosis of the central nervous system in a patient presenting with sensorineural hearing loss. Neuroradiology 40(5):312-4, 1998 Castelli ML et al: Superficial siderosis of the central nervous system: an underestimated cause of hearing loss. J Laryngol Otol111(1):60-2, 1997 Tapscott SJ et al: Surgical management of superficial siderosis following cervical nerve root avulsion. Ann Neurol 40(6):936-40, 1996 Offenbacher H et al: Superficial siderosis of the central nervous system: MRI findings and clinical significance. Neuroradiology 38 Suppl1:S51-6, 1996 Maurizi CP: Superficial siderosis of the brain: roles for cerebrospinal fluid circulation, iron and the hydroxyl radical. Med Hypotheses 47(4):261-4,1996 Irving RM et al: Cochlear implantation in superficial siderosis.J Laryngol Otol110(12):1151-3, 1996 Fearnley JM et al: Superficial siderosis of the central nervous system. Brain 118:1051-66, 1995

may be made in absence of symptoms

Image Interpretation

Pearls

• CNS surfaces including cranial nerves appear "outlined in black" on T2 MR images

Subarachnoid Hemorrhage and Aneurysms

SUPERFICIAL SIDEROSIS

I IMAGE GALLERY Typical (Left) Axial T2* GRE MR in patient with ataxia and bilateral SNHL shows intense hemosiderin staining of the surface of the cerebellum as hypointense, blooming stripes (arrows). (Right) Coronal T2* GRE MR in patient with superficial siderosis shows low signal along all dural and cerebellar surfaces in the posterior fossa (arrows). This results from hemosiderin staining secondary to chronic subarachnoid hemorrhage.

Variant (Left) Axial T2WI MR reveals juvenile pilocytic astrocytoma (arrow) causing chronic subarachnoid hemorrhage yielding superficial siderosis of adjacent brain surfaces. Open arrow: midbrain staining. Curved arrow: medial temporal lobe staining. (Right) Axial T2WI MR in a patient with juvenile pilocytic astrocytoma shows superficial siderosis from chronic subarachnoid hemorrhage as a dark line on the surface of the high cervical spinal cord (arrow).

Variant (Left) Axial T2WI MR w/large basilar tip aneurysm (arrow), siderosis w/hypointense hemosiderin stain on pontine surface (open arrow) & adjacent tentorium cerebelli (curved arrow) (Courtesy B. Wallace, MO). (Right) Axial T2WI MR shows siderosis of superior cerebellar surfaces (arrow). Hemosiderin stain marks surface of midbrain as hypointense line (open arrow); has basilar tip aneurysm (Courtesy B. Wallace, MO).

Subarachnoid Hemorrhage and Aneurysms

3 11

SACCULAR ANEURYSM

3 12 Frontal graphic of the COW shows a large ACoA aneurysm with a long "aspect ratio." The "tit" at its apex has ruptured, causing SAH. A second small IC-PCoA aneurysm is present.

o Narrow or broad-based

ITERMINOLOGY Abbreviations • Intracranial

Axial oblique CTA in a patient with aSAH. A multilobulated ACoA aneurysm (open arrow) ruptured. Two unruptured aneurysms are indicated by solid arrows (Courtesy;. Farkas, MO).

origin from parent vessel

CT Findings

and Synonyms

saccular aneurysm (SA), true aneurysm

Definitions • Arterial outpouching that lacks internal elastic lamina (IEL), muscular layers

IIMAGING FINDINGS General Features • Best diagnostic clue: Round/lobulated outpouching from circle of Willis (COW) or MCA bifurcation • Location o 90-95% arise from COW • 90% anterior circulation (IC-PCoA, ACoA most common sites) • 10% posterior (BA bifurcation, PICA most common sites) • 5% distal to COW (often traumatic, mycotic, oncotic) o Vessel bifurcation> lateral wall, short> long segment • Size: Small (2-3 mm) to giant (> 2.5 em) • Morphology o Round, lobulated or bleb-like outpouching

• NECT o Ruptured SAs have high density blood in basal cisterns, sulci o Patent aneurysm • Well-delineated round/lobulated extra-axial mass • Slightly hyperdense to brain (may have mural Ca++) o Partially/completely thrombosed aneurysm • Moderately hyperdense (Ca++ common) • Patent lumen enhances • CECT o Lumen of patent SA enhances strongly, uniformly o Completely thrombosed SA may have reactive rim enhancement • CTA o Multi-slice CTA positive in 95% of patients with aSAH o If screening for unruptured SA, negative CTA = very low probability of "clinically important" aneurysm

MR Findings • TlWI o Patent aneurysm (signal varies) • 50% have "flow void" on T1WI • 50% iso/heterogeneous signal o Partially/completely thrombosed aneurysm

DDx: Saccular Intracranial Aneurysm

PCoA Infundibulum

ACA Vessel Loop

Aerated Clinoid

Subarachnoid Hemorrhage and Aneurysms

Suprasellar Lipoma

SACCULAR ANEURYSM Key Facts Terminology • Arterial outpouching that lacks internal elastic lamina (IEL), muscular layers

Pathology

Imaging Findings • Best diagnostic clue: Round/lobulated outpouching from circle of Willis (COW) or MCA bifurcation • Ruptured SAs have high density blood in basal cisterns, sulci • Multi-slice CTA positive in 95% of patients with aSAH • 50% have "flow void" on T1WI • Typically hypointense on T2WI • Best imaging tool: NECT for aSAH + multislice CTA

Top Differential

Diagnoses

• Vessel loop • Infundibulum

• Signal depends on age(s) of clot • Common = mixed signal, laminated thrombus • T2WI o Typically hypointense on T2WI o May be laminated with very hypointense rim • FLAIR: Acute aSAH = high signal in sulci, cisterns • DWI: +/- Foci of restricted diffusion secondary to vasospasm, ischemia

• SA development reflects complex combination of inherited susceptibility + acquired mechanically-mediated vessel wall stresses • 10% prevalence in FIAs • 1-2% incidental finding of unruptured SA at autopsy, angiography

Clinical Issues • Low rupture risk if < 10 mm, high if > 2.5 cm • ISUIA: 22.6% relative, 6% absolute risk reduction (coiling vs surgery); others show little/no difference

Infundibulum • < 3 mm, conical, small PCoA arises directly from apex

Pseudoaneurysm • Often arises distal to COW • May be indistinguishable from true SA

"Flow void" mimic on MR • Aerated anterior clinoid or supraorbital

• T1 C+

o Slow flow in patent lumen may enhance o Increases phase artifact in patent SAs • MRA o 3D TOF = DSA for aneurysms 3 mm or greater o 3T TOF better than 1.5T

Angiographic

• Pseudo aneurysm • "Flow void" mimic on MR • Short T1 on MRA

Findings

• Conventional o Role of DSA • Identify SA, define neck • Identify perforating arteries that may arise from dome • Assess potential for collateral circulation • Detect multiple aneurysms o Multiple projections with cross-compression needed for complete COW delineation • Round/lobulated, focal outpouching, may have apical "tit" • Narrow or broad-based • Rare = contrast extravasation with active SAH o 3D DSA with shaded surface display optimal

Imaging Recommendations • Best imaging tool: NECT for aSAH + multi slice CTA • Protocol advice o Thin slices, low pitch CTA, 3D TOF contrast-enhanced MRA o If CTA/MRA negative, DSA

I DIFFERENTIAL DIAGNOSIS Vessel loop • Use multiple projections

cell

Short T1 on MRA • Lipoma • Pituitary gland (contrast-enhanced

MRA)

I PATHOLOGY General Features • General path comments o SA development reflects complex combination of inherited susceptibility + acquired mechanically-mediated vessel wall stresses o SA rupture risk also complex, multifactorial • Genetics o General inheritance pattern • Autosomal recessive 57%, dominant 36% o Abnormal expression/polymorphism of some genes • Endoglin, MMP-9, apolipoprotein(a) genes • Overexpression of other genes encoding extracellular matrix components (such as collagen, ()(2(I)elastin) • Endothelial NO synthase (eN OS) gene o Familial intracranial aneurysms (FIAs) • No known heritable connective tissue disorder • Occur in "clusters" (two first-order relatives) • 10% prevalence in FIAs • Younger patients, no female predominance compared to sporadic SAs • Accounts for up to 20% of all aSAH • Etiology o Aneurysm formation multifactorial o Flow-related "bioengineering fatigue" in vessel wall o Abnormal vascular hemodynamics

Subarachnoid Hemorrhage and Aneurysms

3 13

SACCULAR ANEURYSM

3 14

• Arises at areas of high biomechanical stress • Abnormal slipstream vectors • Higher/disturbed flow, increased pulsatility • Epidemiology o 1-2% incidental finding of unruptured SA at autopsy, angiography o 20% multiple o Annual risk of de novo aneurysm following previous clipping = 0.8% • Associated abnormalities o Hereditary/connective tissue disorders • Fibromuscular dysplasia • Autosomal dominant polycystic kidney disease (10%) • Ehlers-Danlos type IV, NFl (usually fusiform, not SA) o Anomalous/aberrant vessel • Intraoptic Al ACA • Persistent trigeminal artery • +/- Fenestrated vessel o Flow-related (30-35% on feeding pedicle of AVM) o Trauma, infection, tumor, etc (usually pseudoaneurysms)

Gross Pathologic & Surgical Features sac, thin or thick wall, +/- SAH

• Round/lobulated

Microscopic

Features

• Disrupted/absent internal elastic lamina • Muscle layer absent • May have "tit" of fragile adventitia

• Multilobed > round/ovoid shape • Apical "tit" or "bleb" present • Aspect ratio (length vs neck) > 1.6 o "Perianeurysmal environment" (contact with other structures) o Other (hypertension, female gender, smoking) • Untreated "giant" aneurysm (> 2.5 cm) o 68% mortality rate at 2 y, 85% after 5 y o Most/all survivors have marked neurologic dysfunction

Treatment • Endovascular (coiling, liquid, embolics) o ISUIA: 22.6% relative, 6% absolute risk reduction (coiling vs surgery); others show little/no difference • Clipping (high volume institutions and surgeons have significantly lower morbidity)

I DIAGNOSTIC

CHECKLIST

Consider • aSAH vs nonaneurysmal

SAH or pseudoSAH

Image Interpretation

Pearls

• "Angiogram-negative" SAH may be caused by "blister-like" aneurysm o Look for asymmetric hemispheric bulge • ACoA is most frequent site of "initially occult aneurysm"

I SELECTED REFERENCES

I CLINICAL ISSUES

1.

Presentation • Most common signs/symptoms o SAH 60-85% • Headache (often "thunderclap") o Cranial neuropathy 15-30% • Pupil-involving CN 3 palsy most common (PCoA aneurysm) o Other: "Migraine", TIA, seizure • Clinical profile: Middle-aged patient with "worst headache of my life"

Demographics • Age o From 1.22/100,000 persons/yr (age 0-34) to 44.47/100,000 persons/yr (age 65-74) o Rare in children • 1-2% of all aneurysms • Different location (ICA bifurcation, M2 MCA) • Trauma most common cause • Gender: Women> men (especially with multiple aneurysms)

Natural History & Prognosis • Rupture risk o Size most important (but not only) factor • Low rupture risk if < 10 mm, high if> 2.5 cm • eNOS genotype may influence size at which aneurysm ruptures o Configuration vs rupture risk increased if

Yoneyama T et al: Collagen type I ]1 2 (COUA2) is the susceptible gene for intracranial aneurysms. Stroke 35:443-8, 2004 2. Rasmussen PA et al: Defining the natural history of unruptured aneurysms. Stroke 35:232-3, 2004 3. Juvela S et al: Treatment options of unruptured intracranial aneurysms. Stroke 35:372-4, 2004 4. Henkes H et al: Endovascular coil occulsion of 1811 intracranial aneurysms: Early angiographic and clinical results. Neurosurg 54:268-85, 2004 5. Gibbs GF et al: Improved image quality intracranial aneurysms. Stroke 35:372-4, 2004 6. Baker FG et al: Age-dependent differences in short-term outcome after surgical or endovascular treatment of unruptured intracranial aneurysms in the United States, 1996-2000. Neurosurg 54:18-30, 2004 7. Nanda A et al: Management of intracranial aneurysms: factors that influence clinical grade and surgical outcome. South Med]. 96(3):259-63, 2003 8. Wiebers DO et al: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 362(9378):103-10, 2003 9. Inamasu Jet al: "Occult" ruptured cerebral aneurysms revealed by repeat angiography: result from a large retrospective study. Clin Neurol Neurosurg 106:33-7, 2003 10. Gonsoulin M et al: Death resulting from ruptured cerebral artery aneurysm: 219 cases. Am]Forensic Med Pathol. 23(1):5-14,2002 11. Grond-Ginsbach C et al: Ultrastructural connective tissue aberrations in patients with intracranial aneurysms. Stroke. 33(9):2192-6, 2002

Subarachnoid Hemorrhage and Aneurysms

SACCULAR ANEURYSM

I IMAGE GALLERY Typical (Left) Axial T2WI MR shows a rounded "flow void" adjacent to the circle of Willis (open arrow). Incidental finding in this 60 year old female who was scanned for non focal headaches. (Righ~ Anteroposterior OSA of the right internal carotid artery slightly oblique, shows a 7 mm saccular aneurysm (open arrow) at the ICA bifurcation. Aneurysm was successfully coiled.

Variant (Left) Axial CECT shows a rim-enhancing mass with edema in the adjacent temporal lobe. Note elevation of the sylvian fissure, medial displacement of the ICA and MCA. (Right) Coronal FLAIR MR shows the mass contains multiple laminated layers of variable signal intensity. A central "flow void" is causing phase artifact across the image. Giant, mostly thrombosed aneurysm.

Other (Left) Lateral OSA shows a lobulated aneurysm that arises from the distallCA (open arrow). Note presence of a small persistent trigeminal artery arising from the cavernous ICA (arrow). (Right) Axial gross pathology shows a large unruptured ACA aneurysm (arrows) found incidentally at autopsy (Courtesy R. Hewlett, MO).

Subarachnoid

Hemorrhage

and Aneurysms

3 15

PSEUDOANEURYSM

3 16 Sagittal graphic shows sequelae of CHI. A pseudoaneurysm of distal ACA is seen. Note lesion is contained by cavitated clot (insert, arrow), communicates with ACA (curved arrow).

I TERMINOLOGY Abbreviations

MR Findings • TIWI o Hematoma usually subacute, hyperintense o +/- Associated "flow void" within hematoma • T2WI: Varies with age of hematoma • FLAIR: Hematoma usually hyperintense • T2* GRE: Hypointense • DWI: May demonstrate associated ischemic foci • Tl C+: Enhances strongly • MRA o Tl shortening from subacute hematoma may obscure PsAneur o Contrast-enhanced MRA recommended

and Synonyms

• Pseudoaneurysm

(PsAneur)

Definitions • Focal arterial dilatation normal arterial wall

IMAGING

Anteroposterior DSA shows avascular mass effect with "square" shift (arrows), pseudoaneurysm of the distal ACA (open arrow) caused by closed head injury.

not contained

by layer(s) of

FINDINGS

General Features • Best diagnostic clue: Irregular/lobulated arterial outpouching • Location o 50% MCA (Ml or distal cortical branches) o 25% distal ACA (adjacent to falx) o 259·6petrous/cavernous ICA (BOS fx) or BA/VA • Size: Variable; may be quite large • Morphology: Usually more irregular than typical saccular aneurysm

Angiographic Findings • Conventional o Contrast slowly fills, empties PsAneur cavity o +/- Avascular mass effect (hematoma)

Imaging Recommendations • Best imaging tool: MR + contrast-enhanced

CT Findings • NECT: Focal hematoma adjacent to intracranial vessel • CECT: Enhancing focus within hematoma • CTA: Contrast accumulation +/- communication with true lumen of parent vessel

I DIFFERENTIAL DIAGNOSIS Saccular aneurysm • Circle of Willis> VA or distal ICA branches

DDx: Intracranial Pseudoaneurysm

Saccular Aneurysm

STA dAVF

MeA Dissection

Subarachnoid Hemorrhage and Aneurysms

MRA

PSEUDOANEURYSM Key tacts Terminology • Focal arterial dilatation normal arterial wall

not contained

by layer(s) of

• Contusion • Traumatic dAVF

Pathology

Imaging Findings

• Trauma

• Contrast slowly fills, empties PsAneur cavity

Clinical Issues

Top Differential

• Clinical profile: Patient with delayed stroke following CHI

Diagnoses

• Saccular aneurysm • Dissecting aneurysm

=

most common

cause

Dissecting aneurysm

Natural History & Prognosis

3

• VA>ICA • Contained

• Variable; may continue

17

by vessel wall (media, adventitia)

Contusion • Dorsolateral (CHI)

Treatment • Endovascular

callosal contusion

(stent) vs surgical (occlusion)

with closed head injury

I DIAGNOSTIC

Traumatic dAVF • Superficial temporal

to expand

artery (STA)

CHECKLIST

Consider • Patient who develops delayed hematoma CHI may harbor PsAneur

IPATHOLOGY

Image Interpretation

General Features • General path comments: Cavitated clot communicates with parent vessel • Etiology o Trauma = most common cause • Most common = indirect injury (artery impacts against skull/dura) • Direct (penetrating or surgical) injury less common o Other • Infection, inflammation ("mycotic" aneurysm) • Drug abuse, neoplasm ("oncotic") aneurysm • Spontaneous dissection, underlying vasculopathy • Epidemiology o 1-2% of CHI cases o 3% of cases with infective endocarditis • Associated abnormalities: Other sequelae of trauma, infection +/- ischemic complications

following

Pearls

• Enhancing focus within hematoma that slowly opacifies/empties may represent PsAneur

ISELECTED REFERENCES 1.

2. 3.

Mizutani T et al: Healing process for cerebral dissecting aneurysms presenting with subarachnoid hemorrhage. Neurosurg 54:342-8, 2004 Lath R et al: Traumatic aneurysm of the callosomarginal artery. J Clin Neurosci. 9(4):466-8, 2002 Nomura M et al: Ruptured irregularly shaped aneurysms: pseudoaneurysm formation in a thrombus located at the rupture site. J Neurosurg. 93(6):998-1002, 2000

IIMAGE GALLERY

Gross Pathologic & Surgical Features • Large paravascular

Microscopic • Wall

=

focal hematoma

Features

cavitated clot, no surrounding

arterial layers

ICLINICALISSUES Presentation • Most common signs/symptoms: Delayed ischemia/infarction • Clinical profile: Patient with delayed stroke following CHI

Demographics • Age: Occurs at all ages

(Left) Axial TlWI MR in a patient with remote CHI shows a hyperintense mass (arrows) in the ambient cistern. Hypointense focus (open arrow) is seen within the mass. Note small "flow void" (curved arrow). (Right) Axial MRA with contrast shows a strongly enhancing area of contrast accumulation (open arrow) that communicates with the PCA (curved arrow). Traumatic pseudoaneurysm of P2 was found at surgery.

Subarachnoid Hemorrhage and Aneurysms

FUSIFORM ANEURYSM, ASVD

3 18 Submentoverlex gross pathology shows vertebrobasilar ASVO (curved arrow). More focal aneurysmal dilatation of the basilar artery is present (open arrows) (Courtesy R. Hewlett, MO).

• T2WI: Lumen, clot often hypointense • 1'1 C+: Residual lumen enhances strongly • MRA: Precontrast 3D-TOF inadequate because of flow saturation, phase dispersion

TERMINOLOGY Abbreviations

and Synonyms

• Atherosclerotic fusiform aneurysm (ASVD FA); aneurysmal dolichoectasia

Imaging Recommendations

Definitions • Ectatic vessel + focal aneurysmal

I

Lateral OSA of the vertebrobasilar circulation shows ectasia with focal aneurysmal dilatation (arrows) in this 65 year old patient with TlAs, history of myocardial infarction.

outpouching

I

IMAGING FINDINGS

• Best imaging tool: Dynamic contrast-enhanced 3D-TOF MRA or CTA • Protocol advice: Giant ASVD FAs require dynamic 1'1 C+ sequences for accurate delineation

I DIFFERENTIAL DIAGNOSIS

General Features • Best diagnostic clue: Long segment irregular fusiform or ovoid arterial dilatation • Location: Vertebrobasilar > carotid circulation • Size: Usually large; may be giant (> 2.5 em) • Morphology: Solitary/multifocal dolichoectatic vessel with focal aneurysmal dilatation

Atherosclerotic

dolichoectasia

• No focal fusiform/saccular dilatation • Posterior circulation most commonly

Giant serpentine aneurysm (GSA) • Large, partially thrombosed mass without definable neck • May be indistinguishable from ASVD FA

CT Findings • NECT: Hyperdense; Ca++ common • CECT: Lumen enhances; intramural clot doesn't • CTA: Exaggerated arterial ectasia(s) + focal fusiform/saccular enlargement

Nonatherosclerotic

of

DDx: FA, ASVD

Ehlers-Danlos

Subarachnoid

fusiform vasculopathy

• Younger patient with inherited vasculopathy, disorder

MR Findings • T1WI: Signal varies with flow, presence/age hematoma

affected

CSA

Hemorrhage

ASVD

and Aneurysms

immune

FUSIFORM ANEURYSM, ASVD Key Facts Imaging Findings

Top Differential

• Best diagnostic clue: Long segment irregular fusiform or ovoid arterial dilatation • Location: Vertebrobasilar > carotid circulation • NECT: Hyperdense; Ca++ common • CECT: Lumen enhances; intramural clot doesn't • Best imaging tool: Dynamic contrast-enhanced 3D-TOF MRA or CTA

• • • •

Diagnostic Checklist • DSA or contrast-enhanced delineate patent lumen

• Vertebral> basilar artery; lacks changes of ASVD in other vessels

1.

2.

I PATHOLOGY

3.

General Features • Etiology: Atherosclerosis usual cause of basilar FA in older adults • Epidemiology: ASVD FA less common than vertebrobasilar dolichoectasia (VBD), saccular aneurysm

4.

5. 6.

Gross Pathologic & Surgical Features • Generalized ASVD with focally dilated fusiform arterial ectasia(s)

7.

Features

• Plaques of foam cells with thickened thrombus

I CLINICAL

CTA/MRA necessary to

I SELECTED REFERENCES

Dissecting aneurysm

Microscopic

Diagnoses

Atherosclerotic dolichoectasia Giant serpentine aneurysm (GSA) Nonatherosclerotic fusiform vasculopathy Dissecting aneurysm

intima, organized

8. 9.

ISSUES

Presentation • Most common signs/symptoms: Vertebrobasilar TIAs > cranial neuropathy • Clinical profile: Elderly patient with hypertension, generalized ASVD

Caird J et al: Apolipoprotein(A) expression in intracranial aneurysms. Neurosurgery. 52(4):854-8; discussion 858-9, 2003 Findlay JM et al: Non-atherosclerotic fusiform cerebral aneurysms. CanJ Neurol Sci. 29(1):41-8, 2002 Sakata N et al: Different roles of arteriosclerosis in the rupture of intracranial dissecting aneurysms. Histopathology. 38(4):325-37, 2001 Tanoi Y et al: Binswanger's encephalopathy: serial sections and morphometry of the cerebral arteries. Acta Neuropathol (Bed). 100(4):347-55,2000 Sakata N et al: Pathology of a dissecting intracranial aneurysm. Neuropathology. 20(1):104-8, 2000 Nakatomi H et al: Clinicopathological study of intracranial fusiform and dolichoectatic aneurysms. Stroke 31:896-900, 2000 Mizutani T et al: Clinicopathological features of non-atherosclerotic cerebral arterial trunk aneurysms. Neuropathology. 20(1):91-7, 2000 Jager HR et al: Contrast-enhanced MR angiography of intracranial giant aneurysms. AJNR21:1900-7, 2000 Endo T et al: Multiple arteriosclerotic fusiform aneurysms of the superficial temporal artery--case report. Neurol Med Chir (Tokyo). 40(6):321-3, 2000

IMAGE GALLERY

Demographics • Age: Peak age

=

seventh, eighth decades

Natural History & Prognosis • Slow but progressively increasing ectasia, enlargement

Treatment • Often none; combined option

DIAGNOSTIC

surgical, endovascular

may be

CHECKLIST

Image Interpretation

Pearls

• Slow/complex flow in lumen may give heterogeneous signal • DSA or contrast-enhanced CTA/MRA necessary to delineate patent lumen

Subarachnoid

(Left) Sagittal T7WI MR shows a large extra-axial posterior fossa mass (OSA shown on previous page). Note mixed hyper-, isointense signal caused by slow flow, laminated clot in this classic ASVO FA. (Right) Sagittal T2WI MR shows the mass is predominately hypointense, representing a combination of slow intraluminal flow and subacute mural thrombus.

Hemorrhage

and Aneurysms

3 19

FUSIFORM ANEURYSM, NON-ASVD

3 20 Axial gross pathology shows non-ASVD fusiform vasculopathy in a child (arrow). Common causes are inherited connective tissue disorder, HIV-associated vasculopathy (Courtesy L. Rourke, MD).

Anteroposterior DSA shows fusiform vasculopathy involving the vertebrobasilar circulation (arrow). 6 year old male with probable Ehlers-Danlos syndrome (Courtesy L. Leong, MD).

ITERMINOLOGY Abbreviations

and Synonyms

• Non-ASVD fusiform aneurysm/vasculopathy

(FA)

Definitions • Fusiform enlargement by inherited/acquired

• of intracranial vasculopathy

vessel(s) caused

IIMAGING FINDINGS

• •

General Features • Best diagnostic clue: Long segment of fusiform or ovoid arterial dilatation in absence of ASVD • Location o Long, nonbranching vessel segments; vertebrobasilar > carotid circulation o Can be solitary or multifocal • Size: Varies from a few mm to several cms • Morphology: Elongated, ectatic vessel +/- more focal aneurysmal outpouching

• •

o Elongated, tortuous "flow void" o Mixed signal intensity common, varies with • Flow velocity, direction, turbulence • Slow flow seen as high signal • +/- Clot (laminated layers of organized thrombus) T2WI o Mixed signal intensity (varies with flow, presence/age of hematoma) • Hypointense rim surrounding "flow void" (patent lumen) FLAIR: Clot usually hyperintense DWI: May show restriction from distal embolic complications Tl C+: Residual lumen enhances strongly MRA o Exaggerated arterial ectasia(s) o May require dynamic Tl C+ for accurate delineation

Angiographic Findings • Conventional: Solitary/multifocal aneurysmal outpouchings

ectasias, +/- focal

Imaging Recommendations • Best imaging tool: MR + contrast-enhanced

CT Findings • NECT: Hyperdense; Ca++ common • CECT: Lumen enhances strongly, clot doesn't

MR Findings • TlWI

DDx: Non-ASVD

Fusiform Vasculopathy

ASVD

Pseudoaneurysm

Subarachnoid

Hemorrhage

Atypical Aneurysm

and Aneurysms

MRA

FUSIFORM ANEURYSM, NON-ASVD Key Facts Top Differential

Terminology • Fusiform enlargement by inherited/acquired

I

of intracranial vasculopathy

vessel(s) caused

Imaging Findings

Pathology

• Long, nonbranching vessel segments; vertebrobasilar > carotid circulation • Mixed signal intensity (varies with flow, presence/age of hematoma)

• • • •

DIFFERENTIAL DIAGNOSIS

Demographics

Vertebrobasilar

dolichoectasia

• Older patient with ASVD in other cranial vessels

Diagnoses

• Vertebrobasilar dolichoectasia • Atypical saccular or pseudo aneurysm Collagen vascular disorders (Le., SLE) Viral, other infectious agents (e.g., varicella) Immune deficiency (e.g., HIV) Inherited (e.g., Marfan, Ehlers-Danlos, NFl)

3

• Age: Any age

21

Natural History & Prognosis

Atypical saccular or pseudoaneurysm

• • • •

• May look identical to FA

Treatment

!PATHOLOGY

• Often combined surgical, endovascular measures • 80% of patients with giant fusiform "unclippable" aneurysms dead/disabled at 5 years

Giant serpentine aneurysm • Large, partially thrombosed

mass

Type Type Type Type

1: 2: 3: 4:

Rebleed common Benign clinical course Slow but progressive enlargement Rerupture risk high

General Features • General path comments o Nonatherosclerotic FA, dissecting aneurysm • Type 1: Typical dissecting aneurysm • Type 2: Segmental ectasias • Type 3: Dolichoectatic dissecting aneurysms • Type 4: Atypically located saccular aneurysm (Le., lateral wall, unrelated to branching zones) • Etiology o Collagen vascular disorders (Le., SLE) o Viral, other infectious agents (e.g., varicella) o Immune deficiency (e.g., HIV) o Inherited (e.g., Marfan, Ehlers-Danlos, Nfl) • Epidemiology: FA less common than saccular aneurysm

Gross Pathologic & Surgical Features • Focally dilated fusiform arterial ectasia(s)

Microscopic

I DIAGNOSTIC

CHECKLIST

Consider • Non-ASVD FA in young patient with dilated intracranial vessels

I SELECTED REFERENCES 1.

2.

Nakatomi H et al: Clinicopathological study of intracranial fusiform and dolichoectatic aneurysms. Stroke 31:896-900, 2000 Jager HR et al: Contrast-enhanced MR angiography of intracranial giant aneurysms. AJNR 21:1900-7,2000

I IMAGE GALLERY

Features

• Type 1: Widespread disruption of the internal elastic lamina (IEL), no intimal thickening • Type 2: Extended and/or fragmented IEL with intimal thickening • Type 3: IEL fragmentation, multiple dissections of thickened intima, organized thrombus • Type 4: Absent IEL, muscular layer

I CLINICAL ISSUES Presentation

(Left) Axial CECT shows unusual mass in the right sylvian fissure in

• Most common signs/symptoms: Pain, SAH > TIA, cranial neuropathy • Clinical profile: Young patient with vasculopathy

this 28 year old female with seizures. (Right) Lateral MRA performed with contrast-enhancement shows the mass (open arrow) has an enhancing channel (arrow). Non-ASVO partially clotted fusiform aneurysm was found at surgery (same case as on left).

Subarachnoid Hemorrhage and Aneurysms

BLOOD BLISTER-LIKE ANEURYSM

3 22 Sagittal graphic shows a blood blister-like aneurysm that arises from the dorsal (superolatera/) wall of the supraclinoid ICA (arrow). The BBA is covered only by a thin fibrous wall.

Sagittal (latera/) view of an internal carotid angiogram in a patient with aSAH shows a hemispherical bulge on the undersurface of the ICA (arrow). BBA was found at surgery.

ITERMINOlOGY

• FLAIR: Hyperintense CSF if SAH present • MRA: +/- Seen on high-resolution MRA

Abbreviations

Angiographic Findings

and Synonyms

• Blood blister-like aneurysm (BBA); blister-like pseudoaneurysm; trunk aneurysm

• Conventional o DSA • Initial angiogram often read as normal ("angiographically negative SAH") • Slight irregularity/small focal bulge of arterial wall may be only finding!

Definitions • Broad-based, "side-wall" aneurysm composed primarily/exclusively of fibrous tissue

Imaging Recommendations

I IMAGING FINDINGS

• Best imaging tool: High-resolution DSA • Protocol advice: Obtain multiple obliques, angled lateral views of circle of Willis

General Features • Best diagnostic clue: Small broad-based hemispherical bulge of lateral arterial wall • Location: Supraclinoid ICA = most common site • Size: Usually small « 10 mm) • Morphology: "Tissue paper thin" asymmetrical bulge in vessel wall

I DIFFERENTIAL DIAGNOSIS Saccular aneurysm • Usually arises at arterial bifurcation/branching point • Round, lobulated, narrow-based> broad-based bulge

CT Findings • NECT: Aneurysmal subarachnoid hemorrhage (aSAH) • CTA: +/- Asymmetric bulging of supraclinoid ICA below terminal bifurcation

Vasospasm • Usually symmetrical, asymmetric bulge

concentric

MR Findings • Tl WI: CSF may appear isointense to brain if subarachnoid hemorrhage (SAH) present

DDx: BBA

ASVD

Vasospasm

Saccular Aneurysm

Subarachnoid Hemorrhage and Aneurysms

narrowing

of vessel>

BLOOD BLISYI.:R-LIKE ANEURYSM Key Facts Imaging Findings • Best diagnostic clue: Small broad-based hemispherical bulge of lateral arterial wall • Location: Supraclinoid ICA = most common site • Initial angiogram often read as normal ("angiographically negative SAH")

Top Differential

Diagnoses

• Atherosclerosis (ASVD) • PCoA infundibulum

Clinical Issues • Clinical profile: Middle-aged patient with "angiogram-negative" aSAH • Tend to rupture earlier, at smaller size than saccular aneurysm

• Saccular aneurysm • Vasospasm

Atherosclerosis (ASVD)

I DIAGNOSTIC

• ASVD common to distinguish

Consider

in patients with BBAs, may be difficult

• "Angiogram-negative"

PCoA infundibulum • Funnel-shaped,

PCoA arises from apex

I PATHOLOGY General Features • General path comments: Blister-like pseudoaneurysm • Etiology: Atherosclerosis with ulceration, hematoma formation • Epidemiology: < 1% of all intracranial aneurysms • Focal arterial wall defect covered only with fibrous tissue

2.

3.

4. 5. 6.

I CLINICAL

ISSUES

Presentation • Most common signs/symptoms: aSAH • Clinical profile: Middle-aged patient with "angiogram-negative" aSAH

Pearls

I SELECTED REFERENCES

Features

• Dome of fibrous tissue/adventitia without other vessel wall elements • Significant ASVD in parent vessel common

aSAH may be caused by BBA!

Image Interpretation

1.

Nutik 5L: 5ubclinoid aneurysms. J Neurosurg. 98(4):731-6, 2003 Ogawa A et al: Aneurysms at nonbranching sites in the surpaclinoid portion of the internal carotid artery: internal carotid artery trunk aneurysms. Neurosurgery. 47(3):578-83; discussion 583-6, 2000 McNeely PD et al: Endovascular treatment of a "blister-like" aneurysm of the internal carotid artery. Can J Neurol 5ci. 27(3):247-50, 2000 Kobayashi 5 et al: Blisterlike aneurysms. J Neurosurg 91:164-6, 1999 Charbel IT et al: Distal internal carotid artery pseudoaneurysms. Neurosurg 45:643-9,1999 Abe M et al: Blood blisterlike aneurysms of the internal carotid artery. J Neurosurg 89:419-24, 1998

I IMAGE GALLERY

Demographics • Age: Peak incidence = mid 50s • Gender: Females approximately

2x males

Natural History & Prognosis • Tend to rupture earlier, at smaller size than saccular aneurysm • High surgical mortality/morbidity o Small size, very thin wall, wide base o Avulse readily, intraoperative rupture common o Parent vessel lumen easily compromised o Wrapping may permit regrowth

Treatment • Options: "Trapping" or stenting, coiling

Sagittal (lateral) view of vertebrobasilar angiogram with compression of ipsilateral ICA in a patient with aSAH shows asymmetrical bulge of the PCoA (arrow). The rest of the angiogram was negative. (Right) Sagittal MRA shows the asymmetric bulge of the PCoA seen in the same patient (arrow). No other lesions were identified on this 3D-TOF study. Blood blister-like aneurysm was found at surgery.

(Left)

Subarachnoid Hemorrhage and Aneurysms

3 23

• Look for subtle asymmetry/bulging of supra clinoid ICA wall when saccular aneurysm not seen in patient with aSAH

Gross Pathologic & Surgical Features

Microscopic

CHECKLIST

PART I SECTION 4 Stroke "Stroke" is a lay term meaning sudden onset of an adverse neurologic event. Stroke continues to be a major cause of di ability among adult Americans and the third leading cause of death. Strokes are caused by a pathologically heterog neous group of disorders that have widely differing clinical presentations, etiology, treatment and prognosis. Four major type f" troke" are recognized: (1) erebral ischemia/infarction; (2) primary (non traumatic) intracranial hem rrhage (ICH); (3) subarachnoid hemorrhage; (4) venou cclusions. ubarachnoid hemorrhage, including nonaneurysmal non traumatic SAH, is discu ed in the preceding section on aneurysms. We introduce this section with an anatomic vasculature with arterial and venous territories.

overview of the cerebral

We follow with four subsections, begining with a general di cu sion of non traumatic intracerebral hemorrhage that focuses on the evolution of blood on imaging studies. We then continue with spontaneous ICH and its various cau es. Primary lCH causes approximately 15% of all strokes. Because hyperten ion causes between 40% and 60% of primary acute ICH in older adult, it i included as a separate diagnosi . A rare but important neurosurgical complication, remote cerebellar hemorrhage, i also di cussed. The next two ub ection focus on atherosclerosis (ASVD) and nonatheromatous vasculopathy. ASVD and its sequelae are a major cause of disability and the third leading cause of death in industrialized countries. ASVD is ubiquitous and affects arteries of all sizes from the aortic arch to the cerebral microvasculature. Here we cover ASVD, the determination of clinically significant extracranial carotid stenosis (a slight departure from our focu on the brain), intracranial ASVD and arteriolosclerosis. A spectrum of nonatheromatous disorders i then presented. erebral ischemic disease causes approximately 80% of all strokes. It has many manifestations and occurs in all age groups, spanning the spectrum from fetal and perinatal ischemia to lacunar infarction in the elderly. In addition, imaging findings vary with infarct age. Here we discuss the following specific diagnoses: Hydranencephaly Hypoxic-ischemic encephalopathy, Hypoxic-ischemic encephalopathy Acute cerebral i chemia/infarction Subacute cerebral infarction Chronic c rebral infaraction Hypotensive cerebral infarction

preterm in term infants

Finally, we conclude the subsection on ischemic di ease with the important category of venous occlusions. While cerebral venoocclusive disease accounts for only 1% of all strokes, it is often misdiagnosed or overlooked. We cover the imaging spectrum of venous occlusion from dural inu thrombosis to cortical and deep venous thrombosis.

SECTION 4: Stroke

Introduction and Overview Stroke Anatomy and Imaging Issues

1-4-4

Nontraumatic Intracranial Hemorrhage Intracerebral Hematoma Spontaneous Intracranial Hemorrhage Hypertensive Intracranial Hemorrhage Remote Cerebellar Hemorrhage

1-4-8 1-4-12 1-4-16 1-4-20

Atherosclerosis and Carotid Stenosis Atherosclerosis, Intracranial Atherosclerosis, Extracranial Arteriolosclerosis

1-4-24 1-4-28 1-4-32

Nonatheromatous Vasculopathy Persistent Trigeminal Artery Sickle Cell Disease Moyamoya Primary Arteritis of the CNS Vasculitis Systemic Lupus Erythematosus Cerebral Amyloid Disease CADASIL

Cerebral

1-4-36 1-4-38 1-4-42 1-4-46 1-4-50 1-4-54 1-4-58 1-4-62

Ischemia and Infarction

Hydranencephaly HIE, Preterm HIE, Term Acute Cerebral Ischemia-Infarction Subacute Cerebral Infarction Chronic Cerebral Infarction Lacunar Infarction Hypotensive Cerebral Infarction Dural Sinus Thrombosis Cortical Venous Thrombosis Deep Cerebral Venous Thrombosis

1-4-66 1-4-68 1-4-72 1-4-76 1-4-80 1-4-84 1-4-88 1-4-92 1-4-96 1-4-100 1-4-104

STROKE ANATOMY AND IMAGING ISSUES

Graphic shows usual distribution of major supratentorial arterial territories. Green = AOI. Red = MOl. Blue = POI. Superficial (cortical) "watershed zone" = confluence of 3 territories.

4

ITERMINOlOGY Abbreviations

and Synonyms

• Circle of Willis = COW • External, internal carotid/vertebral/basilar arteries = ECA, ICA, VA, BA • Anterior, middle, posterior cerebral arteries = ACA, MCA, PCA • Anterior, posterior communicating arteries = ACoA, PCoA • Superior sagittal, straight, transverse, cavernous sinuses = SSS, SS, TS, CS • Internal cerebral veins, basal vein of Rosenthal = ICVs, BVRs

IIMAGING ANATOMY Anatomic Relationships

• cow o Components • Both ICAs • Horizontal (AI) ACAs • ACoA, PCoA • BA

• Precommunicating (PI) PCAs o COW surrounds suprasellar cistern, lies below hypothalamus/3rd ventricle o A1s normally pass above CNs 2, 3 o Normal variants common (60% of COWs have one or more hypoplastic/absent segments) • Hypoplastic (10%) or absent (1-2%) Al • Duplicated/fenestrated ACoA in 15-20%; absent ACoA 5% • Hypoplastic/absent PCoA in one-third of cases • PCoA "infundibulum" (funnel-shaped junctional dilatation of PCoA origin from ICA) in 5-15% • "Fetal" PCA origin from ICA (PCoA large, PI PCA hypoplastic) 20-30% o Anomalies (persistent carotid-basilar anastomoses)

Axial graphic shows posterior fossa vascular territories. Blue = pontine perforating arteries. Green = SOl. Yellow = A/OI. Red = PIOI. Purple = medullary perforating arteries.

• Persistent trigeminal artery (PTA): 0.1-0.5% of cases; passes through or around sella, anastomoses with BA in the midline; vascular anomalies, aneurysms commonly associated • All others (hypoglossal, proatlantal intersegmental arteries) very rare • ACA o Al (horizontal) segment = from ACA origin to ACoA junction o A2 (vertical) segment = from ACoA junction to corpus callosum genu o Perforating branches • Medial lenticulostriate arteries • Recurrent artery of Heubner o A3 (major cortical) branches = orbital, frontal arteries; bifurcates near corpus callosum genu into pericallosal, callosomarginal arteries o Vascular territory: Inferomedial basal ganglia, ventromedial frontal lobes, medial 2/3rd of hemispheres, brain convexity o Variations: Hypoplastic Al common; "bihemispheric" ACA (supplies both medial hemispheres) uncommon o Anomalies (e.g., infraoptic AI, azygous ACA) rare, increased association with aneurysms • MCA o M1 (horizontal) segment = from MCA origin to bi-/trifurcation ("genu") o M2 (insular) segment = over insula, divides into 6-8 major branches o M3 (sylvian) segment = from insula through lateral cerebral fissure o M4 (cortical) branches = ramifications over frontal/parietal/temporal lobes o Vascular territory: Basal ganglia, insula, most of lateral hemisphere surface o Variations • "Early" branching MeA • "Accessory" M1 segment o Anomalies (true "duplicated" M1, absent/hypoplastic M1, etc) rare

STROKE ANATOMY AND IMAGING ISSUES DIFFERENTIAL DIAGN Congenital abnormalities

• Remote cerebellar hemorrhage

• • • • • •

Vasculopathies

Aplasia, hypoplasia eurocutaneous syndromes (e.g., Nfl, TS) Marfan syndrome Ehlers-Danlos type IV Idiopathic progressive arteriopathy of childhood Sickle cell disease

Intracranial hemorrhage • • • •

Trauma Hypertensive hemorrhage Hemorrhagic transformation of ischemic infarct "Spontaneous" intracranial hemorrhage (e.g., underlying neoplasm, vascular malformation, etc) • Cerebral amyloid disease • Venous thrombosis

• Atherosclerosis • Primary angiitis of the CNS • Systemic disease with CNS involvement (e.g., SLE, antiphospholipid syndromes) • Vasomotor disorders (e.g., eclampsia, PRES) • Infection-related (e.g., HIV vasculopathy, septic emboli) • Oncotic vasculopathy (e.g., intravascular lymphoma)

Diseases of the cerebral microvasculature • • • •

Cerebral amyloid angiopathy Hypertensive angiopathy with microbleeds CADASIL Arteriolosclerosis

4 • PCA o PI (horizontal or precommunicating) segment = BA to PCoA junction o P2 (ambient) segment = curves around midbrain o P3 segment = behind midbrain to bifurcation o P4 (cortical) branches = anterior/posterior temporal, calcarine, parietooccipital arteries o Choroidal arteries (posterolateral, posteromedial) o Penetrating arteries (thalamoperforating, etc) o Vascular territory: Thalami, midbrain, posterior 1/3 of medial hemisphere, occipital lobe, most of inferolateral temporal lobe o Variations: Hypoplastic PI, "fetal" PCA origin from ICA common o Anomalies: Rare; with PTA, PCAs arise from anterior (carotid) circulation • Major dural venous sinuses and drainage patterns o Superior sagittal sinus (SSS) • > 95% single midline channel from crista galli to sinus confluence • Variations: Absent anterior segment (uncommon) • SSS + cortical veins (including Trolard) drain upper hemispheres, subcortical WM o Straight sinus (SS) • Courses posteroinferiorly from falcotentorial apex to sinus confluence • 85% single midline channel from V of G to sinus confluence • Variations: 15% double or triple parallel channels • Anomalies: Absent SS (rare; usually seen in VOGMs with persistent embryonic falcine sinus) • SS + V of G, ICVs, BVRs drain basal ganglia, thalami, deep WM o Transverse sinus (TS) • Runs from sinus confluence laterally within tentorial attachment to calvarium • 75% right> left TS • Variations: Up to one-third have hypoplastic/absent TS segment (should not be mistaken for occlusion) • TS + tentorial tributaries, vein of Labbe drain most of occipital/posterior temporal lobes o Sigmoid sinus (SigS)

• Junction between TS, jugular bulb/IJV • Significant asymmetry in size of jugular bulb, IJVs common o Cavernous sinus (CS) • Multiseptated trabeculated venous channels on either side of sphenoid body • Lateral dural wall thick, easily recognized; inner very thin, difficult to delineate • Contains ICA, CN 6 within CS; CNs 3, 4, 5 (1st, 2nd divisions) in lateral dural wall • Communicates with orbit, clival and pterygoid plexus (deep face), superior/inferior petrosal sinuses • Drains medial temporal lobes, basal brain structures • Major superficial cortical veins (variations common; exist in reciprocal relationship) o Superficial middle cerebral vein (SMCV) drains brain around sylvian fissure o Vein of Trolard: Superior anastomotic vein between SMCV, SSS o Vein of Labbe: Inferior anastomotic vein between SMCV, transverse sinus • Major deep veins o Internal cerebral veins (ICVs) + subependymal, deep medullary veins (normally always present) o Basal vein of Rosenthal + deep middle cerebral veins (variable)

IANATOMY-BASED IMAGING

ISSUES I

Imaging Pitfalls • Arterial vascular territories quite variable (minimum to maximum areas of supply) • Variations in COW common o Beware: "Absent" PCA on vertebral angio may be fetal origin (check ICA injection!) o Flow direction within COW can be assessed by phase-contrast MRA • Vascular "watershed" = confluence of ACA/MCA/PCA territories

STROKE ANATOMY AND IMAGING ISSUES

Axial graphic shows venous drainage territories. Yellow = TS, v of Labbe. Red = deep WM veins, ICVs, v of Galen, SS Blue = CS, SMCv; OMCV. Green = SSS, cortical veins.

4

Axial gross pathology in a case with occlusion of both ICVs shows bithalamic hemorrhagic infarcts in the deep venous drainage territory (Courtesy j. Garcia, MO).

6

•

•

• •

o Hypotensive infarcts commonly affect cortical watershed, basal ganglia A "deep internal watershed" within the WM represents border between penetrating cortical, deep arteries o "Rosary-like" lesions along deep watershed common in severe carotid stenosis "Filling defects" within TS, sigmoid sinuses may be giant arachnoid granulations (round/ovoid> long, linear) TS variations with hypoplastic/absent segment(s) are common and may mimic occlusion Jugular bulbs, ljVs may be very asymmetric in size; slow/turbulent flow may mimic thrombosis/mass

Other Imaging Issues • Assessing entire COW very important in evaluating patients with aSAH both for aneurysms, potential for collateral flow • Both intra-, extracranial circulations must be evaluated in patients with unexplained non traumatic ICH, patients who may become candidates for ECA-ICA bypass, etc

• Drug abuse • Idiopathic progressive arteriopathy • Blood dyscrasia, clotting disorder

"Stroke" in middle-aged, • • • • • • • • • •

1.

ICLINICAL IMPLICATIONS 3.

Clinical Importance • cow variations are the rule, not exception;

I CUSTOM

DIFFERENTIAL DIAGNOSIS I

"Stroke" in children, young adults • CHD with emboli • Vascular malformation • Dissection

with hemorrhage

older adults

Arterial thromboembolism Hypertensive ICH Cerebral amyloid disease Aneurysmal, non aneurysmal SAH Vascular malformation Neoplasm (primary or metastatic) Dural sinus/cerebral venous occlusion Drugs Coagulopathy Venous collagenosis

ISELECTED REFERENCES

2.

hypoplastic/absent segments limit potential collateral flow in case of major vessel occlusion • Venous occlusions represent < 1% of all "strokes" but have variable clinical presentation, are often overlooked on imaging studies

of childhood

4.

5.

6.

Jongen JC et al: Direction of flow in posterior communicating artery on magnetic resonance angiography in patients with occipital lobe infarcts. Stroke. 35(1):104-8, 2004 Nonaka H et al: Microvasculature of the human cerebral white matter: arteries of the deep white matter. Neuropathology. 23(2):111-8, 2003 Macchi C et al: Relationship between the calibre of carotid arteries and the configuration of the circle of Willis in healthy older persons. J Cardiovasc Surg (Torino). 44(2):231-6,2003 Tanriover N et al: Microsurgical anatomy of the early branches of the middle cerebral artery: morphometric analysis and classification with angiographic correlation. J Neurosurg. 98(6):1277-90, 2003 Avci E et al: Branches of the anterior cerebral artery near the anterior communicating artery complex: an anatomic study and surgical perspective. Neurol Med Chir (Tokyo). 43(7):329-33; discussion 333, 2003 Welsh LW et al: Incompetent circle of Willis and vertebrobasilar insufficiency. Ann Otol Rhinol Laryngol. 112(8):657-64,2003

STROKE ANATOMY AND IMAGING ISSUES

I IMAGE GALLERY Normal vs. Pathology (Left) Graphic shows typical ACA territory in green. ACA supplies anterior 2/3 of medial hemisphere + a small strip of lateral cortex over the convexity. (Right) Axial OWl MR in a patient with acute thromboembolism shows diffusion restriction in the distal ACA territory. Compare with anatomic graphic on left.

4 7

Normal vs. Pathology (Left) Graphic shows typical

MCA vascular territory in red. The MCA supplies the lateral brain surface except for a small strip over the convexity, the occipital pole and undersurface of the temporal lobe. (Right) Axial NECT shows classic wedge-shaped left MCA infarct approximately 3 days after ictus. The watershed zone between ACA, MCA (arrow) is clearly seen; the MCA/PCA border is less well-defined.

Normal vs. Pathology (Left) Graphic shows usual

PCA vascular territory in blue. The PCA normally supplies the occipital lobe and undersurface of the temporal lobe plus a small strip of brain along the posterior convexity. (Right) Axial T2WI MR shows a "top of the basilar" infarct. Hyperintensity in both occipital, left temporal lobes shows extent of PCA involvement. Superior vermis is also infarcted.

INTRACEREBRAL

Axial graphic illustrates right basal ganglia acute hematoma with early peripheral edema (in gray). Mild mass effect partially effaces right lateral ventricle; a heme-fluid level is forming.

4 8

ITERMINOlOGY Abbreviations • Intracerebral

(ICH)

Definitions • Brain parenchymal blood collection secondary to local loss of vascular integrity

IIMAGING FINDINGS General Features • Best diagnostic clue o Hyperdense (50-70 HU) mass on NECT o MRI: ICH staging based on T1 & T2 appearances o Factors influencing ICH MRI appearance • Intrinsic factors: Clot macroscopic structure, Hgb oxidative state, RBC morphology, protein concentration, clot hydration, size/location, edema • Extrinsic factors: Pulse sequences, field strength • Location: Supra> infratentorial brain • Size: Small (nearly microscopic) to very large; solitary> multiple • Morphology: Ovoid to rounded; small to large; fluid-fluid levels possible

DDx: Common

Hypertensive

Axial T2WI MR shows T2 hypointense (T7 isointense, not shown) intracerebral hematoma in patient with GBM; intracellular deoxyhemoglobin in acute bleed. Peripheral edema from tumor and bleed.

CT Findings

and Synonyms

hematoma

HEMATOMA

Causes of Intracerebral

• NECT o Acute: Hyperdense mass • Central hypodensity possible: Rapidly accumulating hematoma & unretracted semiliquid clot; "swirl sign" • Isodense if Hgb < 8-10 g/dl or with bleeding diatheses (e.g., hemophilia) • Fluid-fluid levels with coagulopathies or thrombolytic therapy o Subacute: Isodense mass; 1-6 weeks o Chronic: Hypodense mass; hyperdense foci means rebleed has occurred o Attenuation decreases 1.5 HU/day; liquification/resorption begins at periphery o Residua: !Attenuation foci (37%), no residua (27%), slit-like lesions (25%), calcifications (10%) o Findings suggesting underlying structural cause: Subarachnoid/intraventricular hemorrhage, abnormal Ca++, prominent vessels, atypical hemorrhage site (e.g., perisylvian) • CECT o Active bleeding ~ contrast pooling o Subacute: Peripheral, "ring"-enhancement possible within a few days in vascularized capsule o Chronic: Enhancement disappears 2-6 months

Hematoma

Neoplastic

Drug Abuse

Stroke

AVM

INTRACEREBRAL HEMATOMA Key Facts Terminology

Top Differential

• Brain parenchymal blood collection secondary to local loss of vascular integrity

• • • • •

Imaging Findings • Hyperdense (50-70 HU) mass on NECT • MRI: ICH staging based on T1 & T2 appearances • Tl C+: Subacute: Peripheral, "ring" enhancement possible within a few days in vascularized capsule • MRI: Signal change proceeds peripherally to centrally • ICH "rim" may age faster than its "center" • Initial diagnosis: NECT • For staging/workup: MRI, MRA, MRV • Angiography when no clear cause, particularly young, normotensive, stable, surgical candidates

Diagnoses

Hypertensive ICH Underlying neoplasm (primary or metastatic) Drug abuse Vascular malformation, vasculopathy Cortical vein thrombosis

Pathology • Epidemiology:

Incidence: 15 per 100,000

Clinical Issues • Headache (40%), vomiting (50%), I consciousness (50%), t blood pressure (90%), seizures (10%) • Clinical profile: t Age and HTN most important risk factors • 14-38% expand within first 24 hours

4

MR Findings

Angiographic

• TlWI o Hyperacute (intracellular oxy-Hgb): Isointense o Acute (intracellular deoxy-Hgb): Isointense o Subacute-early (intracellular met-Hgb): Hyperintense o Subacute-late (extracellular met-Hgb): Hyperintense o Chronic-early (extracellular met-Hgb & ferritin/hemosiderin wall): Hyperintense o Chronic-late (hemosiderin): Isointense • T2WI o Hyperacute (intracellular oxy-Hgb): Hyperintense, although may have hypo intense rim o Acute (intracellular deoxy-Hgb): Hypointense o Subacute-early (intracellular met-Hgb): Hypointense o Subacute-late (extracellular met-Hgb): Hyperintense o Chronic-early (extracellular met-Hgb & ferritin/hemosiderin wall): Hyperintense with pronounced low signal rim o Chronic-late (hemosiderin): Hypointense • T2* GRE o Hypointense at all stages, often profoundly o Exquisitely sensitive to local field inhomogeneities of hematoma, scar, cavernous malformation(s) • DWI o Since clinical DWI utilizes T2 technique, findings parallel that of conventional T2WI o Significant correlation between ICH volume & degree of ADC elevation in perihematoma edema o ADC t in ipsi-/contralateral normal appearing brain • Tl C+: Subacute: Peripheral, "ring" enhancement possible within a few days in vascularized capsule • MRA: For detection of vascular malformation • MRV: Evaluation of sinus thrombosis as cause • MRI: Signal change proceeds peripherally to centrally o Can result in two temporally different content pools o ICH "rim" may age faster than its "center" • MRI: Dataset for stereotactic-guided procedure

• DSA is gold standard to evaluate for vascular anomaly o 84% positive when lesion suspected; 24% otherwise o Low yield in patients> 45 years with h/o hypertension (HTN) & thalamic, putaminal, or posterior fossa ICH

Ultrasonographic • Intraoperative

Imaging Recommendations • Best imaging tool o Initial diagnosis: NECT o For staging/workup: MRI, MRA, MRV o Angiography when no clear cause, particularly young, normotensive, stable, surgical candidates • Protocol advice: Spin echo better than fast imaging; GRE increases sensitivity

I DIFFERENTIAL DIAGNOSIS Hypertensive

ICH

• Basal ganglia/ext capsule bleed in patient with HTN • Use GRE to look for microbleeds

Underlying neoplasm (primary or metastatic) • May show enhancement, time

procedure

atypical clot evolution with

Drug abuse • Often multiple drugs; HTN common

Vascular malformation,

vasculopathy

• Use GRE to detect other lesions (e.g., cavernous malformations, amyloid)

Cortical vein thrombosis • Often (but not always!) occurs with dural sinus thrombosis

I PATHOLOGY

Findings

US for imaging-guided

Findings

General Features • General path comments

Stroke

9

INTRACEREBRAL HEMATOMA

4 10

o Edema forms rapidly & progresses for 24-48 hrs, dissecting along white matter tracts o May decompress into ventricles/subarachnoid space • Etiology o Very common: HTN (most common non traumatic cause in adults), trauma, aneurysm, vascular malformation, prematurity o Common: Stroke with reperfusion, amyloid angiopathy, coagulopathy, blood dyscrasia, drug abuse, tumor o Uncommon: Venous infarction (from sinus thrombosis), eclampsia, infective endocarditis with septic emboli, vasculitis (fungal), encephalitis • Epidemiology: Incidence: 15 per 100,000

lictJN1CAl..iISsl.J~s

Gross Pathologic

• Age: All: Likelihood 1 with age • Gender: Men> women • Ethnicity o African-American> Caucasians of similar ages o Asian populations> Caucasians in US & Europe

& Surgical Features

• Acute to early subacute: Blood-filled cavity surrounded by inflammation • Early subacute to early chronic: Organizing clot with vascularized wall • Late chronic: Hemosiderin scar

Microscopic

Features

• Immediate o Liquid hematoma; 95-98% oxygen-saturated Hgb o Platelet thrombi form; erythrocytes aggregate o Unretracted fibrin mass forms gel matrix o Contains RBCs, WBCs, platelet clumps, serum • Hyperacute: 4-6 hrs o Peripheral edema develops o Hemoconcentration (hematocrit rises 70-90%), clot retraction begins o RBCs form spherocytes, contain oxygenated Hgb o Glucose depletion, hypoxia centrally • Acute: 12-48 hrs o RBCs dehydrate, shrink, lose spherical shape; acquire spiculations forming "echinocytes" • Intracellular deoxygenated Hgb in intact RBCs o Pronounced peripheral edema present • Subacute: Early o Starts a few days after hemorrhage; contains intracellular met-Hgb • Subacute: Late o Begins about 1 week after hemorrhage o Shrunken, crenated RBCs lyse, releasing met-Hgb into extracellular space o Edema and mass effect begin to subside o Perivascular inflammation begins; macrophages collect in clot wall (accounts for ring-enhancement) • Chronic: Early o Edema, inflammation regress/disappear; reactive astrocytosis increases o Vascular proliferation ~ hematoma cavity size o Still contains extracellular met-Hgb o Activated macrophages in vascularized wall contain ferritin & hemosiderin • Chronic: Late o Cystic/slit-like cavities with dense collagenous capsule o Contains ferritin-/hemosiderin-Iaden macrophages • May disappear in infants; small scar persists for years in others • Because clot center is profoundly hypoxic, changes first occur peripherally & progress centrally

Presentation • Most common signs/symptoms o Acute focal neurologic deterioration; clot size & location determine character/degree of deficit(s) • 51-63% patients have symptom progression • 34-38% have maximal symptoms at onset o Headache (40%), vomiting (50%), ~ consciousness (50%), 1 blood pressure (90%), seizures (10%) • Clinical profile: 1 Age and HTN most important risk factors

Demographics

Natural History & Prognosis • Without rebleed: Evolution with retraction to scar • With rebleed: Enlargement, 1 morbidity/mortality o 14-38% expand within first 24 hours • 50% rupture into ventricles; poor prognosis, esp if involves 4th ventricle • 25% hypertensive ICH die within 24 hrs • 60% MI thrombolytic therapy ICH die • Of 37,000 Americans with ICH in 1997 o 35-52% were dead at 1 month o 50% deaths occurred within first 2 days o 10% patients were living independently at 1 month; 20% at 6 months

Treatment • Medical therapy: BP,ICP, and seizure control • Surgery: Per American Heart Association guidelines • Minimally invasive, stereotactic-guided surgery possible, yet unproven • No definitive literature evidence to support decisions about surgical vs medical therapy o Prospective "International Surgical Trial in ICH" underway to help formulate evidence-based recommendations regarding role of surgery

I DIAGNOSTIC CHECKLIST Image Interpretation

Pearls

• NECT shows unexplained hyperdense mass? Evaluate further!

IS.Et~(JTEDiREFERcEN¢;Est 1.

2.

Stroke

Kamal AK et al: Temporal evolution of diffusion after spontaneous supratentorial intracranial hemorrhage. AJNR Am J Neuroradiol. 24(5):895-901, 2003 Carhuapoma JR et al: Human brain hemorrhage: quantification of perihematoma edema by use of diffusion-weighted MR imaging. AJNRAm J Neuroradiol. 23(8):1322-6, 2002

INTRACEREBRAL

HEMATOMA

I IMAGE GALLERY Typical (Left) Axial CECT shows ring-enhancement with peripheral edema around resolving intracerebral hematoma. (Right) Axial CECT demonstrates minimal enhancement around subacute-late intracerebral hematoma.

4 Typical

11 (Left) Axial TlWI MR shows Tl hyperintensity of extracellular methemoglobin within subacute-late intracerebral hematoma. (Right) Axial T2WI MR demonstrates T2 hyperintensityof extracellular methemoglobin within subacute-late intracerebral hematoma.

Variant (Left) Axial NECT shows bilateral intracerebral hematomas with fluid-fluid (fluid-heme) levels in a patient with coagulopathy. (Right) Axial Tl C+ MR demonstrates hyperacute intracerebral hematoma containing intracellular oxyhemoglobin (white arrow) as well as active bleeding!contrast extravasation (black arrow).

Stroke

SPONTANEOUS

INTRACRANIAL HEMORRHAGE

Coronal gross pathology in an elderly patient who died from spontaneous plCH (arrows) is shown. Large lobar hemorrhage from cerebral amyloid angiopathy (Courtesy;. Townsend, MO).

4

Axial NECT shows large acute right frontal ICH with considerable mass effect and subfalcine herniation. SAH is also present. This hemorrhage was secondary to an M3 branch aneurysm bleed.

12

o Typically rounded or oval shaped o Two distinct patterns seen with hypertensive hemorrhage • Acute focal hematoma • Multiple subacute/chronic "microbleeds"

TERMINOLOGY Abbreviations

and Synonyms

• Primary intracranial • "Stroke"

hemorrhage

(pICH)

CT Findings

Definitions • Acute intracranial etiology

hemorrhage

• NECT o Round/elliptical parenchymal mass o May be mixed iso-/hyperdense if rapid bleeding, coagulopathy o Peripheral low density (edema) o Acute ICH usually hyperdense o Ganglionic ICH may extend into lateral ventricle • CECT: No pathologic enhancement • CTA o Usually normal in setting of hypertensive hemorrhage o May be positive in setting of vascular malformation

of non-traumatic

IMAGING FINDINGS General Features • Best diagnostic clue: Acute intracerebral hematoma without history of trauma • Location o Varies depending on etiology (from intra- to supratentorial, cortex to deep gray nuclei) • Deep (ganglionic) hematoma common in HTN • Most spontaneous pontine hemorrhages also caused by HTN o Lobar/subcortical hematoma in cerebral amyloid angiopathy (CAA), cerebral vascular malformation (CVM), venous occlusion • Size: Varies from sub-centimeter ("microbleeds") to multiple centimeters • Morphology

MR Findings • TlWI o Hyperacute « 6 hrs) o Center (oxygenated hematoma): Isointense o Periphery (deoxygenated Hgb, clot-tissue interface): Isointense o Rim (vasogenic edema): Hypointense • T2WI o Hyperacute « 6 hrs)

DDx: Various Types of Spontaneous ICH

,

~ Amyloid Angiopathy

~~

• .

Cocaine Use

) Vein of Labbe Infarct

Stroke

AVM with Hemorrhage

SPONTANEOUS INTRACRANIAL HEMORRHAGE Key Facts • Anticoagulation

Terminology • Primary intracranial hemorrhage (pICH) • "Stroke" • Acute intracranial hemorrhage of non-traumatic etiology

Pathology • May range from petechial "micro" hemorrhages to gross parenchymal hematomas • Nontraumatic pICH causes 15-Z0% of acute "strokes" • HTN, CAA, coagulopathy most common causes of pICH in elderly • Patients < 45 Y often have underlying vascular lesion (aneurysm, cerebral vascular malformation), venous occlusion)

Imaging Findings • NECT scan; if older patient with HTN and typical hematoma, stop • If no clear cause of hemorrhage or atypical appearance, consider MR

Top Differential • • • •

• • • • • •

•

Diagnostic Checklist

Diagnoses

• Gross hemorrhage should prompt search for microbleeds with GRE (TZ*) MR • Microbleeds may signal a diffuse hemorrhage-prone vasculopathy (like amyloid)

Cerebral amyloid angiopathy (CAA) Hypertensive bleed vs neoplasm Cortical vein thrombosis Vascular malformation

o Center (oxygenated hematoma): Iso-/hyperintense, heterogeneous o Periphery (deoxygenated Hgb, clot-tissue interface): Hypointense o Rim (vasogenic edema): Hyperintense, TZ* GRE: Multifocal hypointense lesions on TZ* in setting of HTN and CAA DWI: Hypo- or mixed hypo/hyperintense (early hematoma) T1 C+: May see enhancement if hemorrhage secondary to neoplasm MRA: Usually normal MRV: May show dural sinus thrombosis if venous hemorrhage Signal intensity varies with numerous factors including o Pulse sequence o Flip angle o Susceptibility effects (Hgb deoxygenation) o RBC status (lysed or intact) May see evidence of previous hemorrhage in other areas

Angiographic • Conventional: malformation

Findings May not demonstrate in acute stage (DSA)

vascular

I DIFFERENTIAL DIAGNOSIS Cerebral amyloid angiopathy (CM) • • • •

Occurs in older patients May have evidence for previous hemorrhages Usually lobar Amyloid usually> 70 y, normotensive, demented

Hypertensive

bleed vs neoplasm

• HTN unusual in young patients unless drug abuse (e.g., cocaine) • HTN usually ganglionic • Neoplasm often has disordered evolution of hemorrhage, foci of contrast enhancement

Cortical vein thrombosis • Adjacent dural sinus often (but not always!) thrombosed

Vascular malformation • Rate of ICH in patients with AVMs of the basal ganglia or thalamus (9.8% per year) much higher than rate in patients with AVMs in other locations • The risk of incurring a neurological deficit with each hemorrhagic event is high

Anticoagulation

Imaging Recommendations • Best imaging tool o NECT scan; if older patient with HTN and typical hematoma, stop o If no clear cause of hemorrhage or atypical appearance, consider MR o If MR shows co-existing multifocal"black dots," stop o If MR shows atypical hematoma, CTA o If CTA inconclusive, consider DSA • Protocol advice o DSA if suspicious for thrombosed CVM o MRV if suspicious for venous infarction o If atypical hematoma or unclear history, do contrast-enhanced MR (with GRE for co-existing microhemorrhage)

• Check history • "Growing" hematoma,

fluid-fluid levels common

I PATHOLOGY General Features • General path comments o May range from petechial "micro" hemorrhages to gross parenchymal hematomas o May be arterial or venous, cortical or deep, microscopic or gross • Genetics o Matrix metalloproteinases (MMPs) are overexpressed in the presence of some neurological diseases in which blood-brain barrier disruption exists

Stroke

4 13

SPONTANEOUS INTRACRANIAL HEMORRHAGE

4 14

o Expression of MMP-9 is raised after acute spontaneous ICH • Etiology o Older patients • Cerebral amyloid angiopathy • Neoplasm • Coagulopathy • Venous occlusion • Cerebral vascular malformation o Younger patients o Drug use o Vasculitis o Venous thrombosis • Epidemiology o Nontraumatic pICH causes 15-20% of acute "strokes" o HTN, CAA, coagulopathy most common causes of pICH in elderly o Patients < 45 Y often have underlying vascular lesion (aneurysm, cerebral vascular malformation), venous occlusion) o Neoplasm (2-14% of "spontaneous" ICH) o 90% of patients with recurrent pICH are hypertensive

Gross Pathologic & Surgical Features • Acute ganglionic/lobar hematoma • May range from petechial hemorrhages parenchymal hematomas

Microscopic

• Prognosis related to location, size of ICH • Recovery poor; most survivors have significant deficits

Treatment • Control of ICP and hydrocephalus • Surgical evacuation controversial

1.·[)lAGNOSTIC/(]flt(J®l.f~1" Consider • Underlying etiology for hemorrhage neoplasm, drug use, etc)

Image Interpretation

I SELECTED REFERENCES 1.

2.

to frank 3.

common in amyloid,

4.

Staging, Grading or Classification Criteria

5.

• Clinical ICH score correlates with 30 day mortality o Admission GCS o Age> 80 y, ICH volume o Infratentorial o Presence of IVH

6.

I CUNICALiIS.SlJES

8.

Presentation

9.

• Most common signs/symptoms o 90% of patients with recurrent pICH are hypertensive o Large ICHs present with sensorimotor deficits, impaired consciousness

10.

7.

11.

Demographics • Age: May occur anytime from perinatal through adulthood • Gender: No gender predisposition

Pearls

• Gross hemorrhage should prompt search for microbleeds with GRE (T2*) MR • Microbleeds may signal a diffuse hemorrhage-prone vasculopathy (like amyloid)

Features

• Co-existing microangiopathy HTN

(i.e., CVM, CAA,

12. 13.

Natural History & Prognosis • Hematoma enlargement common in first 24-48 hrs o Risk factors == EtOH, low fibrinogen, coagulopathy, irregularly shaped hematoma, disturbed consciousness • Development of edema is known to contribute to poor outcome after spontaneous intracerebral hemorrhage • Mortality 30-55% in first month • 30% of patients rebleed within 1 year

Stroke

Chalela JA et al: Multiple cerebral microbleeds: MRI marker of a diffuse hemorrhage-prone state. J Neuroimaging. 14:54-7,2004 Wessels T et al: CT findings and clinical features as markers for patient outcome in primary pontine hemorrhage. AJNR. 25: 257-60, 2004 Lee SH et al: Comparative analysis of the spatial distribution and severity off cerebral microbleeds and old lacunes. J Neurol Neurosurg Psychiatry 75:423-7, 2004 Sansing LH et al: Edema after intracerebral hemorrhage: correlations with coagulation parameters and treatment. J Neurosurg. 98(5):985-92, 2003 Schellinger PD et al: Stroke MRI in intracerebral hemorrhage: is there a perihemorrhagic penumbra? Stroke. 34(7):1674-9,2003 Abilleira S et al: Matrix metalloproteinase-9 concentration after spontaneous intracerebral hemorrhage. J Neurosurg. 99(1):65-70, 2003 Fleetwood IG et al: Deep arteriovenous malformations of the basal ganglia and thalamus: natural history. J Neurosurg. 98(4):747-50, 2003 Kalaria RN et al: Introduction: Non-atherosclerotic cerebrovascular disorders. Brain Pathol. 12(3):337-42, 2002 Skidmore CT et al: Spontaneous intracerebral hemorrhage: epidemiology, pathophysiology, and medical management. Neurosurg Clin N Am. 13(3):281-8, v, 2002 Woo D et al: Spontaneous intracerebral hemorrhage: epidemiology and clinical presentation. Neurosurg Clin N Am. 13(3):265-79, v, 2002 Bernardini GL et al: Critical care of intracerebral and subarachnoid hemorrhage. Curr Neurol Neurosci Rep. 1(6):568-76, 2001 Qureshi AI et al: Spontaneous intracerebral hemorrhage. N EnglJ Med. 344(19):1450-60, 2001 Roob G et al: Magnetic resonance imaging of cerebral microbleeds. Curr Opin Neurol. 13(1):69-73, 2000

SPONTANEOUS INTRACRANIAL HEMORRHAGE

Typical (Left) Axial NECT shows acute hematoma in right frontal lobe (open arrow), secondary to GBM which has hemorrhaged (see image on right). Small halo of edema along the posteromedial cortex (arrow). (Right) Axial Tl C+ MR shows peripheral ring enhancement (arrow) around GBM in same patient as on left. This image is slightly more superior, above the level of the acute hemorrhage.

4 15

Typical

(Left) Axial NECT shows bilateral hematomas in a patient with underlying coagulopathy. Layering fluid/fluid levels are present. There is also a small left frontal hematoma (arrow). (Right) Axial NECT shows acute posterior frontal hemorrhage within underlying tumor. Note large halo of surrounding edema (arrows), more than would be expected from a simple, or "bland" hemorrhage.

(Left) Axial TlWI MR shows hemorrhagic transformation of small, watershed-distribution right parietal infarction (arrow), with hyperintense intracellular methemoglobin. (Right) Axial T2WI MR shows same patient on left with surrounding edema (arrows) better appreciated on fluid-weighted sequences.

Stroke

HYPERTENSIVE INTRACRANIAL HEMORRHAGE

Axial graphic shows acute hypertensive basal ganglionic/external capsule hemorrhage with dissection into the lateral ventricle. Hemorrhage extends through foramen of Monro to 3rd ventricle.

16

Abbreviations

• Morphology o Typically rounded or oval shaped o Two distinct patterns seen with hlCH • Acute focal hematoma • Multiple subacute/chronic "microbleeds"

and Synonyms

• Hypertensive intracranial hemorrhage (hICH) • "Stroke" (common lay term for sudden onset of neurologic deficit)

CT Findings • NECT o Elliptical high density parenchymal mass o Most common = between putamen, insular cortex o Other sites = thalamus, brainstem, cerebellum o Acute ICH usually hyperdense o Mixed density if coagulopathy, active bleeding o Other: Hydrocephalus, IVH, herniation • CECT: No enhancement in acute hlCH

Definitions • Acute non traumatic ICH secondary to systemic hypertension (HTN)

General Features • Best diagnostic clue o Round/elliptical high density mass with epicenter in basal ganglia/external capsule o Most characteristic sign = putamen/external capsule hematoma in patient with HTN • Location o Striatocapsular (putamen/external capsule) 60-65% o Thalamus 15-25% o Pons, cerebellum 10% o Multifocal"microbleeds" 1-5% o Lobar 5-15% • Size: Varies from sub-centimeter ("microbleeds") to multiple centimeters

DDx: Nontraumatic

't' r

.•

;

~. Cocaine

Axial NEeT shows classic acute intraparenchymal hematoma in the left basal ganglia/external capsule in this elderly female with longstanding poorly controlled systemic hypertension.

MR Findings • TlWI o Varies with age of clot • Hyperacute hematoma « 6 hrs): Oxyhemoglobin (Hgb) (iso-/hypointense) • Acute hematoma (48-72 hrs): DeoxyHgb (iso-/hyperintense) • Subacute hematoma (several days): Intracellular metHgb (hyperintense) • Chronic hematoma (week-months): Extracellular metHgb (hyperintense) • T2WI o Varies with stage

Intra-axial Hemorrhage

)

"

Induced

Venous

Occlusion

Thrombosed

Stroke

AVM

Cerebral Amyloid

HYPERTENSIVE INTRACRANIAL HEMORRHAGE Key Facts • Lobar hemoqhage (e.g., amyloid) • Multifocal"black dots" (microbleeds from HTN vs amyloid, etc)

Terminology • Acute nontraumatic ICH secondary to systemic hypertension (HTN)

Pathology

Imaging Findings

• Striatocapsular hematoma is most common autopsy finding in patients with hlCH • 50% of primary nontraumatic ICHs caused by hypertensive hemorrhage • HTN most common cause of spontaneous ICH between 45-70 years • 10-15% of all cases of "stroke"; associated with highest mortality rate

• Round/elliptical high density mass with epicenter in basal ganglia/external capsule • Striatocapsular (putamen/external capsule) 60-65% • Thalamus 15-25% • Pons, cerebellum 10% • Multifocal"microbleeds" 1-5% • Lobar 5-15% • DSA almost always normal if HTN + deep ganglionic hemorrhage

Top Differential • Nonhypertensive

•

• •

•

Clinical Issues • 80% mortality in massive ICH with IVH

Diagnoses basal ganglionic hemorrhage

• Hyperacute hematoma « 6 hrs): OxyHgb (hyperintense) • Acute hematoma (hrs-several days): DeoxyHgb (hypointense) • Subacute hematoma (first several days): Intracellular metHgb (hypointense) • Chronic hematoma (several days-months): Extracellular metHgb (hyperintense) • Remote hematoma (months-yrs): Hypointense hemosiderin scar +/- small central hyperintense cavity T2* GRE o Multifocal hypointense lesions ("black dots") on T2* o Common with longstanding HTN o Also commonly seen with amyloid angiopathy DWI: Hypo- or mixed hypo/hyperintense (early hematoma) T1 C+ o Typically no enhancement o Contrast extravasation = active hemorrhage, growing hematoma MRA: Negative

Angiographic

Findings

• Conventional o DSA almost always normal if HTN + deep ganglionic hemorrhage o May show avascular mass effect o Rare: "Bleeding globe" microaneurysm on lenticulostriate artery (LSA)

Imaging Recommendations • Best imaging tool o If older patient with HTN and high suspicion for hICH, NECT o If hyperacute ischemic "stroke" suspected, MR with T2* and DWI o If MR shows classic hematoma + co-existing multifocal"black dots," stop o If MR shows atypical hematoma, CTA o If CTA inconclusive, consider DSA • Protocol advice o Initial screen = NECT in patients with HTN

o Otherwise MRI (include T2* sequences, DWI, + MRA; T1 C+ optional)

I DIFFERENTIAL DIAGNCJSIS Nonhypertensive hemorrhage

basal ganglionic

• Vascular malformation (younger patients) • Hemorrhagic neoplasm (often mixed signal, enhancing) • Other: Coagulopathy, drug abuse

Lobar hemorrhage

(e.g., amyloid)

• Only 5-15% of hICHs are lobar but HTN so common that it is always a diagnostic consideration • Amyloid angiopathy (elderly, demented, normotensive; rarely involves deep subcortical nuclei) • Thrombosed AVM or dAVFs (younger patients with stagnating vessels, early draining veins on angiography) • Cortical vein thrombosis (co-existing dural sinus thrombosis often-but not always-present) • Hemorrhagic neoplasm (primary or secondary)

Multifocal "black dots" (microbleeds from HTN vs amyloid, etc) • Microbleeds have many causes o Chronic HTN o Hemorrhagic diffuse axonal injury o Multiple cavernous/capillary malformations o Cerebral amyloid angiopathy (CAA) o Hemorrhagic metastases (rare) o Artificial heart valve (metallic micro emboli)

I PATHCJl..CJG¥ General Features • General path comments o Striatocapsular hematoma is most common autopsy finding in patients with hICH

Stroke

4 17

HYPERTENSIVE INTRACRANIAL HEMORRHAGE o Diffuse "microbleeds" also common • Etiology o Chronic HTN with atherosclerosis, fibrinoid necrosis, abrupt wall rupture +/- pseudoaneurysm formation o "Bleeding globe" (penetrating LSA aneurysm) • Epidemiology o 50% of primary nontraumatic ICHs caused by hypertensive hemorrhage o HTN most common cause of spontaneous ICH between 45-70 years o 10-15% of all cases of "stroke"i associated with highest mortality rate o 10-15% of hypertensive patients with spontaneous ICH have underlying aneurysm or AVM

\[)IAGINOST1CiCHECK.HsT Consider • Does the patient have a history of poorly-controlled systemic HTN? • Could there be an underlying coagulopathy, hemorrhagic neoplasm or vascular malformation? • Check for history of substance abuse in young patients with unexplained hICH

Image Interpretation

Gross Pathologic & Surgical Features • Large ganglionic hematoma +/- IVH • Subfalcine herniation, hydrocephalus common • Co-existing small chronic hemorrhages, ischemic lesions common

Microscopic 18

Features

ISE LECTED.·•R~iFE({~~(J;ES •

• Fibrous balls (fibrosed miliary aneurysm) • Severe arteriosclerosis with hyalinization, pseudoaneurysm (lacks media/IEL)

1.

2.

IClIN1CAl..ISSlJES

3.

Presentation • Most common signs/symptoms o Large ICHs present with sensorimotor deficits, impaired consciousness o Seasonal, diurnal blood pressure variations cause higher incidence of ICH in colder months • Clinical profile: Most common in hypertensive, elderly African-American males

4.

Demographics

7.

• Age: Elderly • Gender: Males • Ethnicity: African-American

Pearls

• The underlying cause of lobar intracerebral hemorrhage (ICH) is often difficult to determine • Subarachnoid extension of hematoma on CT strongly indicates a non-hypertensive cause more specifically, it suggests lobar ICH caused by vascular abnormalities • The definite diagnosis of CAA vs HTN-related hemorrhage requires histopathological confirmation and should not be based solely on hemorrhage pattern interpretation

5. 6.

8.

most common

Natural History & Prognosis • Bleeding can persist for up to 6 hr following ictus • Neurologic deterioration common within 48 hr o Increasing hematoma oEdema o Development of hydrocephalus o Herniation syndromes • Recurrent hICH in 5-10% of cases, usually different location • Prognosis related to location, size of ICH • 80% mortality in massive ICH with IVH • Only one-third of patients with hICH survive first year • One-third of survivors are severely disabled

9.

10.

11.

12. 13.

Treatment • Stereotaxic evacuation may improve outcome in some cases • Control of ICP and hydrocephalus

Stroke

Lee SH et al: Comparative analysis of the spatial distribution and sevarity of cerebral microbleeds and old lacunes. J Neurol Neurosurg Psychiatry 75:423-7, 2004 Narayan P et al: Surgical treatment of a lenticulostriate artery aneurysm. J Neurosurg. 100: 340-2, 2004 Hanley DF et al: Critical care and emergency medicine neurology: Intracerebral hemorrhage. Stroke. 35: 365-6, 2004 Ohtani R et al: Clinical and radiographic features of lobar cerebral hemorrhage: hypertensive versus non-hypertensive cases. Intern Med. 42(7):576-80, 2003 Lammie GA: Hypertensive cerebral small vessel disease and stroke. Brain Pathol. 12(3):358-70, 2002 Skidmore CT et al: Spontaneous intracerebral hemorrhage: epidemiology, pathophysiology, and medical management. Neurosurg Clin N Am. 13(3):281-8, v, 2002 Woo D et al: Spontaneous intracerebral hemorrhage: epidemiology and clinical presentation. Neurosurg Clin N Am. 13(3):265-79, v, 2002 Yanagawa Y et al: Relationship between stroke and asymptomatic minute hemorrhages in hypertensive patients. Neurol Med Chir (Tokyo). 41(1):13-7i discussion 17-8,2001 Lang EW et al: Stroke pattern interpretation: the variability of hypertensive versus amyloid angiopathy hemorrhage. Cerebrovasc Dis. 12(2):121-30,2001 Blumenfeld JD et al: Management of hypertensive crises: the scientific basis for treatment decisions. Am J Hypertens. 14(11 Pt 1):1154-67, 2001 Dickinson CJ: Why are strokes related to hypertension? Classic studies and hypotheses revisited. J Hypertens. 19(9):1515-21,2001 Qureshi AI et al: Spontaneous intracerebral hemorrhage. N EnglJ Med. 344(19):1450-60, 2001 Voelker JL et al: Intraparenchymal hemorrhage. New Horiz. 5(4):342-51, 1997

HYPERTENSIVE INTRACRANIAL HEMORRHAGE

Typical (Left) Axial FLAIRMR shows late subacute hemorrhage in the basal ganglia, extending into the insula. Signal is from extracellular methemoglobin, showing hyperintensity on T2WI. (Right) Axial NECT shows acute right basal ganglia/thalamic hemorrhage with intraventricular rupture. Very little surrounding edema, in contrast to hemorrhage associated with tumor (see spontaneous ICH).

4 Variant

19 (Left) Axial T2WI MR shows

different pattern of chronic hypertension, with numerous scattered" microbleeds" (arrows) which show magnetic susceptibility. No acute hemorrhage present. (Right) Axial T2WI MR shows numerous deeper "microbleeds" in different patient. These findings can be seen with CAA, chronic hypertension, and numerous small vascular malformations.

Variant (Left) Axial NECT shows a less typical location for a

hypertensive hemorrhage, i.e., within the pons. This is a patient with cocaine-induced hypertension. Note marked mass effect on 4th ventricle (arrow). (Right) Axial TlWI MR shows less typical location for a hlCH (in the anterior right temporal lobe, lateral to the basal ganglia). Clot is about 7 week old (hyperintensity is due to extracellular metHgb).

Stroke

REMOTE CEREBELLAR HEMORRHAGE

Axial T2WI MR shows spontaneous ("remote") cerebellar hemorrhage (arrows) in this patient following uncomplicated supratentorial surgery (not shown).

4 20

ITERM1NQlOGY Abbreviations

and Synonyms

• Remote cerebellar hemorrhage

(RCH)

Definitions • Cerebellar hemorrhage following cerebral surgery, remote to the primary site of intervention, without underlying pathologic lesion • Smaller subset of patients with supratentorial hemorrhage following infra tentorial (remote) surgery • A few reported cases of RCH following spinal surgery

Axial TIWI MR shows spontaneous hemorrhage in the vermis (open arrows) in a padent with supratentorial craniotomy. Appearance is typical for late acute "remote" cerebellar hemorrhage.

• Isolated vermian (9%) o Subarachnoid vs superficial parenchymal bleed likely in most o Occasionally occurs above tentorium, remote to infratentorial surgery • Size: Varies, usually localized • Morphology o Superior cerebellar folia most typical pattern o Lobar hemorrhage or mixed pattern less common

CT Findings • NECT: Hyperdense hemorrhage acutely • CECT: No nodular enhancement (late hematoma peripheral enhancement may occur)

I IMAGING FINDINGS

MR Findings

General Features

• T1WI: Varies with age/stage of hematoma • T2WI: Usually mixed hypo-/hyperintense

• Best diagnostic clue: Hemorrhage in cerebellum following craniotomy, and less commonly after spinal surgery, without other explanation • Location o Cerebellar vermis classic original description, but location in cerebellum varies o Side of remote hemorrhage in summary of known cases (unknown in 16%) • Contralateral to side of surgery (29%) • Ipsilateral (22%) • Bilateral (33%)

DDx: Mimics of Remote Cerebellar

Tentorial AVM

• T2* GRE

o Useful to confirm hemorrhage on MRI ("blooms") • Most sensitive sequence for parenchymal blood products • DWI: Varied signal intensity depending on age • T1 C+: No underlying vascular lesion or tumor enhancement • MRA: Negative for vascular lesion

Angiographic Findings • Conventional

Hemorrhage

Cavernoma

Dural AVF

Stroke

Metastasis

REMOTE CEREBELLAR HEMORRHAGE Key Facts Imaging Findings

Pathology

• Best diagnostic clue: Hemorrhage in cerebellum following craniotomy, and less commonly after spinal surgery, without other explanation • Superior cerebellar folia most typical pattern • DSA negative for underlying vascular etiology; avascular mass effect

• CSF (cerebrospinal fluid) hypovolemia may lead to transient occlusion or tearing of superior bridging veins in the posterior fossa, resulting in hemorrhagic venous infarct • Not associated with hypertension, coagulopathy, or vascular malformation • RCH usually seen in immediate postoperative period • Hemorrhagic necrosis without underlying vascular malformation or tumor

Top Differential • • • • •

Diagnoses

Hypertensive hemorrhage Neoplasm with hemorrhage Vascular malformation Cerebral amyloid angiopathy (CAA) Coagulopathy-related spontaneous hemorrhage

Diagnostic Checklist • Cerebellar bleed in patient with history of craniotomy or spinal surgery probably represents RCH

o DSA negative for underlying vascular etiology; avascular mass effect o No major cortical venous or dural sinus occlusion

I

plus

DIFFERENTIAL DIAGNOSIS

Hypertensive

hemorrhage

• Cerebellar location not uncommon, but hypertensive not typically superficial/foliar pattern • Clinical history may be helpful • T2* imaging may reveal additional foci typical of prior hypertensive bleeds (e.g., basal ganglia, putamen)

Neoplasm with hemorrhage • Metastatic most common, also gliomas • Vasogenic edema, nodular enhancement, lesions are clues

additional

Vascular malformation • Cavernoma • AVM (arteriovenous malformation) • dAVF (dural arteriovenous fistula)

Cerebral amyloid angiopathy (CM) • T2* imaging helpful to assess for additional foci of prior amyloid bleeds in typical locations (e.g., subcortical white matter)

Coagulopathy-related hemorrhage

spontaneous

• Iatrogenic: Coumadin, Heparin, Aspirin • Disseminated intravascular coagulation (DIe)

21

General Features

Imaging Recommendations • Best imaging tool o NECT initial screen o MRI with and without contrast, MRA o DSA if conventional imaging negative o Diagnosis of exclusion • Protocol advice: MRI with T2*, gadolinium, vascular imaging (MRA and/or DSA)

4

I PATHOLOGY • General path comments: Hemorrhage without underlying pathologic lesion • Etiology o Controversial; several theories o CSF (cerebrospinal fluid) hypovolemia may lead to transient occlusion or tearing of superior bridging veins in the posterior fossa, resulting in hemorrhagic venous infarct o Cisterns or ventricles opened in nearly all cases of RCH, supporting theory of CSF hypovolemia o Rotated, extended position of neck during surgery may cause compression of internal jugular vein and subsequent increased venous pressure o Reported predisposing conditions • Pre-operative aspirin use • Elevated intraoperative systolic blood pressure • Intraoperative esmolol infusion • Supine positioning intraoperatively for cerebellar hemorrhage; sitting position intraoperatively for supratentorial remote hemorrhage • Post-operative epidural drainage or lumbar drain • Epidemiology o Association with frontotemporal and frontal craniotomies performed in supine position o Incidence of RCH after craniotomy • 0.08-0.29% after supratentorial craniotomy • 2.8-3.5% after unruptured aneurysm surgery • 1.4-5% after temporal lobectomy • Associated abnormalities o Not associated with hypertension, coagulopathy, or vascular malformation o RCH usually seen in immediate postoperative period • Within hours to 1 day postoperatively in majority of cases

Gross Pathologic & Surgical Features • Hemorrhagic necrosis without underlying malformation or tumor

Stroke

vascular

REMOTE CEREBELLAR HEMORRHAGE 5.

Microscopic Features • Hemorrhagic necrosis of cerebellar parenchyma, occasional small vessel thrombosed (no large cortical venous or sinus thrombosis) • Non-specific, but consistent with hemorrhagic venous infarct

ICLlNil¢,L\~iISSil.JES

6. 7.

8. 9.

Presentation • Most common signs/symptoms o Decreased level of consciousness, seizures most common o Cerebellar signs, from primary bleed, or secondary to herniation (less common) o Frequently asymptomatic o No rebleeding on follow-up imaging at site of RCH • Clinical profile o Rare complication following craniotomy or spinal surgery o Cause unclear

10.

11. 12.

13.

14.

22

Demographics • Age: Average 50 years, range 10-83 years of age • Gender: Male> female

15.

Natural History & Prognosis

16.

• Outcome in review of known published cases o "Good" outcome (44%) o "Fair" recovery (23%) o "Poor" outcome (8%) o Death (25%) • Occasionally asymptomatic; true incidence unknown (occult bleeds often not imaged)

Treatment • Intervention for RCH rarely indicated • Avoid Aspirin 7 days prior to cranial and spinal surgery

I DI,L\<J]1~()STI¢¢HEC~LlSt

17.

18. 19.

20. 21.

22.

Consider • MRI initial evaluation after screening NECT • DSA gold standard to exclude underlying causes

Image Interpretation

Pearls

• Cerebellar bleed in patient with history of craniotomy or spinal surgery probably represents RCH

I SELECTED REFERENCES 1.

2.

3. 4.

Kelly GR et al: Sinking brain syndrome: craniotomy can precipitate brainstem herniation in CSF hypovolemia. Neurology. 62: 157, 2004 Bloch J et al: Brain stem and cerebellar dysfunction after lumbar fluid drainage: case report. J Neurol Neurosurg Psychiatry 74:942-4, 2003 Friedman JA et al: Cerebellar hemorrhage after spinal surgery. Neurosurgery 50:1361-3,2002 Marquardt G et al: Cerebellar hemorrhage after supratentorial craniotomy. Surg Neurol 57:241-52, 2002

Stroke

Honegger J et al: Cerebellar hemorrhage arising postoperatively as a complication of supratentorial surgery. J Neurosurg 96:248-54, 2002 Friedman JA et al: Remote cerebellar hemorrhage after supratentorial surgery. Neurosurgery 49:1327-40,2001 Seoane E et al: Compression of the internal jugular vein by the transverse process of the atlas as the cause of cerebellar hemorrhage after supratentorial craniotomy. Surg Neurol 51:500-505, 1999 Koller M et al: Posterior-fossa haemorrhage after supratentorial surgery. Acta Neurochir 141:587-92, 1999 Cloft HJ et al: Posterior fossa hemorrhage after supratentorial surgery. AJNR 18:1573-80, 1997 Brisman MH et al: Intracerebral hemorrhage occurring remote from the craniotomy site. Neurosurgery 39:1114-21, 1996 Toczek MT et al: Cerebellar hemorrhage complicating temporal lobectomy. J Neurosurg 85:718-22, 1996 Papanastassiou V et al: Contralateral cerebellar hemorrhagic infarction after pterional craniotomy. Neurosurgery 39:841-52, 1996 Mikawa Y et al: Cerebellar hemorrhage complicating cervical durotomy and revision C1-C2 fusion. Spine 19:1169-71, 1994 Yoshida S et al: Cerebellar hemorrhage after supratentorial craniotomy - report of three cases. Neurol Med Chir 30:738-43, 1990 Konig A et al: Cerebellar hemorrhage as a complication after supratentorial craniotomy. Acta Neurochir 88:104-108, 1987 Seiler RW et al: Supratentorial intracerebral hemorrhage after posterior fossa operation. Neurosurgery 18:472-4, 1986 Miyamoto Y et al: Postoperative intracerebral hematoma remote from the site of craniotomy. Neurol Med Chir 25:219-222, 1985 Standefer M et al: The sitting position in neurosurgery. Neurosurgery 14:649-658, 1984 Waga S et al: Intracerebral hemorrhage remote from the site of the initial neurosurgical procedure. Neurosurgery 13:662-665, 1983 Chadduck WM et al: Cerebellar hemorrhage complicating cervical laminectomy. Neurosurgery 9:185-9, 1981 Heros RC et al: Intracerebral hemorrhage after microsurgical revascularization. Neurosurgery 6:371-5, 1980 Haines SJ et al: Supratentorial intracerebral hemorrhage following posterior fossa surgery. J Neurosurg 49:881-6, 1978

REMOTE CEREBELLAR HEMORRHAGE

Typical (Left) Coronal FLAIRMR shows heterogenous signal in spontaneous left cerebellar hemorrhage (arrows) following frontal craniotomy in a patient with sudden clinical deterioration. (Right) Axial T2WI MR in the same case shows heterogenous signal and mild edema in remote cerebellar hemorrhage (arrows).

4 Typical

23 (Left) Axial OWl MR shows

heterogeneous signal, largely hyperintense. Blood products can cause field distortions and may result in heterogenous signal and/or areas of ischemia on OWl. (Right) Axial T2* GRE MR shows hypointense signal in the cerebellar hematoma. No other abnormalities were identified. Same case as above and on left.

(Left) Axial NECT in a patient

with uneventful left temporal craniotomy (curved arrow) for drainage of an left middle fossa arachnoid cyst with SOH shows remote right cerebellar hemorrhage (open arrows). (Right) Axial NECT in the same case shows no evidence for recurrent SOH at the craniotomy site (curved arrow). The RCH (open arrow) was initially read as post-surgical subarachnoid hemorrhage,

Stroke

ATHEROSCLEROSIS, INTRACRANIAL

Coronal graphic shows atherosclerotic plaques (open arrows) involving major intracranial arteries. Inset shows penetrating arteries (white arrows) and lacunar infarcts (black arrows).

4 24

Lateral DSA, common caroud artery injection, shows internal carotid occlusive disease. Distal ICA (open arrow) is reconstituted via ophthalmic artery collaterals (arrow).

• CTA: Calcifications

Abbreviations • Intracranial

MR Findings

and Synonyms

arterial stenosis

Definitions • Focal narrowing of intracranial

in wall may reduce specificity

arterial lumen

General Features • Best diagnostic clue: Stenotic intracranial artery on angiogram • Location o Usually involves • Distal basilar (BA) or internal carotid artery (ICA) o Less common sites • Circle of Willis (COW) • Middle cerebral artery stenosis rare (2% of cases) but high stroke death risk • Size: Variable, usually focal • Morphology o Variable • Usually eccentric, irregular +/- ulceration

• TlWI o Decreased/absent flow void in expected position of artery (slow flow or occlusion) o Also seen with slow flow from upstream (extracranial) stenosis, dissection • T2WI: Decreased flow void in expected position of artery (slow flow or occlusion) • FLAIR: Slow flow or occlusion may appear hyperintense ("dot sign") ·MRA o Focal stenosis, ectasia or irregularity on 3D TOF (time of flight) or contrast-enhanced MRA (CE-MRA) • Caveat 1: Contralateral vessel must be normal caliber throughout • Caveat 2: 3D TOF MRA tends to overestimate stenosis due to spin saturation (poor evaluation of slow flow and in-plane flow) • CE-MRA less affected by spin saturation and much faster imaging sequence • Combined with CTA, sensitivity and specificity approach DSA

Ultrasonographic

Findings

• Trans-Cranial Doppler (TCD): Increased velocities

CT Findings • NECT: Mural calcifications

DDx: Atherosclerosis Mimics

Vasospasm, Drugs

VA Dissection

Vasculitis

Stroke

Moyamoya

ATHEROSCLEROSIS, INTRACRANIAL Key Facts Terminology

Pathology

• Focal narrowing

• Atherosclerosis is a systemic, multifactorial disease • Third most common cause of thromboembolic stroke, after carotid and cardiac sources • Flow limiting beyond 70% stenosis (based on diameter ratios) • Ischemic symptoms depend on collaterals

of intracranial

arterial lumen

Imaging Findings • Distal basilar (BA) or internal carotid artery (ICA) • Circle of Willis (COW) • DSA: Focal stenosis, luminal irregularities, thrombosis, occlusion • Less common: Ectasia and elongation, serpentine aneurysms

Top Differential • • • •

Diagnoses

Vasculitis/arteritis Vasospasm Moyamoya Dissection

Angiographic

Findings

• Conventional o DSA: Focal stenosis, luminal irregularities, thrombosis, occlusion • Less common: Ectasia and elongation, serpentine aneurysms o DSA most sensitive and specific test; goals include • Grade extracranial stenosis, criteria standardized by NASCET (North American Symptomatic Carotid Endarterectomy Trial) • Identify "tandem" lesions • Assess collateral status • Potential assessment of plaque ulceration • Potential intervention (angioplasty +1- stenting)

Clinical Issues • Most common signs/symptoms: Transient ischemic attack, due to emboli, severe stenosis, progressive occlusion

Diagnostic Checklist • CTA and/or MRA as excellent screening tool • DSA gold standard, allows potential intervention

• TI hyperintense crescent = thrombus, best seen with fat-sat • Younger patients • Can have minimal or no history of trauma

Non-occlusive

thrombus or embolus

• Appearance of rounded, central non-opacification with peripheral enhancing rim on contrast study

I P~1"HOLOG'Y General Features

• Usually involve distal ICA and proximal COW with relative sparing of basilar artery • Frequently bilateral

• General path comments o Atherosclerosis is a systemic, multifactorial disease o Intracranial atherosclerosis associated with atherosclerosis of carotids, coronaries, aorta, renal arteries, iliofemoral system o Anatomy • Most often involves arterial bifurcations, e.g., ICA and BA • May involve distal arterioles leading to vasculitis pattern of alternating stenosis and dilatation • Etiology o Probably multiple etiologies; main three are • Lipid hypothesis: High plasma LDL leads to LDL-cholesterol deposition in intima • Response to injury hypothesis: Focal endothelial change or intimal in'fury leads to platelet aggregation and plaque formation • Unifying hypothesis: Endothelial injury leads to increased permeability of LDL: Plaques grow by thrombus formation on plaque surface and trans endothelial leakage of plasma lipids • Epidemiology o Third most common cause of thromboembolic stroke, after carotid and cardiac sources o Basis for cerebral thromboembolism in over 90% o Most common cause of intracranial vascular stenosis in adults

Dissection

Gross Pathologic & Surgical Features

Imaging Recommendations • Best imaging tool: DSA remains gold standard • Protocol advice o CTA or MRA followed by DSA if equivocal • CTA or MRA for proximal intracranial stenoses

I DIFFER.EN1"I~LDI~GNOSI$ Vasculitis/arteritis • • • • •

Usually involves smaller (tertiary) branches More likely associated with hemorrhage Can be primary or secondary Often associated with systemic disease Elevated ESR, autoimmune parameters

Vasospasm • Subarachnoid hemorrhage related, maximal 7 days post-bleed • Drug-related (sympathomimetics)

Moyamoya

• Smooth tapering

• Earliest macroscopic finding: Intimal fatty streaks

Stroke

4 25

ATHEROSCLEROSIS, INTRACRANIAL • Fibrous atheromatous plaques contain o Smooth muscle cells, monocytes, other leukocytes o Connective tissue: Collagen, elastic fibers, proteoglycans o Intra- and extracellular lipid deposits o Angiogenesis produces new capillaries at plaque periphery • Leads to intraplaque hemorrhage and ulceration • Hemorrhage leads to dystrophic ferrocalcinosis (seen as calcification on CT, as iron on MR) • Arterial narrowing due to plaque o Flow limiting beyond 70% stenosis (based on diameter ratios) o Ischemic symptoms depend on collaterals • Slow occlusion leads to more collaterals, fewer symptoms • Rapid occlusion (from thrombosis or emboli) does not permit time for collaterals to develop, infarct likely • Arterial irregularity from disrupted endothelium may form thrombogenic surface leading to thrombosis or emboli 26

Microscopic

• Plaque stabilization ("statin" drugs) may decrease stroke • Angioplasty and/or stenting in some cases

I [)IAGNostICiCI-fE(tl\l.~S"f Consider • CTA and/or MRA as excellent screening tool • DSA gold standard, allows potential intervention

Image Interpretation

1.

2. 3.

4.

5.

6. 7.

8.

Staging, Grading or Classification Criteria • NASCET criteria (used in cervical disease), greater than 70% stenosis considered flow-limiting

9. lO. 11.

Presentation • Most common signs/symptoms: Transient ischemic attack, due to emboli, severe stenosis, progressive occlusion • Plaque rupture usually leads to stroke • Vascular stenosis leads to stuttering ischemia from intermittent thrombosis

Demographics • Age: Older age • Gender: Males = females • More common in Western countries

better

I SELECTED REFERENCES

Features

• Earliest findings o Lipid deposition, cellular reaction in intima • Later findings and determinants of stability in atherosclerotic plaques (MR holds promise for characterization of intraplaque composition) o Lipid core o Fibrous cap (thicker cap is more stable and less likely to rupture) o Inflammatory changes

Pearls

• Status of collaterals important; patients with developed collaterals tolerate stenosis/occlusion

12.

13. 14. 15. 16.

Natural History & Prognosis • Progressive disease unless treated aggressively • Poor prognosis without treatment, better prognosis with treatment

17.

Treatment

19.

• Low saturated fat and cholesterol diet; exercise (probably secondary) • Cholesterol lowering drugs (primary source of cholesterol so main treatment)

20.

18.

Stroke

Zaidat 00 et al: Asymptomatic middle cerebral artery stenosis diagnosed by magnetic resonance angiography. Neuroradiology. 46: 49-53, 2004 Suwanwela NC et al: Risk factors for atherosclerosis of cervicocerebral arteries. Neuroepidemiology 22:37-40,2003 Hirai T et al: Prospective evaluation of suspected stenoocclusive disease of the intracranial artery. AJNR 23:93-lO1,2002 Lernfelt B et al: Cerebral atherosclerosis as predictor of stroke and mortality in representative elderly population. Stroke 33:224-9, 2002 Pico F et al: Longitudinal study of carotid atherosclerosis and white matter hyperintensities. Cerebrovasc Dis 14:109-15,2002 Kramer CM: Magnetic resonance imaging to identify the high-risk plaque. AmJ CardioI21:90(lOC):15L-17L, 2002 Droste DW et al: Evaluation of progression and spread of atherothrombosis. Cerebrovasc Dis 13 Suppl1:7-11, 2002 Carr JC et al: Contrast-enhanced magnetic resonance angiography of the carotid circulation. Top Magn Reson Imaging 12:349-57, 2001 Summers PE et al: MR Angiography in cerebrovascular disease. Clin Radiol 56:437-56, 2001 Thijs VN et al: Symptomatic intracranial atherosclerosis. Neurology 55:490-7, 2000 Osborn AG: Atherosclerosis and carotid stenosis. in: Diagnostic cerebral angiography (2nd Ed), Lippincott Williams and Wilkins, Philadelphia, 359-79, 1999 Krinsky G et al: Gadolinium-enhanced 3D MRA of the aortic arch vessels in the detection of atherosclerotic cerebrovascular occlusive disease. JCAT 22:167-78, 1998 Garcia JH et al: Carotid atherosclerosis: definition, pathogenesis, and clinical significance. Neuroimaging Clinics of North America 6: 801-10, 1996 Consigny PJ: Pathogenesis of atherosclerosis. AJR 164: 553-8, 1995 Heiserman JE et al: Intracranial vascular occlusions. Radiol 185:667-73, 1992 Wolpert SM et al: Current role of cerebral angiography in the diagnosis of cerebrovascular diseases. AJR 159:191-7, 1992 North American Symptomatic Carotid Endarterectomy Trial Collaborators. NEJM 325:445-53, 1991 Schwaighofter BW et al: MR imaging of vertebrobasilar vascular disease. JCAT 14:895-904, 1990 Okazaki H: Fundamentals of Neuropathology, ed 2, pp 27-70, Tokyo: Igaku-Shoin, 1989 Beckman CF et al: The effect of sequential arterial stenosis on flow and pressure. RadioI140:655-58, 1981

I

A_T_H_E_R_O_S_C_LE_R_O_S_I_S_,_IN_T_R_A_C_RA __ N_I_A_L

_

Typical (Left) Anteroposterior

common carotid arteriogram shows origin occlusion of the internal carotid artery from atherosclerosis (arrow). DSA goals include assessment of cervical and intracranial stenosis. (Right) Lateral common carotid arteriogram shows focal intracranial internal carotid artery stenosis (arrow), a "tandem" lesion in a patient with cervical carotid bulb stenosis (not shown).

4 Typical

27 (Left) Lateral common

carotid arteriogram shows internal carotid artery" string sign" (arrows), which requires emergent intervention. Distinction from occlusion critical as occlusion requires no treatment. (Right) Lateral common carotid arteriogram shows severe proximal MCA stenosis (arrow). Note delayed arterial contrast phase in area supplied, while normally perfused brain is capillary phase.

Variant (Left) Axial FLAIRMR shows

high signal in the right cavernous internal carotid artery (curved arrow), which can be due to slow flow or occlusion. In this case, diagnostic angiography revealed slow flow. (Right) Axial T7 C+ MR shows enlarged tortuous SA (open arrow). Classic vertebrobasilar dolichoectasia in this patient with posterior circulation T1As.Slow, stagnant flow caused intravascular enhancement.

Stroke

ATHEROSCLEROSIS, EXTRACRANIAL

Graphic of ASVD. (A) Mild: "Fatty streaks"; slight intimal thickening. (B) Severe: Intraplaque hemorrhage; ulceration; platelet emboli. NASCET calculation % stenosis = b-a/bX700

4 28

Lateral DSA shows severe, focal stenosis involving the proximal ICA immediately post bulb. By NASCET criteria this is an approximately 85% stenosis (assuming ICA distal to stenosis is "b").

o Progresses to more focal and prominent eccentric thickening (subintimal macrocyte and smooth muscle cell deposition) o Subintimal hemorrhage from "new vessels" further narrows the lumen o Ulceration with rupture of fibrous cap and intima occurs, resulting in the "ulcerated plaque"

11ER.M.IN~L()GY Abbreviations

and Synonyms

• ASVD (atherosclerotic

vascular disease)

Definitions • Pathologic degenerative process resulting from deposition of plasma lipids in arterial walls

CT Findings

o

I IMAGING FIN liNGS General Features • Best diagnostic clue o Smooth or irregular narrowing of proximallCA o Calcium deposition in arterial walls • Location: Internal carotid and basilar arteries most common sites in head and neck • Size o Vessels affected are large, medium and small arteries and arterioles o Plaque ranges from microscopic lipid deposition to fatty streaks • Vary from 0.3-1.5 cm in diameter o "Fatty streaks" may coalesce to form larger masses • Morphology o Begins initially as smooth, slight eccentric thickening of the vessel intima

• NECT o Calcification in the vessel walls o Large plaques may show low density foci o Ectasia, tortuosity and fusiform vessel dilatation may also be present • CECT: Opacifies the vessel lumen, can mask ability to visualize calcified plaque • CTA o Enables visualization of degree stenosis vs occlusion o Correlates poorly with ulceration

MR Findings • TlWI o Wall thickening and luminal narrowing o Absence of "flow-void" may occur if vessel occluded or severely stenotic • FLAIR: May see secondary signs of extracranial ASVD (Le., lacunes, infarcts) • MRA o Degree of stenosis visualized

DDx: Atherosclerosis, Extracranial

ICA Dissection

VA Dissection

Stroke

ATHEROSCLEROSIS, EXTRACRANIAL Key Facts • Best imaging tool: DSA still gold standard for evaluating carotid stenosis; at least 4 projections recommended (AP, lateral, both obliques)

Terminology • Pathologic degenerative process resulting from deposition of plasma lipids in arterial walls

Top Differential

Imaging Findings

• Dissection • Fibromuscular • Vasospasm

• Smooth or irregular narrowing of proximal ICA • Location: Internal carotid and basilar arteries most common sites in head and neck • Plaque surface irregularity associated with increased risk of stroke at all degrees of stenosis • Tandem lesions (distal stenoses) present in approximately 2% of patients with significant cervical ICA lesions • Late phase angiogram important in setting of high grade stenosis or suspected occlusion to rule out "pseudo-occlusion"

Pathology

Clinical Issues • Endarterectomy if symptomatic 2': 70% (NASCET)

I DIFFERENTIAL DIAGNOSIS Dissection • Typically spares carotid bulb; no calcification • Seen in young-middle age groups • Smoother, longer narrowing without intracranial involvement

Findings

• Conventional o Identifies degree of stenosis, morphology of plaque, tandem stenoses, potential collateral pathways as coexisting pathology (Le., aneurysm) o Plaque surface irregularity associated with increased risk of stroke at all degrees of stenosis o Tandem lesions (distal stenoses) present in approximately 2% of patients with significant cervical ICA lesions o Hemodynamic effect of tandem stenoses is additive if both lesions are severe enough to reduce flow separately; if only one tandem lesion is critical, flow is governed by the more severe lesion o Late phase angiogram important in setting of high grade stenosis or suspected occlusion to rule out "pseudo-occlusion"

Nuclear Medicine

Findings

4

• Best imaging tool: DSA still gold standard for evaluating carotid stenosis; at least 4 projections recommended (AP, lateral, both obliques) • Protocol advice o Color Doppler ultrasound as initial screening procedure o CTA/MRA o Consider DSA prior to endarterectomy or in equivocal cases, or if CTA/MRA shows "occlusion" o Contrast-enhanced MRA

Findings

• (111) In-platelet scintigraphy may be used to detect thrombotic complications in carotid plaques

carotid stenosis than

Imaging Recommendations

• Grayscale imaging allows visualization of hypo (non-calcified) or hyper (calcified) plaque in vessel wall • Hypoechoic plaques are independent risk factors for stroke; strong correlation with 1 lipoprotein(a) • Doppler imaging measures flow velocity; peak systolic velocity best single velocity parameter for quantifying a stenosis • Spectral analysis allows evaluation of waveform; morphologic changes in waveform occur with increasing stenosis • Color Doppler may detect high grade occlusions more reliably than conventional Doppler

Angiographic

dysplasia (FMD)

• Leading cause of morbidity and mortality in West • NASCET method: % stenosis = normal lumen minimal residual lumen/normal lumen x 100 • Mild < 50%; moderate 50-70%; severe 70-99%

o Signal loss may occur if high-grade (Le., > 95%) stenosis o Severe narrowing causes "flow gap" (recovery of signal beyond stenosis)

Ultrasonographic

Diagnoses

Fibromuscular dysplasia (FMD) • "String of beads" » long segment stenosis

Vasospasm • Usually iatrogenic (catheter-induced),

transient

I PATHOLOGY General Features • General path comments o Complex, multifactorial process, pathogenesis of which remains controversial o Probably no single cause, no single initiating event, and no exclusive pathogenetic mechanism o Irregular plaque surface correlates with increased stroke risk; collateral circulation with lower stroke risk o Significant ICA narrowing identified in 20-30% of carotid territory strokes (vs 5-10% general population)

Stroke

29

ATHEROSCLEROSIS,

30

• Genetics o Probably multigenic o Many polymorphisms identified • Etiology o Three main hypotheses have been proposed: Lipid hypothesis, response to injury hypothesis, and "unifying theory" • Lipid hypothesis: Relates ASVD to high plasma LDL levels causing LDL-cholesterol deposits in the arterial intima • Response to injury hypothesis: ASVD is initiated by focal endothelial damage that initiates platelet aggregation and plaque formation • Unifying theory: Suggests that endothelial injury is accompanied by increased permeability to macromolecules such as LDL o Other factors include diet, genes, mechanical stress (e.g., wall shear, anatomic variations), inflammation, hyperhomocysteinemia • Epidemiology o Leading cause of morbidity and mortality in West o Ischemic stroke accounts for up to 40% of deaths in elderly o Cerebral infarctions occur in > 70% of patients with carotid occlusion o 90% of large, recent infarcts caused by thromboemboli o Strong epidemiological and experimental evidence that increased dietary lipid (especially cholesterol, saturated fats) correlates with development of atherosclerotic lesions

Gross Pathologic & Surgical Features • Two well accepted lesions described: Atheromatous plaque and fatty streak o Atheromatous plaque: Most important lesion, being principal cause of arterial narrowing in adults o Fatty streak: Important precursor of atheromatous plaque; present universally in children, even in first year of life • Intimal "fatty streaks" are earliest macroscopically visible lesions • Plaques are whitish-yellow, protrude intraluminally and vary in size

Microscopic

Features

• Fibroatheromatous plaques are basic lesion of ASVD; and develop following lipid deposition • Plaques contain cells (monocytes/macrophages, leukocytes, smooth muscle); connective tissue; intra/extracellular lipid deposits • A necrotic core of lipid material, cholesterol, cellular debris, lipid-laden foam cells and fibrin form deep within plaque • Neovascularization occurs; may lead to vessel rupture causing intraplaque hemorrhage and ulceration • Atheromatous plaque itself may also rupture (fibrous cap weakens and fractures); may lead to distal embolization

EXTRACRANIAL • NASCET method: % stenosis = normal lumen minimal residual lumen/normal lumen x 100 • Mild < 50%; moderate 50-70%; severe 70-99%

Presentation • Most common signs/symptoms: Variable; including asymptomatic, carotid bruit, TIA, stroke (may be silent) • Clinical profile: Patient with typical risk factors for stroke: Smoking, HTN, diabetes, obesity, . hypercholesterolemia, advanced age

Demographics • Age: Usually middle aged to elderly • Gender: Male> female • Ethnicity: African-American with highest risk of ASVD

Natural History & Prognosis • Progressive, significant stenosis may cause decreased cerebral perfusion

Treatment • Endarterectomy if symptomatic carotid stenosis than ~ 70% (NASCET) • Symptomatic moderate stenosis (50-69%) also benefits from endarterectomy (NASCET) • Asymptomatic patients benefit even with stenosis of 60% (ACAS) • Percutaneous carotid stenting depending on surgical risk factors

1[)IAC~()$tl<E}iCt-tEC~~ISj Consider • For calculation of degree of stenosis on DSA at least two projections are required to profile plaque adequately • For preop patients undergoing CEA, adequacy of collateral circulation becomes critical; consider MRA or DSA • Pseudo-occlusion (very high grade stenosis) may be seen only on late phase angiogram; CEA still option if ICA patent

1.

2.

3.

Staging, Grading or Classification Criteria • Methods for calculating degree of stenosis vary; NASCET, ACAS, ECST AND VACSG

Stroke

Chen C-J et al: Multislice CT angiography in diagnosing total versus near occlusions of the internal carotid artery: comparison with catheter angiography. Stroke 35:83-5, 2004 Moll R et al: Value of the CT angiography in the diagnosis of common carotid artery bifurcation disease: CT angiography versus digital subtraction angiography and color flow Doppler. Eur J Radiol. 39(3):155-62, 2001 Binaghi S et al: Three-dimensional computed tomography angiography and magnetic resonance angiography of carotid bifurcation stenosis. Eur Neurol. 46(1):25-34, 2001

ATHEROSCLEROSIS,

EXTRACRANIAL

I IMAGE GALLERY Typical (Left) Lateral DSA shows

extensive ASVD with tandem lesion of common (white arrow) and internal carotid (black arrow) arteries. Note the ulcerated plaque (open arrow) in ICA. (Right) Lateral DSA shows complete ICA occlusion (arrow) from severe ASVD. Delayed phase run (important in cases such as these with occlusion or pseudo-occlusive disease) showed no "string sign".

4 Typical

31 (Left) Ultrasound images

(transverse upper; sagittal lower) demonstrate predominately hyperechoic (calcified) plaque (arrows) involving the common and internal carotid arteries. (Right) Axial NECT shows typical appearance of ASVD of the carotid arteries. Moderate calcified plaque is seen along the posterior wall of the left carotid bulb (arrow); mile on the right.

Typical (Left) Lateral DSA shows a

left CCA injection. Hemostats mark an area of moderately severe ASVD affecting post-bulbar ICA. (Right) Lateral DSA in the same case post carotid stent placement (arrow) shows an excellent angiographic result with marked improvement in ICA narrowing.

Stroke

ARTERIOLOSCLEROSIS

Axial graphic shows atrophy, cortical infarcts (arrows) and multiple foci of abnormality in deep nue/ei (open arrows), typical in small vessel disease and/or multi-infarct dementia.

4 32

o Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) • Large number of causes other than arteriopathy (demyelination, infection, inflammatory, drug related, metabolic) • Clinical + radiographic picture overlaps with multi-infarct and/or vascular dementia and subcortical arteriosclerotic disease = Binswanger disease

ITERMINOlOGY Abbreviations

and Synonyms

• Small vessel disease, microangiopathy • Imaging correlate = leukoariosis or periventricular leukoencephalopathy

Definitions • Sclerosis of small sized arteries (arterioles), common from chronic hypertension and/or DM, often leading to dementia

I IMAGING

Axial T2WI MR shows multiple patchy and confluent periventricular white matter hyperintensities, typical for arteriolose/erotic disease.

CT Findings • NECT: Multifocal/confluent areas ~ 5 mm • CECT: No enhancement

FINDINGS

ill-defined hypodense

MR Findings

General Features • Best diagnostic clue: White matter rarefaction on CT; patchy/confluent hyperintensity on PD/T2Wl/FLAIR • Location: PVWM (periventricular white matter) and deep white matter, basal ganglia • Size: Varies, progress with age • Morphology: Patchy or confluent • Significance of PVWM hyperintensities controversial; findings non-specific, likely due to several types of arteriopathy o Arteriolosclerosis o Chronic hypertension and/or diabetes mellitus (DM) o Cerebral amyloid angiopathy

DDx: Mimics of Arteriosclerotic

• T1WI: Patchy or confluent hypointense foci in PVWM • T2WI: Ill-defined hyperintensities ~ Smm • PD/Intermediate: Patchy or confluent hyperintense foci in PVWM • FLAIR: Most conspicuous sequence for PVWM hyperintensities • T2* GRE: +/- Multifocal "black dots" on T2* (overlap with chronic hypertension, amyloid) • DWI: No associated restriction (isointense) • Tl C+: Nonenhancing • MRS: Reduced N-acetyl aspartate (NAA), NAA/Cr • +/- Generalized atrophy (large ventricles, sulci)

Disease

I

,f

.. / '

\

"

.

\ Senescent

ChanRes

Enlarged

Demyelination

Stroke

PVSs

"

/ CADASIL

ARTERIOLOSCLEROSIS Key Facts Terminology

Pathology

• Small vessel disease, micro angiopathy

• "Microangiopathy-related cerebral damage" = PVWM hyperintensities, lacunar infarcts • Imaging PVWM hyperintensities have spectrum of histopathologic correlates

Imaging Findings • Best diagnostic clue: White matter rarefaction on CT; patchy/confluent hyperintensity on PD/T2WI/FLAIR • Location: PVWM (periventricular white matter) and deep white matter, basal ganglia • T2* GRE: +/- Multifocal "black dots" on T2* (overlap with chronic hypertension, amyloid)

Top Differential

Diagnoses

• Use FLAIR, GRE sequences in all elderly patients

• Long-standing hypertension, progressive decline in mental function, gait disturbances, with or without minor strokes • Large, small infarcts • Decreased rCBF

lesions found in 2-6% of normal

Angiographic

Findings

• Conventional: common

Small and larger vessel arterial stenoses

Nuclear Medicine

CADASIL

Findings

• Younger age patient ::0; 40 yo with PVWM hyperintensities • Stronger predilection for temporal lobe involvement than other PVWM hyperintensities

• PET/SPECT: In absence of atrophy, rCBF/rMRGlu usually normal

Imaging Recommendations • Best imaging tool: MR • Protocol advice: NECT screen, MRI with FLAIR + GRE

I PATHOLOGY General Features

I DIFFERENTIAL DIAGNOSIS Age-related

white matter changes

• Significant overlap with normal vs demented elderly • Normal rCBF • Other risk factors (hypertension, DM) common

Perivascular (Virchow-Robin)

spaces (PVSs)

• Variable size, well-delineated • Most common around anterior commissure, deep white matter • Signal, attenuation like CSF • Peripheral high signal on FLAIR can be seen with both lacunar infarcts and perivascular spaces

Demyelinating

• Clinical profile: Older patient with cerebrovascular risk factors (hypertension, age, hypercholesterolemia, diabetes, etc) • PVWM hyperintensities almost universal after 65 y

Diagnostic Checklist

• Age-related white matter changes • Perivascular (Virchow-Robin) spaces (PVSs)

• Extensive/confluent elderly!

Clinical Issues

disease

• MS > ADEM • Usually ovoid, periventricular • Callososeptal interface involved (rare with ASVD)

Vascular dementia (VaD) overlaps with arteriolosclerotic disease • Cognitive impairment o Multi-infarct dementia (MID) o Subcortical arteriosclerotic encephalopathy ("Binswanger" type vascular dementia) • Clinical (not imaging) diagnosis

• General path comments o "Microangiopathy-related cerebral damage" = PVWM hyperintensities, lacunar infarcts o PVWM hyperintensities on imaging does not always have pathologic correlate • Genetics o General risk factors for peripheral/cerebral vascular diseases • APOE E4 alleles • Angiotensinogen gene promoter o CADASIL • Notch3 mutations • Etiology o Hypertensive occlusive disease of small penetrating arteries • Results in lacunar infarcts, deep white matter lesions o Venous collagenosis (controversial) • Epidemiology: Vascular dementia (VaD) third most common cause of dementia (after Alzheimer disease, Lewy body disease), accounts for 15% of cases

Gross Pathologic & Surgical Features • Prominent sulci, ventricles common • Periventricular WM spongiosis • Multifocallacunes often present

Stroke

4 33

ARTERIOLOSCLEROSIS 3.

Microscopic Features • Normal age-related changes • Imaging PVWM hyperintensities have spectrum of histopathologic correlates o Degenerated myelin (myelin "pallor") o Axonal loss, increased intra-/extracellular fluid o Gliosis, spongiosis o Arteriosclerosis, small vessel occlusions o Dilated perivascular spaces

4.

5. 6. 7.

Staging, Grading or Classification Criteria

34

8.

• European Task Force on Age-Related White Matter Changes (ARWMC) rating scale for MRI and CT (for ill-defined lesions ~ 5 mm) o White matter lesions • 0 = no lesions (including symmetrical caps, bands) • 1 = focal lesions • 2 = beginning confluence of lesions • 3 = diffuse involvement, with or without U-fibers o Basal ganglia lesions • 0 = no lesions • 1 = 1 focal lesion (~ 5 mm) • 2 = > 1 focal lesion • 3 = confluent lesions

I CUNr(jA\.LiIS$LJES

9.

10.

11.

12.

13.

14.

Presentation • Most common signs/symptoms o Broad range • From normal, minimal cognitive impairment to demented • Clinical profile: Older patient with cerebrovascular risk factors (hypertension, age, hypercholesterolemia, diabetes, etc)

Demographics

Natural History & Prognosis

17.

Treatment of known cerebrovascular

19.

20.

• Little known

I DIAGNOSTIC

16.

18.

• Age o PVWM hyperintensities almost universal after 65 y o Lacunar infarcts in 1/3 of asymptomatic healthy patients> 65 y • Gender: Males = females

• Modification

15.

risk factors

CHECKLIST

Consider

21.

22.

23.

• Use FLAIR, GRE sequences in all elderly patients

1.

2.

Lee SH et al: Comparative analysis of the spatial distribution and severity of cerebral microbleeds and old lacunes. J Neurol Neurosurg Psychiatry 75:423-7, 2004 Gass A et al: Diffusion-weighted MRI for the "small stuff": the details of acute cerebral ischemia. Lancet Neurol. 3: 39-45,2004

Stroke

Arboix A et al: New concepts in lacunar stroke etiology: the constellation of small-vessel arterial disease. Cerebrovasc Dis 17 Suppl1:58-62, 2004 van Straaten EC et al: Operational definitions for the NINDS-AIRENcriteria for vascular dementia: an interobserver study. Stroke 348:1907-12, 2003 Udaka F et al: White matter lesions and dementia. Ann N Y Acad Sci 977:411-5,2002 van Den Boom R et al: Subcortical lacunar lesions. Radiol 224:791-6,2002 Schmidt R et al: The natural course of MRI white matter hyperintensities. J Neurol Sci. 203-204:253-7, 2002 Schmidt R et al: Evolution of white matter lesions. Cerebrovasc Dis.13:Supp12:16-20, 2002 Cohen RA et al: The relationship of subcortical MRI hyperintensities and brain volume to cognitive function in vascular dementia. J Int Neuropsychol Soc. 8:743-52, 2002 Varma AR et al: Diagnostic value of high signal abnormalities on T2 weighted MRI in the differentiation of Alzheimer's, frontotemporal and vascular dementias. Acta Neurol Scand 105:355-64, 2002 Schmidt R et al: Risk factors and progression of small vessel disease-related cerebral abnormalities. J Neural Transm Suppl. 62:47-52, 2002 Wahlund LO et al: A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:1318-22,2001 Schmidt H et al: Angiotensinogen gene promoter haplotype and microangiopathy-related cerebral damage. Stroke 32:405-412, 2001 Marti-Fabregas J et al: Blood pressure variability and leukoariosis amount in cerebral small-vessel disease. Acta Neurol Scand 104:358-63, 2001 Auer DP et al: Differential lesion pattern in CADASILand sporadic subcortical arteriosclerotic encephalopathy. Radiol 218:443-51,2001 Yao H et al: Cerebral blood flow in nondemented elderly subjects with extensive deep white matter lesions on MRI. J Stroke Cerebrovasc Dis 9:172-5,2000 Hirono N et al: Effect of the apolipoprotein E epsilon4 allele on white matter hyperintensities in dementia. Stroke 31:1263-8,2000 Schelten et al: White matter changes on CT and MRI: an overview of visual rating scales. European Task Force on Age-Related White Matter Changes. Eur Neurol139:80-9, 1998 Sultzer DL et al: Cortical abnormalities associated with subcortical lesions in vascular dementia. Clinical and position emission tomographic findings. Arch Neurol 52:773-80, 1995 Scheltens P et al: Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging. Neurology 45:883-8, 1995 Wahlund LO et al: White matter hyperintensities in dementia: does it matter? Magn Reson Imaging 12:387-94, 1994 Fazekas F et al: Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 43:1683-9, 1993 De Cristofaro MT et al: Subcortical arteriosclerotic encephalopathy: single photon emission computed tomography-magnetic resonance imaging correlation. Am J Physiol Imaging 5:68-74, 1990

ARTERIOLOSCLEROSIS

Typical (Left) Axial NEeT shows

characteristic confluent periventricular white matter low density in arteriolosclerosis (microangiopathic changes). (Right) Axial FLAIRMR shows typical high signal foci in the white matter in arteriolosclerosis.

4 35 (Left) Axial NEeT shows

multiple infarcts and patchy periventricular white matter low density in a patient with dementia. Multi-infarct dementia overlaps with other causes, and is likely multifactorial. (Right) Axial T2WI MR shows multiple chronic infarcts and extensive white matter volume loss and high signal changes in a patient with dementia.

Variant

(Left) Axial T2* eRE MR shows multiple hypointense foci in the brainstem and occipital lobe (arrows) in a patient with chronic hypertensive microangiopathy. (Right) Axial T2WI MR shows multiple rounded high signal foci in the deep nuclei, "etat crible". Most of these "white spots" are prominent VRSs. The confluent WM disease is probably ASVD.

Stroke

PERSISTENT TRIGEMINAL ARTERY

Lateral view, selective internal carotid angiogram, shows classic "Neptune's trident" formed by the ICA and a Saltzman type 1 persistent trigeminal artery (arrow) (Courtesy H. Alvarez, MO).

4 36

Sagittal MRA shows a low trigeminal artery (arrow).

• T2WI: Prominent anomalous vessel between ICA and BA, may pass through sella and dorsum on axial view • MRA: Depicts carotid basilar anastomosis, associated lesions (e.g., aneurysm)

ITERMINOlQ(jY Abbreviations

and Synonyms

• Persistent trigeminal

origin of a persistent

artery (PTA)

Definitions

Angiographic Findings

• Persistent (embryonic) carotid basilar anastomosis (PCBA) between cavernous ICA, basilar artery (BA) • Most common carotid basilar anastomosis

• Conventional o Saltzman type I • PTA supplies distal vertebrobasilar system, PCoAs usually absent • BA below anastomosis usually hypoplastic o Saltzman type II • PTA fills superior cerebellar arteries • Posterior cerebral arteries supplied via patent PCoAs o Other vascular anomalies in 25% of cases (aneurysms: 15%)

I IMAGING FINDINGS General Features • Best diagnostic clue: Abnormal vessel between BAjlCA below level of PCoA • Location: lntra- or posterior to sella turcica • Morphology: Vessel from cavernous ICA courses posteriorly, then medially to join BA

Imaging Recommendations • Best imaging tool: MRI + MRA followed by DSA for confirmation

CT Findings • CECT: Large caliber vessel between BA and ICA • CTA: Delineates presence and course of vascular anomaly, associated abnormalities (e.g., saccular aneurysm)

I DIFFERENTIAL

DIAGNOSIS

MR Findings

"Fetal" origin of posterior cerebral artery (PCA)

• T1WI: "Neptune's trident" on sagittal view

• Common;

above sella

DDx: PCBAs

PIA

Stroke

Fetal peA

PERSISTENT TRIGEMINAL ARTERY Key Facts • Persistent otic artery (POA) • Proatlantal intersegmental artery (PIA)

Imaging Findings • Morphology: Vessel from cavernous ICA courses posteriorly, then medially to join BA • Tl WI: "Neptune's trident" on sagittal view • Best imaging tool: MRI + MRA followed by DSA for confirmation

Top Differential

Pathology • Associated with small PCoA, vertebral arteries, proximally hypoplastic BA • Epidemiology: Present in 0.1-0.2% of cerebral angiograms • 25% prevalence of other vascular anomalies (e.g., aneurysm)

Diagnoses

• "Fetal" origin of posterior cerebral artery (PCA) • Persistent hypoglossal artery (PHA)

• Associated abnormalities a 25% prevalence of other vascular anomalies (e.g., aneurysm) a Rare: Carotid-cavernous fistula, AVM, arterial fenestration, NFl a Very rare: Moyamoya, subclavian steal, absent CC/ICA, BA; aorta coarctation

• PCoA prominent; PI segment of PCA hypoplastic/ absent

Persistent hypoglossal artery (PHA) • 2nd most common PCBA a Found in 0.03-0.26% of angiograms a Partly parallels CN 12 a Connects cervical ICA (approximately with BA

Cl-2 level)

Presentation

• Very rare • Courses from petrous ICA through internal acoustic meatus to caudal BA • Vertebral arteries may be absent or hypoplastic, POA may be dominant or only supply to BA

Proatlantal intersegmental

37

I CLINICAL ISSUES

Persistent otic artery (POA)

• Most common signs/symptoms a Incidental finding at imaging a Trigeminal neuralgia (rare) a Pituitary dysfunction • Associated vascular anomaly may cause ICH

artery (PIA)

• Most caudal of PCBAs • Originates from cervical ICA (approximately C2-3 level) or (less commonly) from ECA • Communicates with vertebral artery coursing between arch of C1 and occiput • Vertebral arteries may be absent or hypoplastic, PIA may be dominant or only supply to BA

Natural History & Prognosis • Asymptomatic,

no treatment

(unless aneurysms)

I SELECTED REFERENCES 1. 2.

!PATHOlOGY 3.

General Features • General path comments a Embryology • Several transient segmental connections between primitive carotid, hindbrain circulations appear in early fetal development • Connections are named according to cranial nerves they parallel • Embryonic trigeminal artery supplies BA before PCoA, vertebral arteries develop a Anatomy • PTA arises from cavernous ICA • Runs posterolaterally along trigeminal nerve (41 %) or directly through dorsum sellae (59%) • Associated with small PCoA, vertebral arteries, proximally hypoplastic BA • Etiology: Embryonic trigeminal artery regresses as definitive circulation develops, failure to regress causes PTA • Epidemiology: Present in 0.1-0.2% of cerebral angiograms

4.

Uchina A et al: Persistent trigeminal artery variants detected by MR angiography. Eur Radiol 10: 1801-4, 2000 Suttner et al: Persistent trigeminal artery: A unique anatomic specimen analysis and therapeutic implications. Neurosurg 47(2): 428-33, 2000 Hirai T et al: MR angiography of the persistent trigeminal artery variant. ]CAT 19: 495-497, 1995 Silbergleit et al: Persistent trigeminal artery detected with standard MRI.]CAT 17: 22-25,1993

I IMAGE GAllERY

(Left) Axial MRA source view shows left sided persistent trigeminal

artery (arrow). Here the PTA courses posterolaterally around the dorsum sellae. (Right) Sagittal MRA in the same patient shows the anomalous artery (arrow). This is a Saltzman type 1 PTA.

Stroke

4

SICKLE CELL DISEASE

Axial FLAIR MR shows bifrontal cortical and left frontal deep white matter infarctions with mild bifrontal atrophy in a patient with classic cerebral complications ofSCD.

Axial MRA shows bilateral narrowed ICAs and MCAs with subtle enlargement of lateral lenticulostriate arteries causing early moyamoya ("puff of smoke") pattern (arrows).

38

CT Findings Abbreviations

and Synonyms

• Sickle cell disease (SCD)

Definitions • Abnormality in hemoglobin (Hgb) ~ change in shape ("sickling") ~ increased "stickiness" of erythrocytes (RBCs) ~ capillary occlusions, ischemia, infarctions, premature RBC destruction (hemolytic anemia)

General Features • Best diagnostic clue o Narrowing of the distal ICAs ~ moyamoya • Moyamoya (lenticulostriate collaterals) • Location: ICAs; deep white matter, cortex; bone marrow • Use MRI to document previous ischemic events • Caveat: Cognitive impairment does not correlate with imaging findings

Radiographic Findings • Radiography o Thick skull with expanded diploic space o Opacified paranasal sinuses

• NECT o Focal encephalomalacia due to cortical infarction o Adult moyamoya: Intraventricular bleed may be initial presentation • CECT: Punctate enhancement in basal ganglia due to moyamoya collaterals • CTA: Stenosis of distal ICA, proximal COW

MR Findings • TlWI o Hemorrhagic infarcts may be seen o Punctate flow voids in basal ganglia correspond to moyamoya collaterals o Abnormal signal intensity in bone marrow which may be expanded • T2WI: Cortical, deep white matter infarcts (often in distal watershed ACA/MCA) • PD/lntermediate: Same as T2WI • FLAIR: Multifocal hyperintensities +/- ivy sign of moyamoya • DWI: Focal hyperintensities due to acute infarctions • Tl C+: Vascular stasis and leptomeningeal collaterals in MCA territory with proximal MCA stenosis ·MRA o Aneurysms in atypical locations o Stenosis of distal ICA, proximal COW

DDx: Sickle Cell Disease Mimics

Homocystinuria

PACNS

Homocystinuria

Stroke

Thalassemia

SICKLE CELL DISEASE Key Facts Terminology

Pathology

• Abnormality in hemoglobin (Hgb) ~ change in shape ("sickling") ~ increased "stickiness" of erythrocytes (RBCs) ~ capillary occlusions, ischemia, infarctions, premature RBC destruction (hemolytic anemia)

• Hgb S becomes "stiff" (hence, erythrocytes are sickle-shaped) when deoxygenated • Primary cause of stroke in African-American children • Stroke incidence decreased if Hgb S kept to less than 30% by transfusion (but need initial ischemic event to initiate therapy)

Imaging Findings • Moyamoya (lenticulostriate collaterals) • Hemorrhagic infarcts may be seen • T2WI: Cortical, deep white matter infarcts (often in distal watershed ACA/MCA) • Stenosis of distal ICA, proximal COW

Top Differential

Clinical Issues • Age: Infarctions are generally first seen in children about 10 years of age • Hgb S found in 10% of African-Americans

Diagnoses

Diagnostic Checklist • African-American child with cerebral infarction: Always consider SCD!

• Vasculitis • Connective tissue disorders • Thick skulfwith expanded diploe

• Caveat: Turbulent dephasing due to anemia, rapid flow can mimic stenosis on "bright blood" MRA • Suggestion: Use lowest possible TE for bright blood MRA or use black blood MRA if stenosis suspected o MRA source images: Multiple dots in basal ganglia due to moyamoya • MRS: 1 Lactate, !NAA, !Cho, !Cr in areas of infarction (lactate seen only in acute infarctions) • Perfusion studies: ! rCBF, ! rCB\!; 1 TIP, 1 MTI

Ultrasonographic

Angiographic

flow in MCA

Findings

• Conventional o DSA: Stenosis of distal ICA, proximal COW; fusiform aneurysms; moyamoya EC-IC and collaterals • Risk of stroke higher than in other populations • Hydrate, transfuse before catheter study o Moyamoya may be associated to persistent primitive carotid-basilar arterial communications

Nuclear Medicine

• Marfan, Ehlers-Danlos, homocystinuria • Progressive arterial narrowing and occlusion

Thick skull with expanded diploe • Other chronic anemias (thalassemia)

I

PATHOLOGY

General Features

Findings

• Transcranial Doppler: Hyperdynamic secondary to proximal stenosis

Connective tissue disorders

Findings

• PET: Focal areas of low brain perfusion

Imaging Recommendations • Best imaging tool: MRI with MRA +/- DSA • Protocol advice o MRI to exclude previous infarcts o Short TE bright blood MRA or black blood MRA (to exclude distal ICA stenosis and moyamoya collaterals)

I DIFFERENTIAL DIAGNOSIS Vasculitis • Infectious, autoimmune or substance abuse etiologies • Classic imaging findings: Cortical and deep white matter infarcts and parenchymal hemorrhage • Radiation-induced: May cause moyamoya picture but history provides clue

• General path comments o Initial endothelial injury from abnormal adherence of sickled RBCs o Subsequently internal elastic lamina fragmentation and degeneration of muscularis result in large vessel vasculopathy and aneurysm formation • May be reversed with transfusion • Genetics o Homozygous for Hgb S o Mutation in 0-globin, changes glutamic acid to valine • Etiology o Heterozygous Hgb S affords increased resistance to malaria (hence prevalence) o Hgb S becomes "stiff" (hence, erythrocytes are sickle-shaped) when deoxygenated • RBCs loose pliability required to traverse capillaries • RBCs have "sticky" membrane • Result: Microvascular occlusion, cell destruction (hemolysis) o Homozygous SS leads to sickling and vascular occlusion ("crisis") • Epidemiology o Primary cause of stroke in African-American children • Stroke incidence decreased if Hgb S kept to less than 30% by transfusion (but need initial ischemic event to initiate therapy) o By 10 years of age

Stroke

4 39

• 44% have cerebral ischemia, infarction, atrophy (35% are silent) • 55% have vasculopathy o Incidence of cerebral lesions in sickle cell trait: 10-19% • Associated abnormalities o Anemia, reticulocytosis, granulocytosis o Susceptibility to pneumococci (due to malfunctioning spleen) o Occasionally causes pseudotumor cerebri (idiopathic intracranial hypertension without evidence for venous sinus occlusion, etc)

Gross Pathologic & Surgical Features

Treatment • Repeated transfusions to keep Hgb S less than 30% decreases both incidence of stroke and intimal hyperplasia in COW vessels • Folic acid for anemia • Hydration and oxygenation during crises

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• African-American child with cerebral infarction: Always consider SCD!

• Bone, brain, renal and splenic infarcts; hepatomegaly

Microscopic

Features

I SELECTED REFERENCES

• Severe anemia with sickled cells on smear • Vascular occlusions due to masses of sickled RBCs

1.

2.

4 40

Presentation

3.

• Most common signs/symptoms o Vasoocclusive crisis with infarctions involving • Spleen, brain, bone marrow, kidney, lung, bone, formation of gallstones, priapism, neuropathy, skin ulcers • Clinical profile o Stroke in African-American children • 75% are ischemic, 25% are hemorrhage • 17-26% of all patients with SCD • Bone infarcts, avascular necrosis during crisis • Osteomyelitis, especially Salmonella • Gross hematuria from renal papillary necrosis and ulceration • Splenic infarction from exposure to high altitude, e.g., flying • Infections common, especially pneumococcus after splenic infarction

4.

5. 6.

7. 8.

9.

10.

Demographics • Age: Infarctions are generally first seen in children about 10 years of age • Gender: No predilection • Ethnicity o Hgb S found in 10% of African-Americans o SCD found primarily in African-Americans and their decendents

11.

Natural History & Prognosis

15.

• Unrelenting, severe hemolytic anemia beginning at a few months of age after Hgb S replaces Hgb F (fetal) o Cognitive dysfunction occurs even in absence of cerebral infarctions • Repeated ischemic events leading to strokes with worsening motor and intellectual deficits • Poor for homozygous SCD without transfusions • Usually live to adulthood albeit with complications

12.

13. 14.

16.

17.

Stroke

Henry M et al: Pseudotumor cerebri in children with sickle cell disease: A case series. Pediatrics 113 (3 pt 1): e265-9, 2004 Kral MC et al: Transcranial Doppler ultrasonography and neurocognitive functioning in children with sickle cell disease. Pediatrics. 112(2):324-31, 2003 Yerys BE et al: Memory strategy training in children with cerebral infarcts related to sickle cell disease. J Pediatr Hematol Oncol. 25(6):495-8, 2003 Kwiatkowski JL et al: Transcranial Doppler ultrasonography in siblings with sickle cell disease. Br J Haematol. 121(6):932-7,2003 Steen RG et al: Brain imaging findings in pediatric patients with sickle cell disease. Radiology. 228(1):216-25, 2003 Steen RG et al: Prospective brain imaging evaluation of children with sickle cell trait: initial observations. Radiology. 228(1):208-15, 2003 Alam M et al: Cerebrovascular accident in sickle cell disease. J Coli Physicians Surg Pak. 13(1):55-6, 2003 Oguz KK et al: Sickle cell disease: continuous arterial spin-labeling perfusion MR imaging in children. Radiology. 227(2):567-74,2003 Steen RG et al: Cognitive impairment in children with hemoglobin SS sickle cell disease: relationship to MR imaging findings and hematocrit. AJNR Am J Neuroradiol. 24(3):382-9, 2003 Moster ML: Coagulopathies and arterial stroke. J Neuroophthalmol. 23(1):63-71, 2003 Driscoll MC et al: Stroke risk in siblings with sickle cell anemia. Blood. 101(6):2401-4,2003 Riebel T et al: Transcranial Doppler ultrasonography in neurologically asymptomatic children and young adults with sickle cell disease. Eur Radiol. 13(3):563-70, 2003 Carvalho KS et al: Arterial strokes in children. Neurol Clin. 20(4):1079-100, vii, 2002 Fixler Jet al: Sickle cell disease. Pediatr Clin North Am. 49(6):1193-210, vi, 2002 Oyesiku NM et al: Intracranial aneurysms in sickle-cell anemia: clinical features and pathogenesis. J Neurosurg 75: 356-63, 1991 Wiznitzer M et al: Diagnosis of cerebrovascular disease in sickle cell anemia by magnetic resonance angiography. J Pediatr 117(4): 551-5,1990 Rothman SM et al: Sickle cell anemia and central nervous system infarction: a neuropathological study. Ann Neurol 20: 684-90, 1986

SICKLE CELL DISEASE

I IMAGE

GALLERY

Typical (Left) Axial T2WI MR in a patient with SCD shows moyamoya caused by supra clinoid ICA stenosis + enlarged, tortuous lenticulostriate arteries (arrows). (Right) Axial T2WI MR obtained at the basal ganglia level in the same patient shows large thalamoperforating arteries (arrows). These collateral vessels arise from the COW and posterior cerebral arteries.

4 Typical

41 (Left) Axial OWl MR shows left MCA acute infarction and subacute infarction in the right parietal region. (Right) Lateral angiogram shows in the same patient marked narrowing of the supraclinoid left ICA (arrow). SCD vasculopathy with acute stroke.

Typical (Left) Axial MR perfusion study shows increased CBF in the posterior regions and decreased CBF in both MCA territories. (Right) Coronal MRA in the same patient shows occluded ICAs (arrows) with hypertrophy and proliferation of deep perforating arteries arising from the PCAs.

Stroke

MOYAMOYA

Coronal graphic shows severe tapering of both distal internal carotid arteries (arrows) and strikingly enlarged lenticulostriate arteries (open arrows) ("puff of smoke "/moyamoya) pattern.

4 42

o Adults: Hemorrhage (esp intraventricular) • CECT: Enhancing dots (big lenticulostriates) in BG & abnormal "net-like" vessels at base of brain • CTA: Abnormal COW & "net-like" collaterals • Xe-133 CT: j Cerebral reserve with acetazolamide challenge

I TERMINOLOGY Abbreviations

and Synonyms

• Idiopathic progressive arteriopathy of childhood; spontaneous occlusion of the circle of Willis

Definitions • Progressive narrowing of distal ICA and proximal circle of Willis (COW) vessels with secondary collateralization • Moyamoya-likecollateralization may occur with ANY progressive vascular occlusion (inherited or acquired)

IMAGING FINDINGS General Features • Best diagnostic clue: Multiple punctate dots (CECT) & flow-voids (MR) in basal ganglia (BG) • Location: COW; Anterior »> posterior circulation • Size: Large vessel occlusion • Morphology: "Puff or spiral of smoke" (moyamoya in Japanese) = cloud-like lenticulostriate and thalamostriate collaterals on angiography

CT Findings • NECT o Children: 50-60% show anterior>

Lateral view, selective internal carotid angiogram, shows severe stenosis of the supraclinoid ICA (arrow) with "puff of smoke" (open arrow) from collateral lenticulostriate vessels.

MR Findings • TlWI: Multiple dot-like flow voids in BG • T2WI o t Signal small vessel cortical and white matter infarcts o Collateral vessels = "net-like" cisternal filling defects • FLAIR o Bright sulci = leptomeningeal "ivy sign" • Slow-flowing engorged pial vessels, thickened arachnoid membranes • T2* GRE: Hemosiderin if prior hemorrhage • DWI: Positive in acute stroke; VERYuseful in "acute on chronic" disease • Tl C+ o Lenticulostriate collaterals ~ enhancing "dots" in BG and "net-like" thin vessels in cisterns o Leptomeningeal enhancement (contrast-enhanced "ivy sign") j after "effective bypass surgery" • MRA: Narrowed distal ICA and proximal COW vessels, +/- synangiosis

posterior atrophy

DDx: "Ivy Sign" look-alikes

Metastases

Metastases

Meninf{itis

Stroke

700% 02

Key Facts Terminology • Idiopathic progressive arteriopathy of childhood; spontaneous occlusion of the circle of Willis • Progressive narrowing of distal ICA and proximal ~~~~~a:~~i~~COW)

vessels with secondary

• Moyamoya-like collateralization may occur with ANY progressive vascular occlusion (inherited or acquired) entity

Imaging Findings • Best diagnostic clue: Multiple punctate dots (CECT) & flow-voids (MR) in basal ganglia (BG) • Morphology: "Puff or spiral of smoke" (moyamoya in Japanese) = cloud-like lenticulostriate and thalamostriate collaterals on angiography • Bright sulci = leptomeningeal "ivy sign"

• MRV: Some vasculopathies leading to moyamoya may also involve veins • MRS o Lactate in acutely infarcted tissue o NAA/Cr and Cho/Cr ratios frontal white matter improve/increase after revascularization • Perfusion-weighted imaging (PWI): ! Perfusion deep hemispheric white matter, relative t perfusion posterior circulation o PWI may be abnormal when MRI still normal o Regional cerebral blood volume (rCBV) and time to peak (TIP) correlate with stage of disease

Ultrasonographic

Findings

• Real Time: Reduction of ICA lumen size • Pulsed Doppler o Doppler spectral waveforms in ICA show no flow (occluded) or high resistance (stenotic) flow pattern o t End-diastolic flow velocity and! vascular resistance in ECA collaterals • Color Doppler: Aliasing suggests stenoses • Power Doppler: Contrast injection improves visualization of slow flow stenotic vessels and collaterals

Angiographic

Findings

• Conventional o MRA or catheter angiography: Predominantly (not exclusively) anterior circulation • Narrow proximal COW & ICA (earliest) • Lenticulostriate & thalamoperforator collaterals (intermediate) • Transdural & transosseous EC-IC collaterals (late) o Dilatation and branch extension of anterior choroidal artery predicts adult hemorrhagic events

Nuclear Medicine

Findings

• PET: ! Hemodynamic reserve capacity • SPECT 123I-Iomazenil: Neuronal density preserved if asymptomatic, ! if symptomatic

Imaging Recommendations • Best imaging tool: MRA

• •

• Protocol advice o MRA: COW o DWI: Seek "acute on chronic" ischemia o MR: FLAIR & Tl C+ illustrate "ivy sign" (reversible if patent bypass) o Contrast material improves visualization of synangiosis and collaterals o Catheter angiography defines anatomy of occlusions pre-bypass

I DIFFERENTIAL DIAGNOSIS "Ivy sign" • Leptomeningeal metastases, hemorrhage, also seen with high inspired oxygen

meningitis;

Punctate foci in basal ganglia • Cribriform lacunar state: No enhancement

Severely attenuated • Subarachnoid encasement

circle of Willis

hemorrhage,

meningitis,

tumor

IPATHOi.OGY General Features • General path comments o Nearly endless list of etiologies reported o Results from any slowly progressive intracranial vascular occlusion • Genetics o Inherited (primary) moyamoya • Several gene loci: Chr 3p26-p24.2 and 17q25 (amongst others) o Disorders with t association secondary moyamoya • Down syndrome, tuberous sclerosis, sickle cell disease, connective tissue disease, progeria • Midline anomalies (morning glory syndrome); syndromes with aneurysms, cardiac & ocular defects

Stroke

4 43

• Nfl, irradiation & suprasellar tumor a disastrous combination • Inflammatory: CNS angiitis (of childhood), basal meningitis (TB), leptospirosis, atherosclerosis, local infection (tonsillitis/otitis) • Vasculopathies and prothrombotic states: Kawasaki, anticardiolipin antibody, Factor V Leiden, polyarteritis nodosa, Bechet, SLE • Etiology: Many: Idiopathic, genetic, inflammatory, congenital mesenchymal defects, premature aging syndromes, prothrombotic states • Epidemiology o 10% of cases are familial o 1:100,000 in Japan • Associated abnormalities: Dependent upon primary etiology

o Remains most frequent cause of stroke in Asian children

Natural History & Prognosis • Progressive narrowing, collateralization and ischemia • Prognosis depends on etiology, ability to form collaterals, age/stage at diagnosis • Pediatric cases usually advance to stage V within 10 yrs onset o Infantile moyamoya progresses faster • Hemorrhagic moyamoya has poorer outcome

Treatment • Anticoagulation; correct/control prothrombotic states and inflammatory etiologies • Hypertransfusion regimens for sickle cell related moyamoya • Encephalo-duro-arterio-synangiosis (EDAS), a method of indirect bypass o 5 yr risk of ipsilateral stroke post EDAS 15% • Perivascular sympathectomy or superior cervical ganglionectomy (adult)

Gross Pathologic & Surgical Features

4

• Increased perforating (early) and EC-IC (late) collaterals in atrophic brain • Intracranial hemorrhage (adults) • Increased saccular aneurysms (esp basilar in adults)

44

Microscopic

Features

liDIAGNOSIIC;('}t1e(,}l<~t~J

• Intimal thickening and hyperplasia • Excessive infolding and thickening of internal elastic lamina • Increased periventricular pseudoaneurysms (cause of hemorrhage)

Consider • Moyamoya outside of Asia: Need to seek etiology

Image Interpretation

Staging, Grading or Classification Criteria • Staging criteria (after Suzuki) o Stage I: Narrowing of ICA bifurcation o Stage II: ACA, MCA, PCA dilated o Stage III: Maximal basal moyamoya collaterals; small ACA/MCA o Stage IV: Fewer collaterals (vessels); small PCA o Stage V: Further reduction in collaterals; absent ACA, MCA, PCA o Stage VI: Extensive pial collaterals from external carotid branches

I SELECTED

I ell NICALISSUES

3.

Presentation • Most common signs/symptoms o In childhood: TIAs, alternating hemiplegia (exacerbated by crying), headache, occasionally just developmental delay and poor feeding o In adulthood: SAH and intraventricular hemorrhage • Clinical profile o Children more likely to have TIAs and to progress, adults more likely to infarct (but slower progression) o Children more likely to have ipsilateral anterior PLUS posterior circulation involvement

Demographics

Pearls

• Enhance asymmetric atrophy found on childhood CT, look for abnormal vascular pattern • Moyamoya in children typically presents with cerebral ischemia vs hemorrhage in adults

1.

2.

4.

5.

6.

7.

8.

• Age: Bimodal age peaks: 6 yrs > 35 yrs • Gender: F:M = 1.8:1 • Ethnicity o Initially described in Japanese children as a specific entity

Stroke

REFERENCES

Goda M et al: Long-term effects of indericet bypass surgery on collateral vessel formation in pediatric moyamoya disease. J Neurosurg. 100: 156-62, 2004 Scott RM et al: Long-term outcome in children with moyamoya syndrome after cranial revasculization by pial synangiosis. J Neurosurg. 100:142-9, 2004 Anzai Y et al: Pramagnetic effect of supplemential oxygen on CSF hyperintensity on FLAIR MR images. AJNR. 25:274-9,2004 Urn SM et al: Localized IH-MR spectroscopy in moyamoya disease before and after revascularization surgery. Korean J Radiol 4(2):71-8, 2003 Morioka M et al. Angiographic dilatation and branch extension of anterior choroidal and posterior communicating arteries are predictors of hemorrhage in adult moyamoya patients. Stroke. 34(1):90-5, 2003 Yoon HK et al: "Ivy sign" in childhood moyamoya disease: Depiction on FLAIR and contrast-enhanced Tl W MR images. Radiology 223(2):384-389, 2002 Wityk RJ et al: Perfusion-weighted MRI in adult moyamoya syndrome: Characteristic patterns and change after surgical intervention. Neurosurgery 51 (6): 1499-505, 2002 Isono M et al: Long-term outcomes of pediatric moyamoya disease treated by EDAM. Pediatr Neurosurg 36(1):14-23, 2002

Typical (Left) Axial MRA shows occlusion of both distallCAs (arrows), non-visualization of MCAs and ACAs, stenosis of PCAs (open arrows) in 8 yo with hemiparetic migraines. Idiopathic arteriopathy of childhood. (Right) Axial MRA in another patient with idiopathic progressive arteriopathy of childhood shows occluded supraclinoid ICAs (arrows). Note bilateral synangioses (open arrows).

4 45

Typical

(Left) Axial TlWI MR shows right frontal and left tempora-occipital atrophy (open arrows) from remote ischemia. There are multiple small basal ganglia flow-voids (arrow) from lenticulostriate collaterals. (Right) Axial TI C+ MR in the same case shows multifocal white "dots" (arrows) due to slow flow in multiple enlarged lenticulostriate collaterals with intravascular enhancement.

Typical

(Left) Axial T2WI MR shows curvilinear "net-like" filling defects (arrows) within the ambient (circummesencephalic) cistern corresponding to collateral moyamoya vessels. Note asymmetric atrophy. (Right) Axial FLAIR MR shows "ivy sign" due to engorged vessels (arrows) within sulci in another patient with moyamoya. Sulcal signal is so striking this FLAIR scan resembles a T2WI.

Stroke

PRIMARY ARTERITIS OF THE eNS

Coronal oblique graphic illustrates alternating segmental areas of narrowing & dilatation, as well as ischemia within underlying brain from primary arteritis of the CNS.

Lateral OSA of internal carotid artery shows subtle pattern of arterial stenoses with dilatation (arrows) typical for (but not diagnostic of) primary arteritis of the CNS.

46

Abbreviations

o Areas of smooth or slightly irregularly shaped stenoses alternating with dilated segments o Nonspecific (appearance similar to other vasculitides)

and Synonyms

• Primary arteritis of the CNS (PACNS) • Vasculitis, vasculopathy

CT Findings • NECT o Relatively insensitive; often normal o May see secondary signs such as ischemia or infarction • Multifocallow density areas especially in basal ganglia, subcortical white matter o May see hemorrhage (less typical) • CECT: May see patchy areas of enhancement

Definitions • Primary arteritis confined to intracranial any evidence of secondary vasculitis

CNS without

General Features • Best diagnostic clue o Irregularities, stenoses & vascular occlusions in a pattern atypical for atherosclerotic disease o Imaging workup can be normal; requires clinical/laboratory correlation • Location o Pathologically leptomeningeal arteries & veins are affected, but involves intracranial vessels of any size o The brain is primary site but spinal cord can also be involved • Size: Degree of vessel narrowing may range from normal or minimally stenotic to completely occluded • Morphology

MR Findings • Tl WI: Multifocal deep gray & subcortical hypointensities • FLAIR: Multifocal deep gray & subcortical hyperintensities • T2* GRE: May show petechial hemorrhage • DWI: Restricted diffusion in acute stages • Tl C+: May see patchy areas of enhancement • MRA o Relatively insensitive, most often normal o May see some classic angiographic signs if larger vessels involved or in with vascular occlusion

DDx: Other Vasculidites

Vertebral AsVO

Severe AsVO

Amphetimine Abuse

Stroke

Moyamoya Pattern

PRIMARY ARTERITIS OF THE eNS Key Terminology Primary arteritis confined to intracranial any evidence of secondary vasculitis

CNS without

Imaging Findings • Irregularities, stenoses & vascular occlusions in a pattern atypical for atherosclerotic disease • Pathologically leptomeningeal arteries & veins are affected, but involves intracranial vessels of any size • Nonspecific (appearance similar to other vasculitides) • Conventional angiography is "gold standard"

Top Differential • • • •

Diagnoses

Intracranial atherosclerotic Arterial vasospasm Drug abuse Moyamoya

Ultrasonographic

vascular disease (ASVD)

Findings

• Conventional o Alternating stenosis with dilatation primarily involving 2nd, 3rd order branches o Less common: Long segment stenoses, pseudoaneurysms, occlusions

Nuclear Medicine

4

Arterial vasospasm

Findings

• Color Doppler o TCD may be used to monitor cerebral blood flow velocities if large arteries are involved o May also be used to evaluate therapy response

Angiographic

to

Findings

• [11 C] ( R )-PK11195 PET shows increased binding o A specific ligand for peripheral benzodiazepine binding site o Particularly abundant on cells of mononuclear phagocyte lineage o May be helpful in patients in suspected vasculitis with normal or ambiguous MR findings

• Temporal relationship to subarachnoid • Involves proximal vasculature

hemorrhage

Drug abuse • Younger patient population • Commonly multi-drug users • DSA appearance indistinguishable

from PACNS

Moyamoya • Sometimes referred to as "idiopathic progressive arteriopathy of childhood" • Moyamoya is an angiographic pattern, not a specific disease; may be acquired as well as inherited • Any slowly progressive occlusion of the supraclinoid ICAs may develop moyamoya pattern

Systemic lupus erythematosus vasculitis • A "secondary" vasculitis • Systemic disease with characteristic findings & labs • DSA appearance indistinguishable from PACNS

Imaging Recommendations • Best imaging tool o Conventional angiography is "gold standard" o MRI C+; consider MRA • Protocol advice o Conventional angiography if lab studies +, MRl/MRA negative, & high clinical suspicion o CTA/MRA is useful for screening; spatial resolution may be insufficient for subtle disease

IOlFFERENTIALDIAGNOS1S Intracranial atherosclerotic (ASVD)

vascular disease

• Advanced patient age • Typical distribution (carotid siphon, proximal intracranial vessels)

[PATHOLOGY General Features • General path comments o Brain biopsy may be required to confirm diagnosis • Definite diagnosis made from mononuclear inflammation of vessel wall • 75-80% sensitive although negative biopsy does not necessarily exclude PACNS o Diagnosis can be established on clinical grounds, typical findings on DSA, & other investigatory grounds excluding other diseases o Must be distinguished from other causes of CNS inflammation & noninflammatory vascular disease • Etiology: Unknown • Epidemiology: Rare

Gross Pathologic & Surgical Features • Characterized hemorrhages

Stroke

by ischemic lesions & small petechial

47

PRIMARY ARTERITIS OF THE eNS • Vessels of any size can be involved • May see venulitis with parenchymal

Microscopic

Natural History & Prognosis

hemorrhages

• Prognosis greatly improved with early recognition & therapy • Delay in diagnosis may lead to additional morbidity • PACNS patients are more likely to develop symptoms subacutely & remain undiagnosed for months • BACNS patients are more likely to have relatively acute presentations & be diagnosed within weeks of onset • Risk of permanent cognitive dysfunction with untreated PACNS • Often diagnosed posthumouslYi high index of suspicion is necessary to make the correct diagnosis in a timely basis

Features

• Mononuclear inflammation with necrosis of blood vessel walls is PACNS hallmark • Variable degree of granulomatous & non-granulomatous angiitis of small vessels • Typically involves media, adventitia of small leptomeningeal arteries & veins

Staging, Grading or Classification Criteria

4 48

• PACNS is a highly heterogeneous group of vasculitides limited to the CNS o Two subsets have been described: Granulomatous angiitis of CNS (GACNS) & benign angiopathy of central nervous system (BACNS) o Majority of cases fulfilling the originally proposed diagnostic criteria fail to fit either of these subsets • Clinical manifestations of PACNS and BACNS may be identical o BACNS has a more favorable outcome o Headache, focal weakness, seizures, hemorrhage, confusion, memory disorders, altered consciousness o Despite "benign" designation in "BACNS", some patients sustain significant neurological damage o Acute onset, headache, normal to mildly abnormal CSF findings, female predominance o Patients often have histories of heavy nicotine or caffeine use, OTC cold remedy use (e.g., ephedrine), & oral contraceptive or estrogen replacement o Precise relationship (if any) of these exposures to development of BACNS remains unclear

Treatment • There are few controlled studies on the treatment of vasculitis, with considerable variation between centers on current therapeutic regimens • Therapy typically comprises an aggressive immunosuppressive approach • High-dose steroid therapy with a prolonged course and gradual taper controls disease in most cases • Close monitoring of patients mandatory • Without treatment, patients with PACNS tend to have progressively downhill courses often leading to death • In contrast, BACNS patients may require less aggressive treatment than PACNS

I DIA(jNOSTI(t/(JHE(tl
Presentation • Most common signs/symptoms: Stroke from vascular involvement (stenoses, occlusion, aneurysm) • Clinical profile o Clinical presentation is highly variable, with focal to diffuse manifestations & acute to chronic evolution o Subacute presentation over weeks or months is typical o Mean duration of symptoms before diagnosis is approximately 5 months o Headache & mental status change with focal deficits o No evidence of secondary vasculitis or other diseases mentioned in the differential diagnosis should arouse suspicion

Demographics • Age o Childhood to adulthood o Mean age"" 42 years, but range is wide • Has been detected in children as young as 3 • Frequently occurs in elderly o BACNS patients tend to be young women • Gender: The distribution of PACNS is nearly equally between the sexes, with perhaps a slight male predominance

• DSA when clinical suspicion of PACNS is strong, regardless of findings on MR • Some investigators suggest PACNS should be diagnosed only if patient presents with headache & combination of o Focal neurological deficits of at least 6 months duration (except in cases of "devastating onset") o Several areas of segmental arterial narrowing demonstrated on cerebral angiography o Systemic inflammation or infection has been excluded o Leptomeningeal or parenchymal biopsy demonstrates vascular inflammation but no signs of infection, atherosclerosis, or neoplastic disease

Image Interpretation

Pearls

• Atherosclerosis is by far most common cause of vasculitis-like DSA pattern in adults, not PACNS

I SELECTED REFERENCES 1. 2. 3.

4.

Stroke

Carolei A et al: Central nervous system vasculitis. Neurol Sci. 24 Suppll:S8-S10, 2003 West SG: Central nervous system vasculitis. Curr Rheumatol Rep. 5(2):116-27, 2003 Ay H et al: Primary angiitis of the central nervous system and silent cortical hemorrhages. AJNR Am J Neuroradiol. 23(9):1561-3, 2002 Lanthier S: Primary angiitis of the central nervous system in children: 10 cases proven by biopsy. J Rheumatol. 29(7):1575-6,2002

PRIMARY ARTERITIS OF THE eNS

Typical (Left) Axial collapsed MRA shows PACNS with diffuse segmental narrowing of supraclinoid ICAs and posterior circulation (arrows), in a pattern which would be typical for any advanced vasculitis. (Right) Coronal T1 C+ MR shows gyriform enhancement (arrows) secondary to PACNS. Fairly symmetric posterior circulation involvement is shown, although anterior circulation is also involved.

4 49

Typical

(Left) Axial T1 C+ MR shows small area of enhancement adjacent to right foramen of Monroe (arrow) in patient with PACNS. Subtle edema is also present, with slight mass-effect upon the frontal horn. (Right) Axial FLAIR MR reveals hyperintensity within right cerebral peduncle (arrow) & parahippocampal gyrus (open arrow) secondary to PACNS vasculitis.

Variant

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.\

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.

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.,..

/

,J

~

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~~ • v

'. .-..

'I: .

\

" ..

...

~-< .• ~

~

.

, ...

'~

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~.~

Stroke

iL '

...• ,,

(Left) Axial NECT shows patient with PACNS. Bilateral edema is present (arrows), with hemorrhagic infarction seen in left posterior temporal & parietal lobes; hemorrhage is atypical for PACNS. (Right) Axial T2WI MR shows a PACNS patient with severe brainstem involvement (arrow), and relative sparring of the cerebral hemispheres.

Coronal oblique graphic shows vasculitis with parenchymal changes seen as multifocal areas of edema (arrows), scattered hemorrhages within basal ganglia and at gray-white junction.

Lateral DSA with selective ICA injection shows classic vasculitis with typical findings of alternating areas of constriction and dilatation (arrows). Drug-related vasculitis.

50

Abbreviations

o Classic appearance: Multifocal areas of smooth or slightly irregularly shaped stenosis alternating with dilated segments o Variety of angiographic appearances depending on etiology including vascular irregularities, stenoses, aneurysms and occlusions

and Synonyms

• Inflammatory vasculopathy (more general term indicating any vascular pathology) • Arteritis (specifies arterial inflammation) • Angiitis (inflammation of either arteries or veins)

Definitions • Heterogeneous group of CNS disorders characterized by non atheromatous inflammation and necrosis of blood vessel walls • Involves either arteries or veins

CT Findings • NECT o Relatively insensitive; may be normal o May see secondary signs such as ischemia/infarction: Multifocallow density areas in basal ganglia, subcortical white matter o May see hemorrhage • CECT: May see patchy areas of enhancement

MR Findings General Features • Best diagnostic clue o Irregularities, stenoses and vascular occlusions in a pattern atypical for atherosclerotic disease o Imaging workup can be normal; need clinical/laboratory correlation • Location: Arteries and veins are affected; occurs in intracranial vessels of any size • Size: Degree of vessel narrowing may range from normal/minimally stenotic to occluded • Morphology

• Tl WI: Can be normal early; +/- multifocal cortical/subcortical hypointensities • T2WI: Multifocal hyperintensities • FLAIR: Subcortical, basal ganglia hyperintensities • T2* GRE: May show hemorrhage • DWI: Can see restricted diffusion in acute stage • Tl C+: May see patchy areas of enhancement • MRA: May see some classic angiographic signs if larger vessels involved/vascular occlusion; may be normal

Ultrasonographic

Findings

• Pulsed Doppler

DDx: Vasculitis vs Atherosclerosis

PACNS

ASVD

Stroke

ICAASVD

VASCULITIS Key Facts Terminology

Pathology

• Inflammatory vasculopathy (more general term indicating any vascular pathology) • Heterogeneous group of CNS disorders characterized by non atheromatous inflammation and necrosis of blood vessel walls

Imaging Findings

• Pattern of vessel wall inflammation, necrosis common to all vasculitides • Can be primary or secondary, caused by broad spectrum of infectious, inflammatory agents, drugs, etc • Atherosclerosis is by far the most common cause of a vasculitis-like angiographic pattern in adults

• Irregularities, stenoses and vascular occlusions in a pattern atypical for atherosclerotic disease • Classic appearance: Multifocal areas of smooth or slightly irregularly shaped stenosis alternating with dilated segments

• Diagnosis is frequently made on the basis of clinical presentation, brain MRI, and cerebral angiography without pathologic confirmation

Top Differential

Diagnostic Checklist

Diagnoses

• Intracranial ASVD • Arterial vasospasm

o TCD may be used to monitor cerebral blood flow velocities if large arteries are involved o May also be used to evaluate therapy response if large arteries are involved

Angiographic

Findings

• Conventional o Alternating stenosis and dilatation primarily involving 2nd, 3rd order branches o Less common: Long segment stenoses, pseudoaneurysms

Imaging Recommendations • Best imaging tool o DSA is cornerstone diagnostic procedure o MR imaging findings may be negative in the setting of CNS vasculitis confirmed on angiography • Protocol advice o DSA if lab studies positive, MRI/MRA negative o CTA/MRA useful screening; spatial resolution may be insufficient for subtle disease

I.DIFFER.ENTIJ\.L ••DJAGNe>SIS Intracranial ASVD • Advanced patient age • Typical distribution (carotid siphon, proximal intracranial vessels); extracranial manifestations disease

of

Arterial vasospasm • Temporal relationship to subarachnoid (SAH) • Involves proximal vasculature

hemorrhage

I PATHOLOGY General Features • General path comments o Pattern of vessel wall inflammation, common to all vasculitides

necrosis

o Can be primary or secondary, caused by broad spectrum of infectious, inflammatory agents, drugs, etc • Etiology o Bacterial meningitis • Infarction due to vascular involvement seen in 25% • H. Influenzae most common organism; common in children o Tuberculous meningitis • Vessels at the skull base most commonly involved, Le., supraclinoid ICA and Ml producing occlusions and stenoses o Mycotic arteritis (aspergillus, cocci, etc) • Actinomyces may invade vessel walls leading to hemorrhage • Narrowing of the basal cerebral or cortical vessels on angiography o Viral arteritis • Herpes simplex most common in North America • HIV-associated vasculitis increasing, especially in children o Syphilis arteritis • Two forms: Syphilitic meningitis and gummatous vasculitis • Diffuse vasculitis involves cortical arteries and veins • Gummatous vasculitis usually affects proximal MCA branches o Polyarteritis nodosa • Most common systemic vasculitis to involve the CNS (though late) • Microaneurysms due to necrosis of the internal elastic lamina in 75% o Cell mediated arteritides • Giant cell arteritis (granulomatous infiltration of the arterial walls) • Takayasu (primarily involves aorta, great vessels, branches) • Temporal arteritis (systemic; involves temporal, other extracranial arteries) o Wegener

Stroke

4 51

4 52

• May cause intracerebral and meningeal granulomas or vasculitis • CNS involved in 15-30% due to direct invasion from nose/sinuses • Chronic systemic arteritis involving lungs, kidneys and sinuses o Sarcoid (CNS involvement in 3-5% of cases) • Can extend along perivascular spaces, involve penetrating arteries • Meningitis, vasculitis involving vessels at the base of the brain o Granulomatous angiitis (PACNS) • Primary angiitis isolated to the CNS (idiopathic) • Manifest as multiple intracranial stenoses o Collagen vascular disease (SLE, rheumatoid, scleroderma) • SLE: Most common to involve the CNS • Vasculitis relatively uncommon (variable findings; small vessel irregularities/stenoses/occlusions up to fusiform aneurysms) • CVA seen in 50% due to cardiac disease or coagulopathy o Drug abuse vasculitis • Drug can injure vessels directly or secondarily (usually hypersensitivity to contaminants) • Associated with both legitimate and illegal "street" drugs including amphetamines, cocaine, heroin, and phenylpropanolamine and ergots o Radiation • Acute arteritis produces transient white matter edema • Chronic changes more severe with vessel obliteration and brain necrosis, leukomalacia, calcifying micro angiopathy and atrophy • Effects compounded with concomitant chemotherapy o Moyamoya disease • Sometimes referred to as "idiopathic progressive arteriopathy of childhood" • Moyamoya is an angiographic pattern, not a specific disease; may be acquired as well as inherited • Any slowly progressive occlusion of the supraclinoid ICAs may develop Moyamoya pattern • Pattern has been reported with NF, atherosclerosis, radiation therapy • Prognosis depends upon the rapidity and and extent of the vascular occlusions as well as the development of effective collaterals • Epidemiology o Atherosclerosis is by far the most common cause of a vasculitis-like angiographic pattern in adults o CNS vasculitis occurs in a variety of clinical settings, some of which exhibit a distinct age preference; others a tissue tropism • Associated abnormalities: May have many, particularly with vasculitis secondary to systemic disease

Gross Pathologic & Surgical Features • Characterized by ischemic lesions and small petechial hemorrhages • Vessels of any size can be involved

• May see venulitis with parenchymal

hemorrhages

Microscopic

Features

• Inflammation

and necrosis of blood vessel walls

Staging, Grading or Classification Criteria • Several different classification systems have been proposed o Can be primary intracranial or secondary to a systemic disease o Can be divided into true vasculitis (angiitis) and noninflammatory vasculopathy o Can be divided into those due to immune complex deposition vs cell-mediated disorders vs miscellaneous o Can be infectious or noninfectious

[ClINICAL/ISSLJES Presentation • Most common signs/symptoms o Stroke related to manifestations of vascular involvement (stenosis, occlusion, aneurysm) o Patients presenting with symptoms suggestive of vasculitis require brain neuroimaging, lumbar puncture, and angiography, but only biopsy allows a definite diagnosis

Demographics • Age: Variable from childhood (moyamoya disease) to adulthood • Gender: Depends upon the type of vasculitis; generally no gender predilection

Natural History & Prognosis • Varies depending if untreated

upon etiology; typically progressive

Treatment • Most patients with CNS vasculitis should be treated aggressively with a combination of immunosuppressive medications I. [1 IAGNOSTI

CYCHECKllST

Consider • Diagnosis is frequently made on the basis of clinical presentation, brain MRI, and cerebral angiography without pathologic confirmation • Despite the high sensitivity of MR imaging for CNS vasculitis, angiography may still be required to render an accurate diagnosis

I.SElECTE[)R.EFERENCES 1. 2. 3.

Stroke

West SG: Central nervous system vasculitis. Curr Rheumatol Rep. 5(2):116-27, 2003 Carolei A et al: Central nervous system vasculitis. Neurol Sci. 24 Suppll:S8-SlO, 2003 Calabrese LH et al: Diagnostic strategies in vasculitis affecting the central nervous system. Cleve Clin J Med 69 Suppl 2: SIIl05-8, 2002

Typical (Left) Axial OWl MR shows acute cerebral ischemia/infarction (arrows) in the temporal and occipital distributions in patient with non-atheromatous vasculitis. (Right) Axial FLAIRMR shows secondary parenchymal changes from severe nonatheromatous vasculitis, with edema/infarction affecting the frontal and left parietal lobes, as well as bilateral caudate nuclei.

4 53 (Left) Axial FLAIRMR shows

severe ischemia affecting the deep gray nuclei and peri ventricular white matter around the frontal horns. Vasculitis in this patient is PACNS. (Right) Anteroposterior DSA shows supraclinoid ICA narrowing, marked development of telangiectatic basal collaterals causing "moyamoya" pattern (arrows) in this adult with slowly progressive arteriopathy.

Typical

(Left) Axial MRA shows

collapsed 3D TOF image with diffuse subtle beading of intracranial vessels (arrows). Disease begins proximally at the cavernous ICAs and involves numerous distal branches. (Right) Axial T7 C+ MR shows marked gyral enhancement (arrows) involving the left parietal lobe in patient with nonatheromatous vasculitis. Some of the T7 weighted signal is secondary to hemorrhage.

Stroke

SYSTEMIC LUPUS ERYTHEMATOSUS

Axial T2WI MR shows typical white matter lesions in neuropsychiatric 5LE. There are numerous foci of abnormal signal in white matter of frontal and parietal lobes.

4 54

o Focal infarcts, cerebral calcification o Patchy cortical/subcorticallucencies o Extensive, reversible WM changes (cerebral edema) • CECT: Contrast-enhancement has 1 sensitivity for acute/subacute cerebral lesions • CTA: Often completely normal in NPSLE

1··TER.MI~()I.()CY Abbreviations

and Synonyms

• Systemic lupus erythematosus (SLE) • Neuropsychiatric SLE (NPSLE)

Definitions

MR Findings

• Autoimmune disorder that affects many organ systems, including CNS

1··.IMJ.\Git~G/iFili~r)INGS General Features • Best diagnostic clue o Most common overall MR finding = small multifocal WM lesions o Focal infarcts of various sizes o Symptomatic "migratory" edematous areas • Location o White matter (WM), gray matter (GM) o Most common: Frontal, parietal subcortical WM • Size: Variable • Morphology: Rounded or patchy lesions

CT Findings • NECT o Most common

finding

=

DDx: Multifocal

MS

Axial FLAIR MR shows periventricular white matter hyperintensities, large bilateral infarcts with cortical atrophy in a patient with 5L£.

cerebral atrophy

• T2WI o Four patterns of involvement • Focal infarcts (I anticardiolipin, 1 lupus anticoagulant antibodies) • Multiple T2WI hyperintensities (microinfarctions) • Focal areas of increased intensity, primarily in GM • Diffuse steroid-responsive subcortical lesions (associated 1 antineurofilament antibodies) o Acute lesions on T2WI suggesting active NPSLE • New infarct, discrete GM lesions, diffuse GM hyperintensities, and cerebral edema • FLAIR: Multifocal WM hyperintensities • DWI o Restricted diffusion (cytotoxic edema) in ischemia/infarct o Increased diffusion (vasogenic edema) in vasculopathy • Tl C+: Acute/active CNS lesions may enhance • MRA: Can confirm thrombotic lesions of extracranial/intracranial vessels

Cerebral lesions

Granulomatous Angiitis

Stroke

Susac Syndrome

PAN

SYSTEMIC LUPUS ERYTHEMATOSUS Key Facts Imaging Findings • Most common overall MR finding = small multifocal WM lesions • Focal infarcts of various sizes • Symptomatic "migratory" edematous areas

Top Differential • • • • • •

Diagnoses

• No pathognomonic brain lesion • Lupus-related myelitis (transverse myelitis)

• MRV: May show dural venous sinus thrombosis (especially in antiphospholipid syndrome) • MRS o IH MRS in NPSLE patients • tN-acetyl aspartate in both lesions, normal-appearing WM/GM • t Choline related to disease activity, stroke, inflammation, chronic WM disease • No t in lactate ~ anaerobic metabolism is not fundamental characteristic of NPSLE o MRS findings directly correlate with severity of neuropsychiatric symptoms

Findings

Angiographic

Findings

• Conventional:

Rarely detects cerebral vasculitis

Nuclear Medicine

• CNS involvement in up to 75% of cases • Gender: Strong female predominance (as high as 5:1 during childbearing years) • Difficult to differentiate active from old NPSLE lesions • Obtain MR study within 24 hours of neurologic event onset • Most important role of imaging in NPSLE: Assessment of acute focal (stroke-like) neurologic deficits • Negative brain MRI does not exclude cerebral lupus

Pathology

• Transcranial Doppler ultrasound can confirm thrombotic lesions of extracranial/intracranial

Clinical Issues

Diagnostic Checklist

Multiple sclerosis (MS) Antiphospholipid antibodies (non-SLE) Lyme encephalopathy Small vessel cerebrovascular disease Susac syndrome Other vasculitides (e.g., PACNS)

Ultrasonographic

• Libman-Sacks endocarditis, emboli • True vasculitis of CNS is rare in SLE

vessels

Findings

• PET: Parieto-occipital hypometabolism = most conspicuous finding in MRI-negative NPSLE • Technetium-99m ethyl cysteinate dimer brain SPECT o Sensitive tool for early detection of brain abnormalities in SLE (more sensitive than MRI) o Relatively nonspecific regional cerebral cortical hypoperfusion • Most hypoperfused areas: Parietal, frontal, and temporal lobes (MCA territory) • Least hypoperfused area: Cerebellum o Positive findings also seen in patients without neuropsychiatric signs/symptoms • Secondary to subclinical brain involvement or cerebral atrophy (due to steroid therapy)

Imaging Recommendations • Best imaging tool: MRI more sensitive than CT • Protocol advice o T2WI, FLAIR o Consider PET in NPSLE if standard MR normal

I DIFFERENTIAE DIAGN@SIS Multiple sclerosis (MS) • • • •

Hyperintense WM lesions on T2WI Lesions radially oriented along WM tracts Periventricular WM (callososeptal interface) SLE lesions not confined to periventricular WM, favor gray-white junction or involve cortex/deep nuclei

Antiphospholipid

antibodies (non-SLE)

• "Anti phospholipid syndrome" in non-SLE patients o Early stroke, recurrent arterial + venous thromboses o Spontaneous fetal loss, thrombocytopenia • Infarcts of various sizes and T2 hyperintense WM foci

Lyme encephalopathy • Hyperintense periventricular WM lesions on T2WI • May enhance, resemble MS or ADEM

Small vessel cerebrovascular disease • Caused by diabetes, HTN, arteriolosclerosis • T2WI hyperintense lesions within deep GM (basal ganglia, thalamus), centrum semiovale • Diffuse, confluent regions of periventricular hyperintense WM involvement (leukoariosis)

Susac syndrome • Microangiopathy of unknown etiology • Triad of HA/encephalopathy, branch retinal artery occlusions, hearing loss • Deep WM, corpus callosum multifocal hyperintense lesions on T2WI, FLAIR o Central CC > callososeptal interface o May enhance (acute) o Central callosal "holes" in subacute/chronic • Usually self-limited, fluctuating, monophasic illness o Duration 2-4 y (from 6 months up to 5 y)

Other vasculitides (e.g., PACNS) • Primary angiitis of CNS, polyarteritis nodosa (PAN), Wegener, Be~het disease, syphilis, Sjogren syndrome

Stroke

4 55

SYSTEMIC LUPUS ERYTHEMATOSUS General Features

56

• General path comments o No pathognomonic brain lesion o Diverse nonspecific lesions of varying intensity • Genetics o Genetic predisposition to SLE • HLA-DR2, HLA-DR3, null complement alleles • Congenital deficiencies of complement (C4, C2) • Etiology o Pathogenesis of NPSLE is likely multifactorial o Diffuse neuropsychiatric symptoms • Neuronal dysfunction mediated by antibodies: Anti-neuronal, anti-ribosomal P-protein, and anti-cytokines o Focal neurologic symptoms • Circulating immune complexes ~ vascular injury • Endothelial cell activation by cytokines and complement activation ~ occlusive vasculopathy • Antiphospholipid antibodies (APL-Ab) ~ macroand microvascular thrombosis o Later stages of SLE: Accelerated atherosclerosis (ATS) • i Intravascular complement turnover and APL-Ab • Epidemiology o US incidence of SLE is 14.6-50.8/100,000 people o NPSLE affects 14-75% of SLE patients • Associated abnormalities o Lupus-related myelitis (transverse myelitis) o Libman-Sacks endocarditis, emboli

• Clinical profile o Cerebral involvement may precede full-blown SLE picture or may develop during course of disease • Most frequently within first 3 years o Diffuse psychiatric or focal neurologic symptoms o Movement disorders (chorea, parkinsonism)

Demographics • Age: All age groups affected; peak incidence in young adulthood (20-45 y) • Gender: Strong female predominance (as high as 5:1 during childbearing years) • Ethnicity: High prevalence in African-American women

Natural History & Prognosis • Neurologic complications worsen prognosis of SLE o Transient neurologic deficits, chronic brain injury • SLE patients with APL-Ab have additional risk for neuropsychiatric events • Mortality rate in NPSLE: 7-40%

Treatment • Immunosuppressive agents (steroids, cyclophosphamide) for suspected vasculitis • Lifelong anticoagulation for APL-Ab-mediated thromboembolic events • Intrathecal methotrexate and dexamethasone for severe cases • Primary prevention of ATS and narrowing of blood vessels: Prophylactic Aspirin, lipid-lowering drugs

Gross Pathologic & Surgical Features • Vasculitis ~ CNS ischemia or hemorrhage (in traparenchymal! subarachnoid) • Edema ~ reversible leukoencephalopathy • WM degeneration + myelin vacuolation of spinal cord

Microscopic

Features

• Vasculopathy o Most common, but nonspecific finding • Hyalinization, endothelial proliferation, and perivascular gliosis, mainly of small blood vessels • True vasculitis of CNS is rare in SLE • Hemorrhage, ischemic demyelination, MS-like demyelination, gliosis • Subtle cerebral edema in diffuse NPSLE

Staging, Grading or Classification Criteria • Central or peripheral NPSLE • Active and/or previously active NPSLE • Acute or chronic NPSLE

li9LINlCAlISSLJES

I DIAONOSTICCHEeKl.IS"[ Consider • Difficult to differentiate active from old NPSLE lesions • Obtain MR study within 24 hours of neurologic event onset

Image Interpretation

I SELECTED REFERENCES 1.

Presentation • Most common signs/symptoms o CNS involvement in up to 75% of cases • Migraine, seizures, stroke, chorea • Transverse myelopathy, cranial neuropathies, aseptic meningitis • Psychosis, mood disorders, acute confusional state, cognitive dysfunction o Subclinical CNS disease in SLE: Transient event

Pearls

• Most important role of imaging in NPSLE: Assessment of acute focal (stroke-like) neurologic deficits o Lupus-related CNS vasculitis o Thromboembolic events due to vasculopathy or cardiomyopathy (Libman-Sacks) o APL-Ab-mediated thrombosis o Microangiopathy (including thrombotic thrombocytopenic purpura) o Accelerated ATS • Negative brain MRI does not exclude cerebral lupus

2.

3.

Stroke

Jennings JE et al: Value of MRI of the brain in patients with systemic lupus erythematosus and neurologic disturbance. Neuroradiol 46:15-21, 2004 Janardhan V et al: Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attach. Stroke. 35:736-41, 2004 Susac JO et al: MRI findings in Susac's syndrome. Neurology 61:1783-7,2003

1

Sy_S_T_E_M_I_C_L_U_P_U_S_E_R_y_T_H_E_M_A_T_O_S_U_S

_

Typical (Left) Axial T2WI MR shows an extensive infarct in the right cerebral hemisphere (middle cerebral artery territory) in an SLE patient. Contralateral subcortical white matter hyperintense foci also observed. (Right) Lateral view of carotid angiogram in a different SLE patient shows multiple areas of arterial narrowing consistent with vasculitis. This is a rare finding in neuropsychiatric lupus.

4 57 (Left) Axial NECT shows diffuse white matter hypodensity consistent with cerebral edema in an SLE patient. (Right) Sagittal T1 WI MR in another patient with SLE myelopathy shows expansion of the cervical spinal cord with hypointense signal abnormality.

Typical (Left) Axial FLAIR MR shows infarction in the right anterior cerebral artery and middle cerebral artery territory in an SLE patient. (Right) Axial Tl C+ MR in a different SLE patient shows multiple enhancing infarcts in the thalami and basal ganglia.

Stroke

CEREBRAL AMYLOID DISEASE

Axial graphic shows acute hematoma (black arrow) with fluid level. MulUple microbleeds (white arrows), old lobar hemorrhages (curved arrows) are also findings in cerebral amyloid disease.

4 58

o Parietal + occipital lobes most common at autopsy; also frontal + temporal on imaging o Less common in brainstem, deep gray nuclei, cerebellum, hippocampus • Size o Acute lobar hemorrhage tends to be large o Punctate foci of dark T2*/susceptibility sequences (blooming) seen with chronic microbleeds (MB), but not specific for CAA • Morphology: Acute hematomas are large, often irregular, with dependent blood sedimentation

[l'ERiMINOLOc;¥ Abbreviations

and Synonyms

• Cerebral amyloid angiopathy (CAA) = "congophilic angiopathy", also cerebral amyloidosis

Definitions • Cerebral amyloid deposition occurs in 3 morphologic varieties o CAA (common) o Amyloidoma (rare) o Diffuse (encephalopathic) white matter (WM) involvement (rare) • CAA is common cause of "spontaneous" lobar hemorrhage in elderly

CT Findings • NECT o Patchy or confluent cortical/subcortical hematoma with irregular borders, surrounding edema o Hemorrhage may extend to SAS or into ventricles o Rare: Gyriform Ca++ o Generalized atrophy common • CECT: No enhancement, unless amyloidoma (rare)

[IMAGING FINDINGS General Features • Best diagnostic clue o Normotensive demented patient with • Lobar hemorrhage(s) of different ages • Multifocal"black dots" (T2, T2*), corresponding chronic microbleeds (MB), particularly when subcortical • Location o Subcortical WM (gray/white junction)

DDx:

Axial T2* GRE MR shows mulUple hypointense foci (arrows) in bilateral subcorUcal white matter, most prominently in the frontal lobes. Pattern, distribuUon are typical for CAA.

MR Findings to

• Tl WI: Lobar hematoma (signal varies with age of clot) • T2WI o Acute hematoma iso/hypointense • 1/3 have old hemorrhages (lobar, petechial) seen as multifocal punctate "black dots" o Focal or patchy/confluent WM disease associated in nearly 70%

CM Imaging Mimics

Cap Malformation

Hypertensive MB

Mu/t Cav Mals

Stroke

Venous Thromb

CEREBRAL AMYLOID DISEASE Key Facts • Protocol advice: Include T2*-weighted sequence in all patients> 60 y

Top Differential • • • •

Diagnoses

Hypertensive microhemorrhages Ischemic stroke with micro hemorrhage Multiple vascular malformations Other causes of multifocal"black dots"

Pathology • APOE4 allele associated with CAA-related hemorrhage • Amyloidosis = rare systemic disease caused by extracellular deposition of B-amyloid • 1% of all strokes • Causes up to 15-20% of plCH in patients> 60 y • 27-32% of normal elderly (autopsy) • 82-88% in patients with Alzheimer disease (AD)

• •

•

o Rare form: Nonhemorrhagic diffuse encephalopathy: Confluent WM hyperintensities o MB: Small foci of dark T2 variably present; T2* much more sensitive • T2* GRE: Multifocal"black dots" (best sequence to detect chronic MB) • T1 C+

o CAA, lobar hemorrhages usually don't enhance o Amyloidoma (focal, nonhemorrhagic mass(es) • Mass effect generally minimal/mild • May show moderate/striking enhancement, mimic neoplasm • Often extends medially to lateral ventricular wall with fine radial enhancing margins • Rare: Patchy, infiltrating

Angiographic

Findings

• Conventional:

Normal or avascular mass effect

Imaging Recommendations • Best imaging tool o NECT = best initial screening study (for acute hemorrhage) o MRI with T2* for non-acute evaluation (dementia) • Protocol advice: Include T2*-weighted sequence in all patients> 60 y

o Look for "locules" of blood with fluid-fluid levels o Capillary malformations may show faint, "brush-like" enhancement o Can occur anywhere but brainstem > lobar location • Capillary telangiectasias o Type IV seen as multifocal"black dots" o Brainstsem, cerebellum, spinal cord most common sites

Other causes of multifocal "black dots" • Traumatic diffuse axonal injury o History of trauma o Location in corpus callosum, subcortical/deep white matter, brainstem • Hemorrhagic metastases o Location similar to CAA (gray-white junction) o Variable enhancement, edema • CADASIL o Usually nonhemorrhagic o Most common site = cortical-subcortical (up to 27% in thalami/brainstem) • Metallic micro emboli from artificial heart valves

r.

PAl HQ LOGY

General Features

1.·OIF/FERENJ"liNt.ID]"'\{)NOSIS Hypertensive

microhemorrhages

• Deep structures (basal ganglia, thalami, cerebellum) > cortex, subcortical WM • Often coexists with CAA • Younger patients than CAA « 65 yo)

Ischemic stroke with microhemorrhage • Multifocal hemosiderin deposits o Found in 10-15% of patients with acute ischemic strokes • Hemorrhagic lacunar infarcts

Multiple vascular malformations

• Genetics o Sporadic • APOE4 allele associated with CAA-related hemorrhage • Polymorphisms in presenilin-1 gene o Hereditary cerebral hemorrhage with amyloidosis • Autosomal dominant inheritance • Dutch type = mutated amyloid B precursor protein on chromosome 21 • Other types include British, Flemish, etc • Etiology o Amyloidosis = rare systemic disease caused by extracellular deposition of B-amyloid o 10-20% localized form, including CNS o Can be idiopathic/primary

• Cavernous malformations

Stroke

4 59

CEREBRAL AMYLOID DISEASE o Can be secondary/reactive (e.g., dialysis-related amyloidosis) • Epidemiology o 1% of all strokes o Causes up to 15-20% of plCH in patients> 60 y o Frequency of CAA in elderly • 27-32% of normal elderly (autopsy) • 82-88% in patients with Alzheimer disease (AD) • Common in Down syndrome o Other associations: Kuru, C]D, plasmacytoma

Gross Pathologic & Surgical Features • Lobar hemorrhage(s) • Multiple small cortical hemorrhages

Microscopic

4 60

Treatment • Evacuate focal hematoma if patient < 75 y, no IVH, not parietal • Consider immunosuppressive therapy in inflammatory CAA • Adverse prognostic factors: Low Glasgow coma scale scores, APOE4 allele

I

DIAGNOSTIC

CHECKLIST

Consider • Susceptibility weighted imaging (T2*) in all elderly

Features

• Interstitial, vascular/perivascular deposits of amorphous protein o Shows apple-green birefringence when stained with Congo red, viewed under polarized light o 3 components • Fibrillar protein component (varies, defines amyloidosis type) • Serum amyloid P • Charged glycosaminoglycans (ubiquitous) • Microaneurysms • Fibrinoid necrosis • Hyaline thickening • 15% have CAA-related perivascular inflammation

I SELECTED 1.

2. 3.

4.

5.

Staging, Grading or Classification Criteria • WHO classification of amyloidoses o Primary systemic amyloidosis o Secondary amyloidosis o Hereditary systemic amyloidosis o Hemodialysis-related systemic amyloidosis o Medullary thyroid carcinoma o Type II diabetes

6.

I Cli NICf\L1SSUES

10.

Presentation

11.

• Most common signs/symptoms o Acute: Stroke-like clinical presentation with "spontaneous" lobar ICH • Incidence of CAA in such patients = 4-10% o Chronic: Dementia (CAA) • Clinical profile o CAA common in demented elderly patient • 2/3 normotensive; 1/3 HTN • 40% with subacute dementia/overt AD (overlap common)

7. 8.

9.

12.

13.

14. 15.

16.

Demographics • Age o Usually older when sporadic (> 60 y) o Inflammatory CAA younger • Gender: No gender predilection

Natural History & Prognosis

17.

18.

• Multiple, recurrent hemorrhages • Progressive cognitive decline

Stroke

REFERENCES

Tian J et al: Relationships between arteriosclerosis, cerebral amyloid angiopathy and myelin loss from cerebral cortical white matter in Alzheimer's disease. Neuropathol Appl Neurobiol 30:46-56, 2004 Georgiades CS et al: Amyloidosis: Review and CT manifestations. Radio Graphics 24:405-16,2004 Arboix A et al: New concepts in lacunar stroke etiology: the constellation of small-vessel arterial disease. Cerebrovasc Dis 17 Suppl1:58-62, 2004 Chalela JA et al: Multiple cerebral microbleeds: MRI marker of a diffuse hemorrhage-prone state. J Neuroimaging . 14:54-7,2004 Eng JA et al: Clinical manifestations of cerebral amyloid angiopathy-related inflammation. Ann Neurol. 55:250-6, 2004 Georgiades CS et al: Amyloidosis: Review and CT manifestations. RadioGraphics. 24: 405-16, 2004 Gandhi D et al: CT and MR imaging of intracerebral amyloidoma. A]NR 24:519-22, 2003 Dichgans M et al: Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study. Stroke 33:67-71, 2002 Gallucci M et al: Neuroradiological findings in two cases of isolated amyloidoma of the central nervous system. Neuroradiology 44:333-37, 2002 Pfeifer LA et al: Cerebral amyloid angiopathy and cognitive function. Neurology 58:1629-34, 2002 Yamada M: Risk factors for cerebral amyloid angiopathy in the elderly. Ann NY Acad Sci 977:37-44,2002 Lang EW et al: Stroke pattern interpretation: the variability of hypertensive versus amyloid angiopathy hemorrhage. Cerebrovasc Dis 12:121-30, 2001 Caulo M et al: Cerebral amyloid angiopathy presenting as nonhemorrhagic diffuse encephalopathy. AJNR 22:1072-76, 2001 Smadja P et al: Amyloidoma of the central nervous system. J Radiol 81:975-78, 2000 McCarron MO et al: Cerebral amyloid angiopathy-related hemorrhage. Stroke 30:1643-6, 1999 Greenberg SM et al: MRI detection of new hemorrhages: potential marker of progression in cerebral amyloid angiopathy. Neurology 53:1135-8, 1999 Fazekas F et al: Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage. AJNR 20:637-42, 1999 Miller JH et al: Intracerebral haemorrhage and cerebral amyloid angiopathy: CT features with pathologic correlation. Clin Radiol 7:422-9, 1999

CEREBRAL AMYLOID DISEASE

Typical (Left) Axial T2WI MR demonstrates a few subcortical foci of low signal intensity (arrows) in this elderly demented patient. (Right) Axial T2* CRE MR in the same case shows striking "blooming" of innumerable hypointense foci, particularly in the subcortical white matter wiith sparing of the deep nuclei. CAA.

4 Typical

61 (Left) Axial NECT shows an

acute lobar hematoma in this normotensive older patient with known "congophilic angiopathy." (Right) Axial T2* CRE MR in the same patient obtained a few weeks later shows blooming of the resolving parenchymal hematoma (open arrow). Note multiple peripherally located chronic MBs (arrows).

Variant (Left) Axial T1 C+ MR shows

multiple infiltrating enhancing foci involving both basal ganglia (arrows). Biopsy disclosed CAA and multiple foci of amyloid deposition, so-called "amyloidoma(s)". (Right) Axial T2WI MR in the same case shows T2 signal prolongation and mild mass effect in the areas of enhancement (arrows) with a few scattered hypointense foci consistent with microhemorrhages.

Stroke

Axial T2WI MR shows confluent hyperintense lesions in both anterior temporal lobes (arrows) in this patient who initially presented with epilepsy, proven CAOASIL (Courtesy H. Markus, MO).

62

• Morphology:

I TERIMINQl-0C¥ Abbreviations

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Definitions • Hereditary small-vessel disease due to mutations in Notch3 gene on chromosome 19, which causes stroke in young adults

IIMI\(JINGFINOINCS General Features • Best diagnostic clue: Characteristic subcortical lacunar infarcts and leukoencephalopathy in young adults • Location o Frontal lobe has highest lesion load o Temporal lobe and insula o Other frequent locations • Periventricular regions and centrum semiovale • Internal and external capsule • Basal ganglia and brain stem o Spared fronto-orbital and occipital subcortical areas o Cerebral cortex is generally spared • Size: Multiple infarcts of various sizes

Chronic HTN

shows areas

Various shapes

CT Findings

and Synonyms

DDx: Multiple

Axial T2WI MR in the same patient periventricular white matter hyperintense (arrows). Proven CAOASIL.

• NECT: Subcortical hypodense lesions • CECT: Lesions do not contrast-enhance

MR Findings • TlWI o Two types of lesions • Large, coalescent lesions in white matter (WM), isointense on T1WI • Small, well-delineated lesions that spare cortex, hypointense on T1WI o Total T1lesion volume correlates significantly with degree of disability and neuropsychological impairment (attention, memory, conceptual and visuospatial function) • T2WI o WM ischemia (seen in pre symptomatic CADASIL) • Diffuse WM hyperintensities (WMHs) = leukoariosis • Discrete hyperintense lacunar infarctions o Anterior temporal pole and external capsule lesions have higher sensitivity and specificity for CADASIL • DWI: Lesions may have bright signal in acute phase • PD/Intermediate, FLAIR: Same as T2WI • Circumscribed lesions found predominantly within centrum semiovale, thalamus, basal ganglia, and pons

Deep White Matter Infarcts

Prat S Deficiency

CNS Lupus

Stroke

Vasculitis

CADASIL Key Facts Terminology • Hereditary small-vessel disease due to mutations in Notch3 gene on chromosome 19, which causes stroke in young adults

• Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) • Primary angiitis of the CNS • Hypercoagulable states

Imaging Findings

Pathology

• Best diagnostic clue: Characteristic subcortical lacunar infarcts and leukoencephalopathy in young adults • Anterior temporal pole and external capsule lesions have higher sensitivity and specificity for CADASIL • Digital subtraction angiogram is normal in CADASIL

• Hallmark of CADASIL: Granular osmiophilic material adjacent to basement membrane of smooth muscle cells of arterioles on electron microscopy

Top Differential

Diagnoses

• Sporadic subcortical arteriosclerotic (sSAE)

Ultrasonographic

encephalopathy

Findings

• Transcranial Doppler: t C02 reactivity + t basal middle cerebral artery mean flow velocity in WMHs • Functional impairment of cerebral vasoreactivity due to vascular smooth muscle cell (VSMC) dysfunction • t C02 reactivity in nondisabled CADASIL individuals (early impaired cerebral vasoreactivity) • C02 reactivity is higher in nondisabled CADASIL individuals than in disabled patients

Angiographic

Findings

• Digital subtraction

Nuclear Medicine

angiogram

is normal in CADASIL

Findings

• PET o 18F-FDG PET: Severely t cortical and subcortical glucose metabolism in CADASIL patients o Lowest metabolic rates in thalamus and striatum o Worst cortical changes: Frontal, temporal, parietal o Asymmetric regional rate of cerebellar glucose metabolism o Crossed cerebellar diaschisis: Hypometabolism in one cerebral hemisphere associated with hypometabolism in contralateral cerebellar hemisphere o Subcortical disconnection suggested by t cortical metabolism and crossed cerebellar diaschisis • SPECT: t Cerebral blood flow {=} lesion load

Diagnostic Checklist • Radiologic hallmark: Subcortical WMHs and small cystic lesions • Characteristic WMHs visualized on MRI > 21 Y • Temporal WM involvement = major abnormality differentiating CADASIL from sSAE

• Diffuse, confluent regions of periventricular WM involvement (leukoaraiosis) • CADASIL vs sSAE o More extensive bilateral involvement of anterior temporal and superior frontal WM in CADASIL o Bilateral signal intensity reductions within dentate nucleus, deep cerebellar WM, crus cerebri, and thalamus in CADASIL

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) • Bilateral multifocal cortical and subcortical hyperintense lesions on FLAIR images • New infarct-like lesions have high signal on DWI and much higher ADC than normal-appearing regions • Early 1 ADC in acute/subacute phase reflects vasogenic rather than cytotoxic edema • Normal/I ADC values within 48 hours of neurological deficit of abrupt onset should raise possibility of MELAS, especially if conventional MR images show infarct-like lesions • Lesions disappear with clinical improvement and ADC returns to normal (tissue recovery)

Primary angiitis of the eNS • Lumen irregularities in distal cerebral arteries on digital subtraction angiogram

Imaging Recommendations

Hypercoagulable

• Best imaging tool: MR imaging • Protocol advice: T2WI and DWI

• Antiphospholipid antibodies, protein S deficiency • Stroke in young and middle-aged adults, with high rate of recurrence • "Antiphospholipid syndrome": Early stroke, recurrent arterial and venous thromboses, spontaneous fetal loss, and thrombocytopenia • Cortical and lacunar infarcts of various sizes • T2 WMHs; dural sinus thrombosis • Abnormal angiogram: Vasculitis-like findings and stenoses at origin of great vessels (infrequent in general stroke population)

I DIFFERENTIAL DIAGNOSIS Sporadic subcortical arteriosclerotic encephalopathy (sSAE) • Associated with hypertension • Multiple lacunar infarcts in lenticular nuclei, pons, thalamus, internal capsule, and caudate nuclei

Stroke

states

4 63

General Features

64

• General path comments o Pathologic hallmark: Nonarteriosclerotic, amyloid-negative angiopathy primarily affecting leptomeningeal and long perforating arteries of brain o Distinctive angiopathy: Granular osmiophilic material within vascular basal membrane, in close contact with degenerating VSMC • Genetics o Point mutations in Notch3 gene on chromosome 19q13.1 • Notch3 codes for a large transmembrane receptor physiologically expressed in VSMC • Notch3 gene product's extracellular domain accumulates at cell surface of brain VSMC • Genetic heterogeneity: Multiple point mutation sites in Notch3 gene (ex on 4, but also 3, 5, 6) o Autosomal dominant transmission o De novo mutations in patients without family history of CADASIL • Etiology o Two types of lesions affecting small cerebral arteries are present and affect cerebral hemodynamics • Narrow arteriolar lumen due to fibrous thickening of arterial wall ~ I baseline blood flow • Destroyed VSMC may impair vasodilatory response to hypoxia o In CADASIL patients with minor WMHs • Total cerebral blood flow I at rest • Cerebral va sodilatory capacity is preserved • Epidemiology: Prevalence is at least 1 per 100,000 • Associated abnormalities o Neuropathological findings of Alzheimer disease (senile plaques and neurofibrillary tangles) o 1 Risk of early acute myocardial infarction in mutation carriers, which predates major neurological symptoms of CADASIL • Typical CADASIL arteriopathic changes in coronary vasculature

Gross Pathologic & Surgical Features • Subcortical lacunar infarcts • Diffuse myelin pallor with periventricular preference • Macroscopic appearance of cortex is usually normal

Microscopic

Features

• Hallmark of CADASIL: Granular osmiophilic material adjacent to basement membrane of smooth muscle cells of arterioles on electron microscopy • Clinical features usually confined to CNS, but CADASIL is systemic vasculopathy

o Psychiatric disorders (20-30%): Major depression, adjustment disorder o Seizures (6-10%), most often following strokes • Clinical profile o Young or middle-aged patient with recurrent transient ischemic attacks leading to infarction o Substantial/complete recovery after individual strokes, particularly early in disease process

Demographics • Age o Onset of ischemic symptoms in mid-adulthood o Migraine (with aura) and stroke can occur in Notch3 mutation carriers < 35 y, while physical function and cognition are still intact • Gender: No gender preference

Natural History & Prognosis • Classic phenotype o Migraine develops in 3rd-4th decades (40-60%) o Strokes occur in 4th-5th decades ~ • ~ Dementia in 6th-7th decades, depression • ~ Pseudobulbar palsy, hemi- or quadriplegia o Dysarthria if high lesion load in posterior fossa o Death usually in 7th decade • Unusual presentation: Reversible, ± recurrent acute encephalopathy, lasting 1-2 weeks o Fever, acute confusion, coma, seizures o Full recovery after acute episode • Higher lesion burden in brain stem, basal ganglia, cerebellum ~ higher degree of disability

Treatment • No specific therapy

1[)IAGN.OSTIC ••<=.EfEC!l(LISJ Consider • Awareness of clinical and radiological features of CADASIL in patients < 35 Y allows early diagnosis • Consider CADASIL in acute unexplained encephalopathy

Image Interpretation

I SELECTED REFERENCES 1.

2.

ICUNICALISSUES

Pearls

• Radiologic hallmark: Subcortical WMHs and small cystic lesions • Characteristic WMHs visualized on MRI > 21 Y • Temporal WM involvement = major abnormality differentiating CADASIL from sSAE

3.

Presentation • Most common signs/symptoms o Recurrent ischemic episodes (TIA, stroke) (70-80%) o Cognitive deficits (30-50%) o Migraine (20-40%), mostly with aura

Stroke

Schon F et al: "CADASIL coma": an underdiagnosed acute encephalopathy. J Neurol Neurosurg Psychiatry 74:249-252, 2003 Oberstein L et al: Incipient CADASIL. Arch Neurol 60:707-712,2003 Tatsch K et al: Cortical hypometabolism and crossed cerebellar diaschisis suggest subcortically induced disconnection in CADASIL: and 18F-FDG PET study. J Nucl Medicine 44:862-869, 2003

(Left) Axial FLAIR MR image in a patient with CAOASIL shows basal ganglia, peri ventricular and deep white matter hyperintense lesions. (Right) Axial FLAIR MR shows multiple subcortical white matter hyperintense areas consistent with infarctions in a patient with proved Notch] mutation.

4 Typical

65 (Left) Axial FLAIR MR shows multiple hyperintense WM lesions. (Courtesy C. Gibbs, MO and P. Lindell, MD. Copyright 2004, used with permission of Mayo Foundation for Medical Education and Research). (Right) Axial OWl MR in the same patient shows that the lesions are hyperintense, consistent with restricted diffusion due to infarction.

Typical (Left) Axial T2WI MR shows diffuse white matter hyperintense lesions throughout the centrum semiovale. (Right) Axial NECT in a different patient shows diffuse white matter hypodensity consistent with chronic ischemic change. On this single image, it would be difficult to distinguish CAOASIL from sSAE.

Stroke

Coronal graphic shows hydranencephaly. Absent cerebral hemispheres with intact thalami, brainstem, cerebellum. Falx cerebri (arrow) appears to "float" in CSF-filled rostral cranial vault.

4

NECT shows near complete absence of the cerebral hemispheres and ventricles with small bilateral parietal lobe remnants (arrows). The falx cerebri is thin (no adjacent brain) but intact.

66

MR Findings • • • •

Fluid (CSF intensity) fills supratentorial cranial vault Any remaining brain normal signal (no gliosis) Falx cerebri partially/completely intact MRA: Hypo-/aplastic, stenotic, occluded, malformed ICAs common • Fetal MR: Severe hydrocephalus or hemorrhage may precede hydranencephaly

Definitions • In-utero cerebral hemispheric destruction with preservation of thalamus, brainstem (BS), cerebellum • Term from "hydrocephalus" + "anencephaly"

Ultrasonographic

General Features

Findings

• Real Time o Anechoic supratentorial cranial vault + hyperechoic falx, choroid plexus o Prenatal: Severe hydrocephalus/hemorrhage may precede hydranencephaly

• Best diagnostic clue: CSF-filled cranial vault + absent cortical mantle/ventricles, intact falx cerebri/p fossa • Location o Supratentorial (unilateral variant, hemihydranencephaly, is rare) • Thalamus, BS, cerebellum, choroid plexus intact • Lobar remnants (temporal/occipital) common • Morphology: "Water bag brain"

Imaging Recommendations • Best imaging tool o Prenatal ultrasound: Allows therapeutic intervention o Postnatal MR best delineates extent of destruction

CT Findings • NECT o CSF attenuation fills supratentorial cranial vault o Falx cerebri partially/completely intact, basal ganglia separated • CTA: Supraclinoid ICAs atretic, stenotic, occluded, malformed, or normal

I DIFFERENTIAL

Severe hydrocephalus • Thin mantle of cortex along inner table, falx

DDx: "Water Bag Brain" (Increased Supratentorial

Max Hydrocephalus

DIAGNOSIS

Holoprosencephaly

Stroke

CSF)

Schizencephaly

HYDRANENCEPHALY Key Facts • Alobar holoprosencephaly • Severe bilateral schizencephaly

Terminology • In-utero cerebral hemispheric destruction with preservation of thalamus, brainstem (BS), cerebellum

Pathology • Intrauterine compromise of supraclinoid intact posterior circulation

Imaging Findings • Best diagnostic clue: CSF-filled cranial vault + absent cortical mantle/ventricles, intact falx cerebri/p fossa

Top Differential

ICAs with

Clinical Issues • Most common signs/symptoms: (choroid plexus secretes CSF)

Diagnoses

• Severe hydrocephalus

Macrocranium

• Clinical profile: Infant with macrocranium, developmental failure, calvarial transillumination • Other signs/symptoms o Hyperirritability, hyperreflexia, seizures

Alobar holoprosencephaly • Absent/deficient falx cerebri • Fusion midline structures; midline facial anomalies

Severe bilateral schizencephaly

Demographics

• MCA distribution to falx

• Age: Diagnosis usually made first few weeks of life

defect lined by GM; brain adjacent

Natural History & Prognosis

Cystic encephalomalacia

• Neurological function limited to brainstem • Prognosis: Death in infancy; prolonged survival rare

• Hemispheric destruction less severe, multifocal • Gliotic brain with cystic parenchymal cavities

Treatment • CSF shunt treats macrocephaly;

I PATH 0 LOG¥ General Features • General path comments: Liquefactive necrosis brain 20-27 weeks gestation • Genetics o Sporadic; rare, syndromic autosomal recessive • Fowler: Hydranencephaly, fetal akinesia deformation sequence, CNS vasculopathy • Microhydranencephaly: Hydranencephaly, microcephaly, small body size (Chr 16p13.3-12.1) • Familial hydranencephaly, renal hypoplasia, cardiac anomalies • Etiology o Intrauterine compromise of supraclinoid ICAs with intact posterior circulation o Implicated: Hereditary thrombophilic states, intrauterine infection, maternal irradiation/toxin exposure, twin-twin transfusion, intrauterine anoxia • Epidemiology: < 1:10,000 births; 0.2% infant autopsies; lOx 1 teenage mothers • Associated abnormalities: Vascular malformations

I DIAGNOSTIC

no change cognition

CHECKLIST

Image Interpretation

Pearls

• Presence of intact falx cerebri distinguishes hydranencephaly from alobar holoprosencephaly • Thin cortical mantle adjacent to inner table/falx distinguishes hydrocephalus from hydranencephaly

I SELECTED REFERENCES 1.

2.

Hahn JS et al: Hydranencephaly owing to twin-twin transfusion: serial fetal ultrasonography and magnetic resonance findings. J Child Neurol. 18: 367-70, 2003 Sutton LN et al: Hydranencephaly versus maximal hydrocephalus: an important clinical distinction. Neurosurgery. 6(1):34-8, 1980

I IMAGE GALLER¥

Gross Pathologic & Surgical Features • Leptomeningeal-lined hemispheres

Microscopic

CSF-filled "sacs" in lieu of

Features

• Hemosiderin-laden

macrophages

over remnant brain

I CLINICAL ISSUES Presentation • Most common signs/symptoms: (choroid plexus secretes CSF)

Macrocranium

(Left) NECT shows only thalami, 85, cerebellum and inferior temporal lobe remnant (arrow); C5F fills the remaining cranial vault. Note shunt catheter in right subcutaneous tissue. (Right) CT scout shows macrocranium and shunt catheter in an infant with hydranencephaly.

Stroke

4 67

Coronal cranial ultrasound in a 34 week premature newborn shows periventricular foci of hyperechogenicity (PVL) (arrows).

4

Coronal cranial ultrasound shows periventricular white matter (arrows).

cavitation

of

68

rIERMINOL(lGY Abbreviations

and Synonyms

• Hypoxic-ischemic encephalopathy (HIE), periventricular leukomalacia (PVL), anoxic-ischemic encephalopathy (AlE)

Definitions • PVL is the HIE-driven periventricular white matter (WM) necrosis seen in very low birth weight (VLBW) premies o Other preterm HIE-related injuries • Germinal matrix and intraventricular hemorrhage (IVH)

• Periventricular hemorrhagic • Cerebellar infarction

infarction

• NECT o Early: Limited ability to document non-hemorrhagic PVL o Late: Ventriculomegaly, undulating lateral ventricular borders, periventricular WM volume loss

General Features • Best diagnostic clue o Periventricular leukomalacia • Best early ultrasound clue: Hyperechoic periventricular "flare", with loss of normal tissue echo texture • Most specific ultrasound clue: Periventricular white matter cavitation

Trigonal Blush

Radiographic Findings • Radiography: Microcephaly

CT Findings

r·IM;\GING/FINifJINGS

DDx: Periventricular

• Best early MR clue: Restricted diffusion (DWI) in affected areas • Best late MR clue: Periventricular volume loss, ventriculomegaly, and gliosis • Location: PVL may be focal (adjacent to frontal horns and trigones) or diffuse • Size: Periventricular cysts in PVL typically in the 2-3 mm range; larger cysts carry poorer prognosis • Morphology: Undulating ventricular borders, ventriculomegaly, volume loss strongly suggest diagnosis of PVL

leukomalacia

MR Findings • TlWI o Early: 1 Tl signal in PV WM (hemorrhagic necrosis), +/- 1 Tl signal in dorsal pons, thalami or basal ganglia o Late: Passive ventricular enlargement, PV WM volume loss, +/- PV cavitation, thin callosum

Mimics

PMD

Congenital CMV

Stroke

HIE, PRETERM Key Facts Terminology • PVL is the HIE-driven periventricular white matter (WM) necrosis seen in very low birth weight (VLBW) premies

Imaging Findings • Best early ultrasound clue: Hyperechoic periventricular "flare", with loss of normal tissue echo texture • Most specific ultrasound clue: Periventricular white matter cavitation • Best early MR clue: Restricted diffusion (DWI) in affected areas • Best late MR clue: Periventricular volume loss, ventriculomegaly, and gliosis

• T2WI o Early: 1 T2 signal in PV WM (edema, ischemia, or infarction), focal! T2 signal (hemorrhagic necrosis) o Late: Ventriculomegaly, volume loss, gliosis, thalamic scarring, and demyelination • PD/Intermediate: Early: 1 Signal in affected periventricular WM, hypointensity at sites of hemorrhagic necrosis • FLAIR o 1 Periventricular signal (gliosis) if> 24-26 week gestation, +/- periventricular cysts, WM volume loss o If preterm HIE was profound look for bright flair signal (gliosis) in: Brainstem, thalamus, striatum, amygdala • T2* GRE: ! Signal at sites of hemorrhagic necrosis • DWI o Restricted diffusion in affected areas, ADC values may "normalize" within 10-12 days • White matter adjacent to frontal horns and trigones or more diffuse PV WM diffusion restriction • Profound preterm HIE: Dorsal pons, midbrain, amygdala, striatum, and thalamus • MRS: 1 Lactate, ! NAA, 1 excitatory neurotransmitters

Ultrasonographic

Findings

• Real Time o Early • Edema: Effaced sulci and compressed ventricles • Focal PVL: Hyperechogenicity (flare) adjacent to frontal horns and trigones • Diffuse PVL: More generalized periventricular white matter hyperechogenicity o Late: +/- Cavitation, unexplained ventriculomegaly, WM volume loss

Nuclear Medicine

Findings

• PET: The normal preterm white matter shows: ! Global values for cerebral blood flow

Imaging Recommendations • Best imaging tool

• Early: t T1 signal in PV WM (hemorrhagic necrosis), +/- t T1 signal in dorsal pons, thalami or basal ganglia • Late: Ventriculomegaly, volume loss, gliosis, thalamic scarring, and demyelination • Cranial sonography: Acute and subacute screening of preterm neonates at risk

Top Differential • • • •

Diagnoses

Normal periventricular halo Pelizaeus-Merzbacher disease (PMD) Congenital CMV infection Oculocerebrorenal syndrome (Lowe syndrome)

Diagnostic Checklist • In a high risk VLBW preterm newborn, cranial ultrasound may underestimate PVL

o Cranial sonography: Acute and subacute screening of preterm neonates at risk o MRI, DWI, MRS • Expands understanding of abnormal screening US findings • Sensitive for defining injury in VLBW neonates with "normal" cranial ultrasounds • Protocol advice o Ultrasound screening: First, between 7 and 14 days, repeat before discharge from the hospital o MRI • When US is abnormal: MRI ASAP to clarify scope of injury and aide in prognosticating, include DWI • At discharge for "at risk" VLBW neonates with "normal" screening cranial sonograms

I DIFFERENTIAL. DIAGNQSIS Normal periventricular

halo

• Normal hyperechoic "blush" posterosuperior to the ventricular trigones, seen on para sagittal sonography • Suspect PVL if echogenicity is: Asymmetric, coarse, globular or more hyperechoic than glomi of the choroid plexus

Pelizaeus-Merzbacher

disease (PMD)

• Sudanophilic leukodystrophy, classically X-linked recessive, may mimic cerebral palsy • MR shows striking lack of myelination

Congenital CMV infection • Microcephaly, periventricular periventricular demyelination polymicrogyria

Oculocerebrorenal syndrome)

calcifications, variable and gliosis, +/-

syndrome (Lowe

• Congenital ocular abnormalities, mental retardation, renal tubular dysfunction, and metabolic bone disease • MR shows periventricular cysts, demyelination, and gliosis

Stroke

4 69

o Risk factors for preterm HIE related injury • Pregnancy: I Gestational age/weight, previous preterm birth, spontaneous preterm labor • Intrapartum: Abruption, pre-eclampsia, premature rupture of membranes, chorioamnionitis, group B strep • Peri & postnatal factors: Respiratory distress, patent ductus arteriosus, I PaC02, sepsis, anemia, apnea, bradycardia, cardiac arrest

General Features

70

• General path comments o Embryology-anatomy • I Perfusion of periventricular white matter (site of immature oligodendroglia) causes PVL • Genetics: t Spontaneous preterm delivery with the fetal carriage of ILlB+3953*1 (African) and ILlRN*2 (Hispanic) alleles • Etiology o Oligodendrocyte vulnerable due to • Periventricular vascular anatomical and physiological factors (arterial end zones) • Cerebral ischemia-impaired cerebrovascular autoregulation-pressure passive cerebral circulation • Intrinsic vulnerability of cerebral white matter of the preterm newborn (free radicals, glutamate, and cytokines) o New model: Prenatal hypoxia induces WM damage via inflammatory response, oxidative stress linked to re-oxygenation during perinatal period • Epidemiology o Birth weight < 1500 g =} 45% incidence of PVL (higher if associated with intraventricular hemorrhage) o Gestational age < 33 weeks =} 38% incidence of PVL o > 50% of patients with PVL or grade III IVH develop cerebral palsy • Associated abnormalities: Intraventricular hemorrhage, basal ganglia and thalamic necrosis, dorsal pontine and amygdala infarction

I DIAGNOSTIC

Gross Pathologic & Surgical Features

Consider

• Autopsy: Pontosubicular necrosis (59%), germinal matrix hemorrhage (50%), PVL (24%)

• PVL when US, CT or MRI shows unexplained ventricular dilation, look for gliosis and volume loss

Microscopic

Demographics • Age: Incidence of PVL in VLBW infants « 1000 g) is approximately 25-45% • Gender: Caucasian males at greater risk for PVL, African-American females somewhat "immune" • Ethnicity: Poor antepartum care increases the fetal risk for PVL

Natural History & Prognosis • Spastic diplegia/quadriplegia, seizures, microcephaly, blindness, deafness • Mental retardation, learning disability, attention deficit disorder • Poor outcome if IVH plus PVL, PVL with volume loss, widespread infarction, or seizures

Treatment • Prenatal care significantly reduces preterm birth (35% down to 8%) • Supportive, cerebral cooling, possible future for free radical scavengers

CHECKLIST

Image Interpretation

Features

Pearls

• In a high risk VLBW preterm newborn, cranial ultrasound may underestimate PVL

• Focal PVL: Coagulative necrosis and infarction at arterial end zones, tissue dissolution and cavitation • Diffuse PVL: HIE affects differentiating oligodendroglia, causing more diffuse infarction of periventricular white matter

I SELECTED REFERENCES

Staging, Grading or Classification Criteria

1.

• Reperfusion of ischemic tissue =} t susceptibility to hemorrhage o Grade I: Confined to the germinal matrix (ganglionic eminence) o Grade II: Germinal matrix hemorrhage ruptures through ependyma to ventricle but does not dilate o Grade III: Hemorrhage expands one or both ventricles o Grade IV: Hemorrhage involves PV parenchyma (venous infarction)

28:87-92,2004 2.

3.

Baud 0 et al: Gestational hypoxia induces white matter damage in neonatal rats: A new model of periventricular leukomalacia. Brain Pathol. 14: 1-10,2004 Ment LRet al: Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice committee of the Child Neurology Society. Neurology 58(12): 1726-38,2002

4.

Gururaj A et al: CT and MR patterns of hypoxic ischemic brain damage following perinatal asphyxia. J Trap Pediatr 48(1):5-9,2002

ICLINI.tALISSlJES

5.

Presentation • Most common signs/symptoms: Spastic diplegia visual impairment =} cognitive impairment • Clinical profile

Righini A et al: Prenatal magnetic resonance imaging evaluation of ischemic brain lesions in the survivors of monochorionic twin pregnancies. J Comput AssistTomogr.

=}

Stroke

Is LTet al: MR Patterns of hypoxic-ischemic brain damage after prenatal, perinatal or postnatal asphyxia. Neuropediatrics 31:128-36, 2000

Typical (Left) Axial T1WI MR shows periventricular T1 shortening indicative of hemorrhagic necrosis (arrows). (Right) Axial T1 WI MR shows basal ganglia and thalamic T1 shortening indicating profound pre term hypoxic ischemic insult (arrows).

4 Typical

71 (Left) Axial OWl MR (AOC map), shows diffuse basal ganglia and thalamic hypointensity consistent with restricted diffusion following preterm neonatal asphyxia (arrows). (Right) Coronal T2* eRE MR shows asymmetric hemorrhagic PVL (arrow). Note the bilateral germinal matrix hemorrhages (curved arrows).

Typical (Left) Axial T2WI MR shows ventricular enlargement with irregular margins (arrows), and diffuse periventricular white matter volume loss as a result of previous periventricular leukomalacia. (Right) Coronal cranial sonogram in an two month old, 32 week preterm infant shows unexplained ventriculomegaly (arrows) secondary to diffuse periventricular volume loss (PVL).

Stroke

Axial graphic shows edema of the cortex and subcortical white matter. There is sparing of the deep structures in prolonged partial hypoxic ischemia of the newborn.

4 72

Abbreviations

and Synonyms

• Hypoxic ischemic encephalopathy (HIE); formerly perinatal or birth asphyxia, asphyxia neonatorium

Definitions • Cerebral hypoperfusion injury • An acquired condition in term neonates who o Show signs of fetal distress prior to delivery o Have low Apgar, require resuscitation at birth o Have metabolic acidosis (cord pH < 7) o Have neurological abnormalities in first 24 hours • PP (prolonged partial) injury: As in nuchal cord o Chronic repetitive stress, intermittent recovery =*' CBF redistribution, preserved deep structures • PA (profound acute) injury: As in uterine rupture, uterine abruption or cord prolapse o No cerebral blood flow (CBF) redistribution =*' areas with high metabolic demand damaged

Axial graphic shows sparing of the cortex and edema of the lateral thalami and of the posterior putamina in profound, acute hypoxic ischemia of the newborn.

o PA: BG damaged, WM/cortex spared • Location o PP: Para sagittal "border zone" injury o PA: Deep gray matter (GM), posterior mesencephalon, hippocampi and peri-Rolandic cortex injury o Mixed: Border zone AND deep gray matter

Radiographic Findings • Radiography: Microcephaly,

secondary craniostenosis

CT Findings • NECT o PP acute: Loss of cortical, insular "ribbon"; white matter (WM) edema o PP chronic: Ulegyria (border zone volume loss), diffuse atrophy o PA acute: Subtle j density BG, blurred GM/WM interface; +/- petechial bleed o PA chronic: Atrophy or slit-like lacunes BG, thalami; +/- hazy Ca++ (status marmoratus)

MR Findings General Features • Best diagnostic clue o PP: White matter (WM)/cortex damaged, deep gray nuclei/basal ganglia (BG) spared

• TlWI o PP acute: "Bright" cortex at bottom of sulci (laminar necrosis) o PA acute: j Tl signal of normally myelinated posterior limb internal capsule (Ie) if term ~ 37 wks; spuriously normal ~ 72 hrs!

DDx: Abnormal Signal in Globus Pallidus

Acute Kernicterus

Late Kernicterus

Methylmalonic

Stroke

Manganese in TPN

HIE, TERM Key Facts • Hypoxic ischemic encephalopathy (HIE); formerly perinatal or birth asphyxia, asphyxia neonatorium • Cerebral hypoperfusion injury • PP (prolonged partial) injury: As in nuchal cord • PA (profound acute) injury: As in uterine rupture, uterine abruption or cord prolapse

• Restricted diffusion &: L ADC values, even if T1WI/T2WI normal • MRV: More than coincidental r sinovenous occlusion • Lactate in full-term (> 37 weeks gestation) may be only abnormal finding in first 24 hours! • Useful US signs in full term infant: r Echogenicityof gyral white matter, cortex AND sulci

Imaging Findings

Pathology

• PP: Parasagittal "border zone" injury • PA: Deep gray matter (GM), posterior mesencephalon, hippocampi and peri-Rolandic cortex injury • PA acute: ! T1 signal of normally myelinated posterior limb internal capsule (IC) if term ?c 37 wks; spuriously normal s 72 hrs!

• Seek inborn errors of metabolism if apparent HIE with normal Apgar OR if > 1 HIE child in family • HIE: Up to 2/1,000 (0.2%) live births

Terminology

•

•

• •

• • • •

o PA acute: r T1 signal in ventrolateral thalamus, BG (especially posterior putamina), peri-Rolandic cortex o Mixed acute: ! T1 in normally myelinated posterior limb IC &: bright cortex T2WI o PP acute: Blurring of gray-white junction o PP chronic: Border zone damage gliosis +/- cystic encephalomalacia o PA chronic: Atrophy/ r signal posterior putamina/lateral thalami and Rolandic cortex o Mixed chronic: Border zone &: posterior putamina/lateral thalamic atrophy and r signal FLAIR o Acute: Documents cystic change, edema is poorly shown o Chronic: Useful to document extent of gliosis T2* GRE: Hemosiderin if subarachnoid hemorrhage or petechial hemorrhagic conversion of ischemia DWI o Restricted diffusion &: L ADC values, even if T1WI!T2WI normal o Limited window of opportunity to document injury, underestimates damage if performed at wrong time • May be normal within first 24-48 hours if just hypoxia and not arterial obstruction • Normalizes around 7 days, even in damaged areas T1 C+: Subacute enhancement ~ poor outcome MRA: Confirms arterial obstruction in focal stroke MRV: More than coincidental r sinovenous occlusion MRS o Lactate normal feature of developing brain < 37 weeks gestation o Lactate in full-term (> 37 weeks gestation) may be only abnormal finding in first 24 hours! o NAA ! for age correlates with poor prognosis o r (){-glutamate/glutamine peaks in BG correlate with r severity of injury

Ultrasonographic

Findings

• Real Time o More useful in pre-term than full term: Flare &: cysts o Useful US signs in full term infant: r Echogenicity of gyral white matter, cortex AND sulci

Diagnostic Checklist • DWI crucial, but limited window of opportunity • Typical periventricular leukomalacia (PVL) pattern may occur in full-terms with HIE AND sepsis

• Color Doppler: Variable resistive indices &: anterior cerebral artery blood flow waveform

4 73

Nuclear Medicine

Findings

• PET: Selective damage in BG and areas of primary myelination: r Rates of oxygen-glucose utilization • Brain Scan o 1-123 iodobenzamide SPECT: Striatum: Cerebellum ratio! as r severity of perinatal HIE event o 99mTC annexin V: Animal studies show neuronal apoptosis after HIE event even with normal DWI! ADC (may explain development of cerebral palsy with normal neonatal imaging)

Imaging Recommendations • Best imaging tool o MRS: Lactate may be first or only abnormal finding o DWI: Extremely sensitive for early, acute ischemia o T1 axial: Documents loss of internal capsule in HIE (infants ?c 37 weeks gestational age) • Protocol advice o MRS crucial in first 24 hours o DWI crucial, but may take> 48 hours to become "positive" (and may "pseudonormalize" in 1 wk) o Standard MR imaging limited by hypomyelination &: r water content of neonatal brain

I DIFFERENTIAL

DIAGNOSIS

Kernicterus (accentuated

by sepsis, hypoxia)

• Mimics profound injury on acute T1WI; has confirmed hyperbilirubinemia • Globus pallidus, (not putamen or thalamus) abnormal on follow-up

Metabolic

disorder

• Inherited: Mitochondrial encephalopathy, methylmalonic acidemia • Manganese (TPN) mimics T1 BG changes of HIE

Stroke

74

General Features

Presentation

• General path comments: Ischemia often multi-organ (e.g., cardiac, renal) • Genetics o Seek inborn errors of metabolism if apparent HIE with normal Apgar OR if > 1 HIE child in family o Inherited prothrombotic disorders =} arterial or venous occlusions: Protein CIS deficiencies, factor V Leiden mutation, antiphospholipid antibodies • Etiology o PP (as in nuchal cord): Mild or moderate hypoperfusion • "Diving reflex" redistribution cerebral blood flow (CBF) to basal ganglia/brainstem/cerebellum o PA (as in uterine rupture): Profound hypoperfusion • No time to shift CBF, areas of highest metabolic demand damaged o Mixed pattern of injury: Mild or moderate hypoperfusion converts to profound at or near time of delivery • Early compensatory adjustment to ~ CBF fails =} "pressure-passive" CBF (dependent on systemic BP) • BP falls, CBF falls, brain hypoxia/intracellular energy failure follow o Asphyxia triggers cascade of cellular biochemical events leading to abnormal function, edema or death of cell • Extracellular glutamate accumulates, activates postsynaptic excitatory amino-acid receptors • Postsynaptic receptor distribution changes with development =} different damage patterns at different gestational ages o Many chances for cell loss • Primary neuronal (death at time of insult) • Reactive cell death (reperfusion injury hours or days later) • Seizure related cell injury • Epidemiology o HIE: Up to 2/1,000 (0.2%) live births o Venous thrombosis: 0.4/1,000 (0.04%) live births o Arterial stroke: 0.9/1,000 (0.09%) live births • Associated abnormalities o Maternal: Infection, pre-eclampsia, diabetes, cocaine o Infant: ~ Gestational age, growth retardation, ~ Ca++/glucose, sepsis, hyperthermia, seizures, congenital heart disease; t urine SlOOB protein

• Most common signs/symptoms o Sarnat I (mild): Hyperalert/irritable, mydriasis, EEG normal o Sarnat II (moderate): Lethargy, hypotonia, ~ HR, Sz o Sarnat III (severe): Stupor, flaccid, reflexes absent; Sz • Clinical profile o Periventricular leukomalacia (PVL): Lower extremity spasticity o Unilateral/focal lesions: Hemiplegia o Parasagittal cystic encephalomalacia: Spastic tetra paresis o Bilateral BG damage: Extrapyramidal cerebral palsy

Gross Pathologic & Surgical Features

2.

• PP: Para sagittal ulegyria, gliosis and atrophy • PA: Hippocampal, BG, thalamic, peri-Rolandic

Microscopic

atrophy

Demographics • Age: Full-term perinatal = immediate intrapartum, and postnatal period

Natural History & Prognosis • Varies from normal outcome (Sarnat I) to spastic quadriparesis, developmental delay, microcephaly, and Sz (Sarnat III) • Severe HIE: 50% mortality, significant morbidity in 80% of survivors • Choreoathetosis after 1 year common in PA survivors

Treatment • Correct hypoxia, metabolic disturbances • Treat seizures and hyperthermia

f.DIA.G·N(J$ .•..I~·(1ifle(]K~I$T' Consider • Prenatal HIE with recovery OF. inborn errors of metabolism if imaging doesn't fit history

Image Interpretation

of

Staging, Grading or Classification Criteria

Pearls

• DWI crucial, but limited window of opportunity • Typical periventricular leukomalacia (PVL) pattern may occur in full-terms with HIE AND sepsis

1.

3.

Features

• < 30 gestational weeks: Liquefaction, resorption parenchyma • > 30 weeks: Reactive astrogliosis, macrophages

prenatal,

4.

5.

• Sarnat stages of HIE encephalopathy

Stroke

Gazzolo D et al: Urinary SlOOBprotein measurements: A tool for early identification of hypoxic-ischemic encephalopathy in asphyxiated full-term infants. Crit Care Med. 32:131-6, 2004 Barkovich AJ et al: Proton spectroscopy and diffusion imaging on the first day of life after perinatal asphyxia: "rl~,iminary report. AJNR22(9):1786-94,2001 \r.crew ME et al: Thromboembolic disease and entithrombotic therapy in newborns. Hematology (Am Soc ]L~lLatol Educ Program):358-74, 2001 Gwenendaal F et al: Glutamate in cerebral tissue of ,bI'hyxiated neonates during the first week of life (bnonstrated in vivo using proton MRS. Bioi Neonate ;')3-4):254-257,2001 ',", nquart F et al: D2 receptor imaging in neonates using ·123 iodobenzamide brain SPECT.Clin Nucl Med 26 1):36-40, 11139051,2001

Typical (Left) Coronal OWl MR shows extensive diffusion restriction in the cortex and subcortical white matter in an infant with prolonged partial HIE. Note relative sparing of deep gray structures and brainstem. (Right) Coronal T2WI MR shows late atrophy and gliosis in the border zones (arrows) following neonatal prolonged partial HIE. Note relative deep grey matter and brainstem sparing.

4 Typical

75 (Left) Axial TlWI MR in early prolonged partial HIE shows loss of signal in the posterior limb of internal capsule (curved arrow) and increased signal in posterior putamen, CP and lateral thalamus (arrows). (Right) Axial FLAIR MR shows atrophy and gliosis of posterior putamina (arrow) and lateral thalami (curved arrow) in a survivor of profound acute HIE. Patient suffers from extrapyramidal cerebral palsy.

Typical (Left) Axial NEeT shows calcification of thalami (arrow) and posterior basal ganglia (curved arrow) from status marmoratus. There is diffuse atrophy and a collapsed calvarium following remote mixed HIE. (Right) Coronal NEeT with 30 reconstruction shows microcephaly and overlapping, fused sutures in an infant with craniostenosis due to failure of brain growth foJ/owing mixed HIE.

Stroke

ACUTE CEREBRAL ISCHEMIA-INFARCTION

Coronal graphic illustrates left M7 occlusion. Such proximal occlusion will affect the entire MCA territory, including the deep nuclei, which are perfused by lenticulostriate arteries.

4 76

Abbreviations

and Synonyms

• Stroke = lay term for sudden onset neurologic symptoms • Cerebrovascular accident (CVA)

Definitions • Interrupted blood flow to brain resulting in cerebral ischemia/infarction with variable neurologic deficit

I IMAGING FINOING$ General Features • Best diagnostic clue: Diffusion restriction with correlating ADC map • Location: One or more vascular territories, or at border-zones ("watershed") • Size: Dependent on degree of compromise, collateral circulation • Morphology: Wedge shaped when gray matter involved, variable white matter involvement

CT Findings • NECT o Hyperdense vessel on NECT (high specificity, low sensitivity)

Axial NECT demonstrates a hyperattenuating ("dense") MCA (arrow) in this patient with acute stroke symptoms.

• Caused by acute thrombus in cerebral vessel(s) • Hyperdense M1 MCA in 35-50% • "Dot sign" = occluded MCA branches in sylvian fissure (16-17%) o Loss of gray-white matter distinction in first 3 hrs seen in 50-70% • Obscuration of deep nuclei • Loss of insular "ribbon" o Parenchymal hypodensity on NECT • If> 1/3 MCA territory initially, large lesion later • Temporary transition to isodensity (up to 54%) at 2-3 weeks post-ictus = CT "fogging" o Gyral swelling, sulcal effacement 12-24 hrs o "Hemorrhagic transformation" in 15-45% • Delayed onset (24-48 hrs) is most typical • Can be gross (parenchymal) or petechial • CECT o Enhancing cortical vessels = slow flow or collateralization acutely, absent vessels = occlusion o Triphasic perfusion CT: Assess ischemic core vs penumbra to identify patients who will benefit most from revascularization • Perfusion CT determines perfused CBV and/or CBF, mean transit time (MTT) o Cortical/gyral enhancement after 48-72 hrs • CTA: Identifies occlusions, stenoses, status of collaterals

·~

DDx: Stroke Imaging Mimics

I

.

Y ,

\l)/ Astrocytoma

Cerebral Contusion

Cerebritis

Stroke

Encephalitis

ACUTE CEREBRAL ISCHEMIA-INFARCTION Key Facts Terminology

Top Differential Diagnoses

• Interrupted blood flow to brain resulting in cerebral ischemia/infarction with variable neurologic deficit

• Hyperdense vessel mimics • Parenchymal hypodensity (nonvascular

causes)

Imaging Findings

Pathology

• Best diagnostic clue; Diffusion restriction with correlating ADC map • Location: One or more vascular territories, or at border-zones ("watershed") • Morphology: Wedge shaped when gray matter involved, variable white matter involvement • DWI/PWI "mismatch" "penumbra" or "at risk" tissue • Conventional MR sequences positive in 70-80% • Restricted diffusion improves accuracy to 95% • Best imaging tool: MR + T2*, DWI • NECT, perfusion CT, CTA if MR not available • DSA with thrombolysis in selected patients

• Second most common worldwide cause of death • Number one cause of US morbidity

=

Clinical Issues • Most common symptom: Focal acute neurologic deficit • Clinical diagnosis inaccurate in 15-20% of "strokes" • "Time is brain"; IV rTPA window < 3 hrs; IA rTPA window < 6 hrs

Diagnostic Checklist • DWI positive for acute stroke only if ADC correlates

MR Findings • Tl WI: Early cortical swelling & hypointensity, loss of gray-white borders • T2WI o Early cortical swelling, hyperintensity in affected distribution o May normalize 2-3 weeks post-ictus = MR "fogging" • PD/Intermediate: Loss of flow voids = slow flow vs occlusion • FLAIR o May be positive (hyperintense) when other sequences normal (as early as 6 hrs post-ictus) o MR intra-arterial signal on FLAIR = early specific sign of major vessel occlusion • T2* GRE o Sensitive for detection of acute blood products o Shows thrombosed vessel as arterial "blooming" from clot susceptibility • DWI o Hyperintense restriction from cytotoxic edema • DWI improves hyperacute stroke detection to 95% • Usually correlates to "ischemic core" (final infarct size); some diffusion abnormalities reversible • May have reduced sensitivity in brain stem and medulla in first 24 hours • High signal can persist up to 57 days post-ictus, (after 10 days, T2 effect may predominate over low ADC = "T2 shine-through") o Corresponding low signal on ADC maps • May normalize after tissue reperfusion • Note: Hyperintensity on ADC map (T2 "shine-through") may mimic diffusion restriction o Distinguishes cytotoxic from vasogenic edema in complicated cases; especially helpful for evaluation of new deficits following tumor-resection • Tl C+ o Variable enhancement patterns evolve over time • Immediate: Intravascular enhancement (stasis from slow antegrade or retrograde collateral flow) • Early: Meningeal enhancement (pial collateral flow appears in first 24-48 hrs, then resolves over 3-4 days)

• • •

•

• Late acute: Parenchymal enhancement (appears after 24-48 hrs, can persist for weeks/months) MRA: Demonstrates major vessel occlusions, stenoses, collateral status MRS o Elevated lactate, decreased NAA • At mid TE (e.g., 135) lactate doublet inverts Perfusion MRI o Bolus-tracking T2* Gadolinium perfusion imaging (PWI) with rCBV map • !Perfusion; 75% larger than DWI abnormality • With arterial input can calculate rCBF, rMTT o DWI/PWI "mismatch" = "penumbra" or "at risk" tissue Conventional MR sequences positive in 70-80% o Restricted diffusion improves accuracy to 95%

Angiographic Findings • Conventional o Vessel occlusion (cutoff, tapered, tram track) o Slow antegrade flow, retrograde collateral flow • Interventional: rTPA thrombolysis o Fibrinolytic therapy for treatment of selected acute nonhemorrhagic stroke within a 6 hr window o Significantly improves clinical outcomes

Nuclear Medicine Findings • SPECT: Voxel-based maps reflect viable neurons, potentially salvageable tissue

Imaging Recommendations • Best imaging tool: MR + T2*, DWI • Protocol advice o MRI with FLAIR, GRE, DWI, MRA, PWI (if available) o NECT, perfusion CT, CTA if MR not available o DSA with thrombolysis in selected patients

I DIFFERENTIAL DIAGNOSIS Hyperdense vessel mimics • High hematocrit (polycythemia) • Microcalcification in vessel wall

Stroke

4 77

ACUTE CEREBRAL ISCHEMIA-INFARCTION o Usually older adults o Children, young adults ~ consider underlying disease; sickle cell, moyamoya, Nfl, cardiac, drugs • Gender: No gender predilection

• Low density brain (e.g., diffuse cerebral edema) makes vessels appear relatively hyperdense • Normal circulating blood always slightly hyperdense to normal brain

Natural History & Prognosis

Parenchymal hypodensity (nonvascular causes) • • • •

• Clinical diagnosis inaccurate in 15-20% of "strokes" • "Malignant" MCA infarct (coma, death) o Up to 10% of all stroke patients o Fatal brain swelling with increased ICP

Infiltrating neoplasm (e.g., astrocytoma Cerebral contusion Inflammation (e.g., cerebritis or encephalitis) Evolving encephalomalacia

Treatment • "Time is brain": IV rTPA window < 3 hrs; IA rTPA window < 6 hrs • Patient selection = most important factor in outcome o Symptom onset < 6 hrs o CT shows no parenchymal hematoma o < 1/3 MCA territory hypodensity

fpA\TI--t.QI-OG¥ General Features

4 78

• Etiology o Many causes of acute cerebral ischemia (thrombotic vs embolic, dissection, vasculitis, hypoperfusion) o Early: Critical disturbance in CBF • Severely ischemic core has CBF < 6-8 cm3/100g/min (normal ~ 60 cm3/lOOg/min) • Causes oxygen depletion, energy failure, terminal depolarization, ion homeostasis failure • Represents bulk of final infarct ~ cytotoxic edema, cell death o Later: Evolution from ischemia to infarction depends on many factors (e.g., hyperglycemia influences "destiny" of ischemic brain tissue) o Ischemic "penumbra" CBF between 10-20 cm3/100g/min • Theoretically salvageable tissue • Target of thrombolysis, neuroprotective agents • Epidemiology o Second most common worldwide cause of death o Number one cause of US morbidity o Newly-identified stroke risk factors: C-reactive protein, homocysteine • Associated abnormalities: Cardiac disease, prothrombotic states

IbIAGN()STICCf-fEGI<~IS"" Consider • Adding DWI to all brain MRIs; time cost < 1 min

Image Interpretation

I SELECTED REFERENCES 1.

2. 3.

4.

5.

Gross Pathologic & Surgical Features

6.

• Acute thrombosis of major vessel • Pale, swollen brain; GM/WM boundaries

7.

Microscopic

"smudged"

Features

8.

• After 4 hrs: Eosinophilic neurons with pyknotic nuclei • 15-24 hrs: Neutrophils invade, necrotic nuclei look like "eosinophilic ghosts" • 2-3 days: Blood-derived phagocytes • 1 week: Reactive astrocytosis, t capillary density • End result: Fluid-filled cavity lined by astrocytes

I CLtNl(:A\lIS$l..JES

9. 10.

11.

12.

Presentation • Most common signs/symptoms o Most common symptom: Focal acute neurologic deficit o Weakness, aphasia, decreased mental status

Pearls

• DWI positive for acute stroke only if ADC correlates

13.

14.

Demographics • Age

Stroke

Fiebach JB et al: Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage. Stroke. 35: 502-7, 2004 Javedan SP et al: Pseudoenhancement from polycythemia. Neurology. 62: 150, 2004 Gass A et a1: Diffusion-weighted MRI for the "small stuff": the details of acute cerebral ischemia. Lancet Neurol. 3: 39-49,2004 Nakajima M et al: Relationships between angiographic findings and NIH stroke scale score in cases of hyperacute arterial ischemic stroke. AJNR 25:238-41, 2004 Diaz J et al: Cerebral ischemia: New risk factors. Cerebrovasc Dis. 17 Suppl1:43-50, 2004 Kelly PS et al: Inflammation, homocysteine, and vitamin B6 status after ischemic stroke. Stroke 35:12-5, 2004 Bourekas EC et al: Intraarterial thrombolytic therapy with 3 hours of the onset of stroke. Neurosurg 54:39-46, 2004 Mahagne MH et al: Voxel-based mapping of cortical ischemic damage. J Neuroimaging 14:23-32, 2004 Fiehler J et al: Predictors of apparent diffusion coefficient normalization in stroke patients. Stroke. 35: 514-9, 2004 Vo, KD et al: MR imaging enhancement patterns as predictors of hemorrhagic transformation in acute ischemic stroke. AJNR 24(4):674-9,2003 Leary, MC et al: Validation of computed tomographic middle cerebral artery "dot" sign; an angiographic correlation study. Stroke 34:2636-40, 2003 Borisch, I et al: Preoperative evaluation of carotid artery stenosis: comparison of contrast-enhanced MR angiography and duplex sonography with digital subtraction angiography. AJNR 24: 1117 -22, 2003 Eastwood, JD et al: Quantitative assessment of the time course of infarct signal intensity on diffusion-weighted images. AJNR 24:680-687,2003 Toyoda, K et al: Fluid-attenuated inversion recovery intraarterial signal: an early sign of hyperacute cerebral ischemia. AJNR 22:1021-29, 2001

ACUTE CEREBRAL ISCHEMIA-INFARCTION

I IMAGE GALLERY Typical (Left) Axial OWl MR in a patient 2 hours after stroke onset shows restricted diffusion. Correlative AOC hypointensity was also demonstrated within the same geographic area (not shown). (Right) Axial T1 C+ MR in the same case demonstrates intravascular enhancement within insular branches of the left MCA indicating slow flow.

4 79 (Left) Axial CECT shows abrupt right MCA cut-off (arrow) in a patient with hyperacute stroke symptoms (Courtesy j. Eastwood, MO). (Right) Axial CT perfusion map in the same case reveals significantly prolonged mean transit time within the MCA distribution (red region).

Typical (Left) Axial OWl MR shows restricted diffusion within the right occipital lobe in a patient with sudden onset of visual symptoms (Courtesy j. Provenza Ie, MD. With permission from AjR 175:207-20,2000). (Right) Axial PWI rCBV map in the same case reveals a larger area of perfusion abnormality (blue area); a classic" diffusion-perfusion" mismatch of ischemic "penumbra".

Stroke

SUBACUTE CEREBRAL INFARCTION

Axial T7 C+ MR demonstrates classic gyriform enhancement of subacute cerebral infarction. Some underlying T7 hyperintense hemorrhage is masked by extensive enhancement.

4

Axial NECT shows wedge-shaped non-hemorrhagic infarct. Lack of mass effect as well as not yet CSF-like hypodensity aid in diagnosing subacute age.

80

TERMINOLOGY Abbreviations

CT Findings

and Synonyms

• Subacute stroke with or without hemorrhagic transformation (HT)

Definitions • Focal brain necrosis that follows obstruction of blood flow to a localized area of the brain • Subacute infarction is approximately 2-14 days following initial ischemic event

IMAGING FINDINGS General Features • Best diagnostic clue: Gyral edema & enhancement, occasional with hemorrhagic transformation within basal ganglia, cortex • Location: Cerebral hemispheres, brainstem, cerebellum in territorial vascular distribution • Size: Extremely variable ranging from focal ("lacunes") to global (hemispheric) • Morphology o Variable depending on location, size & etiology o Typically wedge-shaped abnormality involving gray & white matter within vascular distribution

• NECT o Wedge-shaped area of decreased attenuation involving gray/white matter in typical vascular distribution o Mass effect initially increases, then begins to diminish by 7-10 days; often less than expected given lesion size as acuity resolves o HT of initially ischemic infarction occurs in 15-20% of MCA occlusions, usually by 48-72 hrs • Common locations are basal ganglia & cortex • Hemorrhagic foci detected in majority of medium & large-sized subacute infarcts • CECT o Enhancement patterns typically patchy or gyral o May appear as early as 2-3 days after ictus, persisting up to 8-10 weeks o "2-2-2" rule = enhancement begins at 2 days, peaks at 2 weeks, disappears by 2 months • CTA o CTA evidence of occlusion correlates strongly & independently with poor clinical outcome • Have significantly worse discharge National Institutes of Health Stroke Scale (NIHSS) score • CT Perfusion o Provides valuable information to predict tissue outcome between infarcted & viable brain tissue

DDx: Subacute Infarct Mimics

(~t •• ".

I

\

-

.•... ".:~; 1, 0

~\

.,r." '. ~ .

. -",0

'f

.

"" '--/ Low Grade Glioma

Venous Infarct

Encephalitis

Stroke

Late Cerebritis

SUBACUTE CEREBRAL INFARCTION Key Facts Top Differential

Terminology • Subacute infarction is approximately following initial ischemic event

2-14 days

Diagnoses

• Neoplasm • Venous infarction • Encephalitis/cerebritis

Imaging Findings • Best diagnostic clue: Gyral edema & enhancement, occasional with hemorrhagic transformation within basal ganglia, cortex • Wedge-shaped area of decreased attenuation involving gray/white matter in typical vascular distribution • HT of initially ischemic infarction occurs in 15-20% of MCA occlusions, usually by 48-72 hrs • "2-2-2" rule = enhancement begins at 2 days, peaks at 2 weeks, disappears by 2 months • t Lactate, !NAA within infarcted tissue

o Significant difference between infarct & peri-infarct tissue for both rCBF, rCBV

Clinical Issues • Acute onset focal neurologic deficit • In first month after infarction, mortality predominantly from neurologic complications; 1 in 4 will die of a recurrent stroke event • Acute anticoagulation after first infarction reduces mortality

Diagnostic Checklist • Enhancement key to defining subacute stage of cerebral infarction

• MR T2* Perfusion o !rCBV of acute infarct increases in subacute stage, reflecting reperfusion hyperemia o Decreases again in chronic stage

MR Findings • TlWI o Hypointense edema with mass effect o HT: Signal changes of evolving hemorrhage • T2WI o Hyperintense edema with mass effect o "Fogging effect" = normal T2WI with striking enhancement on T1 C+ 1-2 weeks following ictus o HT: Signal changes of evolving hemorrhage o Early Wallerian degeneration can occur; well-defined hypointense band in corticospinal tract • FLAIR o Hyperintense edema with mass effect o Hyperintensity ("dot sign") in vessels that do not recanalize • T2* GRE: May see hemosiderin if HT has occurred • DWI o t Diffusion restriction, ! ADC initially, reversing as proceeds into & through subacute stage o DWI & Tl C+ complement each other in detecting subacute infarcts • DWI signal inversely correlated with Tl C+ • ADC is linearly correlated with T1 C+ • T1 C+

o Intravascular enhancement in initial 48 hrs, disappears at 3-4 days as vessels recanalize o Parenchymal enhancement (patterns typically patchy or gyral) • May appear as early as 2-3 days after ictus • Can persist up to 8-10 weeks • MRA: Vessel occlusion (large vessel) • MRS o t Lactate, !NAA within infarcted tissue o In subacute & chronic infarction, lactate/choline & NAA/choline ratios correlate with outcome • Positive correlation between NAA & Scandinavian Stroke Scale (SSS) scores • Positive correlation between NAA reduction & Barthel Index scores • Lactate presence correlates with lower SSS scores

Angiographic Findings • Conventional o May see intraluminal thrombus and/or vessel occlusion o Slow antegrade flow with delayed arterial emptying o Slow retrograde filling through collateral vessels o "Bare" areas = regions of nonperfused or slowly perfused brain tissue

Nuclear Medicine

Findings

• Diminished/absence of perfusion with SPECT or PET • HMPAO SPECT may show reflow hyperemia after reperfusion in acute & subacute stages

Imaging Recommendations • Best imaging tool: MR with DWI, T2*, T1 C+ • Protocol advice oCT: Add CT perfusion o CT & MRI: C+ for assessing subacute age

I DIFFERENTIAl.. DIAGNOSIS Neoplasm • DWI: Vasogenic ("tumoral") edema rather than cytotoxic edema • Enhancing mass rather than patchy, gyral enhancement • Will not regress on follow-up imaging

Venous infarction • Non-arterial distribution • Venous rather than arterial occlusion, typically major dural sinus • More commonly hemorrhagic, primarily affecting white matter rather than cortex • Different clinical presentation/setting (trauma, hypercoagulable states, pregnancy, dehydration)

Stroke

4 81

SUBACUTE CEREBRAL INFARCTION • Clinical profile: Elderly patient with typical risk factors: Hypertension, diabetes, smoking history, obesity, hypercholesterolemia, etc

Encephalitis/ cerebritis • DWI: Vasogenic ("tumoral") edema rather than cytotoxic edema • Non-vascular distribution • Gyriform, ring enhancing patterns (late cerebritis) • Different clinical presentation

Demographics • Age o Usually> 55 years o Women typically older than men (77.8 vs 73.2) • Gender o After age adjustment, females often more disabled o Fatality rates are similar

IPATflQL.QGY General Features

4 82

• General path comments o Ischemia/infarction involves typical vascular territories or watershed (border-zone) distributions depending on etiology o Results of infarction vary with sensitivity of individual cell types to ischemia o Other factors include adequacy of collateral blood supply, degree, duration, distribution of flow reduction • Genetics: Hypercholesterolemia, diabetes, hypertension, homocysteine increase stroke risk • Etiology o Prolonged cerebral ischemia o Duration as well as severity of ischemic insult determines cellular viability o Less commonly, may be result of infectious etiologies, such as sequelae of meningitis (bacterial, mycobacterial, etc) o May also be result of inflammatory diseases, such as vasculopathy, angiitis, etc o Uncontrolled unilateral supratentorial expanding lesions can cause tentorial herniation leading to ischemic infarction of occipital lobe • Epidemiology o Third cause of US adult mortality o Largest cause of US adult morbidity

Gross Pathologic & Surgical Features • Blurring of gray/white matter demarcation • Mass effect with narrowing of sulci, displacement of adjacent structures • Softening of ischemic tissues from water retention

Microscopic

Features

• Fragmentation ofaxons & early disintegration of myelin sheaths; loss of oligodendrocytes, astrocytes • 48 hrs: Neutrophils begin to pass through vessel walls into brain tissue • 72-96 hrs: Macrophages aggregate around vessels • 2 wks: Macrophages are predominate reactive cells

Natural History & Prognosis • In first month after infarction, mortality predominantly from neurologic complications; 1 in 4 will die of a recurrent stroke event • Later mortality from respiratory, cardiovascular causes • Survival after first infarction: 92% at 1 week, 83% at 30 days, 77% at 6 months, 71% at 1 year, 46% at 5 years, 28% at 10 years

Treatment • To improve long-term survival, aggressive management of pulmonary & cardiac disease critical • Acute anticoagulation after first infarction reduces mortality • Current research includes therapeutic hypothermia as well as gene therapy (anti-apoptotic protein BCL-2) during acute stroke event

I DIAGNOSTICicHECi(LI$T Consider • Could affected area be other space-occupying pathology (Le., tumor) • Recommend short-term follow-up to ensure expected course of resolution

Image Interpretation

I SELECTED REFERENCES 1.

2.

3.

4.

s. Presentation • Most common signs/symptoms o Acute onset focal neurologic deficit o Approximately 50% of patients with infarction resulting in permanent neurologic deficits have preceding TIAs

Pearls

• Enhancement key to defining subacute stage of cerebral infarction

6.

7.

Stroke

Thomalla GJ et al: Prediction of malignant middle cerebral artery infarction by early perfusion- and diffusion-weighted magnetic resonance imaging. Stroke. 34(8):1892-9, 2003 Wijman CA: Editorial commentnCan we predict massive space-occupying edema in large hemispheric infarctions? Stroke. 34(8):1899-900, 2003 Vernino S et al: Cause-specific mortality after first cerebral infarction: a population-based study. Stroke. 34(8):1828-32, 2003 Verro P et al: CT angiography in acute ischemic stroke: preliminary results. Stroke. 33(1):276-8, 2002 Klingebiel R et al: Multi-slice CT angiography in the evaluation of patients with acute cerebrovascular diseasena promising new diagnostic tool. J Neurol. 249(1):43-9, 2002 Koenig M et al: Quantitative assessment of the ischemic brain by means of perfusion-related parameters derived from perfusion CT. Stroke. 32(2):431-7, 2001 Mayer TE et al: Dynamic CT perfusion imaging of acute stroke. AJNR AmJ Neuroradiol. 21(8):1441-9, 2000

SUBACUTE CEREBRAL INFARCTION

Typical (Left) Axial OWl MR demonstrates hyperintense restricted diffusion of cytotoxic edema within both right ACA (arrow) and MCA (open arrow) vascular territories. (Right) Axial NECT shows classic non-hemorrhagic left MCA territory infarction, involving basal ganglia. Note relatively mild ventricular & sulcal mass-effect given size of lesion during subacute stage.

4 Typical

83 (Left) Axial T7WI MR shows hemorrhagic subacute infarction involving gray matter as well as a small portion of subcortical white matter. Gyri/arm enhancement was also present. (Right) Axial CECT demonstrates extensive gyral subacute infarct enhancement 6 weeks after ictus. Note absence of mass effect given lesion size as acuity diminishes.

Typical (Left) Axial NECT demonstrates cortical hemorrhage of subacute left MCA distribution infarction. Note lack of mass effect given lesion size. (Right) Axial MRA collapsed view M RA reveals lack of flow in the right posterior cerebral artery (curved arrow).

Stroke

CHRONIC CEREBRAL INFARCTION

Axial graphic shows chronic infarct involving the posterior left MCA territory. Infarct is lined with gliotic white matter. Small lacunar infarctions and atrophy also depicted.

84

Abbreviations

o Extremely variable • Ranging from focal ("lacunes") to lobar or global (hemispheric) • Morphology o Extremely variable depending on location, size, etiology of vascular insult o Classic is "wedge-shaped" area of encephalomalacia

and Synonyms

• Cerebral infarction • Encephalomalacia • Stroke

(CI)

Definitions • End result of prolonged

Axial NEeT shows large, chronic left MCA distribution infarct seen here as low density encephalomalacic brain with ipsilateral ventricular enlargement.

CT Findings

cerebral ischemia

General Features • Best diagnostic clue: Volume loss with gliosis along affected margins • Location o Cerebral hemispheres, brain stem, cerebellum o Territorial infarction involves brain tissue supplied by major cerebral artery • Supratentorial: MCA, ACA, PCA distribution • Infratentorial: BA, PICA distribution o Watershed ("border zone") infarction involves brain tissue between main vascular territories o Lacunar infarctions are small infarcts in deep penetrating artery distributions (typically located in basal ganglia/thalami, white matter (WM)) • Size

• NECT o Focal, well-delineated low-attenuation areas in affected vascular distribution o Adjacent sulci become prominent; ipsilateral ventricle enlarges o Dystrophic Ca++ may occur in infarcted brain but is very rare • CECT: No enhancement • CTA: May see lack of flow in affected vessel

MR Findings • TlWI o Isointense to CSF in affected areas o Adjacent sulci become prominent o Ipsilateral ventricle enlarges • T2WI o Isointense to CSF in affected areas o Borders of infarction may show increased signal secondary to gliosis/spongiosis

DDx: Stroke Mimics

!

I

I\ Porencephalic Cyst

~. Arachnoid Cyst

Encephalomalacia

Stroke

Astrocytoma

CHRONIC CEREBRAL INFARCTION Key Facts

• us estimates

Imaging Findings

contributes

• Best diagnostic clue: Volume loss with gliosis along affected margins • Classic is "wedge-shaped" area of encephalomalacia

Top Differential • • • •

Clinical Issues • Most common signs/symptoms: Focal neurologic deficit • Varies greatly depending on size of CI and degree of neurologic deficit • The most consistent predictor of 30 day mortality after stroke is stroke severity • Stroke mortality in the US is predicted to rise 3 times as fast as the general population over the next 30 years • Lacunar stroke is most common stroke subtype associated with vascular dementia

Diagnoses

Porencephalic cyst Arachnoid cyst Post-surgicalJpost-traumatic Low attenuating tumors

encephalomalacia

Pathology • Volume loss and gliosis pathological hallmarks • Four major types of stroke are cerebral infarction (80%); primary ICH (15%); SAH (5%); venous occlusions « 5%)

•

• • • • •

o Differentiation of subacute from chronic infarction on standard SE sequences may be difficult because relaxation times prolonged in both FLAIR o Hyperintense gliotic white matter at margins o Low signal in encephalomalacic area T2* GRE: May see hemosiderin staining in gliotic areas or along borders of infarction DWI: No restricted diffusion T1 C+: No enhancement MRA: May see lack of flow in affected vessel MRS: Shows loss of NAA peak in affected area

Angiographic

Findings

• Conventional: May see lack of flow in affected vessel and its vascular territory

Imaging Recommendations • Best imaging tool: CT or MRI • Protocol advice: No contrast necessary if imaging typical (I.e., lack of mass effect)

I DIFFERENTIAL DIAGNOSIS Porencephalic cyst • Congenital cyst typically seen in younger age groups • Also lined by gliotic white matter

Arachnoid cyst • No gliotic margins • Usually in locations atypical for vascular territory • Intact gray matter lining brain, displaced by cyst

Post-su rgical/ post - traumatic encephalomalacia • History and associated findings help to distinguish • May see leptomeningeal cyst in post-traumatic setting

low attenuating tumors • Typically shows mass effect • Usually slightly hyperdense/intense

range from 760,000-780,000 annually; to approximately 150,000 deaths per year

compared to CSF

I PATHOLOGY General Features • General path comments o Volume loss and gliosis pathological hallmarks o Typically in main vascular territories or watershed (border-zone) distribution depending on etiology o Results of CI vary with the sensitivity of individual cell types to ischemia o Other factors include adequacy of collateral blood supply, degree, duration and distribution of flow reduction • Genetics: Hypercholesterolemia, diabetes, hypertension, homocysteine increase stroke risk • Etiology o Prolonged cerebral ischemia o Duration as well as severity of ischemic insult determines cellular viability o Four major types of stroke are cerebral infarction (80%); primary ICH (15%); SAH (5%); venous occlusions « 5%) o Less commonly, may be result of infectious etiologies, such as sequelae of meningitis (bacterial, mycobacterial, etc) o May also be result of inflammatory disease, such as vasculopathy, angiitis, etc o Uncontrolled unilateral supratentorial expanding lesions can cause tentorial herniation; common complications include ischemic infarction of occipital lobe • Epidemiology o Second or third leading cause of death in the Western world (after non-cerebral cardiovascular disease and cancer) o Major cause of long~term disability o One in 5 patients with first-ever stroke will survive to 10 years o US estimates range from 760,000-780,000 annually; contributes to approximately 150,000 deaths per year

Stroke

4 85

CHRONIC

CEREBRAL INFARCTION

Gross Pathologic & Surgical Features • Liquefaction resulting in cyst formation • Cystic areas traversed by trabeculations of blood vessels, surrounded by firm glial tissue

Microscopic

5. 6.

Features 7.

• Fibrillary gliosis along margin of infarction • Macrophages may persist in interstices of infarcts; some may contain hemosiderin

8.

9.

ICLINICALISSUES Presentation

4 86

• Most common signs/symptoms: Focal neurologic deficit • Clinical profile o Elderly patient with typical risk factors as • Hypertension, diabetes, smoking history, obesity, hypercholesterolemia, etc

10.

11. 12.

Demographics • Age: Usually> 55 years • Gender o Women typically older than men (77.8 vs 73.2 years) o After age adjustment, females often more disabled o Fatality rates similar

13.

14.

Natural History & Prognosis • Varies greatly depending on size of CI and degree of neurologic deficit • The most consistent predictor of 30 day mortality after stroke is stroke severity • Mortality rates in the US have declined dramatically in the 1970s and 1980s, but have plateaued in the 1990s • Stroke mortality in the US is predicted to rise 3 times as fast as the general population over the next 30 years • Lacunar stroke is most common stroke subtype associated with vascular dementia

15.

Treatment • To improve long-term survival after CI, aggressive management of pulmonary and cardiac disease critical • Acute anticoagulation after first CI associated with reduced mortality

I DIAGNOSTIC

CHECKLIST

Consider • Could lesion be an arachnoid cyst?

cyst or porencephalic

I SELECTED REFERENCES 1.

2. 3. 4.

Arboix A et al: New concepts in lacunar stroke etiology: the constellation of small-vessel arterial disease. Cerebrovasc Dis. 17 Suppll:63-9, 2004 Giele JLP et al; Silent brain infarcts in patients with manifest vascular disease. Stroke. 35: 742-6, 2004 Sumer MM et al: Predictors of outcome after acute ischemic stroke. Acta Neurol Scand. 107(4):276-80, 2003 Hardie K et al: Ten-year survival after first-ever stroke in

Stroke

the perth community stroke study. Stroke. 34(8):1842-6, 2003 Truelsen T et al: Advances in ischemic stroke epidemiology. Adv Neurol. 92:1-12, 2003 Hankey GJ: Long-term outcome after ischaemic stroke/transient ischaemic attack. Cerebrovasc Dis. 16 Suppll:14-9,16,2003 Zweifler RM: Management of acute stroke. South Med]. 96(4):380-5,2003 Glader EL et al: Sex differences in management and outcome after stroke: a Swedish national perspective. Stroke. 34(8):1970-5, 2003 O'Sullivan M et al: Frequency of subclinical lacunar infarcts in ischemic leukoaraiosis and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. AJNR Am J Neuroradiol. 24(7):1348-54, 2003 Rumpel H et al: Serial FLAIR imaging after Gd-DTPA contrast: pitfalls in stroke trial magnetic resonance imaging. Stroke. 34(3):797-8, 2003 Nagaratnam N et al: Multiple cerebral infarcts following septic shock. J Clin Neurosci. 9(4):473-6, 2002 Kato H et al: Near-infrared spectroscopic topography as a tool to monitor motor reorganization after hemiparetic stroke: a comparison with functional MRI. Stroke. 33(8):2032-6, 2002 Rovira A et al: Diffusion-weighted MR imaging in the acute phase of transient ischemic attacks. AJNR Am J Neuroradiol. 23(1):77-83, 2002 Shimoda M et al: Asymptomatic versus symptomatic infarcts from vasospasm in patients with subarachnoid hemorrhage: serial magnetic resonance imaging. Neurosurgery. 49(6):1341-8; discussion 1348-50, 2001 Huang I] et al: Time course of cerebral infarction in the middle cerebral arterial territory: deep watershed versus territorial subtypes on diffusion-weighted MR images. Radiology. 221(1):35-42, 2001

CHRONIC

CEREBRAL INFARCTION

I IMAGE GALLERY Typical (Left) Axial T2WI MR shows small left MCA distribution infarction (open arrow). Infarct is lined with gliotic white matter (see image on right). Left lateral ventricle slightly dilated. (Right) Axial FLAIR MR corresponding FLAIR-weighted image to T2WI on left. Gliotic white matter better appreciated with FLAIR weighting (arrows).

4 Typical

87 (Left) Axial NECT shows small chronic infarction involving the right ACA territory within the right superior frontal gyrus (open arrow), with surrounding halo of gliosis (arrow). (Right) Axial NECT shows a chronic appearing right MCA territory infarction (black arrow). Note low-attenuating gliotic margins (white arrow), distinguishing this from an arachnoid or porencephalic cyst.

Other (Left) Lateral gross pathology shows encephalomalacia from old left MCA distribution infarction (arrows) (Courtesy R. Hewlett, MO). (Right) Axial gross pathology, section through the ventricles (same case as left) shows the right MCA infarct (open arrow). A smaller; left parietal infarct (arrow) is also present (Courtesy R.Hewlett, MO).

Stroke

LACUNAR INFARCTION

Axial graphic illustrates numerous bilateral lacunar infarctions within thalami and basal ganglia (open arrows). Also shown are perivascular (Virchow-Robin) spaces (arrows).

4

Axial FlAIR MR demonstrates multiple bilateral chronic lacunar infarctions with central encephalomalacia. A halo or rim of surrounding gliosis helps to distinguish from VR spaces.

88

• Morphology:

I TERMINOLOGY Abbreviations

CT Findings

and Synonyms

• Lacunar infarction • "Lacunes"

Typically round or ovoid

(LI)

Definitions • Small, deep cerebral infarcts typically located in basal ganglia (BG), thalamus • From Latin word "lacuna" meaning hole o Used to describe small cavity of encephalomalacia, mostly in basal ganglia • "L'etat crib Ie" or "cribriform state" = many round small holes representing dilatations of lenticulostriate perivascular spaces • "L'etat lacunaire" or "lacunar state" = multifocal basal ganglia lacunar infarcts with surrounding gliosis

IIMAGING FINDINGS

• NECT o Because of their small size, most "true" lacunar infarcts not seen on CT scans o Visible lacunes seen as small, well circumscribed areas of low (CSF) attenuation o Usually seen in setting of more extensive white matter disease; typically multiple • CECT: May enhance if late acute/early subacute

MR Findings • • • •

Tl WI: Small, well circumscribed hypointense foci T2WI: Small, well circumscribed hyperintense foci FLAIR: Typically increased in signal DWI o Restricted diffusion (hyperintense) if acute/subacute o May show small lesions otherwise undetectable • Tl C+: May enhance if late acute/early subacute • MRA: Normal

General Features

Imaging Recommendations

• Best diagnostic clue: Small, well circumscribed areas of parenchymal abnormality (encephalomalacia) in BG, thalamus • Location: Deep gray nuclei, especially putamen, thalamus, internal capsule, caudate nuclei, pons • Size: Range in size from microscopic to 15 mm

• Best imaging tool: NECT for chronic lacunesi MRI with DWI for acutely symptomatic patient • Protocol advice: MRI with DWI if acute

'Etat Crib Ie

VR Spaces

VR Spaces

Stroke

Cysticercosis

LACUNAR INFARCTION Key Facts Terminology

Pathology

• Small, deep cerebral infarcts typically located in basal ganglia (BG), thalamus

• Embolic, atheromatous or thrombotic lesions in long, single penetrating end arterioles supplying deep cerebral gray matter • Lacunar infarcts account for 15-20% of all strokes • Strong association with systemic hypertension • Lacunar stroke is most common stroke subtype associated with vascular dementia

Imaging Findings • Location: Deep gray nuclei, especially putamen, thalamus, internal capsule, caudate nuclei, pons • Size: Range in size from microscopic to 15 mm • Usually seen in setting of more extensive white matter diseasej typically multiple • Best imaging tool: NECT for chronic lacunes; MRI with DWI for acutely symptomatic patient

Top Differential

Diagnoses

• Prominent perivascular spaces • 'Etat crible • Neurocysticercosis

I DIFFERENTIAL DIAGNOSIS Prominent perivascular spaces • Normal variant resulting from accumulation of interstitial fluid within enlarged Virchow-Robin spaces • Found in all areas but tend to cluster around anterior commissure and in cerebral WM • Similar to CSF signal on all pulse sequences • Found in patients of all ages • Increase in size & frequency with advancing age • 25% have slight halo of increased signal on FLAIR or T2WI • Can expand, occur in clusters (mimic neoplasm)

'Etat crible • Multiple enlarged Virchow-Robin spaces most commonly in basal ganglia • Blood vessels in etat crible are thickened, ectatic, with sclerotic walls • Perivascular tissues may show reactive astrocytosis & isomorphic gliosis with glial fibers extending along degenerated axons

Neurocysticercosis • May mimic benign intraparenchymal cysts • Imaging findings vary with developmental stage of cyst, as well as host response • Solitary in 20-50%; when multiple, usually small number of cysts • Inflammatory response around cyst may seal sulcus, making lesions appear intra-axial

IPATHOLOG¥ General Features • General path comments o Small vessel cerebrovascular disease is an important vascular cause of cognitive impairment o Most lacunar infarctions have been considered clinically "silent", although this is being increasingly questioned

Clinical Issues • Variable symptoms, ranging from clinically "silent" to focal neurologic deficit to cognitive impairment to dementia • Elderly, hypertensive patient • A few years after infarct, there is an increased risk of death, mainly from cardiovascular causes

o Often multiple (sometimes referred to as leukoariosis) • Genetics o Usually sporadic o May occur secondary to genetic disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is a hereditary disease • CADASIL has been linked to mutation in Notch3 gene locus (chromosome 19); genetic testing available for clinical diagnosis • Etiology o Embolic, atheromatous or thrombotic lesions in long, single penetrating end arterioles supplying deep cerebral gray matter o Some studies suggest there is evidence of chronic endothelial dysfunction in cerebral small vessel disease and LI o Endothelial prothrombotic changes may be important in mediating ischemic leukoariosis phenotype • Epidemiology o Lacunar infarcts account for 15-20% of all strokes o Strong association with systemic hypertension o Lacunar stroke is most common stroke subtype associated with vascular dementia o There exists a statistically significant incidence of isolated ipsilateral carotid stenosis (CS) in patients with LI located in the carotid territory

Gross Pathologic & Surgical Features • Similar to other types of cerebral infarction • Earliest visible change is slight discoloration & softening of affected area; gray matter structures become blurred & white matter loses its normal fine-grained appearance • Within 48-72 hours necrosis well established & there is softening, disintegration of ischemic area with circumlesional swelling • As resolution proceeds, liquefaction results in cyst formation; more apparent in lesions of larger size • Cysts may be traversed by trabeculations of blood vessels & are surrounded by firm glial tissue

Stroke

4 89

LACUNAR INFARCTION Microscopic

Features

• Gliosis along margin of infarction • Hypertensive hyalinization of supplying arterioles • Pigmented macrophages can be found in some lacunes, suggesting possible hemorrhagic component

I ell NJ(jA\I-ISSiUES Presentation

4 90

• Most common signs/symptoms o Many different presentations, depending on size, location, number o Variable symptoms, ranging from clinically "silent" to focal neurologic deficit to cognitive impairment to dementia o Vascular lesions within thalami may produce "Vascular syndromes" (sensorimotor and behavioral syndromes) depending on which nuclei are involved • Reflect reciprocal cerebral cortical-thalamic connections that have been interrupted o Tuberothalamic territory strokes produce impairments of arousal, orientation, learning, memory, personality, & executive function; superimposition of temporally unrelated information; emotional facial paresis o Paramedian thalamic infarcts cause decreased arousal (particularly if bilateral), impaired learning & memory o Left paramedian & left tuberothalamic lesions that include ventrolateral nucleus result in language deficits o Right thalamic lesions in both these vascular territories produce visual-spatial deficits, including hemispatial neglect o Inferolateral territory strokes produce contralateral hemisensory loss, hemiparesis, hemiataxia, & pain syndromes; more common after right thalamic lesions o Posterior choroidal lesions result in visual field deficits, variable sensory loss, weakness, dystonia, tremors, occasionally amnesia & language impairment • Clinical profile o Elderly, hypertensive patient o Typical risk factors for cerebrovascular disease: Hypertension, diabetes, smoking history, obesity, hypercholesterolemia, etc

Demographics • Age o Usually> SS years o Patients with coronary arteryperipheral vascular disease are at risk for silent infarcts at younger age o Patients with CADASIL present slightly earlier, with symptoms beginning at about 4S years of age; cognitive decline can start as early as age 3S years • Gender: Not gender-specific

• A few years after infarct, there is an increased risk of death, mainly from cardiovascular causes • Risk of recurrent stroke after lacunar infarct is similar to that for most other types of stroke • Patients have an increased risk of developing cognitive decline & dementia • Age, vascular risk factors, high nocturnal blood pressure, & severity of cerebral small-vessel disease at onset have significant prognostic implications for almost all outcomes • Presence of multiple LIs may be an important prognostic indicator both for functional recovery as well as higher rate of recurrence

Treatment • Typical treatment is targeted toward underlying etiology of vasculopathy • More studies on mechanisms, prevention, & treatment are needed to provide specific guidance on long-term management of LI patients • Risk-factor modification is likely to playa large part in therapeutic interventions targeted at this stroke subtype

I DIAGNOSTIC CHECKLIST Consider • Are "lacunes" VR spaces? • Is there a treatable embolic source?

Image Interpretation

Pearls

• To be classified as LI, location must be an end-artery territory

ISELECTED REFERENCES 1.

2.

3. 4.

5.

6. 7.

8. 9.

Natural History & Prognosis • Ranges from clinically "silent" to focal neurological deficit

Stroke

Lee SH et al: Comparative analysis of the spatial distribution and severity of cerebral microbleeds and old lacunes. J Neurol Neurosurg Psychiatry 75:423-7, 2004 Arboix A et al: New concepts in lacunar stroke etiology: the constellation of small-vessel arterial disease. Cerebrovasc Dis. 17 Suppl1:58-62, 2004 Giele JLP et ali Silent brain infarcts in patients with manifest vascular disease. Stroke. 35: 742-6,2004 Gass A et al: Diffusion-weighted MRI for the "small stuff": the details of acute cerebral ischaemia. Lancet Neurol. 3(1):39-45, 2004 Aharon-Peretz Jet al: Progression of dementia associated with lacunar infarctions. Dement Geriatr Cogn Disord. 16(2):71-7, 2003 Schmahmann JD: Vascular syndromes of the thalamus. Stroke. 34(9):2264-78, 2003 O'Sullivan M et al: Frequency of subclinical lacunar infarcts in ischemic leukoaraidsis and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. AJNR Am J Neuroradiol. 24(7):1348-54, 2003 Tejada J et al: Does a relationship exist between carotid stenosis and lacunar infarction? Stroke. 34(6):1404-9, 2003 Hassan A et al: Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis. Brain. 126(Pt 2):424-32, 2003

LACUNAR INFARCTION

Typical (Left) Axial OWl MR shows acute, moderate to large lacunar infarction in right caudate head and anterior internal capsule (arrow). (Right) Axial FLAIR MR shows diffusion positive (not shown) acute lacune in caudate body (arrow), VR space (open arrow), & smaller chronic (diffusion negative, not shown) lacunes (curved arrows).

4 91

Typical (Left) Axial NECT shows chronic-appearing lacunar infarction in anterior limb of the right internal capsule (white arrow). Chronic, small left MCA distribution infarct is also present (black arrow). (Right) Axial NECT shows acute to subacute lacune in anteromedial right thalamus (arrow). Notice subtle inward bowing of the third ventricular lateral wall indicating mild mass effect.

Typical (Left) Axial FLAIR MR shows multiple subcortical and periventricular hyperintense lesions. This technique alone cannot distinguish the acute lesion from surrounding chronic lesions. (Right) Axial OWl MR confirms which lesion is acute in this patient with numerous FLAIR T2 subcortical and peri ventricular hyperintense chronic lacunar infarctions.

Stroke

HYPOTENSIVE CEREBRAL INFARCTION

Coronal graphic shows "border-zone" infarcts between AG4/MG4 territories (black arrows); deep nuclei are often involved (curved arrows); also note pseudolaminar necrosis (white arrows).

4

Coronal STIR MR demonstrates bilateral encephalomalacia distributions (arrows).

92

o Pseudolaminar necrosis = curvilinear gyriform cortically-based abnormality o Diffuse supratentorial abnormality following severe global asphyxia ("white cerebellar" or "reversal sign")

[TERM INOLOG¥ Abbreviations

chronic infarctions as within watershed

and Synonyms

• "Border-zone" or water-shed infarction

Definitions

CT Findings

• Infarction resulting from insufficient cerebral blood flow to meet metabolic demands (low flow state)

• NECT o Hypodensity involving gray matter (GM)-WM junction peripherally between vascular territories • May be due to hemodynamic compromise (Le., significant hypotensive event) • Can have similar appearance to "directed embolization" • "White cerebellum" or "cerebellar reversal" in severe asphyxia (normal cerebellar density appears relatively bright next to supratentorial hypodensity) o When involving deep WM watershed, can have "string of pearls" appearance • 2: 3 deep WM lesions within centrum semiovale • Linear orientation in AP direction • Parallel to lateral ventricle • Unilateral if predisposing major vessel stenosis on ipsilateral side of infarcts • Bilateral if bilateral vessel stenoses and/or significant hemodynamic event • CECT: Parenchymal enhancement can occur when subacute

I

(MAGI NGFINDINGS

General Features • Best diagnostic clue: Diffusion restriction with correlating ADC map • Location o Border-zone between major arterial territories o DeepWM o May be isolated to deep nuclei, basal ganglia o Supratentorial structures in severe perinatal asphyxia • Size: Variable • Morphology o Cortically-based wedge-shaped abnormality at border-zone between vascular territories o Deep white matter (WM) watershed with "rosary" or "string of pearls/beads" appearance • Multiple round foci in linear orientation within centrum semiovale

DDx: Imaging Mimics of Hypotensive

Embolic Infarcts

Infarcts

Arteriosclerosis

PRES

Stroke

Acute Vasculitis

HYPOTENSIVE CEREBRAL INFARCTION Key Facts Terminology

Top Differential

• "Border-zone" or water-shed infarction • Infarction resulting from insufficient cerebral blood flow to meet metabolic demands (low flow state)

• • • •

Imaging Findings

Diagnoses

Acute embolic stroke Arteriosclerosis ("small vessel disease") Posterior reversible encephalopathy (PRES) Vasculitis

Pathology

• Best diagnostic clue: Diffusion restriction with correlating ADC map • Cortically-based wedge-shaped abnormality at border-zone between vascular territories • Deep white matter (WM) watershed with "rosary" or "string of pearls/beads" appearance • Pseudolaminar necrosis = curvilinear gyriform cortically-based abnormality • Diffuse supratentorial abnormality following severe global asphyxia ("white cerebellar" or "reversal sign")

• Epidemiology: Hypotensive 0.7-3.2% of infarcts

infarcts account for

Clinical Issues • Most common signs/symptoms: Altered mental status, coma • Patient with high-grade ICA stenosis, transient hypotension leading to acute cerebral infarction • Resustitated patient with profound asphyxia or prolonged systemic hypotension

• CTA: Multi-detector row/multi-slice CTA useful, accurate in determining total vs near occlusion of ICA • CT Perfusion o Reduced CBF to affected areas

• Protocol advice o MRI with DWI, MRA cervical and intracranial o NECT, Perfusion CT, CTA if MR not available

MR Findings

I DIFFERENTIAL DIAGNOSIS

• Tl WI: Curvilinear, gyriform high Tl signal along cortex = pseudo laminar necrosis • T2WI o Hyperintense edematous gyri, CSF cisterns/sulci compressed o High T2 signal in subacute & chronic infarcts • PD/Intermediate: Look for absent flow voids at skull base indicative of recent occlusion or slow flow • FLAIR o Thrombosed vessel may appear hyperintense o More sensitive to early infarction than T2 • DWI o Hyperintense restriction from cytotoxic edema o Corresponding low signal on ADC maps o Distinguishes cytotoxic from vasogenic edema in complicated cases; especially helpful for evaluation following intraoperative anoxic episode o Pitfall: Global hypoxic-ischemic encephalopathy (HIE) may be diffusely hyperintense, creating a nearly "pseudonormal" appearance • Tl C+ o Subacute infarcts enhance • Gyriform pattern common • +/- Basal ganglia • MRA: Major vessel stenoses predispose to watershed infarction following hypotensive event • MRS o Elevated lactate, decreased NAA • At mid TE (e.g., 135) lactate doublet inverts

Angiographic

• Often bilateral, may also occur at border-zones ("directed embolization" common)

Arteriosclerosis ("small vessel disease") • Scattered, multifocallesions without predilection for watershed • Confluent lesions around atria of lateral ventricles common in hypertensive patients

Posterior reversible encephalopathy

(PRES)

• Lacks DWI restriction (vasogenic edema) • Location often subcortical, not isolated to cortex or deep white matter • Basal ganglia involvement less common

Vasculitis • Often subcortical • Patchy enhancement ganglia

in cortex, subcortical WM, basal

Pseudolaminar necrosis (other causes) • Associations with numerous other entities: Reye, lupus, central pontine myelinolysis, immunosuppressive therapy • Petechial hemorrhage ("hemorrhagic transformation") in subacute thrombolic infarct

I PATHOLOGY

• Conventional: DSA: Proximal and/or significant major intracranial vessel stenosis predispose to watershed infarct

Imaging Recommendations

vessels

Acute embolic stroke

Findings

• Best imaging tool: MR + GRE, DWI

4

General Features • General path comments: "Border-zone" infarction resulting in encephalomalacic brain, "ulegyria" • Etiology o Global brain injury due to disruption of perfusion or oxygenation

Stroke

93

HYPOTENSIVE CEREBRAL INFARCTION

4 94

o Causes include severe prolonged hypotension, cardiac arrest with resuscitation, profound asphyxia, & carbon monoxide inhalation o Major vessel stenoses predispose patient to infarcts at "border-zone" between vascular territories during times of hemodynamic compromise • Deep WM infarcts ("rosary" pattern) correlate well with clinical hemodynamic compromise • Assoc with proximal ICA stenosis/occlusion o Embolic infarcts also occur at "border-zones" thus complicate clinical and radiographic picture • Cortical "border-zone" infarcts occur in 3.2% in patients with cardiac embolic sources, compared to 3.6% in those with severe ICA obstruction • "Directed embolization" may account for many embolic-type "border-zone" infarcts (directional flow at bifurcations occurs from vessel size imbalances in the circle of Willis) • Epidemiology: Hypotensive infarcts account for 0.7-3.2% of infarcts

Gross Pathologic & Surgical Features • Pale, swollen brain; GM/WM boundaries • Encephalomalacia (chronic)

Microscopic

"smudged"

• Clinical outcome usually poor, depends on degree of injury • Diffusion abnormalities restricted to deep nuclei without involvement of cerebral cortex suggest milder injury, and significant neurological recover can occur

Treatment • Treatment of underlying conditions o Correction of hypotension as rapidly as possible o Revascularization of major vessel stenoses

liDIAG.NOSTIC.Cl-IECKllS"r Consider • MRA, CTA of cervical, intracranial vessels as proximal large vessel disease often present in setting of hypotensive infarction

Image Interpretation

I SELECTED REFERENCES

Features

• After 4 hrs: Eosinophilic neurons with pyknotic nuclei • 15-24 hrs: Neutrophils invade, necrotic nuclei look like "eosinophilic ghosts" • 2-3 days: Blood-derived phagocytes • 1 week: Reactive astrocytosis, 1 capillary density • End result: Fluid-filled cavity lined by astrocytes • Pseudo laminar necrosis affects third, fifth, sixth cortical layers

1.

2.

3.

4.

Staging, Grading or Classification Criteria • Pattern classifications o Cortical "border-zone" infarcts (bi- or unilateral) o Deep WM infarcts (penetrating artery "water-shed zone") o Cortical pseudo laminar necrosis o Predominately deep gray nuclei

5.

6.

7.

I CLINICAL ISSUES 8.

Presentation • Most common signs/symptoms: Altered mental status, coma • Clinical profile o Patient with high-grade ICA stenosis, transient hypotension leading to acute cerebral infarction o Resuscitated patient with profound asphyxia or prolonged systemic hypotension

Demographics

9.

10. 11. 12.

• Age: Any age • Gender: No gender predilection

Natural History & Prognosis

Pearls

• "Rosary" or "string of beads" appearance in centrum semiovale highly specific for hemodynamic compromise

13.

• Experimental literature suggests isolated hypoxic injury tolerated better than hypoxia complicated by hypotension

Stroke

Chen C-J et al: Multi-slice CTA in diagnosing total versus near occlusions of the internal carotid artery. Stroke 39:83-5,2004 Takeoka M et al: Diffusion-weighted images in neonatal cerebral hypoxic-ischemic injury. Pediatric Neurol 26:274-281,2002 Singhal et al: Diffusion MRI in three types of anoxic encephalopathy. Journal of the Neurological Sciences. 196:37-40,2002 Derdeyn CP et al: Severe hemodynamic impairment and border zone-region infarction. Radiology 220:195-201, 2001 Bargallo N et al: Cortical laminar necrosis caused by immunosuppressive therapy and chemotherapy. AJNR 21:479-84, 2000 Susa S et al: Acute intermittent porphyria with central pontine myelinolysis and cortical laminar necrosis. Neuroradiol 41:835-9, 1999 Kashihara K et al: Laminar cortical necrosis in central nervous system lupus: sequential changes in MR images. Clin Neurol Neurosurg 101:145-7, 1999 Krapf H et al: Small rosary-like infarctions in the centrum semiovale suggest hemodynamic failure. AJNR 19: 14 79-84, 1998 Hennerici M et al: Failure to identify cerebral infarct mechanisms from topography of vascular territory lesions. AJNR 19:1067-1074, 1998 Kinoshita T et al: Reye's syndrome with cortical laminar necrosis: MRI. Neuroradiol 38:269-72, 1996 van der Zwan A et al: Variability of the territories of the major cerebral arteries. J Neurosurg 77:927-940, 1992 Yamauchi H et al: High-intensity area in the deep white matter indicating hemodynamic compromise in internal carotid artery occlusive disorders. Arch NeuroI48:1067-71, 1991 Waterston JA et al: Small deep cerebral infarcts associated with occlusive internal carotid artery disease: a hemodynamic phenomenon? Arch NeuroI47:953-57, 1990

HYPOTENSIVE CEREBRAL INFARCTION

Typical (Left) Axial PO demonstrates

high signal in deep nuclei (black arrows) and subtle cortical high signal, particularly posteriorly (white arrows), in this patient following anoxic injury. (Right) Axial T2WI MR shows subacute infarcts at "border-zone" between anterior & middle cerebral artery (open arrows) as well as between the anterior & posterior circulation territories (arrows).

4 Typical

95 (Left) Axial OWl MR shows

diffuse restriction of cortical gray matter (open arrows) and deep nuclei (arrows) in a pediatric patient following an hypoxic-ischemic event. (Right) Axial T2WI MR demonstrates increased signal intensity and volume loss within bifrontal white matter related to chronic deep white matter watershed infarctions (arrows).

Typical (Left) Axial OWl MR shows acute deep white matter

infarct within the watershed zone between anterior and middle cerebral artery territories in a patient with underlying severe right carotid stenosis. (Right) Axial PO image reveals loss of right cavernous carotid flow void (arrow). MRA confirmed severe stenosis of right leA (not shown), predisposing the patient to watershed infarction.

Stroke

DURAL SINUS THROMBOSIS

Sagittal graphic shows thrombosis of the superior sagittal sinus (SSS) (black arrows) and straight sinus (white arrow). Inset: Thrombus in SSS in cross section ("delta" sign).

4 96

• CECT o "Empty delta" sign in 25-30% of cases • Enhancing dura surrounds non enhancing thrombus o "Shaggy," irregular veins (collateral channels) • CTA: CT venogram (CTV) shows thrombus as filling defect(s) in dural sinus

rTe/RM1NOl(j)G¥ Abbreviations

and Synonyms

• Dural sinus thrombosis thrombosis (CVT)

(DST), cerebral vein

Definitions • Thrombotic

occlusion of intracranial

Axial T7 C+ MR shows an "empty delta sign" caused by enhancing dura surrounding c/ot in a thrombosed SSS (arrow).

dural sinuses

MR Findings

!IMACINyi/FINJ/DfNOS General Features • Best diagnostic clue o "Empty delta" on CECT, contrast-enhanced MR o Early imaging findings often subtle • Location: Thrombus in dural sinus +/- adjacent cortical vein(s) • Size: Variable • Morphology: Varies with age

CT Findings • NECT o Hyperdense dural sinus> cortical vein ("cord sign") o Venous infarct in 50% • Cortical/subcortical petechial hemorrhages, edema • If SS/ICVs occlude, thalami/basal ganglia hypodense

• TlWI o Acute thrombus Tl isointense o Subacute thrombus becomes hyperintense • T2WI o Clot initially hypointense • Caution: If thrombus is hypointense, can mimic normal sinus "flow void" on T2WI o If venous infarct, mass effect with mixed hypo-/hyperintense signal in adjacent parenchyma o Subacute thrombus appears hyperintense o Chronically occluded, fibrotic sinus eventually appears isointense • PD/Intermediate o Loss of normal flow voids o More sensitive sequence than T2WI, less sensitive than FLAIR • FLAIR o Thrombus hyperintense o Venous infarcts hyperintense

DDx: Dural Sinus Thrombosis Mimics

Fat in Sinus

Arach Granulation

NI Sinus, Infant

Stroke

Hypoplasia

DURAL SINUS THROMBOSIS Key Facts • "Giant" arachnoid

Terminology • Thrombotic

occlusion of intracranial

dural sinuses

Pathology • Resistance to activated protein C (typically due to factor V Leiden mutation) = most common cause of sporadic CVT • Wide spectrum of predisposing causes (> 100 identified) • Epidemiology: 1% of acute "strokes" • Type 1: No abnormality • Type 2: High signal on T2WI/FLAIR; no enhancement • Type 3: High signal on T2WI/FLAIR; enhancement present • Type 4: Hemorrhage or venous infarction

Imaging Findings • • • • • • • • •

"Empty delta" on CECT, contrast-enhanced MR Early imaging findings often subtle Hyperdense dural sinus> cortical vein ("cord sign") Cortical/subcortical petechial hemorrhages, edema Acute thrombus Tl isointense 40% have hyperintense clot in occluded vessel Absence of flow in occluded sinus on 2D TOF MRV If CT scan negative, MRI with MRV If MRV equivocal, DSA

Top Differential

granulation

Diagnoses

• Normal • Anatomic variant

• T2* GRE o Thrombus hypointense, "blooms" o Petechial and/or parenchymal hemorrhages hypointense • DWI o 40% have hyperintense clot in occluded vessel o DWI/ ADC findings in parenchyma variable, heterogeneous • Mixture of vasogenic + cytotoxic edema; cytotoxic edema may precede vasogenic • Parenchymal abnormalities more frequently reversible than in arterial occlusions • Tl C+ o Peripheral enhancement around acute clot o Chronic sinus thrombosis can enhance due to organizing fibrous tissue • MRV o Absence of flow in occluded sinus on 2D TOF MRV • "Frayed" or "shaggy" appearance of venous sinus • Abnormal collateral channels (e.g., enlarged medullary veins) o Tl hyperintense (subacute) clot can masquerade as flow on MRY, evaluate standard sequences and source images to exclude artifacts o Contrast-enhanced MRV (CE-MRV) better demonstrates thrombus, small vein detail, and collaterals, much faster than 2D TOF o PC MRV not limited by Tl hyperintense thrombus • MRS: Helpful if equivocal (differentiate from tumor)

Angiographic

Findings

• Occlusion of involved sinus • Slow flow in adjacent patent cortical veins • Collateral venous drainage develops

Imaging Recommendations • Best imaging tool o NECT, CECT scans +1- CTV as initial screening o MR, MRV (include T2*, DWI, T1 C+) • Protocol advice o If CT scan negative, MRI with MRV o If MRV equivocal, DSA

I DIFFERENTIAL DIAGNOSIS

97

Normal • Blood in vessels normally slightly hyperdense on NECT scans • Common in newborns (combination of unmyelinated low density brain, physiologic polycythemia)

Anatomic variant • Congenital hypoplastic/absent transverse sinus (transverse sinus flow gaps 31 %, usually non dominant sinus) • Right transverse sinus dominant 59%, left dominant in 25%, codominant in 16% • "High-splitting" tentorium • Fat in sinus

"Giant" arachnoid granulation • Round/ovoid filling defect (clot typically long, linear) • CSF density/signal intensity • Arachnoid granulations normal in 24% of CECT, 13% ofMR o Transverse sinus most common location by imaging, L>R o SSSmost common location for arachnoid granulations on histopath (in lateral lacunae, not well seen by imaging)

False "empty delta" sign • SDH, subdural empyema

Neoplasm • Venous infarct can enhance, mimic neoplasm • Intravascular lymphomatosis (rare)

I PATHOLOGY General Features • Genetics o Genetics (inherited predisposing

Stroke

4

conditions)

DURAL SINUS THROMBOSIS

98

• Resistance to activated protein C (typically due to factor V Leiden mutation) = most common cause of sporadic CVT • Protein S deficiency • Prothrombin (factor II) gene mutation (G20210A) • Etiology o Wide spectrum of predisposing causes (> 100 identified) • Trauma, infection, inflammation • Pregnancy, oral contraceptives • Metabolic (dehydration, thyrotoxicosis, cirrhosis, etc) • Hematological (coagulopathy) • Collagen-vascular disorders (e.g., APLA syndrome) • Vasculitis (e.g., Behcet) o Most common pattern: Thrombus initially forms in dural sinus • Clot propagates into cortical veins • Venous drainage obstructed, venous pressure elevated • BBB breakdown with vasogenic edema, hemorrhage • Venous infarct with cytotoxic edema ensues • Epidemiology: 1% of acute "strokes" • Associated abnormalities: dAVF (venous occlusive disease may be underlying etiologic factor)

Gross Pathologic & Surgical Features • Sinus occluded, distended by acute clot • Thrombus in adjacent cortical veins • Adjacent cortex edematous, usually with petechial hemorrhage

Microscopic

Treatment • Heparin +/- rtPA • Endovascular thrombolysis

I DIAGNOSTIC ..CHECK.L1ST Consider • DSA in patients with suspected chronic DST • Could a venous "filling defect" be a prominent arachnoid granulation?

Image Interpretation

fibrous tissue in

Staging, Grading or Classification Criteria • Venous ischemia o Type 1: No abnormality o Type 2: High signal on T2WI!FLAIR; no enhancement o Type 3: High signal on T2WI!FLAIR; enhancement present o Type 4: Hemorrhage or venous infarction

1.

2. 3.

4. 5. 6.

7.

8.

9.

10.

11.

I ClINIC;\LISSUES

12.

Presentation • Most common signs/symptoms o Headache, nausea, vomiting +/- neurologic deficit o Clinical diagnosis often elusive

13.

Demographics

15.

14.

• Age: Any • Gender: F > M

Natural History & Prognosis

segment

I SELECTED REFERENCES

Features

• Thrombosis of veins, proliferative chronic thromboses

Pearls

• Review MRV source images • Transverse sinus common site for hypoplastic variations that can mimic occlusion

16.

• Extremely variable (from asymptomatic to coma, death) o Up to 50% of cases progress to venous infarction o Can be fatal if severe brain swelling, herniation

Stroke

Favrole P et al: Diffusion-weighted imaging of intravascular clots in cerebral venous thrombosis. Stroke 35:99-103, 2004 Ferro JM et al: Prognosis of cerebral vein and dural sinus thrombosis. Stroke. 35: 664-70, 2004 Hinman JM et al: Hypointense thrombus on T2-weighted MR imaging: a potential pitfall in the diagnosis of dural sinus thrombosis. Eur J RadioI41:147-152, 2002 Lovblad KO et al: Fast contrast-enhanced MR whole-brain venography. Neuroradiology 44:681-688,2002 Kawaguchi T et al: Classification of venous ischemia with MRI. J Clin Neurosci 8 (suppl1): 82-88, 2001 Liang L et al: Evaluation of the intracranial dural sinuses with a 3D contrast-enhanced MP-RAGE sequence. AJNR 22:481-92,2001 Ayanzen RH et al: Cerebral MR Venography: Normal anatomy and potential diagnostic pitfalls. AJNR 21:74-78, 2000 Lovblad KO et al: Diffusion-weighted MRI suggests the coexistence of cytotoxic and vasogenic oedema in a case of deep cerebral venous thrombosis. Neuroradiology 42:728-731, 2000 Kenez J et al: Can intravascular lymphomatosis mimic sinus thrombosis? A case report with 8 months' follow-up and fatal outcome. Neuroradiology 42:436-440, 2000 Bergui M et al: Brain lesions due to cerebral venous thrombosis do not correlate with sinus involvement. Neuroradiology 41:419-424,1999 Provenzale JM et al: Dural sinus thrombosis associated with activated protein C resistance. AJR 170:499-502, 1998 Provenzale JM et al: Dural sinus thrombosis: Findings on CT and MR imaging and diagnostic pitfalls. AJR 170:777-83, 1998 Ozsvath RR et al: Cerebral venography: comparison of CT and MR projection venography. AJR 169:1699-1707, 1997 Kim SYet al: Direct endovascular thrombolytic therapy for dural sinus thrombosis. AJNR 18:639-45, 1997 LeachJL et al: Normal appearance of arachnoid granulations on contrast-enhanced CT and MR of the brain: differentiation from dural sinus disease. AJNR 17:1523-1532, 1996 Isensee CH et al: Magnetic resonance imaging of thrombosed dural sinuses. Stroke 25:29-34, 1994

DURAL SINUS THROMBOSIS

Typical (Left) 20 TOF MRV MIP

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image shows occluded left transverse and sigmoid sinus and left UVocclusion. (Right) Axial T2WI MR shows hypointense signal in this thrombosed left transverse sinus (arrows), which is frequently a false negative finding. T2* imaging is more sensitive to clot, as it "blooms".

I

~/ /

4

Typical

99 (Left) Coronal CECT shows

bilateral nonenhancement of the cavernous sinuses (arrows) compatible with thrombosis, from associated sinusitis. (Right) Axial CECT shows lack of normal enhancement in cavernous sinus (arrows), secondary to septic thrombosis. Note irregular narrowing of the right ICA (curved arrow) and associated sinus disease.

Variant (Left) Axial FLAIRMR in patient with a seizure shows a hyperintense left posterior parietal/occipital mass. (Right) Axial T1 C+ MR in the same case shows patchy enhancement. Initial diagnosis was neoplasm. MRV (not shown) disclosed subacute transverse sinus occlusion.

Stroke

CORTICAL VENOUS THROMBOSIS

Axial N feT demonstrates hyperdense "cord sign" of superficial cortical venous thrombosis (black arrow) with propagating clot into superior sagittal sinus (white arrow).

4 100

1/"fE.RiMtNOtOGY Abbreviations

and Synonyms

• Cortical or cerebral venous thrombosis

(CVT)

Definitions • Superficial cerebral vein thrombotic occlusion with/without associated dural sinus thrombosis

(DST)

• Enhancing dura surrounds non enhancing thrombus o "Shaggy," irregular veins (collateral channels) • CTV o Depicts thrombus as filling defect in cortical veins o Abnormal collateral channels (e.g., enlarged medullary veins) o Limited value in chronic CVT (organizing thrombosis also enhances)

MR Findings

~1/~AGINGiflNiOI.NGS General Features • • • •

Axial FLAIR MR shows hypointense thrombus within Vein of Labbe (arrows) as well as edema from early venous infarction (open arrow).

Best diagnostic clue: "Cord sign" on NECT, T2* GRE Location: Cortical veins (supra- > infratentorial) Size: Varies from small to extensive clot Morphology: Linear, cigar-shaped thrombus

CT Findings • NECT o Hyperdense cortical vein ("cord sign") +/- DST o May have parenchymal abnormality • Petechial hemorrhage, edema • If internal cerebral veins (lCV) occlude, thalami and/or basal ganglia become hypodense • CECT o "Empty delta" sign in 25-30% of cases

• TlWI o Clot: Early Tl isointense, later hyperintense o Most conspicuous sequence if clot subacute o Venous infarct: Gyral swelling, hypointense edema, may be hemorrhagic • T2WI o Clot: Often T2 hypointense mimicking flow void, much later hyperintense o Venous infarct: Gyral swelling, hyperintense edema, may be hemorrhagic • FLAIR o Thrombus usually hyperintense o Best demonstrates hyperintense edema • T2* GRE o Clot: Hypointense with blooming o Venous infarct: More sensitive for hemorrhage, often petechial

DDx: Cortical Venous Thrombosis & Venous Infarct Mimics

Normal but Dense

Arach Granulation

Stroke

CORTICAL VENOUS THROMBOSIS Key Facts Terminology

Pathology

• Superficial cerebral vein thrombotic occlusion With/without associated dural sinus thrombosis

• No cause identified on 20-25% of cases • Wide spectrum of predisposing causes (> 100 identified) • Ulcerative colitis is commonly associated with DST, less frequently with CVT

(DST)

Imaging Findings • Best diagnostic clue: "Cord sign" on NECT, T2* GRE • 2D time of flight (TOF) MRV depicts thrombus as sinus discontinuity, loss of vascular flow signal • Tl hyperintense thrombus falsely appears as patent flow on MIP • If initial CT scan negative, MRI with MRV • If MR, MRV equivocal ...•DSA

Top Differential

Diagnoses

• Normal • Anatomic variant • "Giant" arachnoid

granulation

Clinical Issues • Most common symptom is headache (95%) • Up to 50% of cases progress to venous infarction • Overall mortality = 10%i recurrence as high as 12%

Diagnostic Checklist • 2D TOF MRV should not be interpreted without benefit of standard imaging sequences • Subtle early imaging findings often overlooked

• DWI o DWI/ ADC imaging findings heterogeneous dependent on presence of ischemia, type of edema, hemorrhage o Distinguishes cytotoxic from va sogenic edema o Restriction can be seen in clot properi occluded veins at time of diagnosis might be predictive of low rate of vessel recanalization 2 or 3 months later • T1 C+

o Acute/early subacute clot: Peripheral enhancement outlines clot o Late clot: Thrombus, fibrous tissue often enhances o Venous infarct: Patchy enhancement • MRV o 2D time of flight (TOF) MRV depicts thrombus as sinus discontinuity, loss of vascular flow signal • May see abnormal collateral channels (e.g., enlarged medullary veins) o Contrast-enhanced MRV (CE-MRV) • Fasteri better depicts non enhancing thrombus & small veins than TO F o TOF limitations • Tl hyperintense thrombus falsely appears as patent flow on MIP • Must evaluate source images & conventional MRI sequences o Phase contrast MRV: Tl hyperintense thrombus not misrepresented as flow • MR Perfusion o T2* Gadolinium perfusion may show extensive venous congestion, but without perfusion deficits o May playa role in detecting venous congestion vs venous infarction in CVT

Ultrasonographic

Angiographic Findings • Conventional: More accurate than MRI, particularly for isolated cortical vein thrombosis • Interventional: Treatment with thrombolytics and/or mechanical de clotting

Imaging Recommendations • Best imaging tool o NECT, CECT scans +/- CTV o Conventional DSA most sensitive for CVT (useful if intervention planned) • Protocol advice o If initial CT scan negative, MRI with MRV o If MR, MRV equivocal ...•DSA

I DIFFERENTIAL DIAGNOSIS Normal • Intravascular blood in vessels normally slightly hyperdense on NECT

Anatomic variant • Congenital hypoplasia of transverse sinus • Vein of Trolard, Labbe, superficial middle cerebral vein have reciprocal relationship

"Giant" arachnoid granulation • Round/ovoid filling defecti clot is long, linear • CSF density, signal intensity

Cerebral hemorrhage • Mimics venous infarct • Amyloid, contusion, hypertensive

Findings

• Transcranial Doppler (TCD) ultrasound o Monitor venous flow velocities at ICU bedside o Follow therapy as decreasing velocities o Caveat: Normal venous velocities in serial measurements do not exclude a diagnosis of CVT

I PATHOLOGY General Features • Genetics o Resistance to activated protein C: Typically due to factor V Leiden mutation, most common cause of sporadic cerebral vein thrombosis

Stroke

4 101

CORTICAL VENOUS THROMBOSIS

I

102

o Protein S deficiency o Prothrombin (factor II) gene mutation (G2021OA) o Antithrombin III deficiency • Etiology o No cause identified on 20-25% of cases o Wide spectrum of predisposing causes (> 100 identified) • Trauma, infection, inflammation • Pregnancy, oral contraceptives • Metabolic (dehydration, thyrotoxicosis, cirrhosis, hyperhomocysteinemia etc) • Hematological (coagulopathy) • Collagen-vascular disorders (e.g., APLA syndrome) • Vasculitis (e.g., Beh\;et) • Drugs (androgens, ecstasy) o Most common pattern • Thrombus initially forms in dural sinus • Clot propagates into cortical veins • Venous drainage obstructed ~ t venous pressure • Blood-brain barrier breakdown with vasogenic edema, hemorrhage • Venous infarct with cytotoxic edema ensues o Isolated CVT without DST occurs but is uncommon • Epidemiology: 1% of acute strokes • Associated abnormalities o Association with aneurysmal subarachnoid hemorrhage reported • Clot progressed even while anticoagulated • Close imaging follow-up needed to assess clot dynamics o Up to 14% may have thrombosis elsewhere; lower extremity DVT, pulmonary embolism o Ulcerative colitis is commonly associated with DST, less frequently with CVT

Demographics • Age: Any • Gender: F > M

Natural History & Prognosis • • • • •

•

•

•

Clinical diagnosis often elusive Extremely variable outcome; asymptomatic to death Up to 50% of cases progress to venous infarction Pulmonary embolism is uncommon but carries a poor prognosis Poor outcome associated with papilledema, altered consciousness, coma, age> 33, diagnostic delay> 10 days, intracerebral hemorrhage, involvement of straight sinus Good outcome associated with isolated intracranial hypertension presentation, delta sign on CT (leading to earlier diagnosis) One year following CVT, 40% have lifestyle restrictions, 40% are unable to resume previous level of economic activity, 35% have altered consciousness, 6% are dependent Overall mortality = 10%; recurrence as high as 12%

Treatment • Heparin +/- rTPA • Endovascular thrombolysis; mechanical disruption

thrombolytic

and/or

Consider • DSA when imaging findings inconclusive, if clinical suspicion is high, or if intervention is planned

Gross Pathologic & Surgical Features

Image Interpretation

• Sinus occluded, distended by acute clot • Thrombus in adjacent cortical veins • Adjacent cortex edematous, usually with petechial hemorrhage

• 2D TOF MRV should not be interpreted without benefit of standard imaging sequences • Subtle early imaging findings often overlooked • Cord sign should be considered for early & accurate diagnosis

Microscopic • Thrombus

Features

Pearls

in cortical vein(s) and sinus(es)

Staging, Grading or Classification Criteria • Venous ischemia o Type 1: No abnormality o Type 2: High signal on T2WI/FLAIR; no enhancement o Type 3: High signal on T2WI/FLAIR; enhancement present o Type 4: Hemorrhage or venous infarction

2.

3. 4.

[CLINICALISSl.JES· .

5.

Presentation

6.

• Most common signs/symptoms o Most common symptom is headache (95%) o Seizure (47%), paresis (43%), papilledema (41%) o Altered consciousness (39%), comatose (15%) o Isolated intracranial hypertension (20%)

7.

8.

Stroke

y Nievas M et al: Cerebral vein thrombosis associated with aneurysmal subarachnoid bleeding: implications for treatment. Surg Neurol. 61(1):95-8; discussion 98, 2004 Favrole P et al: Diffusion-weighted imaging of intravascular clots in cerebral venous thrombosis. Stroke. 35(1):99-103, 2004 Ahn TB et al: A case of cortical vein thrombosis with the cord sign. Arch Neurol. 60(9):1314-6, 2003 Kimber J: Cerebral venous sinus thrombosis. QJM. 95(3):137-42, 2002 Rigamonti A et al: Cerebral vein thrombosis and mild hyperhomocysteinemia. Neurol Sci 23:225-7,2002 Lovblad KO et al: Fast contrast-enhanced MR whole-brain venography. Neuroradiology 44:681-688,2002 HinmanJM et al: Hypointense thrombus on T2-weighted MR imaging: a potential pitfall in the diagnosis of dural sinus thrombosis. EurJ RadioI41:147-152, 2002 Kawaguchi T et al: Classification of venous ischemia with MRI. J Clin Neurosci 8 (suppl1): 82-88, 2001

CORTICAL VENOUS THROMBOSIS

Typical (Left) Axial NECT demonstrates subtle hyperdense "cord sign" of CVT (arrow) in the vein of Trolard. The 555 is more hyperdense than normal, appears slightly shaggy (open arrow). (Right) Axial T2* GRE MR in the same case shows "cord sign" as blooming hypointense thrombus within cortical veins (arrows) with propagating clot into superior sagittal sinus (open arrow).

4 Typical

103 (Left) Frontal DsA of a selective left ICA injection, venous phase, shows thrombus within left Vein of Trolard (arrow). Note numerous enlarged veins from collateralization. (Right) Axial T1 C+ MR demonstrates hypointense thrombus within Vein of Labbe with peripheral enhancement outlining clot (arrows). Same case as Figure 2 on first page of dx.

Typical (Left) Axial post-contrast thin section sPGR demonstrates thrombus within superior sagittal sinus (black arrow) and associated draining cortical vein (white arrow). (Right) Axial NECT shows edema, mass effect, and hemorrhage within venous infarct. DsA (not shown) disclosed occlusion of the left Ts and vein of Labbe.

Stroke

DEEP CEREBRAL VENOUS THROMBOSIS

Axial NEeT shows bithalamic low density edema/ischemia (arrows) and increased density in internal cerebral, thalamostriate veins & straight sinus from thrombosis (open arrows).

4

Lateral DSA shows absence of deep cerebral veins and straight sinus consistent with deep cerebral venous thrombosis. The deep venous system should always be seen on DSA.

104

CT Findings Abbreviations

and Synonyms

• Deep cerebral venous thrombosis (DCVT) • Internal cerebral vein (lCV) thrombosis

Definitions • Thrombotic occlusion of deep cerebral veins • DCVT usually affects both lCVs +/- vein of Galen (V of G), straight sinus (SS) • More widespread dural sinus thrombosis (DST), cortical vein occlusion may occur

General Features • Best diagnostic clue: Hyperdense ICV on NECT +/bithalamic hypodense edema, variable DST • Location o Clot in ICV +/- V of G, SS, basal veins of Rosenthal o Bilateral ICV thrombosis »> unilateral o Deep gray nuclei, internal capsule, medullary WM typically affected o Variable involvement of midbrain, upper cerebellum (V of G, SS territory) • Size: Parenchymal involvement varies in extent • Morphology: Cigar shaped, "cord-like"

DDx: Abnormalities

(

, , \

r-

• NECT o Hyperdense vein = "cord sign" +/- DST o +/- Parenchymal abnormality • If ICVs occlude, thalami/basal ganglia appear hypodense with loss of GM/WM interfaces • Petechial hemorrhages may be present • CECT o "Empty delta" (if DST) o "Shaggy," irregular veins (collateral channels) in deep WM, around tentorium • CTV o Loss of ICV enhancement, presence of enlarged collateral channels o Limited value in chronic organizing thrombosis as also enhances

MR Findings • TlWI o Clot: Early Tl isointense, later hyperintense o Most conspicuous sequence if clot subacute o Venous hypertension: Hypointense swelling of thalami, basal ganglia o Venous infarct: Hypointense edema, may be hemorrhagic • T2WI o Clot: Often T2 hypointense mimicking flow void ("pseudo flow void"), much later hyperintense

of Thalami & Basal Ganglia

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Bithalamic Glioma

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Hypoxia

Stroke

Basilar Tip CVA

DEEP CEREBRAL VENOUS THROMBOSIS Key Facts • Non-venous ischemic injury: Global hypoxia, arterial (tip of basilar occlusion, artery of Percheron) infarcts

Terminology • Internal cerebral vein (ICV) thrombosis • DCVT usually affects bQth ICVs +/- vein of Galen (V of G), straight sinus (SS)

Pathology • No cause identified on 20-25% of cases • ICV thrombosis = 10% of venous "strokes"

Imaging Findings • Best diagnostic clue: Hyperdense ICV on NECT +/bithalamic hypodense edema, variable DST • Unlike quite variable superficial veins, deep cerebral veins are always present on angiography • If CT scan negative, MRI with MRV • If MRV equivocal - DSA

Top Differential

Diagnostic Checklist • DSA in equivocal cases and for intervention • 2D TOP MRV should not be interpreted without benefit of standard imaging sequences • Subtle early imaging findings often overlooked

Diagnoses

• Bilateral abnormalities of thalami, basal ganglia (e.g., glioma, toxic/metabolic disorders)

•

•

•

•

•

o Venous hypertension: Hyperintense swelling of thalami, basal ganglia • Corresponds to vasogenic +/- cytotoxic edema o Venous infarct: Parenchymal swelling, hyperintense edema, may be hemorrhagic PLAIR o High signal in occluded veins o Best demonstrates hyperintense edema T2* GRE o Clot: Hypointense with blooming o Venous infarct: More sensitive for hemorrhage, often petechial DWI o Distinguishes cytotoxic from vasogenic edema o DWlj ADC imaging findings heterogeneous o May restrict early (hyperintense BG/thalami) normalize later o Restriction can be seen in clot proper; occluded veins at time of diagnosis might be predictive of low rate of vessel recanalization 2 or 3 months later T1 C+ o Acute/early subacute clot: Peripheral enhancement outlines clot o Late clot: Thrombus, fibrous tissue often enhances o Venous stasis in deep WM (medullary) veins seen as linear enhancing foci radiating outwards from ventricles o Venous hypertension: No parenchymal enhancement o Parenchymal venous infarct: Patchy enhancement MRV o 2D time of flight (TOP) MRV shows "missing" ICVs, variable absent signal in V of G, SS • May see abnormal collateral channels o Contrast-enhanced MRV (CE-MRV) • Paster; better depicts non enhancing thrombus & small veins than TOP o TOP limitations • T1 hyperintense thrombus falsely appears as patent flow on MIP • Always evaluate source images & conventional MRI sequences

o Phase contrast MRV: T1 hyperintense thrombus not misrepresented as flow • MRS: Reduced metabolites, lactate in infarcts may help differentiate from non-vascular pathology (bithalamic glioma) in equivocal cases • MR perfusion o T2* Gadolinium perfusion may show extensive venous congestion, but without perfusion deficits o May playa role in detecting venous congestion vs venous infarction in CVT

Angiographic Findings • Conventional o DSA more accurate than MRI o Unlike quite variable superficial veins, deep cerebral veins are always present on angiography • In DCVT, occluded ICVs don't opacify • Collateral venous channels (e.g., pterygoid veins) enlarge • Interventional: Treatment with thrombolytics and/or mechanical de clotting

Imaging Recommendations • Best imaging tool o NECT, CECT scans +/ - CTV venogram o Conventional DSA most sensitive & useful if intervention planned • Protocol advice o If CT scan negative, MRI with MRV o If MRV equivocal ~ DSA

I DIFFERE~IIAU. DIAG~€)$I$ Bilateral abnormalities of thalami, basal ganglia (e.g., glioma, toxic/metabolic disorders) • Tumors: Lymphoma, glioma o Normal venous system o Elevated choline o Vasogenic not cytotoxic edema • Toxic/metabolic: Carbon monoxide

Stroke

poisoning

4 105

DEEP CEREBRAL VENOUS THROMBOSIS o Normal venous system o Positive carboxyhemoglobin o Classic cherry red skin is rare • Non-venous ischemic injury: Global hypoxia, arterial (tip of basilar occlusion, artery of Percheron) infarcts o Normal venous system o History of hypoxic event o Abnormal arterial evaluation

r.CEINI<:A.L.IS$l.JES

General Features

• Clinical diagnosis of CVT often elusive • Outcome of CVT extremely variable, from asymptomatic to death o Majority have no residual deficits at 16 months o Subgroup (13%) have poor outcome; predictors of death/dependence • Hemorrhage on admission CTD • DCVT • DWI demonstration of cytotoxic edema (infarction) also portends poor prognosis

Presentation • Most common signs/symptoms: Common: Headache, nausea, vomiting +/- neurologic deficit, seizure

Demographics • Age: Any age, although elderly or debilitated patients are more likely to have spontaneous thrombosis • Gender: F > M

Natural History & Prognosis

4 106

• Genetics o Resistance to activated protein C: Typically due to factor V Leiden mutation, most common cause of sporadic cerebral vein thrombosis o Prothrombin (factor II) gene mutation (G20210A) o Protein S deficiency o Antithrombin III deficiency • Etiology o No cause identified on 20-25% of cases o Wide spectrum of causes (> 100 identified) • Trauma, infection, inflammation • Pregnancy, oral contraceptives • Metabolic (dehydration, thyrotoxicosis, cirrhosis, etc) • Hematological (coagulopathy) • Collagen-vascular disorders (e.g., APLA syndrome) • Vasculitis (e.g., Behcet) • Drugs (androgens, ecstasy) o Most common pattern • Thrombus initially forms in dural sinus • Clot propagates into cortical veins • Venous drainage obstructed, venous pressure elevated • Blood-brain barrier breakdown with vasogenic edema, hemorrhage • Venous infarct with cytotoxic edema ensues • Epidemiology o Cerebral venous thrombosis represents 1% of strokes o ICV thrombosis = 10% of venous "strokes" • Associated abnormalities o May have thrombosis elsewhere; lower extremity DVT, pulmonary embolism o Ulcerative colitis is commonly associated with DST

Treatment • Heparin +/- rTPA • Endovascular thrombolysis

I DIACNOS.,.ICiiCH!ECK!LfS-r Consider • DSA in equivocal cases and for intervention

Image Interpretation

I SELECTED REFERENCES 1. 2. 3.

Gross Pathologic & Surgical Features • ICVs occluded, distended by acute clot • Venous hypertension ensues • Adjacent thalami edematous with variable hemorrhage

Microscopic • Thrombus

4. 5.

Features

in occluded vessels

6.

Staging, Grading or Classification Criteria • Venous ischemia o Type 1: No abnormality o Type 2: High signal on T2WI/FLAIR; no enhancement o Type 3: High signal on T2WI/FLAIR; enhancement present o Type 4: Hemorrhage or venous infarction

Pearls

• 2D TOF MRV should not be interpreted without benefit of standard imaging sequences • Subtle early imaging findings often overlooked • Non-visualization of deep venous system on vascular studies always abnormal

7.

8.

Stroke

Sarma D et al: Reversal of restricted diffusion in cerebral venous thrombosis. Neuroradiology 46:118-21,2004 Ferro JM et al: Prognosis of cerebral vein and dural sinus thrombosis. Stroke. 35: 664-70, 2004 Favrole P et al: Diffusion-weighted imaging of intravascular clots in cerebral venous thrombosis. Stroke. 35(1):99-103, 2004 Kawaguchi T et al: Classification of venous ischemia with MRI. J Clin Neurosci 8 (suppl1): 82-88, 2001 Liang L et al: Evaluation of the intracranial dural sinuses with a 3D contrast-enhanced MP-RAGE sequence. AJNR 22: 481-92,2001 Keller E et al: Diffusion- and perfusion-weighted magnetic resonance imaging in deep cerebral venous thrombosis. Stroke. 30(5):1144-6, 1999 Lafitte F et al: Deep cerebral vein thrombosis: imaging in eight cases. Neuroradiology 41:410-418, 1999 Provenzale JM et al: Dural sinus thrombosis: Findings on CT and MR imaging and diagnostic pitfalls. AJR 170: 777-83, 1998

DEEP CEREBRAL VENOUS THROMBOSIS

I IMAGE

GALLERY

Typical (Left) Axial T7 C+ MR shows

enhancing striated vessels, characteristic of dilated medullary veins secondary to deep cerebral venous thrombosis. (Right) Axial T7 C+ MR in the same case shows thrombosed isointense, nonenhancing ICVs (open arrow) with extensive caudate nuclei enhancement, engorged deep medullary WM veins with contrast stasis (arrows).

4 Typical

107 (Left) Axial T2WI MR shows

hypointense T2 signal, masquerading as flow voids in thrombosed internal cerebral veins (arrow). Bithalamic high signal reflects both cytotoxic & vasogenic edema. (Right) Lateral OSA shows non-filling of deep cerebral veins consistent with thrombosis; the deep venous system should always be seen on OSA. Note increased flow within petrosal sinuses (arrow).

Typical (Left) Axial OWl MR in a

case with ICV thrombosis, extensive bithalamic edema (not shown) has only mild diffusion restriction (arrows). Most of abnormality was vasogenic edema r to venous hypertension. (Right) Axial gross pathology section shows hemorrhagic infarction in bilateral thalami, left basal ganglia, & left hemisphere from bilateral ICVocclusion (Courtesy j. Garcia, MO).

Stroke

PART I SECTION 5 Vueular MaIfo•.•••tlon. The traditional pathologic clas ification of cerebro a cular malformation ( VMs) is based on the caliber, configuration, and histologi compo ition of the compon nt ve el; their relationship to the normal cer bral va ulature; and the pre ence/amount of intervening brain parenchyma. Four ba ic type are r ognized: (1) Arteriovenous malformation; (2) V nou a cular malformations (al 0 known a "venou angioma" or developmental nou anomalie, DV ); (3) apillary telangiecta ia ; and (4) avernou malformation or "angiomas." Tran itional and hi tologically mix d malformation are al 0 de cribed. With th advent of endo a cular therapy, VM have recently been recla ified according to th pre en e or ab ence of arteriov nous ( -V) shunting within the malformation. In thi ection we discuss the following 7 p ifi va cular malformation: VM

with -V hunting rteriovenous malformation Dural A-V fistula Vein of Galen malformation M without A-V shunting Developmental venou anomaly inus pericranii avernous malformation apillar telangiectasia

ariant and hi tologi ally-mixed VMs, the most common of which i a ca ernou -v nou malformation, are discussed under their dominant omponent.

SECTION 5: Vascular Malformations

CVMs With A-V Shunting Arteriovenous Malformation Dural A-V Fistula Vein of Galen Malformation

1-5-4 1-5-8 1-5-12

CVMs Without A-V Shunting Developmental Venous Anomaly Sinus Pericranii Cavernous Malformation Capillary Telangiectasia

1-5-16 1-5-20 1-5-24 1-5-28

ARTERIOVENOUS

Coronal graphic shows a classic cerebral AVM. Note nidus (curved arrow) with intranidal aneurysm (open arrow) and enlarged feeding arteries with a "pedicle" aneurysm (arrow).

ITERMINOlOGY Abbreviations and Synonyms

5 4

• Arteriovenous

malformation

(AVM)

Definitions • Vascular malformation with arteriovenous no intervening capillary bed

shunting,

MALFORMATION

Axial CECT in a patient with temporal lobe epilepsy. Note multifocal curvilinear foci of contrast enhancement representing an AVM nidus with enlarged arterial feeders and draining veins.

o May be normal with very small AVM • lso/hyperdense serpentine vessels • Ca++ in 25-30% • Variable hemorrhage • CECT: Strong enhancement • CTA: Enlarged arteries, draining veins usually depicted well

MR Findings

IIMAGING FINDINGS General Features • Best diagnostic clue: "Bag of black worms" (flow voids) on MR with minimal/no mass effect • Location o May occur anywhere in brain, spinal cord o 85% supratentorial; 15% posterior fossa o 98% solitary, sporadic o Rare: Multiple AVMs (usually syndromic) • Size o Varies from microscopic to giant o Most symptomatic AVMs are 3-6 cm • Morphology: Tightly packed mass of enlarged vascular channels

CT Findings • NECT

• TlWI o Signal varies with flow rate, direction, presence/age of hemorrhage o Classic: Tightly packed mass looks like "honeycomb" of "flow voids" • T2WI o "Flow voids" o Variable hemorrhage o Little/no brain inside (some gliotic, high signal tissue may be present) • FLAIR: "Flow voids" +/- surrounding high signal (gliosis) • T2* GRE: May show some hypointense "blooming" if hemorrhage present • DWI: Usually normal • T1 C+: Strong enhancement • MRA o Helpful for gross depiction of flow, post-embo/XRT o Does not depict detailed angioarchitecture

DDx: Arteriovenous Malformation \

;

~

"

)i I

~

Vascular Malformations

-

.

•

ARTERIOVENOUS MALFORMATION Key Facts Top Differential

Terminology • Vascular malformation with arteriovenous no intervening capillary bed

shunting,

Diagnoses

• Patent AVM vs glioblastoma

with AV shunting

Pathology

Imaging Findings • Best diagnostic clue: "Bag of black worms" (flow voids) on MR with minimal/no mass effect • 85% supratentoriali 15% posterior fossa • 98% solitary, sporadic • Signal varies with flow rate, direction, presence/age of hemorrhage • Classic: Tightly packed mass looks like "honeycomb" of "flow voids" • Best imaging tool: DSA with superselective catherization

• General path comments: AVMs have dysregulated angiogenesis, undergo continued vascular remodeling • Sporadic AVMs have multiple up-, down-regulated genes • Multiple AVMs in HHT 1 (endoglin gene mutation) • Cerebrofacial arteriovenous metameric syndromes (CAMS) have orbit/maxillofacial + intracranial AVMs • Most common symptomatic cerebral vascular malformation (CVM)

Clinical Issues • Headache with hemorrhage 50% • Age: Peak presentation 20-40 Y (25% by age 15)

=

• MRV: May be useful for delineating of venous drainage

presence/direction

General Features

Angiographic Findings • Conventional o Delineates internal angioarchitecture (superselective best) o Depicts three components of AVMs • Enlarged arteries • Nidus of tightly packed vessels • Draining veins (AV shunting with early appearance of contrast in enlarged veins) o 27-32% of AVMs have "dual" arterial supply (pial, dural) • Dural supply to AVMs occurs through leptomeningeal anastomoses or transdural anastomoses (TDAs) with normal cortical arteries • Essential to examine ICA, ECA, vertebral circulations completely! • Frequency of TDAs increases with AVM volume, patient age • Identification of TDAs affects treatment decision (embolization, surgery)

Imaging Recommendations • Best imaging tool: DSA with supers elective catherization • Protocol advice: Standard MR (include contrast-enhanced MRA, GRE sequences)

I DIFFERENTIAl.. DIAGN(})SIS Patent AVM vs glioblastoma with AV shunting • GBM enhances, has mass effect • Some parenchyma between vessels

Thrombosed • • • •

• General path comments: AVMs have dysregulated angiogenesis, undergo continued vascular remodeling • Genetics o Sporadic AVMs have multiple up-, down-regulated genes • Homeobox genes such as Hox D3 and B3 involved in angiogenesis may malfunction o Syndromic AVMs (2% of cases) • Multiple AVMs in HHT 1 (endoglin gene mutation) • Cerebrofacial arteriovenous metameric syndromes (CAMS) have orbit/maxillofacial + intracranial AVMs • Etiology o Dysregulated angiogenesis • Vascular endothelial growth factors (VEGFs), receptors mediate endothelial proliferation, migration • Cytokine receptors mediate vascular maturation, remodeling • Epidemiology o Most common symptomatic cerebral vascular malformation (CVM) o Prevalence of sporadic AVMs = .04-.52% • Associated abnormalities o Flow-related aneurysm on feeding artery 10-15% o Intranidal"aneurysm" > 50% o Vascular "steal" may cause ischemia in adjacent brain • PET studies may show hemodynamic impairment

Gross Pathologic & Surgical Features • Wedge-shaped,

("cryptic") AVM versus

Cavernous angioma Calcified neoplasm Oligodendroglioma Low-grade astrocytoma

I PATI"t(})I..(})G~

compact mass of tangled vessels

Microscopic Features • Wide phenotypic spectrum o Feeding arteries usually enlarged but mature (may have some wall thickening)

Vascular Malformations

5 5

ARTERIOVENOUS MALFORMATION o Enlarged draining veins (may have associated varix, stenosis) o Nidus • Conglomeration of numerous AV shunts ("micro AVFs") • Thin-walled dysplastic vessels (no capillary bed) • Disorganized collagen, variable muscularization • Lack subendothelial support • Loss of normal contractile properties • No normal brain (may have some gliosis) o Perinidal capillary network (PDCN) • Nidus surrounded by dilated capillaries in brain tissue 1-7 mm outside nidus border • Vessels in PDCN 1O-25x larger than normal capillaries • PDCN connects both to nidus, feeding arteries/draining veins, surrounding narrowed brain vessels • May be cause of recurrence of surgically resected AVMs

Staging, Grading or Classification Criteria

6

• Spetzler-Martin scale o Size • Small « 3 cm) = 1 • Medium (3-6 cm) = 2 • Large (> 6 cm) = 3 o Location • In "noneloquent" area = 0 • If involves eloquent brain = 1 o Venous drainage • Superficial only = 0 • Deep = 1 o Sum of above estimates surgical risk • Craniofacial arteriovenous metameric syndromes (CAMS) o CAMS 1 = prosencephalic metameric AVMs (hypothalamus/hypophysis, nose) o CAMS 2 = lateral prosencephalic group (occipital lobe, thalamus and maxilla) o CAMS 3 = rhombencephalic group (cerebellum, pons, mandible)

o Vast majority will become symptomatic during patient's lifetime • Spontaneous obliteration rare « 1% of cases) o 75% have small lesion « 3 cm), single draining vein o 75% have "spontaneous" ICH

Treatment • Embolization, surgery

latl\qN.OS"[IC:i~I"Ii~C:I}!ILI~! Consider • MR of a vascular-appearing lesion that has brain parenchyma in-between "flow voids" may be a vascular neoplasm, not AVM

Image Interpretation

I SELECTED REFERENCES 1. 2.

3.

4.

5.

6.

7.

Presentation

8.

9.

10. 11.

Demographics • Age: Peak presentation = 20-40 Y (25% by age 15) • Gender: M = F • Ethnicity: Occurs in all ethnic groups

Natural History & Prognosis • All brain AVMs are potentially hazardous o Risk of first hemorrhage is lifelong, rises with age (2-4%/year, cumulative)

Pearls

• Look carefully for pedicle, intranidal aneurysms • A partially or completely thrombosed AVM may have little/no nidus, enlarged arteries at angiography o Look for subtle "early draining veins" - they may be the only clue to the diagnosis!

I Cli N1C:1;\lfSSl..1ES • Most common signs/symptoms o Headache with hemorrhage 50% o Seizure 25% o Focal neurologic deficit 20-25% • Clinical profile: Young adult with spontaneous (nontraumatic) ICH

stereotaxic radiosurgery, microvascular

12.

13.

Sato S et al: Perinidal dilated capillary network in cerebral arteriovenous malformation. Neurosurg 54: 163-70, 2004 Mori H et al: Two-dimensional thick-slice MR digital subtraction angiography in the assessment of small to medium-size intracranial arteriovenous malformations. Neuroradiol45: 27-33, 2003 Suzuki M et al: Contrast-enhanced MRA for investigation of cerebral arteriovenous malformations. Neuroradiol 45: 231-5,2003 Berg J et al: Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALKI mutations. J Med Genet. 40(8):585-90, 2003 Shenkar R et al: Differential gene expression in human cerebrovascular malformations. Neurosurgery. 52(2):465-77; discussion 477-8,2003 Shah RK et al: Hereditary hemorrhagic telangiectasia: a review of 76 cases. Laryngoscope. 112(5):767-73,2002 Sabba C et al: Hereditary hemorrhagic teleangiectasia (Rendu-Osler-Weber disease). Minerva Cardioangiol. 50(3):221-38, 2002 Warren DJ et al: Cerebral arteriovenous malformations: Comparison of novel MRA techniques and conventional catheter angiography. Neurosurg 48: 973-83, 2001 Uranishi R et al: Vascular smooth muscle cell differentiation in human cerebral vascular malformations. Neurosurg 49: 671-80, 2001 Vikkula M et al: Molecular genetics of vascular malformations. Matrix BioI. 20(5-6):327-35, 2001 Battacharya JJ et al: Wyburn-Mason or Bonnet-Dechaume-Blanc as cerebrofacial arteriovenous metameric syndromes (CAMS) : A new concept and classification. IntervNeuroradiol 7:5-17, 2001 Hashimoto T et al: Abnormal balance in the angiopoietin-tie2 system in human brain arteriovenous malformations. Circ Res. 89(2):111-3, 2001 Herzig R et al: Familial occurrence of cerebral arteriovenous malformation in sisters: case report and review of the literature. Eur J Neurol. 7(1):95-100,2000

Vascular Malformations

ARTERIOVENOUS MALFORMATION

Typical (Left) Axial TlWI MR shows a classic deep thalamic AVM (arrows). Note relative lack of mass effect, markedly enlarged draining veins (open arrow). There is no normal brain within the lesion. (Right) Lateral DSA in the same case shows the nidus (arrows) plus arteriovenous shunting (seen as early appearance of contrast in an enlarged vein of Galen (open arrow), and straight sinus).

Typical (Left) Axial NECT shows a large temporal lobe hematoma in this patient with spontaneous ICH. (Right) Lateral DSA in the same case shows a large mass effect with a small central AVM nidus. Partially thrombosed AVM was documented at surgical evacuation of the hematoma.

Variant (Left) Lateral DSA of a selective ICA injection shows a parietal AVM with ACA feeders. Examination of the vertebral and external carotid circulations is essential for complete delineation of blood supply. (Right) Lateral DSA of the ECA shows dural perforators from enlarged superficial temporal and middle meningeal arteries also supply AVM (arrows). Mixed pial-dural supply in supratentorial AVMs is rare.

Vascular Malformations

5 7

Lateral graphic shows chronically thrombosed transverse sinus with dAVF consisting of innumerable "crack-like" vessels in wall. Multiple dural & transosseousfeeders arise from ECA, lCA.

Lateral D5A shows thrombosis at the junction of the transverse and sigmoid sinus (open arrow) with retrograde filling of T5, type /fA dAVF supplied by dural and transosseousECA branches.

• Morphology: Collection of innumerable dural sinus wall

Abbreviations

and Synonyms

• Dural arteriovenous fistula (dAVF) 8

CT Findings

shunt; dural AV arteriovenous

Definitions • dAVF = heterogeneous group of lesions with common angioarchitecture (AV shunts within dura)

General Features • Best diagnostic clue o Adult-type dAVF = network of tiny ("crack-like") vessels in wall of thrombosed dural venous sinus o Infantile dAVF (rare) = multiple high-flow AV shunts involving several different thrombosed dural sinuses • Location o Can occur anywhere but usually near skull base • Most common site = transverse sinus (TS) • Next most common = cavernous sinus (CS) o Most aggressive dAVFs = tentorial; other dAVFs associated with retrograde leptomeningeal venous drainage (RLVD) • Size: Variable but actual shunt usually < 2 cm

• NECT: Often normal • CECT o May be normal with small shunts o +/- Tortuous dural feeders, enlarged dural sinus o Enlarged superior ophthalmic vein (with carotid cavernous fistula) o Enlarged cortical draining veins with aggressive dAVF • CTA: 3D/CTA may be useful in static depiction of angioarchitecture

MR Findings • TlWI o May be normal o Isointense thrombosed dural sinus +/- "flow voids" • T2WI o Isointense thrombosed sinus +/- "flow voids" o Focal hyperintensity in adjacent brain = RLVD, venous perfusion abnormalities • FLAIR: Isointense thrombosed sinus +/- adjacent edema if venous congestion/ischemia present • T2* GRE

o Usually normal (no blooming) dAVF

DDx: dAYS

Pial-dural AVM

tiny AVSs in

CS Thrombophlebitis

Vascular Malformations

Thrombosed

TS

in uncomplicated

DURAL A-V FISTULA Key Facts Terminology

Top Differential Diagnoses

• dAVF = heterogeneous group of lesions with common angioarchitecture (AV shunts within dura)

• Mixed pial-dural AVM • Thrombosed dural sinus • Vascular neoplasm

Imaging Findings • Adult-type dAVF = network of tiny ("crack-like") vessels in wall of thrombosed dural venous sinus • Can occur anywhere but usually near skull base • Most aggressive dAVFs = tentorial; other dAVFs associated with retrograde leptomeningeal venous drainage (RLVD) • Isointense thrombosed dural sinus +/- "flow voids" • Focal hyperintensity in adjacent brain = RLVD, venous perfusion abnormalities • Best imaging tool: DSA with superselective catheterization of dural, transosseous feeders

o May show parenchymal hemorrhage in dAVF with cortical venous drainage • DWI: Normal unless venous infarct/ischemia • T1 C+

o Chronically thrombosed sinus usually enhances o Rare: Diffuse dural enhancement o Dynamic contrast-enhanced sequence may show disturbed cerebral hemodynamics even in absence of RLVD ·MRA o TOF MRA may be negative with small or slow flow shunts or yield incomplete depiction of high flow lesions o Time resolved contrast augmented MRA useful for gross depiction of angioarchitecture and dynamics • MRV o Depicts occluded parent sinus, collateral flow o 3D PC MRA with low velocity encoding can identify fistula, feeding arteries, flow reversal in draining veins • PET/SPECT/perfusion MRl: May show increased rCBY, decreased rCBF (venous ischemia)

Angiographic Findings • Conventional o Most common site = wall of TS or SS (35-40% of all dAVFs) • Multiple arterial feeders are typical with dural/transosseous branches from ECA most common followed by tentorial/dural branches from lCA, VA • Arterial inflow into a parallel venous channel ("recipient pouch") common, can be embolized with preservation of parent sinus • Involved dural sinus often thrombosed • Flow reversal in dural sinus/cortical veins correlates with progressive symptoms, risk of hemorrhage • Tortuous engorged pial veins ("pseudophlebitic pattern") with venous congestion/hypertension (clinically aggressive) • High flow "through draining veins" may cause progressive stenosis, outlet occlusion, hemorrhage

Pathology • Adult dAVFs are usually acquired, not congenital • Pathological activation of neoangiogenesis • Epidemiology: 10-15% of all cerebrovascular malformations with AV shunting • Cognard classification of intracranial dAVFs correlates venous drainage pattern with clinical course

Clinical Issues • Prognosis, clinical course depends on location, venous drainage pattern

o Carotid cavernous fistula (CCF) = second most common site; classified on basis of arterial supply + venous drainage pattern • Barrow Type A: Direct lCA-cavernous sinus high-flow shunt (not true dAVF) • Type B: Dural lCA branches-cavernous shunt • Type C: Dural ECA-cavernous shunt • Type D: ECA/lCA dural branches shunt to cavernous sinus

Imaging Recommendations • Best imaging tool: DSA with superselective catheterization of dural, transosseous feeders • Protocol advice o Screening MR, contrast augmented MRA o DSA to delineate vascular supply, venous drainage

I DIFFERE~l'IAI..DIA6~e5IS Mixed pial-dural AVM • True pial supply to dAVF is rare • Usually occurs with large posterior fossa or superficial hemispheric AVM

Thrombosed dural sinus • Collateral/congested venous drainage can mimic dAVF • Can be spontaneous, traumatic, infectious (thrombophlebitis)

Vascular neoplasm • Acutely thrombosed dAVF may enhance, have edema/mass effect, mimic neoplasm • Neoplasm usually doesn't invade dura, cause sinus thrombosis

I PAl'Hel..e6Y General Features • General path comments: Collection of "crack-like" vessels in wall of thrombosed sinus • Etiology

Vascular Malformations

5 9

o Adult dAVFs are usually acquired, not congenital • May be idiopathic • Can occur in response to trauma, venous occlusion, or venous hypertension o Pathological activation of neoangiogenesis • Proliferating capillaries within granulation tissue in dural sinus obliterated by organized thrombi • Budding/proliferation of microvascular network in inner dura connects to plexus of thin-walled venous channels, creating microfistulae • High bFGF, VEGF expression in dAVFs • Epidemiology: 10-15% of all cerebrovascular malformations with AV shunting • Associated abnormalities: Cortical drainage associated with edema, encephalopathy

Gross Pathologic & Surgical Features • Multiple enlarged dural feeders converge on dural sinus

Microscopic

Staging, Grading or Classification Criteria

10

Treatment • Observation (benign dAVF carries only 2% risk of developing CVD) • Treatment options o Endovascular o Surgical resection o Stereotaxic radiosurgery

Features

• Arterialized veins with irregular intimal thickening, variable loss of internal elastic lamina

5

Natural History & Prognosis • Prognosis, clinical course depends on location, venous drainage pattern o Anterior fossa, tentorial, SSS or SPS location correlated with aggressive course (hemorrhage, encephalopathy, progressive neurologic deterioration) o 98% of dAVFs without RLVD have benign course o dAVF with RLVD have aggressive clinical course • Spontaneous closure rare

• Cognard classification of intracranial dAVFs correlates venous drainage pattern with clinical course o Type I: Located in sinus wall, normal ante grade venous drainage, benign clinical course o Type IIA: Located in main sinus, reflux into sinus but not cortical veins o Type lIB: Reflux (retrograde drainage) into cortical veins, 10-20% hemorrhage rate o Type III: Direct cortical drainage, no venous ectasia, 40% hemorrhage o Type IV: Direct cortical drainage, venous ectasia, 2/3rds hemorrhage o Type V: Spinal perimedullary venous drainage, progressive myelopathy

lidUl~I€;\U"ISSUES Presentation • Most common signs/symptoms o Varies with site, type of shunt • TS/SS = pulsatile tinnitus • Cavernous sinus = pulsatile exophthalmos • Cranial neuropathy o Uncommon: Encephalopathic symptoms (venous hypertension, ischemia/thrombosis) • Progressive dementia • Parkinsonism o Rare • Life-threatening congestive heart failure • Usually neonates, infants • Clinical profile: Middle-aged patient with pulse-synchronous tinnitus

Demographics • Age: Adult dAVF usually present in middle-aged, patients • Gender: M = F • Ethnicity: None

older

Consider • Venous collateral flow in dural sinus thrombosis become very prominent, mimic dAVF

Image Interpretation

can

Pearls

• ALWAYSexamine both internal, external carotid arteries when performing angiography in patient with spontaneous ICH

1.

Rucker JC et al: Diffuse dural enhancement in cavernous sinus dural arteriovenous fistula. Neuroradiology. 45(2):88-9,2003 2. Kai Y et al: Pre- and post-treatment MR imaging and single photon emission CT in patients with dural arteriovenous fistulas and retrograde leptomeningeal venous drainage. AJNRAmJ Neuroradiol. 24(4):619-25, 2003 3. Burrows PE et al: Venous variations of the brain and cranial vault. Neuroimaging Clin N Am. 13(1):13-26, 2003 4. van DijkJM et al: Venous congestive encephalopathy related to cranial dural arteriovenous fistulas. Neuroimaging Clin N Am. 13(1):55-72,2003 5. Klisch J et al: Transvenous treatment of carotid cavernous and dural arteriovenous fistulae: results for 31 patients and review of the literature. Neurosurgery. 53(4):836-56: discussion 856-7, 2003 6. Chung SJ et al: Intracranial dural arteriovenous fistulas: analysis of 60 patients. Cerebrovasc Dis. 13(2):79-88, 2002 7. Coley SC et al: Dural arteriovenous fistulae: noninvasive diagnosis with dynamic MR digital subtraction angiography. AJNR Am J Neuroradiol. 23(3):404-7, 2002 8. Nomura S et al: Subarachnoid hemorrhage caused by dural arteriovenous fistula of the sphenobasal sinus--case report. Neurol Med Chir (Tokyo). 42(6):255-8, 2002 9. Biondi A et al: Intracranial extra-axial cavernous (HEM) angiomas: tumors or vascular malformations? J Neuroradiol. 29(2):91-104, 2002 10. Satomi J et al: Benign cranial dural arteriovenous fistulas: outcome of conservative management based on the natural history of the lesion. J Neurosurg. 97(4):767-70, 2002

Vascular Malformations

Tvpical

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(Left) Axial T2WI MR in an elderly patient with pulsatile tinnitus shows a thrombosed left transverse sinus with multiple "flow voids" characteristic of a long-standing dAVF. (Right) Axial T1 C+ MR in the same case shows the chronically occluded left TS enhances strongly. Note presence of innumerable "flow voids" within the enlarged sinus wall.

!

Variant (Left) Lateral OSA of an internal carotid angiogram shows a type IV dAVF with enlarged tentorial branches from the meningohypophyseal trunk (arrows) and deep cortical venous drainage (open arrows). (Right) Lateral OSA of the ECA shows enlarged dural feeders (arrows) to the dAVF. The deep cortical venous drainage is well seen (open arrows). Tentorial dAVFs are especially dangerous lesions.

Variant (Left) Axial T1 C+ MR shows a left parieto-occipital mass with patchy parenchymal and sulcal enhancement (arrows). Initial imaging diagnosis was infiltrating primary brain tumor (Courtesy P. Skejo, MO). (Right) Lateral OSA of a selective left ECA angiogram in the same case shows a dAVF supplied primarily by the middle meningeal artery. Thrombosis of draining cortical veins caused the edema, mass effect.

Vascular Malformations

5 11

Sagittal graphic depicts a classic vein of Galen malformation (VGM). The dilated median prosencephalic vein of Markowski (MPV) drains via the embryonic falcine sinus.

Abbreviations

12

and Synonyms

• Vein of Galen Malformation (VGM), vein of Galen "aneurysm", Galenic varix • VGM is misnomer; malformation actually involves the median prosencephalic vein (MPV) of Markowski

Definitions • Arteriovenous fistula (AVF) involving aneurysmal dilatation of the MPV

General Features • Best diagnostic clue: Dilated arteries feeding into large midline venous pouch (MPV) in neonate/infant • Location: Quadrigeminal plate cistern, cistern of velum interpositum • Size: Variable (few to several cms) • Morphology: Well-defined, large, tubular vein

Radiographic Findings • Radiography: Cardiomegaly, edema on chest X-ray

wide mediastinum,

o Venous pouch mildly hyperdense to brain • +/- Wall Ca++ (older children, thrombosed aneurysm) o +/- Hydrocephalus o +/- Ischemia, parenchymal Ca++, atrophy o Rare intraventricular hemorrhage (IVH) • CECT: Strong enhancement feeding arteries and vein • CTA: Excellent pre-angiographic delineation of VGM

MR Findings • TlWI o Arterial feeders: Flow voids o MPV: Flow void or mixed intensity due to fast or turbulent flow o Hyperintense foci within pouch: Thrombus o Hyperintense foci within brain: Ca++, ischemia • T2WI o Arterial feeders: Flow voids o MPV: Flow void or mixed intensity due to fast or turbulent flow o Ischemic foci poorly seen due to unmyelinated infant brain • DWI: Restriction in areas of acute ischemia/infarction • MRA: Delineates arterial feeders and draining MPV

Ultrasonographic

Findings

• Real Time: MPV mildly echogenic midline mass • Color Doppler: Arterial feeders; arterialized flow within MPV

CT Findings • NECT

DDx: Vascular Malformations

Complex OVA

Sagittal TlWI MR shows a classic VGM. The MPV (open arrow) drains via the falcine sinus (arrow). The straight sinus is absent (curved arrow) (Courtesy 5. Willing, MO).

Presenting in Childhood

Solitary dAVF

Multiple dAVFs

Vascular Malformations

Thalamic AVM

VEIN OF GALEN MALFORMATION Key Facts • VGM is misnomer; malformation actually involves the median prosencephalic vein (MPV) of Markowski

• Up to 30% of all pediatric vascular malformations • Most common extracardiac cause of high-output CHF in newborn period

Imaging Findings

Clinical Issues

Terminology

• Best diagnostic clue: Dilated arteries feeding into large midline venous pouch (MPV) in neonate/infant

Top Differential • • • •

Diagnoses

Childhood dural arteriovenous fistula (dAVF) Multifocal, large, fast-flow fistulas common Arteriovenous malformation (AVM) Complex developmental venous anomaly (DVA)

Pathology

• Most common signs/symptoms: CHF, hydrocephalus • Age: Neonatal> infant presentation most common; rare adult presentation • Gender: M:F = 2:1 • Neonatal prognosis worse than infant/child (choroidal vs mural VGM) • Antenatal Dx associated with improved outcome • Up to 60% treated VGMs neurologically normal at F/U in some series

• AVF of MPV occurrs in 6-11 weeks gestation • < 1% cerebral vascular malformations at any age

• Antenatal US/MRI: VGM identified in 3rd trimester o High resistance in middle cerebral artery ~ vascular steal o Cardiac dilatation, hydrops fetalis = poor prognosis

Echocardiographic

Findings

• Dilatation RT heart, SVC, ascending aorta/great vessels • 80% LV output diverted to low resistance VGM • Poor prognostic indicators o Descending aorta diastolic flow reversal o Suprasystemic pulmonary artery hypertension o PDA with significant RT to LT shunt

Angiographic

Findings

• Conventional o "Choroidal" or "mural" classification based on angioarchitecture of VGM • Choroidal: Multiple feeders from pericallosal, choroidal, and thalamoperforating arteries • Mural: Few feeders from uni- or bilateral collicular or posterior choroidal arteries o Frequent dural venous sinus (DVS) anomalies • Embryonic falcine sinus drains MPV in 50%, associated with absent straight sinus • Variable absence and stenoses other sinuses

I DIFFERENTIAl.. Childhood • • • •

DIAGlNIfLlSIS

dural arteriovenous fistula (dAVF)

Neonatal presentation similar to VGM Multifocal, large, fast-flow fistulas common Frequent giant aneurysms, venous varices Meningeal/occipital arterial supply to torcular, transverse or superior sagittal sinus

Arteriovenous

malformation

(AVM)

• Congenital web of arteriovenous connections without intervening capillary network • Most common cause nontraumatic ICH children < 15 yrs old • Other sx: Seizure, headaches, neurological deficit • Includes vein of Galen aneurysmal dilatation (VGAD) o AVM (usually thalamic) involving true vein of Galen

Complex developmental

venous anomaly

(DVA) • Rare • Dilatation of several superficial or deep veins draining normal brain parenchyma • No nidus or AV shunting • Associated with blue rubber-bleb nevus syndrome

Imaging Recommendations • Best imaging tool o Initial evaluation • Antenatal US/MRI or postnatal US • MRI/MRA for better definition vascular anatomy, status of brain/ventricles; also for F/U o Catheter angiogram ideally performed with first embolization (6 months of age or later) • Protocol advice o Thin sagittal images define anatomy and relationship of VGM to cerebral aqueduct o MRA C+ often superior to MRA C-; additional MRV usually not necessary

I PATHfLl I..fLlG1Y General Features • General path comments o Embryology • 5th week: Arterial supply to choroid plexus established from meninx primitiva • 7th-8th week: Choroid plexus drains via single temporary midline vein (MPV) • 10th week: Internal cerebral veins annex drainage of choroid plexus ~ regression MPV • Caudal MPV persists, joins internal cerebral veins (ICVs) to form vein of Galen • +/- Absent or hypoplastic straight sinus with persistant falcine sinus (angles up from VGM)

Vascular Malformations

I

5 13

14

• Genetics o Sporadic o Rare reports hereditary vascular dysplasia syndromes • Etiology oVGM • AVF of MPV occurrs in 6-11 weeks gestation • t Flow through VGM prevents involution of normally transient fetal venous drainage pattern o DVS occlusions/stenoses • Primary atresia vs occlusion 2° to turbulent flow • Protect against cardiac overload • More common in mural VGM o Cerebral ischemia/atrophy • Arterial "steal" and/or chronic venous HTN o Hydrocephalus • 1 CSF resorption 2° to elevated DVS pressure • More common in mural VGM (t DVS pressure from downstream sinus stenoses) • Occasionally seen in choroidal VGM (t DVS pressure from right heart failure) • +/- Cerebral aqueduct obstruction • Epidemiology o Rare • < 1% cerebral vascular malformations at any age • Up to 30% of all pediatric vascular malformations o Most common extracardiac cause of high-output CHF in newborn period • Associated abnormalities o Sinus venosus atrial septal defects o Aortic coarctation

Gross Pathologic & Surgical Features • Dilated arterial feeders and midline venous pouch • DVS anomalies • Malformations of structures adjacent to MPV o Pineal gland, tela choroidea of 3rd ventricle

Microscopic

Features

• Thickened wall of venous pouch +/- Ca++

Staging, Grading or Classification Criteria • "Choroidal" or "mural" classification based on angioarchitecture of VGM o Choroidal: Multiple feeders from pericallosal, choroidal, and thalamoperforating arteries o Mural: Few feeders from uni- or bilateral collicular or posterior choroidal arteries

Presentation • Most common signs/symptoms: CHF, hydrocephalus • Clinical profile o Neonate: CHF, cranial bruit (choroidal VGM) o Infant: Hydrocephalus (macrocranium), +/- mild CHF (mural VGM) o Older infant/child: Developmental delay, hydrocephalus, seizure, headache (mural VGM)

Natural History & Prognosis • Neonatal presentation: Death from intractable CHF and multi-system failure without treatment • Mural type in infants/children: Spontaneous thrombosis of slow flow VGM rare • Prognosis o Primarily related to volume of shunt • Neonatal prognosis worse than infant/child (choroidal vs mural VGM) o Antenatal Dx associated with improved outcome o Up to 60% treated VGMs neurologically normal at F/U in some series

Treatment • Choroidal VGM (neonatal presentation) o Medical therapy for CHF until 5-6 months of age • Failure of therapy warrants earlier neuro-intervention o Transcatheter embolization (TCE) at 5-6 months • TCE performed only in absence of intractable CHF, multi-system organ failure, and brain damage • Arterial embolization more effective than venous • CHF decreased by 30-40% A-V shunt 1 o Frequent neurological and MRI F/U after TCE • Evidence of deterioration warrants further therapy • Mural VGM (infant presentation) o TCE can be performed later (slower flow VGM) o TCE technically easier (fewer arterial feeders) • Treatment for hydrocephalus controversial o Shunt placement associated with complications • Alters venous drainage ~ exacerbates brain damage • Engorged subependymal veins t risk IVH (especially post TCE) o Shunt placement reserved for refractory hydrocephalus after all TCEs performed • Occasional treatment of VGM in older child with shunt therapy alone

I DIAGN(')Sj'J(]

Image Interpretation

Pearls

• Imaging appearance diagnostic in the appropriate clinical setting • DVS anomalies abound o Look for persistent fa1cine sinus

I SELECTED REFERENCES 1.

2.

Jones B et al: Vein of Galen aneurysmal malformation: Diagnosis and treatment of 13 children with extended clinical follow-up. AJNR 23:1717-24,2002 Mitchell PJ et al: Endovascular management of vein of Galen aneurysmal malformation presenting in the neonatal period. AJNR 22(7):1403-9,2001

Demographics • Age: Neonatal> infant presentation rare adult presentation • Gender: M:F = 2:1

<::I-fE<::Kl.ISj'

most commoni

Vascular Malformations

Tvpical (Left) Sagittal T2WI fetal MR of a vein of Galen malformation (VGM): A tuft of arterial flow voids communicate with an enlarged midline vein, the embryonic median prosencephalic vein of Markowski (arrow). (Right) Anteroposterior radiograph of the chest in a neonate with a vein of Galen malformation (VGM) shows enlargement of the cardiac silhouette and pulmonary vascular congestion.

Typical (Left) Axial T2WI MR shows a neonatal VGM. The dilated median prosencephalic vein of Markowski (arrow) drains via the falcine sinus (open arrow). Note ventriculomegaly with peri-atrial T2 hyperintensity. (Right) Axial NECT shows a calcified mural VGM in an older patient. Although brain parenchyma appears preserved, parenchymal calcifications (arrow) indicate chronic venous ischemia (Courtesy V. Mathews, MO).

Typical (Left) Lateral internal carotid angiogram shows a choroidal VGM supplied by the pericallosal branches of the anterior cerebral arteries (open arrows). Note persistence of the fetal occipital sinus (arrow). (Right) Lateral vertebral angiogram shows a choroidal VGM supplied by choroidal branches of the posterior cerebral arteries (arrows). Note venous drainage is via the straight sinus (open arrow), not falcine.

Vascular Malformations

5 15

Coronal oblique graphic shows a classic OVA with the umbrella-like "Medusa head" of enlarged medullary white matter veins, dilated transcortical collector vein that drains into the 555.

Abbreviations

o Usually solitary • Can be multiple in blue rubber-bleb nevus syndrome

and Synonyms

5

• Developmental venous anomaly (DVA);venous angioma

16

Definitions • Congenital cerebral vascular malformation with angiogenic ally mature venous elements • May represent anatomic variant of otherwise normal venous drainage

General Features • Best diagnostic clue: "Medusa head" (dilated medullary white matter veins) • Location o At angle of ventricle • Near frontal horn = most common site • Other: Adjacent to fourth ventricle • Size: Varies (may be extensive) but usually < 2-3 cm • Morphology o Umbrella-like collection of enlarged medullary (white matter) veins o Large "collector" vein drains into dural sinus or deep ependymal vein

DDx: Developmental

TS Occlusion

Lateral OSA, venous phase, shows the classic "Medusa head" (arrow) of a typical OVA. The arterial and capillary phases of the angiogram were normal. Incidental finding.

CT Findings • NECT o Usually normal o Occasional: Ca++ if mixed cavernous malformation o Rare: Acute parenchymal hemorrhage (if draining vein spontaneously thromboses) • CECT o Numerous linear or dot-like enhancing foci • Well-circumscribed round/ovoid enhancing areas on sequential sections • Converge on single enlarged tubular draining vein • Occasionally seen as linear structure in a single slice

MR Findings • TlWI o Can be normal if DVAis small o Variable signal depending on size, flow • "Flow void" o Hemorrhage may occur if mixed malformation draining vein thromboses • T2WI o +/- "Flow void" o +/- Blood products

Venous Anomaly

Mixed Capl Venous

Anaplastic Oligo

Vascular Malformations

Cav Malf + OVA

or

DEVELOPMENTAL VENOUS ANOMALY Key Facts Terminology

Pathology

• Congenital cerebral vascular malformation angiogenically mature venous elements

with

Imaging findings • Best diagnostic clue: "Medusa head" (dilated medullary white matter veins) • At angle of ventricle • Stellate, tubular vessels converge on collector vein • Collector vein drains into dural sinus/ependymal vein

Top Differential

Diagnoses

• Mixed vascular malformation (usually cavernous) • Vascular neoplasm • Dural sinus occlusion (with venous stasis, collateral drainage)

• FLAIR: Usually normal; may show hyperintense region if venous ischemia or hemorrhage present • T2* GRE: Hypointense may bloom if co-existing cavernous malformation (CM) with hemorrhage • DWI o Usually normal o Rare: Acute venous infarct seen as hyperintense area of restricted diffusion • Tl C+ o Strong enhancement • Stellate, tubular vessels converge on collector vein • Collector vein drains into dural sinus/ependymal vein • MRA o Arterial phase usually normal o Contrast-enhanced MRA may demonstrate slow-flow DVA • MRV: Delineates "Medusa head" and drainage pattern • MRS: Normal

Angiographic Findings • Conventional o DSA • Arterial phase normal in > 95% of cases • Capillary phase usually normal (rare: Prominent "blush" +1- A-V shunt) • Venous phase: "Medusa head" • 5% atypical (transitional form of venous-arteriovenous malformation with enlarged feeders, A-V shunting)

Imaging Recommendations • Best imaging tool: Tl C+ MR plus MRV • Protocol advice: Include T2* sequence to look for hemorrhage, mixed malformation

[DIFFERENTIAL DIAGNOSIS Mixed vascular malformation cavernous) • Hemorrhage

often associated

(usually

• Mutations in chromosome 9p • Most common cerebral vascular malformation at autopsy • 15-20% occur with co-existing cavernous malformation • Radially oriented dilated medullary veins • Venous radicals are separated by normal brain

Clinical Issues • Usually asymptomatic • Stenosis or thrombosis hemorrhage risk

of draining vein increases

Vascular neoplasm • Enlarged medullary veins • Mass effect, usually enhances

Dural sinus occlusion (with venous stasis, collateral drainage) • Sinus thrombosis • Medullary veins enlarge as collateral drainage

Sturge-Weber

syndrome

• May develop strikingly enlarged medullary, subependymal, choroid plexus veins • Co-existing facial angioma

Venous varix (isolated) • Occurs but is rare without associated DVA

Demyelinating

disease

• Rare: Active, aggressive demyelination prominent medullary veins

may have

I PATHOLOGY General Features • General path comments o Embryology • Arrested medullary vein development at time when normal arterial development nearly complete • Developmental arrest results in persistence of large primitive embryonic deep white matter veins • Genetics o Mutations in chromosome 9p • Encodes for surface cell receptors • Tie-2 mutation results in missense activation • Segregates pedigrees with skin, oral and GI mucosa, brain venous malformations o Approximately 50% inherited as autosomal dominant • Etiology o Does not express growth factors

Vascular Malformations

5 17

o May represent extreme anatomic variant of otherwise normal venous drainage o Expresses structural proteins of mature angiogenesis • Epidemiology o Most common cerebral vascular malformation at autopsy o 60% of cerebral vascular malformations o 2.5-9% prevalence on contrast-enhanced MR scans • Associated abnormalities o 15-20% occur with co-existing cavernous malformation o Blue rubber bleb nevus syndrome (BRBNS) o Sinus pericranii o Sulcation-gyration disorders (may cause epilepsy) o Cervicofacial venous or lymphatic malformation (CAMS-3)

Gross Pathologic & Surgical Features • Radially oriented dilated medullary veins • Venous radicals are separated by normal brain • Enlarged transcortical or subependymal draining vein

Microscopic

18

Features

• Dilated thin-walled vessels diffusely distributed in normal white matter (no gliosis) • Occasional: Thickened, hyalinized vessel walls • 20% have mixed histology (CM most common), may hemorrhage • Variant: "Angiographically occult" DVM with malformed, compactly arranged vessels with partly degenerated walls

Presentation • Most common signs/symptoms o Usually asymptomatic o Uncommon • Headache • Seizure (if associated with cortical dysplasia) • Hemorrhage with focal neurologic deficit (if associated with cavernous malformation) • Clinical profile: Asymptomatic patient with DVM found incidentally on MR

Consider • DVAs contain (and provide main venous drainage for) intervening normal brain!

Image Interpretation

Pearls

• If you aren't seeing one or two DVAs a month in usual outpatient setting, you're probably overlooking them • If you aren't doing much contrast-enhanced MR, you're probably missing incidental DVAs

1.

Wurm G et al: Recurrent cryptic vascular malformation associated with a developmental venous anomaly. Br J Neurosurg. 17(2):188-95, 2003 2. Gabikian P et al: Developmental venous anomalies and sinus pericranii in the blue rubber-bleb nevus syndrome. J Neurosurg 99: 409-11, 2003 3. Abe M et al: Histologically classified venous angiomas of the brain: a controversy. Neurol Med Chir (Tokyo). 43(1):1-10; discussion 11, 2003 4. Desai K et al: Developmental deep venous system anomaly associated with congenital malformation of the brain. Pediatr Neurosurg. 36(1):37-9, 2002 5. Brice G et al: Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24. J Med Genet. 39(7):478-83,2002 6. Hammoud D et al: Ischemic complication of a cerebral developmental venous anomaly: case report and review of the literature. J Comput Assist Tomogr. 26(4):633-6, 2002 7. Agazzi S et al: Developmental venous anomaly with an arteriovenous shunt and a thrombotic complication. Case report. J Neurosurg. 94(3):533-7, 2001 8. Clatterbuck RE et al: The juxtaposition of a capillary telangiectasia, cavernous malformation, and developmental venous anomaly in the brainstem of a single patient: case report. Neurosurgery. 49(5):1246-50, 2001 9. Kilic T et al: Expression of structural proteins and angiogenic factors in cerebrovascular anomalies. Neurosurg 46: 1179-92,2000 10. Komiyama M et al: Venous angiomas with arteriovenous shunts. Neurosurg 44: 1328-35, 1999 11. Naff NJ et al: A longitudinal study of patients with venous malformations. Neurol 50: 1709-14, 1998

Demographics • Age: All ages • Gender: M = F • Ethnicity: None known

Natural History & Prognosis • Hemorrhage risk 0.15% per lesion/per year o Stenosis or thrombosis of draining vein increases hemorrhage risk o Co-existing cavernous malformation increases hemorrhage risk

Treatment • Solitary VA: None (attempt at removal may cause venous infarction) • Histologically mixed VA: Determined by co-existing lesion

Vascular Malformations

DEVELOPMENTAL VENOUS ANOMALY

(Left) Axial T1 C+ MR shows a typical OVA in the frontal

lobe. Note umbrella-like enlarged deep white matter veins (arrows) converging on an enlarged deep "collector" vein (open arrow). (Right) Sagittal contrast-enhanced MRV in the same case shows the OVA drains into an enlarged internal cerebral vein (arrow).

Variant (Left) Axial T1 C+ MR shows an unusual collection of

tubular enhancing structures adjacent to the atrium of the left lateral ventricle. (Right) Frontal OSA in the same case shows dilated medullary veins (arrow) with early venous opacification indicating A-V shunting (open arrow). Transitional (mixed) form of veno-arteriovenous malformation.

Variant (Left) Axial T2WI MR shows a bizarre mixed signal

..

'f ~I.~ ,

,.

):

~. ,

~

~ )

•

Vascular Malformations

occipital mass, initially thought to be a neoplasm. (Right) Axial T1 C+ MR shows prominent draining veins (arrows) that drain into enlarged internal cerebral veins (open arrow). Mixed cavernous-OVA was found at surgery (Courtesy C. Looney, MO).

5 19

Coronal graphic shows a complex sinus pericranii (SP). In addition to extracranial venous varix (open arrow), a OVA (curved arrow), intracranial varix/cor/kal vein (arrows) comprise SP.

Abbreviations

and Synonyms

5

• SP (sinus pericranii)

20

• Abnormal communication between dural venous sinus (DVS), extracranial venous system o Extracranial venous component (EVe) = venous varix, venous malformation (VM), or multiple veins • Rare EVC = arteriovenous malformation (AVM) o EVC communicates with DVS either directly or indirectly via transcalvarial vein • Direct communication: EVC directly over DVS • Indirect communication: EVC adjacent to DVSi trans calvarial vein communicates with DVS via intracranial cortical vein or varix

Definitions

Axial T7 C+ MR shows a typical SP.A vascular scalp mass (arrow) overlies an intracranial varix (open arrow), adjacent to the superior sagittal sinus. The transcalvarial vein is not seen.

o Frontal (40%), parietal (34%), occipital (23%), temporal (4%) o Midline or paramediani lateral location uncommon o Superior sagittal sinus most commonly involved • Transverse sinus distant second o EVC immediately adjacent to outer table • Size o EVC: Varies 1-13 cmi most 2-6 cm o Bone defect: Single/multiple 1-4 mm holesi rare large defect • Morphology: EVC: Well-defined tubular, round, or lobular mass(es) • Intracranial cortical vein or varix occasionally associated with developmental venous anomaly (DVA)

Radiographic Findings • Radiography: Normal or focal "bone" or "calvarial" defect, thinning, erosion

CT Findings General Features • Best diagnostic clue o Vascular scalp mass communicates with DVS via trans calvarial vein o Transcalvarial vein courses through well-defined bone defect • Location

• NECT o Varix: Homogeneous soft tissue density mass o VM: Heterogeneous mass • Frequent cysts/septations • Occasional phleboliths o Bone algorithm • Single/multiple well-defined bone defects • Pressure erosion from overlying VM/varix • CECT

DDx: Enhancing Pediatric Scalp Masses

DVS Cephalocele

IH

VM

Vascular Malformations

Neuroblastoma Met

SINUS PERICRANII Key Facts Terminology

Pathology

• Abnormal communication between dural venous sinus (DVS), extracranial venous system

• Can be congenital spontaneous • Rare

Imaging Findings • Vascular scalp mass communicates with DVS via transcalvarial vein • Transcalvarial vein courses through well-defined bone defect • Frontal (400/0), parietal (34%), occipital (23%), temporal (4%)

Top Differential

o Varix: Strong homogeneous "vascular" enhancement • Heterogeneous if thrombus present o VM: Heterogeneous enhancement typical • CTV: Delineates all vascular components of SP as well as bone defect

MR Findings • TlWI o Iso-, hypo-, or mixed iso-/hypointense • Flow voids in rapidly flowing varix/VM • Hyperintense if thrombus present • T2WI o Majority VMs hyperintense o Mixed signal in large varix/VM 2° turbulent o Flow voids in rapidly flowing varix/VM

flow

• 1'1 C+

o Varix: Homogeneous, "vascular" enhancement o VM: Heterogeneous enhancement • Peripheral puddling with delayed "fill in" classic • MRV: Delineates all vascular components of SP

Findings

• Real Time: EVC: Hypoechoic mass • Color Doppler: Demonstrates communication EVC and DVS

Angiographic

between

Findings

Findings

• Bone Scan: t Activity venous and blood pool phases

Other Modality

Clinical Issues • • • • •

Nontender, fluctuant, bluish forehead/scalp mass Reduces in upright position Children, young adults Stable or slow enlargement Prognosis excellent following surgical removal

• Consider blue rubber-bleb nevus syndrome if SP associated with multiple intracranial DVAs

• Visualization of transcalvarial vein, intracranial cortical vein/varix, and DVS inconstant

Imaging Recommendations • Best imaging tool o MRI C+/MRV • Scalp veins best separated from cortical veins on MRV source images • Transcalvarial vein may not be identified on conventional sequences • Protocol advice o CT/CTV suitable alternative to MRI o Angiography or PV may be required to accurately demonstrate venous anatomy pre-operatively o US suitable for lesions in infants (requires open fontanelle and sutures)

I DIFFERENTIAL DIAGNOSIS· Cephalocele • Brain/CSF-filled dural herniation through skull defect • No enhancement unless vessels/DVS herniate

• Conventional o SP identified during venous phase o Rare arterial blush/contrast puddling during arterial phase of ECA angiogram (VM) o "Closed" and "drainer" classification based on venous drainage pattern • Closed: Blood comes from and drains into DVS • Drainer: Blood comes from DVS and drains into scalp veins

Nuclear Medicine

or

Diagnostic Checklist

Diagnoses

• Cephalocele • Isolated vascular scalp anomalies (e.g., infantile hemangioma) • Scalp/calvarial masses (e.g., histiocytosis)

Ultrasonographic

or acquired, traumatic,

Findings

• Percutaneous venography (PV) o Visualization of EVC and draining scalp veins

Isolated vascular scalp anomalies (e.g., infantile hemangioma) • Infantile hemangioma (IH), AVF,AVM, VM • No direct communication with DVS • IH, AVM, AVF: High flow lesions with flow voids on MR arterial phase abnormalities on DSA

Scalp/calvarial

masses (e.g., histiocytosis)

• Rhabdomyosarcoma, Langerhans cell histiocytosis, neuroblastoma metastases • Enhancing, destructive calvarial/extracalvarial mass • Bone involvement erosive, "malignant" appearing • Invasion of DVS appears as filling defect

I PATHOLOGY General Features • Etiology

Vascular Malformations

5 21

o Can be congenital or acquired, traumatic, or spontaneous o Congenital • SP part of VM or other congenital vascular malformation • Incomplete sutural fusion over prominent/abundant diploic or emissary veins • In utero DVS thrombosis • DVS/internal jugular vein (UV) hypoplasia/atresia o Traumatic • Disruption of diploic/emissary veins at outer table • Skull fx with laceration of DVS, diploic/emissary veins • Skull fx with DVS thrombosis o Spontaneous • "Spontaneous" SPs likely 2° to remote, "forgotten" trauma • Subclinical, post-natal DVS thrombosis • Epidemiology o Rare o 11% of patients presenting for treatment of craniofacial VMs • Associated abnormalities o Blue rubber-bleb nevus syndrome o Systemic VMs o Multi-sutural craniosynostosis • SP occurs 2° to DVS/UV hypoplasia/atresia o Isolated report of cutis aplasia congenita 22

Gross Pathologic & Surgical Features • Extracranial VM/varix: Bluish, blood-filled sac or network of sacs beneath> above calvarial periosteum • Transcalvarial vein = diploic/emissary vein

Microscopic

Features

• Extracranial VM/varix: Non-muscular venous channel(s) o Endothelial lining = congenital origin o Fibrous lining/capsule = traumatic origin • +/- Hemosiderin laden macrophages, thrombus

Staging, Grading or Classification Criteria • Classification based on venous drainage pattern o "Closed drainage": Blood comes from and drains into DVS o "Drainer pattern": Blood comes from DVS, drains into scalp veins

• Gender: M

Natural History & Prognosis

Treatment • Once medical attention sought, surgery usually performed o Cosmesis o SP-related symptomatology o Potential lifetime risk of hemorrhage or air embolus • Surgery o Removal of EVC; closure of bone holes with bone wax, diamond drilling o Rare craniectomy with cranioplasty for large bone defects o Small risk of significant blood loss from uncontrollable venous hemorrhage • Endovascular therapy o Suitable for single/small drainer SPs o Percutaneous injection sclerosants/coils into draining scalp veins o Risk of overlying skin necrosis

I·DIAGNOS'fICGHECKtIS-r Consider • Consider blue rubber-bleb nevus syndrome if SP associated with multiple intracranial DVAs • Consider multi-organ (systemic) VMs if multiple SPs

Image Interpretation

Demographics • Age o Children, young adults o Range: Newborn - 70 yrs

Pearls

• Identification of DVS/UV stenoses important o SP may serve as major venous outlet o Consider SP preservation during craniofacial repair for multi-sutural craniosynostosis • Diagnostic imaging appearance characteristic o Unless thrombosed, main competing DDx is cephalocele with herniated DVS

I SELECTED 2.

• Most common signs/symptoms o Nontender, fluctuant, bluish forehead/scalp mass • Reduces in upright position • Distends when prone or with Valsalva o Rare: Pain, headache, nausea, dizziness • Clinical profile: Child with long history of reducible scalp mass

cases M > F)

• Stable or slow enlargement • Rare spontaneous regression • Potential lifetime risk hemorrhage, air embolus if SP injured • Prognosis excellent following surgical removal o Very rare recurrence

1.

Presentation

= F (post-traumatic

3. 4. 5.

6.

REFERENCES

Burry MV et al: Use of gadolinium as an intraarticular contrast agent for pediatric neuroendovascular procedures. ] Neurosurg 100:150-5, 2004 Burrows FE et al: Venous variations of the brain and cranial vault. Neuroimaging Clin N Am 13:13-26, 2003 Kurosu A et al: Craniosynostosis in the presence of a sinus pericranii: case report. Neurosurgery 34:1090-93, 1994 Nakasu Y et al: Multiple sinus pericranii with systemic angiomas: case report. Surg NeuroI39:41-5, 1993 Bollar A et al: Sinus pericranii: radiological and etiopathological considerations. ] Neurosurg 77:469-72, 1992 Sherry RG et al: Sinus pericranii and venous angioma in the Blue-Rubber bleb nevus syndrome. AJNR 5:832-34, 1984

Vascular Malformations

SINUS PERICRANII

I IMAGE GAllERY (Left) Anteroposterior skull radiograph of a sinus pericranii shows a well-defined right-sided calvarial defect (arrow). (Right) Transcranial color Doppler shows the extracranial (arrow), transcalvarial (open arrow) and intracranial components of a sinus pericranii in an infant.

Typical (Left) Coronal reconstruction from CT venogram shows a focal area of "vascular" enhancement (curved arrow) immediately adjacent to the outer table of the parietal bone near the superior sagittal sinus. (Right) Coronal bone algorithm reconstruction from CT venogram shows the small bony defect (arrow) through which the transcalvarial vein passes, connecting the superior sagittal sinus to the venous varix.

(Left) Sagittal maximum intensity projection from TOF MR venogram shows the vascular components of a sinus pericranii: Superior sagittal sinus, transcalvarial vein (arrow), and venous varix (open arrow). (Right) AP view venous phase angiogram best shows the vascular components of a drainer SP: Superior sagittal sinus, transcalvarial vein (curved arrow), venous varix (arrow), draining scalp vein (open arrow).

Vascular Malformations

5 23

CAVERNOUS MALFORMATION

Sagittal graphic shows cavernous malformation (CM) of the brainstem with multiple locules filled with blood in different stages of degradation. Note hemosiderin (arrows) around the mass.

o Complete hemosiderin

TERMINOLOGY Abbreviations

5 24

• Benign vascular hamartoma with masses of closely apposed immature blood vessels ("caverns"), intralesional hemorrhages, no neural tissue • CMs exhibit range of dynamic behaviors (enlargement, regression, de novo formation)

• NECT o Negative in 30-50% o Well-delineated round/ovoid hyperdense lesion, usually < 3 cm • 40-60% Ca++ • No mass effect unless recent hemorrhage o Surrounding brain usually appears normal • CECT: Little/no enhancement unless mixed with other lesion (e.g., DVA) • CTA: Usually negative

(CM); "cavernoma"

Definitions

FINDINGS

MR findings

General features • Best diagnostic clue: "Popcorn ball" appearance with complete hypointense hemosiderin rim on T2WI MR • Location o Occurs throughout CNS o Brain CMs common; spinal cord rare • Size o CMs vary from microscopic to giant (> 6 cm) o Majority are between 0.5-4 cm • Morphology o Discrete, lobulated mass of interwoven vessels o Locules of variable size contain blood products at different stages of evolution

• TlWI o Variable, depending on hemorrhage/stage • Common: "Popcorn ball" appearance of mixed hyper-, hypointense blood-containing "locules" • Less common: Acute hemorrhage (nonspecific) • T2WI o Reticulated "popcorn-like" lesion most typical • Mixed signal core, complete hypointense hemosiderin rim • Locules of blood with fluid-fluid levels o Less common: Hypointense • FLAIR: May show surrounding edema in acute lesions • T2* GRE

DDx: Cavernous Malformation

Hemangioblastoma

rim surrounds lesion

CT findings

and Synonyms

• Cavernous malformation

I IMAGING

Axial T2WI MR shows classic "popcorn ball" appearance of a type 2 cavernous malformation. Fluid-fluid levels and a complete hemosiderin rim (arrows) characterize this solitary lesion.

Metastasis

Vascular Malformations

CAVERNOUS MALFORMATION Key Facts Terminology

Pathology

• Benign vascular hamartoma with masses of closely apposed immature blood vessels ("caverns"), intralesional hemorrhages, no neural tissue

• Multiple (familial) CMsyndrome is autosomal dominant, variable penetrance • CMs are . ically immature lesions with endothelial n, increased neoangiogenesis • CM =:: most common angiographically "occult" vascular malformation • 75% occur as solitary, sporadic lesion • 10-30% multiple, familial

Imaging Findings • Mixed signal core, complete hypointense hemosiderin rim • Locules of blood with fluid-fluid levels • Prominent susceptibility effect (hypointense "blooming") • DSA usually normal ("angiographically occult vascular malformation") • Best imaging tool: MRI (use T2* sequence; standard Tl-, T2WI may be negative in small Type 4 lesions!)

• • • •

o Prominent susceptibility effect (hypointense "blooming") o If> 3 lesions, numerous punctate hypointense foci ("black dots") on GRE scans most common finding DWI: Usually normal Tl C+: Minimal or no enhancement (may show associated VM) MRA: Normal (unless mixed malformation present) Large acute hemorrhage may obscure more typical features of CM

Angiographic Findings • Conventional o DSA • DSA usually normal ("angiographically occult vascular malformation") • Slow intralesional flow without AV shunting • Avascular mass effect if large or acute hemorrhage • +/- Associated other malformation (e.g., DVA) • Rare: Venous pooling, contrast "blush"

Imaging Recommendations • Best imaging tool: MRI (use T2* sequence; standard Tl-, T2WI may be negative in small Type 4 lesions!) • Protocol advice o Use T2* GRE sequence with long TE (35 msec) o Include TIC+ to look for associated anomalies (i.e., DVA)

I IDIFFERENllt\1L IDIt\(JN(i)$I$ "Popcorn ball" lesion • AVM ("flow voids" +/- hemorrhage, usually single blood product) • Hemorrhagic neoplasm (incomplete hemosiderin rim, disordered evolution of blood products, strong enhancement) • Calcified neoplasm (e.g., oligodendroglioma; usually shows some enhancement)

Multiple "black dots" • Old trauma (DAI, contusions)

Clinical Issues • Clinical profile: Familial CM ""young adult Hispanic-American with repeated spontaneous intracranial hemorrhages • Broad range of dynamic behavior (may progress, enlarge, regress)

• Hypertensive microbleeds (history of longstanding HTN) • Amyloid angiopathy (elderly, demented, white matter disease) • Capillary telangiectasias (faint brush-like enhancement)

I Pt\IH(i)l(i)(J¥ General Features • General path comments: Discrete collection of endothelial-lined, hemorrhage-filled vessels without intervening normal brain • Genetics o Three separate loci implicated (CCMl, CCM2, CCM3 genes) o Multiple (familial) CM syndrome is autosomal dominant, variable penetrance • Mutation in chromosomes 3,7q (KRITI mutation at CCMllocus) • Nonsense, frame-shift or splice-site mutations consistent with two-hit model for CM • Mutations encode a truncated KRITI protein • KRITl interacts with endothelial cell microtubules; loss of function leads to inability of endothelial cells to mature, form capillaries o Sporadic CM • No KRITl mutation • Etiology o CMs are angiogenically immature lesions with endothelial proliferation, increased neoangiogenesis o VEGF, SFGF, TGF(){expressed o Receptors (e.g., Flk-l) upregulated • Epidemiology o CM = most common angiographically "occult" vascular malformation o Approximate prevalence 0.5% o 75% occur as solitary, sporadic lesion o 10-30% multiple, familial • Associated abnormalities o DVA

Vascular Malformations

5 25

o Superficial siderosis o Cutaneous abnormalities • Cafe au lait spots • Hyperkeratotic capillary-venous ("cherry angiomas")

malformations

Gross Pathologic & Surgical Features • Discrete, lobulated, bluish-purple ("mulberry-like") nodule • Pseudocapsule of gliotic, hemosiderin-stained brain

Microscopic • • • • • •

Features

Thin-walled epithelial-lined spaces Embedded in collagenous matrix Hemorrhage in different stages of evolution +/- Ca++ Does not contain normal brain May be histologically mixed (VM most common)

Staging, Grading or Classification Criteria • Zabramski classification of CMs o Type 1 = subacute hemorrhage (hyperintense on Tl WI; hyper- or hypointense on T2WI) o Type 2 = mixed signal intensity on Tl-, T2WI with degrading hemorrhage of various ages (classic "popcorn ball" lesion) o Type 3 = chronic hemorrhage (hypo- to iso on Tl-, T2WI) o Type 4 = punctate microhemorrhages ("black dots"), poorly seen except on GRE sequences

o Sporadic = .25-.7%/year o Risk factor for future hemorrhage = previous hemorrhage o Rehemorrhage rate high initially, decreases after 2-3 years • Familial CMs at especially high risk for hemorrhage, forming new lesions o 1% per lesion per year

Treatment • Total removal via microsurgical resection o Caution: If mixed DVA, venous drainage must be preserved • Stereotaxic XRT limited effectiveness

Consider • In patients with spontaneous ICH, do a T2* scan to look for additional lesions • Atypical appearance of CM in setting of recent hemorrhage requires F/U imaging to confirm diagnosis

Image Interpretation

Pearls

• CM should not be confused with cavernous hemangioma (true vasoproliferative neoplasm) • "Giant" CMs can mimic neoplasm

26 1.

Presentation • Most common signs/symptoms o Seizure 50% o Neurologic deficit 25% (may be progressive) o 20% asymptomatic • Clinical profile: Familial CM = young adult Hispanic-American with repeated spontaneous intracranial hemorrhages

Demographics • Age o Peak presentation = 40-60 Y but may present in childhood o Familial CMs tend to present earlier than sporadic lesions • Gender: M = F • Ethnicity o Multiple (familial) CM syndrome in Hispanic Americans of Mexican descent • Founder mutation in KRITl (Q445X) • Positive family history = 90% chance of mutation resulting in CM o CMs may occur in any ethnic population

Natural History & Prognosis • Broad range of dynamic behavior (may progress, enlarge, regress) • De novo lesions may develop • Propensity for growth via repeated intralesional hemorrhages

Shenkar R et al: Differential gene expression in human cerebrovascular malformations. Neurosurgery. 52(2):465-77; discussion 477-8, 2003 2. Reich P et al: Molecular genetic investigations in the CCM1 gene in sporadic cerebral cavernomas. Neurology. 60(7):1135-8,2003 3. Al-Shahi R et al: Prospective, population-based detection of intracranial vascular malformations in adults: the Scottish Intracranial Vascular Malformation Study (SIVMS).Stroke. 34(5):1163-9,2003 4. Rivera PP et al: Intracranial cavernous malformations. Neuroimaging Clin N Am. 13(1):27-40,2003 5. Wang CC et al: Surgical management of brain-stem cavernous malformations: report of 137 cases. Surg Neurol. 59(6):444-54; discussion 454, 2003 6. Wang CH et al: Multiple deep-seated cavernomas in the third ventricle, hypothalamus and thalamus. Acta Neurochir (Wien). 145(6):505-8; discussion 508, 2003 7. Mathiesen T et al: Deep and brainstem cavernomas: a consecutive 8-year series. J Neurosurg. 99(1):31-7, 2003 8. Musunuru K et al: Widespread central nervous system cavernous malformations associated with cafe-au-lait skin lesions. Case report. J Neurosurg. 99(2):412-5, 2003 9. Kehrer-Sawatzki H et al: Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1). Acta Neuropathol (Bed). 104(3):231-40,2002 10. Biondi A et al: Intracranial extra-axial cavernous (HEM) angiomas: tumors or vascular malformations? J Neuroradiol. 29(2):91-104, 2002 11. Cave-Riant F et al: Spectrum and expression analysis of KRIT1mutations in 121 consecutive and unrelated patients with Cerebral Cavernous Malformations. Eur J Hum Genet. 10(11):733-40,2002

Vascular Malformations

Typical (Left) Axial T1WI MR shows classic CM with hemorrhage of mixed ages. Subacute hemorrhage appears bright while acute blood is isointense. T1WI does not show hemosiderin rim well. (Right) Axial T2* CRE MR shows striking "blooming" of the lesion caused by the peripheral rim of hemosiderin and inhomogeneous clot. No normal brain is present within the CM.

Typical (Left) Axial NECT of a CM shows a hyperdense lesion in the left internal capsule (open arrow). (Right) Axial T2* CRE MR in a patient with multiple familial CM syndrome shows several hypointense foci characteristic of Type 4 CMs.

Variant (Left) Axial T1WI MR shows a large mixed

acute/subacute hematoma in the left temporal lobe in this 15 year old Hispanic male. Surgery disclosed cavernous malformation. No other lesions were present. (Right) Axial FLAIRMR shows a giant cavernous malformation that occupies most of the right hemisphere.

Vascular Malformations

5 27

Axial T2' GRE MR shows a poorly-demarcated moderately hypointense pontine BCT (arrow). The susceptibility effect is caused by slow intralesional blood flow and hemoglobin desaturation.

Lateral graphic shows a stippled-appearing lesion of the pons with dilated thin-walled capillaries interspersed with normal brain. Note absence of mass effect. Capillary telangiectasia.

Abbreviations

• T2WI: 50% normal; 50% stippled foci of hyperintensity • FLAIR: Usually normal; may show hyperintense foci • T2* GRE o Lesion moderately but not profoundly hypointense • Slow blood flow with oxy- to deoxyhemoglobin o Less common: Multifocal BCTs ("gray dots") • DWI: Usually normal • Tl C+ o Faint stippled or speckled "brush-like" enhancement o May show punctate, linear/branching vessels +/collecting vein (if mixed with DVA) • MRV: High-resolution BOLD (blood oxygen level dependent) venography (HRBV) may be even more sensitive than standard T2*

and Synonyms

• Brain capillary telangiectasia

(BCT)

Definitions 28

• Cluster of capillaries interspersed parenchyma

with normal brain

General Features • Best diagnostic clue: Hypointense lesion on T2* + faint "brush-like" enhancement • Location o Midbrain, pons, medulla, spinal cord most common o One-third found elsewhere (subcortical WM, etc) • Size: Usually < 1 cm • Morphology: Small, poorly-demarcated lesion; no mass effect or edema

Angiographic Findings • Conventional o Usually normal o Faint vascular "stain" or draining vein if mixed with DVA

CT Findings

Imaging Recommendations

• NECT: Usually normal (occasionally may have Ca++) • CECT: Usually normal

• Best imaging tool: MR with T2*, Tl C+ sequences • Protocol advice: Consider HRBV for problematic lesions

MR Findings • TIWI: Usually normal

DDx: Brain Capillary Telangiectasia

h

~t"

;.•••. I:t... ,.". . 'It ., ~ '\ ''

,

-

,

'~ ...~,!1 Pontine OVA

Cavernous

Malfs

Vascular Malformations

Metastasis

CAPILLARY TELANGIECTASIA Key Facts Top Differential

Terminology • Cluster of capillaries interspersed parenchyma

with normal brain

Imaging Findings • Best diagnostic clue: Hypointense lesion on T2* + faint "brush-like" enhancement • Slow blood flow with oxy- to deoxyhemoglobin • Less common: Multifocal BCTs ("gray dots") • Best imaging tool: MR with T2*, T1 C+ se uences

I DIFFERENTIAL Developmental

DIAGNOSIS

venous anomaly (OVA)

Diagnoses

• Developmental venous anomaly (DVA) • Metastasis • Cavernous malformation

Diagnostic Checklist • Enhancing pontine lesion that becomes moderately hypointense on T2* is usually a BeT

• Clinical profile: Asymptomatic middle-aged patient with a poorly-delineated brains tern lesion seen incidentally on T1 C+ MR scan

• Often mixed with BCT

Demographics

Metastasis

• Age: Any age but 30-40 y most common

• Strong> faint enhancement • Pons/cerebellum rare locations

Natural History & Prognosis • Clinically benign, quiescent unless histologically mixed • Rare reports of aggressive course

Cavernous malformation • Blood locules with fluid-fluid levels • Complete hemosiderin rim • Can be mixed with BCTs, cause hemorrhage

Treatment • None

IPATHOLOG¥

I DIAGNOSTIC

5 CHECKLIST

General Features

Image Interpretation

• General path comments: Usually found incidentally at autopsy or imaging • Genetics: None known • Etiology o Sporadic BCTs: Unknown o May develop as complication of radiation (20% of children after cranial irradiation) • Epidemiology: 15-20% of all intracranial vascular malformations • Associated abnormalities o Osler-Weber-Rendu disease (HHT) • BCTs rare (AVMs more common)

• Enhancing pontine lesion that becomes moderately hypointense on T2* is usually a BCT

Pearls

I SELECTED REFERENCES 1.

2.

Koike S et al: Asymptomatic radiation-induced telangiectasia in children after cranial irradiation: Frequency latency, and dose relation. Radiol 203:93-9, 2004 Castillo M et al: MR imaging and histologic features of capillary telangiectasia of the basal ganglia. AJNR Am J Neuroradiol. 22(8):1553-5, 2001

Gross Pathologic & Surgical Features • Rarely identified unless unusually large (up to 2 em reported) or hemorrhage (from other vascular malformation) present

I IMAGE GALLERY

Microscopic Features • Cluster of dilated but histologically normal capillaries • Normal brain in-between vascular channels • Uncomplicated CTs have no gliosis, hemorrhage, Ca++

I CLINICAL

ISSUES

Presentation • Most common signs/symptoms o Asymptomatic, discovered incidentally o Rare: Headache, vertigo, tinnitus

(Left) Axial T2WI MR shows no definite abnormality. (Right) Axial T1 C+ MR shows the lesion has faint stippled enhancement (open arrow). Lesion was found incidentally in a patient with migraine

headaches and normal neurological examination. Presumed BCT.

Vascular Malformations

29

PART I SECTION' Neoplasms and Tumorlike Lesions

The curr nt meta tati neopla m of origin"), as w II a neopla m ar ubdi

110

Turn f ur epith lial Tissue Tum of Peripheral er es Turn r f the Meninge L III ph ma and Hemopoieti eopla rm II Tumor Turn r of th ellar Region aloha

III

e created standard nom

SECTION 6: Neoplasms and Tumorlike Lesions

Introduction and Overview Neoplasms Pathology and Imaging Issues

Pineal Parenchymal Tumors 1-6-4

Pineoblastoma Pineocytoma

1-6-84 1-6-88

Astrocytic Tumors-Infiltrating Diffuse Astrocytoma, Low Grade Pediatric Brainstem Glioma Anaplastic Astrocytoma Glioblastoma Multiforme Gliosarcoma Gliomatosis Cerebri

1-6-8 1-6-12 1-6-16 1-6-20 1-6-24 1-6-26

1-6-30 1-6-34 1-6-38

Oligodendroglial and Miscellaneous Tumors Oligodendroglioma Anaplastic Oligodendroglioma Astroblastoma

1-6-42 1-6-46 1-6-50

Ependymal Tumors Ependymoma Subependymoma

1-6-52 1-6-56

Choroid Plexus Tumors Choroid Plexus Papilloma Choroid Plexus Carcinoma

1-6-60 1-6-64

Neuronal, Mixed Neuronal-Glial Tumors Ganglioglioma Dysplastic Cerebellar Gangliocytoma Desmoplastic Infantile Ganglioglioma DNET Central Neurocytoma

Medulloblastoma (PNET-MB) Supratentorial PNET Atypical Teratoid-Rhabdoid Tumor Neuroblastoma, Metastatic

Tumors of Cranial/Peripheral

Astrocytic Tumors-localized Pilocytic Astrocytoma Pleomorphic Xanthoastrocytoma Subependymal Giant Cell Astrocytoma

Embryonal and Neuroblastic Tumors

1-6-66 1-6-70 1-6-74 1-6-76 1-6-80

Schwannoma Neurofibroma

1-6-92 1-6-96 1-6-100 1-6-104

Nerves 1-6-108 1-6-112

Blood Vessel and Hemopoietic Tumors Hemangioblastoma Hemangiopericytoma Primary CNS Lymphoma Intravascular (Angiocentric) Lymphoma Leukemia

1-6-114 1-6-118 1-6-122 1-6-126 1-6-128

Germ Cell Tumors Germinoma Teratoma Embryonal Carcinoma

1-6-132 1-6-136 1-6-138

Metastatic Tumors and Remote Effects of Cancer Parenchymal Metastases Paraneoplastic Syndromes

1-6-140 1-6-144

NEOPLASMS PATHOLOGY AND IMAGING ISSUES

Graphic representation of approximate relative prevalence of primary vs. metastatic brain tumors in adults. In clinical series, nearly half of all adult eNS neoplasms are metastases.

ITERMINOlOGY

6 4

Definitions • Neuroepithelial tumors: Primary neoplasms derived from the embryonic neural tube • Glioma: Generic term for neoplasm derived from glial cells (astrocytes, oligodendrocytes, ependymal cells including choroids plexus) • Hamartoma: Nonneoplastic tumor-like mass arising from normal cellular constituents • Paraneoplastic syndrome: Remote effect of systemic cancer on the CNS without metastases

I PATHOLOGY

ISSUES

General Considerations • CNS neoplasms are a histologically diverse group that occur at many sites in the brain or its linings • Can be derived from o Primitive totipotential embryologic precursor cells o Nonneoplastic normal cellular constituents (hamartomas) o Embryologically misplaced tissues o Neoplastic transformation of normal cellular constituents o Other intra- or extracranial neoplasms (metastases) o A spectrum of nonneoplastic conditions that can mimic tumor Classification • World Health Organization (WHO) divides CNS neoplasms into primary (9 basic groups) and secondary tumors (metastases) • Neuroepithelial tumors o Astrocytic neoplasms: Derived from neoplastic astrocytes; vary in location, peak age, genetics, clinical features and biological behavior as well as imaging appearance • Diffusely infiltrating (most commonly fibrillary) astrocytomas

Graphic shows relative prevalence of brain tumors in children. Metastases, M/GBMs are rare. Low grade astrocytomas, PNETs {including medulloblastoma} are more common compared to adults.

• Diffuse astrocytoma • Anaplastic astrocytoma • Glioblastoma multiforme • Gliomatosis cerebri • Gliosarcoma • Localized astrocytic neoplasms • Pilocytic astrocytoma • Pleomorphic xanthoastrocytoma • Subependymal giant cell astrocytoma o Oligodendroglioma: Putative origin from oligodendrocytes, differ genetically from diffusely infiltrating astrocytoma • Oligodendroglioma • Anaplastic oligodendroglioma • Mixed glioma (2 or more neoplastic elements; mixed oligo-astro most common) o Other gliomas of uncertain origin • Astroblastoma • Chordoid glioma of the 3rd ventricle o Ependymal tumors: Tumors that arise from ependymal lining of ventricles, central canal of spinal cord • Ependymoma • Subependymoma o Choroid plexus tumors • Choroid plexus papilloma • Choroid plexus carcinoma • Neuronal, mixed glial-neuronal and neurocytic tumors (neoplasms with variable neuronal and/or glial differentiation) o Ganglioglioma and gangliocytoma (in cerebellum = Lhermitte-Duclos disease) o Desmoplastic infantile ganglioglioma/astrocytoma o Dysembryoplastic neuroepithelial tumor (DNET) o Hypothalamic hamartoma o Central neurocytoma and parenchymal (extraventricular) neurocytic tumors • Pineal parenchymal tumors: Derived from pineocytes (pineal parenchymal cells) or embryonic prercursors, with wide spectrum of differentiation o Pineoblastoma

NEOPLASMS PATHOLOGY AND IMAGING ISSUES DIFFERENTIAL DIAGNOSIS Astrocytic tumors

Pineal parenchymal and germ cell tumors

• Diffusely infiltrating astrocytoma (e.g., fibrillary, protopla mic; includes gliomatosis cerebri) • " ircumscribed" astrocytoma (e.g., pilocytic, SGCA)

• Pineocytoma/blastoma • Germinoma, teratoma, yolk sac tumor, etc.

Nonastrocytic neuroepithelial tumors

• Schwan noma, neurofibroma,

• Oligodendroglial tumors • Ependymal, choroid plexus tumors

Meningeal tumors

Neuronal/mixed neuronal-glial tumors • Ganglioglioma/cytoma • DI IDIA • D ET • entral neurocytoma

(including

Lhermitte-Duclos)

o Pineocytoma • Embryonal tumors: Round-cell tumors with variable spectrum of differentiation; some neuropathologists classify all these as primitive neuroectodermal tumors (PNETs) o Medulloepithelioma o Ependymoblastoma o Medulloblastoma (posterior fossa primitive neuroepithelial tumor or PNET-MB) o Primitive neuroepithelial tumor (supratentorial small round cell embryonal tumor) o Atypical teratoid/rhabdoid tumor (AT/RT) • Peripheral neuroblastic tumors: Tumors with wide range of neuronal differentiation, may involve/invade CNS o Neuroblastoma (when involves CNS, is usually metastatic from extracranial site) • Tumors of cranial and spinal or peripheral nerves: Tumors with wide range of histopathological features; multiple tumors in skull/brain are associated with inherited familial tumor syndromes (Le., neurofibromatosis) o Neurofibroma o Schwannoma o Malignant peripheral nerve sheath tumor (MPNST) • Meningeal tumors o Meningothelial cell tumors (e.g., meningioma) o Mesenchymal, nonmeningothelial cell tumors (e.g., chondrosarcoma) o Tumors of uncertain histogenesis (e.g., hemangioblastoma) • Lymphoma and tumors of hemopoietic system: May be primary or secondary, variably involve skull, meninges, and/or brain o Lymphoma o Plasmacytoma o Leukemia (granulocytic sarcoma) • Germ cell tumors: Broad histopathological spectrum of extragonadal germ cell neoplasms with variable biological behavior o Germinoma o Teratoma o Embryonal carcinoma

Peripheral/cranial nerve tumors MP ST

• Meningioma (all) • Me enchymal, nonmeningothelial tumor hemangiobla toma, most arcomas)

(e.g.,

Lymphoma, hematopoietic neoplasms • Malignant lymphoma (includes both primary, econdary) • Plasmacytoma, granulocytic sarcoma/leukemia

o Others (e.g., yolk sac tumor, choriocarcinoma, mixed germ cell tumors) • Metastatic tumors and remote effects of cancer on the CNS o Metastases (brain parenchyma, other sites such as meninges and pituitary gland) o Paraneoplastic syndromes

Coding • International Classification of Diseases for Oncology (ICD-O), Systematized Nomenclature of Medicine (SNOMED) o 0 = benign tumors (e.g., hypothalamic hamartoma) o /l = low or uncertain malignant potential/borderline malignancy o /2 = in situ lesions o /3 = malignant tumors

Grading • Varies according to neoplasm type; example = astrocytoma • Astrocytoma grading parameters/features o Nuclear atypia, mitoses o Microvascular proliferation, necrosis • Grade I = reserved for circumscribed astrocytomas (such as pilocytic) • Grade II = one parameter (astrocytoma) • Grade III = two features ("anaplastic" or "malignant astrocytoma) • Grade IV = presence of 3 or 4 variables (glioblastoma multiforme)

IANATOMY-BASED

IMAGING

ISSUES

Key Concepts or Questions • Some neoplasms commonly occur in certain locations (e.g., pilocytic astrocytoma in cerebellum and 3rd ventricle), are rare in others (e.g., hemispheric PAs) • Tumors in children other than newborns tend to be infratentorial whereas primary neoplasms in adults are mostly supratentorial

I

NEOPLASMS PATHOLOGY AND IMAGING ISSUES

Survival of adults with malignant eNS tumors is depicted (mets underrepresented for purposes of illustration). Some high grade astrocytomas and metastases may experience prolonged survival but this is the exception, not the rule.

I CLINICAL

IMPLICATIONS

Clinical Importance

6

• Prevalence of brain neoplasms o In USA,estimated crude incidence = 4.5/100,000 o Approximately 2% in autopsies, 1% of hospital admissions • Influence of age on tumor type o Some neoplasms occur primarily in children (e.g., ependymoma) o Other primary neoplasms are generally (but not exclusively) in older adults (e.g., primary GBM) • Influence of presenting symptoms on tumor type: While often nonspecific, some tumors are strongly associated with certain clinical presentations o Chronic, longstanding epilepsy: Slowly growing, cortically-based neoplasms (e.g., DNET, ganglioglioma) • Influence of tumor type on survival rates o Infiltrative worse than circumscribed (e.g., AAvs PA) o Higher grade = generally shorter survival o Metastases generally shorter survival than primary malignant tumors

I\CUSTOM DIFFERENTIAL DIAGNOSISI Tumors in children < 2 yrs • Astrocytoma • Choroid plexus papilloma • Teratoma • Embryonal tumors Cortically-based tumors • DNET • Ganglioglioma • Oligodendroglioma • PXA

Intraventricular tumors • Ependymoma, subependymoma

Table depicts the mutually-exclusive genetic events that lead to formation of a secondary vs primary CBM. Patients with low grade astrocytomas are at risk for malignant degeneration.

• Central neurocytoma • Choroid plexus papilloma/carcinoma Pineal region tumors • Pineal parenchymal tumors (pineocytoma/blastoma) • Germ cell tumors (germinoma, teratoma, etc) • "Other" tumors/masses in o Meningioma (tentorial apex) o Astrocytoma (rare in pineal gland; more common in tectum, thalamus) o Nonneoplastic pineal cyst Dural-based tumors and mimics • Meningioma • Metastasis • Inflammatory pseudotumor • Infection (e.g., tuberculosis) • Extramedullary hematopoiesis Local intracranial extension from extracranial neoplasms • Chordoma • Paraganglioma • Carcinomas (e.g., nasopharyngeal squamous cell), sarcomas (rhabdomyosarcoma) Neoplasms that often have cyst • Pilocytic astrocytoma • Craniopharyngioma • Ganglioglioma • Hemangioblastoma

+ nodule

I SELECTED REFERENCES 1. 2.

Burger PC et al: Surgical Pathology of the Nervous System and its Coverings, pp 160-378. Churchill Livingstone, 2002 Kleihues P, Cavenee WK: Pathology and Genetics of the Nervous System, IARC Press, Lyon, 2000

NEOPLASMS PATHOLOGY AND IMAGING ISSUES

I IMAGE

GAllERY

Pathology (Left) Axial T2WI MR in a young patient with long history of low grade astrocytoma, serial scans showing stable hyperintense medial temporal/parietal tumor mass (arrows). (Right) Axial Tl C+ MR shows a faint focus of contrast-enhancement (arrow) that was not present on previous studies. Stereotaxic biopsy disclosed malignant transformation. Secondary glioblastoma.

Pathology (Left) Coronal gross pathology shows a deep basal ganglionic CBM (open arrow) with hemorrhage, necrosis, mass effect. Note tumor spread into the internal capsule (arrows) (Courtesy E.T. Hedley-Whyte, MO). (Right) Axial gross pathology in the same case shows tumor infiltrating down the pons (open arrow), into the brachium pontis (arrows). Not shown: Tumor in the cerebral peduncles, medulla, upper spinal cord.

Normal (Left) Axial gross pathology, section shows meningeal (open arrow) and parenchymal (arrow) metastases. Note rounded, relatively discrete morphology of the metastatic focus (Courtesy R. Hewlett, MO). (Right) Axial TlWI MR shows relatively discrete, nodular hyperintense metastasis at the gray-white junction (arrow). Note relative lack of edema, mass effect (compare to autopsy case on left).

7

DIFFUSE ASTROCYTOMA,

Coronal graphic shows an infiltrative mass centered in the white matter expanding the left temporal lobe. Axial insert shows mild mass effect upon the midbrain. Low grade astrocytoma.

ITERMINOLOGY Abbreviations

and Synonyms

• Diffuse astrocytoma, grade II astrocytoma, astrocytoma, astrocytoma

fibrillary

Definitions • Primary brain tumor of astrocytic origin with intrinsic tendency for malignant progression, degeneration into anaplastic astrocytoma (AA) • Well-differentiated but infiltrating neoplasm, slow growth pattern 8

IIMAGING FINDINGS General Features • Best diagnostic clue: Focal or diffuse nonenhancing white matter (WM) mass • Location o Cerebral hemispheres, supratentorial 2/3 • Frontal lobes 1/3, temporal lobes 1/3 • Relative sparing of occipital lobes o Infratentorial1/3 • Brainstem (50% of brain stem "gliomas" are low-grade astrocytoma) • Occur in pons and medulla of children/ adolescents

LOW GRADE

Axial T2WI MR shows an apparently well-circumscribed left frontal lobe mass. At surgery, tumor cells were found infiltrating the adjacent brain, extending beyond the MR signal changes.

o Tumors of white matter, may extend into cortex • 20% involve deep gray matter structures, thalamus, basal ganglia o Less commonly occur in spinal cord • Size: Variable • Morphology o Homogeneous mass with enlargement and distortion of affected structures o May appear circumscribed on imaging but isn't; tumor cells typically found beyond imaged signal abnormality!

CT Findings • NECT o Ill-defined homogeneous hypodense/isodense mass o 20% Ca++; cysts are rare o Calvarial erosion in cortical masses (rare) • CECT o No enhancement or very minimal • Enhancement should raise suspicion of focal malignant degeneration

MR Findings • TlWI o Homogeneous hypointense mass o May expand white matter and adjacent cortex o Appears circumscribed, but infiltrates adjacent brain o Ca++ and cysts uncommon o Hemorrhage or surrounding edema (rare)

DDx: low Grade Astrocytoma

AA

PCA Ischemia

Cerebritis

Neoplasms and Tumorlike lesions

Oligodendroglioma

DIFFUSE ASTROCYTOMA, LOW G Terminology • Primary brain tumor of astrocytic origin with intrinsic tendency for malignant progression, degeneration into anaplastic astrocytoma (AA)

Imaging Findings • Best diagnostic clue: Focal or diffuse nonenhandng white matter (WM) mass • Cerebral hemispheres, supratentorial 2/3 • May appear drcumscribed on imaging but isn't; tumor pically found beyond imaged signal abnor

• T2Wl o Homogeneous hyperintense mass o May appear circumscribed, but often infiltrates adjacent brain o Ca++ and cysts uncommon o Hemorrhage or surrounding edema are rare o May expand adjacent cortex • PD/lntermediate: Homogeneous hyperintense mass • FLAIR: Homogeneous hyperintense mass • DWI: Restricted diffusion usually absent • TI C+ o Usually no enhancement o Enhancement suggests progression to higher grade • MRS o High choline, low NAA typical but not specific o High MI/Cr ratio (0.82 +/- 0.25) o May delineate tumor extent better than conventional MR • Dynamic contrast-enhanced T2* weighted imaging o Relatively lower rCBV compared to AA, GBM o Lower permeability values than high grade tumors

Nuclear Medicine

I [)1J.:J.:EREN"'IAIi[)I~u~mll$ Anaplastic astrocytoma (M) • Hemispheric WM lesion, usually non enhancing • Focal or diffuse mass • May be indistinguishable without biopsy

Ischemia • Vascular territory (MCA, ACA, PCA), acute onset • Diffusion restriction (acute/early subacute) • Often wedge-shaped, involves GM & WM

Cerebritis

6

• Edema, patchy enhancement characteristic • Usually shows restricted diffusion • Typically more acute onset

9

Oligodendroglioma • Cortically-based mass with variable enhancement • Ca++ common • May be indistinguishable

Herpes encephalitis

Findings

• PET o Low grade astrocytomas have FDG uptake similar to normal white matter o FDG uptake within an astrocytoma has good correlation with histologic grade of tumor o FDG, 18F-Choline and IIC-Choline PET useful for biopsy (most hypermetabolic area)

• Confined to limbic system, temporal lobes • Hemorrhage and enhancement common • Acute onset

Status epilepticus • Active seizures may cause signal abnormalities enhancement • Clinical history of seizures

and

Imaging Recommendations • Best imaging tool o MR is most sensitive o Newer techniques such as diffusion tensor imaging coming into uSe • Protocol advice o Contrast-enhanced MR o MRS and dynamic contrast-enhanced T2* weighted imaging may be helpful

I PA"'I"t~~Ou~ General Features • General path comments o Astrocytic neoplasm characterized by high degree of cellular differentiation, slow growth, diffuse infiltration of adjacent structures o If oligodendroglioma components, oligoastrocytoma • Genetics o TP53 mutation> 60%

Neoplasms and Tumorlike

Lesions

o Overexpression of platelet-derived growth factor receptor alpha (PDGFR-alpha) o Chromosomal abnormalities: Gain of 7q; 8q amplification; LOH lOp, 22q; chromosome 6 deletions o Recent cases in patients with inherited multiple enchondromatosis type 1 (Ollier disease) • Etiology: Arise from differentiated astrocytes or astrocytic precursor cells • Epidemiology o Represents 25-30% of gliomas in adults o 10-15% of all astrocytomas o 2nd most common astrocytoma of childhood (pilocytic is 1st) o Approximately 1.4 new cases per million/year

Gross Pathologic & Surgical Features • Enlargement, distortion of invaded structures • Diffusely infiltrating mass with blurring of GM/WM interface • May appear grossly circumscribed but diffusely infiltrates adjacent brain • Occasional cysts, Ca++

Microscopic Features

10

• Well differentiated fibrillary or gemistocytic neoplastic astrocytes • Background of loosely structured, often microcystic tumor matrix • Moderately increased cellularity • Occasional nuclear atypia • Mitotic activity generally absent or very rare • No microvascular proliferation or necrosis • Histologic variants o Fibrillary (most frequent) o Gemistocytic (most likely to progress to AA, GBM) o Protoplasmic (rare) • MIB-1, a proliferation index, is low « 4%) • Immunohistochemistry: GFAP +

Staging, Grading or Classification Criteria • WHO grade II

Presentation • Most common signs/symptoms o Seizures, increased intracranial pressure o Other signs/symptoms: Varies with tumor location • Seizure, focal neurologic deficit, behavior changes

Demographics • Age o Majority occur between ages of 20-45 years o Occur at all ages, mean age: 34 years • Gender: Slight male predominance

Natural History & Prognosis • Patients rarely succumb to spread of low grade tumor • Inherent tendency for malignant progression to AA = major cause of mortality • Recurrent disease associated with dedifferentiation in 50-75% cases

• Median survival 6-10 years • Malignant progression tends to occur after a mean time interval of 4-5 years • Increased survival: Young age, gross total resection • Radiation therapy in patients with subtotal resection improves survival • Prognosis worse for pontine, better for medullary (especially dorsally exophytic) tumors

Treatment • Resection, +/- chemotherapy,

XRT

Consider • Acute/subacute ischemia may mimic low grade astrocytomas, history and follow-up imaging often helpful • Low grade astrocytoma may be indistinguishable from other tumors including AA, oligodendroglioma

Image Interpretation

Pearls

• T2 hyperintense expansile mass largely confined to WM? Think low grade astrocytoma!

1.

Wessels PH et al: lOq25.3 (DMBTl) copy number changes in astrocytoma grades II and IV. Genes Chromosomes Cancer 39:22-8, 2004 2. Vuori K et al: Low-grade gliomas and focal cortical developmental malformations: differentiation with proton MR spectroscopy. Radiology 230:703-8, 2004 3. Plathow C et al: Fractionated stereotactic radiotherapy in low-grade astrocytomas: long-term outcome and prognostic factors. lnt J Radiat Oncol Bioi Phys. 57(4):996-1003,2003 4. Kuznetsov YE et al: Proton magnetic resonance spectroscopic imaging can predict length of survival in patients with supratentorial gliomas. Neurosurgery. 53(3):565-76, 2003 5. Hara T et al: Use of 18F-choline and llC-choline as contrast agents in positron emission tomography imaging-guided stereotactic biopsy sampling of gliomas. J Neurosurg. 99(3):474-9, 2003 6. Wessels PH et al: Supratentorial grade II astrocytoma: biological features and clinical course. Lancet Neurol. 2(7):395-403, 2003 7. Hanzely Z et al: Role of early radiotherapy in the treatment of supratentorial WHO Grade II astrocytomas: long-term results of 97 patients. J Neurooncol. 63(3):305-12, 2003 8. Burger PC et al: Surgical pathology of the nervous system and its coverings: The Brain: Tumors. 4th ed. Philadelphia, Churchill Livingstone. 160-77,2002 9. Henderson KH et al: Randomized trials of radiation therapy in adult low-grade gliomas. Semin Radiat Oncol. 11(2):145-51,2001 10. Kleihues P et al: Pathology and genetics of tumours of the nervous system: Diffuse astrocytoma. Lyon, IARC Press, 22-6,2000 11. Castillo M et al: Correlation of Myo-inositollevels and grading of cerebral astrocytomas. AJNR 21:1645,2000 12. Knopp EA et al: Glial neoplasms: Dynamic contrast-enhanced T2*-weighted MR imaging. Radiology 211:791-8, 1999

Neoplasms and Tumorlike Lesions

Typical (Left) Axial T1 WI MR shows a focal homogeneous hypointense mass in the left parietal lobe (arrow) with minimal mass effect. No enhancement was seen after contrast, typical of low grade astrocytomas. (Right) Axial FLAIR MR shows a focal hyperintense mass in the left parietal lobe, predominantly in white matter with mild gray matter involvement. 30 year old male with headaches. Low grade astrocytoma.

Typical (Left) Axial T2WI MR shows a diffuse hyperintense white matter frontal lobe mass with central hyperintensity, suggesting cystic change. Note infiltrative margins and cortical involvement. (Right) Axial T1 C + M R shows no enhancement of the frontal lobe mass, characteristic of a low grade astrocytoma. There is low signal present (arrow) which may represent cystic change, an uncommon feature.

Typical (Left) Axial FLAIR MR shows a heterogeneous hyperintense mass with infiltrative margins and mild mass effect. Partially resected low grade astrocytoma, grade II. 38 year old male with progressive symptoms. (Right) Axial T1 C+ MR shows heterogeneous enhancement of the mass suggesting malignant progression of this low grade astrocytoma. Anaplastic astrocytoma diagnosed at repeat resection.

Neoplasms and Tumorlike Lesions

11

Sagittal graphic shows diffuse brainstem involvement by intrinsic pontine glioma (fibrillary astrocytoma). BA (axial insert, open arrow) is engulfed, pontomedullary notch is effaced (arrow).

Abbreviations

and Synonyms

• Brainstem glioma (BSG) o Tectal glioma (tectal) o Focal tegmental mesencephalic (FTM) o Diffuse (intrinsic) pontine glioma (DPG) o Pilocytic astrocytoma (PA) o Fibrillary astrocytoma (FA)

Definitions • Heterogeneous group of focal or diffuse gliomas involving mesencephalon, pons, or medulla 12

General Features • Best diagnostic clue o Classic imaging appearance varies with tumor type and location • Tectal: Pilocytic, focal, variable enhancement/Ca++ • FTM: Pilocytic, cyst plus nodule • DPG: Fibrillary, diffuse, nonenhancing • Location o All BSG are not equal! Geography predict prognosis

Aqueductal Stenosis

Alexander Disease

Neoplasms

Sagittal T2WI MR shows diffuse swelling and increased signal intensity in an intrinsic pontine glioma. Note lack of hydrocephalus. Fibrillary astrocytoma, WHO grade II.

• Tectal: Indolent course, most only need CSF diversion • FTM: Surgery, radiation, or chemo; do well • DPG: Most are infiltrative ~ poor survival despite chemo-, XRT • Size o Tectal: Even small tectal gliomas will obstruct aqueduct, cause early hydrocephalus o DPG: Often large when present, hydrocephalus occurs late • Morphology o Borders/margins predictive of prognosis • Focal: Long clinical prodrome; good prognosis • Infiltrative: Symptoms < 6 months; poor prognosis o Tectal: Variable signal mass expands tectal plate o FTM: Comma-shaped, extends along cerebral crus to thalamus o DPG: Nonenhancing mass markedly expands pons; engulfs basilar artery

Radiographic Findings • Radiography: Split sutures if hydrocephalus

CT Findings • NECT o Tectal: Hazy increased density over time; hydrocephalus common o FTM: Low attenuation; cyst with mural nodule

NFl Brainstem FASI

and Tumorlike Lesions

NFl FASI

PEDIATRIC BRAINSTEM GLIOMA Key Facts Terminology

Top Differential

• • • •

• • • •

Tectal glioma (tectal) Focal tegmental mesencephalic (FTM) Diffuse (intrinsic) pontine glioma (DPG) Heterogeneous group of focal or diffuse gliomas involving mesencephalon, pons, or medulla

Imaging Findings • Classic imaging appearance varies with tumor type and location . • Tectal: Pilocytic, focal, variable enhancement/Ca++ • FTM: Pilocytic, cyst plus nodule • DPG: Fibrillary, diffuse, nonenhancing • All BSG are not equal! Geography predict prognosis • Borders/margins predictive of prognosis

o DPG: Decreased density; Ca++ rare; hydrocephalus only 10% at presentation • CECT o Tectal • Variable enhancement: t As slowly t density and t Ca++ o FTM • Cyst plus brightly enhancing variable sized nodule, clean margins o DPG: Variable enhancement • Exophytic component» intrinsic pons • Increased enhancement/necrosis over time • Worse prognosis if enhancement present at initial diagnosis

MR Findings • TlWI o Tectal: High signal (Ca++) o FTM & DPG: Low signal • T2WI o All are variably hyperintense o Tectal: High signal T2; minority isointense • Expands tectum; obstructs aqueduct early • Remains focal: Tectum/tegmental; (+/-) cerebral peduncles, thalami o FTM: High signal T2; expands cerebral peduncle o DPG: High signal T2; expands pons; obstructs but does not invade 4th V; engulfs basilar artery • FLAIR: High signal • T2* GRE: Tectal: Hazy calcification, may extend up crura to thalami • T1 C+: Variable enhancement • MRS o NAA levels higher in DPG with NFl than without • Pediatric NFl associated with less malignant course

Imaging Recommendations • Best imaging tool: MRI with contrast • Protocol advice: Include thin sagittal T2 for tectal, DPG

Diagnoses

Congenital aqueductal stenosis vs tectal glioma Alexander disease vs tectal glioma Neurofibromatosis type 1 vs DPG Other brainstem gliomas

Pathology • General path comments: No metastases outside CNS • Epidemiology: 10-20% pediatric brain tumors

Diagnostic Checklist • Not all expansile brainstem lesions are neoplasms • Geography predicts prognosis

I DIFFERENTIAL

DIAGNOSIS

Congenital aqueductal stenosis vs tectal glioma • Aqueduct "funnel-shaped"

on sagittal imaging

Alexander disease vs tectal glioma • Metabolic: Enhancing Alexander disease

Rosenthal fibers obstruct in

Brainstem encephalitis vs DPG • More acute clinical course • Febrile, recovery

6

ADEM vs DPG • ADEM: Other CNS demyelinating upper respiratory infection

Granuloma • Granuloma

foci; preceding

(TB) vs DPe (TB): May simulate focal pontine glioma

Neurofibromatosis

type 1 vs DPG

• Neurofibromatosis type 1: Brainstem hamartoma o Other focal areas of signal intensity (FASI) on T2

Histiocytosis vs DPG • Hypothalamic/infundibular • Diabetes insipidus • Strong contrast-enhancement

involvement

common

Other brainstem gliomas • Dorsal exophytic medullary gliomas: Fungate into (and obstruct) 4th ventricle, have better prognosis • Cranial nerve root entry zone CPA gliomas: Fill CPA • Intrinsic medullary gliomas or gangliogliomas: Expand medulla, extend to and may involve inferior pons

I PATHOLOGY General Features • General path comments: No metastases outside CNS • Genetics o Fibrillary (not pilocytic)

Neoplasms and Tumorlike Lesions

13

• Mutations p53 (tumor suppressor gene) 30-70% DPG • Inactivation p53 ~ Poor outcome o Tectal and DPG associated with Nfl • Tectal: Better prognosis with NFl • DPG children: Better prognosis with NFl than without NFl • DPG adults: Worse prognosis with Nfl than without Nfl • Etiology o Progression to higher grade gliomas associated with • Inactivation of tumor suppressor gene (p53) • Loss of heterozygosity (LOH) chromasomes 10, 17p • Epidemiology: 10-20% pediatric brain tumors

Treatment • Tectal o CSF diversion only o 80% 5 year progression free survival o Progression or dissemination EXTREMELYRARE • FTM: Resect, +/- chemo or radiotherapy, do well • DPG: Experimental chemotherapy; XRT o Child: Poor, median survival < 1 yrs despite TX o Adult: Better, median survival 7 yrs

Gross Pathologic & Surgical Features

Consider

• Tectal: Grayish, ill-defined mass, same consistency as gliotic WM o Obstructs aqueduct of Sylvius • FTM: Involves cerebral peduncle between thalamus and upper pons • DPG: "Hypertrophied," swollen pons o Diffuse tumor infiltration ventral pons o Caudal/cranial extent along fiber tracts

• Not all expansile brains tern lesions are neoplasms

Image Interpretation

• Pilocytic: Alternating spongy, compact cellular areas o Spongy areas: Astrocytes outline microcysts o Compact regions: Bipolar cells with Rosenthal fibers • Fibrillary o Increased cellularity/mitotic activity o Pleomorphism/nuclear atypia o Necrosis o Endothelial proliferation

2.

3. 4. 5.

Staging, Grading or Classification Criteria • Pilocytic: WHO I • Fibrillary: WHO II-IV

6.

7.

Presentation • Most common signs/symptoms o Tectal: Macrocrania; headache o FTM: Hemiparesis o DPG • Multiple cranial nerve palsies • Nausea and vomiting • Headache • Bulbar signs • Ataxia • Clinical profile: Varies with location of brainstem glioma

8.

9. 10. 11.

12.

Demographics 13.

• Age: Mean age 7 yrs • Gender: M = F

Pearls

• Location, location, location! • Geography predicts prognosis

1.

Microscopic Features

14

• DPG: CSF dissemination; caudal/cranial extension o Dissemination occurs in 50% prior to death

Vuori K et al: Low-grade gliomas and focal cortical developmental malformations: differentiation with proton MR spectroscopy. Radiology 230:703-8,2004 Daglioglu E et al: Tectal gliomas in children: The implications for natural history and management strategy. Pediatr Neurosurg 38(5):223-31, 2003 Cohen KJ et al: Pediatric glial tumors. Cur Treat Options Oncol 2(6):529-36, 2001 Guillamo JS et al: Brainstem gliomas in adults: Prognostic factors and classification. Brain 124(Pt 12):2528-39, 2001 Arnautovic KI et al: Cranial nerve root entry zone primary cerebellopontine angle gliomas: A rare and poorly recognized subset of extraparenchymal tumors. J NeurooncoI49(3):205-12,2000 Fisher PG et al: A clinicopathologic reappraisal of brainstem tumor classification: Identification of pilocytic astrocytoma and fibrillary astrocytoma as distinct entities. Cancer 89(7):1569-76, 2000 Bowers DC et al: Tectal gliomas: Natural history of an indolent lesion in pediatric patients. Pediatr Neurosurg 32(1):24-9,2000 Gavriel H et al: Diffuse intrinsic brainstem disease with neurologic deterioration: Not what it seemed. Medi Pediatr Oncol 34(3):213-4, 2000 Oka K et al: Neuroendoscopic approach to tectal tumors. J Neurosurg 91(6):964-70, 1999 Rubin G et al: Pediatric brain stem gliomas: An update. Child's Nerv Syst 14:167-73, 1998 Donahue B et al: Patterns of recurrence in brain stem gliomas: Evidence for craniospinal dissemination. Int J Radiat Oncol BioI Phs 40(3):677-80, 1998 Broniscer A et al: Brain stem involvement in children with neurofibromatosis type 1: Role of magnetic resonance imaging and spectroscopy in the distinction from diffuse pontine glioma. Neurosurgery 40(2):331-7, 1997 Raffel C. Molecular biology of pediatric gliomas. J Neurooncol 28(2-3):121-8, 1996

Natural History & Prognosis • Tectal: Hydrocephalus; otherwise extremely benign clinical course • FTM: Will progress without therapy

Neoplasms and Tumorlike Lesions

Typical (Left) Axial T2WI MR shows engulfment of basilar artery (open arrow) by pons swollen with intrinsic pontine glioma (fibrillary astrocytoma). (Right) Coronal T7 C+ MR shows pontine expansion by predominantly low T7 signal mass. Minimal focal (arrow) enhancement is present. Note absence of hydrocephalus despite size of mass.

(Left) Axial T7 C+ MR shows

expansion of the mesencephalic tegmentum and cerebral peduncle by a sharply delineated "comma-shaped" cystic mass with enhancing nodule. Pi/ocytic astrocytoma. (Right) Coronal T7 C+ MR in the same case shows expansion into thalamus and displacement and partial obstruction of 3rd ventricle. Tegmental pi/ocytic astrocytoma, WHO grade I.

Typical (Left) Axial NECT shows a bulbous tectum with slight, hazy increased density (arrow). The lateral and third ventricles are obstructed and there is interstitial edema (open arrows). (Right) Sagittal T2WI MR in the same case shows ventricular enlargement. The aqueduct of Sylvius is obstructed by a slightly high signal intensity tectal mass (arrow). Presumed pi/ocytic astrocytoma.

Neoplasms and Tumorlike Lesions

15

Axial graphic shows an infiltrative white matter mass with extension along corpus callosum with focal hemorrhage & mass effect. White matter extension is typical of anaplastic astrocytoma.

Axial FLAIR MR shows an infiltrative frontal lobe white matter mass with extension across the corpus callosum. 43 year old with seizures. Anaplastic astrocytoma, rapidly progressive.

o Neoplastic cells almost always found beyond areas of abnormal signal intensity

Abbreviations

and Synonyms

• Anaplastic astrocytoma (AA), grade III astrocytoma, malignant astrocytoma, high grade astrocytoma

Definitions • Diffusely infiltrating astrocytoma with focal or diffuse anaplasia and a marked proliferative potential

16

CT Findings • NECT o Low density ill-defined mass o Ca++ and hemorrhage rare • CECT o Majority do not enhance o Enhancement often focal, patchy, heterogeneous o If ring enhancement, consider malignant progression to GBM

MR Findings

General Features • Best diagnostic clue o Infiltrating mass that predominately involves white matter (WM) o Variable enhancement, typically none; may be focal or patchy • Location o Hemispheric WM, frontal & temporal lobes common o In children, may involve pons, thalamus o Less commonly involves brains tern, spinal cord • Size: Variable • Morphology o Ill-defined hemispheric WM mass typical o May appear well-circumscribed

• TlWI o Mixed isointense to hypointense WM mass o Ca++, hemorrhage, cysts rare o May involve and expand overlying cortex • T2WI o Heterogeneously hyperintense o May appear discrete, but infiltrates adjacent brain o May involve and expand overlying cortex o Ca++, hemorrhage, cysts rare o Rarely prominent flow voids are present, but suggests progression to GBM • FLAIR o Heterogeneously hyperintense o May appear discrete, but infiltrates adjacent brain • DWI: No diffusion restriction is typical

DDx: Anaplastic Astrocytoma

I~ \ Grade /I Astra

GBM

Cerebritis

Neoplasms and Tumorlike

Lesions

Ischemia

ANAPLASTIC ASTROCYTOMA Key Facts Terminology • Diffusely infiltrating astrocytoma with focal or diffuse anaplasia and a marked proliferative potential

Imaging Findings

• • • •

Ischemia Oligodendroglioma Status epilepticus Herpes encephalitis

Pathology

• Infiltrating mass that predominately involves white matter (WM) • Variable enhancement, typically none; may be focal or patchy • Hemispheric WM, frontal & temporal lobes common • Neoplastic cells almost always found beyond areas of abnormal signal intensity

• AA have histologic and imaging characteristics along spectrum between low grade astrocytoma and GBM • 113 of astrocytomas . • M ete but tumor always infiltrates adjacen • WHO grade III

Top Differential

Clinical Issues

Diagnoses

• Low grade glioma • Glioblastoma multuorme • Cerebritis

• T1

• Median survival 2·3 years • Commonly arise as recurrence after resection of a grade II tumor

(GBM)

c+

o Usually no enhancement o Less common: Focal, nodular, homogeneous, patchy enhancement o Ring enhancement is suspicious for GBM! • MRS o Elevated Cho/Cr ratio, decreased NAA o Lower myo-inositol (MI)/Cr ratio (0.33 +/- 0.16) than low grade (diffuse) astrocytoma • Dynamic contrast-enhanced T2* weighted imaging o Elevated maximum rCBV compared to low grade astrocytoma o Increased permeability compared to low grade astrocytoma • Diffusion tensor imaging (DTI) of white matter tracts may help surgical planning in future

Nuclear Medicine

Findings

• PET o Higher metabolism than low grade astrocytomas o FDG shows high grade gliomas have uptake similar to or exceeding normal grey matter o Tumor/WM> 1.5 and tumor/GM > 0.6 suggests high grade tumors o FDG has sensitivity of 81-86%, specificity of 50-94% in differentiation of recurrent tumor from radiation brain injury

Imaging Recommendations • Best imaging tool: MR is most sensitive • Protocol advice o Contrast-enhanced MR o MRS and T2* weighted imaging may be helpful

Glioblastoma

multiforme

(GBM)

• 95% necrotic core, enhancing rim • Extensive surrounding T2/FLAIR signal • Hemorrhage not uncommon

Cerebritis • T2 hyperintensity and patchy enhancement • Diffusion restriction typical

Ischemia • • • •

Vascular territory (MCA, ACA, PCA) Restricted diffusion if acute/subacute Often wedge-shaped, involves GM & WM Gyriform enhancement in subacute ischemia

6

Oligodendroglioma

17

• Cortical mass with variable enhancement • Ca++ common • May be indistinguishable

Status epilepticus • Active seizures may cause signal abnormalities enhancement • History of seizures • Follow-up imaging may be necessary

and

Herpes encephalitis • Confined to limbic system, temporal lobes • Blood products and enhancement common • Typically acute onset

I PATIHOlOG't General Features

I DIFFERENTIAL DIAGNOSIS Low grade glioma • Focal or diffuse white matter mass • Typically non enhancing hemispheric mass • May be indistinguishable without biopsy

• General path comments o Biologically aggressive astrocytoma characterized by cytologic atypia and mitotic activity o AA have histologic and imaging characteristics along spectrum between low grade astrocytoma and GBM o Intrinsic tendency for progression to GBM o May have oligodendroglioma components, anaplastic oligoastrocytoma

Neoplasms and Tumorlike

Lesions

• Genetics o High frequency of TP53 mutations (> 70%) o Abnormal cell cycle regulatory genes o p16 deletion, RB alterations, p19ARF deletion, CDK4 amplification reported o PTEN/MMAC1 mutations reported o Loss of heterozygosity: Chromosome 10q, 19q, 22q o Deletion of chromosome 6 (30%) • Etiology o Usually evolves from low grade (diffuse) astrocytoma (WHO grade II), approximately 75% o Evidence that progression from low grade to AA is associated with multiple genetic alterations o Occasionally arises de novo o Derived from differentiated astrocytes or precursor cells committed to astrocytic differentiation • Epidemiology o 1/3 of astrocytomas o 25% of gliomas o Diffusely infiltrating gliomas including WHO grades II, III, IV account for > 60% of all primary tumors

Gross Pathologic & Surgical Features • Infiltrating mass with poorly delineated margins • Often expands invaded structures • May appear discrete but tumor always infiltrates adjacent brain • Cysts, hemorrhage uncommon

Microscopic

18

• Commonly arise as recurrence after resection of a grade II tumor • Progression to secondary GBM common o 2 years is typical time for progression • Spreads along white matter tracts commonly o May spread along ependyma, leptomeninges and CSF • Increased survival: Younger age, high Karnofsky score, gross total resection • Other factors associated with longer survival o Absence of ring enhancement, proliferation index of 5.1 % or lower, oligodendroglial component

Treatment • Resection and radiation therapy, +/- chemotherapy

Consider • AA may mimic other tumors, particularly diffuse low grade astrocytomas • Non-neoplastic mimics such as cerebritis may be differentiated with help of clinical history

Image Interpretation

Pearls

• AA are typically non enhancing hemispheric masses • If new areas of enhancement are seen, malignant degeneration is likely

Features

• Characterized by increased cellularity, marked mitotic activity, distinct nuclear atypia • High nuclear/cytoplasmic ratio • Nuclear/cytoplasmic pleomorphism • Coarse nuclear chromatin • No necrosis or microvascular proliferation • Immunohistochemistry: GFAP+ common • MIB-1: 5-10% (proliferation index)

Staging, Grading or Classification Criteria • WHO grade III • Intermediate between low grade (diffuse) astrocytoma (WHO grade II), GBM (grade IV)

Presentation • Most common signs/symptoms o Acceleration in clinical deterioration in a patient with low grade (diffuse) astrocytoma o Varies with location • Seizures, focal neurologic deficit common • May have headache, drowsiness, vomiting • Increased intracranial pressure • Personality or behavioral changes

Demographics • Age: Occurs at all ages, most common • Gender: M:F = 1.8:1

Natural History & Prognosis

40-50 years

1.

Jellison BJ et al: Diffusion tensor imaging of ceredral white matter: a pictorial review of physics. Fiber tract anatomy, and tumor imaging patterns. AJNR 25:356-69,2004 2. Tortosa A et al: Prognostic implication of clinical, radiologic, and pathologic features in patients with anaplastic gliomas. Cancer. 97(4): 1063-71,2003 3. Mori S et al: Brain white matter anatomy of tumor patients evaluated with diffusion tensor imaging. Ann Neurol. 51(3): 377-80, 2002 4. Provenzale JM et al: Comparison of permeability in high-grade and low-grade brain tumors using dynamic susceptibility contrast MR imaging. AJR 178:711-6, 2002 5. Nelson SJ et al: Characterization of untreated gliomas by magnetic resonance spectroscopic imaging. Neuroimag Clin N Am 12:599-613, 2002 6. Wong TZ et al: Positron emission tomography imaging of brain tumors. Neuroimag Clin N Am 12:615-26, 2002 7. Burger PC et al: Surgical pathology of the nervous system and its coverings: The Brain: Tumors. 4th ed. Philadelphia, Churchill Livingstone. 177-80, 2002 8. Ironside JW et al: Diagnostic pathology of nervous system tumours: Astrocytic tumors. 1st ed. Edinburgh, Churchill Livingstone, 53-120, 2002 9. Wild-Bode C et al: Molecular determinants of glioma cell migration and invasion. J Neurosurg 94: 978-84, 2001 10. Castillo M et al: Correlation of Myo-inositollevels and grading of cerebral astrocytomas. AJNR 21:1645,2000 11. Kleihues P et al: Pathology and genetics of tumours of the nervous system: Anaplastic astrocytoma. Lyon, IARC Press, 27-8,2000 12. Rutherfood GS et al: Contrast enhanced imaging is critical to glioma nosology and grading. I]NR 1: 28-38, 1995

• Median survival 2-3 years

Neoplasms and Tumorlike Lesions

Typical (Left) Axial TlWI MR shows a hypointense infiltrative

mass in the left temporal region with mild mass effect for size of lesion. No enhancement was seen after contrast, typical of anaplastic astrocytoma. (Right) Axial T2WI MR shows a hyperintense temporal mass centered in white matter. Although the mass appears discrete, tumor cells often extend beyond the abnormal signal. 34 year old male, seizures. AA.

Typical (Left) Axial FLAIRMR shows a focal mass involving the left temporal white matter and overlying cortex with minimal mass effect. Young adult male with temporal lobe epilepsy. (Right) Axial Tl C+ MR shows moderate enhancement of the anterior portion of the temporal lobe mass. Enhancement is typically absent in anaplastic astrocytomas. Despite therapy. tumor progressed to CBM.

Variant (Left) Axial T2WI MR shows

heterogeneous frontal mass with hypointense signal related to acute blood products. Surrounding hyperintensity (arrow) may represent edema or tumor cells. 50 year old with AA. (Right) Axial Tl C+ MR shows peripheral enhancement of the frontal lobe mass. This pattern of enhancement suggests CBM rather than AA. Hemorrhagic anaplastic astrocytoma at resection.

Neoplasms and Tumorlike Lesions

6 19

Axial graphic shows a centrally necrotic infiltrating mass with extension across the corpus callosum. There is a peripheral rind of tumor surrounding the necrotic core, typical of GBM.

Abbreviations

and Synonyms

• Glioblastoma multiforme (GBM), glioblastoma, IV astrocytoma, malignant astrocytoma

grade

Definitions • Rapidly enlarging malignant astrocytic tumor characterized by necrosis and neovascularity • Most common of all primary intracranial neoplasms

20

General Features • Best diagnostic clue: Thick, irregular-enhancing rind of neoplastic tissue surrounding necrotic core • Location o Supratentorial white matter most common • Frontal, temporal, parietal lobes • Occipital lobes relatively spared o Cerebral hemispheres> brainstem > cerebellum o Brainstem, cerebellum more common in children • Size: Variable • Morphology o Poorly-marginated, diffusely-infiltrating necrotic hemispheric mass

DDx: Supratentorial

Abscess

Axial TlWI MR shows a hemorrhagic mass crossing the corpus callosum, a "butterfly glioma." Note involvement of both frontal lobes with extension across white matter tracts, typical of GBM.

o Tumor typically crosses white matter tracts to involve contralateral hemisphere • Corpus callosum ("butterfly glioma") • Anterior and posterior commissures o May invade meninges (rarely) o Rarely may be multifocal, multicentric

CT Findings • NECT o Irregular isodense or hypodense mass with central hypodensity representing necrosis o Marked mass effect and surrounding edema/tumor infiltration o Hemorrhage not uncommon o Ca++ rare (related to low grade tumor degeneration) • CECT: 95% have strong, heterogeneous, irregular rim-enhancement

MR Findings • TlWI o Irregular isointense, hypointense white matter mass o Necrosis, cysts and thick irregular margin common o May have subacute hemorrhage • T2WI o Heterogeneous, hyperintense mass with adjacent tumor infiltration/vasogenic edema o Viable tumor extends far beyond signal changes! o Necrosis, cysts, hemorrhage, fluid/debris levels, flow voids (neovascularity) may be seen

Enhancing Mass

eNS Lymphoma

Tumefactive

MS

Neoplasms and Tumorlike Lesions

Hemorrhagic

AVM

GLIOBLASTOMA MULllFORME Key Facts Terminology

Pathology

• Rapidly enlarging malignant astrocytic tumor characterized by necrosis and neovascularity • Most common of all primary intracranial neoplasms

• Two types, primary (de novo) and secondary (degeneration from lower grade astrocytoma) • 50-600/0 of astrocytomas • WHO grade IV

Imaging Findings • Best diagnostic due: Thick, irregular-enhancing of neoplastic tissue surrounding necrotic core

rind

Top Differential Diagnoses • • • • • • •

Abscess Metastasis Primary CNS lymphoma Anaplastic astrocytoma (AA) "Tumefactive" demyelination Subacute ischemia Status epilepticus

Clinical Issues • Age: Peak 45- 70 years but may occur at any age • Relentless progression • Prognosis is dismal (death in 9-12 months)

Diagnostic Checklist • Viable tumor extends far beyond signal abnormalities!

• FLAIR: Heterogeneous, hyperintense mass with adjacent tumor infiltration/vasogenic edema • T2* GRE: Susceptibility artifact on T2* common related to blood products • DWI o Lower measured ADC than low grade gliomas o No diffusion restriction typical • T1 C+

o Thick, irregular rind of enhancement surrounding central necrosis typical o Enhancement may be solid, ring, nodular or patchy • MRS o Decreased NAA, myo-inositol o Elevated choline, lactate/lipid peak (1.33 ppm) • Dynamic contrast-enhanced T2* weighted imaging o Elevated maximum rCBV compared to low grade o Increased permeability compared to low grade tumors, may help assess tumor grade • Diffusion tensor imaging (DTI) of white matter tracts may help surgical planning in future

Angiographic Findings • Conventional o DSA: Hypervascular mass, prominent tumor blush • A-V shunting and early draining veins common • Rarely may mimic an AVM

Nuclear Medicine Findings • PET o Malignant tumors have high glucose metabolism and avidly accumulate FDG, uptake similar to or exceeding gray matter o Tumor/WM > 1.5 and tumor/GM > 0.6 suggests high-grade tumors

[DIFFERENTIAL DIAGNOSIS Abscess • Ring-enhancement typically thinner than GBM • T2 hypointense rim, diffusion restriction + typical • MRS may show metabolites such as succinate, amino acids

Metastasis • • • •

Typically multiple lesions at gray-white junctions Round> infiltrating lesion Primary tumor often known Single lesion may be indistinguishable

Primary CNS lymphoma • • • •

Periventricular enhancing mass Often crosses corpus callosum Typically isointense/hypointense on T2WI Necrosis common in AIDS related lymphoma

Anaplastic astrocytoma (AA) • Often nonenhancing white matter mass • Enhancement may indicate degeneration • May be indistinguishable

to GBM

"Tumefactive" demyelination • Often incomplete, "horseshoe-shaped" enhancement, open towards cortex • Lesions in typicallocationsi younger patients

Subacute ischemia • Typical vascular territory (MCA, PCA, ACA) • May have mass effect and enhancement (gyriform) • Follow-up imaging may be helpful to differentiate

Status epilepticus

Imaging Recommendations • Best imaging tool o MR is most sensitive o Newer techniques are being developed to improve diagnosis and biopsy accuracy: MRS, T2* imaging, perfusion, hypoxia imaging, PET, DTI • Protocol advice: Contrast-enhanced MRi MRS, DWI may be helpful

• Active seizures may cause signal abnormality and enhancement • Enhancement often diffuse, affecting GM and WM • Clinical history of seizures

Arteriovenous malformation

(AVM)

• Multiple flow voids with minimal mass effect • If associated with hemorrhage, may mimic GBM

Neoplasms and Tumorlike

Lesions

6 21

22

General Features

Presentation

• General path comments o Two types, primary (de novo) and secondary (degeneration from lower grade astrocytoma) • Genetically distinct, same appearance o Giant cell glioblastoma, a histologic variant of GBM (5%), slightly improved prognosis • Genetics o Primary GBM (de novo) • Older patients, biologically more aggressive • Develops de novo (without pre-existing lower grade tumor) • Amplification, overexpression of EGFR, MDM2 • PTEN mutation • Chromosome lOp loss of heterozygosity (LOH) o Secondary GBM (degeneration from lower grade) • Younger patients, less aggressive than primary GBM • Develops from lower grade astrocytoma • TP53 mutations • PDGFR amplification, overexpression • Chromosomes 109, 17p LOH • Increased telomerase activity and hTERT expression o Occurs sporadically or as part of heritable tumor syndrome • NFl, Li-Fraumeni syndrome (p53 mutation) • Turcot syndrome, Ollier disease, Maffucci syndrome • Etiology o Spreads by creating "permissive environment" • Produces proteases • Deposits extracellular matrix (ECM) molecules • Expresses integrins (neoangiogenesis, cellular invasion) • Neoplastic cells adhere to ECM, detach, migrate, proliferate o Rare cases related to irradiation • Epidemiology o Most common primary brain tumor o Approximately 12-15% of all intracranial neoplasms o 50-60% of astrocytomas o Multifocal in up to 20% (2-5% synchronous independent tumors)

• Most common signs/symptoms o Varies with location: Seizures, focal neurologic deficits common o Increased intracranial pressure, mental change o Typically short duration of symptoms

Demographics • Age: Peak 45-70 years but may occur at any age • Gender: Male predominance, M:F = 3:2

Natural History & Prognosis • Relentless progression • Prognosis is dismal (death in 9-12 months) • Patterns of dissemination o Most common: Along white matter tracts, perivascular spaces o Less common: Ependymal/subpial spread, CSF metastases o Uncommon: Dural/skull invasion o Rare: Extraneural spread (lung, liver, nodes, bone) • Independent predictors of longer survival o Age (younger), Karnofsky Performance Scale (higher), extent of resection (gross total vs subtotal) o Degree of necrosis, enhancement on pre-op MR

Treatment • Biopsy/tumor

Consider • Corpus callosum involvement may be seen in GBM, lymphoma, and rarely metastases, demyelination

Image Interpretation

1.

2. 3.

• Reddish-gray "rind" of tumor surrounds necrotic core o Necrosis is the hallmark of GBM • Most GBMs have marked vascularity, +/- gross hemorrhage

4.

5.

Features

• Necrosis, microvascular proliferation hallmarks • Pleomorphic astrocytes, marked nuclear atypia, numerous mitoses • GFAP + but low expression • High MIB-1 (proliferation index), ranges from 9-31 %

Pearls

• Viable tumor extends far beyond signal abnormalities!

Gross Pathologic & Surgical Features

Microscopic

debulking followed by XRT, chemo

6. 7.

Fan G et al: In vivo single voxel proton MR spectroscopy in the differentiation of high-grade gliomas and solitary metastases. Clin Radiol. 59:77-85, 2004 Maldarin MV et al: Cystic glioblastoma multiforme: survival outcomes in 22 cases. J Neurosurg. 100:61-7, 2004 Provenzale JM et al: Comparison of permeability in high-grade and low-grade brain tumors using dynamic susceptibility contrast MR imaging. AJR 178:711-6, 2002 Ludemann L et al: Comparison of dynamic contrast-enhanced MRI with WHO tumor grading for gliomas. Eur Radiolll:1231-41, 2001 Lacroix M et al: A multivariate analysis of 416 patients with GBM: Prognosis, extent of resection, and survival. J Neurosurg. 95:190-8, 2001 Castillo M et al: Correlation of Myo-inositollevels and grading of cerebral astrocytomas. AJNR21:1645, 2000 Kleihues P et al: Pathology and genetics of tumours of the nervous system: Glioblastoma. Lyon, IARC Press, 29-41, 2000

Staging, Grading or Classification Criteria • WHO grade IV

Neoplasms and Tumorlike Lesions

Typical

.,

.

'

..•... "

~w ~~

'-

,

,~~

~.;

, f

,

(Left) Axial T2WI MR shows a heterogeneous hyperintense mass with central necrosis and surrounding signal abnormality likely related to tumor extension and edema. Typical imaging of GBM. (Right) Axial T7 C+ MR shows peripheral enhancement with central necrosis and extension across the splenium of the corpus callosum, characteristic of GBM. 60 year old with acute onset of seizures.

Typical (Left) Axial CECT shows a peripherally enhancing, centrally necrotic mass with surrounding mass effect and midline shift. There is uncal herniation and early entrapment of the ventricular system. GBM. (Right) Single voxel MRS shows elevated Cho and decreased NAA. Note the lactate doublet at 1.33 (arrow), typical of high grade tumors. Patient with a history of AA that progressed to GBM.

Variant (Left) Axial T7 C+ MR shows two separate areas of enhancement representing multifocal GBM. (Right) Axial PO/intermediate MR in another case shows hyperintense periventricular signal (diffuse ependymal spread of GBM) (Courtesy i. Tarwal, MO).

Neoplasms and Tumorlike Lesions

6 23

Coronal graphic shows a peripherally located heterogeneous, necrotic mass with invasion of dura and adjacent skull, typical of gliosarcoma. Infiltrative tumor involves corpus callosum.

Coronal T1 c+ MR shows a heterogeneously enhancing mass with dural invasion and possible skull involvement (open arrow). Note significant mass effect and midline shift.

MR Findings Definitions • Rare malignant neoplasm with both glial, mesenchymal elements

General Features

24

• Best diagnostic clue o Heterogeneously enhancing mass with dural invasion, +/- skull involvement o May be indistinguishable from GBM • Location o Cerebral hemispheres o Temporal> parietal> frontal> occipital lobes • Size: Variable, typically 3-8 cm • Morphology: Infiltrating mass, may have a discrete portion

• Tl WI: Heterogeneous, hypointense mass • T2WI o Heterogeneous mass related to hemorrhage, o Marked surrounding edema • Tl C+ o Heterogeneous, thick irregular enhancement central necrosis o May see dural involvement

• NECT o Heterogeneous mass with surrounding edema o Hemorrhage may be seen • CECT o Heterogeneous, thick irregular enhancement o May see dural involvement

• Pial and parenchymal

vascular supply to tumor

Imaging Recommendations • Protocol advice: Multiplanar

Glioblastoma

multiforme

contrast-enhanced

(GBM) necrosis

Metastasis • Multiple lesions common; primary often known

Abscess • Ring-enhancing • T2 hyperintense

lesion with central necrosis rim and DWI + typical

DDx: Peripherally Located Enhancing Masses

GBM

Metastasis

Neonlasms

with

Angiographic Findings

• Typically indistinguishable • Heterogeneous mass with hemorrhage,

CT Findings

necrosis

Abscess

ana TLJmorlikfl Iflsions

Hemangiopericytoma

MR

GLIOSARCOMA

Hemangiopericytoma

Natural History & Prognosis

• Extra-axial mass with dural and skull invasion

• Poor prognosis, median survival of 6-12 months • Local recurrence typical • Extracranial metastases common, 15-30%

Malignant

meningioma

• Extra-axial mass with parenchymal

invasion

Treatment • Surgery followed by adjuvant radiation, +/chemotherapy

Ip}\G]mm(;mm~ General Features • General path comments o Sarcomatous features often resemble fibrosarcoma or malignant fibrous histiocytoma o Cartilage, smooth and striated muscle, bone, and chondroid elements have been reported • Genetics: Similar to GBM • Etiology o Sarcomatous elements thought to arise from transformed vascular elements within a GBM o Some reports 'Suggest irradiation induces sarcomatous change in GBM • Epidemiology: Rare, account for 2-8% of GBM

I DIAGNOSTIC Consider

• Gliosarcomas may mimic GBM and metastases

Image Interpretation

ISELECTED REFERENCES 1.

• At surgery, may mimic a metastasis or meningioma • Firm, lobular mass with central necrosis • Often meningeal invasion

2.

Features

• Malignant glial and mesenchymal elements • Glial portion: Anaplasia, neovascularity, necrosis • Sarcomatous portion: Spindle cells with reticulin network, nuclear atypia, mitotic activity, necrosis

Pearls

• Peripherally located mass with dural invasion, think gliosarcoma • Tumor cells extend beyond enhancing mass

Gross Pathologic & Surgical Features

Microscopic

CHECKLIST

3.

Lutterbach] et al: Gliosarcoma: a clinical study. Radiotherapy and Oncology. 61:57-64, 2001 Ohgaki H et al: Pathology and genetics of tumours of the nervous system: Gliosarcoma. Lyon, IARC Press, 42-4, 2000 Perry]R et al: Clinicopathologic features of primary and postirradiation cerebral gliosarcoma. Cancer. 75:2910-8, 1995

IIMAGE GAllER~

Staging, Grading or Classification Criteria • WHO grade IV

I CLINICAL

ISSUES

Presentation • Most common signs/symptoms: Increased intracranial pressure: Headache • Other signs/symptoms o Related to location: Seizure, focal neuro deficit (Left) Axial T2WI MR shows a peripherally located temporal lobe

Demographics • Age: Typically sixth to seventh decade • Gender: Male predominance, M:F = 1.6:1

mass with heterogeneity, surrounding T2 hyperintensity and significant mass effect. 45 year old male with headaches. Cliosarcoma. (Right) Axial T1 C+ MR shows heterogeneous, thick irregular enhancement with central necrosis, typical of gliosarcoma. Imaging appearance often indistinguishable from CBM.

Neoplasms and Tumorlike Lesions

6 25

Axial graphic shows an infiltrating tumor involving both frontal lobes and basal ganglia with preservation of underlying cerebral architecture. Note focal malignant degeneration (arrow).

Axial T2WI MR shows diffuse hyperintensity extending through the white matter of the frontal and temporal lobes, basal ganglia and splenium of the corpus callosum. Gliomatosis cerebri.

• Morphology: Infiltrates, enlarges yet preserves underlying brain architecture

Abbreviations

and Synonyms

CT Findings

• Gliomatosis cerebri (GC), gliomatosis, gliomatosis

diffuse cerebral

Definitions • Diffusely infiltrating glial tumor involving two or more lobes, frequently bilateral • Infiltrative extent of tumor is out of proportion to histologic and clinical features

26

• NECT o Poorly defined, asymmetric low density (may be subtle) o Loss of gray-white differentiation with expansion and mild mass effect o May be normal in some cases • CECT o No enhancement typical o Enhancement may indicate malignant progression or a focus of malignant glioma

MR Findings

General Features • Best diagnostic clue: T2 hyperintense infiltrating mass with enlargement of involved structures • Location o Typically hemispheric white matter involvement, may also involve cortex (19%) o Two or more lobes, diffuse white matter plus • Basal ganglia, thalami (75%) • Corpus callosum (50%) • Brainstem, spinal cord (10-15%) • Cerebellum (10%) o May cross corpus callosum or massa intermedia

DDx: Infiltrating/Confluent

• T1WI o Isointense or hypointense infiltrating mass o Typically homogeneous • T2WI o Homogeneous hyperintense infiltrating mass o Mass effect with mild diffuse sulcal and ventricular effacement o May cause hydrocephalus (rare) • FLAIR: Homogeneous hyperintense infiltrating mass • DWI: Usually no restriction • T1 C+

o Typically no or minimal enhancement o Patchy enhancement rarely

White Matter lesions

(l ~\ ,

\. Arteriolosclerosis

Vasculitis

Neoplasms and Tumorlike

AA Lesions

I

~

, MLD

'

)

GLIOMATOSIS CEREBRI Key Facts Terminology

Top Differential

• Diffusely infiltrating glial tumor involving two or more lobes, frequently bilateral • Infiltrative extent of tumor is out of proportion to histologic and clinical features

• • • •

Diagnoses

Arteriolosclerosis Anaplastic astrocytoma Viral encephalitis Lymphoma

(AA)

Imaging Findings

Pathology

• Best diagnostic clue: T2 hyperintense infiltrating mass with enlargement of involved structures • Typically hemispheric white matter involvement, may also involve cortex (19%) • May cross corpus callosum or massa intermedia • Morphology: Infiltrates, enlarges yet preserves underlying brain architecture • Typically no or minimal enhancement • Marked elevation of myo-inositol (mI)

• Underlying brain architecture • Usually WHO grade III

o Enhancement may indicate malignant progression or a focus of malignant glioma • MRS o Marked elevation of myo-inositol (mI) o Normal/mildly increased choline (Cho) o Decreased NAA o +/- Lactate, lipid peaks at 1.33 ppm • Dynamic contrast-enhanced T2* weighted MR o Low rCBV which correlates with lack of vascular hyperplasia • Diffusion tensor imaging (DTI) o Early reports show preservation of nerve fibers in GC compared with other tumors

Nuclear Medicine

Findings

• PET: FDG shows marked hypometabolism

Imaging Recommendations • Best imaging tool: MR is most sensitive • Protocol advice o Multiplanar contrast-enhanced MR o MRS and dynamic contrast-enhanced T2* weighted imaging may help further characterize

I [)IFFEREN"'I~I..[)IA(TIN@SIS

preserved

Clinical Issues • Peak incidence between 40-50 years • Poor prognosis

Diagnostic Checklist • Rare diffusely infiltrating glial tumor that can be mistaken for nonneoplastic WM disease

• +/- Meningeal involvement • Herpes involves temporal lobes, limbic system

Demyelination • • • •

Usually multiple lesions in typical locations Typically lack significant mass effect Often enhances, incomplete ring open at cortex May involve white matter and deep gray nuclei (BG, thalami)

Progressive multifocalleukoencephalopathy (PMl) • Asymmetric T2 hyperintensity in periventricular, subcortical white matter • No or minimal enhancement typical • Often parieto-occipital region, may cross corpus callosum • Immunosuppressed patients, typically AIDS

lymphoma

Inherited/acquired

• • • •

• Metachromatic leukodystrophy (MLD): Confluent periventricular WM T2 hyperintensity • Alexander disease: Frontal lobe WM hyperintensity and enhancement

without biopsy

27

• Periventricular/deep GM enhancing mass in primary CNS lymphoma o Corpus callosum involvement classic o Isointense/hypointense on T2WI • Intravascular lymphoma may appear diffusely infiltrating

Arteriolosclerosis Aging brain, microvascular disease No mass effect; spares cortex Often associated volume loss Some cases may be indistinguishable

6

metabolic disorder

Vasculitis • Often multifocal areas of ischemia • Patchy, multifocal enhancement may be seen • May be indistinguishable without biopsy

IPAl'H@I..@(TIY

Anaplastic astrocytoma (M)

• General path comments o Underlying brain architecture preserved o Diffuse neoplastic overgrowth o Extensive tumor infiltration is disproportionate histologic features • No necrosis or neovascularity

• May appear discrete or infiltrating, • Variable enhancement

often less diffuse

Viral encephalitis • More acute presentation,

history may distinguish

General Features

Neoplasms and Tumorlike

lesions

to

o Diagnosis typically nude on basis of histology and imaging • Genetics o Karyotype consistent with clonal neoplasm arising from single cell • Chromosomal changes different from astrocytoma • May belong to separate category of brain tumor • Etiology o Controversial, classified as neoplasm of unknown histogenesis o Shares some, but not all, features of diffusely infiltrating astrocytoma o Rarely oligodendroglioma is predominant cell type • Epidemiology o Rare o Just over 200 reported cases

• Survival ranges from weeks to years o Median survival of 38 months • Karnofsky performance scale 2: 70 correlates with increased survival • Ki-67 labeling index may correlate with survival time • Rarely GC is complicated by hydrocephalus or herniation • Extremely rarely GC is complicated by hemorrhage

Treatment • Stereotaxic biopsy (enhancing nodule, if present) • Poor response to chemotherapy, radiation therapy o Some reports show increased survival with treatment • Steroids may help as initial treatment • Surgical decompression, ventricular shunting occasionally required

Gross Pathologic & Surgical Features • Two gross pathologic GC types recognized o Type I: Neoplastic overgrowth, expansion of existing structures without circumscribed tumor mass o Type II: Diffuse lesion + focal neoplastic mass with malignant features (may develop from type I) • Blurring of gray-white junction borders +/- distinct tumor nodule

Microscopic

28

Features

• Neuroepithelial neoplasm with diffuse invasion of parenchyma with tumor cells • Elongated glial cells with hyperchromatic nuclei, variable mitoses • Neoplastic cells often arranged in parallel rows • Diffuse infiltration along, between myelinated nerve fibers • Microvascular proliferation, necrosis usually absent • Immunohistochemistry: Often GFAP+, S-100 + • MIB-l (proliferation index) = 6-8%

Consider • Rare diffusely infiltrating glial tumor that can be mistaken for nonneoplastic WM disease

Image Interpretation

1.

Staging, Grading or Classification Criteria • Usually WHO grade III • May be WHO grade II

2. 3.

Presentation • Most common signs/symptoms: Corticospinal tract deficits, dementia, headaches, seizures • Other signs/symptoms: Cranial nerve signs, increased intracranial pressure, altered mental status, personality changes o Rare: Hydrocephalus

Natural History & Prognosis

4. 5.

6.

7.

Demographics • Age o Peak incidence between 40-50 years o Occurs at all ages, reports show neonates to 83 years • Gender: No gender predominance

Pearls

• Extensive MR findings and tumor infiltration are disproportionate to histologic features • MR often underestimates extent of disease when correlated with postmortem findings • Two or more contiguous regions of involvement characterizes GC

8.

9.

Mohana-Borges et al: Role of proton magnetic resonance spectroscopy in the diagnosis of gliomatosis cerebri: a unique pattern of normal choline but elevated myo-inositol metabolite levels. ] Comput Assist Tomogr 28:103-5,2004 Vates GE et al: Gliomatosis cerebri: a review of 22 cases. Neurosurgery. 53(2): 261-71: discussion 271, 2003 Galanaud D et al: Use of proton magnetic resonance spectroscopy of the brain to differentiate gliomatosis cerebri from low-grade glioma.] Neurosurg. 98(2): 269-76, 2003 Peretti-Viton P et al: Histological and MR correlations in Gliomatosis cerebri.] Neurooncol. 59(3): 249-59, 2002 Meligonis G et al: Gliomatosis of the brain and spinal cord masquerading as infective lesions. Surg Neurol. 57(6): 399-404, 2002 Yang S et al: Dynamic contrast-enhanced T2*-weighted MR imaging of gliomatosis cerebri. A]NR Am] Neuroradiol. 23(3): 350-5, 2002 Rust P et al: Gliomatosis cerebri: pitfalls in diagnosis.] Clin Neurosci. 8(4): 361-3, 2001 Lantos P et al: Pathology and genetics of turn ours of the nervous system: Gliomatosis cerebri. Lyon, rARC Press, 92-3,2000 Bendszus M et al: MR spectroscopy in gliomatosis cerebri. A]NR Am] Neuroradiol. 21(2): 375-80, 2000

• Relentless progression • Poor prognosis o 50% mortality at 1 year o 75% by 3 years

Neoplasms and Tumorlike Lesions

Typical (Left) Axial FlAIR MR shows

abnormal hyperintensity and mild enlargement of the midbrain and left temporal lobe. Note relative preservation of underlying brain architecture, typical of gliomatosis cerebri. (Right) Axial FlAIR MR shows diffuse signal abnormality and enlargement of the pons with involvement of the cerebellum. No enhancement after contrast. 43 year old, subtle cranial neuropathy. cc.

(Left) Axial NECT shows

diffuse hypodensity in the frontal, temporal and basal ganglia white matter with mild mass effect and subtle ventricular effacement. Imaging mimics other white matter diseases. Cc. (Right) Axial FlAIR MR shows diffuse periventricular hyperintensity with mild mass effect and subtle ventricular effacement. Involvement of two or more lobes is typical of Cc. 45 year old, headaches.

Variant (Left) Axial FlAIR MR shows

diffuse hyperintensity of thalami with extension across the massa intermedia, and hydrocephalus. Patient also had involvement of midbrain, pons and temporal lobes. cc. (Right) Axial T7 C+ MR shows abnormal enhancement in this 54 year old diagnosed with CC six months prior. New enhancement represented malignant degeneration (Courtesy M. Warmuth-Metz, MO).

Neoplasms and Tumorlike Lesions

6 29

Axial graphic shows nodule" appearance posterior fossa.

Abbreviations

characteristic "cyst with mural of pilocytic astrocytoma in

and Synonyms

• Pilocytic astrocytoma (PA), juvenile pilocytic astrocytoma OPA) • Synonym: Polar spongioblastoma

Definitions • Pilocytic astrocytoma = typically well-circumscribed tumor, often cystic, slow growing • Characterized by Rosenthal fibers and/or eosinophilic granular bodies, or both, at microscopy 30

General Features • Best diagnostic clue o Cystic cerebellar mass with enhancing mural nodule o Enlarged optic nerve/chiasm/tract with variable enhancement • Location: Cerebellum (60%) > optic nerve/chiasm (25-30%) > adjacent to 3rd ventricle> brainstem • Size o Large lesions in cerebellum o Optic nerve lesions typically smaller • Morphology

DDx: Cerebellar

Medulloblastoma

Axial T1 C+ MR shows enhancing cerebellar mass with cystic components compressing fourth ventricle. Enhancement is somewhat heterogeneous, and includes wall of cyst.

o Overall morphology often determined by cystic component o Optic nerve tumors elongate and widen nerve, causing buckling in orbit: "Dotted i"

CT Findings • NECT o Discrete cystic/solid mass o May have little or no surrounding edema o Solid component hypo- to isodense o Ca++ 20%, hemorrhage rare o Often cause obstructive hydrocephalus • CECT o > 95% enhance (patterns vary) • 50% non enhancing cyst, strongly enhancing mural nodule • 40% solid with necrotic center, heterogeneous enhancement • 10% solid, homogeneous • Cyst may accumulate contrast on delayed images

MR Findings • TlWI o Solid portions o Cyst contents • T2WI o Solid portions o Cyst contents • FLAIR

iso/hypointense to GM iso- to slightly hyperintense hyperintense hyperintense

to GM to CSF

Masses

Ependymoma

Hemangioblastoma

Neoplasms and Tumorlike

Lesions

Rhabdoid Tumor

to CSF

PILOCYTIC ASTROCYTOMA Key Facts Pathology

Terminology • Pilocytic astrocytoma astrocytoma OPA)

(PA), juvenile pilocytic

Imaging Findings • Cystic cerebellar mass with enhancing mural nodule • Enlarged optic nerve/chiasm/tract with variable enhancement • Paradoxical finding: MRS does not accurately reflect historical behavior of tumor • Multiplanar or 3D volume post contrast imaging key to showing point of origin and degree of extension

Top Differential

Diagnoses

• Medulloblastoma (PNET-MB) • Pilomyxoid astrocytoma

o Solid portions hyperintense to GM o Cyst contents do not suppress: Hyperintense to CSF o Margins of chiasmatic/hypothalamic tumors in patients with NFl difficult to resolve • May blend into nonspecific signal abnormalities of NFl

• 15% of NFl patients develop PAs, most commonly in optic pathway • Up to 1/3 of patients with optic pathway PAs have NFl • WHO grade I

Clinical Issues • Peak incidence: 5-15 years of age • Older than children with medulloblastoma

Diagnostic Checklist • Generally not a reasonable diagnostic consideration in adults • An enhancing intra-axial tumor with cystic change in a "middle-age" child is more likely to be PA than anything else

I DIFFERENTIAL

DIAGNOSIS

Medulloblastoma

(PNET-MB)

• Hyperdense enhancing midline mass fills 4th ventricle • Younger patient age (2-6 y)

• T1 C+

Ependymoma

o Intense but heterogeneous enhancement of solid portion o Cyst wall occasionally enhances o Rare: Leptomeningeal metastases • MRS o Aggressive-appearing metabolite pattern • High choline, low NAA, high lactate o Paradoxical finding: MRS does not accurately reflect historical behavior of tumor

• "Plastic" tumor, extends out 4th ventricle foramina • Ca++, cysts, hemorrhage common; heterogeneous enhancement

Ultrasonographic

relative to brain

Nuclear Medicine

Atypical teratoid-rhabdoid

31

tumor

Ganglioglioma • Discrete, solid/cystic, cortically-based • Ca++ common

Angiographic Findings • Conventional o Avascular mass • Occasional neovascularity

6

• Large mass with cyst or necrosis • Variable enhancement pattern

Findings

• Real Time o Solid components are hyperechoic parenchyma o Cysts may contain debris

Pilomyxoid astrocytoma • Chiasmatic/hypothalamic tumor in infants • Solid and enhancing • More likely to disseminate, more aggressive

enhancing

mass

Hemangioblastoma seen in solid portion

Findings

• Large cyst with small enhancing mural nodule • Adult tumor! • Associated with von Hippel Lindau disease

Demyelination/inflam

• PET o 18F-fluorodeoxyglucose (FDG) studies show increased tumor metabolism in PAs o Paradoxical finding: PET does not accurately reflect historical behavior of tumor

Imaging Recommendations • Best imaging tool: Contrast-enhanced MR • Protocol advice o Multiplanar or 3D volume post contrast imaging key to showing point of origin and degree of extension o MRS pattern is contradictory to clinical behavior • Small residual tumor on post-operative studies may not negatively impact prognosis

mation

• Optic neuritis in acute multiple sclerosis, acute disseminated encephalomyelitis, or sarcoid can mimic optic nerve glioma • Will not cause "dotted i" sign

I PATHOLOGY General Features • General path comments: Gross appearance clinical impact varies with location • Genetics o Syndromic: Association with NFl

Neoplasms and Tumorlike Lesions

and

• 15% of NFl patients develop PAs, most commonly in optic pathway • Up to 1/3 of patients with optic pathway PAs have NFl o Sporadic: No definite loss of tumor suppressor gene identified • Etiology: Astrocytic precursor cell • Epidemiology o 5-10% of all gliomas o Most common primary brain tumor in children o Analysis often divides into subtypes based on location • Associated abnormalities o Major source of morbidity in NFl o Frequently causes obstructive hydrocephalus • May be a greater clinical management problem than tumor itself

Gross Pathologic & Surgical Features • Well-circumscribed,

soft, gray mass +/- cyst

Microscopic Features • Classic "biphasic" pattern of two astrocyte populations o Compacted bipolar cells with Rosenthal fibers • Rosenthal fibers = electron dense GFAP staining cytoplasmic inclusions o Loose-textured multipolar cells with microcysts, eosinophilic granular bodies • Highly vascular with glomeruloid features • MIB-1 (histological marker of cellular proliferation) = 0-3.9% (mean 1.1%)

Staging, Grading or Classification Criteria

• Tumor may spread through subarachnoid cases (but is still WHO grade I) • Median survival rates at 20 y > 70%

space in rare

Treatment • Cerebellar or hemispheric: Resection o Adjuvant chemotherapy or radiation only if residual progressive unresectable tumor • Opticochiasmatic/hypothalamic: Often none o Stable or slowly progressive tumors watched o Debulking or palliative surgery considered after vision loss o Radiation or chemotherapy for rapidly progressive disease

Consider • Generally not a reasonable diagnostic consideration adults • May rarely present with subarachnoid metastatic disease or as a hemorrhagic mass

Image Interpretation

in

Pearls

• Differentiate cerebellar lesions from medulloblastoma o Medulloblastoma arises from vermis and fills/expands 4th ventricle o PA arises from hemisphere, compresses 4th ventricle • Aggressive appearance of tumor is misleading o An enhancing intra-axial tumor with cystic change in a "middle-age" child is more likely to be PA than anything else

• WHO grade I

6

I SELECTED REFERENCES Komotar RJ et al: Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas. Neurosurg. 54:72-80,2004 2. Bernaerts A et al: Juvenile pilocytic astrocytoma. JBR-BTR. 86(3):142-3,2003 3. Fernandez C et al: Pilocytic astrocytomas in children: prognostic factors--a retrospective study of 80 cases. Neurosurgery. 53(3):544-53; discussion 554-5, 2003 4. Arslanoglu A et al: MR imaging characteristics of pilomyxoid astrocytomas. AJNR Am J Neuroradiol. 24(9):1906-8, 2003 5. Burger PC et al: Pilocytic astrocytoma. In Kleihues P, Cavenee WK (eds), Tumours of the Central Nervous System, 45-51. IARC Press, 2000 6. Rollins NK et al: The use of early postoperative MR in detecting residual juvenile cerebellar pilocytic astrocytoma. AJNR Am J Neuroradiol. 19(1):151-6, 1998 7. Kaschten B et al: Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med. 39(5):778-85, 1998 8. Hwang JH et al: Proton MR spectroscopic characteristics of pediatric pilocytic astrocytomas. AJNR 19:535-540, 1998 9. Leisti EL et al: Spontaneous decrease of a pilocytic astrocytoma in neurofibromatosis type 1. AJNR Am J Neuroradiol. 17(9):1691-4, 1996 10. Brown PD et al: Adult patients with supratentorial piocystic astrocytomas: a prespective multi center trial. Int J Radiat Oncol Bioi Phys 58:1153-60, 2004 1.

32

Presentation • Most common signs/symptoms o Headache, nausea and vomiting (consequence of hydrocephalus and increased ICP) o Visual loss (optic pathway lesions) o Ataxia, cerebellar signs (cerebellar lesions) o Cranial nerve palsies, diplopia (compression in posterior fossa) • Clinical profile o "Middle-aged" child, 5-15 years old o Prolonged duration of symptoms on close inquiry: Months to years

Demographics • Age o > 80% under 20 y o Peak incidence: 5-15 years of age • Older than children with medulloblastoma • Gender: M = F

Natural History & Prognosis • Slowly growing o Mass effect tolerated due to accommodation o Rarely involute without treatment or after partial resection or biopsy

Neoplasms and Tumorlike

Lesions

Typical (Left) Axial T1 C+ MR with

fat saturation shows enlargement and enhancement of the right optic nerve (arrow), classic for intra-orbital optic nerve glioma. (Right) Axial T1 C+ MR with fat saturation shows characteristic "dotted i" appearance of intra-orbital optic nerves (arrow), caused by buckling of the elongated nerve just proximal to the globe.

Typical (Left) Axial NECT shows mixed cystic/solid cerebellar mass with punctate calcification (arrow) associated with solid component. (Right) Axial T1 C+ MR shows a large cystic/solid mass in the right hemisphere, with heterogeneous enhancement of the solid components and little surrounding vasogenic edema.

6 33

Other (Left) MRS shows depression of NAA (arrow), rise in choline (curved arrow) and a broad lipid/lactate doublet (open arrow); this aggressive pattern belies the typically benign clinical behavior of PA. (Right) Coronal T1 C+ MR shows cystic/solid tumor centered in left cerebral peduncle, causing hydrocephalus by its mass effect on the inferior third ventricle.

Neoplasms and Tumorlike Lesions

Coronal graphic shows a cystic and solid cortical mass with thickening of the adjacent meninges (curved arrow), characteristic of PXA. The mural nodule often abuts the pial surface.

Abbreviations and Synonyms • Pleomorphic

6 34

xanthoastrocytoma

(PXA)

Coronal T1 C+ MR shows an enhancing cortical mass with thickening of the adjacent meninges (arrow), skull remodeling (curved arrow). Seizure patient with PXA.

o Discrete round to oval mass typical (may be ill-defined) o Despite circumscribed appearance, tumor often infiltrates into brain, VRSs

Definitions

CT Findings

• Distinct type of (usually) benign supratentorial astrocytoma found almost exclusively in young adults

• NECT o Cystic/solid mass: Hypodense with mixed density nodule o Solid mass: Variable; hypodense, hyperdense or mixed o Minimal or no edema is typical o Ca++, hemorrhage, frank skull erosion rare • CECT: Strong, sometimes heterogeneous enhancement of tumor nodule

General Features • Best diagnostic clue o Supratentorial cortical mass with adjacent enhancing dural "tail" o Cyst and enhancing mural nodule typical • Location o Peripherally located hemispheric mass, often involves cortex and meninges • 98% supratentorial o Temporal lobe most common • Parietal> occipital> frontal lobes o Rarely found in cerebellum, sella, spinal cord, retina • Size: Variable • Morphology o 50-60% cyst + mural nodule that abuts meninges (may be solid)

DDx: Cortically-based

Canglioglioma

Supratentorial

Pilocytic Astrocytoma

MR Findings • TlWI o Mass is hypointense or isointense to gray matter o Mixed signal intensity may be seen o Cystic portion isointense to CSF o Associated cortical dysplasia may be seen (rare) • T2WI o Hyperintense or mixed signal intensity mass o Cystic portion isointense to CSF o Surrounding edema rare • FLAIR o Hyperintense or mixed signal intensity mass o Cystic portion isointense to CSF

Tumors

DNET

Neoplasms and Tumorlike Lesions

Oligodendroglioma

PLEOMORPHIC XANTHOASTROCYTOMA Key Facts Terminology

Pathology

• Distinct type of (usually) benign supratentorial astrocytoma found almost exclusively in young adults

• Superficial, circumscribed astrocytic tumor noted for cellular pleomorphism and xanthomatous change • < 1% of all astrocytomas • Cystic mass with mural nodule abutting meninges • Deep margin may show infiltration of parenchyma • WHO grade II

Imaging Findings • Supratentorial cortical mass with adjacent enhancing dural"tail" • Temporal lobe most common

Top Differential • • • • • •

Diagnoses

Ganglioglioma Pilocytic astrocytoma Dysembryoplastic neuroepithelial tumor (DNET) Oligodendroglioma Meningioma Low grade astrocytoma (Grade II)

• T1 C+

o Enhancement usually moderate/strong, well-delineated o Enhancement of adjacent meninges, dural"tail" common (approximately 70%) • Enhancing nodule often abuts pial surface o Rare: Deep tumor extension, distant metastases

Clinical Issues • Majority with long-standing epilepsy, often partial complex seizures (temporal lobe) • Tumor of children/young adults

Diagnostic Checklist • Cortical mass & meningeal thic adult with long seiZUre history?

• T2 hyperintense mass with rare, mild enhancement • May remodel calvarium

Oligodendroglioma • Heterogeneous, Ca++ mass • Typically larger and more diffuse than PXA • May remodel/erode calvarium

Meningioma

Angiographic Findings • Typically avascular • Vascular blush may indicate necrotic or aggressive PXA

• Diffusely enhancing dural-based mass with dural "tail" • Usually older patients

Nuclear Medicine

• Demarcated but infiltrative white matter mass • No enhancement

Findings

• PET: FDG-PET may show hypermetabolic low grade PXA

foci even in

• Best imaging tool o Multiplanar MR is most sensitive o CT may be helpful for calvarial changes • Protocol advice: Contrast-enhanced MR including coronal images to better evaluate temporal lobes

DIAGNOSIS

Ganglioglioma • • • •

Cortically based hemispheric mass, solid/cystic or solid Mural nodule typical, often not adjacent to meninges Variable enhancement, no enhancing dural "tail" Ca++ is common; may remodel calvarium

Pilocytic astrocytoma • Supratentorial location other than hypothalamus/chiasm rare • Typically solid and cystic or solid mass • Enhancement but no dural "tail"

Dysembryoplastic (DNET)

neuroepithelial

• Superficial cortical tumor, well demarcated • Multicystic "bubbly" ,appearance

6 35

IPATHOlOG¥

Imaging Recommendations

I DIFFERENTIAL

Low grade astrocytoma (Grade II)

tumor

General Features • General path comments o Superficial, circumscribed astrocytic tumor noted for cellular pleomorphism and xanthomatous change o PXA may occur with ganglioglioma and oligodendroglioma (rare) • Genetics o No definite association with hereditary tumor syndromes o Rare reports of PXA in Nfl patients o PXA with TP53 mutations reported • Etiology o May originate from cortical (subpial) astrocytes o May arise from multipotential neuroectodermal precursor cells common to both neurons, astrocytes • Epidemiology o < 1% of all astrocytomas o Rare but important cause of temporal lobe epilepsy

Gross Pathologic & Surgical Features • • • • •

Cystic mass with mural nodule abutting meninges May be completely solid Leptomeningeal adhesion/attachment is common Dural invasion is rare Deep margin may show infiltration of parenchyma

Neoplasms and Tumorlike Lesions

Microscopic

Features

• "Pleomorphic" appearance o Fibrillary and giant multinucleated neoplastic astrocytes o Large xanthomatous (lipid-containing) cells are GFAP positive o Dense reticulin network o Lymphocytic infiltrates • Tumor sharply delineated from cortex, but infiltration maybe seen • Some positive for synaptophysin, neurofilament proteins, S-100 protein • CD34 antigen may help differentiate PXA from other tumors • Necrosis, mitotic figures rare/absent o MIB-l index generally < 1% • May be associated with cortical dysplasia

Consider • Cortical mass & meningeal thickening in a young adult with long seizure history? Think PXA! • Ganglioglioma may mimic PXA clinically and by imaging

Image Interpretation

1.

2.

Staging, Grading or Classification Criteria • WHO grade II • PXA with anaplastic features o Significant mitoses (5 or more per 10 HPF) and/or necrosis o Has been associated with poorer prognosis: Increased recurrence and decreased survival o Some classify these PXA as WHO grade III

3.

4.

5.

6.

Presentation

36

• Most common signs/symptoms o Majority with long-standing epilepsy, often partial complex seizures (temporal lobe) o Other signs/symptoms: Headache, focal neurologic deficits

7.

8.

Demographics

9.

• Age o Tumor of children/young adults • Typically first three decades • 2/3 < 18 years • Ranges from 2-82 years, mean 26 years • Gender: No gender predominance

10.

Natural History & Prognosis

11.

12.

• Usually circumscribed, slow growing • Aggressive PXA with malignant progression, dissemination occasionally occurs • Malignant transformation in 10-25% of cases • Survival 70% at 10 years • Recurrence of tumor is uncommon • Hemorrhage is a rare complication • Extent of resection and mitotic index are most significant predictors of outcome

Pearls

• Meningioma-like lesion in young patient should raise suspicion of PXA

13.

14. 15.

Reifenberger G et al: Expression of the CD34 antigen in pleomorphic xanthoastrocytomas. Acta Neuropathol (Berl). 105(4):358-64,2003 Etzl MM Jr et al: Positron emission tomography in three children with pleomorphic xanthoastrocytoma. J Child Neurol. 17(7):522-7,2002 Burger PC et al: Surgical pathology of the nervous system and its coverings: The Brain: Tumors. 4th ed. Philadelphia, Churchill Livingstone. 215-20, 2002 Koeller KK et al: From the archives of the AFIP: superficial gliomas: radiologic-pathologic correlation. Armed Forces Institute of Pathology. Radiographics. 21(6):1533-56, 2001 Fouladi M et al: Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical resection. Neuro-oncol. 3(3):184-92,2001 Tsuyuguchi N et al: Evaluation of pleomorphic xanthoastrocytoma by use of positron emission tomography with. AJNR Am J Neuroradiol. 22(2):311-3, 2001 Kepes JJ et al: Pathology and genetics of tumours of the nervous system: Pleomorphic xanthoastrocytoma. Lyon, IARC Press, 52-4, 2000 Chakrabarty A et al: Malignant transformation in pleomorphic xanthoastrocytomana report of two cases. Br J Neurosurg. 13(5):516-9, 1999 Ohta S et al: Eighteen-year survival of a patient with malignant pleomorphic xanthoastrocytoma associated with von Recklinghausen neurofibromatosis. Br J Neurosurg. 13(4):420-2, 1999 Giannini C et al: Pleomorphic xanthoastrocytoma: what do we really know about it? Cancer. 85(9):2033-45, 1999 Prayson RA et al: Anaplastic pleomorphic xanthoastrocytoma. Arch Pathol Lab Med. 122(12):1082-6, 1998 Giannini C et al: Classification and grading of low-grade astrocytic tumors in children. Brain Pathol. 7(2):785-98, 1997 Levy RA et al: Pleomorphic xanthoastrocytoma presenting with massive intracranial hemorrhage. AJNR Am J Neuroradiol. 17(1):154-6, 1996 Russo CP et al: Pleomorphic xanthoastrocytoma: Report of two cases and review of the literature. IJNR 2:570-8, 1996 Lach B et al: Association of pleomorphic xanthoastrocytoma with cortical dysplasia and neuronal tumors: a report of three cases. Cancer. 78:2551-63, 1996

Treatment • Surgical resection is treatment of choice • Repeat resection for recurrent tumors • Radiation therapy and chemotherapy show no significant improvement in outcome

Neoplasms and Tumorlike Lesions

Typical (Left) Axial NECT shows a

cystic and solid mass with associated calcification. 20 year old male with a long history of seizures. Imaging mimics a ganglioglioma. PXA at resection. (Right) Axial T1 C+ MR shows a cystic mass with a markedly enhancing mural nodule, typical of PXA. These cortically based masses are most common in the temporal lobes (Courtesy C. Sutton, MO).

Typical (Left) Coronal T7WI MR shows a cortically based temporal lobe cystic and solid mass. Patient with a long-standing history of temporal lobe epilepsy. (Right) Axial T1 C+ MR shows strong heterogeneous enhancement of the solid portion. PXA with anaplastic features was found at resection which is associated with increased recurrence and decreased survival.

6 37

Variant (Left) Axial T1 C+ MR shows extensive leptomeningeal carcinomatosis in this patient with recurrent PXA (same case as above, two years later). Malignant transformation occurs in 70 to 25% of patients. (Right) Axial T2WI MR shows a large heterogenous solid and cystic parietal mass with surrounding mass effect and hypointensity related to calcification (arrow). PXA at resection. 78 year old, seizures.

Neoplasms

and Tumorlike

Lesions

Coronal graphic shows hydrocephalus secondary to a subependymal giant cell tumor arising near the left foramen of Monro (open arrow). Note the subependymal tubers (arrows).

Coronal T1 C+ MR shows a robustly enhancing left foramen of Monro subependymal giant cell tumor. Also note ipsilateral ventricular obstruction (arrow), subependymal nodule (curved arrow).

o Frond-like margins mimicking choroid plexus tumor

Abbreviations

CT Findings

and Synonyms

• Sub ependymal giant cell astrocytoma (SGCA) • Subependymal giant cell tumor (SGCT) • Intraventricular astrocytoma of tuberous sclerosis (TS)

Definitions • Intraventricular glioneuronal foramen of Monro

tumor arising near the

38

General Features • Best diagnostic clue o Enlarging, enhancing intraventricular mass in patient with tuberous sclerosis complex (TSC) o Origin of mass from ventricular wall near foramen of Monro o Other findings of TS (cortical tubers, SE nodules) • Location: Almost always near foramen of Monro • Size o Variable, slow growing o Often presents when 2-3 em, causes obstructive hydrocephalus • Morphology o Well marginated, often lobulated

• NECT o Hypodense =} isodense o Heterogeneous o Ca++ variable o Hydrocephalus • CECT o Heterogeneous, strong enhancement o Presence of interval growth suggests SGCT o Initially tumor typically> lcm • CT Perfusion o May be mildly hypervascular

MR Findings • TlWI o Hypointense to isointense to GM o ± Ca++ (hyperintense to hypointense) • T2WI o Heterogeneous • Isointense to hyperintense o Ca++ foci hypointense o Hydrocephalus • PD/Intermediate: Hyperintense • FLAIR o Heterogeneously hyperintense o Periventricular interstitial edema from ventricular obstruction

DDx: Foramen of Monro Neoplasms in Children

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) PNET

Neoplasms and Tumorlike Lesions

Neurocytoma

SUBEPENDYMAL GIANT CELL ASTROCYTOMA Key Facts • Subependymoma

Imaging Findings • Enlarging, enhancing intraventricular mass in patient with tuberous sclerosis complex (TSC) • Location: Almost always near foramen of Monro • Well marginated, often lobulated • Heterogeneous, strong enhancement • Presence of interval growth suggests SGCT • Enhancement alone does not allow discrimination from hamartoma • FLAIRMR to detect subtle CNS features of TSC • Recommend brain MR with contrast every 1-2 years for SGCT follow-up

Top Differential

Diagnoses

Pathology • Most common CNS neoplasm in TSC • Does not seed CSF pathways • WHO grade I

Clinical Issues • Increased ICP secondary to tumor obstructing foramen of Monro

Diagnostic Checklist • SGCA in tuberous sclerosis patient with worsening seizures and/or symptoms of ventricular obstruction

• Choroid plexus tumors • Astrocytoma • Germinoma • T2* GRE: Low signal from Ca++ • DWI: ADC values less than parenchymal hamartomas ofTS • T1 C+ o Robust enhancement • Enhancement alone does not allow discrimination from hamartoma o Enlarging foramen of Monro mass strongly suggests SGCT o Size of intraventricular SGCT > 1.2 em o No predilection for CSF spread • MRS: Less than "expected" ~ NAA due to neuronal elements in tumor

Ultrasonographic

Findings

• Intraoperative o Hyperechoic intraventricular mass o Heterogeneous shadowing foci of Ca++

Angiographic

• Origin ~ septum pellucidum fornices or medial basal ganglia o Common pediatric intra-axial neoplasm o Variable enhancement, Ca++ rare

Germinoma • Hugs midline, often arises near third ventricle • Early diabetes insipidus • Early CSF spread

Subependymoma • Inferior fourth and frontal horn most common locations • Nonenhancing mass • Tumor of middle age and elderly

Central neurocytoma

Findings

• Conventional o Variable vascularity o +/- Stretched thalamostriate

Astrocytoma

veins (hydrocephalus)

• • • •

Well defined, variably vascularized lobulated mass Origin near foramen of Monro or septum pellucidum Necrosis and cyst formation are common Seen in young adults

Supratentorial

Imaging Recommendations • Best imaging tool: MR brain demonstrates extent of mass, delineates associated TSC features • Protocol advice o FLAIRMR to detect subtle CNS features of TSC o Recommend brain MR with contrast every 1-2 years for SGCT follow-up

I PATHOLOGY General Features

I DIFFERENTIAL DIAGNOSIS Choroid plexus tumors • Papilloma and carcinoma o Vivid enhancement o ± CSF seeding o Parenchymal invasion and peritumoral choroid plexus carcinoma

PNET

• May exophytically extend into ventricle • Lack of peritumoral edema • Highly cellular tumor, isointense ~ slightly hyperintense on T2WI

edema with

• General path comments o Benign, slow growing tumor o Most common CNS neoplasm in TSC o Rarely (if ever) arises in absence of TSC o Recurrence after resection rare o Ca++ and hemorrhage may be seen • Genetics o 50% of TSC patients have positive family history • High rate of de novo mutations o In affected kindreds

Neoplasms and Tumorlike Lesions

6 39

SUBEPENDYMAL GIANT CELL ASTROCYTOMA • Inheritance: Autosomal dominant • High penetrance • Considerable phenotypic variability o Molecular genetics • Two distinct TSC loci (chromosome 9q => TSCI & 16p => TSC2) • TSCI and TSC2 are likely tumor suppressor genes • Etiology: SGCA probably arises from subependymal nodule • Epidemiology o Incidence of SGCA => up to 15% of patients with TSC o 1.4% of all pediatric brain tumors • Associated abnormalities: Other CNS and extraneural manifestations of TSC

Gross Pathologic & Surgical Features • Well marginated mass arising from lateral ventricular wall near foramen of Monro o ± Cysts, Ca++, and hemorrhage • Does not seed CSF pathways

• Rarely, massive spontaneous

Treatment • Surgical resection (open vs endoscopic) • Massive hemorrhage possible complication

Consider • SGCA in tuberous sclerosis patient with worsening seizures and/or symptoms of ventricular obstruction

Image Interpretation

• Tumor cells of SGCAs show wide spectrum of astroglial phenotypes o Giant pyramidal ganglioid astrocytes o Perivascular pseudopalisading • Immunohistochemistry o Variable immunoreactivity for GFAP and S 100 protein o Some tumor cells express glial and neuronal antigens

Staging, Grading or Classification Criteria • WHO grade I 40

Presentation • Most common signs/symptoms o Increased ICP secondary to tumor obstructing foramen of Monro • Headache, vomiting, obtunded o Other signs/symptoms • Worsening epilepsy • Massive spontaneous hemorrhage • Clinical profile o Patient with TSC develops signs and symptoms of ventricular obstruction o Worsening of epilepsy.

Pearls

• Enlarging, enhancing intraventricular mass near the foramen of Monro in TSC patient • Foramen of Monro mass and associated intraventricular hemorrhage

1.

Microscopic Features

hemorrhage

Cuccia V et al: Subependymal giant cell astrocytoma in children with tuberous sclerosis. Childs Nerv Syst. 19(4):232-43,2003 2. Rashidi M et al: Nonmalignant pediatric brain tumors. CUff Neurol Neurosci Rep. 3(3):200-5, 2003 3. Sener RN: Diffusion MR imaging of giant cell tumors in tuberous sclerosis, J Comput Assist Tomogr. 27(3):431-3, 2003 4. Nishio S et al: Tumours around the foramen of Monro: clinical and neuroimaging features and their differential diagnosis. J Clin Neurosci. 9(2):137-41, 2002 5. Medhkour A et al: Neonatal subependymal giant cell astrocytoma. Pediatr Neurosurg. 36(5):271-4, 2002 6. Yamamoto K et at: Rapid regrowth of solitary subependymal giant cell astrocytoma--case report. Neurol Med Chir (Tokyo). 42(5):224-7, 2002 7. Koeller KKet al: From the archives of the AFIP.Cerebral intraventricular neoplasms: radiologic-pathologic correlation. Radiographies. 22(6):1473-505, 2002 8. Kim SKet al: Biological behavior and tumorigenesis of subependymal giant cell astrocytomas. J Neurooncol. 52(3):217-25,2001 9. Beems T et al: Subependymal giant cell-astrocytoma in tuberous sclerosis: endoscopic images and the implications for therapy. Minim Invasive Neurosurg. 44(1):58-60, 2001 10. Kashiwagi N et al: Solitary subependymal giant cell astrocytoma: case report. Eur J Radiol. 33(1):55-8, 2000 11. Wiestler OD et al: Tuberous sclerosis complex and subependymal giant cell astrocytoma. In Kleihues P, Cavenee WK (eds): Tumours of the Nervous System, pp 227-30, IARC Press, Lyon, 2000

Demographics • Age o SGCA typically occurs during the first two decades o Mean age 11 years • Gender: No gender predilection • Ethnicity: No race predilection

Natural History & Prognosis • Solitary, slow growing benign tumor • Symptoms from ventricular obstruction • Good outcome and low recurrence rate with complete resection

Neoplasms and Tumorlike Lesions

SUBEPENDYMAL

GIANT CELL ASTROCYTOMA

IIMAGE GALLERY Typical (Left) Axial gross pathology

shows subependymal giant cell tumor at the foramen of Monro in a patient with tuberous sclerosis (Courtesy R. Hewlett, MO). (Right) Axial NECT shows a bi-Iobed subependymal giant cell tumor of the left foramen of Monro. Note the heavy tumor calcification (arrow).

Typical (Left) Axial FLAIRMR shows

hyperintense bilateral subependymal giant cell tumors (arrows). Also note the hyperintense parenchymal tubers common to tuberous sclerosis complex (open arrows). (Right) Coronal T2WI MR shows a mixed signal intensity subependymal giant cell tumor. In addition to obstructive hydrocephalus, note the bosselated tumor margins that mimic a choroid plexus tumor (arrow).

Typical (Left) Axial T1 C+ MR shows

bilateral vividly enhancing subependymal giant cell tumors arising near the foramina of Monro (arrows). (Right) Axial T1 C+ MR shows a large lobulated strongly enhancing subependymal giant cell tumor arising from the left foramen of Monro. Also note ipsilateral ventricular obstruction (arrow).

Neoplasms and Tumorlike Lesions

6 41

OLIGODENDROGLIOMA

Axial graphic shows a heterogeneous cystic & solid mass of cortex and subcortical WM, typical oligodendroglioma. Note deep infiltrative margin (arrow), calvarial remodeling (curved arrow).

I TERMINOLOGY

CT Findings • NECT o Mixed density (hypodense/isodense) hemispheric mass that extends to cortex o Majority calcify, nodular or clumped Ca++ (70-90%) o Cystic degeneration common (20%) o Hemorrhage, edema are uncommon o May expand, remodel, erode calvarium • CECT o Approximately 50% enhance o Enhancement varies from none to striking

Abbreviations and Synonyms • Oligo, low grade oligodendroglioma

Definitions • Well-differentiated, slowly growing but diffusely infiltrating cortical/subcortical tumor

6 42

IMAGING FINDINGS General Features • Best diagnostic clue: Partially Ca++ subcortical/cortical mass in middle-aged adult • Location o Typically involves subcortical white matter (WM) and cortex o Majority supratentorial (85%), hemispheric WM • Most common site is frontal lobe • May involve temporal, parietal or occipital lobes • Posterior fossa rare • Intraventricular rare (1-10%) • Extremely rare: Brainstem, spinal cord, primary leptomeningeal • Size: Variable • Morphology: Infiltrative mass that appears well demarcated

DDx: Superficial, Cortically-based

Grade /I Astra

Axial T2WI MR shows a heterogeneous cortical and subcortical mass with calcification and cystic change. Despite its discrete appearance, infiltration is typical of oligodendroglioma.

Ganglioglioma

MR Findings • TlWI o Hemispheric mass, hypointense to isointense to GM o Typically heterogeneous o Cortical and subcortical with cortical expansion o May appear well circumscribed with minimal associated edema • T2WI o Typically heterogeneous, hyperintense mass • Heterogeneity related to Ca++, cystic change, blood products o May appear well circumscribed with minimal associated. edema o Typically expands overlying cortex o Hemorrhage, necrosis rare unless anaplastic o May expand, erode calvarium

Hemispheric Mass

ONET

Neoplasms and Tumorlike

Lesions

Cerebritis

OLIGODENDROGLIOMA Key Facts Terminology

Top Differential Diagnoses

• Well-differentiated, slowly growing but diffusely infiltrating cortical/subcortical tumor

• • • • • • •

Imaging Findings • Best diagnostic clue: Partially Ca++ subcortical/cortical mass in middle-aged adult • Typically involves subcortical white matter (WM) and cortex • Majority supratentorial (85%), hemispheric WM • Most common site is frontal lobe • May involve temporal, parietal or occipital lobes • Morphology: Infiltrative mass that appears well demarcated • Majority calcify, nodular or clumped Ca++ (70-90%)

• FLAIR o Typically heterogeneous, hyperintense o Typically expands overlying cortex o May appear well circumscribed but infiltrative • T2* GRE: Ca++ seen as areas of "blooming" • DWI: No diffusion restriction is typical • TI C+ o Heterogeneous enhancement is typical o Approximately 50% enhance o Rarely, leptomeningeal enhancement is seen • MRS: Elevated Cho, decreased NAA • PWI: Foci of elevated rCBV can mimic high grade tumor!

Anaplastic oligodendroglioma (AO) Astrocytoma Ganglioglioma Dysembryoplastic neuroepithelial tumor (DNET) Pleomorphic xanthoastrocytoma (PXA) Cerebritis Ischemia

Pathology • WHO grade II

Clinical Issues • Seizures, headaches • Peak incidence 4th and 5th decades • Surgical resection is primary treatment

Dysembryoplastic

neuroepithelial

tumor

(DNET) • • • •

Sharply demarcated cortical neoplasm Heterogeneous, "bubbly" appearance Variable enhancement Childhood, young adult tumor

Pleomorphic xanthoastrocytoma • • • •

(PXA)

Supratentorial cortical mass, dural "tail" common Often cyst and mural nodule, may be solid Enhancing nodule abuts pial surface Childhood, young adult tumor

Nuclear Medicine Findings

Cerebritis

6

• PET o FDG uptake similar to normal white matter o lIC-methionine studies show marked uptake differences between oligo & anaplastic oligo

• T2 hyperintensity and patchy enhancement • Diffusion restriction typical

43

Imaging Recommendations • Best imaging tool o MR is most sensitive to delineate tumor o CT helpful for identifying Ca++ • Protocol advice: Contrast-enhanced MR, with T2* GRE

IDIFFERENTIAI..DIAGNC)SIS Anaplastic oligodendroglioma

(AD)

• May require biopsy to distinguish • PET can be helpful

Ischemia • • • •

Typical vascular distribution (MCA, ACA, PCA) Diffusion restriction if acute/subacute Involves GM and WM, often wedge-shaped Cortical, gyriform enhancement if subacute

Arteriovenous malformation

(AVM)

• Typically multiple enlarged flow voids • Often calcified • If thrombosed, may be indistinguishable

Herpes encephalitis • Confined to limbic system, temporal lobes • Blood products and enhancement common • Acute onset is typical

Astrocytoma • Calcification less common • Usually involve white matter, cortex relatively spared • May be indistinguishable

I PATHC)I..c)G¥

Ganglioglioma

• General path comments o Well-differentiated (grade II) and anaplastic (grade III) types • 20-50% are aggressive (anaplastic oligos) o Solid, infiltrative lesions involve cortex/subcortical WM

• Usually temporal lobe, cortical • Sharply demarcated, commonly nodule; Ca++ common • Childhood, young adult tumor

cystic with enhancing

General Features

Neoplasms and Tumorlike

Lesions

o Rarely may be multifocal or multicentric o Oligoastrocytoma (mixed tumor with 2 distinct neoplastic cell types) are common (50%) o Majority of "intraventricular oligodendrogliomas" are central neurocytomas • Difficult to distinguish on light microscopy • EM, immunohistochemistry demonstrate neuronal nature of most "intraventricular oligos" o Rarely occurs with other tumors, pleomorphic xanthoastrocytoma (PXA) o Primary leptomeningeal oligodendrogliomatosis extremely rare o Oligodendroglial gliomatosis cerebri reported o Oligodendrogliomas carry better prognosis than astrocytomas of same grade • Genetics o Loss of heterozygosity for Ip and 19q (50-70%) • Often occur together suggesting synergistic effect o Familial cases have been reported • Etiology: Arises from neoplastic transformation of mature oligodendrocytes or immature glial precursors • Epidemiology o 5-10% of primary intracranial neoplasms o 5-25% of all gliomas

Natural History & Prognosis • More favorable outcome correlated with o Younger age o Frontal location o Lack of enhancement o Complete resection o Radiation therapy after partial resection • Worse prognosis correlated with o Necrosis, increased cellularity o Mitotic activity, nuclear atypia o Cellular pleomorphism o Microvascular proliferation • Median survival time = 10 years • 5 year survival rate 50-75% • Local recurrence common • Malignant progression may occur • CSF seeding uncommon • Loss of heterozygosity for Ip, 19q associated with a more favorable prognosis, better response to chemotherapy

Treatment • Surgical resection is primary treatment • Adjuvant radiation therapy + chemotherapy

Gross Pathologic & Surgical Features • • • •

Well-defined, grayish-pink soft unencapsulated mass Located in cortex, subcortical white matter Ca++ frequent; +/- cystic degeneration, hemorrhage Rare: Infiltrates leptomeninges

Microscopic

44

Features

• Moderately cellular tumors with occasional mitoses • Rounded, homogeneous nuclei and clear cytoplasm o "Fried egg" and "honeycomb" patterns probably artifactual, perinuclear halos • +/- Microcalcification, mucoid/cystic degeneration • May have dense network of branching capillaries • Marked nuclear atypia may be seen • MIB-l < 5% (proliferation index) • Immunohistochemistry: Oligl+, GFAP-

1[)IA6h4()S-rI(](]H<E
Image Interpretation

Pearls

• Oligos cannot be reliably differentiated from AOs on imaging alone • Oligos are most common intracranial tumor to calcify • New enhancement in a previously nonenhancing oligodendroglioma often indicates malignant progression

Staging, Grading or Classification Criteria • WHO grade II • Anaplastic oligodendroglioma = WHO grade III o Mitoses, microvascular proliferation, +/- necrosis

1.

Presentation

2.

• Most common signs/symptoms o Seizures, headaches o Patients have relatively long-standing history of symptoms • Other signs/symptoms: Focal neurologic deficits, depending on location

Demographics

3. 4.

5.

• Age o Peak incidence 4th and 5th decades o Occurs at all ages • Gender: Slight male predominance

Lev MH et al: Glial tumor grading and outcome prediction using dynamic spin-echo MR susceptibility mapping compared with conventional contrast-enhanced MR: confounding effect of elevated rCBV of oligodendrogliomas. AJNR 25:214-21,2004 Azzarelli B et al: Immunolocalization of the oligodendrocyte transcription factor (Oligl) in brain tumors. J Neuropathol Exp Neurol 63: 170-9, 2004 Perry JR: Oligodendrogliomas: clinical and genetic correlations. Curr Opin Neurol. 14(6): 705-10, 2001 Derlon JM et al: Non-invasive grading of oligodendrogliomas: correlations between in vivo metabolic pattern and histopathology. Eur J Nucl Med. 27:778-87, 2000 Prayson RA et al: Clinicopathologic Study of Forty-Four Histologically Pure Supratentorial Oligodendrogliomas. Ann Diagn Pathol. 4:218-27, 2000

Neoplasms and Tumorlike Lesions

Typical (Left) Axial T2WI MR shows a demarcated hyperintense mass with involvement of the cortex and subcortical white matter with mild associated mass effect. 43 year old male with headaches. Oligodendroglioma. (Right) Axial T1 C+ MR shows a mass with cystic change (arrow), no enhancement. Enhancement is variable in oligodendroglioma and seen in 50% of cases. New enhancement may indicate malignant progression.

Typical (Left) Axial NECT shows a calcified cortically-based frontal mass (arrow). Calcification is seen in the vast majority of oligodendrogliomas, typically nodular or clumped. (Right) Axial T2WI MR in the same case shows a heterogeneously hyperintense cortically-based mass with infiltration into the subcortical white matter. Cystic change is seen, but the Ca++is not visualized.

Variant

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j~ ~~ Neoplasms and Tumorlike Lesions

(Left) Axial T2WI MR shows a hyperintense mass primarily involving the cortex with minimal white matter involvement. This appearance mimics other cortically-based masses. Oligodendroglioma at surgery. (Right) Axial FLAIR MR in a 48 year old male with seizures shows bilateral hyperintense infiltrative masses involving the cortex and subcortical WM. Proven multicentric oligodendroglioma.

6 45

ANAPLASTIC OLIGODENDROGLIOMA

Axial graphic shows a heterogeneous frontal cortical and subcortical mass with areas of necrosis and hemorrhage. Note the mass effect and infiltrative margins, typical of AD.

Axial T2WI MR shows a large heterogeneous mass involving the cortex and white matter. Note the cystic change and mass effect upon the lateral ventricles. Patientwith seizures, AG.

o Neoplastic cells almost always found beyond areas of abnormal signal intensity

Abbreviations

and Synonyms

• Anaplastic oligodendroglioma oligodendroglioma (oligo)

CT Findings

(AO), high grade

Definitions • Highly cellular diffusely infiltrating glioma • Oligodendroglioma with focal or diffuse histologic features of malignancy

6

• NECT o Mixed density (hypodense/isodense) mass o Majority calcify, nodular or clumped Ca++ • May see gyriform Ca++ o Cystic degeneration common o May see hemorrhage or necrosis o May expand, remodel or erode calvarium • CECT: Variable enhancement

MR Findings

46

General Features • Best diagnostic clue: Calcified frontal lobe mass involving cortex/subcortical white matter (WM) • Location o Supratentorial hemispheric mass, involves cortex & subcortical WM o Frontal lobe most common, followed by temporal o May involve parietal or occipital lobes o Often expands overlying cortex • Size: Variable • Morphology o Diffusely infiltrative mass o May appear discrete, but always infiltrative

• TlWI o Heterogeneous hypointense infiltrative mass o May appear circumscribed o May see blood products, edema, necrosis o Cortical expansion may be seen • T2WI o Heterogeneous hyperintense infiltrative mass • Heterogeneity related to Ca++, cystic change, blood products o Typically expands overlying cortex o May see hemorrhage, necrosis • FLAIR o Heterogeneous hyperintense infiltrative mass o Typically expands overlying cortex • T2* GRE: Ca++ seen as areas of "blooming"

DDx: Diffusely Infiltrating Hemispheric Mass

Oligodendroglioma

AA

GBM

Neoplasms and Tumorlike Lesions

Cerebritis

ANAPLASTIC OLIGODENDROGLIOMA Key Facts Terminology

Pathology

• Oligodendroglioma with focal or diffuse histologic features of malignancy

• Well-differentiated (grade II) and anaplastic (grade III) types of oligodendroglioma • Oligo astrocytoma (mixed tumor with 2 distinct neoplastic cell types) are common (50%) • Oligos have better prognosis than astrocytomas of same grade • Average number of chromosomes involved is higher in grade III than grade II oligos • 20-50% of oligodendrogliomas are anaplastic • WHO grade 1II

Imaging Findings • Best diagnostic clue: Calcified frontal lobe mass involving cortex/subcortical white matter (WM) • May appear discrete, but always infiltrative • Neoplastic cells almost always found beyond areas of abnormal signal intensity

Top Differential • • • • •

Diagnoses

Clinical Issues

Oligodendroglioma Anaplastic astrocytoma (AA) Glioblastoma multiforme (GBM) Cerebritis Ischemia

• Peak incidence fourth through sixth decade • Median survival 4 years • Local tumor recurrence common

• DWI: No diffusion restriction typical • Tl C+ o Variable enhancement o New enhancement suggests malignant progression o 50% of all oligodendrogliomas enhance o AOs more likely to enhance than low grade oligo • MRS o Increased Cho/Cr; decreased NAA o Lipid/lactate peak may be seen • PWI o High rCBV common; does not distinguish from low grade oligo

Nuclear Medicine

Findings

• PET o High glucose metabolism, accumulate FDG similar to or exceeds gray matter o FDG shows high grade gliomas have uptake similar to or exceeding normal gray matter o Tumor/WM> 1.5 and tumor/GM > 0.6 suggests high grade tumors o llC-methionine studies show marked uptake differences between oligo, AO

• Hemorrhage

common

Cerebritis • • • •

T2 hyperintensity and patchy enhancement Diffusion restriction is typical May appear "mass-like" Acute onset common

Ischemia • • • •

Typical vascular distribution (MCA, ACA, PCA) Diffusion restriction if acute/subacute Involves GM and WM, often wedge-shaped Cortical, gyriform enhancement if subacute

Herpes encephalitis

6

• Confined to limbic system, temporal lobes • Blood products and enhancement common • Acute onset is typical

47

Meningioma • • • •

Enhancing extra-axial dural based mass Often calcified with a broad dural base, dural "tail" Hyperostosis and Ca++ is characteristic Older patients

Imaging Recommendations • Best imaging tool: MR to delineate tumor; CT for Ca++ • Protocol advice: Contrast-enhanced MR with T2* GRE

I PATHOLOGY General Features

I [)IFFERENTIAL [)IAGNOSIS Oligodendroglioma • Calcified mass involving gray matter and white matter • May appear more circumscribed • Indistinguishable without biopsy

Anaplastic astrocytoma (AA) • Infiltrative mass, predominantly • Often nonenhancing • May be indistinguishable

Glioblastoma

multiforme

involves white matter

(GBM)

• 95% necrotic core, enhancing rim • Extensive surrounding T2/FLAIR signal

• General path comments o Well-differentiated (grade II) and anaplastic (grade III) types of oligodendroglioma o Oligoastrocytoma (mixed tumor with 2 distinct neoplastic cell types) are common (50%) • WHO grade II (oligoastrocytoma) • WHO grade III (anaplastic oligo astrocytoma) • Decreased survival compared with pure oligo o Primary leptomeningeal oligodendrogliomatosis occurs but extremely rare o Oligodendroglial gliomatosis cerebri reported o Rarely may be multifocal or multicentric o Oligos have better prognosis than astrocytomas of same grade

Neoplasms and Tumorlike

Lesions

o Some authors propose dividing AOs into WHO grades III and IV • Genetics o Loss of heterozygosity for Ip and 19q (50-70%) • Often occur together suggesting synergistic effect o Deletions on short arm of chromosome 9 and/or 10 o CDKN2A tumor suppressor gene deletions (25%) o Average number of chromosomes involved is higher in grade III than grade II oligos • Etiology o Arises from neoplastic transformation of mature oligodendrocytes or immature glial precursors o May arise de novo or from malignant progression of a pre-existing grade II oligo • Epidemiology o 20-50% of oligodendrogliomas are anaplastic o Oligos represent 5-10% of all primary intracranial neoplasms o Oligos represent 5-25% of all gliomas Well-defined, grayish-pink soft unencapsulated Located in cortex/subcortical WM Ca++ is extremely common Cystic degeneration, hemorrhage common Necrosis may be present Rarely infiltrates overlying leptomeninges

Microscopic

48

mass

Features

• Rounded, homogeneous nuclei and clear cytoplasm o Perinuclear halos, "fried egg" and "honeycomb" patterns related to fixation artifact • Microcalcifications, mucoid/cystic degeneration • Dense network of branching capillaries ("chicken-wire ") • Increased cellularity, marked atypia • High mitotic activity • Microvascular proliferation and necrosis

Staging, Grading or Classification Criteria • WHO grade III

Presentation • Most common signs/symptoms: Headache, seizures • Other signs/symptoms o Focal neurologic deficits may be present depending on location • Duration of symptoms shorter than in grade II oligos

Demographics • Age o Peak incidence fourth through sixth decade o Occurs at all ages, mean age 49 years o Older on average than WHO grade II patients • Gender: Slight male predominance

Natural History & Prognosis • • • •

Poor prognosis Median survival 4 years 5 year survival 40-45%; 10 year survival 15% Local tumor recurrence common

Treatment • Surgical resection + adjuvant chemotherapy radiation therapy

and

Consider

Gross Pathologic & Surgical Features • • • • • •

• CSF metastasis uncommon • Systemic metastasis rare • Leptomeningeal oligodendrogliomatosis, spinal cord metastasis extremely rare • Ip and 19q LOH associated with prolonged survival • CDKN2A tumor suppressor gene deletions associated with shorter survival • Positive prognostic factors o Age < 50 years o Karnofsky performance status (KPS) 90-100 o Tumors :::;4 cm o Complete tumor resection

• Many gliomas may mimic AO • Presence of Ca++, cortical expansion may help distinguish AOs from other gliomas

Image Interpretation

Pearls

• AOs cannot be reliably differentiated from oligos on imaging features alone • Neoplastic cells almost always found beyond areas of abnormal signal intensity • New enhancement in a previously non enhancing oligodendroglioma may indicate malignant progression

1.

Lev MH et al: Glial tumor grading and outcome prediction using dynamic spin-echo MR susceptibility mapping compared with conventional contrast-enhanced MR: confounding effect of elevated rCBV of oligodendrogliomas. AJNR25:214-21,2004 2. Engelhard HH et al: Oligodendroglioma and anaplastic oligodendroglioma: clinical features, treatment, and prognosis. Surg Neurol. 60(5):443-56, 2003 3. McBryde CW et al: Anaplastic oligodendroglioma with metastasis to the spinal cord. Br J Neurosurg. 17(4):364-6, 2003 4. Naugle DK et al: Oliogastrocytoma. Radio Graphics 24:598-600, 2002 5. Wong TZ et al: Positron emission tomography imaging of brain tumors. Neuroimag Clin N Am 12:615-26, 2002 6. Reifenberger G et al: Pathology and genetics of tumours of the nervous system: Oligodendroglioma. Lyon, rARC Press, 56-69,2000 7. Burton EC et al: Malignant gliomas. Curr Treat Options Oncol. 1(5):459-68, 2000 8. Derlon JM et al: Non-invasive grading of oligodendrogliomas: correlations between in vivo metabolic pattern and histopathology. Eur J Nucl Med. 27:778-87, 2000 9. Prayson RA et al: Clinicopathologic Study of Forty-Four Histologically Pure Supratentorial Oligodendrogliomas. Ann Diagn Pathol 4:218-27, 2000 10. Jeremic B et al: Combined treatment modality for anaplastic oligodendroglioma: a phase II study. J Neurooncol. 43(2):179-85, 1999

Neoplasms and Tumorlike Lesions

Typical (Left) Axial T1WI MR shows a discrete mass with solid

and cystic components and expansion of the cortex. Hyperintensity likely represents calcium and/or blood products (arrow). AO at resection. (Right) Axial T2WI MR in the same case shows a heterogeneous mass with cortical expansion, mild mass effect. Although it appears discrete, this AO is infiltrative, has poor prognosis. Imaging mimics oligo.

Typical (Left) Axial T2WI MR shows

hyperintensity involving the temporal and parietal lobes in this patient diagnosed with an occipital oligodendroglioma 4 years prior. AO was found at repeat resection. (Right) Axial T1 C+ MR in the same case shows intense heterogeneous enhancement with ependymal extension (arrow). New enhancement represents malignant progression of this previously treated oligo.

Variant (Left) Axial NECT shows a

hemorrhagic frontal lobe mass crossing the corpus callosum. AO at resection. Imaging mimics a CBM. Hemorrhage is relatively uncommon in AO. (Right) Axial PO/Intermediate MR shows a heterogeneous mass with solid and cystic portions involving the corpus callosum with mild edema despite its large size. AOs rarely involve the corpus callosum.

Neoplasms and Tumorlike Lesions

6.··. 49

Axial TlWI MR shows a circumscribed solid and cystic mass with a heterogeneous appearance of the solid portion, typical of astroblastoma. Note lack of edema. Young adult with weakness.

Definitions • Rare glial neoplasm with perivascular pseudorosettes and variable biological behavior

General Features

6 50

• Best diagnostic clue: Large hemispheric circumscribed solid and cystic mass with a "bubbly" appearance • Location o Cerebral hemispheres typical, often superficial o Other locations: Corpus callosum, cerebellum, optic nerves, brainstem, cauda equina • Size: Variable, typically large at presentation • Morphology: Circumscribed, lobular solid/cystic mass

CT Findings • NECT o Solid and cystic lobular mass, solid portion may be mildly hyperdense o Occasional punctate Ca++ • CECT: Heterogeneous enhancement

MR Findings • T1WI: Solid/cystic mass; solid portion hypointense

DDx: Hemispheric

Ependymoma

Axial Tl C+ MR shows the classic enhancement pattern of astroblastoma. There is heterogeneous enhancement of the solid portion and rim enhancement of the cystic portion (arrow).

• T2WI o Solid and cystic mass with heterogeneous "bubbly" appearance of solid portion o Solid portion isointense to gray matter o Relative lack of peritumoral hyperintensity • T1 C+: Heterogeneous enhancement of solid portion, rim-enhancement of cystic portion • MRS o Rare reports show decreased NAA, increased Cho • Additional peaks: Lipids, myo-inositol, glycine

Imaging Recommendations • Protocol advice: Multiplanar

contrast-enhanced

Ependymoma • Supratentorial (1/3): Heterogeneous parenchymal/periventricular enhancing mass • Hemorrhage, necrosis, Ca++, and edema common

Primitive neuroectodermal

tumor (PNET)

• Pediatric tumor, infants and young children • Peripheral, heterogeneous parenchymal mass • Hemorrhage, cysts, and Ca++ common

Atypical teratoid-rhabdoid

tumor (AT/RhT)

• Pediatric tumor, infants and young children

Enhancing Masses

PNET

MR

Oligodendroglioma

Neoplasms and Tumorlike Lesions

Metastases

ASTROBLASTOMA •

Imaging Findings • Best diagnostic clue: Large hemispheric circumscribed solid and cystic maSS with a "bubbly" appearance • Tl C+: Heterogeneous enhancement of solid portion, rim-enhancement of cystic portipn

Top Differential

Diagnoses

• Ependymoma • Primitive neuroectodermal • Atypical teratoid-rhabdoid

• Occur at all ages} most commonly children and young adults • Surgical resection is treatment of choice

tumor (PNET) tumor (AT/RhT)

• Heterogeneous solid mass with hemorrhage, Ca++, cyst formation

necrosis,

Oligodendroglioma • Peripheral, cortically-based mass +/- enhancement • Ca++ common; minimal surrounding edema

Glioblastoma

Clinical Issues

multiforme

(GBM)

• Poorly marginated, infiltrating mass with edema • Thick, irregular enhancing rind with central necrosis

Natural History & Prognosis • Low grade astroblastomas may have long term survival • Anaplastic histology is associated with recurrence, tumor progression

Treatment • Surgical resection is treatment of choice • Adjuvant radiation therapy and chemotherapy high grade lesions

for

Metastases • Older patients, primary often known • Multiple lesions common with marked edema

I DIAGNOSTIC

CHECKLIST

Consider • Solid and cystic circumscribed patient, may be astroblastoma

I PATHOLOGY

mass in a young

General Features • General path comments: Cell of origin debated as they share features of astrocytomas and ependymomas • Etiology o Controversial, thought to arise from an embryonic cell programmed to become an astrocyte o Some authors support a tanycyte cell origin • Epidemiology: Rare, 0.5-2.8% of primary gliomas

Gross Pathologic & Surgical Features • Circumscribed solid mass, homogeneous cut surface • Cysts are common; necrosis may be seen

Microscopic Features • Perivascular pseudorosettes: Astrocytic cell processes radiate toward a central, often hyalinized blood vessel • Oval to elongated hyperchromatic nuclei; +/- Ca++ • Immunohistochemistry: GFAP +, vim en tin +, S-100 +

ISELECTED REFERENCES 1.

2.

3.

Burger PC et al: Surgical pathology of the nervous system and its coverings: The Brain: Tumors. 4th ed. Philadelphia, Churchill Livingstone. 254-6, 2002 PortjD et al: Astroblastoma: radiologic-pathologic correlation and distinction from ependymoma. AJNRAm J Neuroradiol. 23(2):243-7, 2002 Brat DJ et al: Astroblastoma: clinicopathologic features and chromosomal abnormalities defined by comparative genomic hybridization. Brain Pathol. 10(3):342-52, 2000

I IMAGE

GALLERY

Staging, Grading or Classification Criteria • Low grade or high grade based on histologic features

I CLINICAL ISSUES Presentation • Most common

signs/symptoms:

Seizures, focal deficit

Demographics • Age o Occur young o Rarely • Gender:

at all ages, most commonly children and adults in infants; congenital cases reported No significant gender predominance

(Left) Axial T2WI MR shows a solid and cystic mass with a heterogeneous "bubbly" appearance of the solid portion, typical of astroblastoma. Note the focal calcification (arrow) and lack of edema. (Right) Axial T7 C+ MR shows mass with peripheral rim and nodular enhancement (solid portion, arrow). Note lack of significant mass effect for size of the lesion (Courtesy;. AufderHeide, MO).

Neoplasms and Tumorlike Lesions

6 51

Sagittal graphic shows posterior fossa ependymoma extending out through 4th ventricle foramen. This pattern of growth increases difficulty of surgical resection.

Axial T1 C+ MR shows lobular enhancing mass extending out 4th ventricle through foramen of Luschka into left cerebellopontine angle, classic cellular ependymoma.

Radiographic Findings Abbreviations • Ependymoma

and Synonyms (subtypes

=

cellular, papillary, etc)

May be helpful in showing "drop"

CT Findings

Definitions • Slow-growing tumor of ependymal

cells

General Features 52

• Myelography: metastases

• Best diagnostic clue o Heterogeneous signal o Soft or "plastic" tumor: Squeezes out through 4th ventricle foramina into cisterns o Indistinct interface with floor of 4th ventricle • Location o 2/3rd infra tentorial, 4th ventricle o 1/3rd supratentorial, majority periventricular WM • Size: 2-4 cm • Morphology o Irregular shape in posterior fossa • Accommodates to shape of ventricle or cisterns o Spherical in cerebral hemisphere

• NECT o Infratentorial • 4th ventricle tumor, extends into CPA/cisterna magna • Ca++ common (50%); +/- cysts, hemorrhage • Hydrocephalus common o Supratentorial • Large heterogeneous periventricular mass • Ca++ common (50%) • CECT: Variable heterogeneous enhancement

MR Findings • TlWI o Heterogeneous, usually iso- to hypointense o Cystic foci slightly hyperintense to CSF o Hyperintense Ca++, blood products • T2WI o Heterogeneous, usually iso-to hyperintense o Hyperintense cystic foci o Hypointense Ca++, blood products • FLAIR o Can show sharp interface between tumor and CSF o Tumor cysts very hyperintense to CSF

DO'': Pediatric Posterior Fossa Masses

PNET-MB

Pilocytic Astrocytoma

AT/RhT

Neoplasms and Tumorlike Lesions

P Fossa Dermoid

EPENDYMOMA Key Facts Terminology

Pathology

• Slow-growing tumor of ependymal

• Arise from ependymal cells or ependymal rests • Third most common posterior fossa tumor in children (after PA and PNET-MB) • WHO grade II (low grade, well-differentiated) • WHO grade III (high grade, anaplastic)

cells

Imaging Findings • Soft or "plastic" tumor: Squeezes out through 4th ventricle foramina into cisterns • 2/3rd infratentorial, 4th ventricle • 1/3rd supratentorial, majority periventricular WM • Ca++ common (50%); +/- cysts, hemorrhage • MR spectroscopy alone does not reliably differentiate ependymoma from astrocytoma or PNET-MB • High-quality sagittal imaging can distinguish point of origin as floor vs roof of 4th ventricle

Top Differential

Diagnoses

• Medulloblastoma

(PNET-MB)

• • • •

• Clinical profile: 1-5 yo with headache, vomiting • Gross total resection + XRT correlates with improved survival

Diagnostic Checklist • Indistinct interface with floor of 4th ventricle = ependymoma • Indistinct interface with roof of 4th ventricle PNET-MB

=

T2* GRE: "Blooming" of hypo intense Ca++ foci DWI: May see hyperintensity (rare) Tl C+: Mild to moderate, heterogeneous enhancement MRS o NAA I, Cho t • NAA:Cho ratio higher than in PNET-MB o Lactate t o MR spectroscopy alone does not reliably differentiate ependymoma from astrocytoma or PNET-MB

Angiographic Findings • Conventional: Variable: Ranges from avascular to hypervascular with shunting

Nuclear Medicine

Clinical Issues

Brainstem glioma • Infiltrating mass expanding brains tern • Homogeneous signal on MR • May project into 4th ventricle

Atypical teratoid-rhabdoid

tumor (AT/RhT)

• Large mass with cyst or necrosis • Variable enhancement pattern

Dermoid/ epidermoid • Congenital epithelial inclusion lesions • Nonenhancing, extra-axial

Choroid plexus papilloma • Vigorously enhancing intraventricular tumor • 4th ventricle location more common in adults

Findings

• PET o Increased FDG uptake o May help differentiate recurrent tumor from radiation necrosis

• Heterogeneous supratentorial mass in young adults • Frontal lobe lesion with Ca++

Oligodendroglioma

Imaging Recommendations

Glioblastoma

• Best imaging tool: MR with contrast • Protocol advice o MR with contrast, CT, MRS before surgery o Need a combination of imaging & clinical findings to distinguish from PNET-MB o High-quality sagittal imaging can distinguish point of origin as floor vs roof of 4th ventricle

• Older adults • Heterogeneous malignant supratentorial • Necrosis, hemorrhage common

I DIFFERENTIAL DIAGNOSIS

IPATHOlOG¥

Medulloblastoma

General Features

• • • •

(PNET-MB)

Hyperdense on NECT Homogeneous mass Arises from roof of 4th ventricle More distinct interface with floor

Cerebellar

pilocytic astrocytoma (PA)

• Heterogeneous tumor of cerebellar hemisphere • Cyst with mural nodule • Solid portion enhances vigorously

multiforme mass

Pleomorphic xanthoastrocytoma • Uncommon supratentorial • Cortically-based tumor

astrocytoma

subtype

• General path comments o 4 subtypes encountered in brain • Cellular: Most common type in 4th ventricle • Papillary: Extensive epithelial surface • Clear-cell: Microscopic features of oligodendroglioma • Tanycytic: Elongated cells resembling pilocytic astrocytoma

Neoplasms and Tumorlike Lesions

6 53

•

•

•

•

o Myxopapillary ependymoma nearly exclusive to filum terminale Genetics o Intracranial tumors associated with aberrations on chromosomes lq, 6q, 9, 13, 16, 17, 19,20,22 • Gain of lq, loss on 9 associated with anaplastic tumors o Spinal lesions associated with chromosome 7, 22 abnormalities • Chromosome 22 abnormalities associated with NF2 (multiple spinal ependymomas) Etiology o Arise from ependymal cells or ependymal rests • Periventricular ependymal rests account for supratentorial tumors o Possible link with simian virus 40 (SV40) • Large percentage express SV40 DNA sequences • SV40 can induce ependymoma when injected in rodents Epidemiology o 3-5% of all intracranial tumors o 15% of posterior fossa tumors in children • Third most common posterior fossa tumor in children (after PA and PNET-MB) Associated abnormalities: Spinal ependymoma known component of NF2

Gross Pathologic & Surgical Features • • • • •

Well demarcated Soft, lobulated, grayish-red mass +/- Cysts, necrosis, hemorrhage Extrudes through 4th ventricle outlet foramina Typically displaces rather than invades adjacent brain parenchyma

Microscopic 54

Features

• Ependymoma o Perivascular pseudorosettes o True ependymal rosettes (less frequent) o Moderately cellular with low mitotic activity o Occasional nuclear atypia o Immunohistochemistry: S-100, GFAP, vimentin + • Anaplastic ependymoma o High cellularity, nuclear atypia, hyperchromatism o Brisk mitotic activity o +/- Microvascular proliferation o Occasional pseudopalisading or necrosis in most malignant lesions

Staging, Grading or Classification Criteria • WHO grade II (low grade, well-differentiated) • WHO grade III (high grade, anaplastic)

o Infants: Irritability, lethargy, developmental vomiting, macrocephaly

Demographics • Age o Bimodal age distribution • Major peak = 1-5 Y • Second smaller peak = mid 30s • Gender: Slight male predominance

Natural History & Prognosis • 3-17% CSF dissemination • Generally poor prognosis o Overall 5 year survival 60-70% o Worse with 1 grade

Treatment • Surgical resection +/- chemo, radiation therapy (XRT) o Gross total resection + XRT correlates with improved survival o 5 year survival after recurrence = 15% • Surgical resection often difficult due to adherence and infiltrating nature of tumor

Consider • Much less common than PNET-MB or PA • Gross total resection has greater impact on survival than in PNET-MB or PA • Surveillance imaging to detect asymptomatic recurrence can increase survival

Image Interpretation

Presentation

Pearls

• Indistinct interface with floor of 4th ventricle ependymoma • Indistinct interface with roof of 4th ventricle PNET-MB

1.

2.

3.

4.

5.

• Most common signs/symptoms: Increased intracranial pressure: Headache, nausea, vomiting • Clinical profile: 1-5 yo with headache, vomiting • Other o Ataxia, hemiparesis, visual disturbances, neck pain, torticollis, dizziness

delay,

6.

7.

= =

Korshunov A et al: The histologic grade is a main prognostic factor for patients with intracranial ependymomas treated in the microneurosurgical era. Cancer 100:1230-7, 2004 Korshunov A et al: Gene expression patterns in ependymomas correlate with tumor location, grade, and patient age. Am] Pathol. 163(5):1721-7, 2003 Fouladi M et al: Clear cell ependymoma: a clinicopathologic and radiographic analysis of 10 patients. Cancer. 98(10):2232-44, 2003 Dyer S et al: Genomic imbalances in pediatric intracranial ependymomas define clinically relevant groups. Am] Pathol. 161(6):2133-41,2002 Good CD et al: Surveillance neuroimaging in childhood intracranial ependymoma: how effective, how often, and for how long? ] Neurosurg. 94(1):27-32, 2001 Hirose Y et al: Chromosomal abnormalities subdivide ependymal tumors into clinically relevant groups. Am] Pathol. 158(3):1137-43,2001 Figarella-Branger D et al: Prognostic factors in intracranial ependymomas in children.] Neurosurg. 93(4):605-13, 2000

Neoplasms and Tumorlike

Lesions

Typical (Left) Sagittal T7 WI MR shows tumor filling and enlarging 4th ventricle and extending inferiorly through foramen magnum. Jet of CSF flow can be seen in cerebral aqueduct (arrow). (Right) Micropathology, low power, H&E stain shows relatively cellular tumor with characteristic perivascular pseudorosettes (arrows), resulting in clear areas around vessels.

(Left) Axial NECT shows irregularly shaped 4th ventricular tumor with Ca++ and cyst (open arrow) extending laterally into right CPA (curved arrow). Classic ependymoma extending from 4th V into CPA cistern. (Right) Axial T7 C+ MR in the same case shows mild to moderate heterogeneous enhancement of the tumor. Note extension from 4th V (open arrow) through foramen of Luschka into CPA cistern (arrows).

Variant (Left) Coronal T7 C+ MR shows heterogeneously enhancing mass centered in white matter of right parietal lobe. Surgery disclosed typical cellular ependymoma. (Right) Axial T2WI MR shows a large cystic parietal lobe mass with moderate vasogenic edema anteriorly. Supratentorial ependymomas are typically extraventricular, centered in parietal peri ventricular WM.

Neoplasms and Tumorlike Lesions

6 55

Sagittal graphic shows a solid, well-circumscribed mass arising from the floor of the 4th ventricle with mild mass effect (arrow). Note lack of hydrocephalus, typical of subependymoma.

Abbreviations

• Morphology o Well-defined solid lobular mass o When large, may see cysts, hemorrhage,

and Synonyms

• Older literature: Subependymal glomerulate astrocytoma, subependymal astrocytoma, subependymal mixed glioma

Definitions • Rare, benign well-differentiated ependymal tumor

Sagittal T2WI MR shows a solid hyperintense mass along the inferior 4th ventricle (arrow). 43 year old male with headaches and trigeminal neuralgia. Subependymoma.

intraventricular

Ca++

CT Findings • NECT o Isodense to hypodense intraventricular mass o Cysts or Ca++ may be seen in larger lesions o Rarely hemorrhage • CECT o No enhancement, mild enhancement typical o Heterogeneous enhancement may be seen

MR Findings

56

General Features • Best diagnostic clue: T2 hyperintense lobular, nonenhancing intraventricular mass • Location o Intraventricular, inferior 4th ventricle typical (60%) • Often protrudes through foramen of Magendie o Other: Lateral> 3rd ventricle> spinal cord • Lateral ventricle: Attached to septum pellucidum or lateral wall o Rare: Periventricular • Size o Typically small, 1-2 cm o May become large, > 5 cm • When large, more commonly symptomatic

DDx: Intraventricular

• TlWI o Intraventricular mass, hypointense or isointense to white matter o Typically homogeneous solid mass o Heterogeneity may be seen in larger lesions • T2WI o Hyperintense intraventricular mass o Heterogeneity related to cystic changes, blood products or Ca++ may be seen in larger lesions o No edema seen in adjacent brain parenchyma • FLAIR o Hyperintense intraventricular mass o No edema seen in adjacent brain parenchyma • T2* GRE: May see Ca++ "bloom" in larger lesions and 4th ventricle location

Masses

""'.

/'

•

(.

Ependymoma

Central Neurocytoma

.I

Giant Cell Astrocytoma

Neoplasms and Tumorlike Lesions

Hemangioblastoma

SUBEPENDYMOMA Key

• Choroid plexus papilloma (CPP) • Hemangioblastoma • Metastases

Terminology • Rare, benign well-differentiated ependymal tumor

Facts

intraventricular

Imaging Findings

Pathology

• Best diagnostic clue: T2 hyperintense lobular, nonenhancing intraventricular mass • Intraventricular, inferior 4th ventricle typical (60%) • Other: Lateral> 3rd ventricle> spinal cord • Well-defined solid lobular mass • When large, may see cysts, hemorrhage, Ca++ • Variable enhancement, typically none to mild

• WHO grade I

Top Differential Diagnoses

. Clinical Issues • Most asymptomatic • Other signs/symptoms: Related to increased intracranial pressure, hydrocephalus • Middle-aged/elderly adult, (typically 5th-6th decades) • Surgical resection is curative in most cases

Diagnostic Checklist

• Ependymoma • Central neurocytoma • Subependymal giant cell astrocytoma

• 4th or lateral ventricular hyperintense elderly male? Think subependymoma!

• Tl C+ o Variable enhancement, typically none to mild o Marked enhancement may be seen: More common in 4th than lateral ventricular subependymomas

Nuclear Medicine Findings • PET o Rare reports show exceedingly low rates of glucose metabolism and kinetic constants • Hypometabolism indicates low cellular density and slow growth

Imaging Recommendations • Best imaging tool o MR is most sensitive o CT may be useful for calcification • Protocol advice: Multiplanar contrast-enhanced including T2WI, FLAIR

mass in an

Hemangioblastoma • Cystic mass with enhancing mural nodule • Typically cerebellar hemispheres, often at pial surface • Rarely intraventricular

Metastases • Primary tumor often known • Often multiple lesions at gray-white junctions • Typically involve choroid plexus if intraventricular

Cavernous malformation • Rarely intraventricular, 2.5-11 % of cases • Ca++ and T2 hypointense hemosiderin rim common • Enhancement variable

MR

57

IPAIHOlOQ¥ General Features

• Typical "bubbly" appearance, Ca++ common • Lateral ventricle, attached to septum pellucidum • Moderate to strong enhancement

• General path comments o Contains both astrocytes and ependymal elements o Occasionally coexists with cellular ependymomas o Rare: Multiple lesions • Genetics o Most are sporadic o Rare familial cases have been reported • Etiology: Proposed cells of origin: Subependymal glia, astrocytes of subependymal plate, ependymal cells • Epidemiology o Reported in 0.4% of 1000 consecutive autopsies o Account for 0.7% of intracranial neoplasms

Subependymal giant cell astrocytoma

Gross Pathologic & Surgical Features

• Enhancing mass at foramen of Monro • Ca++ common • Tuberous sclerosis patients: Subependymal cortical tubers, white matter lesions

• Solid, well delineated, white to grayish avascular mass • Firmly attached to site of origin o Fourth ventricle: Floor typical o Lateral ventricle: Septum pellucidum or lateral wall • Larger lesions are lobulated, more often Ca++; hemorrhage, cyst formation common • Fourth ventricular lesions often protrude out of foramen of Magendie

I DIFFERENTIAl..DIA<JNC1SIS Ependymoma • • • •

Younger patients Heterogeneous, enhancing mass with edema Typically 4th ventricular mass with hydrocephalus Often parenchymal when supratentorial

Central neurocytoma

nodules,

Choroid plexus papilloma (CPP) • Typically pediatric tumors, lateral ventricle • In adults, 4th ventricle • Enhancing papillary mass, hydrocephalus common

6

Neoplasms and Tumorlike Lesions

Microscopic

Image Interpretation

Features

• Highly fibrillar, low cellularity with nuclei clustering • Microcystic change common in tumors near foramen of Monro • Ca++ is commonly seen in 4th ventricle tumors • Mitoses are rare or absent • Immunohistochemistry: Strongly GFAP + • Electron microscopy: Closely packed cell processes filled with glial intermediate filaments

Staging, Grading or Classification Criteria

1.

2.

• WHO grade I 3.

Presentation

4.

• Most common signs/symptoms o Most asymptomatic o 40% become symptomatic, often supratentorial o Other signs/symptoms: Related to increased intracranial pressure, hydrocephalus • Headache, gait ataxia, visual disturbance, cranial neuropathy, nystagmus, vertigo, nausea, vomiting

5.

6.

7.

Demographics • Age o Middle-aged/elderly adult, (typically 5th-6th decades) • Asymptomatic patients: Mean age = 60 years • Symptomatic patients: Mean age = 40 years o Rare in children • Gender: Male predominance

6 58

Natural History & Prognosis • Excellent prognosis for supratentorial • Recurrence is extremely rare • Complications include hydrocephalus hemorrhage

8.

9.

10. 11.

lesions and rarely

12.

13.

Treatment • Surgical resection is curative in most cases o Lateral ventricle lesions, complete resection o Fourth ventricle lesions, subtotal resection more common • Perioperative mortality low, but increased by attachment of tumor to adjacent structures • If hydrocephalus, CSF diversion may be required • Adjuvant radiation therapy is controversial, likely of no benefit • Conservative management with serial imaging if asymptomatic

14. 15. 16.

17.

18.

19.

Consider

20.

• Other intraventricular tumors tend to enhance more prominently • May be indistinguishable from ependymoma, central neurocytoma

Pearls

• 4th or lateral ventricular hyperintense mass in an elderly male? Think subependymoma! • T2WI and FLAIR may be most sensitive

Seol H] et al: A case of recurrent subependymoma with sub ependymal seeding: case report. ] Neurooncol. 62(3):315-20, 2003 1m SH et al: Clinicopathological study of seven cases of symptomatic supratentorial subependymoma. ] Neurooncol. 61(1):57-67, 2003 Burger PC et al: Surgical pathology of the nervous system and its coverings: The Brain: Tumors. 4th ed. Philadelphia, Churchill Livingstone. 250-4, 2002 Ironside ]W et al: Diagnostic pathology of nervous system tumours: Ependymal and choroid plexus tumors. 1st ed. Edinburgh, Churchill Livingstone, 145-83,2002 Nishio S et al: Tumours around the foramen of Monro: clinical and neuroimaging features and their differential diagnosis.] Clin Neurosci. 9(2):137-41, 2002 Fontenele GI et al: Symptomatic child case of sub ependymoma in the fourth ventricle without hydrocephalus. Radiat Med. 19(1):37-42, 2001 Wiestler OD et al: Pathology and genetics of tumours of the nervous system: Subependymoma. Lyon, IARC Press, 80-1,2000 Mineura K et al: Subependymoma of the septum pellucidum: characterization by PET.] Neurooncol. 32(2):143-7, 1997 Duong H et al: Magnetic resonance imaging of lateral ventricular tumours. Can Assoc Radiol]. 46(6):434-42, 1995 Hoeffel C et al: MR manifestations of subependymomas. A]NR Am] Neuroradiol. 16(10):2121-9, 1995 Chiechi MV et al: Intracranial subependymomas: CT and MR imaging features in 24 cases. A]R Am] Roentgenol. 165(5):1245-50, 1995 Furie DM et al: Supratentorial ependymomas and subependymomas: CT and MR appearance. ] Com put Assist Tomogr. 19(4):518-26, 1995 Silverstein]E et al: MRI of intracranial subependymomas.] Comput Assist Tomogr. 19(2):264-7, 1995 Ryken TC et al: Familial occurrence of subependymoma. Report of two cases.] Neurosurg. 80(6):1108-11, 1994 Iqbal Z et al: Subependymoma of the lateral ventricle: case report and literature review. Br] Neurosurg. 8(1):83-5, 1994 Cheng TM et al: Simultaneous presentation of symptomatic subependymomas in siblings: case report and review. Neurosurgery 33:145-50, 1993 Lindboe CF et al: Hemorrhage in a highly vascularized subependymoma of the septum pellucidum: case report. Neurosurgery. 31(4):741-5, 1992 Marra A et al: Intraventricular sub ependymoma presenting as subarachnoid hemorrhage: case report. ] Neurosurg. 35:213-5, 1991 Spoto GP et al: Intracranial ependymoma and subependymoma: MR manifestations. A]NR Am] Neuroradiol. 11:83-91, 1990 Lobato RD et al: Symptomatic subependymoma: report of four new cases studied with computed tomography and review of the literature. Neurosurg. 19:594-8, 1986

Neoplasms and Tumorlike

Lesions

Typical (Left) Coronal graphic shows

a solid, well circumscribed intraventricular mass attached to the septum pellucidum with no mass effect or hydrocephalus. Subependymomas are typically asymptomatic. (Right) Axial T1 C+ MR shows a well circumscribed enhancing mass attached to the septum pellucidum, subependymoma. Older male with headaches. No enhancement or mild enhancement is typical.

Typical

~J, . ..

"

,

. \."

j'

-"

.

,

~.

" ~. 71

\ I \

", .

(Left) Axial NECT shows a calcified 4th ventricular mass in this 52 year old female. Calcification is more commonly seen in 4th ventricular subependymomas. (Right) Sagittal T1 C + M R shows a classic nonenhancing 4th ventricular subependymoma (arrow). 4th ventricular floor origin is typical. The mass may be best seen on T2WI and/or FLAIR. 60 year old mak.

t~/JJJ

Variant (Left) Axial T2WI MR shows a circumscribed

hyperintense subependymal mass. No enhancement was present on contrast images. 56 year old male with headaches. Subependymoma, atypical periventricular location. (Right) Sagittal T2WI MR shows a heterogeneous mass filling the 4th ventricle with inferior extension. Enhancement was present on contrast images. Cysts, blood and Ca++may be seen in larger lesions.

Neoplasms and Tumorlike Lesions

6 59

Axial graphic shows a choroid plexus papilloma arising from glomus of the left lateral ventricular trigone. Note frond-like surface projections (arrow).

Axial CECT shows a vividly enhancing lobulated CPP arising from the trigone of left lateral ventricle. Note normal contralateral choroid plexus (arrow), "overproduction" hydrocephalus.

Radiographic Findings Abbreviations

and Synonyms

• Choroid plexus papilloma (CPP) • Choroid plexus tumor (CPT) (note: Can be papilloma, CPP or carcinoma, CPCA)

Definitions • Intraventricular, papillary neoplasm derived from choroid plexus epithelium

60

General Features • Best diagnostic clue: Child with strongly enhancing, lobulated intraventricular mass • Location o CPPs occur in proportion to amount of normally present choroid plexus o 50% =:> atrium of lateral ventricle, left> right o 40% =:> fourth ventricle (posterior medullary velum) & foramina of Luschka o 10% =:> third ventricle (roof) o 5% =:> multiple sites • Size: Often of remarkable size at diagnosis • Morphology: Cauliflower-like mass

DDx: Intraventricular

• Radiography o Increased cranial-to-facial ratio o Sutural diastasis due to hydrocephalus

CT Findings • NECT o Intraventricular bosselated mass o 75% iso- or hyperattenuating o Ca++ in 25%, hydrocephalus • CECT o Intense, homogeneous enhancement • Heterogeneous enhancement suggests choroid plexus carcinoma (CPCA) o Occasionally, minimal parenchymal invasion o Rarely vascular pedicle twists leading to CPP infarction and dense Ca++ ("brain stone") • CTA: Choroidal artery enlargement for lateral ventricular (trigonal) CPPs

MR Findings • TlWI o Well delineated, lobulated mass o Iso- to hypointense o CSF trapped between papillae =:> a mottled appearance • T2WI o Iso- to hyperintense

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Ependymoma

Astrocytoma

Neoplasms and Tumorlike Lesions

~

Meningioma (NF2)

CHOROID PLEXUS PAPILLOMA Key Facts • Metastasis

Terminology • Intraventricular, papillary neoplasm derived from choroid plexus epithelium

Imaging Findings • Best diagnostic clue: Child with strongly enhancing, lobulated intraventricular mass • 50% ::::> atrium of lateral ventricle, left> right • 40%::::>fourth ventricle (posterior medullary velum) & foramina of Luschka • Hyperechoic mass with frond-like projections • Perform contrast-enhanced MR of entire neuraxis before surgery

Top Differential

Diagnoses

Pathology • Most common brain tumor in children < 1 Y

Clinical Issues • Most common signs/symptoms: Macrocrania, bulging fontanelle, vomiting, headache, ataxia • Lateral ventricular CPPs (infants and children)

Diagnostic Checklist • Intraventricular mass in 1st year of life? Consider CPPl • Imaging alone cannot reliably distinguish CPP from CPCA

• Choroid plexus carcinoma (CPCA) • Ependymoma

o ± Internal linear and branching vascular flow voids o Large CPP may bury itself within brain parenchyma • Extensive invasion suggests CPCA o Hydrocephalus o Foci of diminished signal representing Ca++ o ± Intratumoral hemorrhage • FLAIR o Bright periventricular signal • Transependymal interstitial edema due to ventricular obstruction • T2* GRE: ± Foci of diminished signal if Ca++ and/or blood products are present • Tl C+ o Robust homogeneous enhancement o Occasional cysts and small foci of necrosis o ± CSF seeding lesions ·MRA o Flow related signal within mass o Enlarged choroidal artery (trigonal mass) • MRV: Flow related signal • MRS: !NAA, t choline, lactate if necrotic

Ultrasonographic

Findings

o llC-Methionine ::::>t tumor-to-normal brain ratios in CPP compared to gliomas o FDG ::::> unable to distinguish between CPP and glioma • Tc-99m sestamibi ::::> differentiates CPTs (sestamibi positive) from non-neoplastic lesions (necrosis)

Imaging Recommendations • Best imaging tool: MRI • Protocol advice o Perform contrast-enhanced MR of entire neuraxis before surgery o T2* GRE for detection of blood products and Ca++

6 I DIFFERENFflA[DIAG~~SIS Physiologic enlargement • Collateral venous drainage (Sturge-Weber) • Enlargement of choroid following hemispherectomy

Choroid plexus carcinoma (CPCA) • Difficult to distinguish CPP from CPCA by imaging findings alone • More likely to invade brain

• Real Time o Hyperechoic mass with frond-like projections o Mass echogenicity similar to normal choroid plexus o Hydrocephalus • Pulsed Doppler o Vascular pedicle and internal sampling of mass • Bidirectional flow through diastole • Arterial tracing shows low impedance • Color Doppler: Hypervascular mass with bidirectional flow

Xanthogranuloma

Angiographic

• Known history of primary tumor • Rare in children

Findings

• Conventional o Enlarged choroidal artery o Prolonged vascular stain o A-V shunting

Nuclear Medicine • PET

Findings

61

Ependymoma • More common in 4th ventricle and in children • Juvenile xanthogranuloma::::> histiocytosis

a non-Langerhans

Metastasis

Meningioma • Different age group, more delineated configuration • Consider NF2

Subependymoma • Nonenharicing

Neoplasms and Tumorlike Lesions

intraventricular

mass

and oval in

cell

Vascular lesion

Demographics

• AVM • Cavernous angioma • Many presumed VH cases may be CPPs • Proliferation index (MIB-l) is useful to distinguish

• Age o Lateral o Fourth • Gender o Lateral o Fourth

General Features

• Benign, slowly growing o May seed CSF pathways (CPP & CPCA) • 5 year survival - 100%

Villous hypertrophy

(VH)

ventricular ventricular

CPPs (infants and children) CPPs (adults)

ventricle ~ male/female ventricle ~ male/female

ratio 1:1 ratio 3:2

Natural History & Prognosis

6

• General path comments o Pink or reddish-tan, cauliflower-like, intraventricular mass o CPPs may be invaginated in brain parenchyma & show limited invasion • Genetics o Li-Fraumeni and Aicardi syndromes (possible TP53 germline mutation) o Association of CPP and duplication of short arm of chromosome 9 • Etiology: DNA sequences from simian virus 40 (SV40), have been found in CPTs • Epidemiology o 0.5% of all adult brain tumors o 2-4% of all pediatric brain tumors o Most common brain tumor in children < 1 Y • 50% manifest in first decade • 86% present by 5 years • Associated abnormalities o Diffuse hydrocephalus from • CSF overproduction • Mechanical obstruction • Impaired CSF resorption (due to hemorrhage)

62

Gross Pathologic & Surgical Features • Well-circumscribed lobulated intraventricular • ± Cysts, necrosis, and hemorrhage

Treatment • Total surgical resection

Consider • Intraventricular

Image Interpretation

Pearls

• Imaging alone cannot reliably distinguish CPP from CPCA o Final diagnosis is histologic • Lobulated intraventricular mass with strong enhancement in a young child most likely represents a choroid plexus tumor

I SELECTED REFERENCES 1.

2.

mass 3.

Microscopic Features • Fibrovascular connective tissue fronds, covered by cuboidal or columnar epithelium • Mitotic activity, necrosis, and brain invasion typically absent • Resembles non-neoplastic choroid plexus • Immunohistochemistry o Cytokeratin and vimentin are expressed by CPPs o S-100 protein in 90% of CPPs

mass in 1st year of life? Consider CPP!

4.

5.

6.

Staging, Grading or Classification Criteria

7.

• WHO grade I

8.

Noguchi A et al: Choroid plexus papilloma of the third ventricle in the fetus. J Neurosurg. (Pediatrics 2) 100:224, 2004 D'Ambrosio AL et al: Villous hypertrophy versus choroid plexus papilloma: a case report demonstrating a diagnostic role for the proliferation index. Pediatr Neurosurg. 39:91-6, 2003 Shin JH et al: Choroid plexus papilloma in the posterior cranial fossa: MR, CT, and angiographic findings. J Clin Imaging 25: 154-62,2001 Levy ML et al: Choroid plexus tumors in children: Significance of stromal invasion. Neurosurg 48: 303-9, 2001 Aguzzi A et al: Choroid plexus tumors. In Kleihues P, Cavenee WK (eds): Tumors of the Nervous System, 84-6, IARC Press, 2000 Sarkar C et al: Choroid plexus papilloma: a clinicopathological study of 23 cases. Surg Neurol 52: 37-39,1999 Knierim DS et al: Choroid plexus tumors in infants. Pediatr Neurosurg 16: 276-80, 1991 Valladares JB et al: Malignant choroid plexus papilloma with extraneural metastasis. J Neurosurg 52: 251, 1980

Presentation • Most common signs/symptoms: Macrocrania, bulging fontanelle, vomiting, headache, ataxia • Clinical profile o Child in first two years of life with signs and symptoms of elevated ICP • Focal neurologic signs and symptoms suggests CPCA

Neoplasms and Tumorlike Lesions

Typical (Left) Axial CECT shows an obstructing, robustly enhancing choroid plexus papilloma arising from roof of third ventricle. Note papillary surface projections (arrow). (Right) Sagittal T7 C+ MR shows an enhancing mass with lobulated margins (arrow), obstructing fourth ventricular outlets.

Typical (Left) Axial PO/Intermediate MR shows an expansile intraventricular choroid plexus papilloma with internal flow voids (arrow). (Right) Axial T7 C+ MR shows an enhancing choroid plexus papilloma arising from left foramen of Luschka (arrow).

6 63

Variant (Left) Coronal T7 C+ MR shows a complex, predominantly cystic (curved arrows), partially solid (arrow) enhancing choroid plexus papilloma. (Right) Axial T7 C+ MR shows diffuse basal cistern tumor seeding from a choroid plexus papilloma (arrow).

Neoplasms and Tumorlike Lesions

Sagittal T1 C+ MR shows a heterogeneously enhancing, lobulated trigonal choroid plexus carcinoma with ependymal invasion (arrows).

Abbreviations

• T2* GRE: Low signal from hemorrhage • Tl C+: Heterogeneous enhancement, ± CSF seeding • MRS: I NAA, t choline, t lactate

and Synonyms

• Choroid plexus carcinoma

(CPCA)

Ultrasonographic

Definitions • Malignant tumor originating choroid plexus

Axial T1 C+ MR shows a bosselated vividly enhancing intraventricular choroid plexus carcinoma. Note the peritumoral edema (curved arrow) and parenchymal invasion (arrows).

from epithelium

of

Findings

• Real Time: Hyperechoic intraventricular mass • Pulsed Doppler: Bidirectional flow through diastole • Color Doppler: Hypervascular mass

Angiographic Findings • Conventional: stain 64

Enlarged choroidal artery & vascular

General Features

Nuclear Medicine

• Best diagnostic clue: Child < 5 y, with enhancing intraventricular mass and ependymal invasion • Location: Almost always arise in lateral ventricle • Size: Variable • Morphology: Cauliflower-like mass

• PET: llC-Methionine ~ t tumor-to-normal brain ratios • Tc-99m Sestamibi ~ t in choroid plexus tumors (CPTs)

Findings

Imaging Recommendations • Enhanced MRI of entire neuraxis prior to surgery

CT Findings • NECT o Iso- to hyperattenuating o Ca++ (20-25%) • CECT: Heterogeneous enhancement

Choroid plexus papilloma (CPP) • MR may not distinguish

MR Findings • Tl WI: Iso- to hypointense • T2WI: Mixed, hypo- iso- or hyperintense • FLAIR: Peri tumoral edema

DDx: Intraventricular

papilloma from carcinoma

Ependymoma • In 4th ventricle more common; extraventricular

Tumors

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Ependymoma

Neoplasms and Tumorlike Lesions

often

Meningioma

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CHOROID

PLEXUS CARCINOMA Key Facts

Imaging Findings

• Subependymal

• Best diagnostic due: Child < 5 y, with enhancing intraventricular mass and ependymal invasion • Ca++ (20-25%) • Tl C+: Heterogeneous enhancement, ± CSF seeding • Enhanced MRI of entire neuraxis prior to surgery

Clinical Issues

Top Differential

Subependymal

(CPP)

giant cell tumor

Diagnostic Checklist

Central neurocytoma

• Age: Between 2 and 4 years, median age"" 26 months • Gender: Equal male/female distribution

Natural History & Prognosis

common

• Grows rapidly, 40% 5 year survival • Poor outcome with brain invasion, CSF seeding

Meningioma • Different age group, more delineated configuration

and oval in

Treatment • Gross total resection, chemotherapy,

Metastases • History of previous tumor known

Vascular lesions

I DIAGNOSTIC

• AVM, cavernous malformation

Consider

Image Interpretation

General Features • • • •

General path comments: Lobulated mass Genetics: Li-Fraumeni & Aicardi syndromes Etiology: SV40 virus DNA sequences in 50% of CPTs Epidemiology: First 5 years of life, 80% arise in children • Associated abnormalities: Diffuse hydrocephalus => mechanical obstruction, increased CSF production, decreased resorption

Gross Pathologic & Surgical Features • Well-circumscribed intraventricular • Ependymal invasion

mass

± XRT

CHECKLIST

• CPCA in a child with intraventricular neurologic signs

I PATHOLOGY

Microscopic

.

Demographics

• Associated CNS findings of tuberous sclerosis • Necrosis and cyst formation

• Nausea, vomiting, headache, obtundation • Age: Between 2 and 4 years, median age ::::;26 months • MR may not distinguish papilloma from carcinoma • Heterogeneity, brain invasion, CSF spread favor CPCA

Diagnoses

• Choroid plexus papilloma • Ependymoma

giant cell tumor

mass and focal

Pearls

• MR may not distinguish papilloma from carcinoma • Heterogeneity, brain invasion, CSF spread favor CPCA

I SELECTED REFERENCES 1.

2. 3.

Poussaint T: Magnetic resonance imaging of pediatric brain tumors: state of the art. Topics in magnetic resonance imaging 12(6): 411-434, 2001 Levy ML et al: Choroid plexus tumors in children: significance of stromal invasion. Neurosurg 48: 303-9, 2001 Wolff J et al: Detection of choroid plexus carcinoma with Tc-99m Sestamibi: case report and review of the literature. Medical and pediatric oncology 36:323-325,2001

Features

• Hypercellular, pleomorphic, increased mitotic activity • Cysts, necrosis, hemorrhage, micro calcifications • Brain invasion

I IMAGE GALLERY

Staging, Grading or Classification Criteria • WHO grade III

I CLINICAL ISSUES Presentation • Most common signs/symptoms o Nausea, vomiting, headache, obtundation o Focal neurologic signs and symptoms • Clinical profile: Infant or child with elevated ICP and focal neuro deficits

(Left) Axial FLAIR MR shows left trigonal CPCA with peritumoral edema (arrows) & parenchymal invasion (open arrow). (Right) Sagittal T1 C+ MR shows diffuse CSF spread (arrows) from CPCA.

Neoplasms and Tumorlike

Lesions

6 65

Coronal graphic shows a discrete cystic and solid temporal lobe mass expanding the overlying cortex. Calvarial remodeling is seen, typical of a superficially located ganglioglioma.

Abbreviations • Ganglioglioma

and Synonyms (GG)

Definitions • Well differentiated, slowly growing neuroepithelial tumor composed of neoplastic ganglion cells and neoplastic glial cells • Most common cause of temporal lobe epilepsy (TLE)

6 66

General

Features

• Best diagnostic clue: Partially cystic, enhancing, cortically-based mass in child/young adult with TLE • Location o Can occur anywhere but most commonly superficial hemispheres, temporal lobe • Parietal and frontal lobes next most common o Rare locations: Brainstem, cerebellum, pineal region, optic nerve/chiasm, intraventricular, spinal cord, cranial nerves • Size o Variable, typically 2-3 cm in adults o Larger in children, typically> 4 cm o Up to 6 cm reported

DDx: Peripherally

PXA

located

Supratentorial

DNET

Coronal T7 C+ MR shows a temporal lobe circumscribed cystic and solid mass with intense enhancement of the mural nodule (arrow). Long history of temporal lobe epilepsy. Canglioglioma.

• Morphology o Three patterns • Most common: Circumscribed cyst + mural nodule • Solid tumor (often thickens, expands gyri) • Uncommon: Infiltrating, poorly-delineated mass o Calcification is common o In younger patients « 10 years), gangliogliomas are larger and more cystic

CT Findings • NECT o Variable density • 40% hypodense • 30% mixed hypodense (cyst), isodense (nodule) • 15% isodense or hyperdense o Ca++ common, 35-50% o Superficial lesions may expand cortex, remodel bone • CECT o Approximately 50% enhance • Varies from moderate, uniform to heterogeneous • Can be solid, rim or nodular

MR Findings • TIWI o Mass is hypointense to isointense to gray matter • Rarely hyperintense o Ca++ may be variable intensity o May see associated cortical dysplasia

Mass

Pilocytic Astrocytoma

Neoplasms and Tumorlike Lesions

Grade 1/Astro

GANGLIOGLIOMA Key Facts Pathology

Terminology • Well differentiated, slowly growing neuroepithelial tumor composed of neoplastic ganglion cells and neoplastic glial cells

• Cortical dysplasia is commonly associated • Most common mixed neuronal-glial tumor • WHO grade I or II

Ima

Clinical Issues

indings

• Bes ostic clue: Partially cystic, enhancing, cortically-based mass in child/young adult with TLE • Can occur anywhere but most commonly superficial hemispheres, temporal lobe

Top Differential Diagnoses • • • • •

Pleomorphic xanthoastrocytoma (PXA) Dysembryoplastic neuroepithelial tumor (DNET) Pilocytic astrocytoma Low grade astrocytoma (grade II) Oligodendroglioma '

• T2WI o Hyperintense mass typical o May be heterogeneous • T2* GRE: May show Ca++ as areas of "blooming" • Tl C+ o Variable enhancement, usually moderate but heterogeneous • May be minimal, ring-like, homogeneous o Meningeal enhancement rarely seen • MRS: Elevated Cho has been described

• PET o Typically decreased activity with FDG-PET indicating tumor hypometabolism o May have some hypermetabolic foci • 20lTl-SPECT: Increased activity in high grade gangliogliomas o Typical gangliogliomas have decreased or normal SPECT activity

Imaging Recommendations • Best imaging tool: Multiplanar MR • Protocol advice: Contrast-enhanced MR to include coronal T2 images to better evaluate temporal lobes

OS IS

Pleomorphic xanthoastrocytoma • • • •

Supratentorial cortical mass, Often cyst and mural nodule, Enhancing nodule abuts pial Temporal lobe most common

(PXA)

dural "tail" common may be solid surface location

Dysembryoplastic neuroepithelial tumor (DNET) • • • •

Diagnostic Checklist • In young patient with history of temporal lobe epilepsy, think ganglioglioma! • Cyst with an enhancing mural nodule is classic, but nonspecific for ganglioglioma

Pilocytic astrocytoma • Supratentorial location other than hypothalamus/chiasm rare • Typically solid and cystic or solid mass • Enhancement typical

low grade astrocytoma (grade II) • Circumscribed but infiltrative white matter mass • No enhancement

Oligodendroglioma

Nuclear Medicine Findings

I DIFFE RIB~JEI~I..t)IA(jN

• Clinical profile: Most common neoplasm causing chronic temporal lobe epilepsy • Excellent prognosis if surgical resection complete • Malignant degeneration is rare, approximately 5-10% (glial component)

Superficial cortical tumor, well demarcated Multicystic "bubbly" appearance T2 hyperintense mass with rare, mild enhancement May remodel calvarium

• Calcified, heterogeneous mass • Typically more diffuse than ganglioglioma • May remodel/erode calvarium

6

Neurocysticercosis

67

• Cyst with "dot" inside • Multiple lesions common • Imaging varies with pathologic

stage, host response

IPAJEAOI..Ou¥' General Features • General path comments o Gangliogliomas have been found in association with oligodendroglioma, DNET, tanycytic ependymoma o Malignant transformation into GBM, neuroblastoma has been reported o Cortical dysplasia is commonly associated o Papillary glioneuronal tumor is a recently described ganglioglioma variant • Genetics o Sporadic • Tp53 mutations found in malignant degeneration o Syndromic • GG has been reported in Turcot syndrome • Etiology o Two theories • Neoplastic transformation of glial hamartoma or subpial granule cells • Differentiated remnants of embryonal neuroblastoma/PNETs

Neoplasms and Tumorlike lesions

• Epidemiology o 1% of primary intracranial neoplasms o Most common mixed neuronal-glial tumor o Represents 1-4% of pediatric CNS neoplasms o Most common tumor to cause temporal lobe epilepsy (40%) • Ganglioglioma > DNET > pilocytic astrocytoma> low grade astrocytoma> oligodendroglioma>

• In children under 10 years old, gangliogliomas are larger and more cystic • In young patient with history of temporal lobe epilepsy, think ganglioglioma!

Image Interpretation

PXA

Gross Pathologic & Surgical Features • Solid or cystic mass with mural nodule • Firm, well circumscribed mass, often expands cortex

Microscopic

Consider

Features

• Mix of mature but neoplastic ganglion cells + neoplastic glial cells (usually astrocytes) • Dysmorphic, occasionally binucleate neurons o Immunohistochemistry of neuronal cells • Synaptophysin and neurofilament protein + • Majority exhibit CD34 immunoreactivity • EM shows dense core granules, variable synapses • Neoplastic glial cells are GFAP + • Mitoses rare (75% have Ki-67 < 1%, low MIB)

1.

2.

3.

4.

Staging, Grading or Classification Criteria • WHO grade I or II • Uncommon: Anaplastic ganglioglioma (WHO grade III) • Rare: Malignant with GBM-like glial component (WHO IV)

5.

6.

7. 8.

Presentation 68

Pearls

• Cyst with an enhancing mural nodule is classic, but nonspecific for ganglioglioma

• Most common signs/symptoms o Chronic temporal lobe epilepsy (approximately 90%)

• Often partial complex seizures o Other signs/symptoms: Headache, signs of increased intracranial pressure • Clinical profile: Most common neoplasm causing chronic temporal lobe epilepsy

9. 10.

11.

12.

Demographics • Age o Tumor of children, young adults o 80% of patients < 30 years o Occurs at all ages, peak age 10-20 years • Gender: Slight male predominance

Natural History & Prognosis • Excellent prognosis if surgical resection complete • Vast majority of patients seizure-free after surgery (80%) • Well-differentiated tumor with slow growth pattern • Malignant degeneration is rare, approximately 5-10% (glial component)

Treatment

13.

14. 15.

16.

17.

Aryan HE et al: Hypothalamic ganglioglioma treated by temporal lobectomy: case report and review of the literature. J Neurosurg 100:217-9, 2004 Burger PC et al: Surgical pathology of the nervous system and its coverings: The Brain: Tumors. 4th ed. Philadelphia, Churchill Livingstone. 250-4, 2002 Clusmann H et al: Prognostic factors and outcome after different types of resection for temporal lobe epilepsy. J Neurosurg. 97(5):1131-41, 2002 1m SH et al: Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. J Neurooncol. 57(1):59-66, 2002 Koeller KKet al: From the archives of the AFIP: superficial gliomas: radiologic-pathologic correlation. Armed Forces Institute of Pathology. Radiographies. 21(6):1533-56, 2001 Hayashi Y et al: Malignant transformation of a gangliocytoma/ ganglioglioma into a glioblastoma multiforme: A molecular genetic analysis. J Neurosurg 95: 138-42, 2001 KwonJW et al: Cerebellopontine angle ganglioglioma: MR findings. AJNRAmJ Neuroradiol. 22(7):1377-9, 2001 Meyer PT et al: High F-18 FDG uptake in a low-grade supratentorial ganglioma: a positron emission tomography case report. Clin NucI Med. 25(9):694-7, 2000 Tamiya T et al: Ganglioglioma in a patient with Turcot syndrome. Case report.J Neurosurg. 92(1):170-5, 2000 Provenzale JM et al: Comparison of patient age with MR imaging features of gangliogliomas. AJRAm J Radiol. 174:859-62,2000 Nelson JS et al: Pathology and genetics of tumours of the nervous system: Ganglioglioma and gangliocytoma. Lyon, IARC Press, 96-8, 2000 Provenzale JM et al: Gangliogliomas: Characterization by registered PET-MRimages. AJR 172: 1103-7, 1999 Kumabe T et al: Thallium-201 single-photon emission computed tomographic and proton magnetic resonance spectroscopic characteristics of intracranial ganglioglioma: three technical case reports. Neurosurgery. 45(1):183-7; discussion 187, 1999 Kurian NI et al: Anaplastic ganglioglioma: case report and review of the literature. Br J Neurosurg. 12(3):277-80, 1998 SeIch MT et al: Gangliogliomas: experience with 34 patients and review of the literature. Am J Clin Oncol. 21(6):557-64, 1998 Kincaid PK et al: Cerebral gangliogliomas: preoperative grading using FDG-PET and 201TI-SPECT.AJNRAm J Neuroradiol. 19(5):801-6, 1998 Nakajima M et al: Anaplastic ganglioglioma with dissemination to the spinal cord: a case report. Surg Neurol. 49(4):445-8, 1998

• Surgical resection is treatment of choice • Radiation therapy and/or chemotherapy for aggressive or unresectable tumors

Neoplasms and Tumorlike Lesions

Typical (Left) Axial T2WI MR shows a hyperintense temporal lobe mass without significant edema or mass effect. Temporal lobe is the most common location for ganglioglioma. Patient with temporal lobe epilepsy. (Right) Axial T1 C+ MR shows a cystic and solid temporal lobe mass with marked enhancement of the solid portion, a typical enhancement pattern of ganglioglioma. Patient remains seizure-free since resection.

Typical (Left) Axial FLAIR MR shows a cortically-based hyperintense mass in the right frontal lobe. Note the lack of edema and mass effect. 20 year old male with seizures. (Right) Axial T1 C+ MR shows intense enhancement of the right frontal lobe mass. Ganglioglioma was found at resection. Imaging appearance mimics PXA and

6 •..•

pilocytic astrocytoma.

69

Variant (Left) Axial CECT shows a large frontal cystic and solid mass with calcification (arrow) and mass effect. 8 year old with headaches, vomiting. Gangliogliomas are often large in young pediatric patients. (Right) Axial T1 C+ MR shows a cortically-based enhancing mass with multiple cysts. Note lack of edema and mass effect. Ganglioglioma.

Neoplasms and Tumorlike Lesions

DYSPLASTIC CEREBELLAR GANGLIOCYTOMA

Axial graphic shows thickening and irregularity of folia in right cerebellar hemisphere characteristic of dysplastic cerebellar gangliocytoma.

Axial T2WI MR shows abnormal hyperintense signal and loss of normal cerebellar architecture in the right cerebellar hemisphere of this adult with dysplastic cerebellar gangliocytoma.

o Infiltrative o Distorting, not displacing, cerebellar tissue

Abbreviations

6 70

and Synonyms

• Best known as Lhermitte-Duclos disease (LDD) • Numerous terms have been used to describe this lesion o Benign hypertrophy of the cerebellum, neurocystic blastoma, hamartomoblastoma o Purkinjeoma, hamartoma of the cerebellum, ganglioneuroma, ganglionis of the cerebellum o Granular cell hypertrophy, granulomolecular hypertrophy of the cerebellum o Diffuse hypertrophy of the cerebellar cortex, neurocytoma myelinicum o Gangliocytoma myelinicum diffusum

Definitions • Rare cerebellar mass lesion with malformative, hamartomatous, and neoplastic characteristics

General Features • Best diagnostic clue: Widened cerebellar folia with a striated appearance on MR • Location: Cerebellum, usually unilateral hemispheric • Size: Large, holohemispheric • Morphology

DDx: Diffuse Cerebellar

SCA Infarct

Hemisphere

Acute Cerebellitis

Radiographic Findings • Thinning

of skull may be apparent

CT Findings • NECT o Hypodense cerebellar mass o Sometimes isointense o Rarely calcifies • CECT: Rarely enhances

MR Findings • TlWI o Hypointense to normal cerebellar tissue o May cause tonsillar herniation • Syrinx secondary to tonsillar displacement reported o Striated pattern often apparent • Alternating isointense and hypointense signal o Rare calcifications may cause hyperintense signal • T2WI o Hyperintense o Characteristic "layered" or "striated" pattern of alternating isointense and hyperintense signal • Also called "laminated", "corduroy", "lamellar", "folial" • PD/Intermediate: May be quite subtle

lesions

Tuberous Sclerosis

Neoplasms and Tumorlike Lesions

Cerebellar Dysplasia

DYSPLASTIC CEREBELLAR GANGLIOCYTOMA Key Facts • Leptomeningeal

Terminology • Best known as Lhermitte-Duclos

disease (LDD)

Imaging Findings • Best diagnostic clue: Widened cerebellar folia with a striated appearance on MR • Characteristic "layered" or "striated" pattern of alternating isointense and hyperintense signal • Also called "laminated", "corduroy", "lamellar", "folial" • No diffusion disturbance on ADC maps • Tl C+: Rare lesions enhance • PET: Elevated 18-FDG uptake • Elevated 201-thallium uptake on delayed imaging

Top Differential

Diagnoses

metastatic disease

Pathology • Associated with Cowden syndrome • Characterized by development of multiple hamartomas • Increased risk of thyroid and breast carcinoma • Some evidence supports that all cases of LDD have Cowden syndrome • Replacement and expansion of granular layer by large neurons

Diagnostic Checklist • Striated cerebellar hemisphere LDD

is "Aunt Minnie" for

• Cerebellar infarction • Acute cerebellitis

• STIR: Accentuates findings seen on T2WI • T2* GRE: May identify calcifications • DWI o Bright signal reflects T2 "shine through" o No diffusion disturbance on ADC maps • Tl C+: Rare lesions enhance • MRS o Some have reported elevated lactate, others not o Diminished NAA, choline, and myoinositol • MR Perfusion o Elevated regional cerebral blood volume (rCBV) o Elevated regional cerebral blood flow (rCBF)

Angiographic

Findings

• Conventional:

Avascular mass

Nuclear Medicine

Findings

• PET: Elevated 18-FDG uptake • SPECT o Elevated 201-thallium uptake on delayed imaging

Imaging Recommendations • Best imaging tool o MR with contrast and DWI o MRA if cerebellar infarct is suspected • Protocol advice o If lesion enhances, consider cerebellitis • Assess mastoids • Assess venous sinuses for thrombophlebitis o Initiate work-up for Cowden syndrome

I DIFFERENTIAL DIAGNOSIS Cerebellar

infarction

• Abnormal signal and edema can mimic LDD • Morphology of infarct typically correlates to vascular territory of involved vessel o Superior cerebellar artery (SCA) o Anterior inferior cerebellar artery (AICA) o Posterior inferior cerebellar artery (PICA) • DWI and MRA to define extent of ischemic injury

Acute cerebellitis • Viral or bacterial infection • Characteristic clinical presentation • Complication of adjacent mastoid infection (bacterial)

leptomeningeal

metastatic disease

• From extra-CNS primary (breast, lung, melanoma) • From CNS primary (PNET-MB, glioblastoma multiforme, germinoma)

Rhombencephalosynapsis • Rare cerebellar malformation • Absence of vermis with midline fusion of cerebellar hemispheres

6

Cerebellar dysplasia

71

• Lack of progression differentiates LDD

true dysplasia from

Tuberous sclerosis • Uncommonly causes mass-like dysplastic cerebellar hemisphere lesions

Granulomatous

disease

• Tuberculosis or sarcoidosis • Diffuse leptomeningeal thickening extending into cerebellar sulci

and enhancement

I PATHOLOGY General Features • General path comments o First described by Lhermitte and Duclos in 1920 o Debate continues as to true nature of lesion • Genetics o Mutation of PTEN tumor suppressor gene found in LDD and Cowden syndrome • Gene is found on long arm of chromosome 10 (lOq23) o PTEN mutations also found in other tumors • Etiology o PTEN regulates neuronal size

Neoplasms and Tumorlike Lesions

DYSPLASTIC CEREBELLAR GANGLIOCYTOMA o Mutations result in increased size of cells without significant proliferation • Epidemiology: Sporadic • Associated abnormalities o Associated with Cowden syndrome • Characterized by development of multiple hamartomas • Increased risk of thyroid and breast carcinoma o Some evidence supports that all cases of LDD have Cowden syndrome

Gross Pathologic & Surgical Features • Enlarged cerebellar hemisphere • Hypertrophic folia may be inapparent surface

Microscopic

if deep to

Treatment • Surgical resection

Consider • Patients with LDD should be evaluated for Cowden syndrome • Rare in children, cerebellitis or dysplasia more likely

Image Interpretation

Staging, Grading or Classification Criteria

1.

2.

3.

4.

• WHO Grade I • May progress or recur after surgery 5.

72

is "Aunt Minnie" for

Features

• Replacement and expansion of granular layer by large neurons o Larger than granular cells but smaller than Purkinje cells o Haphazard orientation • Increased myelination in molecular layer • Reduced myelination in central white matter of folia • No mitotic activity, necrosis, or endothelial proliferation • No clearly defined glial component

6

Pearls

• Striated cerebellar hemisphere LDD

6.

Presentation • Most common signs/symptoms o Related to increased intracranial pressure and hydrocephalus • Headache, occipital • Nausea and vomiting • Papilledema o Cerebellar signs and symptoms • Ataxia • Dizziness • Blurred vision o Megalencephaly o Mental retardation o Polydactyly, partial gigantism, vascular malformations, leontiasis ossea • Clinical profile: Young adult with occipital headache and papilledema

Demographics • Age o Young adults o Average age = 34 yrs • Gender: No gender predilection

7.

8.

9. 10. 11.

12.

13.

Spaargaren L et al: Contrast enhancement in Lhermitte-Duclos disease of the cerebellum: correlation of imaging with neuropathology in two cases. Neuroradiology. 45(6):381-5, 2003 Buhl R et al: Dysplastic gangliocytoma of the cerebellum: rare differential diagnosis in space occupying lesions of the posterior fossa. Acta Neurochir (Wien). 145(6):509-12; discussion 512, 2003 Pirotte B et al: Fluorodeoxyglucose and methionine uptake in Lhermitte-Duclos disease: case report. Neurosurgery. 50(2):404-7; discussion 407-8, 2002 Nowak DA et al: Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma): a malformation, hamartoma or neoplasm? Acta Neurol Scand. 105(3):137-45,2002 Patel S et al: Analysis and classification of cerebellar malformations. AJNR Am J Neuroradiol. 23(7):1074-87, 2002 Koeller KKet al: From the archives of the AFIP: superficial gliomas: radiologic-pathologic correlation. Armed Forces Institute of Pathology. Radiographies. 21(6):1533-56, 2001 Klisch J et al: Lhermitte- Duclos disease: assessment with MR imaging, positron emission tomography, single-photon emission CT, and MR spectroscopy. AJNR Am J Neuroradiol. 22(5):824-30, 2001 Robinson S et al: Cowden disease and Lhermitte-Duclos disease: characterization of a new phakomatosis. Neurosurgery. 46(2):371-83, 2000 Kulkantrakorn K et al: MRI in Lhermitte-Duclos disease. Neurology. 48(3):725-31, 1997 Marcus CD et al: Lhermitte-Duclos disease associated with syringomyelia. Neuroradiology. 38(6):529-31, 1996 Awwad EE et al: Atypical MR appearance of Lhermitte-Duclos disease with contrast enhancement. AJNR AmJ Neuroradiol. 16(8):1719-20, 1995 Meltzer CC et al: The striated cerebellum: an MR imaging sign in Lhermitte-Duclos disease (dysplastic gangliocytoma). Radiology. 194(3):699-703, 1995 Thomas DW et al: Lhermitte-Duclos disease associated with Cowden's disease. IntJ Oral Maxillofac Surg. 24(5):369-71, 1995

Natural History & Prognosis • Surgery typically required to reduce mass effect upon fourth ventricle • Lesions may recur after resection • Untreated lesions may progress

Neoplasms and Tumorlike Lesions

Typical (Left) Sagittal TlWI MR

shows increased volume and abnormal signal in cerebellum. Mass effect compresses fourth ventricle, and causes supratentorial ventricle enlargement and inferior tonsillar displacement. (Right) Sagittal Tl C+ MR in same patient shows no appreciable enhancement of the process. Use of contrast is essential in order to exclude the inflammatory pathologies that can mimic LDD.

Typical (Left) Axial T2WI MR shows

well-defined abnormal hyperintense signal in the superior vermis. Affected region does not match any characteristic arterial territory, making infarct a less favored diagnosis. (Right) Axial T2WI MR shows some preservation of cerebellar gray matter signal, giving characteristic "striated" appearance of dysplastic cerebellar gangliocytoma (arrows).

Typical (Left) Coronal T2WI MR shows large cranial to caudal extent of lesion, with prominent "striated" appearance maintained throughout. Note mild associated mass effect. Dysplastic cerebellar gangliocytoma. (Right) Axial PO/Intermediate MR shows asymmetry of signal and morphology of cerebellar hemispheres. Increased volume of affected right hemisphere is also apparent. Dysplastic cerebellar gangliocytoma.

Neoplasms and Tumorlike Lesions

6 73

DESMOPLASTIC INFANTilE GANGLIOGllOMA

Coronal graphic shows a young child with enlarged head caused by DIGIOIA. Note dominant cystic component (arrows) with dural-based desmoplastic stroma (open arrows).Some edema is seen.

Axial Tl C+ MR shows a large cystic neoplasm with solid dural-based enhancing mass. Note "tail" of dural enhancement (arrow).

o Nodule ~ marked enhancement

Abbreviations

MR Findings

and Synonyms

• Desmoplastic infantile ganglioglioma (DIG, DIGG) or desmoplastic infantile astrocytoma (DIA)

Definitions • DIG = prominent desmoplastic stroma + neoplastic astrocytes, variable neuronal component • DIA = desmoplastic stroma + neoplastic astrocytes

6 74

General Features • Best diagnostic clue o Large cyst + cortical-based enhancing tumor nodule o Enhancement of adjacent pia PLUS reactive dural thickening • Location: Frontal> parietal> temporal

• TlWI o Cyst hypointense, may contain septae o Nodule ~ heterogeneous • T2WI o Cyst is hyperintense o Lobular, solid tumor nodule(s) usually low signal, +/- heterogeneous o Degree of surrounding edema dependent upon local ventricular obstruction • Tl C+ o Solid tumor nodule(s) enhance markedly o Enhancement of leptomeninges, dura adjacent to solid tumor is typical

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Contrast-enhanced

MRI

CT Findings • NECT o Well-demarcated hypodense cyst (isodense to CSF) o Solid tumor nodule(s) is isodense/slightly hyperdense to GM, no Ca++ • CECT o Cyst ~ no enhancement

Primitive neuroectodermal

tumor (PNET)

• Solid tumor is hyperdense on CT, hypointense T2WI, contains cysts, Ca++, edema • Large heterogeneously enhancing hemispheric

DDx: Large Cystic Brain Masses

Ependymoma

PXA

Hemangioblastoma

Neoplasms and Tumorlike

Lesions

Piloeytie Glioma

on mass

DESMOPLASTIC INFANTILE GANGLIOGLIOMA Key Facts Terminology

Top Differential

• Desmoplastic infantile ganglioglioma (DIG, DIGG) or desmoplastic infantile astrocytoma (DIA)

• • • • • •

Imaging Findings • • • •

Large cyst + cortical·based enhancing tumor nodule Location: Frontal> parietal> temporal Solid tumor nodule(s) enhance markedly Enhancement of leptomeninges, dura adjacent to solid tumor is typical

Supratentorial

Diagnoses

Primitive neuroectodermal tumor (PNET) Supratentorial ependymoma Pleomorphic xanthoastrocytoma (PXA) Hemangioblastoma Ganglioglioma Pilocytic astrocytoma

I CEll NleAl..lSSIJES

ependymoma

• Nonspecific imaging findings but commonly Ca++

Pleomorphic xanthoastrocytoma

contains

(PXA)

• May appear identical to DIG, but occurs in older patients, temporal lobe most common location

Hemangioblastoma • Older patients • Imaging features similar to DIG but rare above tentorium

Presentation • Most common signs/symptoms: t Head size, bulging fontanels, paresis & seizures (20%)

Demographics • Age o Most are found at 1-24 mo (peak: 3-6 mo) o Children, < 24 mo, usually ::0; 12 months, occasionally older patients (5-17 yrs) • Gender: Slightly more common in males (1.7:1.0)

Ganglioglioma

Natural History & Prognosis

• Similar appearance to DIG but generally smaller in size, Ca++ is common

• Median survival rate is > 75% at 15 yrs after diagnosis • Spontaneous disappearance (rare), anaplasia (very rare)

Pilocytic astrocytoma

Treatment

• Rarely in cerebral hemispheres, cyst is smaller but features may be identical to DIG

• Surgical resection curative, no recurrence with complete resection • Chemotherapy if brain invasion or recurrence

IPATHOI..OG¥

ISEI..ECTED REFERENCES

General Features • General path comments: astrocytes

May arise from subpial

1.

2.

Gross Pathologic & Surgical Features • Two distinct components o Cortical·based solid tumor nodule with adjacent dural thickening o Large associated cyst compresses adjacent ventricular system • Large cyst(s) containing xanthochromic fluid • Tumor firmly attached to dura and brain tissue • No necrosis within solid component of tumor, no hemorrhage

Microscopic

I IMAGE GAI..I..ER¥

Features

• Desmoplasia with mixture of astroglial & neuronal cells • Immature neuronal component & neoplastic astrocytes • Prominent reticulin-rich desmoplastic stroma • Aggregates of poorly differentiated cells • Mitoses are rare, MIB-llabeling rare • Tumor lacks p53 protein expression

Staging, Grading or Classification Criteria • WHO grade 1

Tamburrini G et al: Desmoplastic infantile ganglioglioma. Childs Nerv Syst, 19:292-97, 2003 Shin JH et al: Neuronal tumors of the central nervous system: Radiology findings and pathologic correlation. RadioGraphies 22:1177-89,2002

Axial T2WI MR shows a large multicystic mass in left frontotemporal region with peripherally located predominantly hypointense solid tumor. There is significant associated vasogenic edema. (Right) Axial T1 C+ MR in another case shows a large multicystic mass in the left frontotemporal region that has a peripherally located enhancing solid portion of tumor. Classic DIG. (Left)

Neoplasms and Tumorlike Lesions

6 75

Coronal oblique graphic shows intracortical DNET. The gyrus is expanded by the characteristic multicystic appearing tumor.

Abbreviations

o Large (7 cm lesions involving lobule or large portion of lobe have been reported) • Morphology o Well circumscribed o Wedge-shaped "bubbly" cortical mass o Minimal or no mass effect o Lacks surrounding edema o Very slow growth over many years ~ may remodel overlying bone

and Synonyms

• Dysembryoplastic neuroepithelial o Occasionally called DNT o Formerly called mixed glioma

tumor (DNET)

Definitions • Benign, focal, intracortical mass superimposed background of cortical dysplasia

6

on

CT Findings

·.IMJ\<JjI~~iFI~[)iIN~§

1••

76

General Features • Best diagnostic clue: Well-demarcated, wedge-shaped "bubbly" intracortical mass in young patient with longstanding partial seizures • Location o Temporal lobe (often amygdala/hippocampus) most common site • Parietal cortex, caudate nucleus, septum pellucidum also frequent sites o Intracortical mass scallops inner table of skull and "points" towards ventricle • Size o Variable: Small (involving part of a gyrus)

DDx: Peripheral Cortically-based

Taylor Dysplasia

Neuroepithelial

Coronal T2WI MR shows wedge shaped, multicystic (bubbly) lesion extending from parietal cortex into subcortical white matter.

• NECT o Wedge-shaped low density area • Cortical/subcortical lesion • Extends towards ventricle in 30% • Scalloped inner table in 44-60+% • Calcification in 20-36% o May resemble stroke on initial CT • BUT no temporal evolution to atrophy • CECT o Usually non enhancing o Faint nodular or patchy enhancement in 20% • Slightly higher risk of recurrence if enhancement • CTA: Avascular

MR Findings • TlWI o Pseudocystic, multinodular o Hypointense on Tl

("bubbly") mass

lesions

Cysts

Ganglioglioma Cyst

Neoplasms and Tumorlike lesions

PXA

DNET Key Facts Terminology

Pathology

• Dysembryoplastic neuroepithelial tumor (DNET) • Benign, focal, intra cortical mass superimposed on background of cortical dysplasia

• Approximately 1-2% of primary brain tumors in patients < 20 years • Reported in 5-80% of epilepsy specimens

Imaging Findings

Clinical Issues

• Best diagnostic clue: Well-demarcated, wedge-shaped "bubbly" intracortical mass in young patient with longstanding partial seizures • Temporal lobe (often amygdala/hippocampus) most common site • Intracortical mass scallops inner table of skull and "points" towards ventricle • Minimal or no mass effect

• Clinical profile: Longstanding (difficult to control) partial complex seizures in child or young adult • NO or very slow increase in size over time • Rare recurrence • Beware of atypical features (enhancement) on pre-op imaging

• T2WI o Very hyperintense on T2 o Multinodular or septated appearance well seen on T2WI • PD/Intermediate: Hyperintense rim • FLAIR o Mixed (hypo/isointense) signal with "bright rim" o No peritumoral edema • T2* GRE o Bleeding into DNET uncommon but does occur • Possibly in association with microvascular abnormalities • May simulate cavernoma • DWI: Usually lacks restricted diffusion • Tl C+ o Usually doesn't enhance o Faint focal punctate or ring-enhancement in 20% • MRS: Nonspecific, but lactate present in some

Nuclear Medicine

Findings

• PET o 18F-FDG PET demonstrates glucose hypometabolism o Lower [Ue] methionine (MET) uptake in DNET than in ganglioglioma or gliomas • Tc99m-HMPAO SPECT o Ictal may show hyperperfusion o Interictal hypoperfusion typical

Imaging Recommendations • Best imaging tool: MRI • Protocol advice o MRI with contrast material o FLAIR increases specificity with "bright rim"

Neuroepithelial

cyst

• Nonenhancing single or complex cystic structure • No bright "rim" on FLAIR

Ganglioglioma • Ca++ common • Cyst • Strong enhancement

Pleomorphic

xanthoastrocytoma

77

General

Features

• General path comments: Gyriform configuration with scalloping of overlying inner table • Genetics o Sporadic o Nonneoplastic focal cortical dysplasias may be syndrome related o Reported cases with Nfl • Etiology o Embryology: Dysplastic cells in germinal matrix o Extend along migratory path of neurons towards cortex o Associated cortical dysplasia common • Epidemiology o < 1% of all primary brain tumors o Approximately 1-2% of primary brain tumors in patients < 20 years o Reported in 5-80% of epilepsy specimens

Gross Pathologic

Taylor dysplasia

• Neocortical lesion • Thick gyrus

Single tuberous sclerosis lesion Expands single gyrus Looks like tuber Nonenhancing

6

IPATHOlOG¥

I DIFFERENTIAL DIAGNOSIS • • • •

(PXA)

• Enhancing nodule abuts pia • Look for dural "tail"

Microscopic

& Surgical Features

Features

• Hallmark = "specific glioneuronal element" (SGNE) o Columns of heterogeneous cells oriented perpendicular to cortex

Neoplasms and Tumorlike Lesions

•

• • • •

o Oligodendrocyte-like cells arranged around capillaries o Other cells show astrocytic, neuronal differentiation Several histological types o Complex form • Multinodular architecture • Mixed cellular composition • Foci of cortical disorganization • SGNE o Simple form with SGNE only o A third "nonspecific" form has no SGNE • But has same neuroimaging characteristics as complex form Microcystic degeneration o Neurons "float" in pale, eosinophilic mucoid matrix Calcification and leptomeningeal involvement common Adjacent cortical dysplasia common Low proliferative potential with variable MIB-l index

Staging, Grading or Classification Criteria • WHO grade I

ICllNICAL ilSSUES Presentation • Most common signs/symptoms: Epilepsy • Clinical profile: Longstanding (difficult to control) partial complex seizures in child or young adult

Demographics

6 78

I SELECTED REFERENCES 1.

Vuori K et al: Low-grade gliomas and focal cortical developmental malformations: differentiation with proton MR spectroscopy. Radiology 230:703-8, 2004 2. Maehara T et al: Usefulness of [lIe] methionine PET in the diagnosis of dysembryoplastic neuroepithelial tumor with temporal lobe epilepsy. Epilepsia 45(1):41-5,2004 3. Fernandez C et al: The usefulness of MR imaging in the diagnosis of dysembryoplastic neuroepithelial tumor in children: A study of 14 cases. AJNR 24(5):829-34, 2003 4. Stanescu Cosson R et al: Dysembryoplastic neuroepithelial tumors: CT, MR findings and imaging followup: A study of 53 cases. J Neuroradiol 28(4):230-40, 2001 5. Adamek D et al: Dysembryoplastic neuroepithelial tumor (DNT). Is the mechanism of seizures related to glutamate? An immunohistochemical study. Folia Neuropathol 39(2):111-7, 2001 6. Daumas-Duport C et al: Dysembryoplastic neuroepithelial tumors: In Kleihues P, Cavenee WK (eds), Tumors of the Nervous System, Chapter 6:103-6, IARC Press, Lyon, France, 2000 7. Lee DY et al: Dysembryoplastic neuroepithelial tumor: Radiological findings (including PET, SPECT, and MRS) and surgical strategy. J NeurooncoI47:167-74, 2000 8. Thorn M et al: Spontaneous intralesional hemorrhage in dysembryoplastic neuroepithelial tumours: A series of five cases. J Neurol Neurosurg Psychiatry 67(1):97-101,1999 9. Honavar M et al: Histological heterogeneity of dysembryoplastic neuroepithelial tumor: Identification and differential diagnosis in a series of 74 cases. Histopathology 34(4):342-56, 1999 10. Ostertun B et al: Dysembryoplastic neuroepithelial tumors: MR and CT evaluation. AJNR 17(3):419-30, 1996

• Age o Children and young adults o Typically identified before age 20 • Gender: M = F • Ethnicity: None known

Natural History & Prognosis • Benign lesions • NO or very slow increase in size over time • Rare recurrence o Beware of atypical features (enhancement) imaging

on pre-op

Treatment • Seizures may become intractable o Glutamate receptors shown within tumor and margins may explain typical difficult to control seizures • Surgical resection of epileptogenic foci (may include cortical dysplasia)

I DIAGNOSTIC CHECKUST Image Interpretation

Pearls

• Beware enhancing lesions--they may represent a more ominous lesion than DNET

Neoplasms and Tumorlike Lesions

Typical (Left) Axial T2WI MR in a 5 year old with seizures shows multicentric, "bubbly", DNET with involvement of the body of the caudate nucleus (arrow). (Right) Axial T2WI MR shows bubbly temporal lobe DNET expanding involved gyri and remodeling the inner calvarial table (arrow).

Typical

(Left) Coronal FLAIR MR shows characteristic bright rim (arrows) along the borders of a cortically-based, wedge shaped DNET. (Right) Axial view from magnetoencephalography (MEG) study shows seizure spikes surrounding the margins of a small frontal DNET.

6 79

Variant (Left) Axial NECT shows wedge shaped low density mass (arrows) and fleck (open arrow) of Ca++ in DNET. (Right) Coronal T7 C+ MR in a recurrent DNET shows multinodular enhancement (arrow) in a "bubbly" wedge shaped lesion extending from cortex to ventricle.

Neoplasms and Tumorlike Lesions

Coronal graphic shows a "bubbly" lobular intraventricular mass attached to the septum pellucidum with associated ventricular dilatation, typical of central neurocytoma.

Abbreviations

o Rare extraventricular tumors with neurocytoma features, "extraventricular central neurocytoma" • Brain parenchyma, cerebellum, spinal cord • Size: Variable • Morphology o Circumscribed, lobulated mass with intratumoral "cysts" o Characteristic "bubbly" appearance on imaging studies

and Synonyms

• Central neurocytoma

(CN), neurocytoma

Definitions • Intraventricular neuroepithelial tumor with neuronal differentiation • Well demarcated, intraventricular neurocytic neoplasm located in foramen of Monro region

CT Findings

80

General Features • Best diagnostic clue: "Bubbly" mass in frontal horn or body of lateral ventricle • Location o Typically supratentorial, intraventricular o Intraventricular mass attached to septum pellucidum • > 50% in frontal horn/body lateral ventricle, near foramen of Monro • 15% extend into 3rd ventricle o Both lateral ventricles 13% o 3rd ventricle only 3% o 4th ventricle, extremely rare

DDx: Intraventricular

Coronal T2WI MR shows the characteristic "bubbly" appearance of a central neurocytoma. Note the enlarged temporal horn. These tumors are typically attached to the septum pellucidum.

• NECT o Usually mixed solid and cystic (isodense/hyperdense) o Ca++ common, 50-70% o Hydrocephalus common o Rarely complicated by hemorrhage • CECT: Moderate, heterogeneous enhancement

MR Findings • TlWI o Heterogeneous, mostly isointense to gray matter o Cysts are hypointense o Prominent flow voids may be seen o Hemorrhage is rare • T2WI o Heterogeneous, hyperintense "bubbly" appearance o Associated hydrocephalus is common o Ca++ often hypo intense

Enhancing Mass

/' i

(.

.~ ,

\

~'i'

! \ \ \ Subependymoma

Giant Cell Astrocytoma

Metastasis

Neoplasms and Tumorlike Lesions

Cpp

CENTRAL NEUROCYTOMA Key Facts Terminology • Intraventricular differentiation

neuroepithelial

tumor with neuronal

• Best diagnostic clue: "Bubbly" mass in frontal horn or body of lateral ventricle • Intraventricular mass attached to septum pellucidum • Circumscribed, lobulated mass with intratumoral "cysts" • Ca++ common, 50-70% • • • •

Diagnoses

Subependymoma Subependymal giant cell astrocytoma Metastasis Ependymoma

(SGCA)

Angiographic Findings • Conventional o DSA: Variable appearance • Avascular mass to marked vascularity

Clinical Issues

Metastasis • Uncommon, usually older patients • Primary often known

Ependymoma • Supratentorial ependymomas rarely intraventricular • Heterogeneous, enhancing mass with edema • Aggressive features

Choroid plexus papilloma (CPP) • Typically younger patients, lateral ventricle • In adults, fourth ventricle • Intensely enhancing papillary mass, hydrocephalus common

6

Meningioma

81

• Circumscribed, intensely enhancing • Typically trigone of lateral ventricle • Older patients

Nuclear Medicine Findings • PET o Typically characterized by decreased metabolism FDG-PET o Hypermetabolic activity has been described in atypical central neurocytoma

on

Imaging Recommendations • Best imaging tool: MR is most sensitive • Protocol advice: Multiplanar contrast-enhanced

• < 1% of all primary intracranial neoplasms • Represents 50% of intraventricular tumors in patients 20-40 years • Resembles oligodendroglioma • WHO grade II • Most common signs/symptoms: Headache, increased intracranial pressure, mental status changes, seizure • Hydrocephalus secondary to foramen of Monro obstruction • Complete surgical resection is treatment of choice

• PD/Intermediate o Heterogenous, predominantly hyperintense mass o Prominent flow voids may be seen • FLAIR: Heterogenous, predominantly hyperintense mass • T2* GRE: Ca++ seen as areas of "blooming" • Tl C+: Moderate to strong heterogeneous enhancement • MRS o Large Cho peak and Cho/Cr ratios typical o Unidentifiable peak at 3.55 ppm (inositol or glycine) described

mass

Cavernous malformation • Rarely intraventricular, 2.5-11% • Ca++, T2 hypointense hemosiderin

rim common

Oligodendroglioma • Typically a cortical mass with variable enhancement • Main histologic differential

MR

I DIFFERENTIAL DIAGNOSIS Subependymoma • • • •

(CPP)

Pathology

Imaging Findings

Top Differential

• Choroid plexus papilloma • Meningioma • Cavernous malformation

May be indistinguishable Older patients Usually faint or no enhancement 4th> lateral ventricle

Subependymal giant cell astrocytoma (SGCA) • Mass at foramen of Monro, Ca++ common • Look for stigmata of tuberous sclerosis o Subependymal nodules, cortical tubers, WM lesions

I PATHOLOGY General Features • General path comments o Parenchymal invasion is rare, found in more aggressive tumors o "Central neurocytoma" describes typical intraventricular tumors o "Extraventricular central neurocytoma" refers to rare parenchymal tumor with neurocytoma features o Some authors propose "atypical central neurocytoma" for more aggressive variant • MIB-l index> 2% • Vascular proliferation

Neoplasms and Tumorlike Lesions

o Central neurocytoma rarely found in association with medulloblastoma • Genetics: No consistent chromosomal gains/losses • Etiology: Controversial: May arise from neuronal or bipotential progenitor cells • Epidemiology o < 1% of all primary intracranial neoplasms o Approximately 10% of intraventricular neoplasms o Represents 50% of intraventricular tumors in patients 20-40 years

Natural History & Prognosis • • • •

Usually benign, local recurrence is uncommon Surgical resection is typically curative Rarely complicated by hemorrhage Craniospinal dissemination extremely rare, < 10 cases reported • Tumors with extraventricular extension have poorer clinical outcome • 5 year survival rate = 81 %

Gross Pathologic & Surgical Features

Treatment

• Grayish, friable, circumscribed, intraventricular mass • Moderately vascular; may hemorrhage, calcify • Typically attached to septum pellucidum or lateral ventricular wall

• Complete surgical resection is treatment of choice • If incomplete resection, radiation therapy, chemotherapy and/or radiosurgery may be helpful • Gamma knife radiosurgery may improve local control rates and increase survival

Microscopic Features

82

• Resembles oligodendroglioma o Many CNs were misdiagnosed in the past • Uniform round cells with neuronal differentiation o Stippled nuclei, perinuclear halos • Various architectural patterns (can resemble other neoplasms) o Monotonous sheets of cells o Perivascular pseudorosettes (ependymoma) o Honeycomb appearance (oligodendroglioma) o Large fibrillary areas (pineocytoma) • Benign (low proliferation rate, mitoses rare) • Anaplasia, necrosis rare o Occasionally have brisk mitotic activity o Microvascular proliferation • Immunopositive for synaptophysin and neuron-specific enolase; rarely for GFAP • EM: Finely speckled chromatin, small distinct nucleolus, cell processes with neuritic features (microtubules)

Staging, Grading or Classification Criteria • WHO grade II • "Atypical neurocytoma" for tumors with increased mitoses and proliferation rate (MIB-l)

Presentation • Most common signs/symptoms: Headache, increased intracranial pressure, mental status changes, seizure • Other signs/symptoms o Hydrocephalus secondary to foramen of Monro obstruction o Tumors of septum, 3rd ventricle, hypothalamus may have visual disturbances, hormonal dysfunction o Rare reports of acute ventricular obstruction and death o Rarely asymptomatic

Demographics • Age o Young adults, 20-40 years commonly (75%) o Range: Infants to 67 years, mean age 29 years • Gender: No gender predominance

Consider • Subependymoma and giant cell astrocytoma mimic central neurocytoma, clinical information may help

Image Interpretation

Pearls

• "Bubbly" or "feathery" intraventricular mass near foramen of Monro in a young adult, think central neurocytoma • Central neurocytoma is typically attached to septum pellucidum

I SELECTED REFERENCES Schmidt MH et al: Central neurocytoma: a review. J Neurooncol 66: 377-84, 2004 2. Takao H et al: Central neurocytoma with craniospinal dissemination. J Neurooncol. 61(3):255-9, 2003 3. Kanamori M et al: (201)TI-SPECT, (l)H-MRS, and MIB-1 labeling index of central neurocytomas: three case reports. Acta Neurochir (Wien). 144(2):157-63; discussion 163, 2002 4. Hsu PW et al: Fourth ventricle central neurocytoma: case report. Neurosurgery. 50(6):1365-7, 2002 5. Kulkarni V et al: Long-term outcome in patients with central neurocytoma following stereotactic biopsy and radiation therapy. Br J Neurosurg. 16(2):126-32,2002 6. Rades D et al: Treatment options for central neurocytoma. Neurology. 59(8):1268-70, 2002 7. Koeller KK et al: Cerebral intraventricular neoplasms: radiologic-pathologic correlation. Radiographies. 22:1473-1505,2002 8. Burger PC et al: Surgical pathology of nervous system and its coverings: The Brain: Tumors. 4th ed. Philadelphia, Churchill Livingstone. 250-4, 2002 9. Ohtani T et al: Central neurocytoma with unusually intense FDG uptake: case report. Ann Nucl Med. 15(2):161-5,2001 10. Figarella-Branger D et al: Pathology & Genetics of Tumours of the Nervous System: Central neurocytoma. Lyon, IARC Press. 107-9, 2000 11. Kim DG et al: In vivo proton MRS of central neurocytoma. Neurosurg 46: 329-34, 2000 12. Brandes AA et al: Chemotherapy in patients with recurrent and progressive central neurocytoma. Cancer. 88(1):169-74,2000 1.

Neoplasms and Tumorlike Lesions

Typical (Left) Axial graphic shows a

circumscribed, lobular "bubbly" mass attached to the septum pellucidum. Ventricular dilatation is related to foramen of Monro obstruction. Classic central neurocytoma. (Right) Axial T2WI MR shows a heterogeneous intraventricular mass with associated hydrocephalus related to foramen of Monro obstruction. Extension across midline is less typical of central neurocytoma.

Typical

(Left) Axial TlWI MR shows a heterogeneous lateral

ventricle mass with mild ventricular dilatation. Bowing of the septum pellucidum is typical of central neurocytoma. 33 year old female, headaches. (Right) Axial TI C+ MR shows moderate enhancement of the lobular intraventricular mass. Note the intratumoral cysts are isointense to CSF (arrow). Enhancement is typically heterogeneous.

Variant

(Left) Sagittal T2WI MR shows a heterogeneous

lateral ventricle mass involving the foramen of Monro. No cysts are seen, atypical for central neurocytoma. Asymptomatic 25 year old male, history of trauma. (Right) Sagittal TI C+ MR shows heterogeneous enhancement of the lobular, lateral ventricular mass. Imaging mimics subependymoma and subependymal giant cell astrocytoma. Central neurocytoma at resection.

83

Sagittal graphic shows large, heterogeneous pineal mass with areas of hemorrhage and necrosis. Note compression of adjacent structures, hydrocephalus, and diffuse CSF seeding, typical PB.

Sagittal T2WI MR shows a large, cystic and solid pineal mass with extension into aqueduct, 3rd & 4th ventricles. The solid portion of tumor is only slightly more hyperintense than cortex.

• 15% with spinal metastases on MR (CSF dissemination)

Abbreviations

and Synonyms

• PBi pinealoblastomai primitive neuroectodermal tumor (PNET) of pineal gland

Definitions • Highly malignant, pineal gland

primitive embryonal

tumor of

• NECT o Mixed densityi solid portion frequently hyperdense o Peripheral, "exploded" Ca++ classic • CECT: Weak to moderate heterogeneous enhancement

MR Findings

6 84

CT Findings

General Features • Best diagnostic clue o Large, heterogeneous pineal mass with "exploded", peripheral Ca++ o Solid portion of tumor hyperdense on CT, iso-/hypointense on T2WI (compared to cortical gray matter) • Location o Pineal gland o Frequent extension/invasion into corpus callosum, thalamus, midbrain, vermis • Size: Largei most;:: 3 cm • Morphology: Irregular, lobulated mass with poorly delineated margins • Nearly 100% with obstructive hydrocephalus

• T1WI: Heterogeneousi solid portion iso-/hypointense • T2WI o Heterogeneous • Solid portion iso-, hypo- > minimally hyperintense to cortex • Frequent necrosis/hemorrhage o Mild peritumoral edema characteristic • T2* GRE: Ca++, hemorrhage may bloom • DWI: Solid portion frequently hyperintense • T1 C+: Moderate, heterogeneous enhancement • MRS o t Cho, i NAA o Prominent glutamate and taurine peak (- 3.4 ppm) described at TE 20 ms

Angiographic Findings • Conventional: Variable: Both hyper- and hypovascular mass described

DDx: Pineal Region Tumors

Germinoma

Teratoma

Tectal Glioma

Neoplasms and Tumorlike

Lesions

Meningioma

PIN EOBLASTOMA Key Terminology • Highly malignant, pineal gland

Facts Pathology

primitive embryonal

tumor of

• PBs exhibit little to no differentiation, other PNETs

similar to

Imaging Findings

Clinical Issues

• Large, heterogeneous pineal mass with "exploded", peripheral Ca++ • Nearly 100% with obstructive hydrocephalus

• Elevated ICP (hydrocephalus): Headache, nausea, vomiting, lethargy, papilledema, abducens nerve palsy

Top Differential Diagnoses

Diagnostic Checklist

• • • • •

• Both PBs and genninomas frequently hyperdense on CT (hypointense T2WI) and prone to CSF dissemination • Peripheral "exploded" Ca++ in PB and central "engulfed" Ca++ in germinoma classic but not always identified

Germ cell tumors (GCTs) Astrocytoma Meningioma Pineocytoma (PC) Metastases

Nuclear Medicine Findings

Astrocytoma

• PET: Increased F-18 FDG

• • • •

Other Modality Findings • No elevation of serum tumor markers

Imaging Recommendations • Best imaging tool: Contrast-enhanced MR • Protocol advice o Image entire neuraxis o Sagittal images ideal for pineal region anatomy

Rarely arises from pineal gland More commonly from thalamus or midbrain tectum Pilocytic astrocytoma (WHO grade I) most common Tectal astrocytoma o Nonenhancing, T2 iso- or hyperintense, well-defined expansile tectal mass • Thalamic astrocytoma o T2 hyperintense, paramedian mass, or cyst with enhancing mural nodule

Meningioma

I DIFFERENTIALDIAGINOSIS Germ cell tumors (GCTs) • 1% of CNS tumors in Western populationi 4% CNS tumors in Asia • M > Fi 2nd decade presentation • Germinoma o Most common GCT and pineal region tumor • 50% of all pineal region tumors o Homogeneous, hyperdense (iso-/hypointense T2WI) mass with intense uniform enhancement • Central, "engulfed" Ca++ classic o Coexistent suprasellar mass pathognomonic o Elevation of serum placental alkaline phosphatase (PLAP) characteristic • Mature teratoma o Second most common GCT and pineal region tumor o Heterogeneous, multicystic mass with foci of Ca++ and fat density/intensity • Choriocarcinoma, endodermal sinus tumor, embryonal cell carcinoma o Uncommon, highly malignant tumors o Non-specific imaging appearance but characteristic elevation of serum tumor markers • Choriocarcinoma: l3-hCG • Endodermal sinus tumor: AFP • Embryonal cell carcinoma: l3-hCG and AFP • 10% of GCTs are mixed histology (mixed GCT)

• Older females (5th-7th decade) • Well defined, round dural-based mass isointense to cortex on all sequences with intense, homogeneous enhancement • Pineal region meningiomas arises from tentorium cerebelli, falx • Dural "tail 35-80% II

Pineocytoma (PC) • Differentiated tumor arising from pineal gland parenchymal cell • Older age group compared to PBs • Well defined, round, homogeneous mass with uniform homogeneous enhancement

Metastases • Pineal gland metastases uncommon • Adenocarcinoma reported

I

PATHOLOGY

General Features • General path comments o Pineal parenchymal tumors (PPTs) may have photosensory (retinoblastomas), astrocytic, neuronal or mixed differentiation • Photosensory differentiation unique to PPTs and retinal tumors • Differentiated tumors characteristic of PC

Neoplasms and Tumorlike Lesions

6 85

• PBs exhibit little to no differentiation, similar to other PNETs • Genetics o No TP53 mutations o Some reports of chromosome 11 deletions o "Trilateral retinoblastoma" has bilateral RBs, pineal PNET like PB • Etiology o Derived from embryonic precursors of pineal parenchymal cells ("pinealocytes") o Pinealocytes = cells with photosensory, neuroendocrine function o Common phylogenetic origin of retina and pineal gland as light-sensing organs • Epidemiology o PPTs comprise 0.5-1 % of primary brain tumors and 15% of pineal region neoplasms o PBs comprise 30-45% of PPTs

Gross Pathologic & Surgical Features

6 86

Demographics • Age

o Children> young adults o Mean age at diagnosis in pediatric series = 3 yrs • Gender: M:F = 1:2 • Ethnicity: Equal to slightly greater incidence in Western population compared to Asia

Natural History & Prognosis • CSF seeding (rare reports hematogenous metastases to bone) o 16-45% pediatric and 45% adult patients present with spinal dissemination ([+] MR and/or CSF cytology) • Dismal; median survival 16-25 months from presentation

Treatment

• Soft, friable, poorly marginated (infiltrates adjacent tissues) • Compresses/invades cerebral aqueduct ~ hydrocephalus • CSF dissemination at autopsy frequent

Microscopic

• Clinical profile: Toddler with Parinaud syndrome and signs/symptoms of elevated intracranial pressure

• Surgical resection plus cranial/spinal radiation and chemotherapy

1.·D·IAGN.OST.IC.·.·CHE(illKEISm

Features

• Highly cellular tumor o Sheets of densely packed, small, undifferentiated cells o Round, carrot-shaped hyperchromatic nuclei, scanty cytoplasm • High nuclear: cytoplasmic ratio accounts for hyperdense/hypointense imaging appearance of solid portion of tumor on CT, MR o Occasional Homer-Wright or Flexner-Wintersteiner rosettes o Variable (+) immunolabeling for synaptophysin, neuronal specific enolase, neurofilaments and chromogranin A , but < than PCs, mixed PB/PCs o Necrosis and hemorrhage common o Mitoses common, MIB-l elevated

Consider • Could pineal region mass be GCT (more common than PPTs) o Does patient have elevated serum tumor markers o Is patient male o Is there a coexistent suprasellar mass (germinoma)

Image Interpretation

Pearls

• Both PBs and germinomas frequently hyperdense on CT (hypointense T2WI) and prone to CSF dissemination • Peripheral "exploded" Ca++ in PB and central "engulfed" Ca++ in germinoma classic but not always identified • Clinical pearl: Pineal region astrocytomas typically do not present with Parinaud syndrome

Staging, Grading or Classification Criteria • WHO grade IV • New prognostic grading system for PPTs o Grade 1 = PC o Grade 2 and 3 = PPTs with intermediate differentiation • Grade 2 if < 6 mitoses and (+) immunolabeling neurofilaments • Grade 3 if 2: 6 mitoses or < 6 mitoses but (-) immunolabeling for neurofilaments o Grade 4 = PB

I·SELECTE·[)•••• REF.E~EN.·(2·IES 1. 2.

for 3.

4. 5.

IctINICt\lilSSUIES

6.

Presentation • Most common signs/symptoms o Elevated ICP (hydrocephalus): Headache, nausea, vomiting, lethargy, papilledema, abducens nerve palsy o Other signs/symptoms: Parinaud's syndrome, ataxia

7.

Konovalov AN et al: Principles of treatment of the pineal region tumors. Surg Neurol. 59(4): 250-68, 2003 Lutterbach J et al: Malignant pineal parenchymal tumors in adult patients: patterns of care and prognostic factors. Neurosurgery. 51(1): 44-55; discussion 55-6, 2002 Kondziolka 0 et al: The role of radiosurgery for the treatment of pineal parenchymal tumors. Neurosurgery. 51(4): 880-9, 2002 Hirato J et al: Pathology of pineal region tumors. J Neurooncol. 54(3): 239-49, 2001 Korogi Y et al: MRI of pineal region tumors. J Neurooncol. 54(3): 251-61, 2001 Nakamura M et al: Neuroradiological characteristics of pineocytoma and pineoblastoma. Neuroradio142: 509-14, 2000 Jouvet A et al: Pineal parenchymal tumors: A correlation of histological features with prognosis in 66 cases. Brain Pathol10: 49-60, 2000

Neoplasms and Tumorlike Lesions

Typical (Left) Axial NECT shows a large, hyperdense pineal region mass with peripheral calcification, PB. Cerminomas have a similar appearance, but calcification, when identified, is usually central ("engulfed"). (Right) Axial T2WI MR shows a heterogeneous pineal region tumor. The solid portion of tumor (arrow) is isointense to cortex. The tumor margins are indistinct suggesting infiltration of adjacent structures.

Typical (Left) Axial FLAIRMR shows a pineal region tumor with hydrocephalus, mild transependymal and peritumoral edema. The mass surrounds internal cerebral veins (arrows), an important pre-operative finding, PB. (Right) Sagittal T 7 WI MR shows a mildly heterogeneous pineal region tumor with invasion of midbrain tectum and posterior corpus callosum, typical of pineoblastoma.

(Left) Sagittal T7 C+ MR shows moderate heterogeneous enhancement of the pineal region tumor. Typical enhancement pattern of pineoblastoma. (Right) Coronal T7 C+ MR shows a large, minimally enhancing, pineal region tumor with multiple cysts. Note lobular appearance of tumor with infiltration of brainstem, thalami, and temporal lobe. PB.

Neoplasms and Tumorlike Lesions

6 87

Sagittal graphic shows a cystic pineal gland mass with a fluid/fluid level and nodular tumor along periphery of mass, typical of pineocytoma. No significant mass effect is present.

Axial CECT shows a cystic pineal region mass that "explodes" pre-exisUng pineal calcifications (curved arrow), typical of pineocytoma. 24 year old female with headaches.

CT Findings Abbreviations • Pineocytoma

and Synonyms (PC), pineal parenchymal

tumor (PPT)

Definitions • Slow-growing pineal parenchymal tumor of young adults composed of small, uniform mature cells resembling pineocytes

88

General Features • Best diagnostic clue o Enhancing, circumscribed pineal mass which "explodes" pineal Ca++ o May mimic pineal cyst or pineoblastoma • Location o Pineal region o Rarely extends into 3rd ventricle • Size: Typically less than 3 cm • Morphology o Demarcated round or lobular mass, typically with calcification o Cystic change may be seen o May compress adjacent structures, but no invasion

• NECT o lsodense to hypodense mass, peripheral Ca++ o Cystic change may be seen o Rarely, associated hydrocephalus • CECT: Variable enhancement, typically heterogeneous

MR Findings • Tl WI: Isointense to hypointense round or lobular mass • T2WI o Hyperintense round or lobular pineal mass o May compress adjacent structures o If aqueduct compression, may see hydrocephalus • FLAIR: Hyperintense round or lobular pineal mass • T2* GRE: May see Ca++ as areas of "blooming" along periphery or within mass • Tl C+ o Strong, homogeneous enhancement is typical o Enhancement may be solid or peripheral

Imaging Recommendations • Best imaging tool o MR imaging most sensitive o CT may help identify Ca++ • Protocol advice: Include post-contrast sagittal images

coronal and

DDx: Pineal Region Mass

Pineoblastoma

Pineal Cyst

Germinoma

Neoplasms and Tumorlike Lesions

Tectal Glioma

PINEOCYTOMA Key Facts Terminology

Pathology

• Slow-growing pineal parenchymal tumor of young adults composed of small, uniform mature cells resembling pineocytes

• Pineocytoma and pineoblastomas account for 15% of pineal region neoplasms • Pineocytomas represent approximately 45% of pineal parenchymal tumors • Pineal parenchymal tumors < < germinoma • Cysts and small areas of hemorrh ay be seen • May compress but do not invade a acent structures • WHO grade II

Imaging Findings • Enhancing, circumscribed pineal mass which "explodes" pineal Ca++ • May mimic pineal cyst or pineoblastoma

Top Differential Diagnoses

Clinical Issues

• • • • •

• Overall 5 year survival 86%

Pineoblastoma Nonneoplastic pineal cyst Astrocytoma Other germ cell tumors (GCT) Meningioma

Diagnostic Checklist • PCs "explode" gland Ca++ while germinomas gland Ca++ • Imaging of pineocytoma may be nonspecific

"engulf"

I DIFFERENTIAL DIAGNOSIS

I PATHOLOGY

Pineoblastoma

General Features

• • • • •

• General path comments o Tumor arises from primary neuroepithelial cells of the pineal gland (pineocytes) o Three types of pineal parenchymal tumors • Pineocytoma (PC): Mature well-differentiated tumors • Pineal parenchymal tumor with intermediate differentiation: Tumors with high cellularity, nuclear atypia, occasional mitoses, no pineocytomatous rosettes • Pineoblastoma (PB): Malignant, primitive tumors o Pineal parenchymal tumors may show ganglionic, astrocytic, neuronal or mixed differentiation • Genetics o No TP53 mutations o Inconsistent reports of chromosomal gains/losses • Etiology o Derived from pineal parenchymal cells ("pineocytes") or their embryonic precursors o Pineocytes are cells with photo sensory & neuroendocrine function • Epidemiology o 0.4-1% of primary brain tumors o Pineocytoma and pineoblastomas account for 15% of pineal region neoplasms o Pineocytomas represent approximately 45% of pineal parenchymal tumors o Pineal parenchymal tumors < < germinoma

Large, lobulated heterogeneous mass Heterogeneous enhancement Often mass effect, parenchymal invasion, CSF spread Younger patients May be seen in patients with retinoblastoma, "trilateral retinoblastoma"

Nonneoplastic pineal cyst • • • •

Round, smooth cystic mass Typically < 1 cm, may be up to 2 cm Variable calcification and cyst fluid No or minimal rim enhancement, compressed enhancing gland often seen posteriorly • May be indistinguishable from PC on imaging

Germinoma • • • • •

"Engulfs" calcified pineal gland Intensely enhancing pineal mass, often homogeneous Often CSF spread at diagnosis Hyperdense on CT Typically young male patients

Astrocytoma • Infiltrative T2 hyperintense • Significant mass effect • Variable enhancement

mass

Other germ cell tumors (GCT) • Teratoma, choriocarcinoma, endodermal sinus (yolk sac) tumor, embryonal carcinoma, mixed GCT • Heterogeneous, enhancing pineal region mass • May have fat, hemorrhage, cystic change • Lab studies may help, Le., alpha-fetoprotein, HCG

Meningioma • Intensely enhancing, homogeneous • Older female patients

mass

Gross Pathologic & Surgical Features • Well-circumscribed, gray-tan mass with homogeneous or granular cut surface • Cysts and small areas of hemorrhage may be seen • May compress but do not invade adjacent structures • Rarely extends into 3rd ventricle • Compression of cerebral aqueduct may result in hydrocephalus

Neoplasms and Tumorlike Lesions

6 89

Microscopic

Features

• Well-differentiated tumor composed of small, uniform, mature cells resembling pineocytes • Sheets or lobules of tumor separated by mesenchymal septae • Large fibrillary "pineocytomatous rosettes" characteristic o Large rosettes surround a fine network of processes • Mitoses, necrosis absent • Immunohistochemistry o Stains intensely for synaptophysin, neuron specific enolase (NSE) • EM: Microtubules, clear and dense-core vesicles, and synapses • Pleomorphic subset o Mixed/intermediate differentiation, mitoses, occasional areas of necrosis, endothelial hyperplasia • May show a variable degree of neuronal, ganglionic or astrocytic differentiation

Staging, Grading or Classification Criteria • WHO grade II • New grading system based on mitoses and neurofilament (NF) protein staining for PPTs o Grade I, classic PC with no mitoses, + NF o Grade 2, < 6 mitoses/l0 high-power fields, + NF o Grade 3, < 6 mitoses & - NF or :2: 6 mitoses & + NF o Grade 4, variable mitoses +/- NF, (PB)

Consider • • • •

PC may be cystic and mimic a pineal PC may appear aggressive and mimic Germ cell tumors often have positive Clinical information often helpful to pineal region masses

Image Interpretation

1.

2.

3. 4. 5. 6.

Presentation

6 90

8. 9.

10.

11.

Demographics • Age o Children and young adults o Peak incidence 10-20 years, mean age 3S years o May occur at any age • Gender: No gender predominance

12.

Natural History & Prognosis

14.

• • • • •

Stable or slow growing tumor Overall S year survival 86% PC = 90% (grade II) to 100% (grade I) S year survival Surgical mortality < S% Extremely rarely complicated by hemorrhage

13.

15.

16.

"engulf"

Kondziolka D et al: The role of radiosurgery for the treatment of pineal parenchymal tumors. Neurosurgery. 51(4):880-9,2002 Rickert CH et al: Comparative genomic hybridization in pineal parenchymal tumors. Genes Chromosomes Cancer. 30(1):99-104, 2001 Allmer DM et al: Dorsal midbrain syndrome secondary to a pineocytoma. Optometry. 72(4):234-8, 2001 Hirato J et al: Pathology of pineal region tumors. J Neurooncol. 54(3):239-49, 2001 Kobayashi T et al: Stereotactic gamma radiosurgery for pineal and related tumors. J Neurooncol. 54(3):301-9, 2001 Jouvet A et al: Pineal parenchymal tumors: a correlation of histological features with prognosis in 66 cases. Brain Pathol. 10(1):49-60, 2000 Nakamura M et al: Neuroradiological characteristics of pineocytoma and pineoblastoma. Neuroradiology. 42(7):509-14,2000 Dario A et al: Cytogenetic and ultrastructural study of a pineocytoma case report. J Neurooncol. 48(2):131-4, 2000 Fauchon F et al: Parenchymal pineal tumors: A clinicopathological study of 76 cases. Int J Rad Onc BioI Phys 4: 959-68, 2000 Mena H et al: Pathology and genetics of tumours of the nervous system: Pineocytoma. Lyon, IARC Press, 118-21, 2000 Tsumanuma I et al: Clinicopathological study of pineal parenchymal tumors: correlation between histopathological features, proliferative potential, and prognosis. Brain Tumor Pathol. 16(2):61-8, 1999 Cho BKet al: Pineal tumors: experience with 48 cases over 10 years. Childs Nerv Syst. 14(1-2):53-8, 1998 Matsumoto K et al: Pineocytoma with massive intratumoral hemorrhage after ventriculoperitoneal shunt--case report. Neurol Med Chir (Tokyo). 37(12):911-5, 1997 Chiechi MV et al: Pineal parenchymal tumors: CT and MR features. J Comput Assist Tomogr. 19(4):509-17, 1995 Schild SE et al: Pineal parenchymal tumors. Clinical, pathologic, and therapeutic aspects. Cancer. 72(3):870-80, 1993 Smirniotooulos JG et al: Pineal region masses: differential diagnosis. Radiographics. 12:577-96, 1992

Treatment • • • •

Pearls

• PCs "explode" gland Ca++ while germinomas gland Ca++ • Enhancement often solid, may be peripheral • Imaging of pineocytoma may be nonspecific

7.

• Most common signs/symptoms o Headache, Parinaud syndrome (paralysis of upward gaze) o Other signs/symptoms: Increased intracranial pressure, ataxia, hydrocephalus, mental status changes • Clinical profile: Negative for germ cell markers including alpha-fetoprotein, human chorionic gonadotropin (HCG)

cyst a pineoblastoma serum markers differentiate

Surgical excision or stereotactic biopsy CSF diversion may be necessary Post-operative radiation therapy is controversial Early reports suggest stereotactic radiosurgery may be used as primary therapy

Neoplasms and Tumorlike Lesions

Typical (Left) Sagittal T2WI MR shows a cystic mass (arrow) in pineal region of this 20 year old female with headaches. Note lack of significant mass effect and hydrocephalus, typical of pineocytoma. (Right) Coronal T1 C+ MR shows peripheral and central enhancement of pineal mass. Imaging may mimic a pineal cyst. Follow-up imaging showed no change, similar to pineal cysts. Pineocytoma at resection.

Typical

(Left) Sagittal T1WI MR

shows an isointense pineal mass (arrow) with mild mass effect upon tectum. No associated hydrocephalus is seen. Young adult male with headaches and visual changes. (Right) Axial T2WI MR shows a fluid/fluid level within pineal mass (arrow). This may be seen in pineocytomas and rarely in pineal cysts. Pineocytoma. Pineocytomas are typically T2 hyperintense.

Variant

(Left) Axial T1WI MR shows a large, heterogeneous pineal

region mass with solid and cystic components. 32 year old female with headache and Parinaud syndrome. Common presenting features of pineocytoma. (Right) Axial CECT shows intense enhancement of large pineal mass. Pineocytoma at resection. Pineocytomas are typically less than 3 cm.

Neoplasms and Tumorlike Lesions

6 91

Axial graphic shows spherical tumor centered in the 4th ventricle, typical of medulloblastoma.

Axial T2WI MR shows large mass filling and expanding 4th ventricle and causing obstructive hydrocephalus. Signal is only mildly heterogeneous, due to small cysts and clefts in the tumor.

o May be helpful in identifying "drop" mets o Largely replaced by spinal MR with contrast

Abbreviations • Medulloblastoma PNET-MB

and Synonyms

CT Findings

(MB), posterior fossa PNET,

Definitions • Malignant,

6 92

invasive, highly cellular embryonal

tumor

General Features • Best diagnostic clue: Round, dense, 4th ventricle mass • Location o 4th ventricle tumor, arises from roof (superior medullary velum) • Distinguishes from ependymoma which arises from floor of 4th ventricle o Lateral origin (cerebellar hemisphere) more cominon in older children and adults • Size: 1-3 cm • Morphology: Spherical, pushes brain away on all sides

Radiographic

Findings

• Radiography: Hyperdense bone metastases may occur late in disease course (rare) • Myelography

• NECT o Solid mass in 4th ventricle • 90% hyperdense • Ca++ in up to 20%; hemorrhage rare • Small intra tumoral cysts/necrosis in 40-50% o Hydrocephalus common (95%) • CECT o > 90% enhance • Relatively homogeneous • Occasionally patchy (may fill in slowly)

MR Findings • • • •

T1WI: Hypointense to gray matter (GM) T2WI: Near GM intensity PD/Intermediate: Hyperintense to GM FLAIR o Hyperintense to brain o Good differentiation of tumor from CSF in 4th V • DWI: Restricted diffusion • T1 C+

o > 90% enhance o Often heterogeneous o Contrast essential to detect CSF dissemination • Linear icing-like enhancement over brain surface: "Zuckerguss"

DDx: 4th Ventricular Masses

Ependymoma

ATlRhT

Neoplasms

Brainstem Glioma

and Tumorlike Lesions

MEDULLOBLASTOMA (PNET-MB) Key Facts Terminology

Pathology

• Medulloblastoma (MB), posterior fossa PNET, PNET-MB • Malignant, invasive, highly cellular embryonal

• 15-20% of all pediatric brain tumors • WHO grade IV tumor

Imaging Findings • • • • •

Solid mass in 4th ventricle Hydrocephalus common (95%) > 90% enhance Contrast essential to detect CSF dissemination Contrast-enhanced MR of spine (entire neuraxis)

Top Differential • • • •

Diagnoses

Clinical Issues • • • • •

Ataxia, signs of increased intracranial pressure Relatively short « 1 month) of symptoms Rapid growth with eadysubarachnoid spread "Standard risk" clinical profile "High risk" clinical profile

Diagnostic Checklist • Remember AT/RhT in patients under 3 years • 4th V tumor arising from roof PNET-MB • 4th V tumor arising from floor ependymoma

= =

Cerebellar pilocytic astrocytoma (PA) Ependymoma Choroid plexus papilloma (CPP) Atypical teratoid/rhabdoid tumor (AT/RhT)

• Extensive "grape-like" tumor nodules uncommon o Contrast-enhanced MR of spine (entire neuraxis) • Up to a third have subarachnoid metastatic disease at presentation • Image pre-op to avoid false (+) post-op: Blood in spinal canal may mimic or mask metastases • MRS o !! NAA o t t Choline o Lactate usually present

IPATHOlOG¥

Angiographic

Findings

General Features

• Conventional: fossa mass

Avascular or hypovascular

posterior

Imaging Recommendations • Best imaging tool: Contrast-enhanced MR • Protocol advice o Sagittal images pre- and post-contrast to show site of origin (roof vs floor) o Quality of spine MR better if performed as a separate exam

I DIFFERENTIAI..DIAGNE)SIS Cerebellar

pilocytic astrocytoma (PA)

• Older children • Hemispheric lesion • Cyst with enhancing

nodule

Ependymoma • Older children • More heterogeneous, Ca++ and hemorrhage common • Extension through 4th V foramina/foramen "Plastic tumor"

Choroid plexus papilloma (CPP) • Much less common in 4th V • Vigorous and homogeneous enhancement • Less mass effect

more magnum:

Atypical teratoid/rhabdoid

tumor (AT/RhT)

• Indistinguishable by imaging • Younger children

Dorsally exophytic brainstem glioma • Use MR to show origin from brainstem

• General path comments o Most common posterior fossa tumor in children o Four major PNET-MB subtypes recognized • Classic • Desmoplastic • Extensively nodular with advanced neuronal differentiation • Large cell • Genetics o "Patched-I" and "smoothened" genes implicated in tumor development o Neoplasm and germline mutations (isochromosomes 17q, p53) o Sonic hedgehog (SHH) activation in desmoplastic MB

• Etiology o Two cell lines suspected as source • Cell rests of posterior medullary velum (roof of 4th V) • External granular layer of cerebellum • Epidemiology o 15-20% of all pediatric brain tumors o 30-40% of posterior fossa tumors in children o Rare in adults • Associated abnormalities o Association with familial cancer syndromes • Godin (nevoid basal cell carcinoma) syndrome • Li-Fraumeni syndrome • Turcot syndrome • Gardner syndrome • Cowden syndrome

Neoplasms and Tumorlike

Lesions

6 93

MEDULLOBLASTOMA (PNET-MB) o Also associated with Taybi and Coffin-Siris syndromes

Gross Pathologic & Surgical Features • Firm/discrete to soft/less well defined o Tumor outside of 4th V more likely to be desmoplastic variant

Microscopic

Features

• Densely packed hyperchromatic cells with scanty cytoplasm • Frequent mitoses • Anaplasia 24% • Neuronal/neuroblastic differentiation manifests as pale islands or Homer-Wright rosettes o Homer Wright rosette = central stellate zone of fibrillar processes coming from tumor cells o Neuronal/neuroblastic differentiation often causes nodular growth pattern • Desmoplastic subtype has abundant connective tissue between tumor cells • Immunohistochemistry: +/- Synaptophysin, vimentin o Some have glial differentiation (+ GFAP staining)

Staging, Grading or Classification Criteria

6 94

o Documented metastatic disease • Adult presentation slightly better outcome (may reflect greater resectability of lateral lesions, desmoplastic variant)

Treatment • Surgical excision, adjuvant chemotherapy • Craniospinal irradiation if > 3 years • Complications of treatment o Endocrinopathy, growth failure o Leukoencephalopathy o Mineralizing microangiopathy o Hearing loss

IDIA(iNOStIC<SHECKLI.~1" Consider • Remember AT/RhT in patients under 3 years • Pre-operative evaluation of entire neuraxis and post-operative evaluation of surgical bed are key to prognosis

Image Interpretation

Pearls

• WHO grade IV

• 4th V tumor arising from roof", PNET-MB • 4th V tumor arising from floor = ependymoma

ICLINICf\tISSlJES

I SELECTED

Presentation

1.

• Most common signs/symptoms o Ataxia, signs of increased intracranial pressure o Macrocephaly in infants with open sutures • Clinical profile o Relatively short « 1 month) of symptoms o Symptoms reflect local mass effect and/or increased ICP • Nausea and vomiting • Ataxia • Cranial nerve palsies (less common than in brain stem astrocytomas) o Gastrointestinal workup for N & V may precede diagnostic neuroimaging

2. 3.

4.

5.

6.

Demographics • Age o 75% < 10 years o Most diagnosed by 5 years • Gender: M > F = 2-4:1

7.

8.

Natural History & Prognosis • Rapid growth with early subarachnoid spread • Initial positive response to treatment reflects high mitotic activity • "Standard risk" clinical profile o No metastases or gross residual tumor sip resection o With ERBB-2tumor protein negative = high 5 year survival rate (100%) o With ERBB-2tumor protein positive = low 5 year survival rate (54%) • "High risk" clinical profile o 5 year survival rate is "" 20% o Gross residual tumor after surgery

9.

10. 11.

12.

13.

REFERENCES

Tong CYK et al: Detection of oncogene amplifications in medulloblastomas by comparative genomic hybridization and array-based comparative genomic hybridization. ] Neurosurg 100:187-93, 2004 Fisher PG et al: Biologic risk stratification of medulloblastoma: the real time is now. ] Clin Oncol, 2004 Gajjar A et al: Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. ] Clin Oncol, 2004 Fernandez-Teijeiro A et al: Combining gene expression profiles and clinical parameters for risk stratification in medulloblastomas. ] Clin Oncol, 2004 Chojnacka M et al: Medulloblastoma in childhood: Impact of radiation technique upon the outcome of treatment. Pediatr Blood Cancer. 42(2):155-60, 2004 Suresh TN et al: Medulloblastoma with extensive nodularity: a variant occurring in the very young-clinicopathological and immunohistochemical study of four cases. Childs Nerv Syst. 20(1):55-60, 2004 Eberhart CG et al: Anaplasia and grading in medulloblastoma. Brain Pathol. 13:376-85,2003 Koeller K et al: Medulloblastoma: a comprehensive review with radiologic-pathologic correlation. RadioGraphies 23:1613-37, 2003 Kortmann RD et al: Current and future strategies in the management of medulloblastoma in adults. Forum (Geneva). 13(1):99-110,2003 Taylor MD et al: Mutations in SUFU predispose to medulloblastoma. Nat Genet 31(3):306-10, 2002 Huber H et al: Angiogenic profile of childhood primitive neuroectodermal brain tumours/medulloblastomas. Eur ] Cancer. 37(16):2064-72, 2001 Meyers SP et al: Postoperative evaluation for disseminated medulloblastoma involving the spine. Am] Neuroradiol 21:1757-65,2000 Vezina LG et al: Infratentorial brain tumors of childhood. Neuroimaging Clin North Am 4(2):423-36, 1994

Neoplasms and Tumorlike Lesions

MEDULLOBLASTOMA (PNET-MB) Typical (Left) Sagittal TlWI MR shows large PNET-MB expanding 4th ventricle and uplifting posterior tectal plate (arrow). Interface with superior medullary velum is poorly defined (curved arrow). (Right) Sagittal Tl C+ MR shows mildly heterogeneous enhancement in same tumor. Interface with dorsal brainstem is relatively well defined (arrow), pointing to origin of tumor from roof of 4th ventricle.

Typical (Left) Sagittal Tl C+ MR shows multiple enhancing nodules in cervical spinal canal and posterior fossa in child previously treated with surgery and radiation for posterior fossa PNET-MB. (Right) Axial Tl C+ MR shows enhancing PNET-MB in 4th ventricle and metastatic tumor in both CP angles. Up to one-third of PNET-MB will have subarachnoid metastatic disease at presentation.

Variant (Left) Axial Tl C+ MR shows the classic desmoplastic variant of PNET-MB in a 26 yo female. The lateral cerebellar location is atypical. (Right) Coronal Tl C + M R shows the rare PNET-MB with extensive nodularity. No focal dominant mass is seen but multiple "grape-like" tumor nodules are present.

Neoplasms and Tumorlike

Lesions

6 95

Axial T1 C+ MR shows a bi-Iobed right hemispheric PNET with sharply defined borders and ventricular compression. Also note lack of peritumoral edema (arrows).

o Suprasellar • Size o Variable, based on location and presenting symptoms • Cerebral hemispheric PNETs are larger at diagnosis, mean diameter - 5 ems • Suprasellar PNETs tend to be smaller due to neuroendocrine and visual disturbances • Pineal PNETs cause ventricular obstruction and gaze/convergence difficulties o Hemispheric lesions in newborns and infants: Often huge • Morphology: Vary between sharply delimited to diffusely infiltrative

i··T.E•.RN1IN,O,L();C::;¥ Abbreviations

and Synonyms

• Supratentorial primitive neuroectodermal tumor (S-PNET) • Supratentorial PNET • Supratentorial primitive neuroepithelial tumor • Primary cerebral neuroblastoma • Cerebral ganglioneuroblastoma

6 96

Definitions • Cerebral embryonal tumor composed of undifferentiated neuroepithelial cells o S-PNET: Tumor cells have capacity for differentiation - astrocytic, ependymal, muscular, melanotic

Coronal T1 C+ MR shows a large necrotic hemispheric PNET with irregular marginal enhancement and diffuse CSFtumor seeding (arrows).

neuronal,

Radiographic Findings • Radiography: Macrocephaly (neonate and infant)

"I,MAG1.NG;;.fINIJ.l,IN,GS

and widened sutures

CT Findings

General Features • Best diagnostic clue: Large, complex hemispheric with minimal peritumoral edema • Location o Pineal o Hemispheric • Cortical/subcortical • Thalamic

mass

DDx: Pediatric Cerebral Hemispheric

• NECT o Homogeneous to heterogeneous o Isoattenuating to hyperattenuating o Calcification (50-70%) o Hemorrhage and necrosis common • CECT o Heterogeneous enhancement o Prone to CSF tumor seeding

Masses

,

.

..s·.·If.~ (

-

GBM

'

.. .

Ependymoma

Oligodendroglioma

Neoplasms and Tumorlike

Lesions

Tumefactive MS

SUPRATENTORIAL

PNET

Key Facts Terminology

Top Differential Diagnoses

• Supratentorial primitive neuroectodermal (S-PNET) • Cerebral embryonal tumor composed of undifferentiated neuroepithelial cells

tumor

• • • •

Astrocytoma Ependymoma Oligodendroglioma Atypical teratoid/rhabdoid

Imaging Findings

Pathology

• Best diagnostic clue: Large, complex hemispheric mass with minimal peri tumoral edema • Isoattenuating to hyperattenuating • Calcification (50-70%) • Hemorrhage and necrosis common • Heterogeneous enhancement • DWI: Restricted diffusion common • Best imaging tool: Enhanced MR of brain and spine • Adding post-enhanced FLAIR aids in detecting leptomeningeal metastases

• WHO grade IV

tumor

Clinical Issues • Vary with site of origin and size of tumor • Hemispheric ....•seizures, disturbed consciousness, motor deficit, elevated ICP • Suprasellar"'" visual disturbance, endocrine problems • Clinical profile: Infant presenting with macrocephaly, seizures and large hemispheric mass • S-PNET...., 30-35% 5 year survival

MR Findings

I DIFFERENTIAL DIAGNOSIS

• TlWI o Hypointense to isointense to gray matter o Homogeneous to heterogeneous o ± Hydrocephalus • T2WI o Solid elements isointense to slightly hyperintense gray matter o Heterogeneity common o Sparse peri tumoral edema o Ca++ ~ hypointense foci o Blood products ~ mixed signal intensity • PD/Intermediate: Slightly hyperintense • FLAIR o Solid components hyperintense o Little peritumoral edema o Post-enhanced FLAIR detects leptomeningeal metastases • T2* GRE: Dephasing from blood products • DWI: Restricted diffusion common • T1 C+ o Heterogeneous enhancement o CSF pathway seeding common o Subtraction imaging helpful with hemorrhagic masses • MRS: !!NAA, ! creatine, i i choline, + lipid and lactate

Astrocytoma

to

Ultrasonographic Findings • Congenital S-PNET o Large heterogeneous hyperechoic hemispheric mass • Antenatal sonography o Hydrocephalus and hyperechoic hemispheric mass

• Grade I ~ glioblastoma multiforme (GBM) • Variable enhancement • More anaplastic tumors characterized by extensive vasogenic edema • Calcification uncommon

Ependymoma • When supratentorial (30%), usually intra-axial o Only 15-25% arise within third or lateral ventricle • Large at presentation, Ca++ in 50% • Necrosis and hemorrhage not uncommon

6

Oligodendroglioma

97

• Strong predilection for frontotemporal • Peripheral location • Coarse Ca++ common

Atypical teratoid/rhabdoid

tumor

• Posterior fossa location> 50%, supratentorial 39% • Necrosis, cysts, and vasogenic edema common • Subarachnoid seeding common

Choroid plexus carcinoma • Parenchymal invasion can be dramatic • Extensive vasogenic edema • Strong heterogeneous enhancement

Tumefactive multiple sclerosis (MS) • For "tumor" size, less mass effect than expected • Outer enhancing border & inner T2 hypointense border

Giant cavernoma

Imaging Recommendations • Best imaging tool: Enhanced MR of brain and spine • Protocol advice o Perform enhanced MR of entire neuraxis before surgery o Adding post-enhanced FLAIR aids in detecting leptomeningeal metastases

region

• Can be huge in newborn and infant • Mimics hemorrhagic tumor

Neoplasms and Tumorlike

Lesions

General Features • General path comments: Embryonal tumor of cerebrum, suprasellar or pineal regions • Genetics o Unlike medulloblastoma (PNET-MB), chromosome 17 aberrations (rare) o Somatic mutations in tumor suppressor genes • HASHI • hSNF5 on chromosome 22 o Other chromosome anomalies in S-PNETs • Aberrations of short arm of chromosome 11 • Trisomies of chromosomes 9,13,lq, and 18p telomere maintenance • Etiology: Aberrations in tumor suppressor genes, may playa role • Epidemiology o S-PNETs constitute - 1% of pediatric brain tumors o Of all CNS PNETs, - 5.6% are supratentorial (S-PNET) o An important hemispheric mass to consider in newborn and infant • Associated abnormalities o Hereditary syndromes • Gorlin syndrome • Turcot syndrome • Hereditary retinoblastoma and risk for secondary malignancies • Rubinstein-Taybi syndrome

6 98

• Pineal ~ hydrocephalus, Parinaud syndrome o Other signs/symptoms • Cranial neuropathies due to herniation or diffuse CSF metastases • Clinical profile: Infant presenting with macrocephaly, seizures and large hemispheric mass

Demographics • Age o More common in younger children • Median age at diagnosis 35 months • Gender: M:F = 2:1 • Ethnicity: No ethnic predilection

Natural History & Prognosis • Compared to posterior fossa PNET (PNET-MB), S-PNETs have poorer survival o S-PNET ~ 30-35% 5 year survival o PNET-MB ~ 80-85% 5 year survival • Critical survival factors include o Completeness of surgical resection o Absence of metastases o Patient age> 2 years o Smaller, solid tumor (tumor necrosis is unfavorable) o Immunohistochemical labeling indices (Ki index> 10%, unfavorable) o M stage of tumor • Heavily calcified S-PNETs have slightly better prognosis • No survival advantage for specific supratentorial location

Gross Pathologic & Surgical Features

Treatment

• Variable consistency o Solid and homogeneous ~ cystic, necrotic, hemorrhagic and partially calcified o Solid portions soft pink-red coloration, unless prominent desmoplasia o Necrosis and hemorrhage common o Demarcation between tumor and brain may range from indistinct to sharp

• Aggressive surgical resection, chemotherapy, craniospinal radiation

Microscopic

Features

• Similar to medulloblastoma (PNET-MB) • Composition o Undifferentiated or poorly differentiated neuroepithelial cells o Pleomorphic nuclei o Field necrosis, hemorrhage, Ca++ o Homer-Wright rosettes & Flexner-Wintersteiner rosettes

Staging, Grading or Classification Criteria

IDIAGN()SII(](]I-IE(]I<1~lst Consider • S-PNET in newborn, infant or young child presenting with o Hemispheric tumor lacking edema o Suprasellar or pineal mass

Image Interpretation • Large hemispheric edema

I SELECTED REFERENCES 1.

• WHO grade IV 2.

3.

Presentation • Most common signs/symptoms o Vary with site of origin and size of tumor • Hemispheric ~ seizures, disturbed consciousness, motor deficit, elevated ICP • Suprasellar ~ visual disturbance, endocrine problems

Pearls

mass with sparse peritumoral

4. 5.

Didiano D et al: Telomere maintenance in childhood primitive neuroectodermal tumors. Neuro-oncol 6:1-8, 2004 Yamada T et al: Prenatal imaging of congenital cerebral primitive neuroectodermal tumor. Fetal Diagn Ther. 18(3): 137-9,2003 Etus V et al: Primary cerebral neuroblastoma: a case report and review. Tohoku] Exp Med. 197(1): 55-65, 2002 Reddy AT: Advances in biology and treatment of childhood brain tumors. Curr Neurol Neurosci Rep. 1(2): 137-43, 2001 Young-Poussaint T: Magnetic resonance imaging of pediatric brain tumors: state of the art. Topics in magnetic resonance imaging. 12(6): 411-434, 2001

NeODlasms and Tumorlike

Lesions

Typical (Left) Axial NECT shows a heavily calcified left frontal lobe primitive neuroectodermal tumor (S-PNET). Note increased density of non-calcified tumor (arrow). (Right) Axial T1WI MR shows a supratentorial primitive neuroectodermal tumor demonstrating heterogenous T1 shortening due to intra tumoral hemorrhage (arrows).

Typical (Left) Axial FLAIR MR shows a deep hemispheric PNET with associated subfalcine herniation, ventricular obstruction and interstitial edema (arrows). Also note sparse peritumoral edema (curved arrows). (Right) Axial OWl MR shows restriction of diffusion within hemispheric primitive neuroectodermal tumor (S-PNET) (arrows).

6 99

Variant (Left) Coronal T1 C+ MR shows a predominantly cystic hemispheric PNET with irregularly enhancing mural nodule (open arrow). (Right) Coronal T1 C+ MR shows incomplete marginal enhancement of left hemispheric PNET (arrow). Note lack of peritumoral edema.

Neoplasms and Tumorlike Lesions

ATYPICAL TERATOID-RHABDOID

Coronal graphic shows AT/Rh T. Foci of central necrosis can coalesce, form thick nodular enhancing tumor rind around central cavity.

Axial T1 C+ MR shows a heterogeneously enhancing posterior 3rd ventricular mass with a lobulated contour and small cyst (arrow). Note associated hydrocephalus. 15 month old with AT/Rh T.

• Morphology:

Abbreviations

• AT/RhT, AT/RT • Synonyms: Malignant rhabdoid tumor of brain, cranial rhabdoid tumor

Definitions • Rare aggressive tumor of early childhood composed of rhabdoid cells, areas resembling PNET, and malignant mesenchymal or epithelial tissue

100

General Features • Best diagnostic clue o Heterogeneous intracranial mass in an infant o Think of AT/RhT when medulloblastoma (PNET-MB) is considered • Location o 50% infratentorial (most off-midline) • Cerebello-pontine angle (CPA) • Cerebellum and/or brainstem o 40% supratentorial • Hemispheric or suprasellar o 15-20% present with disseminated tumor • Size: most = 1-3 cm at presentation (can be very large)

Ependymoma

Roughly spherical, irregular

CT Findings

and Synonyms

DDx: Cerebellar

TUMOR

• NECT o Hyperattenuating mass o Commonly contains cysts or hemorrhage o May contain Ca++ o Obstructive hydrocephalus common • CECT: Heterogeneous enhancement

MR Findings • TlWI o Heterogeneous • Isointense to brain with foci of hyperintensity corresponding to hemorrhage • Cysts slightly hyperintense to CSF • T2WI o Heterogeneous • Regions of marked hypointense signal from hemorrhage • Hyperintense cystic foci • FLAIR o Cysts hyperintense to CSF o Solid tumor isointense to hyperintense o Transependymal edema • T2* GRE: Hypointense "blooming" of hemorrhagic foci • DWI o Hyperintense o Decreased apparent diffusion coefficient (ADC)

Masses of Childhood

Medulloblastoma

Piloeytie Astrocytoma

Neoplasms and Tumorlike Lesions

Gliosareoma

ATYPICAL TERATOID-RHABDOID

TUMOR

Key Facts Terminology

Pathology

• Rare aggressive tumor of early childhood composed of rhabdoid cells, areas resembling PNET, and malignant mesenchymal or epithelial tissue

• Rhabdoid cells resemble those in malignant rhabdoid tumor of kidney • Divergent differentiation accounts for "teratoid" label

Imaging Findings

Clinical Issues

• • • • • •

• Clinical profile: Child under 3 with increasing head size, vomiting, and lethargy • Median survival 6 months

Heterogeneous intracranial mass in an infant 15-20% present with disseminated tumor Commonly contains cysts or hemorrhage May contain Ca++ Heterogeneous enhancement Best imaging tool: MRI with contrast

Top Differential

Diagnoses

• Medulloblastoma

(PNET-MB)

• T1 C+ o Heterogeneous enhancement o Leptomeningeal spread • Diffuse linear • Multiple nodular • MRA: May show narrowing of encased vessels • MRS o Aggressive metabolite pattern • Elevated choline • Low or absent NAA and creatine • Lipid/lactate peak

Imaging Recommendations • Best imaging tool: MRI with contrast • Protocol advice o MRA may be of benefit for identifying vascular compromise o Entire CNS must be imaged at presentation to identify subarachnoid spread of tumor

I DIFFERENTIAL. DIAGNOSIS Medulloblastoma

(PNET-MB)

• Posterior fossa tumor • AT/RhT more likely to have cysts than PNET-MB

Pilomyxoid astrocytoma • Chiasmatic/hypothalamic • Solid enhancing tumor

tumor in infants

Pilocytic astrocytoma (PA) • More commonly contains large cyst • Older children (5-15 years)

Choroid plexus papilloma (CPP) • Intraventricular mass • Homogeneous enhancement

Gliosarcoma • High grade glioma • Exophytic from brainstem

=

Diagnostic Checklist • Always consider AT/RhT when large tumor found in child < 3 • More likely to be heterogeneous or supratentorial than PNET-MB

Ependymoma • "Plastic" tumor, extends out 4th ventricle foramina • Ca++, cysts, hemorrhage common; heterogeneous enhancement

Teratoma • More often pineal or parasellar in location • Heterogeneous on imaging due to Ca++, hemorrhage

Hemangioblastoma • Large cyst with small enhancing mural nodule • Adult tumor! • Often associated with von Hippel Lindau disease

I PATHOL.OG¥ General Features • General path comments o Defined as distinct lesion in 1987 o Combination of primitive neuroectodermal, peripheral epithelial, and mesenchymal elements o Divergent differentiation • Genetics o Monosomy of chromosome 22 or deletion of band 22qll • Band 22q11 is site of hSNF5/INIl gene o Chromosome 22 abnormalities are also found in other CNS tumors • Etiology o Unknown o Rhabdoid cells resemble those in malignant rhabdoid tumor of kidney o Divergent differentiation accounts for "teratoid" label • Diverse immunohistological staining suggests multiple cell line • Cells do not develop beyond primitive stage, unlike teratoma • Epidemiology o Rare over 3 years of age

Neoplasms and Tumorlike Lesions

6 101

ATYPICAL TERATOID-RHABDOID o Up to 20% of primitive CNS tumors in children under 3 o No gender predominance

Gross Pathologic & Surgical Features • Frequently unresectable at presentation • Poorly defined tumor margins • Infiltration into parenchyma • Sheets of non-specific cells interrupted by fibrovascular septa • Rhabdoid cells o Large, pale, bland cells with moderate eosinophilic cytoplasm • Embracing cells o Sickle-shaped cells that "embrace" rhabdoid cells • Frequent positive immunoreactivity o Vimentin (VIM) o Neuron specific enolase (NSE) o Glial fibrillary acidic protein (GFAP) o Epithelial membrane antigen (EMA)

Staging, Grading or Classification Criteria

102

1.

3.

4.

5.

6.

7. 8.

I CUN ICALISSUES

9.

• Most common signs/symptoms o Signs of increased intracranial pressure • Lethargy • Vomiting • Increased head circumference o Other signs/symptoms • Torticollis • Seizure • Regression of skills • Clinical profile: Child under 3 with increasing head size, vomiting, and lethargy

Demographics • Age: < 3 Y • Gender: M

=

10.

11.

12.

13. 14.

15.

F

Natural History & Prognosis

16.

• Median survival = 6 months • Death rate = 85%

17.

Treatment • Some question benefit of gross total resection • Radiation rarely an option due to young age • Chemotherapy regimens designed for PNET-MB largely ineffectual

18.

19.

IDIAGNOSTICCHECKUST

20.

Consider • Always consider AT/RhT when large tumor found in child < 3

Image Interpretation • Imaging appearance

or supratentorial

than

I SELECTED REFERENCES

• WHO grade IV

Presentation

6

• More likely to be heterogeneous PNET-MB

2.

Microscopic Features

TUMOR

Lee YK et al: Atypical teratoma/rhabdoid tumor of the cerebellum: Report of two infantile cases, AJNR 25: 481-3, 2004 Arslanoglu A et al: Imaging findings of CNS atypical teratoid/rhabdoid tumors. AJNR 25: 476-80, 2004 Quadery FAet al: Diffusion-weighted MRI of haem angioblastomas and other cerebellar tumours. Neuroradiology. 45(4):212-9, 2003 Wharton SBet al: Comparative genomic hybridization and pathological findings in atypical teratoid/rhabdoid tumour of the central nervous system. Neuropathol Appl Neurobiol. 29(3):254-61, 2003 Gessi M et al: Atypical teratoid/rhabdoid tumors and choroid plexus tumors: when genetics "surprise" pathology. Brain Pathol. 13(3):409-14, 2003 Utsuki S et al: Importance of re-examination for medulloblastoma and atypical teratoid/rhabdoid tumor. Acta Neurochir (Wien). 145(8):663-6; discussion 666, 2003 Dang T et al: Atypical teratoid/rhabdoid tumors. Childs Nerv Syst. 19(4):244-8,2003 Fenton LZ et al: Atypical teratoid/rhabdoid tumor of the central nervous system in children: an atypical series and review. Pediatr Radiol. 33(8):554-8, 2003 Packer RJ et al: Atypical teratoid/~habdoid tumor of the central nervous system: report on workshop. J Pediatr Hematol Oncol. 24(5):337-42, 2002 Chung YN et al: Primary intracranial atypical teratoid/rhabdoid tumor in a child: a case report. J Korean Med Sci. 17(5):723-6,2002 Bambakidis NC et al: Atypical teratoid/rhabdoid tumors of the central nervous system: clinical, radiographic and pathologic features. Pediatr Neurosurg. 37(2):64-70, 2002 Lee MC et al: Atypical teratoid/rhabdoid tumor of the central nervous system: clinico-pathological study. Neuropathology. 22(4):252-60, 2002 Hauser P et al: Atypical teratoid/rhabdoid tumor or medulloblastoma? Med Pediatr Oneal. 36(6):644-8, 2001 Guier E et al: Extraneural metastasis in a child with atypical teratoid rhabdoid tumor of the central nervous system. J Neurooncol. 54(1):53-6, 2001 Lopez-Gines C et al: Complex rearrangement of chromosomes 6 and 11 as the sole anomaly in atypical teratoid/rhabdoid tumors of the central nervous system. Cancer Genet Cytogenet. 122(2):149-52,2000 Tamiya T et al: Spinal atypical teratoid/rhabdoid tumor in an infant. Pediatr Neurosurg. 32(3):145-9, 2000 Ho DM et al: Atypical teratoid/rhabdoid tumor of the central nervous system: a comparative study with primitive neuroectodermal tumor/medulloblastoma. Acta Neuropathol (Berl). 99(5):482-8, 2000 Korones DN et al: A 4-year-old girl with a ventriculoperitoneal shunt metastasis of a central nervous system atypical teratoid/rhabdoid tumor. Med Pediatr Oncol. 32(5):389-91, 1999 aka H et al: Clinicopathological characteristics of atypical teratoid/rhabdoid tumor. Neurol Med Chir (Tokyo). 39(7):510-7; discussion 517-8, 1999 Zuccoli G et al: Central nervous system atypical teratoid/rhabdoid tumour of infancy. CT and mr findings. Clin Imaging. 23(6):356-60, 1999

Pearls

is nonspecific

Neoplasms and Tumorlike Lesions

ATYPICAL TERATOID-RHABDOID

TUMOR

Typical (Left) Axial NECT shows large hyperattenuating mass centered in right cerebellar hemisphere exerting mass effect upon fourth ventricle, with small cystic focus at posterior aspect (arrow). (Right) Axial FLAIRMR shows mass as isointense to brain with region of hyperintense signal (arrow) corresponding to cystic focus seen on NECT.

(Left) Axial T7 C+ MR shows

large enhancing mass centered in right middle cranial fossa with large lateral cystic component, encasing right carotid terminus at origin of middle cerebral artery (arrow). (Right) Axial T2WI MR shows extensive hypointense signal in mass, consistent with hemorrhagic staining and calcification.

6 103

(Left) Sagittal T7 C+ MR

shows multiple "drop mets" (arrows) along ventral and dorsal surfaces of cervical and thoracic cord from posterior fossa AT/RhT. 15-20% of AT/RhT have metastases at presentation. (Right) Short echo proton MR spectroscopy of AT/RhT shows marked elevation of choline (arrow) and a broad lipid/lactate peak (curved arrow).

Neoplasms and Tumorlike

Lesions

Axial CECT shows enhancing soft tissue masses projecting into left orbit and middle cranial fossa (arrows) from metastatic NBT in a child with "raccoon eyes"

Axial NECT with bone windows and edge detail algorithm in same child shows spiculated periostitis associated with soft tissue masses characteristic of NBT

o Cranial suture widening o Periosteal new bone

Abbreviations

and Synonyms

• Neuroblastoma

(NB), NBT, neuroblastic

tumors (NT)

Definitions • Malignant tumor of the sympathetic nervous system arising from primordial neural crest cell derivatives

6 104

General Features • Best diagnostic clue: Bony orbital spiculation in a child with "raccoon eyes" • Location o Nearly always extradural calvarial based mass o Often around orbit and sphenoid wings o Intra-axial lesions rare • Size: Variable • Morphology: Crescentic or lenticular, following contour of bone • Classic imaging appearance o "Hair-on-end" spiculated periostitis of orbits & skull o Mimic epidural or subdural hematomas

Radiographic

Findings

• Radiography

CT Findings • NECT o NECT best modality for demonstrating fine spicules of periosteal bone projecting off skull or sphenoid wings o Soft tissue mass typically isodense to brain o Mass projects into orbit (extraconal) o May project through inner and outer tables of skull • CECT: Soft tissue masses enhance vigorously

MR Findings • TIWI o Slightly heterogeneous o Isointense to gray matter • T2WI o Heterogeneous o Hypointense to brain • PDjIntermediate o Heterogeneous o Iso- and hypointense to brain • FLAIR o Heterogeneous o Hyperintense to brain • T2* GRE: Hypointense • Tl C+: Vigorously enhances • MRV: May narrow dural sinuses significantly

DDx: Calvarial Masses

Subdural Hematoma

Epidural Hematoma

Neoplasms

and Tumorlike Lesions

Leukemia

NEUROBLASTOMA,

METASTATIC

Key Facts Terminology • Malignant tumor of the sympathetic nervous system arising from primordial neural crest cell derivatives

(LCH)

Pathology

Imaging Findings • Best diagnostic clue: Bony orbital spiculation in a child with "raccoon eyes" • "Hair-on-end" spiculated periostitis of orbits & skull • NECT best modality for demonstrating fine spicules of periosteal bone projecting off skull or sphenoid wings • May project through inner and outer tables of skull • Bone scan essential for differentiating stage IV disease from stage IV-S in children < 1 yr

Top Differential

• Langerhans cell histiocytosis • Extra-axial hematoma • Ewing sarcoma

• Calvarial metastases indicate Stage IV disease

Clinical Issues • Cranial metastatic disease rarely occurs in isolation • Ocular involvement in 20% at presentation (poor prognostic indicator)

Diagnoses

• Leukemia

Nuclear Medicine

Ewing sarcoma

Findings

• Bone Scan o MIBG (meta-iodobenzylguanidine) • Labeled with iodine-131 or iodine-123 • Avid uptake by neural crest tumors • 90-100% sensitivity in detecting NBT • Can't distinguish marrow disease from bone disease o Tc-99m-MDP (methylene diphosphonate) • Distinguishes bony from marrow disease • Bone scan essential for differentiating stage IV disease from stage IV-S in children < 1 yr • PET o FDG-PET imaging has shown high sensitivity and specificity for recurrent tumor in small numbers of cases o FDG-PET may identify recurrence when MIBG is negative due to de-differentiation

Imaging Recommendations • Best imaging tool: CT with and without contrast • Protocol advice o Brain/orbit CT performed if nuclear medicine studies (bone scan, MIBG) indicate disease o MR with contrast and fat saturation technique complementary to CT and MIBG

I DIFFER.ENTIAL

DIAGNOSIS

leukemia • Dural or calvarial based masses • More frequent parenchymal masses • Less heterogeneous on MR

langerhans

cell histiocytosis (lCH)

• Lytic bone lesions without periosteal new bone • Often accompanied by diabetes insipidus

Extra-axial hematoma • Subdural or epidural hematoma • Bleeding disorder or child abuse to be considered

• < 1% of cases involve skull • Aggressive bone destruction • Spiculated periosteal reaction

Osteosarcoma • Rarely primary in calvarium

I PATHOLOGY General Features • General path comments o Small round blue cell tumor o NBT is most common and aggressive of neuroblastic tumors • Ganglioneuroblastoma: Malignant • Ganglioneuroma: Benign tumor of mature ganglion cells o Embryology-anatomy • Primitive neural crest cell origin • Arise at sites of sympathetic ganglia • Genetics o Multiple gene loci associated with NBT (lp, 2p, 9p, llq, 16q, and 17q) o High association with chromosome 17 translocations o 35% of primary neuroblastomas have deletion of distal short arm of chromosome 1 o 1-2% of cases inherited • Etiology o Arise from pathologically maturing neural crest progenitor cells o No known causative factor • Epidemiology o Most common solid extracranial tumor in childhood o 8-10% of all childhood cancer • Associated abnormalities o Rarely associated with Beckwith-Wiedemann syndrome, Weaver syndrome o Some association with neurocristopathy syndromes

Neoplasms and Tumorlike lesions

6 105

• Gray-tan soft nodules • Well-demarcated without capsule • Calcifications

o More likely in younger patients • Bad prognostic indicators: Stage IV disease, ocular involvement, presence of HER2/neu oncogene over-expression in tumor o 20% of patients presenting with ocular involvement will suffer vision loss • OMA: Majority have persistent symptoms, including developmental delay

Microscopic Features

Treatment

• Undifferentiated round blue cells o Scant cytoplasm o hyperchromatic nuclei • May form Homer-Wright rosettes • Ganglioneuroblastoma has interspersed mature ganglion cells o Different regions of same tumor may have ganglioneuroblastoma or NBT

• Stage IV-S may not require treatment: spontaneous regression • Surgical resection • Chemotherapy • Bone marrow transplant • Targeted 13lI-MIBG therapy

• Hirschsprung disease • Congenital central hypoventilation • Di-George syndrome

Gross Pathologic & Surgical Features

Follow for

Staging, Grading or Classification Criteria • Calvarial metastases indicate Stage IV disease • Evans anatomic staging system o Stage I: Confined to organ of interest (13.5%) o Stage II: Extension beyond organ but not crossing midline (11 %) o Stage III: Extension crossing midline (include vertebral column) (8.4%) o Stage IV: Systemic with widespread distal metastases (44%) o Stage IV-S: < 1 yr at diagnosis, stage I plus metastatic disease confined to skin, liver, or bone marrow • May spontaneously regress

6 106

Presentation • Most common signs/symptoms: "Raccoon eyes" • Clinical profile o Cranial metastatic disease rarely occurs in isolation o Ocular involvement in 20% at presentation (poor prognostic indicator) • Bilateral periorbital discoloration/ecchymoses: "Raccoon eyes" • Horner syndrome o Opsoclonus, myoclonus, and ataxia (OMA) • Also called myoclonic encephalopathy of infancy (MEI) • Paraneoplastic syndrome • Up to 4% of NBT patients o Elevated vasoactive intestinal peptides (VIP) • Up to 7% of NBT patients • Diarrhea, hypokalemia, achlorhydria

Demographics • Age o Median age diagnosis o 6% by 1 yr o 79% by 4 yrs • Gender: M:F = 1.2:1

= 22

months

Consider • Abdominal imaging (US) to identify primary tumor site • Peripheral blood smear to exclude leukemia

Image Interpretation

I SELECTED REFERENCES Burchill SA: Micrometastases in neuroblastoma: are they clinically important?] Clin Pathol. 57:14-20, 2004 2. Scanga DR et al: Value of FOG PET imaging in the management of patients with thyroid, neuroendocrine, and neural crest tumors. Clin Nucl Med. 29(2):86-90, 2004 3. Varma 0 et al: Acute visual loss as an early manifestation of metastatic neuroblastoma. Eye. 17(2):250-2,2003 4. Stallings RL et al: Are gains of chromosomal regions 7q and 11p important abnormalities in neuroblastoma? Cancer Genet Cytogenet. 140(2):133-7,2003 5. Matthay KK et al: Central nervous system metastases in neuroblastoma: radiologic, clinical, and biologic features in 23 patients. Cancer. 98(1):155-65, 2003 6. ]aing TH et al: Brain metastases in children with neuroblastoma--a single-institution experience. Med Pediatr Oncol. 41(6):570-1, 2003 7. Grover SB et al: Solitary calvarial metastases: an unusual presentation of thoracic neuroblastoma. Indian] Cancer. 40(3):120-2,2003 8. Okuyama C et al: Utility of follow-up studies using meta-[123 I]iodobenzylguanidine scintigraphy for detecting recurrent neuroblastoma. Nucl Med Commun. 23(7):663-72, 2002 9. Lonergan G] et al: Neuroblastoma, ganglioneuroblastoma and ganglioneuroma: Radiologic-pathologic correlation. Radiographies 22:911-34,2002 10. Cooper R et al: Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: Histopathologic features-a report from the Children's Cancer Group. Med Pediatr Onco136(6):623-9, 2001 1.

Natural History & Prognosis • Good prognostic indicators: Locoregional, n-myc gene amplification

Pearls

• CT without contrast can help identify bone spicules, eliminating LCH from differential

stage IVs, t

Neoplasms and Tumorlike

Lesions

NEUROBLASTOMA, METASTATIC

Typical (Left) Sagittal T7 C+ MR shows extensive extradural metastatic disease in stage IV neuroblastoma. Tumor impinges on sagittal sinus and projects into anterior cranial fossa from sphenoid bone(affow).(R~hn Coronal T7 C+ MR in same case shows ability of disease to cross midline in both regions (arrows). Little dural reactive enhancement is seen (no dural "tail").

(Left) Frontal radiography shows periosteal new bone projecting from both inner and outer table of skull (arrows). Bidirectional spiculation can help differentiate from cephalohematoma in infants. (Right) Axial CECT shows soft tissue mass and periosteal new bone in metastatic neuroblastoma. Calvarial metastases rarely occur in absence of more widespread disease.

Typical (Left) Axial FLAIRMR shows heterogeneous signal in extradural metastatic neuroblastoma. Little reactive change is seen in under/ying brain parenchyma despite significant mass effect. (Right) Axial T2WI MR shows heterogen.eous and hypointense signal in metastatic neuroblastoma. Hyperintense signal is seen more frequently in other diagnoses causing extra-axial masses in children.

Neoplasms and Tumorlike Lesions

6 107

Axial T2WI MR in a young adult with epilepsy shows a cystic occipital mass (arrows) with superficial mural nodule (open arrow) that abuts the interhemispheric fissure.

Abbreviations

and Synonyms

• Neurilemoma, neurinoma, schwannoma (VS)

neuroma, vestibular

Definitions • Benign encapsulated nerve sheath tumor composed of differentiated neoplastic schwann cells

Axial T7 C+ MR in same case shows nodule enhances strongly but heterogeneously. Preoperative diagnosis = ganglioglioma. Intraparenchymal schwan noma at surgery (Courtesy j. Rees, MO).

• Other: Cerebellum, brainstem, sella, ventricles, leptomeninges • Size: From 2 mm up to several cms • Morphology o Cranial nerve schwannoma: Slow-growing extra-axial mass • Displaces ("buckles") cortex • CSF-vascular "cleft" between tumor, brain o Intracerebral schwannoma • Cyst with nodule

CT Findings 108

General Features • Best diagnostic clue: VS looks like "ice cream on cone"; parenchymal looks like cyst with nodule • Location o All cranial nerves (exceptions: Olfactory, optic nerves) have myelinated schwann cell sheaths and are sites for intracranial schwannomas • 98% of intracerebral schwannomas arise from cranial nerves (predominately sensory) • 90% arise from CN 8 (vestibular portion) • 10% other (5% CN 5; 7; motor nerve schwannomas rare in absence of NF2) o 1-2% intracerebral • Superficial or periventricular location • Cerebral hemisphere = most common site

DDx: Intraparenchymal

Pilocytic Astra

• NECT o Cranial nerve schwannoma • Noncalcified extra-axial mass • Iso/slightly hyperdense compared to brain • May enlarge bony foramina (lAC, foramen ovale, facial nerve canal) o Parenchymal: Well-delineated hypodense cyst + isodense nodule, variable Ca++ • CECT: Strong, uniform enhancement

MR Findings • TlWI o Usually iso-, sometimes mixed iso-/hypointense o Less common: Intratumoral cyst (occasionally have fluid-fluid level), hemorrhage • T2WI o Hyperintense (nodule may be isointense)

Schwannoma

PXA

Hemangioblastoma

Neoplasms and Tumorlike Lesions

Canglioglioma

SCHWAN NOMA Key Facts ' Iogy liermano

• Hemangioblastoma

• Benign encapsulated nerve sheath tumor composed of differentiated neoplastic schwann cells

' F'd' Imagang an mgs

Pathology

=

• Schwannomas 5-8% of all intracranial • Two types of tissue (Antoni A, B)

• Best diagnostic clue: VS looks like "ice cream on cone"; parenchymal looks like cyst with nodule • All cranial nerves (exceptions: Olfactory, optic n.erves) have myelinated schwann cell sheaths and are sItes for intracranial schwannomas • 1-2% intracerebral

Clinical Issues

Top Differential

• Cystic, calcified, enhancing

• • • •

Diagnoses

Pleomorphic xanthoastrocytoma Pilocytic astrocytoma Ganglioglioma Metastasis

neoplasms

• Age: 70% of parenchymal schwannomas present before age of 30 • Slowly growing; recurrence after surgery < 10% • Malignant degeneration exceptionally rare

D'Iagnos t'IC Chkl' ec

(PXA)

parenchymal a glioma!

IS

t

hemispheric mass in a young patient isn't necessarily

o Surrounding edema common • DWI o Solid portion of schwannomas shows no restriction (isointense to normal brain parenchyma) o Elevated ADC values (reflect increased amount of extracellular water in tumor matrix) • Tl C+ o Enhances strongly • Cranial nerve schwannoma: 2/3 solid; 1/3 ring or inhomogeneous • Parenchymal schwannoma: Nodule enhances strongly

Metastasis

Angiographic

I PATHOLOGY

6

General Features

109

Findings

• Conventional o DSA • Hypovascular mass (adjacent vessels stretched, draped) • Diffuse blush, AV shunting rare

Imaging Recommendations • Best imaging tool: MR without, with contrast

I DIFFERENTIAL DIAGNOSIS Pleomorphic

xanthoastrocytoma

(PXA)

• Cyst and mural nodule typical • Meningeal involvement common • Ca++ rare

Pilocytic astrocytoma • Rare in hemispheres • Typically solid and cystic or solid mass • Surrounding edema rare

Ganglioglioma • • • •

Cortically-based hemispheric mass Solid and cystic or solid mass; Ca++ common Most common site = temporal lobe Can be indistinguishable from intraparenchymal schwannoma

• • • •

Older patients Usually known primary Solid or ring-enhancement> cyst + nodule Bone destruction common if lesion in/near skull base

Hemangioblastoma • • • •

Older patients Posterior fossa location most common Cyst and mural nodule common Benign tumor of vascular origin

• General path comments: Schwannomas involve sensory> motor cranial nerves • Genetics o Solitary • Loss of Merlin expression • Inactivating mutations of NF2 gene in 60% • Loss of remaining wild-type allele on chromosome 22q o Multiple: Associated NF2, less often multiple schwannomatosis (without NF2 stigmata) • Etiology o Parenchymal schwannoma • Schwann cells not normally found in brain parenchyma • May arise from multipotential neural crest cells • Schwannosis (reaction to injury) • Epidemiology o Schwannomas = 5-8% of all intracranial neoplasms o Second most common intracranial extra-axial neoplasm in adults o VS = most common CPA/lAC mass o Parenchymal schwannoma very rare • Associated abnormalities: Multiple schwannomas associated with NF2 or schwannomatosis

Neoplasms and Tumorlike Lesions

Gross Pathologic & Surgical Features • Tan, round/ovoid, encapsulated mass • May have bright yellow patches, hemorrhage • 15-20% associated cysts (intralesional or peritumoral)

Microscopic

3. 4.

5.

Features

• Spindle-shaped neoplastic schwann cells • Arises at glial-schwann cell junction (VS = near porus acusticus) • Two types of tissue (Antoni A, B) o Antoni A • Compact, elongated cells, +/- nuclear palisading o Antoni B • Less cellular, loosely textured, often lipidized • Other variants = melanotic schwannoma

6. 7.

8. 9.

10.

Staging, Grading or Classification Criteria • WHO grade I

11.

ICLl!SJlCALiIS51.JES

12.

Presentation • Most common signs/symptoms o Cranial nerve: Varies depending on which nerve is involved (VS = SNHL, tinnitus) o Parenchymal: Epilepsy, headache, focal neurologic deficit • Age: 70% of parenchymal schwannomas before age of 30 • Gender: Intraparenchymal: M=F

110

14.

15.

Demographics

6

13.

present

16.

17.

Natural History & Prognosis • Slowly growingi recurrence after surgery < 10% • Factors associated with growth o Tumors with cysts, no lAC component, females, younger patients • Malignant degeneration exceptionally rare

18.

19.

Treatment • Microsurgical resection o 90% normal/near-normal CN 8 function (VS removal) o 40% hearing preservation • Stereotactic radiosurgery • Some smaller tumors/older patients managed with observation

20.

21. 22.

23.

IO.I.AO·.N.C1STI.·c:••••• <=HECKLI.§T Image Interpretation

24.

Pearls

• Cystic, calcified, enhancing hemispheric parenchymal mass in a young patient isn't necessarily a glioma!

Reynolds DL et al: Sonographic characteristics of peripheral nerve sheath tumors. A]R. 182:741-4,2004 Beauchesne P et al: Malignant nerve sheath tumor of the right cerebral peduncle: case report. Neurosurg. 54:500-4, 2004 Louis E et al: Intra-cerebral schwannoma simulating glioma. ] Neurooncol. 64(3):279-82, 2003 Chng SM et al: Intracerebral schwannoma--a rare cause of epilepsy. Ann Acad Med Singapore. 32(4):547-9, 2003 Sener RN: Diffusion magnetic resonance imaging of solid vestibular schwannomas. ] Comput Assist Tomogr. 27(2):249-52, 2003 Lin] et al: Intraparenchymal schwannoma of the medulla oblongata. Case report.] Neurosurg. 98(3):621-4, 2003 Erdogan E et al: Schwannoma of the lateral ventricle: eight-year follow-up and literature review. Minim Invasive Neurosurg. 46(1):50-3, 2003 Nakayama K et al: Supratentorial convexity leptomeningeal schwannoma: case report. Neurosurgery. 51(5):1295-7; discussion 1298, 2002 Huang TW et al: Differentiation between cerebellopontine angle tumors in cancer patients. Otol Neurotol. 23(6):975-9,2002 Figarella-Branger D et al: Pituicytomas, a mis-diagnosed benign tumor of the neurohypophysis: report of three cases. Acta Neuropathol (Berl). 104(3):313-9,2002 Ture U et al: Infratentoriallateral supracerebellar approach for trochlear nerve schwannoma. ] Clin Neurosci. 9(5):595-8, 2002 Sperfeld AD et al: Occurrence and characterization of peripheral nerve involvement in neurofibromatosis type 2. Brain. 125(Pt 5):996-1004, 2002 Amador AR et al: Olfactory schwannoma. Eur Radiol. 12(4):742-4,2002 Sarma S et al: Nonvestibular schwannomas of the brain: a 7-year experience. Neurosurgery. 50(3):437-48; discussion 438-9,2002 Whee SM et al: Intrasellar schwannoma mimicking pituitary adenoma: a case report. ] Korean Med Sci. 17(1):147-50,2002 Suh YLet al: Tumors of the central nervous system in Korea: a multicenter study of 3221 cases.] Neurooncol. 56(3):251-9, 2002 Zabel A et al: Management of benign cranial nonacoustic schwannomas by fractionated stereotactic radiotherapy. Int] Cancer. 96(6):356-62, 2001 lanse A] et al: Neurofibromatosis type 2 diagnosed in the absence of vestibular schwannomas. A case report and guidelines for a screening protocol for children at risk. Eur ] Pediatr. 160(7):439-43, 2001 Tan TC et al: Subfrontal schwannoma masquerading as meningioma. Singapore Med]. 42(6):275-7, 2001 Eldevik OP et al: Imaging findings in schwannomas of the jugular foramen. A]NR Am] Neuroradiol. 21(6):1139-44, 2000 Lingawi SS:Oculomotor nerve schwannoma: MRI appearance. Clin Imaging. 24(2):86-8, 2000 Woodruff]M et al: Schwannoma. In Kleihues P, Cavenee WK (eds), Tumours of the Nervous System, 164-6, IARC Press, 2000

I SELECTED REFERENCES 1. 2.

Beaulieu S et al: Position emission tomography of schwannomas. A]NR 182:971-4, 2004 Kurokawa R et al: Spinal accessory schwannoma mimicking a tumor of the fourth ventricle: case report. Neurosurg. 54:510-4,2004

Neoplasms and Tumorlike Lesions

Variant (uft) Axial T2WI MR in a patient with diplopia shows a lobulated, well-delineated mass at the orbital apex that expands superior orbital fissure (curved arrow), extends posteriorly into cavernous sinus. (Right) Axial T1 C+ MR with fat suppression shows the orbital apex mass enhances strongly but heterogeneously. Schwannoma of abducens nerve was found at surgery.

Variant (Left) Axial NECT (bone algorithm) in a patient with multiple right-sided cranial nerve palsies shows extensive remodeling of right middle cranial fossa, orbital fissure, and basisphenoid. (Right) Axial T1 C+ MR shows a huge lobulated dumbbell-shaped extra-axial mass that extends into multiple cranial fossae. Benign schwan noma of trigeminal nerve was found at surgery.

Variant (Left) Axial T2WI MR in a patient with lower cranial nerve palsies shows a large "ice cream cone" shaped CPA mass that extends into lAC (open arrow). An even larger cyst is present (arrows). (Right) Axial T1 C+ MR in the same case shows CPA/lAC portion of mass enhances, extends into labyrinthine segment of facial nerve canal (curved arrow). CN 7 schwan noma with arachnoid cyst.

Neoplasms and Tumorlike Lesions

6·

...

111

Axial graphic shows diffusely infiltrating "worm-like" scalp masses characteristic of plexiform neurofibroma (PNF).

Abbreviations • Neurofibroma

• PNFs may enlarge orbital fissure, extend into cavernous sinus but almost never posterior to Meckel cave • Other sites: Scalp, skull base (e.g., parotid gland; pterygopalatine fossa) • CECT: Moderate/strong enhancement

and Synonyms (NF)

Definitions • Plexiform NF (PNF) = infiltrative extraneural tumor typically associated with neurofibromatosis I (NFl)

MR Findings • T1WI: Plexiform NF = isointense infiltrating mass • T2WI: Hyperintense • TI C+: Enhances strongly, somewhat heterogeneously

Imaging Recommendations

General Features 112

Axial T1 C+ MR with fat-suppression shows a "worm-like" enhancing nodular infiltrating scalp mass in this patient with known NFl. Most likely cause is PNF.

• Best imaging tool: MR without and with contrast • Protocol advice: PNF: Scan entire neuraxis (detect other manifestations of NFl)

• Best diagnostic clue: "Worm-like" soft tissue mass infiltrating scalp, orbit or parotid in patient with NFl • Location o Solitary NFs may affect skin, spinal or peripheral nerve roots, rarely (if ever) involve cranial nerves o PNF = orbit (CN VI) most common site in head/neck, followed by scalp, parotid gland (CN 7) • Size: Varies from small to extensive • Morphology: Can be well-demarcated (solitary NF) or diffusely infiltrating (plexiform NF)

I DIFFERENTIAL

CT Findings

Malignant peripheral nerve sheath tumor (MPNST)

• NECT o Plexiform NF • Mass infiltrates CN VI

DIAGNOSIS

Schwannoma • Usually solitary, well-circumscribed • May involve CNs, spinal nerve roots (rare in scalp)

• Rare (50% occur in setting of NFl) • Skull/scalp uncommon sites

DDx: PNF of the Scalp

r; Scalp AVFs in NFl

Sarcoma

Lymphoma

Neoplasms and Tumorlike Lesions

Metastases

HEMANGIOBLASTOMA Key Facts Terminology • HGBL currently classified as meningeal uncertain histogenesis (WHO, 2000)

tumor of

• Best diagnostic clue: Adult with intra-axial posterior fossa mass with cyst, enhancing mural nodule abutting pia • 90-95% posterior fossa • Size: Size varies from tiny to several cms • 60% cyst + "mural" nodule • 40% solid • von Hippel-Lindau • Metastasis • Astrocytoma

Angiographic

syndrome (VHL)

Findings

SPECT shows fast washout

Imaging Recommendations • Best imaging tool: Contrast-enhanced MR (sensitivity > > CT for small HGBLs) • Protocol advice o Begin MRI screening of patients from VHL families after age 10 Y o Screen complete spine

I DIFFERENTIAl.. DIAGNOSIS von Hippel-Lindau

• Screen entire neuraxis for other HGBLs • Most common posterior fossa intra-axial mass in middle-aged/older adult metastasis, not HGBLl

=

Findings

Nuclear Medicine

• VHL phenotypes (based on presence, absence of pheochromocytoma and renal cell carcinoma) • 1-2% of primary intracranial tumors • 7-10% of posterior fossa tumors • Secondary polycythemia (may elaborate erythropoietin) • WHO grade I

Diagnostic Checklist

Diagnoses

• Conventional o Large avascular mass (cyst) o Highly vascular nodule • Prolonged blush • +/- AV shunting (early draining vein) o Rarely performed as diagnosis established with MR and preoperative embolization not generally used • Thallium-201

syndrome (CM)

Pathology

Imaging Findings

Top Differential

• Vascular neurocutaneous • Cavernous malformation • Clear cell ependymoma

syndrome (VHL)

• 25-40% of HGBLs occur in VHL • Multiple HGBLs are the rule • Other markers (visceral cysts, renal clear cell carcinoma), + family history

Metastasis • Solitary posterior fossa metastasis uncommon • BUT most common parenchymal posterior fossa mass in middle-aged, older adults is metastasis! • May be very vascular • Solid> cystic • Multiple> single • Vascular mets (renal cell carcinoma) do not express inhibin A or GLUTl (HGBL does)

Astrocytoma • Pilocytic astrocytoma (usually in children) • Glioblastoma o Same age range as HGBL

o Posterior fossa uncommon location o Central necrosis with enhancing rim of tumor> with mural nodule

Vascular neurocutaneous

cyst

syndrome

• HHT, Wyburn-Mason • Multiple intracranial AVMs may mimic HGBLs

Cavernous malformation

(CM)

• Gross intratumoral hemorrhage rare in HGBL • Complete hemosiderin rim typical in CMs

Clear cell ependymoma • Rare; younger patients

6

IPATHOI..QG¥

115

General Features • General path comments o VHL phenotypes (based on presence, absence of pheochromocytoma and renal cell carcinoma) • Type 1 = without pheochromocytoma • Type 2A = with pheochromocytoma, renal cell carcinoma (RCC) • Type 2B = with pheochromocytoma, without RCC • Genetics o Familial HGBL (VHL disease) • Autosomal dominant • Chromosome 3p mutation • Suppressor gene product (VHL protein) causes neoplastic transformation • VEGF highly expressed in stromal cells • Other VHL gene mutations common o Sporadic HGBL • Up regulation of erythropoietin common in both sporadic, VHL-related HGBL • Etiology: Precise histogenesis unknown • Epidemiology o VHL 1:36-40,000 o Less than half (25-40%) HGBLs associated with VHL o 1-2% of primary intracranial tumors • 7-10% of posterior fossa tumors

Neoplasms and Tumorlike Lesions

o 3-13% of spinal cord tumors • Associated abnormalities o Secondary polycythemia (may elaborate erythropoietin) o VHL in 25-40% of HGBLs

Gross Pathologic & Surgical Features • Red or yellowish well-circumscribed, unencapsulated highly vascular mass that abuts leptomeninges • +/- Cyst with yellow-brown fluid

Microscopic

Features

• Nodule o Large vacuolated stromal cells • Neoplastic component • Lipid-containing vacuoles ("clear cell" morphology) o Immunohistochemistry • Negative for cytokeratin, EMA • Positive for inhibin A, GLUTl • Overexpress VEGF protein o Rich capillary network • Cyst wall o Usually compressed brain (not neoplasm) o Variable intratumoral hemorrhage

Staging, Grading or Classification Criteria • WHO grade I • Low MIB-l index (mean 0.8%) • No difference between sporadic, VHL-associated HGBLs

Presentation 116

• Most common signs/symptoms o Sporadic HGBL • Headache (85%), dysequilibrium, dizziness o Familial • Retinal HGBL: Ocular hemorrhage often first manifestation of VHL • Other: Sx due to RCe, polycythemia, endolymphatic sac tumor

Demographics • Age o Sporadic HGBL • Peak 40-60 y • Rare in children o Familial • VHL-associated HGBLs occur at younger age but are rare < 15 Y • Retinal HGBL: Mean onset 25 y • Gender: Slight male predominance

Natural History & Prognosis • Usually benign tumor with slow growth pattern o Symptoms usually associated with cyst expansion (may occur rapidly) o Rare: Leptomeningeal tumor dissemination • Two-thirds with one VHL-associated HGBL develop additional lesions o Average = one new lesion every 2 years

o Require period screening, lifelong follow-up o Periods of intermixed growth, relative quiescence common with VHL-associated HGBL o Median life expectancy in VHL = 49 years

Treatment • En bloc surgical resection (piecemeal may result in catastrophic hemorrhage) o 85% 10 year survival rate o 15-20% recurrence rate • Pre-operative embolization o Sometimes used if large tumor nodule present (3.5 cm)

o Partial (not complete) embolization does not reduce operative complications or morbidity

Consider • Screen entire neuraxis for other HGBLs

Image Interpretation

Pearls

• Most common posterior fossa intra-axial mass in middle-aged/older adult = metastasis, not HGBL! • Most common posterior fossa primary tumor in middle-aged/older adult = HMGB!

1.

Wanebo JE et al: The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease. J Neurosurg. 98(1):82-94, 2003 2. Sarkar C et al: August 2002: 21-year-old male with cystic intracerebral tumor. Brain Pathol. 13(1):113-4, 117,2003 3. Reyns N et al: Leptomeningeal hemangioblastomatosis in a case of von Hippel-Lindau disease: case report. Neurosurgery. 52(5):1212-5; discussion 1215-6, 2003 4. Hoang MP et al: Inhibin alpha distinguishes hemangioblastoma from clear cell renal cell carcinoma. Am J Surg Pathol. 27(8):1152-6, 2003 5. Weil RJ et al: Clinical and molecular analysis of disseminated hemangioblastomatosis of the central nervous system in patients without von Hippel-Lindau disease. Report of four cases. J Neurosurg. 96(4):775-87, 2002 6. Conway JE et al: Hemangioblastomas of the CNS in von Hippel-Lindau syndrome and sporadic disease. Neurosurg 48: 55-63, 2001 7. Kondo T et al: Diagnostic value of 201TI-single-photon emission computerized tomography studies in cases of posterior fossa hemangioblastomas. J Neurosurg. 95(2):292-7,2001 8. Wang C et al: Surgical management of medullary hemangioblastoma. Report of 47 cases. Surg Neurol. 56(4):218-26; discussion 226-7, 2001 9. Bohling T et al: von Hippel-Lindau disease and capillary hemangioblastoma. In Kleihues P, Cavenee WK (eds): Tumours of the Nervous System, 223-6, IARC Press, 2000 10. Miyagami M et al: Clinicopathological study of vascular endothelial growth factor (VEGF),p53, and proliferative potential in familial von Hippel-Lindau disease and sporadic hemangioblastomas. Brain Tumor Pathol. 17(3):111-20,2000

Neoplasms and Tumorlike Lesions

Typical (Left) Coronal Tl C+ MR shows a classic solitary HCBL. The tumor nodule (open arrow) abuts the pia and is significantly smaller than the associated cyst (arrows). (Right) Anteroposterior DSA in the same case shows large avascular mass effect caused by the cyst. Note intense, prolonged blush of the small tumor nodule (curved arrow).

Variant (Left) Axial Tl C+ MR with fat-saturation shows a large

ring-enhancing cystic posterior fossa mass (arrows). Differential diagnosis is metastasis, abscess, or glioma vs atypical HCBL. (Right) Axial OWl MR in the same case shows no restriction, making abscess unlikely. Surgery disclosed a necrotic hemangioblastoma with tumor cells in the cyst wall.

6 117

Variant (Left) Axial TlWI MR shows a mixed signal mass in the

right cerebellar hemisphere (arrows). Fluid-fluid levels are present (open arrow), suggesting subacute and chronic hemorrhage. (Right) Axial T2WI MR shows the mass has a complete hemosiderin rim. Pre-operative diagnosis was cavernous malformation. HCBL with intratumoral mixed-age hemorrhage was found at resection.

Neoplasms and Tumorlike Lesions

Axial CECT shows an aggressive appearing, lobular extra-axial mass with bone erosion (arrow), central necrosis, and surrounding edema, typical of hemangiopericytoma.

Abbreviations

and Synonyms

• Hemangiopericytoma (HPC), meningeal hemangiopericytoma • In older literature called "angioblastic meningioma," hemangiopericytic type

Axial T1 C+ MR shows an avidly enhancing mass with . areas of low signal intensity representing necrosis and extension through the calvarium. Involvement of the transversesinus is common.

• Size: Variable, from 2-9 cm, often> 4 cm • Morphology o Lobular dural-based extra-axial mass • Dural attachment may be a narrow pedicle or broad-based o Dural "tail" commonly seen, approximately 50% o Rarely may appear intra-axial

Definitions

CT Findings

• Sarcoma related to neoplastic transformation of pericytes, contractile cells about capillaries o Occur in any region of the body where capillaries are found

• NECT o Hyperdense extra-axial mass with surrounding edema • Low density cystic or necrotic areas are common o Calvarial erosion may be seen o No Ca++ or hyperostosis • CECT: Strong, heterogeneous enhancement

118

MR Findings

General Features • Best diagnostic clue o Lobular enhancing extra-axial mass with dural attachment, +/- skull erosion o May mimic meningioma, but without Ca++ or hyperostosis • Location o Supratentorial: Occipital region most common o Typically involve falx, tentorium, or dural sinuses o Rare reports of skull base, cranial nerve, intraventricular involvement

DDx: Dural-based

Meningioma

• TlWI o Heterogeneous mass, isointense to gray matter o Flow voids may be seen • T2WI o Heterogeneous isointense mass o Prominent flow voids are common o Surrounding edema, mass effect typical o Hydrocephalus may be seen • Tl C+ o Marked enhancement, often heterogeneous o Dural "tail" seen in approximately 50%

Enhancing Mass

Breast Metastases

Lymphoma

Neoplasms and Tumorlike Lesions

Neurosarcoidosis

HEMANGIOPERICYTOMA Key Facts Terminology • Sarcoma related to neoplastic transformation pericytes, contractile cells about capillaries

of

Imaging Findings • Lobular enhancing extra-axial mass with dural attachment, +/- skull erosion • May mimic meningioma, but without Ca++ or hyperostosis • Typically involve falx, tentorium, or dural sinuses • Marked enhancement, often heterogeneous

Top Differential • • • •

Diagnoses

Meningioma Dural metastases Lymphoma Neurosarcoidosis

• Gliosarcoma • Solitary fibrous tumor

Pathology • HPC is a distinctive mesenchymal neoplasm unrelated to meningioma • Represents < 1% of primary CNS tumors • Represents 2-4% of all meningeal tumors • WHO grade II or III (anaplastic)

Clinical Issues • Most common 4th-6th decade, mean age 43 years • Extracranial metastases common, up to 30%

Diagnostic Checklist • When a "meningioma" has atypical features (frank bone erosion, multiple flow voids) think HPC!

o Central necrosis may be seen • MRV: May show occlusion of dural sinuses • MRS: Early reports have shown elevated myoinositol (3.56 ppm) using short TE (20 msec) may help differentiate HPC from meningioma

Lymphoma

Angiographic Findings

• Dural involvement by lymphoma may mimic HPC o Diffusely enhancing dural mass, often multifocal o T2 low signal related to hypercellularity • Calvarial involvement uncommon • Flow voids usually absent

• Conventional o Hypervascular mass with irregular tumor vessels and prolonged, dense tumor stain o Extensive arteriovenous shunting o Mixed dural-pial vascular supply typical

• Dural-based masses can occur, often multifocal • No calvarial involvement • Typically leptomeningeal enhancement

Nuclear Medicine

Gliosarcoma

Findings

Neurosarcoidosis

• Bone Scan: Helpful to detect metastases • PET: Early FDG studies show lower metabolic rate in HPC than gray matter

• Rare glial tumor often with dural involvement • Heterogeneously enhancing parenchymal mass

Imaging Recommendations

• Circumscribed enhancing dural-based mass • May have associated hyperostosis • Extremely rare, < 20 reported cases

• Best imaging tool o Multiplanar MR is most sensitive o CT may be helpful to evaluate bone erosion • Protocol advice o Multiplanar contrast-enhanced MR o MRS utilizing a short TE (20-35 msec) may be helpful o Bone scan useful in patient follow-up as extracranial metastases are common

I DIFFERENTIAl..

DIAGN()SIS

Meningioma • • • •

May be indistinguishable Enhancing extra-axial dural based mass Often calcified. with a broad dural base, dural "tail" Hyperostosis and Ca++ is characteristic

Dural metastases • Dural metastases with calvarial invasion may be indistinguishable • Typically multiple lesions • Primary tumor often known o Breast and prostate cancer most common

Solitary fibrous tumor

I PATH()I..()G¥ General Features • General path comments o HPC is a distinctive mesenchymal neoplasm unrelated to meningioma o Arises from primitive mesenchymal cells throughout the body • Most commonly involves soft tissues of lower extremities, pelvis and retroperitoneum • Approximately 15% occur in head and neck region (scalp, face, neck, sinonasal) o Classified by WHO as a mesenchymal, non-meningothelial tumor • Genetics: No consistent chromosomal losses or gains • Etiology: Thought to arise from pericytes, modified smooth muscle contractile cells surrounding capillaries • Epidemiology o Represents < 1% of primary CNS tumors o Represents 2-4% of all meningeal tumors o HPC: Meningioma = 1:40

Neoplasms and Tumorlike Lesions

6 119

Gross Pathologic & Surgical Features • Extremely vascular with tendency to bleed at surgery • Well circumscribed, encapsulated firm mass with a dural attachment • Cut surface is gray to red-brown with visible vascular spaces

Microscopic

Consider • Bone erosion is most commonly disease • A dural "tail" is nonspecific

Image Interpretation

Features

• Highly cellular, monotonous tumor with randomly oriented plump cells in a dense reticulin network • "Staghorn" vascular pattern characteristic o Lobules of tumor cells surrounding wide, branching capillaries • Immunohistochemistry: Antibodies to factor XIIIa and CD34 may help differentiate from other tumors o Vimentin positive o Epithelial membrane antigen (EMA) negative • Prominent mitotic activity, median Ki-67 index (MlB-1) of 5-10% • Histologic features are not predictive of outcome

1.

2.

3.

• WHO grade II or III (anaplastic) 4.

5.

Presentation

120

6. 7.

8.

Demographics • Age o Most common 4th-6th decade, mean age 43 years o Occur at all ages, uncommon in children • Gender: Slight male predominance

9.

10.

Natural History & Prognosis • Local recurrence common, 50-80% • Extracranial metastases common, up to 30% o Commonly liver, lungs, lymph nodes, bones • Complications o Invasion of dural sinuses, bone, and cranial nerves o Hemorrhage (rare) • May cause oncogenic osteomalacia, a rare paraneoplastic syndrome associated with mesenchymal tumors • 5 year survival rate has improved in recent studies, up to 93%

Treatment • Preoperative embolization may be helpful, tumors are highly vascular • Surgical resection with radiation therapy or radiosurgery is treatment of choice o Reduces risk of local recurrence • Radiosurgery may be an effective alternative to repeated surgical resection in recurrent tumors • Chemotherapy is ineffective in most cases • Careful long-term follow-up is mandatory o Potential for local recurrence and metastases many years after initial diagnosis

Pearls

• When a "meningioma" has atypical features (frank bone erosion, multiple flow voids) think HPC!

Staging, Grading or Classification Criteria

• Most common signs/symptoms: Headache • Other signs/symptoms o Related to tumor location: Focal neurologic deficit, seizure

seen with metastatic

11.

12.

13. 14.

15. 16.

17. 18.

Folpe AL et al: Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol. 28:1-30, 2004 Kim JH et al: Meningeal hemangiopericytomas: long-term outcome and biological behavior. Surg Neurol. 59(1):47-54, 2003 Tihan T et al: Solitary fibrous tumors in the central nervous system. A clinicopathologic review of 18 cases and comparison to meningeal hemangiopericytomas. Arch Pathol Lab Med. 127(4):432-9, 2003 Ecker RD et al: Hemangiopericytoma in the central nervous system: treatment, pathological features, and long-term follow-up in 38 patients. J Neurosurg. 98:1182-7, 2003 Johnson MD et al: Dural lesions mimicking meningiomas. Hum Pathol. 33:1211-26, 2002 Cavalheiro S et al: Fetal meningeal hemangiopericytoma. Case report.J Neurosurg. 97(5):1217-20, 2002 Burger PC et al: Surgical pathology of the nervous system and its coverings: Intracranial meninges. 4th ed. Philadelphia, Churchill Livingstone. 79-83, 2002 Alen JF et al: Intracranial hemangiopericytoma: study of 12 cases. Acta Neurochir (Wien). 143(6):575-86,2001 Dufour H et al: Meningeal hemangiopericytoma: a retrospective study of 21 patients with special review of postoperative external radiotherapy. Neurosurgery. 48(4):756-62,2001 Tan I et al: Hemangiopericytoma of the trigeminal nerve. Australasia Radiol. 45:350-3, 2001 Barba I et al: Magnetic resonance spectroscopy of brain hemangiopericytomas: high myoinositol concentrations and discrimination from meningiomas. J Neurosurg. 94:55-60, 2001 Jaaskelainen J et al: Pathology and genetics of tumours of the nervous system: Haemangiopericytoma. Lyon, IARC Press, 190-2,2000 Huisman TA et al: Meningeal hemangiopericytoma in childhood. Eur Radiol. 10(7):1073-5, 2000 Kracht LW et al: Positron Emission Tomography in a case of intracranial haemangiopericytoma. J. Comput. Assist. Tomogr. 23:365-8, 1999 Galanis E et al: Management of recurrent meningeal hemangiopericytoma. Cancer. 82(10):1915-20, 1998 Spitz FR et al: Hemangiopericytoma: a 20-year single-institution experience. Ann Surg Oncol. 5(4):350-5, 1998 Chiechi MV et al: Intracranial hemangiopericytomas: MR and CT features. AJNRAmJ Neuroradiol. 17:1365-71, 1996 Zattara-Cannoni H et al: The contribution of cytogenetics to the histogenesis of meningeal hemangiopericytoma. J Neurooncol. 29(2):137-42, 1996

Neoplasms and Tumorlike

Lesions

HEMANGIOPERICYTOMA

I IMAGE GALLERY Typical (Left) Axial T2WI MR shows

a heterogeneous extra-axial mass with extension through the calvarium. Hypointense foci are likely related to flow voids or blood products. 49 year old male. Hemangiopericytoma. (Right) Axial T1 C+ MR shows avid heterogeneous enhancement of the mass. Areas of low signal intensity are likely related to necrosis. Involvement of the transverse sinus is common.

Typical (Left) Axial CECT shows a heterogeneously enhancing mass in the occipital region with bone erosion. Note the surrounding edema and mass effect. Location and appearance are typical of hemangiopericytoma. (Right) Axial T1 C+ MR shows a homogeneously enhancing mass in the central skull base and orbit. 45 year old female with visual complaints. Imaging mimics a meningioma. Hemangiopericytoma at resection.

Other (Left) Lateral OSA with

injection of the occipital artery shows multiple irregular tumor vessels and early A-V shunting of this hemangiopericytoma. Mixed dural-pial supply is typical. (Right) Cross pathology cut section shows a lobulated, circumscribed vascular mass with multiple enlarged vascular channels characteristic of hemangiopericytoma (Courtesy R. Hewlett, MOJ.

Neoplasms and Tumorlike Lesions

6 121

PRIMARY eNS LYMPHOMA

Axial graphic shows multiple periventricular lesions in the basal ganglia, thalamus, and corpus callosum typical of PCNSL. Note the extensive subependymal spread of disease (arrow).

I TERMINOLOGY

CT Findings

Abbreviations and Synonyms • Primary CNS lymphoma

(PCNSL), lymphoma

Definitions • Malignant primary CNS neoplasm composed of B lymphocytes

6 122

I IMAGING

Coronal T1 C+ MR shows a homogeneously enhancing mass crossing the corpus callosum and an additional periventricular lesion (arrow), typical of PCNSL. 72 year old male with headache.

FINDINGS

• NECT o Hyperdense classically o May be isodense o +/- Hemorrhage, necrosis (immunocompromised) • CECT o Common: Moderate, uniform (immunocompetent) o Less common: Ring (immunocompromised) o Rare: Nonenhancing (infiltrative, mimics white matter disease)

MR Findings

General Features • Best diagnostic clue: Enhancing lesion(s) within basal ganglia, periventricular WM • Location o 90% supratentorial • Frontal and parietal lobes most common o Deep gray nuclei commonly affected o Lesions cluster around ventricles, GM-WM junction o Often involve, cross corpus callosum o Frequently abut, extend along ependymal surfaces o Infratentorial, sellar, pineal region uncommon o May involve leptomeninges or dura, more commonly in secondary lymphoma • Morphology o Solitary mass or multiple lesions o May be circumscribed or infiltrative

• TlWI o Immunocompetent: Homogeneous isointense/hypointense to cortex o Immunocompromised: Isointense/hypointense to cortex • May be heterogeneous from hemorrhage, necrosis • T2WI o Immunocompetent: Homogeneous isointense/hypointense to cortex • Hypointensity related to high nuclear to cytoplasmic ratio o Immunocompromised: Isointense/hypointense to cortex • May be heterogeneous from hemorrhage, necrosis • Ca++ may rarely be seen, usually after therapy o Mild surrounding edema is typical

DDx: Enhancing Supratentorial Periventricular Mass

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Neoplasms and Tumorlike Lesions

Multiple Sclerosis

PRIMARY eNS LYMPHOMA Key Facts Terminology

Pathology

• Malignant primary CNS neoplasm composed of B lymphocytes

• 98% B cell, non-Hodgkin lymphoma (NHL) • Incidence increasing in immunocompetent, immunocompromised • 1-7% of primary brain tumors, incidence rising • Represents approximately 1% of lymphomas

Imaging Findings • Best diagnostic clue: Enhancing lesion(s) within basal ganglia, periventricular WM • 90% supratentorial • Deep gray nuclei commonly affected • Often involve, cross corpus callosum • Frequently abut, extend along ependymal surfaces

Top Differential • • • •

Diagnoses

Toxoplasmosis Glioblastoma multiforme (GBM) Abscess Progressive multifocalleukoencephalopathy

• Median survival 17-45 months • AIDS median survival 2-6 months • Stereotactic biopsy, followed by radiation therapy and chemotherapy

Diagnostic Checklist (PML)

• FLAIR o Immunocompetent: Homogeneous isointense/hypointense to cortex o Immunocompromised: Isointense/hypointense o May be hyperintense o Mild surrounding edema is typical • T2* GRE: May see blood products or calcium as areas of "blooming" (immunocompromised) • DWI: Restricted diffusion, low ADC map reported • T1 C+

o Immunocompetent: Strong homogeneous enhancement o Immunocompromised: Peripheral enhancement with central necrosis or homogeneous enhancement o Nonenhancement extremely rare o Lymphomatous meningitis is typically related to systemic disease • MRS o MRS: NAA decreased, Cho elevated o Lipid and lactate peaks reported • MR perfusion: Early studies show increased rCBV

Nuclear Medicine Findings • FDG PET: Hypermetabolic • 20l-Thallium SPECT: Hypermetabolic

Imaging Recommendations • Best imaging tool: MR is most sensitive • Protocol advice o Contrast-enhanced MR o PET or 201-Thallium-SPECT may be helpful when toxoplasmosis is considered

I DIFFERENTIAL DIAGNOSIS Toxoplasmosis • • • •

Clinical Issues

Involves basal ganglia, corti co medullary junction Enhancing lesions, "eccentric target sign" No ependymal spread Often indistinguishable on standard MRI o SPECT, PET helpful (iso/hypometabolic)

• Imaging and prognosis varies with immune status • Periventricular location and subependymal involvement is characteristic of PCNSL

Glioblastoma multiforme • • • •

(GBM)

"Butterfly glioma" involving corpus callosum Hemorrhage common Enhancement typically heterogeneous Necrosis with ring enhancement in 95%

Abscess • • • •

T2 hypointense rim, diffusion restriction typical Peripheral enhancement with central necrosis Enhancement often thinner on ventricular side MRS: Elevated amino acids in cystic cavity (low TE)

Progressive multifocalleukoencephalopathy (PML) • White matter T2 hyperintensity, U-fibers • May involve corpus callosum • Typically nonenhancing

involves subcortical

Demyelination • May involve corpus callosum • Often incomplete, "horseshoe-shaped" enhancement, open towards cortex • Other lesions in characteristic locations • Younger patients

Metastases • Multiple lesions common • Significant associated vasogenic edema • Primary tumor often known

Neurosarcoidosis • Lacy leptomeningeal enhancement typical • Dural, leptomeningeal> > parenchymal disease • Most patients have systemic disease

Secondary involvement from systemic lymphoma • Intravascular pattern, lymphomatous meningitis or dural disease common • Can have single/multiple deep, periventricular lesions • Often affects brain and spine

Neoplasms and Tumorlike Lesions

6 123

Natural History & Prognosis General Features • General path comments o 98% B cell, non-Hodgkin lymphoma (NHL) o Rarely T-cell, Burkitt lymphoma, large cell anaplastic types o Solitary subependymallesion in HIV+ patient usually lymphoma o May occur as a second malignancy o Rarely PCNSL is preceded by demyelinating lesions • Etiology o Inherited or acquired immunodeficiency predisposes o EBV plays major role in immunocompromised o Histogenesis poorly understood o Site of origin controversial as CNS does not have lymphoid tissue or a lymphatic circulation • Epidemiology o Incidence increasing in immunocompetent, immunocompromised o 1-7% of primary brain tumors, incidence rising o Represents approximately 1% of lymphomas o Constitutes 3-5% of extranodal NHL o PCNSL is present in 2-6% of AIDS patients • PCNSL is an AIDS defining condition

Gross Pathologic & Surgical Features • Single or multiple masses in cerebral hemispheres • Well-circumscribed> infiltrative mass • Central necrosis, hemorrhage in HIV+

Microscopic

124

Features

• Poor prognosis • Favorable prognostic factors o Single lesion o Absence of meningeal or periventricular disease o Immunocompetent patient o Age < 60 years • Median survival 17-45 months • AIDS median survival 2-6 months • Dramatic but short-lived response to steroids and radiation therapy • Rarely, PCNSL is complicated by systemic disease

Treatment • Stereotactic biopsy, followed by radiation therapy and chemotherapy • Immunocompromised patients are often treated with anti-toxoplasmosis therapy initially • Recent studies suggest treatment with enhanced chemotherapy delivery with blood brain barrier disruption may be helpful

Consider • Corpus callosum involvement may be seen with PCNSL, GBM and rarely metastases, demyelination • Steroids may have a dramatic effect on imaging and biopsy results

Image Interpretation

• Angiocentric: Surrounds, infiltrates vessels and perivascular spaces • Several subtypes (large cell accounts for nearly 50%) • High nuclear/cytoplasmic ratio (high electron density) • MIB-l, proliferation index, usually high, 50%

1.

Presentation • Most common signs/symptoms o Altered mental status, focal neurologic deficits o Other signs/symptoms • Cognitive, neuropsychiatric disturbance • Headache, increased intracranial pressure • Seizure • Clinical profile o CSF shows elevated protein and decreased glucose • Cytology typically negative for lymphoma

2.

3.

4.

5.

Demographics • Age o Immunocompetent: 6th to 7th decades, mean age 60 years o Immunocompromised • AIDS, mean age 39 years • Transplant recipients, mean age 37 years • Inherited immunodeficiency syndromes, mean age 10 years o Occurs at all ages • Gender: Male predominance

Pearls

• Imaging and prognosis varies with immune status • PCNSL is characteristically hyperdense on NECT • Periventricular location and subependymal involvement is characteristic of PCNSL

6.

7.

Plasswilm L et al: Primary central nervous system (CNS) lymphoma in immunocompetent patients. Ann Hematol. 81(8): 415-23, 2002 Stadnik TW et al: Diffusion-weighted MR imaging of intracerebral masses: Comparison with conventional MR imaging and histologic findings. AJNR 22: 969-76, 2001 Schlegel U et al: Primary CNS lymphoma: clinical presentation, pathological classification, molecular pathogenesis and treatment. J Neurol Sci. 181(1-2): 1-12, 2000 Paulus W et al: Malignant lymphomas. Pathology & Genetics of Tumours of the Nervous System, IARC Press 198-203,2000 Bataille B et al: Primary intracerebral malignant lymphoma: Report of 248 cases. J Neurosurgery 92:261-6, 2000 DeAngelis LM: Primary CNS lymphoma: treatment with combined chemotherapy and radiotherapy. J Neurooncol. 43(3): 249-57, 1999 Koeller KKet al: Primary central nervous system lymphoma: radiologic-pathologic correlation. Radiographies. 17(6): 1497-526, 1997

Neoplasms and Tumorlike Lesions

Typical (Left) Axial T2WI MR shows a homogeneous isointense

mass crossing (to CBM) corpus callosum (arrow) with surrounding vasogenic edema, mass effect. PCNSL in immunocompetent patients is typically homogeneous. (Right) Axial CECTshows diffuse homogeneous enhancement of a right periatrial and corpus callosum mass. PCNSL is classically hyperdense on NECT. 62 year old female with seizures. Imaging mimics CBM.

Typical (Left) Axial T2WI MR shows intense mass in the right basal ganglia with surrounding edema. Young adult male with HIV. PCNSL is typically heterogeneous in immunocompromised patients. (Right) Axial T1 C+ MR shows a peripherally enhancing mass with central necrosis. The additional ependymal/subependymal enhancement (arrow) helps diagnose PCNSL rather than Toxoplasmosis in this HIV patient.

Variant (Left) Axial T1 C+ MR shows

diffuse peri ventricular enhancement without a focal mass. 50 year old immunocompetent male with headache. PCNSL. Imaging mimics CMV ventriculitis and metastasis. (Right) Coronal T1 C+ MR shows a peripherally enhancing mass with central necrosis in this HIV patient. Imaging mimics Toxoplasmosis, other brain abscess, or primary or metastatic neoplasm. PCNSL.

Neoplasms and Tumorlike Lesions

6 125

INTRAVASCULAR (ANGIOCENTRIC) LYMPHOMA

Graphic shows malignant lymphoid cells occluding and distending small arteries, veins and capillaries resulting in ischemic regions. Note also meningeal involvement (arrow), typical of IVL.

Coronal T1 c+ MR shows multifocal linear enhancement in the deep white matter (arrows) which corresponded to focal areas of T2 hyperintensity Patient with progressive dementia. IVL.

CT Findings Abbreviations

• NECT o Often normal or nonspecific o Focal, bilateral asymmetric low density lesions in WM, cortex, or basal ganglia • CECT: Variable (none to moderate)

and Synonyms

• Intravascular (angiocentric) lymphoma (IVL), intravascular malignant lymphomatosis, malignant angioendotheliomatosis, angiotropic large-cell lymphoma

MR Findings

Definitions

126

• Rare malignancy characterized by intravascular proliferation of lymphoid cells with a predilection CNS and skin • A form of non-Hodgkin lymphoma (NHL) characterized by angiotropic growth

for

General Features • Best diagnostic clue o Multifocal abnormal T2 hyperintensity in deep WM, cortex or basal ganglia + enhancement o Enhancement variable: Linear, patchy, nodular, gyriform, homogeneous, meningeal • Location o Supratentorial (periventricular/deep WM, G-W junction) o May involve basal ganglia (BG), midbrain

DDx: Supratentorial

• TlWI o Multifocal hypointense lesions o May see blood products • T2WI o 45% hyperintensities in deep WM (edema, gliosis) o 36% cortex hyperintensity, infarct-like lesions o May see hemorrhagic transformation • T2* GRE: May see blood products "blooming" • DWI: Diffusion restriction reported • Tl C+ o Variable enhancement: Linear, punctate, patchy, nodular, ring-like, gyriform, homogeneous o Meningeal and/or dural enhancement

Angiographic Findings • May mimic vasculitis

Imaging Recommendations • Protocol advice: Contrast-enhanced

MR with DWI

White Matter lesions

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Neoplasms and Tumorlike Lesions

Neurosarcoidosis

INTRAVASCULAR (ANGIOCENTRIC) LYMPHOMA Key Facts Terminology

Top Differential

• Rare malignancy characterized by intravascular proliferation of lymphoid cells with a predilection CNS and skin

for

Imaging Findings • Multifocal abnormal T2 hyperintensity cortex or basal ganglia + enhancenlent

in deep WM,

• • • •

Vasculitis Vascular dementia Primary CNS lymphoma Neurosarcoidosis

• Dementia, confusion,

Demographics

Vasculitis

• Age: 5th through

• Multifocal subcortical ischemia, +/- enhancement • DSA suggests diagnosis (IVL may mimic)

Vascular dementia • Large and small infarcts, WM disease • Clinical diagnosis can mimic IVL

memory loss

7th decade, mean age 63 years

Natural History & Prognosis • Mean survival 7-13 months • Mortality rate> 80% • Rarely spontaneous regression of symptoms

occurs

Treatment

Primary CNS lymphoma (PCNSL) WM

Neurosarcoidosis • Dural, leptomeningeal> > parenchymal • Patients often have systemic disease

(PCNSL)

Clinical Issues

! DIFFERENTIA.l.. .[)IAGNClSIS

• Enhancing lesions in BG, periventricular • Ependymal involvement characteristic

Diagnoses

disease

• Diagnosis often made post-mortem • Diagnosis may be made by skin or brain biopsy • Treatment includes steroids and chemotherapy

I DIAGNClSTIC

CHECKI..IST

Image Interpretation

Pearls

• Imaging of IVL is nonspecific, but should be considered in patients with dementia, multifocal lesions and enhancement

I PATHClI..ClG¥ General Features • General path comments o An aggressive B-cell NHL, angiotropic; rarely T-cell o IVL typically in CNS, skin but may affect any organ • Epidemiology: Rare but underdiagnosed

I SEI..ECTED REFERENCES 1.

Gross Pathologic & Surgical Features

2.

• Small infarcts of varying ages throughout subcortical WM; may be hemorrhagic

3.

cortex,

Burger PC et al: Surgical pathology of the nervous system and its coverings: The Brain: Tumors. 4th ed. Philadelphia, Churchill Livingstone. 323-4, 2002 Martin-Duverneuil N et al: Intravascular malignant lymphomatosis. Neuroradiol. 44:749-54, 2002 Williams RL et al: Cerebral MR imaging in intravascular lymphomatosis. AJNR. 19:427-31, 1998

Microscopic Features • Malignant lymphoid cells occlude/distend small arteries, veins, capillaries • Minimal perivascular extension into adjacent brain parenchyma

I IMAGE GAI..I..ER¥

I CI..IN ICAI.. ISSUES Presentation • Most common signs/symptoms o Dementia, confusion, memory loss o Other signs/symptoms • Cognitive failure, focal deficits, seizure, fever • Clinical profile o Skin changes: Raised plaques or nodules over abdomen & thighs (50%) o CSF studies show elevated protein o No malignant cells in peripheral blood smear or bone marrow

(Left) Axial T2WI MR involving the subcortical (arrow). (Right) Axial enhancement and subtle

Neoplasms and Tumorlike Lesions

shows multifocal areas of hyperintensity & deep WM with mild cortical involvement T1 C+ MR shows intense homogeneous

patchy (arrow) enhancement. IVL.

6 127

Coronal graphic shows multiple foci of leukemic infiltrates, in skull base, hypothalamus/infundibulum, basal ganglia, and dura. Green color observed at pathology results in name "chloroma".

Coronal Tl c+ MR shows enhancing chloroma centered in lateral basal ganglia (arrow) in a 5 year old with acute leukemia.

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1··l.MA.G.ING·.··.F1Nflllili .• Abbreviations

General

and Synonyms

• Granulocytic sarcoma, chloroma, extramedullary leukemic tumors (EML) • Extramedullary myeloblastoma, extramedullary myeloid cell tumors (EmMCT)

Definitions

6 128

• Solid tumor of myeloblasts, myelocytes, and promyelocytes occurring in patients with myeloproliferative disorders • Multiple other intracranial manifestations or complications of leukemia and treatment exist o Posterior reversible encephalopathy syndrome (PRES) o Invasive aspergillus infection o Late development of cavernous angiomas after radiation therapy o Post-transplantation lymphoproliferative disease (PTLD) after bone marrow transplantation o Venous thrombosis associated with chemotherapy (L-asparaginase) o Vasculitis • Primary manifestation of leukemia • Secondary to treatment (trans-retinoic acid) • Secondary to infection (aspergillus)

Features

• Best diagnostic clue o Homogeneous enhancing tumor(s) in patient with known or suspected myeloproliferative disorder o Most often a complication of acute myelogenous leukemia (AML) • Location: Variable: May be dural-based or less commonly intraparenchymal • Morphology: Variable

CT Findings • NECT o Isodense or hyperdense to brain o May present with or mimic hematoma o Often has skull base or paranasal sinus involvement o May rapidly become hypodense related to necrosis or liquefaction • CECT o Homogeneous enhancement • Hyperdensity or presence of hemorrhage may mask enhancement o May have rim-enhancement mimicking abscess

MR Findings • TlWI o Hypointense

or isointense to brain

DDx: Dural Masses

Neuroblastoma

Meningioma

Ewing Sarcoma

Neoplasms and Tumorlike

Lesions

LCH

LEUKEMIA Key

Facts

Terminology

Top Differential

• Granulocytic sarcoma, chloroma, extramedullary leukemic tumors (EML) • Extramedullary myeloblastoma, extramedullary myeloid cell tumors (EmMCT) • Multiple other intracranial manifestations or complications of leukemia and treatment exist

• Metastatic neuroblastoma • Meningioma

Imaging Findings • Most often a complication of acute myelogenous leukemia (AML) • Isodense or hyperdense to brain • May present with or mimic hematoma • Homogeneous enhancement • May have rim-enhancement mimicking abscess • Use fat-saturation techniques for contrast MR

o Can distinguish between acute hematoma and non-hemorrhagic mass • T2WI o Heterogeneous and hyperintense to isointense o Leptomeningeal disease in perivascular spaces may appear as patchy bright signal in white matter • FLAIR: More sensitive than T2WI for leptomeningeal disease • T2* GRE: Helpful for identifying cavernous angiomas as very late complication of leukemia treatment • DWI: Can distinguish ischemic lesions from posterior reversible encephalopathy syndrome (PRES) • Tl C+ o Homogeneous enhancement • May become heterogeneous with necrosis/liquefaction o Leptomeningeal or perivascular space enhancement o Fat-saturation technique essential for assessment of skull base disease o Subtraction techniques may help identify enhancement, separate from hyperintense hemorrhagic components ·MRA o May show vasospasm in cases of PRES o May identify medium vessel vasculitis • MRV o Essential in evaluation of hemorrhagic lesions o Identify presence or extent of venous thrombosis

Diagnoses (NBT)

Pathology • 11% of patients with AML

Clinical Issues • May precede marrow diagnosis of leukemia • Age: 60% of patients are < 15 yrs

Diagnostic Checklist • Extramedullary hematopoiesis can present in same patient population with similar appearance

o Use fat-saturation techniques for contrast MR o Consider extramedullary hematopoiesis in differential

I DIFFEREN ..•.IAL DIAG~C)SlS Metastatic neuroblastoma (NBT) • Rarely occurs without extra cranial disease • Characteristic "raccoon eyes" clinical presentation • Spiculated periostitis

Meningioma • May be very difficult to distinguish • Dural "tail" may be more common in meningioma

6

Extra-axial hematoma

129

• Extracranial soft tissue swelling or skull fracture • If no appropriate history, consider possibility of child abuse

Extramedullary hematopoiesis • Markedly hypointense on T2WI • Same at-risk patient population

Langerhans cell histiocytosis (LCH) • Destruction of adjacent bone without periosteal reaction • Diabetes insipidus

Nuclear Medicine Findings

Ewing sarcoma

• Bone Scan o Tc99-m-MDP commonly used for bone disease in leukemia o Soft tissue uptake typically reflects hypercalcemia, not chloroma • PET: Avid uptake on FDG-PET exams

• Aggressive pattern of growth • Destruction of adjacent bone

Neurosarcoidosis • Mimic of leptomeningeal disease • Less commonly presents as dural-based masses

Imaging Recommendations • Best imaging tool o MR with contrast o NECT may provide valuable additional in hemorrhagic lesions • Protocol advice

Extraosseous multiple myeloma • Rare complication

information

Neoplasms and Tumorlike Lesions

General Features

130

• General path comments o CNS leukemia presents in three forms • Meningeal disease, usually with acute lymphoblastic leukemia (ALL) • Intravascular aggregates (leukostasis) that can rupture in patients with markedly high leukocyte counts • Tumor masses (chloroma) o Leukemic masses first described in 1811 o "Chloroma" coined in 1853 oRe-named granulocytic sarcoma in 1966 • Genetics o Children with CNS leukemic infiltrates in AML have higher rate of chromosome 11 abnormalities than those without CNS disease o Chromosomal 8 and 21 translocations reported in cases of AML with chloroma • Etiology o Some association with exposures • Ionizing radiation • Hydrocarbons • Benzene • Alkylating agents • Epidemiology o 11% of patients with AML o 1-2% of patients with chronic myelogenous leukemia (CML) • Associated abnormalities o AML has higher incidence in some genetic syndromes • Down syndrome • Bloom syndrome • Fanconi anemia o Less commonly seen in other myeloproliferative disorders than in AML • Myeloid metaplasia • Hypereosinophilic syndrome • Polycythemia vera

o 50% of cases diagnosed only at autopsy o CNS lesions more likely symptomatic o Focal signs from local mass effect o Headache from hemorrhage • Clinical profile: Child with AML develops new neurological signs or symptoms

Demographics • Age: 60% of patients are < 15 yrs • Gender: M:F = 1.38:1 • Ethnicity o Incident rates are higher among Americans of European descent than among those of African descent o Hispanic children < 19 yrs have highest rates of leukemia

Natural History & Prognosis • Overall survival rates for AML are around 40-50% • Chloroma in setting of other myeloproliferative syndrome is a poor prognostic sign o Implies blastic transformation

Treatment • Options, risks, complications o Chemotherapy for induction • Cytarabine (Ara-C) • Anthracycline o Bone marrow transplant for consolidation

1·.··[)IJ\.GNI·C)S,..I.<::.·•·.·<::··~·ECSl<.itlS~ •. Consider • Extramedullary hematopoiesis can present in same patient population with similar appearance • Hemorrhagic lesions in children with AML can be manifestation of chloroma or complication of therapy

Image Interpretation

Pearls

Gross Pathologic & Surgical Features

• Multiple lesions at multiple sites are suggestive of diagnosis • Remember that chloromas can rarely mimic abscess with enhancing rim

• Called "chloroma" because of green color in 70% of cases o Caused by high levels of myeloperoxidase

I SELECTED REFERENCES 1.

Microscopic Features • Moderate to large cells • Pleomorphic nuclei • Multiple mitoses give "starry sky" appearance

2.

Staging, Grading or Classification Criteria

3.

• French-American-British (FAB) classification divides AML into 8 subtypes • Chloroma is additional variant presentation, not separate subtype

4. 5.

Nikolic B et al: CT changes of an intracranial granulocytic sarcoma on short-term follow-up. A]R Am] Roentgenol. 180(1):78-80,2003 Guermazi A et al: Granulocytic sarcoma (chloroma): imaging findings in adults and children. A]R Am] Roentgenol. 178(2):319-25, 2002 Ahn]Y et al: Meningeal chloroma (granulocytic sarcoma) in acute lymphoblastic leukemia mimicking a falx meningioma.] Neurooncol. 60(1):31-5, 2002 Lee B et al: Granulocytic sarcoma of the temporal bone. A]NR Am] Neuroradiol. 23(9):1497-9, 2002 Chen CY et al: Childhood leukemia: central nervous system abnormalities during and after treatment. A]NR Am ] Neuroradiol. 17(2):295-310, 1996

Presentation • Most common signs/symptoms o May precede marrow diagnosis of leukemia

Neoplasms and Tumorlike

Lesions

Variant (Left) Axial NEeT shows 1 cm hyperdense

intraparenchymal chloroma at gray-white junction of right parietal lobe (arrow). Intraparenchymalleukemic infiltrates are much less common than dural-based disease. (Right) Axial T2WI MR of same lesion shows hyperintense central focus with hypointense rim and small amount of surrounding edema. This imaging appearance is nonspecific.

Typical

(Left) Axial T2WI MR shows

vasogenic edema in left parietal lobe caused by leukemic infiltrate along interhemispheric falx (arrows). Presence of edema is variable and not helpful in confirming diagnosis. (Right) Axial CECT in the same patient shows diffuse enhancement of leukemic infiltrate. Irregular margin and presence on both sides of falx makes meningioma much less likely.

Variant (Left) Axial NECT shows large left temporal lobe hematoma and hyperdense right frontal lobe lesion in a child with AML. Pathologic analysis of left temporal lesion showed both hemorrhage and leukemic cells. (Right) Axial T2WI MR shows poorly defined hyperintense signal in distribution of perivascular spaces (PVS) due to infiltration of leukemia. Normal PVS are more sharply defined, and will not show enhancement.

Neoplasms and Tumorlike Lesions

6 131

Sagittal graphic shows synchronous germinomas in the suprasellar and pineal regions. Note the CSF spread of tumor in the lateral, 3rd, and 4th ventricles (arrows).

Abbreviations

and Synonyms

• Dysgerminoma, extra-gonadal called atypical teratoma

seminoma,

formerly

Definitions • Morphologic homologues of germinal neoplasms arising in the gonads and extragonadal sites

132

General Features • Best diagnostic clue o Pineal region mass that "engulfs" the pineal gland o Suprasellar mass and diabetes insipidus (Dr) • Location o CNS germinomas have a propensity to hug the midline near the 3rd ventricle - 80-90% • Pineal region - 50-65% • Suprasellar - 25-35% • Basal ganglia and thalami - 5-10% • Other sites: Intraventricular (3rd), intra sellar, bulbar, intramedullary, cerebral hemispheric • Size o Location dictates size at presentation

Sagittal T1 C+ MR shows a homogeneously enhancing germinoma in the pineal location (arrow). Note also the seeded tumor within the sella and obex of 4th ventricle (open arrows).

• Suprasellar germinoma: Early presentation with DI, mass may be small • Pineal region germinoma: Due to tectal compression, ± invasion, mass may be small • Basal ganglia and thalamic germinoma: Often large at presentation • Morphology: Often well-delineated, ± CSF tumor seeding

CT Findings • NECT o Sharply circumscribed dense mass (hyperdense to GM) • Pineal: Mass drapes around posterior 3rd ventricle or "engulfs" pineal gland • Suprasellar: Retrochiasmatic, non-cystic, non -calcified o ± Hydrocephalus • CECT o Strong uniform enhancement, ± CSF seeding • Pineal region: Look for posterior 3rd ventricular wall infiltration • Suprasellar: Look for infiltration of 3rd ventricular floor, lateral walls and anterior columns of fornices o Cystic/necrotic/hemorrhagic components not uncommon with larger germinomas (especially in basal ganglia)

DDx: Intracranial Germinoma

Yolk Sac Tumor

Pineoblastoma

Craniopharyngioma

Neoplasms and Tumorlike Lesions

Astrocytoma

GERMINOMA Key Facts Imaging Findings

Pathology

• Pineal region mass that "engulfs" the pineal gland • Suprasellar mass and diabetes insipidus (01) • CNS germinomas have a propensity to hug the midline near the 3rd ventricle - 80-90% • Strong uniform enhancement, ± CSF seeding • Iso-to-hyperintense to GM (high nuclear: Cytoplasmic ratio) • OWl: Restricted diffusion due to high cellularity

• Germinomas ~ 1-2% of all CNS tumors • 2-4% of pediatric CNS tumors

Top Differential • • • •

Diagnoses

Pineal region germ cell tumors (GCTs) Pineoblastoma, pineocytoma Craniopharyngioma Hypothalamic/chiasmatic astrocytoma

Clinical Issues • Parinaud syndrome (upward gaze paralysis and altered convergence) • OI can present for an extended period prior to MR abnormalities • CNS GCTs are primarily seen in young patients

Diagnostic Checklist • Young patient presents with OI? Think germinoma LCH! • Serial repeat MR imaging with contrast may be necessary to clinch diagnosis

MR Findings

Craniopharyngioma

• TlWl o Isointense or hyperintense to GM o Early ~ may only see absent posterior pituitary bright spot • T2Wl o Iso-to-hyperintense to GM (high nuclear: Cytoplasmic ratio) • Cystic or necrotic foci (high T2 signal) • Less common: Hypointense foci (hemorrhage) • FLAIR: Slightly hyperintense to GM • T2* GRE: Calcification, hemorrhage (rare) • OWl: Restricted diffusion due to high cellularity • Tl C+: Strong, homogeneous enhancement, ± CSF seeding, ± brain invasion • MRS: 1 Choline, !NAA, ± lactate

• Cystic, solid, and Ca++ components

Imaging Recommendations • Best imaging tool: Enhanced MR of brain and spine • Protocol advice: MR evaluation of entire neuraxis before surgery

Hypothalamic/chiasmatic • Homogeneous

enhancement,

or

astrocytoma rarely associated with 01

Other pineal region masses • • • •

Astrocytoma Metastasis Meningioma Retinoblastoma o Tri-Iateral ~ evaluate orbits and suprasellar regions

Other suprasellar region lesions • PNET • Hamartoma (Isointense with GM, nonenhancing) • Suprasellar arachnoid cyst (CSF density/intensity; no enhancement) • Langerhans cell histiocytosis (LCH) o Infiltrating enhancing hypothalamic/infundibular lesion, + DI • Sarcoid • Metastases

I DIFFERENTIAl. DIAGNOSIS Pineal region germ cell tumors (GCTs) • Secreting GCTs tumors o Malignant mixed germ cell, yolk sac, choriocarcinoma, embryonal Ca • Heterogeneous, Ca++, and hemorrhage • Nonsecreting GCTs o Immature teratoma, mature teratoma, mixed mature/immature • Soft tissue, Ca++, and fat components

Pineoblastoma,

pineocytoma

• Pineal parenchymal tumors o Mass "explodes" rather than "engulfs" pineal Ca++ • Atypical pineal cyst o Often> 15 mm, rim-enhancing, variable signal of cyst contents, ± tectal compression

IPATHOl.OGY General Features • General path comments o Unencapsulated solid mass, soft and friable, tan-white coloration, ± cystic foci o Necrosis, calcification and hemorrhage uncommon • Genetics o Cytogenetics - 1 risk of CNS germ cell neoplasms • Extranumerary X chromosomes (Klinefelter syndrome) • Alterations of chromosomes 1 (lq21-1qter region) • Over-representation of chromosome 12 (12p duplication) • Other sites of chromosome alteration: 8q, 13q, 18q, 9q, llq o Molecular genetics - 1 risk of CNS germ cell neoplasms

Neoplasms and Tumorlike Lesions

6 133

• TP53 tumor suppressor gene mutations

(exons

5-8)

• MDM2 gene amplification • Etiology o Abnormal histogenesis • Embryonic disc gives rise to primary, secondary yolk sac • Primordial germ cells persist, maldifferentiate into germinoma o Aberrant migration • Yolk sac cells move toward midline ~ enter primitive groove ~ migrate to neural plate • Neural tube folds ~ germ cells incorporated into neuraxis o Toti or pluri-potential stem cells are native to all three embryonic layers • Epidemiology o Germinomas ~ 1-2% of all CNS tumors • 2-4% of pediatric CNS tumors • 9-15% of CNS tumors in Japanese children o Germinomas - 50% of pineal region tumors o Germinomas ~ account for 2/3 of all CNS GCTs • Associated abnormalities o Klinefelter's syndrome (47XXY) o Down syndrome o Nfl o Laboratory derangements • Elevated placental alkaline phosphatase (PLAP) • ± Elevation of serum and CSF HCG

Gross Pathologic & Surgical Features • Soft and friable, tan-white

134

mass, ± necrosis

• Clinical profile o OI can present for an extended period prior to MR abnormalities o Dr may be present with germinomas of: Pineal, suprasellar and basal ganglia origin

Demographics • Age o CNS GCTs are primarily seen in young patients • Peak age: 10-12 years • 90% of patients < 20 years • Gender o Pineal region germinoma • Male:Female "" 10: 1 o Suprasellar germinoma • More common in females o For all CNS germinomas • M:F = 1.5-2:1 • Ethnicity o CNS GCTs far more prevalent in Asia • 9-15% of all CNS tumors in Japan • Basal ganglia and thalamic germinomas more common in Japan and Korea

Natural History & Prognosis • Pure germinoma has favorable prognosis o Low secretion of HCG « 50) ~ favorable o Very radiosensitive • Malignant but relatively benign prognosis due to radiation and chemotherapy sensitivity • CSF dissemination and invasion of adjacent brain common

Microscopic Features

Treatment

• Sheets of large polygonal primitive germ cells o Mitoses o Large vesicular nuclei & prominent nucleoli o Clear, glycogen-rich cytoplasm (PAS-positive) • Lymphocytic infiltrates along fibrovascular septa

• Biopsy to confirm histology, "pure" germinomas best outcome • XRT +/- adjuvant chemotherapy • 5 year survival - 91 %

Staging, Grading or Classification Criteria

1.··DIAG.N.o.STIC.·.CffEC·KLIS"f

• Staging multiple site involvement (pineal, suprasellar, basal ganglia, thalamus) is considered metastatic in USA but synchronous in Canada and Europe

Consider • Young patient presents with OI? Think germinoma LCH!

Image Interpretation

1.(S.LI~;I£"L ••ISS.l..rE.S

have

or

Pearls

• Serial repeat MR imaging with contrast may be necessary to clinch diagnosis

Presentation • Most common signs/symptoms o Pineal region germinoma • Parinaud syndrome (upward gaze paralysis and altered convergence) • Headache due to tectal compression or invasion (hydrocephalus) o Suprasellar germinoma • Diabetes insipidus (OI) • Visual loss • Hypothalamic-pituitary dysfunction (! growth, precocious puberty) o Basal ganglia and thalamic germinoma • Hemiparesis • Mental status change • Precocity

I SELECTED REFERENCES 1.

2.

3.

4. 5.

Veno T et al: Spectrum of germ cell tumors: From head to toe. Radiographies 24:387-404, 2004 Knierim DS et al: Pineal tumors and associated lesions: the effect of ethnicity on tumor type and treatment. Pediatr Neurosurg 38: 307-23, 2003 Rosenblum MK et al: CNS germ cell tumors. In Kleihues P, Cavenee WK (eds), Tumours of the nervous system, Chapter 13; 207-14, IARC Press, Lyon, France, 2000 Halbauer GE et al: Cytogenetic profile of primary pituitary germinoma. J Neurooncol 50(3): 251-5, 2000 Sano K: Pathogenesis of intracranial germ cell tumors reconsidered. J Neurosurg 90:258-64, 1999

Neoplasms and Tumorlike Lesions

Typical (Left) Sagittal T1 C+ MR shows a homogeneously enhancing sellar and suprasellar germinoma (arrow). Note also the small synchronous lesion in the pineal location (open arrow). (Right) Axial NECT shows a suprasellar germinoma with typical increased attenuation (arrow).

Variant (Left) Sagittal T1 C+ MR shows a heterogeneously enhancing pineal region germinoma with a large cystic/necrotic component (arrow). (Right) Sagittal T1 C+ MR shows a heterogeneous partially necrotic sellar and suprasellar germinoma (arrow).

6 135

Variant (Left) Axial T1 C+ MR shows a large partially necrotic left basal ganglia germinoma. (Right) Axial T2WI MR in a different case of a 72 yo female with 01 and a suprasellar germinoma (not shown). A mixed hyperintense periventricular mass infiltrates up the fornix and into septum (arrows).

Neoplasms and Tumorlike Lesions

Sagittal graphic shows a heterogeneous pineal teratoma with solid, calcific (open arrow), and fatty (arrow) composition.

Axial T1WI MR demonstrates a heterogeneous pineal region teratoma with soft tissue, calcific, and fatty (arrow) elements (Courtesy j. Provenzale, MO).

MR Findings Abbreviations • Intracranial (GCT)

and Synonyms

teratoma, intracranial

germ cell tumor

Definitions

6

• Tridermal mass originating from o Displaced embryonic tissue that is misenfolded o Embryonic stem cells o Parthenogenetic => "blighted twins"

• • • • • •

T1WI: 1 Signal from fat, variable signal from Ca++ T2WI: Soft tissue components iso- to hyperintense FLAIR: j Signal from cysts, 1 signal from solid tissue T2* GRE: j Signal from Ca++ Tl C+: Soft tissue enhancement MRS: 1 Lipid moieties on short echo

Ultrasonographic

Findings

• Heterogeneous mass with internal shadowing (Ca++) • In-utero ultrasound: Hydrocephalus, polyhydramnios, intracranial mass

Imaging Recommendations

136

General Features • Best diagnostic clue: Midline mass containing: Ca++, soft tissue, cysts, and fat • Location o Hugs midline, optic chiasm => pineal gland o Majority are supratentorial • Size: Variable, holocranial teratomas are huge • Morphology: Smaller tumors rounded => lobulated

• Best imaging tool o CT demonstrates: Soft tissue, fat, and Ca++ o MR best characterizes relationship of teratoma to midline structures • Protocol advice: Fat suppressed MR

Craniopharyngioma

CT Findings • NECT: Fat, soft tissue, Ca++, cystic attenuation • CECT: Soft tissue components enhance

• Partially Ca++/cystic, suprasellar tumor in children

Dermoid • Minimal/no

enhancement

DDx: Mimics of Midline Intracranial Teratomas

Craniopharyngioma

Dermoid

Yolk Sac Tumor

Neoplasms and Tumorlike Lesions

Pineoblastoma

TERATOMA Key Facts Imaging Findi

Top Differential Diagnoses

• Best diagnostic : Midline mass containing: Ca++, soft tissue, cysts,.and fat • Hugs midli iasm ~ pineal gland • Majority are orial • CECT: Soft tissue components enhance • T1WI: t Signal from fat, variable signal from Ca++ • MR best characterizes relationship of teratoma to midline structures

• Craniopharyngioma • Dermoid • Non-germinoma GeT

Non-germinoma

Diagnostic Checklist • Think teratoma in newborn with holocranial

tumor

• Gender: Males> females • Ethnicity: More common among Asians

GCT

• Yolk sac tumor

Natural History & Prognosis

Other mimics of midline intracranial teratomas

• Varies with size, location and classification • 5 year survival for malignant teratomas 18%

• Pineoblastoma • PNET • Astrocytoma (rarely to calcify)

Treatment

I PATH(})L(})(j¥

I DIA(jN(})STIC

General Features

Consider

• General path comments o Lobulated tridermal mass o t AFP if tumor contains enteric glandular elements • Genetics: Diploid or near diploid • Etiology o Originates during 3rd and 4th week of fetal development o Anomalous development of primitive streak or its derivatives • Epidemiology: 2-4% of intracranial tumors in children • Associated abnormalities: Klinefelter syndrome

• Think teratoma in newborn with holocranial

I SELECTED REFERENCES

Gross Pathologic & Surgical Features

3.

• Mature teratomas ~ fully differentiated tissue • Immature or malignant teratoma ~ resembles fetal tissues

4.

• Operative mortality in 1st year 20%

CHECKliST

Image Interpretation • Midline tumor containing:

1.

2.

tumor

Pearls Fat, soft tissue, and Ca++

1m SH etel: Congenital intracranial teratoma: prenatal diagnosis and postnatal successful resection. Med Pediatr Oncol. 57-61, 2003 Cavalheiro S et al: Fetal brain tumors. Childs Nerv Syst. 19(7-8): 529-36, 2003 ]aing TH et al: Intracranial germ cell tumors: a retrospective study of 44 children. Pediatr Neurol. 26(5): 369-73, 2002 Liang L et al: MRI of intracranial germ-cell tumours. Neuroradiology. 44(5): 382-8, 2002

Microscopic Features • Mature teratoma ~ mature tridermal tissue • Immature or malignant ~ mitotically active stroma, + primitive neuroectodermal elements

IIMA(jE (jALLER¥

Staging, Grading or Classification Criteria • WHO classification: Mature; immature; malignant transformation

teratoma with ,

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I ClIlSJlCALISStJES Presentation • Most common signs/symptoms: Macrocephaly, lesions ~ Parinaud syndrome • Clinical profile: In-utero demonstration of hydrocephalus and heterogeneous mass

Demographics • Age: Detected in-utero or as neonate

pineal

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(Left) Axial NECT shows coarse Ca++ (arrow) within a pineal region teratoma. (Right) Axial TlWI MR in macrocephalic newborn with congenital holocranial immature teratoma. Note heterogeneous mass replaces normal brain tissue (Courtesy C. Clasier, MD).

Neoplasms and Tumorlike Lesions

6 137

Sagittal TlWI MR shows a heterogeneous, partially cystic embryonal carcinoma of the pineal region. Also note the foci of Tl shortening due to hemorrhage (arrows).

Abbreviations • Malignant

and Synonyms

germ cell tumor (GCT)

Definitions • Malignant tumor composed of undifferentiated epithelial cells

Axial Tl C+ MR shows vivid enhancement of the solid components of the pineal region embryonal carcinoma (arrow).

o Tl shortening due to protein, blood or fat • T2WI: Isointense to slightly hyperintense to GM • FLAIR o Hyperintense solid elements o ± Hydrocephalus • T2* GRE: Dephasing from hemorrhagic foci • DWI: ± Restriction within solid components • Tl C+: Heterogeneous enhancement, ± CSF spread • MRS: t Choline, t lipid and lactate, !NAA

Imaging Recommendations • Best imaging tool: MR of brain and spine with contrast • Protocol advice: Pre-operative MR of entire neuraxis

General Features 138

• Best diagnostic clue: Heterogeneous pineal or suprasellar mass in adolescent • Location: Hugs midline as other CNS GCTs • Size: Tumors in suprasellar, pineal region tend to be smaller • Morphology: Typically well circumscribed or lobulated

CT Findings • NECT o Heterogeneous • Isoattenuating • CECT: Enhancing,

• Germinoma • Mixed malignant • Choriocarcinoma,

Supratentorial to hyperattenuating ± cysts, hemorrhage

germ cell tumor, yolk sac tumor teratoma (immature and malignant)

PNET

• Minimal peritumoral

edema

Other suprasellar, pineal tumors • Astrocytoma • Dermoid • Choroid plexus tumors of third ventricle

MR Findings • TlWI o Hypointense

Other intracranial germ cell tumors

to isointense to GM

DDx: Embryonal Carcinoma

Mixed GeT

Malignant Teratoma

Pineoblastoma

Neoplasms and Tumorlike Lesions

PNET

EMBRYONAL CARCINOMA Key

Facts

Imaging Findings

Top Differential Diagnoses

• Best diagnostic clue: Heterogeneous pineal or suprasellar mass in adolescent • Location: Hugs midline as other CNS GCTs • T1 shortening due to protein, blood or fat • Tl C+: Heterogeneous enhancement, ± CSF spread • Best imaging tool: MR of brain and spine with contrast

• Other intracranial germ cell tumors • Supratentorial PNET

I PATH 0

LOG¥

General Features • General path comments: Solid mass often with cysts and hemorrhage • Genetics: Reports of near triploid complex karyotypes • Etiology: Aberrations in: Histogenesis, germ cell migration, or stem cells • Epidemiology: Rare « 1% of all CNS tumors) • Associated abnormalities: Klinefelter syndrome (47XXY)

• Typically part of a mixed malignant

• Soft, often friable mass

Diagnostic Checklist from other CNS GCTs

• Metastasis of embryonal source

carcinoma from testicular

Image Interpretation • Difficult to differentiate

1.

3.

epithelial cells

Staging, Grading or Classification Criteria • Typically part of a mixed malignant

germ cell tumor

Pearls from other CNS GCTs

I SELECTED REFERENCES

4.

Microscopic Features

germ cell tumor

• Difficult to differentiate

2.

Gross Pathologic & Surgical Features

• Undifferentiated

Pathology

5.

Knierim DS et al: Pineal tumors and associated lesions: the effect of ethnicity on tumor type and treatment. Pediatr Neurosurg. 38: 307-23, 2003 Halbauer GE et al: Cytogenetic profile of primary pituitary germinoma. J Neurooncol. 50(3): 251-5, 2000 Sano K: Pathogenesis of intracranial germ cell tumors reconsidered. J Neurosurg .90: 258-64, 1999 Sawamura Y et al: Germ cell tumours of the central nervous system: treatment consideration based 34(1):104-10, 1998 Smirniotopoulos JG et al: Pineal region masses: Differential diagnosis. Radiographies 12: 577-96, 1992

I IMAG E GALLERY

I CtiNICAIiIS.$l,.1ES

139

Presentation • Most common signs/symptoms o t rcp from suprasellar or pineal region mass o Other signs/symptoms - visual, endocrine, Parinaud syndrome • Clinical profile: Obstructing midline mass in vicinity of third ventricle, ± focal neuro deficits

Demographics • Age: Peri pubertal patients, rare < 4 years • Gender: Males show slight increased incidence • Ethnicity: More common in Asians (Left) Axial T2WI MR shows a mixed signal intensity predominantly

Natural History & Prognosis • Local invasive and metastatic potential • Follow-up: PLAP and cytokeratin markers

solid embryonal carcinoma of the pineal gland (arrow). (Right) Axial T7 C+ MR in the same case shows a minimally enhancing predominantly necrotic pineal region embryonal carcinoma (arrow).

Treatment • Surgical resection - chemotherapy radiation

I DIAGNOSTIC

6

- neuraxis

CHECKLIST

Consider • Embryonal carcinoma upon detecting a heterogeneous pineal region or suprasellar mass in adolescent

Neoplasms and Tumorlike

Lesions

Axial graphic shows multifocal metastases at gray-white matter junction, the classic location. Note metastases tend to be spherical rather than infiltrating with variable associated edema.

Abbreviations • Parenchymal

and Synonyms

metastases (mets)

Definitions • Parenchymal tumors that originate from, but are discontinuous with, other CNS primary or extracranial systemic neoplasms

Axial CECT shows innumerable contrast-enhancing foci at gray-white interfaces and basal ganglia. Additional lesion in choroid plexus (arrow). Adenocarcinoma of breast, metastatic to brain.

• Perineural (e.g., adenocystic carcinoma along CN 5 to pons) o Rare: Brainstem • Size: Varies from microscopic to several cm • Morphology o Most mets are discrete, spherical o Number • 50% of metastases are solitary • 20% two metastases, 30% three or more

CT Findings

6 140

General Features • Best diagnostic clue: Discrete parenchymal mass(es) at gray-white interface • Location o Classic: Discrete, focal mass(es) at arterial border zones • 80% hemispheres • 15% cerebellum, 3% basal ganglia o Less common • Choroid plexus, ventricular ependyma • Pituitary or pineal gland • Leptomeninges o Uncommon: Diffusely infiltrating tumors ("carcinomatous encephalitis") • Perivascular (e.g., intravascular lymphoma)

DDx: Multiple

• NECT o Iso- or hypodense mass(es) at gray-white interface o Peritumoral edema variable (none to striking) o Variable intracranial hemorrhage (ICH) • Mets may cause "spontaneous" ICH in elderly • CECT o Intense, punctate, nodular or ring enhancement o Caution: Tumor i volume (enhancement) i if scans delayed

MR Findings • TlWI o Iso/hypointense o Some metastases with intrinsically short Tl (e.g., melanoma) may be hyperintense o Hemorrhage: Disordered/atypical evolution (compared to nonneoplastic ICH) • T2WI

,~

Metastases

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Embolic Infarcts

Multiple Sclerosis

Neoplasms and Tumorlike

Lesions

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Multifocal CBM

PARENCHYMAL METASTASES Key Facts • Demyelinating

Terminology • Parenchymal tumors that originate from, but are discontinuous with, other CNS primary or extracranial systemic neoplasms

Imaging Findings • Best diagnostic clue: Discrete parenchymal mass(es) at gray-white interface • Best imaging tool: Contrast-enhanced MRI > > CECT • Protocol advice: Double or triple-contrast dose increases sensitivity but questionable value on routine basis

Top Differential

• •

•

•

•

Findings

• Conventional o Occasionally very hypervascular, with intense prolonged blush and A-V shunting o Can mimic hemangioblastoma, even AVM

Nuclear Medicine

Findings

• Median survival with whole brain XRT

= 3-6 months

• Protocol advice: Double or triple-contrast dose increases sensitivity but questionable value on routine basis

I DIFFERENTIAls DIAGN€JSIS Abscess • Usually shows increased signal on DWI o Reduced ADC • MRS: Elevated amino acids, lactate in cystic component; no Cho elevation

Malignant glioma

6

• Anaplastic astrocytoma/oligodendroglioma, glioblastoma (GBM) • Tends to be infiltrating, deep location (rather than discrete gray-white junction masses) • Solitary> multifocal more common o Solitary met can mimic GBM

Thromboembolic

141

stroke{s)

• Arterial border-zone location common • Ring-enhancing pattern uncommon • Multiple acute embolic strokes usually show restricted diffusion • Chronic UBOs: If they don't enhance, they aren't mets!

Demyelinating

disease

• Periventricular > gray-white junction • Incomplete ring, "horseshoe-shaped" enhancement • Younger patients

IPATH€JIs€JGY

~

General Features

• Bone Scan: May show systemic lesions

Imaging Recommendations • Best imaging tool: Contrast-enhanced

Clinical Issues

• White matter disease ("UBOs") in elderly patient can be caused by multifocal metastases • Use contrast-enhanced scans

o Variable but usually hyperintense o Widely scattered mets mimic vascular WM disease PD/Intermediate: Usually hyperintense FLAIR o Variable o Usually moderately hyperintense with strikingly hyperintense adjacent edema T2* GRE: Blooms if hemorrhage present DWI o Usually shows no restriction; ADC elevated o DWI with calculated ADC values may not allow reliable differentiation of enhancing necrotic lesions Tl C+ o Almost all mets enhance • Enhancement usually strong (magnetization transfer, fat suppression enhance conspicuity) • Variable patterns (uniform, punctate, solid or ring-enhancement) o Delayed sequences at 20-30 mins often show additional lesions MRS o Strong Cho peak at long TE without elevation in surrounding peritumoral edema characteristic o Lipid or lipid/lac often present (indicates necrosis) o 80-85% of mets lack Cr peak Dynamic susceptibility contrast-enhanced MR may show elevated rCBV in hypervascular metastases (renal carcinoma or melanoma), making them difficult to distinguish from high grade gliomas

Angiographic

Pathology • Prevalence of metastases vs primary CNS neoplasms increasing • Now account for up to 50% of all brain tumors • Seen in 25% of cancer patients at autopsy • Metastases usually displace rather than infiltrate tissue

Diagnostic Checklist

Diagnoses

• Abscess • Malignant glioma • Thromboembolic stroke(s)

• •

disease

MRI > > CECT

• General path comments o With better treatment, patients with systemic cancers are surviving longer o Prevalence of metastases vs primary CNS neoplasms increasing

Neoplasms and Tumorlike Lesions

6 142

• Genetics o Metastasis formation can be a complex genetically-mediated event • Inactivation of tumor suppressor genes • Activation of proto-oncogenes o Organ-specific metastasis formation • Specific receptors mediate attachment, infiltration of circulating tumor cells into CNS • Chromosome 17q (RHO gene family), 8q (c-myc) gains • Overexpression, amplification of EGFR gene common o Some tumor-specific patterns of disease spread • ER+/PR+ breast cancers osseous> brain metastases • ER-/PR- cancers brain> osseous metastases • Etiology o Hematogenous spread from systemic primary neoplasm • Lung, breast, melanoma most common primary malignancies • 10% unknown source o Geographic extension from head/neck primary neoplasm • Tumor extension to dura from calvarium • Directly through skull base or via foramina, fissures (e.g., nasopharyngeal SCCA) • Perineural or perivascular • May eventually involve parenchyma o "Brain to brain" spread from primary CNS neoplasm (e.g., GBM) • Epidemiology o Now account for up to 50% of all brain tumors o Seen in 25% of cancer patients at autopsy • Associated abnormalities o Other organs often involved o In 10% of cases, brain is only site o Limbic encephalitis • Paraneoplastic syndrome (remote effect of cancer) • Resembles herpes encephalitis (subacute clinical presentation)

Gross Pathologic & Surgical Features • Round/confluent, relatively discrete tan or grayish-white mass • Edema, mass effect varies from little to striking • Hemorrhage common with some mets (melanoma, choriocarcinoma, lung/renal cell carcinomas)

Demographics • Age o Incidence increases with age • Rare in children (skull/dura more common site than parenchyma) • Peak prevalence over 65 y • Gender: Slight male predominance

Natural History & Prognosis • Median survival with whole brain XRT = 3-6 months o Younger age, high Karnofsky performance status associated with longer survival • Progressive increase in size, numbers is typical

Treatment • Varies with number, location of metastases • Resection of solitary metastasis may improve survival

I.DIAGNOSIICCRECKLIS-r Consider • "Spontaneous" ICH or new onset seizures in elderly patient may be caused by metastasis

Image Interpretation

I SELECTED REFERENCES 1.

2.

3.

4.

5.

Microscopic Features

6.

• • • •

7.

Usually similar to primary neoplasm Metastases usually displace rather than infiltrate tissue Necrosis, neovascularity common Marked mitoses; labeling index may be greater than primary

tCLlNI()\[lSSI.JES

8.

Presentation • Most common signs/symptoms: Seizure, focal neurologic deficit • Clinical profile: Middle-aged/elderly patient with known systemic cancer, new onset of neurological symptoms

Pearls

• White matter disease ("UBOs") in elderly patient can be caused by multifocal metastases • Use contrast-enhanced scans

9.

Sidhu K et al: Delineation of brain metastases on CT images for planning radiosurgery: concerns regarding accuracy. Br J Radiol 77:39-42, 2004 Kremer S et al: Dynamic contrast-enhanced MRI: differentiating melanoma and renal carcinoma metastases from high-grade astrocytomas and other metastases. Neuroradiology. 45(1):44-9, 2003 Nonaka H et al: The microvasculature of the cerebral white matter: arteries of the subcortical white matter. J Neuropathol Exp Neurol. 62(2):154-61, 2003 Bulakbasi N et al: Combination of single-voxel proton MR spectroscopy and apparent diffusion coefficient calculation in the evaluation of common brain tumors. AJNR Am J Neuroradiol. 24(2):225-33, 2003 Price SJ et al: Diffusion tensor imaging of brain turn ours at 3T: a potential tool for assessing white matter tract invasion? Clin Radiol. 58(6):455-62, 2003 Nadal Desbarats L et al: Differential MRI diagnosis between brain abscesses and necrotic or cystic brain tumors using the apparent diffusion coefficient and normalized diffusion-weighted images. Magn Reson Imaging. 21(6):645-50,2003 Miller KD et al: Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol. 14(7):1072-7,2003 Gajewicz W et al: The use of proton MRS in the differential diagnosis of brain tumors and tumor-like processes. Med Sci Monit. 9(9):MT97-105, 2003 Dorenbeck U et al: Diffusion-weighted echo-planar MRI of the brain with calculated ADCs: a useful tool in the differential diagnosis of tumor necrosis from abscess? J Neuroimaging. 13(4):330-8,2003

Neoplasms and Tumorlike

Lesions

Variant (Left) Axial T2WI MR in an elderly patient with first-time seizure shows a mixed signal left frontotemporal infiltrating mass with marked surrounding edema. (Right) Axial T1 C+ MR in the same case shows lesion enhances strongly but heterogeneously. Preoperative diagnosis was GBM. Surgery disclosed metastasis (unknown primary).

Variant

(Left) Axial T2WI MR shows a multicystic parieto-occipital

mass with fluid-fluid levels and mixed-age hemorrhage. The lesion mimics a cavernous malformation but is a metastasis. (Right) Axial T1 C+ MR shows diffuse peri ventricular and ependymal enhancement, a pattern more commonly seen with GBM. Proven melanoma (Courtesy R. Babbel, MD).

6 143

Variant

(Left) Axial T2WI MR in an elderly patient with progressive dementia shows multifocal hyperintensities ("UBGs") in deep white matter and basal ganglia, indistinguishable from vascular disease. (Right) Axial T1 C+ MR shows many of the lesions enhance. Biopsy disclosed metastases from unknown primary, most likely breast. A good rule: If it doesn't enhance, it probably isn't a metastasis.

Neoplasms and Tumorlike Lesions

Axial FLAIR MR shows hyperintensity within the medial temporal lobes, classic for limbic encephaliUs (LE). Patient with subacute dementia, lung cancer. Imaging mimics herpes encephalitis.

Axial T1 C+ MR shows subtle patchy enhancement of the medial temporal lobes bilaterally (arrows). Typical enhancement pattern for limbic encephalitis. Bilateral involvement is common.

CT Findings Abbreviations • Paraneoplastic

and Synonyms syndromes

(PSs), paraneoplastic

disease

Definitions

6

• Remote neurological effect(s) of cancer, associated with extra-CNS tumors o Most common tumor: Small cell lung carcinoma • Limbic encephalitis (LE) is most common clinical paraneoplastic syndrome o Only PS with clearly defined imaging features

144

General

Features

• Best diagnostic clue o Limbic encephalitis: Hyperintensity in mesial temporal lobes, limbic system • Looks like herpes encephalitis but different clinical course (subacute/chronic) o Initial study normal in 20-40% o Most paraneoplastic syndromes do not have associated imaging findings • Location: LE: Hippocampus, cingulate gyrus, pyriform cortex, frontal orbital surface of temporal lobe, insula, amygdala

DDx: Temporal

• NECT o Initial CT scan normal in > 95% o Rare: Low density within mesial temporal lobes • CECT: Usually no visible enhancement

MR Findings • TlWI o Hypointensity in mesial temporal lobes (hippocampus, amygdala), insula, cingulate gyrus, sub frontal cortex, inferior frontal WM o May see minimal mass effect o May see atrophy in chronic cases o No hemorrhage • T2WI o Hyperintensity in mesial temporal lobes (hippocampus, amygdala), insula, cingulate gyrus, subfrontal cortex, inferior frontal WM o May see minimal mass effect o No hemorrhage • FLAIR o Hyperintensity in temporal lobes, insula, cingulate gyrus, subfrontal cortex, inferior frontal WM o May see minimal mass effect • T2* GRE

o No hemorrhage o If blood products seen, consider herpes encephalitis • Tl C+: Patchy enhancement common

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lobe lesions

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Herpes Encephalitis

Astrocytoma

Status Epilepticus

Neoplasms and Tumorlike Lesions

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PARANEOPLASTIC SYNDROMES Key Facts Terminology

Pathology

• Remote neurological effect(s) of cancer, associated with extra-CNS tumors • Most common tumor: Small cell lung carcinoma • Limbic encephalitis (LE) is most common clinical paraneoplastic syndrome

• PSs divided into disorders of CNS, PNS, CNS/PNS, neuromuscular junction • Immune-mediated by autoantibodies or cytotoxic T-cell related mechanisms • 60% of patients have circulating serum autoantibodies • Epidemiology: < 1% of patients with systemic cancers develop paraneoplastic syndrome

Imaging Findings • Limbic encephalitis: Hyperintensity temporal lobes, limbic system

Top Differential • • • • •

in mesial

Clinical Issues

Diagnoses

• Up to 60% have no known primary tumor at presentation, many have no tumor found at workup • Treatment of primary ancy may improve neurologic symptoms of (25-45%)

Herpes encephalitis Low grade astrocytoma (grade II) Status epilepticus Gliomatosis cerebri (GC) Metastases

• Rare case reports show MR findings in other PSs o Paraneoplastic cerebellar degeneration (PCD): Cerebellar atrophy o Brainstem encephalitis: T2 hyperintensity in pons, cerebellar peduncles, basal ganglia

Nuclear Medicine

Findings

• FDG-PET: Increased glucose metabolism temporal lobes in LE patients

in medial

Imaging Recommendations • Best imaging tool: MR is most sensitive • Protocol advice o Contrast-enhanced MR with coronal T2 or FLAIR o Consider repeat MR if initial scan normal + high clinical suspicion

I DIFFERENTIAl.. DIAGNOSIS Herpes encephalitis • • • • • •

T2 hyperintensity in temporal lobes, limbic system Mass effect common; restricted DWI reported Late acute/subacute may hemorrhage Rapid onset, febrile illness HSV titers (CSF, serum) often negative May be indistinguishable from limbic encephalitis

Low grade astrocytoma (grade II) • Unilateral T2 hyperintense mass • May involve medial temporal lobe • No enhancement typical

Status epilepticus • Seizures may cause abnormal T2/FLAIR of mesial temporal lobes • Cortical enhancement is typical • Clinical history of seizures • Follow-up imaging may be necessary

Gliomatosis cerebri (GC) • Diffuse process, no predilection for limbic system • T2 hyperintensity in multiple contiguous lobes • Enlarges affected area

Metastases • Typically multi focal enhancing lesions • Primary tumor often known • No predilection for limbic system

I PATH 0 1..0GY General Features • General path comments o PSs divided into disorders of CNS, PNS, CNS/PNS, neuromuscular junction • CNS: Paraneoplastic cerebellar degeneration (PCD), opsoclonus/myoclonus, retinopathy • Peripheral NS: Sensory-motor neuropathy, autonomic neuropathy • Both CNS/PNS: Encephalomyelitis (limbic encephalitis, brainstem encephalitis, myelitis, motor neuron disease) • Neuromuscular junction: Lambert-Eaton myasthenic syndrome o Limbic encephalitis most common PS o PCD is second most common PS o Multiple PSs may occur in same patient o Some authors report non-paraneoplastic limbic encephalitis • Etiology o Immune-mediated by autoantibodies or cytotoxic T-cell related mechanisms o 60% of patients have circulating serum autoantibodies • Anti-Hu (lung cancer), limbic encephalitis • Anti-Ta (testicular germ-cell tumors), limbic encephalitis, brain stem encephalitis • Anti-Yo (breast & ovarian), paraneoplastic cerebellar degeneration • Anti-Tr (Hodgkin disease), paraneoplastic cerebellar degeneration • Anti-Ri (lung, breast, ovarian), opsoclonus/myoclonus • Epidemiology: < 1% of patients with systemic cancers develop paraneoplastic syndrome

Neoplasms and Tumorlike Lesions

6 145

Gross Pathologic & Surgical Features

Natural History & Prognosis

• LE: Ill-defined softening, discoloration of GM o Hippocampus, cingulate gyrus, pyriform cortex, frontal orbital surface of temporal lobe, insula, amygdalai typically bilateral • PCD: Cerebellar atrophy, gyral thinning • Brainstem encephalitis: Ill-defined brainstem softening

• Relates to primary neoplasm • Some reports suggest patients with PSs have more indolent primary tumor growth than those without • Relates to type of paraneoplastic syndrome o Slow long-term cognitive decline (limbic encephalitis) o Progressive ataxia, weakness (PCD, spinal cord degeneration)

Microscopic

Features

• Limbic encephalitis o Neuronal loss, reactive gliosis, perivascular infiltration of lymphocytes, microglial nodules o No neoplasm and no viral inclusions • PCD: Purkinje cell loss, microglial proliferation, Bergmann glia hyperplasia, decrease in granule cells • Brainstem encephalitis: Perivascular inflammatory infiltrates, glial nodules, neuronophagia

Presentation

146

• Most common signs/symptoms oLE: Memory loss, cognitive dysfunction, dementia, psychological features (anxiety, depression, hallucinations), seizures • Subacute presentation o PCD: Ataxia, incoordination, dysarthria, nystagmus • In patients> 50 years, cerebellar degeneration is paraneoplastic in 50% of cases, often precedes a remote malignancy o Brainstem encephalitis: Brainstem dysfunction including cranial nerve palsies, visual changes o PSs represent a spectrum of neurologic manifestations o In patients with a known primary tumor, must exclude other complications • Metastases, infection, metabolic disorder, chemotherapy effects • Clinical profile o Up to 60% have no known primary tumor at presentation, many have no tumor found at workup o Identification of antineuronal antibodies in serum or CSF facilitates diagnosis of PS and primary cancer o Primary neoplasm (LE) • Most common: Small cell lung carcinoma • Other =: GI, GU (ovary> renal> uterus), Hodgkin lymphoma, breast, testicular, thymus, neuroblastoma (pediatric) o Primary neoplasm (PCD) • GU (ovary), breast, lung, lymphoma o Primary neoplasm (opsoclonus/myoclonus) • Neuroblastoma, lung cancer o Primary neoplasm (Lambert-Eaton myasthenic syndrome) • Small cell lung cancer oLE: 90% have + CSF (pleocytosis, elevated protein, oligoclonal bands) • EEG reveals involvement of temporal lobes

Demographics • Age: Occurs at all ages, most commonly • Gender: No gender predominance

Treatment • Treatment of primary malignancy may improve neurologic symptoms of PSs (25-45%) • Primary neoplasm usually resected, +/- chemotherapy, radiation therapy • Treatment of paraneoplastic syndromes is variable o Treatment of primary tumor is best therapy o Steroids, immunoglobulins, plasmapheresis show variable success

1··.[)·IAG· •.~.().Sl'IC.·CI--I·.~·C!~tl$OC Consider • LE is only PS with defined imaging features • Paraneoplastic syndromes are often clinically evident before diagnosis of primary tumor • Repeat MR if initial scan normal and high clinical suspicion, as initial MR often normal in LE

Image Interpretation

Pearls

• Herpes encephalitis mimics LE on imaging, but has an acute presentation o Patients often initially treated with antiviral therapy until HSV titers final • Hemorrhage suggests herpes rather than limbic encephalitis

I SELECTED REFERENCES 1.

2.

3.

4.

5. 6.

7.

Messori A et al: Resolution of limbic encephalitis with detection and treatment of lung cancer: clinical-radiological correlation. Eur J Radiol. 45(1): 78-80, 2003 Dadparvar S et al: Paraneoplastic encephalitis associated with cystic teratoma is detected by Fluorodeoxyglucose positron emission tomography with negative magnetic resonance image findings. Clin Nucl Med. 28:893-6, 2003 Barnett M et al: Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody. J Neurol Neurosurg Psychiatry. 70:222-5,2001 Gultekin SH et al: Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 123: 1481-94, 2000 Scaravilli F et al: The Neuropathology of Paraneoplastic Syndromes. Brain Pathol. 9:251-60, 1999 Dalmau J et al: Paraneoplastic neurologic syndromes: pathogenesis and physiopathology. Brain Pathol. 9:275-84, 1999 Voltz R et al: A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N EnglJ Med. 340(23): 1788-95, 1999

adults

Neoplasms and Tumorlike Lesions

PARANEOPLASTIC SYNDROMES

Typical (Left) Coronal T2WI MR shows abnormal hyperintensity in the medial temporal lobes and right insula (arrow). Patient with severe memory loss, dementia. Symptoms improved after primary tumor removal. LE. (Right) Axial T1 C+ MR shows shows patchy enhancement of the medial temporal lobes bilaterally (arrows), typical for limbic encephalitis (LE).

Variant

(Left) Coronal T1 C+ MR

shows abnormal gyriform enhancement in the medial temporal lobes and left insula (arrow). The more typical patchy enhancement pattern of LEis seen in the hippocampi bilaterally. (Right) Axial T1WI MR shows hyperintensity representing blood products in the medial temporal lobes. Patient with treated lung cancer and LE.Blood products are rare in LE. Herpes encephalitis mimic.

Variant

(Left) Axial FLAIRMR shows abnormal hyperintensity in the right medial temporal lobe and midbrain. Patient with a history of limbic encephalitis and new brainstem symptoms. Positive anti-Hu autoantibody. (Right) Axial T1 C+ MR shows enhancement of the midbrain lesions (arrows) and subtle enhancement in the medial temporal lobe (curved arrow). Multiple paraneoplastic syndromes may occur in the same patient.

Neoplasms and Tumorlike Lesions

6. 147

PART I SECTION 7 prl.ary NOD-Neoplutlc cysts A broad spectrum of intracranial cysts can be identified on imaging studies. In this section we focus on nonneoplastic, noninfectious intracranial cysts. These cysts have variable etiologies and can arise from inclusion of embryonic endo- or ectodermal elements as well as acquired insults to the CNS such as trauma, hemorrhage or stroke. Cyst contents vary from watery CSF-Iike fluid to densely inspissated, dessicated mucous and can be lined with glial, epithelial or inflammatory cells. By general pathology category, the cysts covered in this section are: Cysts occurring as normal anatomic variants Enlarged perivascular (Virchow-Robin) spaces Congenital inclusion cysts Dermoid cyst Epidermoid cyst Arachnoid cyst Cysts derived from embryonic endo- or ectoderm Colloid cyst Neuroectodermal (neurenteric) cyst Miscellaneous cysts Neuroglial cyst Ependymal cyst Porencephalic cyst Choroid plexus cyst (xanthogranuloma) Pineal cyst Intratumoral cysts and cysts associated with primary brain tumors such as acoustic schwan noma are discussed in the section on CNS neoplasms. Parasitic cysts are considered in Section 8; cysts that occur with congenital malformations (such as Dandy-Walker spectrum) are covered in Section 1. Cavum septi pellucidi and cavum Vergae are generally not considered true cysts and are discussed in Part II of this book in the section on Ventricles and Cisterns.

SECTION 7: Primary Non-Neoplastic Cysts

Arachnoid Cyst Colloid Cyst Dermoid Cyst Epidermoid Cyst Neuroglial Cyst Enlarged Perivascular Spaces Pineal Cyst Choroid Plexus Cyst Ependymal Cyst Porencephalic Cyst Neurenteric Cyst

1-7-4 1-7-8 1-7-12 1-7-16 1-7-20 1-7-22 1-7-26 1-7-30 1-7-34 1-7-36 1-7-40

ARACHNOID

Coronal graphic shows an arachnoid cyst of the cerebellopontine angle cistern (arrow). The translucent, CSF-containing cyst displaces blood vessels and nerves around it.

and Synonyms

• Arachnoid cyst (AC), subarachnoid

cyst

CT Findings

Definitions • Intra-arachnoid CSF-filled sac that does not communicate with ventricular system

IIMAGING FINDINGS General

7 4

Axial NECT in a patient with head trauma shows a large left middle fossa arachnoid cyst (open arrow). A small acute SOH (arrows) is present over the right frontal, temporal lobes.

o Displays features of extra-axial mass • Displaces cortex • "Buckles" gray-white interface

ITERMINOLOGY Abbreviations

CYST

Features

• Best diagnostic clue: Sharply demarcated round/ovoid extra-axial cyst that follows CSF attenuation/signal • Location o 50-60% middle cranial fossa (MCF) o 10% cerebellopontine angle (CPA) o 10% suprasellar arachnoid cyst (SSAC), variable types • Noncommunicating = cyst of the membrane of Liliequist • Communicating = cystic dilation of interpeduncular cistern o 10% miscellaneous (convexity, quadrigeminal) • Size: Varies from a few mms to giant • Morphology o Sharply delineated translucent cyst

DDx: Arachnoid

• NECT o Usually CSF density • Hyperdense if intracyst hemorrhage present (rare) o May expand, thin/remodel bone • CECT: Doesn't enhance • CTA: Posterior displacement of MCA in MCF ACs • CT: Cisternography may demonstrate communication with subarachnoid space

MR Findings • TlWI o Sharply-marginated extra-axial fluid collection isointense with CSF o "Mickey mouse ears" appearance on coronal scans = SSAC plus lateral ventricles • T2WI: Isointense with CSF • PD/Intermediate: Isointense with CSF • FLAIR: Suppresses completely with FLAIR • T2* GRE: No blooming unless hemorrhage present (rare) • DWI: No restriction • T1 C+: Doesn't enhance • MRA: Cortical vessels displaced away from calvarium • MRV: Can demonstrate anomalies of venous drainage

Cyst

Primary Non-Neoplastic

Cysts

ARACHNOID

CYST

Key Facts • Subdural hygroma • Other nonneoplastic

Terminology • Arachnoid cyst (AC), subarachnoid cyst • Intra-arachnoid CSF-filled sac that does not communicate with ventricular system

Pathology

Imaging Findings • Best diagnostic clue: Sharply demarcated round/ovoid extra-axial cyst that follows CSF attenuation/signal • 50-60% middle cranial fossa (MCF) • Sharply-marginated extra-axial fluid collection isointense with CSF • FLAIR: Suppresses completely with FLAIR • DWI: No restriction

Top Differential

• MRS: Can predict pathology in > 90% of similar-appearing intracranial cystic lesions • Phase-contrast cine MR, flow quantification o Can help distinguish AC from enlarged subarachnoid space

Angiographic

Clinical Issues • Often asymptomatic,

Findings sonolucent

ACs

o Surrounded by gliotic brain, not compressed cortex o History of trauma, stroke common • Neurenteric cyst o Rare; spine, posterior fossa = most common locations o Often proteinaceous fluid • Neuroglial (glioependyma) cyst o Rare o Usually intra-axial

Findings

• Conventional: MCA, sylvian triangle displaced posteriorly in MCF ACs

I PATHOl.OCY

Nuclear Medicine

General Features

Findings

• SPECT o May show hypoperfusion

in brain adjacent to cyst

Imaging Recommendations • Best imaging tool: MR without, with contrast • Protocol advice: Add FLAIR, DWI

I DIFFERENTIAl.

DIACNOSIS

Epidermoid cyst • Scalloped margins • Insinuating growth pattern o Creeps along, into CSF cisterns o Surrounds, engulfs vessels and nerves • Doesn't suppress on FLAIR • Shows restricted diffusion (bright) on DWI

Chronic subdural hematoma • Signal not identical to CSF • Often bilateral, lentiform-shaped • May show enhancing membrane

Subdural hygroma • Often bilateral • Crescentic or flat configuration

Other nonneoplastic • Porencephalic

found incidentally

• FLAIR, DWI best seql,lences for distinguishing etiology of cystic-appearing intracranial masses

• Epidermoid cyst • Chronic subdural hematoma

Ultrasonographic

• 1% of all intracranial masses • If in middle fossa, temporal lobe may appear (or be) hypoplastic • Subdural hematoma (increased prevalence, especially MCF) • ACs displace but don't engulf vessels, cranial nerves

Diagnostic Checklist

Diagnoses

• Real Time: Useful for demonstrating in infants < 1 Y

cysts

cyst

cysts

• General path comments o Arachnoid layers contains CSF o Fluid-containing cyst with translucent membrane • Genetics o Usually sporadic, non-syndromic, rarely familial o Inherited disorders of metabolism • "Sticky" leptomeninges: Mucopolysaccharidoses • Etiology o Old concept = "splitting" or diverticulum of developing arachnoid o New concept (middle fossa ACs) • Frontal, temporal embryonic meninges (endomeninx) fail to merge as sylvian fissure forms • Remain separate, forming "duplicated" arachnoid o Possible mechanisms • Active fluid secretion by cyst wall • Slow distention by CSF pulsations • CSF accumulates by one-way (ball-valve) flow o Rare: ACs may form as shunt complication • Epidemiology o 1% of all intracranial masses o 2% incidental finding on imaging for seizure • Associated abnormalities o If in middle fossa, temporal lobe may appear (or be) hypoplastic o Subdural hematoma (increased prevalence, especially MCF)

Primary Non-Neoplastic Cysts

7 5

o Syndromic ACs • Acrocallosal (cysts in 1/3), Aicardi, Pallister-Hall syndromes

I SELECTED REFERENCES 1.

Gross Pathologic & Surgical Features • Arachnoid bulges around CSF-like cyst • ACs displace but don't engulf vessels, cranial nerves

Microscopic

2.

Features

• Wall consists of flattened but normal arachnoid • No inflammation, neoplastic change

cells

Staging, Grading or Classification Criteria • Galassi classification: 1 With 1 size/mass effect and ~ communication with basal cisterns o Type I: Small, spindle shaped, limited to anterior MCF o Type II: Superior extent along sylvian fissure; temp lobe displaced o Type III: Huge, fills entire MCF; frontal/temp/parietal displacement

3.

4.

5.

6.

7. 8. 9.

Presentation • Most common signs/symptoms o Often asymptomatic, found incidentally o Symptoms vary with size, location of cyst • Headache, dizziness, sensorineural hearing loss, hemifacial spasm/tic • SSACs may cause obstructive hydrocephalus

10.

11. 12.

Demographics • Age o ACs can be found at any age o 75% in children (symptom onset, if any, may be delayed) • Gender: M:F = 3-5:1 especially middle cranial fossa • Ethnicity: None reported

7 6

Natural History & Prognosis

13. 14.

15.

• May (but usually don't) slowly enlarge

Treatment • • • •

Treatment: Often none Resection (may be endoscopic) Fenestration Shunt (cystoperitoneal is common

16.

option) 17.

Consider

18.

• Could a cystic-appearing extra-axial mass be an epidermoid rather than an AC?

19.

Image Interpretation

Pearls

• FLAIR, DWI best sequences for distinguishing of cystic-appearing intracranial masses

etiology

20.

21.

Cokluk C et al: Spontaneous disappearance of two asymptomatic arachnoid cysts in two different locations. Minim Invasive Neurosurg. 46(2):110-2, 2003 Germano A et al: The treatment of large supratentorial arachnoid cysts in infants with cyst-peritoneal shunting and Hakim programmable valve. Childs Nerv Syst. 19(3):166-73,2003 Starzyk J et al: Suprasellar arachnoidal cyst as a cause of precocious puberty--report of three patients and literature overview. J Pediatr Endocrinol Metab. 16(3):447-55,2003 Alkadhi H et al: Somatomotor functional MRI in a large congenital arachnoid cyst. Neuroradiology. 45(3):153-6, 2003 Yu Q et al: Differential diagnosis of arachnoid cyst from subarachnoid space enlargement by phase-contrast cine MRI. Chin MedJ (Engl). 116(1):116-20,2003 Ulmer S et al: Chronic subdural hemorrhage into a giant arachnoidal cyst (Galassi classification type III). J Comput Assist Tomogr. 26(4):647-53, 2002 Mukherji SK et al: Diffusion-weighted magnetic resonance imaging. J Neuroophthalmol. 22(2):118-22, 2002 Koenig R et al: Spectrum of the acrocallosal syndrome. Am J Med Genet. 108(1):7-11, 2002 Gosalakkal JA: Intracranial arachnoid cysts in children: a review of pathogenesis, clinical features, and management. Pediatr Neurol. 26(2):93-8, 2002 Dutt SN et al: Radiologic differentiation of intracranial epidermoids from arachnoid cysts. Otol Neurotol. 23(1):84-92, 2002 Wang HS et al: Transcranial ultrasound diagnosis of intracranial lesions in children with headaches. Pediatr Neurol. 26(1):43-6, 2002 Kirollos RW et al: Endoscopic treatment of suprasellar and third ventricle-related arachnoid cysts. Childs Nerv Syst. 17(12):713-8,2001 Huang T et al: An unusual cystic appearance of disseminated low-grade gliomas. Neuroradiology. 43(10):868-74,2001 Sgouros S et al: Congenital middle fossa arachnoid cysts may cause global brain ischaemia: a study with 99Tc-hexamethylpropyleneamineoxime single photon emission computerised tomography scans. Pediatr Neurosurg. 35(4):188-94, 2001 Santamarta D et al: Arachnoid cysts: entrapped collections of cerebrospinal fluid variably communicating with the subarachnoid space. Minim Invasive Neurosurg. 44(3):128-34,2001 Schlachetzki F et al: Dynamic and three-dimensional trans cranial ultrasonography of an arachnoid cyst in the cerebral convexity. Technical note. J Neurosurg. 94(4):655-9, 2001 Shukla-Dave A et al: Prospective evaluation of in vivo proton MR spectroscopy in differentiation of similar appearing intracranial cystic lesions. Magn Reson Imaging. 19(1):103-10, 2001 Akaishi K et al: Endodermal cyst in the cerebellopontine angle with immunohistochemical reactivity for CA19-9. Clin Neuropathol. 19(6):296-9,2000 Park SH et al: Diffusion-weighted MRI in cystic or necrotic intracranial lesions. Neuroradiology. 42(10):716-21, 2000 Ibarra R et al: Role of MR imaging in the diagnosis of complicated arachnoid cyst. Pediatr Radiol. 30(5):329-31, 2000 Hoffmann KT et al: CSF flow studies of intracranial cysts and cyst-like lesions achieved using reversed fast imaging with steady-state precession MR sequences. AJNR Am J Neuroradiol. 21(3):493-502, 2000

Primary Non-Neoplastic

Cysts

Typical (Left) Axial FLAIRMR in an asymptomatic patient shows an extra-axial cystic-appearing mass in the middle cranial fossa (arrows). The temporal lobe is hypoplastic with posteriorly displaced temporal horn. (Right) Axial OWl MR (in the same case) shows no restriction. Presumptive diagnosis is arachnoid cyst. Epidermoid cyst would not suppress completely on FLAIRand would restrict on OWl.

Variant (Left) Sagittal Tl WI MR shows a large SSAC with elevation, compression of 3rd ventricle (arrow), anteriorly displaced infundibulum (open arrow). SSACs represent 5-70% of all ACs & often cause hydrocephalus. (Right) Coronal TlWI MR shows a very large middle cranial fossa AC that thins the overlying calvarium. Compared with size of the cyst, mass effect is minimal. Asymptomatic ACs of this size are uncommon.

7

Variant (Left) Sagittal TlWI MR shows a middle fossa AC with subacute intracystic hemorrhage (open arrow) and a large convexity subdural hematoma (arrows). (Right) Axial T2WI MR in the same case shows the middle fossa AC (arrow). Note dependent layering of acute intracystic hemorrhage forming a fluid-fluid level (open arrow) with CSF contained within the AC.

Primary Non-Neoplastic

Cysts

7

Axial graphic shows a classic CC at the foramen of Monro causing mild/moderate obstructive hydrocephalus. Note fornices and choroid plexus are elevated, stretched over the cyst (arrows).

Axial NECT shows a round hyperdense foramen of Monro mass (open arrow) causing mild hydrocephalus. Note fornices (white arrows) are draped and splayed around the mass. Classic Cc.

• Morphology: Well-demarcated ovoid/lobulated mass

Abbreviations

and Synonyms

• Colloid cyst (CC), paraphyseal

CT Findings

cyst

Definitions • Unilocular

mucin-containing

third ventricular

cyst

General Features

7 8

round>

• Best diagnostic clue: Hyperdense foramen of Monro mass on NECT • Location o > 99% wedged into foramen of Monro • Attached to anterosuperior 3rd ventricular roof • Pillars of fornix straddle, drape around cyst • Posterior part of frontal horns splayed laterally around cyst o < 1% other sites • Lateral, 4th ventricles • Parenchyma (cerebellum) • Extra-axial (prepontine, meninges) • Size o Variable (few mm up to 3 cm) o Mean size == 15 mm

• NECT o Density correlates inversely with hydration • 2/3 hyperdense • 1/3 iso/hypodense o +/- Hydrocephalus o Rare • Hypodense • Change in density/size • Hemorrhage (cyst "apoplexy") • Calcification • CECT o Usually doesn't enhance o Rare == rim enhancement

MR Findings • TlWI o Signal correlates with cholesterol concentration • 2/3 hyperintense on Tl WI • 1/3 isointense (small CCs may be difficult to see!) o May have associated ventriculomegaly • T2WI o Signal more variable • Generally reflects water content • Majority isointense to brain on T2WI (small cysts may be difficult to see!)

DDx: Colloid Cyst

CSF Flow Artifact

Xanthogranuloma

state

VBO

Primary Non-Neoplastic Cysts

Adenoma

COLLOID CYST Key Facts Imaging Findings

Pathology

• Best diagnostic clue: Hyperdense foramen of Monro mass on NECT • Mean size = 15 mm • Density correlates inversely with hydration state • 2/3 hyperintense on TlWI • Majority isointense to brain on T2WI (small cysts may be difficult to see!) • 25% mixed hypo/hyper ("black hole" effect) • Rare: May show peripheral (rim) enhancement

• From embryonic endoderm, not neuroectoderm! • 0.5-1.0% primary brain tumors • 15-20% intraventricular masses

Top Differential • • • •

• • •

•

Diagnoses

Clinical Issues • • • • •

Headache (50-60%) 3rd-4thdecade 90% stable or stop enlarging 10% enlarge May enlarge rapidly, cause coma/death!

Diagnostic Checklist

Neurocysticercosis CSF flow artifact (MR "pseudocyst") Neoplasm Choroid plexus mass

• Notify referring MD immediately if CC identified (especially if hydrocephalus is present)

o Less common findings • 25% mixed hypo/hyper ("black hole" effect) • Fluid-fluid level FLAIR: Does not suppress DWI: Does not restrict Tl C+ o Usually no enhancement o Rare: May show peripheral (rim) enhancement MRS: None reported

Imaging Recommendations • Protocol advice o NECT scan + contrast-enhanced MR o +/- Serial imaging for asymptomatic cysts < 1 em, no hydrocephalus

I DIFFERENTIAL DIAGNOSIS

o Ca++, rim/nodular enhancement common • Pituitary adenoma o Rare in 3rd ventricle o Enhances (usually strongly, uniformly)

Choroid plexus mass • Choroid plexus papilloma o Rare in 3rd ventricle o Tumor of early childhood • Xanthogranuloma o Rare in 3rd ventricle o Ovoid> round o Can be hyper- or hypodense +/- Ca++ o Can obstruct foramen of Monro o Can be indistinguishable on imaging studies • Choroid plexus cyst o Usually found in infants o Anechoic at ultrasound

Neurocysticercosis • • • •

Multiple lesions within parenchyma and cisterns Associated ependymitis or basilar meningitis common Ca++ common Look for scolex

CSF flow artifact (MR "pseudocyst") • Multiplanar technique confirms artifact • Look for phase artifact

Vertebrobasilar dolichoectasia (VBD)/aneurysm • Extreme VBD can cause hyperdense foramen of Monro mass • Look for "flow void," phase artifact on MR

Neoplasm • Subependymoma o Frontal horn of lateral ventricle o Attached to septum pellucidum o Patchy/solid enhancement • Craniopharyngioma o 3rd ventricle rare location o Usually not wedged into foramen of Monro, fornix

I PATHOLOGY General Features • General path comments: Gross appearance, location virtually pathognomonic • Genetics: None known • Etiology o From embryonic endoderm, not neuroectoderm! • Similar to other foregut-derived cysts (neurenteric, Rathke) • Ectopic endodermal elements migrate into velum interpositum o Contents accumulate from mucinous secretions, desquamated epithelial cells • Epidemiology o 0.5-1.0% primary brain tumors o 15-20% intraventricular masses • Associated abnormalities: Variable hydrocephalus

Gross Pathologic & Surgical Features • Smooth, spherical/ovoid well-delineated cyst o Thick gelatinous center, variable viscosity (mucinous or desiccated)

Primary Non-Neoplastic Cysts

7 9

o Rare

=

evidence for recent/remote

hemorrhage

Microscopic Features • Outer wall = thin fibrous capsule • Inner lining o Simple or pseudostratified epithelium o Interspersed goblet cells, scattered ciliated cells o Rests on thin connective tissue layer • Cyst contents o PAS + gelatinous ("colloid") material o Variable viscosity o +/- Necrotic leukocytes, cholesterol clefts • Immunohistochemistry o +/- Epithelial antigen reactivity (cytokeratins, EMA) • Electron microscopy o Resembles mature respiratory epithelium o Non-ciliated or tall columnar cells o Basal cells contain dense core vesicles

o 50% experience short-term memory disturbance (usually resolves) o Recurrence rare if resection complete • Options o Stereotactic aspiration (difficult with extremely viscous/solid cysts) o Imaging features that may predict difficulty with percutaneous therapy • Hyperdensity on CT/hypointensity on T2WI suggest high viscosity o Ventricular shunting o Observation (rare)

I DIAGNOSTIC

CHECKLIST

Consider • Notify referring MD immediately if CC identified (especially if hydrocephalus is present)

Image Interpretation

Pearls

• Could a possible CC be flow artifact?

Presentation • Most common signs/symptoms o Headache (50-60%) o Less common = nausea, vomiting, memory loss, altered personality, gait disturbance, visual changes o Acute foramen of Monro obstruction may lead to rapid onset hydrocephalus, herniation, death o 40-50% asymptomatic, discovered incidentally • 3-, 5-, 10 year incidence of developing cyst-related symptoms = 0, 0, 8% respectively • Clinical profile: Adult with headache

Demographics • Age o 3rd-4thdecade • Peak = age 40 • Rare in children (only 8% < 15 Y at diagnosis) • Gender: M = F

7 10

Natural History & Prognosis • Varies with presence/rate of growth, development of CSF obstruction • 90% stable or stop enlarging o Older age o Small cyst o No hydrocephalus o Hyperdense on NECT, hypointense on T2 weighted MR

• 10% enlarge o Younger patients o Larger cyst, hydrocephalus o Iso/hypodense on NECT, often hyperintense on T2WI o May enlarge rapidly, cause coma/death! • Prognosis excellent when CCs diagnosed early and excised

I SELECTED REFERENCES Hellwig D et al: Neuroendoscopic treatment for colloid cysts of the third ventricle: the experience of a decade. Neurosurgery. 52(3):525-33; discussion 532-3, 2003 2. Desai KI et al: Surgical management of colloid cyst of the third ventricle--a study of 105 cases. Surg Neurol. 57(5):295-302; discussion 302-4, 2002 Gupta A et al: Intraventricular neurocysticercosis 3. mimicking colloid cyst. Case report. ] Neurosurg. 97(1):208-10, 2002 4. Schroeder HW et al: Endoscopic resection of colloid cysts. Neurosurgery. 51(6):1441-4; discussion 1444-5, 2002 5. ]effree RL et al: Colloid cyst of the third ventricle: a clinical review of 39 cases.] Clinical Neurosci 8: 328-31, 2001 6. Ture U et al: Solid-calcified colloid cyst of the third ventricle. Clin Neurol Neurosurg. 103(1):51-5, 2001 7. ]effree RL et al: Colloid cyst of the third ventricle: a clinical review of 39 cases.] Clin Neurosci. 8(4):328-31, 2001 8. Pollack BE et al: A theory of the natural history of colloid cysts of the third ventricle. Neurosurgery 46:1077-83,2000 9. El Khoury C et al: Colloid cysts of the third ventricle: are MR imaging patterns predictive of difficulty with percutaneous treatment? A]NR Am] Neuroradiol. 21(3):489-92, 2000 10. Aggleton]P et al: Differential cognitive effects of colloid cysts in the third ventricle that spare or compromise the fornix. Brain. 123 (Pt 4):800-15, 2000 11. Pollock BE et al: A theory on the natural history of colloid cysts of the third ventricle. Neurosurgery. 46(5):1077-81: discussion 1081-3, 2000 12. Armao D et al: Colloid cyst of the third ventricle: imaging-pathologic correlation. A]NR Am] Neuroradiol. 21(8):1470-7, 2000 1.

Treatment • Most common treatment = complete surgical resection o Image-guided endoscopic approach increasingly common

Primary Non-Neoplastic Cysts

Typical (Left) Axial T2WI MR shows a colloid cyst (arrow) at the

foramen of Monro. The cyst is isointense with brain and is causing moderate but compensated hydrocephalus. (Right) Axial FLAIRMR in the same case shows the cyst (arrow) does not suppress and is hyperintense to brain. Note absence of transependymal CSF flow around atria of lateral ventricle.

Variant

(Left) Axial Tl WI M R shows a large, lobulated foramen of Monro mass in a

middle-aged patient with headache, obsuucuve hydrocephalus. (Right) Axial T2WI MR shows a mixed signal mass with a focus of profound hypointensity ("black hole" effect), indicated by the arrow. Unusually large, very viscous colloid cyst was found at surgery.

7

Variant

(Left) Axial TlWI MR shows a classic CC at the foramen

of Monro. The patient had only mild headaches. Observation rather than surgical intervention was chosen treatment. (Right) Axial Tl WI MR obtained when the patient developed sudden increase in headaches shows marked interval enlargement of the mass. The CC now appears less hyperintense and hydrocephalus is present.

Primary Non-Neoplastic

Cysts

11

Sagittal graphic illustrates frontal unruptured dermoid as well-circumscribed, fat-containing mass with interstitial ectodermal products/appendages.

o o o o

IIM;\(jIN~fl~prNGS

Round/lobulated, well-delineated, cystic mass Fat hypodensity 20% capsular Ca++ With rupture, droplets of fat disseminate in cisterns, may cause fat-fluid level within ventricles o Skull/scalp dermoid expands diploe o Frontonasal: Bifid crista galli, large foramen cecum + sinus tract o Rare "dense" dermoid: Hyperattenuating on CT • CECT: Generally no enhancement

General Features

MR Findings

• Best diagnostic clue: Fat appearance + droplets in cisterns, sulci, ventricles if ruptured • Location o Most often in sellar/parasellar/frontonasal region o Posterior fossai midline vermis & 4th ventricle o Intraventricular within tela choroidea in lateral, 3rd, or 4th ventricles o Extracranial sites = spine, orbit o Ruptured: Subarachnoid/intraventricular spread of contents • Size: Variable • Morphology: Well-circumscribed lipid containing mass

• TlWI o Unruptured: Hyperintense on Tl WI o Ruptured: Droplets very hyperintense on Tl WI • Fat suppression sequence confirms • Fat-fluid level in cyst, ventricles common o Rare "dense" dermoid: Very hyperintense on Tl WI • T2WI o Unruptured: Heterogeneous, from hypo- to hyperintense on T2WI • Chemical shift artifact in frequency encoding direction with long TR o Ruptured: Typically hyperintense droplets on T2WI o Rare "dense" dermoid: Very hypointense on T2 o With hair: Fine curvilinear hypointense elements • Tl C+: With rupture: Extensive MR enhancement possible from chemical meningitis

I TER.N1I~(!Jt()b¥ Abbreviations

and Synonyms

• Synonym: Ectodermal inclusion cyst

Definitions • Intracranial

7 12

Axial TlWI MR shows unruptured suprasellar dermoid as hyperintense fat-containing mass with fine curvilinear hypointensities from interstitial ectodermal products/appendages.

dermoids are congenital

inclusion cysts

CT Findings • NECT

,. -~

DDx: "Cystic" Intracranial Masses ~ 'I

r l

f

~

\,

Epidermoid

" ~

'1

) Craniopharyngioma

Primary Non-Neoplastic Cysts

Teratoma

DERMOID CYST Key Facts Imaging

Clinical Issues

Finding~

• Best diagnostic clue: Fat appearance + droplets in cisterns, sulci, ventricles if ruptured • T1 C+: With rupture: Extensive MR enhancement possible from chemical meningitis • Use fat-suppression sequence to confirm diagnosis

Top Differential

Diagnoses

• Epidermoid cyst • Craniopharyngioma • Teratoma

Diagnostic Checklist • Follows fat characteristics fat-suppressed MRI

Pathology • Rare: < 0.5% of primary intracranial tumors • Unilocular cyst with thick wall of connective

on NECT and T1WI

tissue

• MRS: Very strong and broad resonances from mobile lipids at 0.9 and 1.3 ppm

Angiographic

• Uncomplicated dermoid: Headache (320/0), seizure (30%) are most common symptoms • 30-50 Y • Gender: Slight male predilection • Larger lesions associated with higher rupture rate • Rupture can cause significant morbidity/mortality • Rare malignant transformation into SCCa • Treatment: Complete microsurgical excision

• Heterogeneous appearance containing CSF, lipid, and soft tissue components

calcification,

Lipoma

Findings

• Conventional o Normal or avascular mass effect o If ruptured, can see vasospasm • Interventional o Can relieve vasospasm with angioplasty o Dermoid-encased vessels may have i rupture risk

Imaging Recommendations • Best imaging tool: MRI, especially in setting of rupture • Protocol advice o Use fat-suppression sequence to confirm diagnosis o Chemical shift-selective sequence useful to detect tiny droplets

I DIFFERENTIAL DIAGNOSIS Epidermoid cyst • • • •

Most epidermoid cysts resemble CSF, not fat No dermal appendages 4-9x more common than dermoid Off-midline> midline: 40-50% in CPA, 10-15% para sellar/middle fossa, 10% diploic • MRI: Isointense to CSF except restricts on diffusion

Craniopharyngioma • Also suprasellar/midline, often with intra sellar component • CT: Cystic but with solid mural nodule, enhances> 90%, nodular calcification in majority • MRI: Commonly T1WI hypointense, T2WI hyperintense, enhances strongly • More common than dermoid: 3-5% primary intracranial tumors

Teratoma • Location similar, but usually pineal region • Mixture of two or more embryologic layers; ectoderm, mesoderm, endoderm • Often multicystic/multiloculated

• Homogeneous

fat> heterogeneous

lipid

IPATHOlOG¥ General Features • General path comments o Secretions, desquamated debris cause slow expansion o Rare "dense" dermoid • Likely from saponification of lipid/keratinized debris with secondary micro calcification in suspension, partially liquified cholesterol, high protein content, and hemosiderin/iron calcium complexes from hemorrhage • All reported (8 cases) occurred in posterior fossa • Genetics: Sporadic, except with Goldenhar syndrome • Etiology o Embryology (two theories) • Sequestration of surface ectoderm at lines of epithelial fuSion/along the course of normal embryonic invaginations • Inclusion of cutaneous ectoderm at time of neural tube closure; 3rd-5th week of embryogenesis • Epidemiology o Rare: < 0.5% of primary intracranial tumors o Intradural dermoid cysts 4-9x less common than epidermoid cysts • Associated abnormalities o Occipital/nasofrontal dermal sinus may be present; 89% of dermal sinuses associated with inclusion cysts o Goldenhar syndrome (aka oculoauriculovertebral dysplasia); congenital condition includes • Cranial lipomas and dermoids • Ocular dermoids • Anomalies of 1st and 2nd branchial arch derivatives

Primary Non-Neoplastic Cysts

7 13

• Cardiovascular, spinal defects

o Postulated prolonged or reparative process from foreign material leads to cellular atypia and neoplasia o May occur years after surgical resection

faeial, oral, auricular, visceral,

Gross Pathologic & Surgical Features • Unilocular cyst with thick wall of connective tissue • Contents = mixture of greasy lipid, cholesterol debris • Often contains hair and may contain bone or cartilage

Microscopic Features • Typical dermoid o Outer wall of fibrous connective tissue/collagen o Lining of keratinized squamous epithelium, dermal appendages (sebaceous/sweat glands, hair follicles) o Desquamated keratin, cellular debris o Calcifications are common, either dystrophic or in form of dental enamel • Malignant transformation into squamous cell carcinoma (SCCa) o Squamous cell predominance with some glandular differentiation o Suggestive of poorly differentiated squamous cell carcinoma with adenomatous component

Staging, Grading or Classification Criteria • Three classifications of dermoid inclusions, based on pathogenesis o Congenital cystic teratoma (true neoplasm derived from all three embryonic germ layers) o Congenital dermoid inclusion cyst (nonneoplastic epithelial-lined inclusion cyst) o Acquired implantation cyst (trauma, surgery, LP)

Treatment • Treatment: Complete microsurgical excision o Residual capsule may lead to recurrence o Rare SCCa degeneration within surgical remnants • Subarachnoid dissemination of contents may occur during operative/postoperative course o Cause aseptic meningitis or other complications (hydrocephalus, seizures, CN deficits) o Alternatively, disseminated fat particles can remain silent without radiological/neurological change • Justifies wait-and-see approach • Regular MRI and clinical exams are necessary to avoid complications

I DIAGNOSTIC

Image Interpretation • Follows fat characteristics fat-suppressed MRI I SELECTED 1.

2.

Presentation

7 14

3.

• Most common signs/symptoms o Uncomplicated dermoid: Headache (32%), seizure (30%) are most common symptoms • Less commonly hypopituitarism, diabetes insipidus, or cranial nerve (CN) defects • Suprasellar may present with visual symptoms • Become symptomatic because of neural/vascular compression o Cyst rupture causes chemical meningitis (6.9%)

Demographics

4.

5.

6.

7.

• Age o 30-50 y • Headache occurs primarily in younger patients • Seizures primarily occur in older patients • Gender: Slight male predilection

8.

9. 10.

Natural History & Prognosis • Benign, slow growing • Larger lesions associated with higher rupture rate • Rvpture can cause significant morbidity/mortality i Relatively rare and typically spontaneous o Seizure, coma, vasospasm, infarction, death • Dermoid + dermal sinus may cause infection, hydrocephalus • Rare malignant transformation into SCCa

CHECKLIST

11. 12.

13.

Pearls on NECT and T1WI

REFERENCES

Jain R et al: Imaging findings associated with childhood primary intracranial squamous cell carcinoma. A]NR Am] Neuroradiol. 24(1):109-11, 2003 Ecker RD et al: Delayed ischemic deficit after resection of a large intracranial dermoid: case report and review of the literature. Neurosurgery. 52(3):706-10; discussion 709-10, 2003 Stendel R et al: Ruptured intracranial dermoid cysts. Surg Neurol. 57(6):391-8; discussion 398, 2002 Brown]Y et al: Unusual imaging appearance of an intracranial dermoid cyst. A]NR Am] Neuroradiol. 22(10):1970-2, 2001 Calabro F et al: Rupture of spinal dermoid tumors with spread of fatty droplets in the CSF pathways. Neuroradiol 42: 572-9, 2000 Carvalho GA et al: Subarachnoid fat dissemination after resection of a cerebellopontine angle dysontogenic cyst: case report and review of the literature. Neurosurgery. 47(3):760-3; discussion 763-4, 2000 Manfre L et al: Absence of the common crus in Goldenhar syndrome. A]NR Am] Neuroradiol. 18(4):773-5, 1997 Martinez-Lage]F et al: Extradural dermoid tumours of the posterior fossa. Arch Dis Child. 77(5):427-30, 1997 Higashi S et al: Occipital dermal sinus associated with dermoid cyst in the fourth ventricle. A]NR Am] Neuroradiol. 16(4 Suppl):945-8, 1995 Poptani H et al: Characterization of intracranial mass lesions with in vivo proton MR spectroscopy. A]NR Am] Neuroradiol. 16(8):1593-603, 1995 Dagher AP et al: Intracranial cysts with and without rupture. I]NR 1:134-44, 1995 Smirniotopoulos]G et al: Teratomas, dermoids, and epidermoids of the head and neck. RadioGraphies 15:1437-55, 1995 Nishio S et al: Primary intracranial squamous cell carcinomas: report of two cases. Neurosurgery . 37(2):329-32, 1995

Primary Non-Neoplastic

Cysts

Typical (Left) Axial NECT shows hypodense, fat-containing pineal region dermoid (black arrow) which has ruptured. Fat droplets are present throughout subarachnoid space (white arrows) (Courtesy T. Swallow, MO). (Right) Axial T1WI MR of ruptured dermoid (black arrow). Fat droplets are present throughout subarachnoid space (white arrows) with ventricular fat-fluid levels (open black arrow) (Courtesy T. Swallow, MO).

Typical (Left) Axial T2WI MR ruptured dermoid (black arrow) contents dispersed in subarachnoid space wlventricular fat-fluid levels, associated with chemical shift artifact (white arrows) (Courtesy T.Swallow, MO). (Right) Axial T1 C+ MR shows ventricular fat-fluid levels (black arrow) and leptomeningeal (white arrow) with ependymal surface (open arrow) enhancement due to chemical meningitis (Courtesy T. Swallow, MO).

7

Other (Left) Coronal T1WI MR

atypical isointense appearance of dermoid in typical sellar midline location. (Right) Micropathology H&E stain demonstrates lining of keratinized squamous epithelium (white arrow) with sebaceous glands (black arrows), and desquamated keratin!cellular debris (open arrow).

Primary Non-Neoplastic Cysts

15

Sagittal graphic illustrates a multilobulated epidermoid, primarily within prepontine cistern. Significant mass effect displaces pons, cervicomedullary junction, and upper cervical spine.

I·TI2RMINQt.OOY

Radiographic Findings

Abbreviations

• Radiography o Diploic space epidermoids • May alter scalp, outer/inner skull tables, and epidural space appearance • Typically round or lobulated • Well delineated with sclerotic rim • Myelography: Intrathecal contrast delineates irregular lobulated tumor borders, extends into interstices

and Synonyms

• Synonym: Ectodermal inclusion cyst

Definitions • Intracranial epidermoids are congenital inclusion cysts

11J\tt}\(l;INqFl.NPlNGS

CT Findings

General Features

7 16

Sagittal TlWI MR demonstrates CSF isointense multilobulated epidermoid within prepontine, interpeduncular, and quadrigeminal cisterns.

• Best diagnostic clue: CSF-like mass insinuates cisterns, encases nerves/vessels • Location o 90% intradural, primarily in basal cisterns • Cerebellopontine angle (CPA) = 40-50% • Fourth ventricle = 17% • Para sellar/middle cranial fossa = 10-15% • Rarely in cerebral hemispheres = 1.5% • Brain stem location exceedingly rare • Intraventricular within tela choroidea of temporal horn, 3rd, or 4th ventricles o 10% extradural: Skull (intradiploic within frontal, parietal, occipital, sphenoid skull) as well as spine • Size: Variable • Morphology: Lobulated, irregular, "cauliflower-like" mass with "fronds"

• NECT o Round/lobulated mass o > 95% hypodense, resembling CSF o 10-25% Ca++ o Intradiplioc epidermoid: Bony erosion with sharply corticated margins o Rare variant = "dense" epidermoid • Secondary to hemorrhage, high protein, saponification of cyst debris to calcium soaps or iron-containing pigment • CECT: Usually none although margin of cyst may show minimal enhancement

MR Findings • TlWI o Often (",75%) slightly hyperintense to CSF on TlWI

DDx: "Cystic" Intracranial Masses

Arachnoid Cyst

Cysticercosis

Craniopharyngioma

Primary Non-Neoplastic

Cysts

Dermoid

EPIDERMOID CYST Key Facts Pathology

Terminology • Intracranial cysts

epidermoids

are congenital

inclusion

• Best diagnostic clue: CSF-like mass insinuates cisterns, encases nerves/vessels • Morphology: Lobulated, irregular, "cauliflower-like" mass with "fronds" • FLAIR: Usually doesn't completely null • Restricted diffusion yields high signal

Top Differential Diagnoses

•

•

• •

•

• •

tumors

Clinical Issues

Imaging Findings

• • • •

• 0.2-1.8% of all primary intracranial

Arachnoid cyst Inflammatory cyst (Le., neurocysticercosis) Cystic neoplasm Dermoid cyst

o Lobulated periphery may be slightly hyperintense than the center o Uncommonly hyperintense to brain ("white epidermoid") due to high triglycerides & unsaturated fatty acids o Uncommonly hypointense to CSF ("black epidermoid") • Presence of solid crystal cholesterol & keratin • Lack of triglycerides & unsaturated fatty acids T2WI o Often isointense (65%) to slightly hyperintense (35%) to CSF on T2WI o Very rarely hypointense due to calcification, t hydration, viscous secretions, iron pigments PD/Intermediate o Usually (95%) hyperintense to CSF o If CSF isodense, may see thin PD hyperintense rim (35%) from trapped CSF at rim interstices FLAIR: Usually doesn't completely null DWI o Restricted diffusion yields high signal o ADC = brain parenchyma Tl C+ o Usually none although margin of cyst may show minimal enhancement ("" 35%) o With malignant degeneration changes into enhancing tumor MRS: Resonances from lactate Significant magnetization transfer

Angiographic Findings • Conventional: Depending on location and size, may show avascular mass effect

Imaging Recommendations • Best imaging tool: MRI • Protocol advice o FLAIRwill often distinguish where as conventional sequences may not o Diffusion definitively distinguishes from arachnoid cyst (Ae)

• • • •

Most common symptom: Headache Cranial nerve 5, 7,8 neuropathy common Age: Presents at 20-60 y with peak at 40 Grows slowly: Epithelial component growth rate commensurate to that of normal epithelium • Rare malignant degeneration into squamous cell carcinoma (SCCa) reported • Treatment: Microsurgical resection

Diagnostic Checklist • Resembles CSF on imaging studies, except usually incomplete nulling on FLAIR

I DIFFER.ENTIAI... DIA~NOSIS Arachnoid cyst • Usually isointense to CSF on all standard sequences o Completely nulls on FLAIR o No restricted diffusion: Contains highly mobile CSF, ADC = stationary water • Rather than insinuate and engulf local structures, ACs displace them • Smooth surface, unlike lobulations of epidermoids

Inflammatory cyst (Le., neurocysticercosis) • Often enhances • Density/signal intensity usually not precisely like CSF • Adjacent edema, gliosis common

Cystic neoplasm • Attenuation/signal • Often enhances

intensity not that of CSF

Dermoid cyst • Usually at or near midline • Resembles fat, not CSF, and contains dermal appendages; often ruptured

I PATHOI...O~¥ General Features • General path comments o Grows by progressive desquamation with conversion to keratin/cholesterol crystals o Soft and pliable, conforms to shape of adjacent local structures/spaces • Genetics: Sporadic • Etiology o Congenital: Embryology • Arise from ectodermal inclusions during neural tube closure, 3rd to 5th week embryogenesis • Congenital intradural CPA epidermoids derived from cells of first branchial groove o Acquired: Develop as a result of trauma • Uncommon etiology for intracranial tumors

Primary Non-Neoplastic Cysts

7 17

• More common as spine etiology following LP • Epidemiology o 0.2-1.8% of all primary intracranial tumors o 4-9x more common than dermoid o Most common congenital intracranial tumor o Third most common CPA/lAC mass, after vestibular schwannoma, meningioma • Associated abnormalities: May have occipital/nasofrontal dermal sinus tract

Gross Pathologic & Surgical Features • Outer surface often has shiny, glistening "mother of pearl" appearance ("beautiful tumor") • Lobulated excrescences • Insinuating growth pattern (extends through cisterns, surrounds and encases vessels/nerves) • Cyst filled with soft, waxy, or flaky material • May invaginate into brain

Microscopic

Features

• Cyst wall = internal layer of simple stratified cuboidal squamous epithelium covered by fibrous capsule • Cyst contents = solid crystalline cholesterol, keratinaceous debris • No dermal appendages

I
18

liD·iIAGNOSTICCl'iECIN,.lIST Image Interpretation

I SELECTED 1.

2.

3. 4.

6. 7. 8.

9.

10. 11.

Demographics • Age: Presents at 20-60 y with peak at 40 • Gender: M = F

12.

Natural History & Prognosis • Grows slowly: Epithelial component growth rate commensurate to that of normal epithelium • Chemical meningitis possible from content leakage • Rare malignant degeneration into squamous cell carcinoma (SCCa) reported o Postulated prolonged or reparative process from foreign material leads to cellular atypia and neoplasia

13. 14.

15.

16.

Treatment • Treatment: Microsurgical resection o Complicated by investment of local structures o Recurrence common if incompletely removed o Subarachnoid dissemination of contents may occur during operative/postoperative course • May cause chemical meningitis • CSF seeding and implantation reported

Pearls

• Resembles CSF on imaging studies, except usually incomplete nulling on FLAIR • Hyperintensity indicating restricted diffusion or DWI is diagnostic

5.

• Most common signs/symptoms o Symptoms depend on location, growth pattern • Most common symptom: Headache • Cranial nerve 5, 7,8 neuropathy common • 4th ventricular cerebellar signs common, yet increased intracranial pressure rare • Less commonly hypopituitarism, diabetes insipidus • Seizures if in Sylvian fissure/temporal lobe o May remain clinically silent for many years

7

• Rare malignant degeneration of resection bed into SCCa reported o Often predated by frequent recurrences o May occur years after surgical resection

17.

18.

REFERENCES

Jain R et al: Imaging findings associated with childhood primary intracranial squamous cell carcinoma. AJNR Am J Neuroradiol. 24(1):109-11, 2003 Kaido T et al: Pathogenesis of intra parenchymal epidermoid cyst in the brain: a case report and review of the literature. Surg Neurol. 59(3):211-6, 2003 Mukherji SKet al: Diffusion-weighted magnetic resonance imaging. J Neuroophthalmol. 22(2):118-22, 2002 Chen S et al: Quantitative MR evaluation of intracranial epidermoid tumors by fast FLAIRimaging and echo-planar DWI. AJNR 22: 1089-96, 2001 Iaconetta G et al: Intracerebral epidermoid tumor: a case report and review of the literature. Surg Neurol. 55(4):218-22,2001 Kachhara R et al: Epidermoid cyst involving the brain stem. Acta Neurochir (Wien). 142(1):97-100,2000 MacKay CI et al: Epidermoid cysts of the pineal region. Childs Nerv Syst. 15(4):170-8, 1999 Murase S et al: Primary intracranial squamous cell carcinoma--case report. Neurol Med Chir (Tokyo). 39(1):49-54, 1999 Ochi M et al: Unusual CT and MR appearance of an epidermoid tumor of the cerebellopontine angle. AJNR Am J Neuroradiol. 19(6):1113-5, 1998 Caruso G et al: Supratentorial dorsal cistern epidermoid cyst in childhood. Pediatr Neurosurg. 29(4):203-7, 1998 Timmer FAet al: Chemical analysis of an epidermoid cyst with unusual CT and MR characteristics. AJNR Am J Neuroradiol. 19(6):1111-2, 1998 Chang KH et al: In vivo single-voxel proton MR spectroscopy in intracranial cystic masses. AJNR Am J Neuroradiol. 19(3):401-5, 1998 Kallmes DF et al: Typical and atypical MR imaging features of intracranial epidermoid tumors. AJR 169: 883-7, 1997 Malcolm GP et al: Microsurgical excision of a pontomedullary epidermoid cyst with prepontine extension: case report. Neurosurgery. 38(3):579-83; discussion 582-3, 1996 Nishio S et al: Primary intracranial squamous cell carcinomas: report of two cases. Neurosurgery. 37(2):329-32, 1995 Nassar SI et al: Epidermoid tumors of the fourth ventricle. Surg Neurol. 43(3):246-51, 1995 Mafee MF et al: Epidermoid cyst (cholesteatoma) and cholesterol granuloma of the temporal bone and epidermoid cysts affecting the brain. Neuroimaging Clin N Am. 4(3):561-78, 1994 Smirniotopoulos JG et al: Cerebellopontine angle masses: radiologic-pathologic correlation. Radiographies. 13(5):1131-47, 1993

Primary Non-Neoplastic Cysts

Typical (Left) Axial CECT shows non-enhancing, off-midline, CSF isodense epidermoid within quadrigeminal cistern (arrow). (Right) Axial OWl MR shows restricted diffusion within Sylvian fissure epidermoid. This sequence was diagnostic; all other sequences revealed CSF isointensity.

Typical (Left) Sagittal TlWI MR demonstrates CSF isointense epidermoid expanding the fourth ventricle. Partially empty sella was unrelated. (Right) Axial T2WI MR shows nearly CSF isointense epidermoid expanding the fourth ventricle.

7

Typical (Left) Axial T2WI MR shows nearly CSF isointense epidermoid within left anterior middle cranial fossa. (Right) Axial OWl MR shows restricted diffusion within left anterior middle cranial fossa epidermoid.

Primary Non-Neoplastic

Cysts

19

Axial graphic shows a classic neuroglial cyst. This well-delineated unilocular lesion does not communicate with the ventricles, contains clear fluid, and the surrounding brain is normal.

Axial T2WI MR shows a small neuroglial cyst adjacent to the frontal horn of the left lateral ventricle (arrow). The lesion contains CSF-like fluid (Courtesy R. Dietz, MD).

• CECT: Wall does not enhance

Abbreviations

MR Findings

and Synonyms

• Neuroglial cyst (NGC), giloependymal

• • • • • • •

cyst

Definitions • Benign epithelial-lined

General

7 20

CNS cyst

to CSF

Imaging Recommendations

Features

• Best diagnostic clue: Nonenhancing CSF-like parenchymal cyst with minimal/no surrounding abnormality • Location o May occur anywhere throughout neuraxis • Frontal lobe most common site • Intraparenchymal > extraparenchymal • Size: Varies from a few mm up to several cm • Morphology: Smooth, rounded, unilocular benign-appearing cyst

signal

• Best imaging tool: MR without, with contrast • Protocol advice: Include FLAIR, DWI

Porencephalic

cyst

• Communicates with ventricles • Usually adjacent brain shows gliosis, spongiosis

Enlarged perivascular

spaces (PVSs)

• Clusters of variable-sized cysts> single, unilocular • Usually midbrain, around anterior commissure

CT Findings • NECT o Well-delineated • Unilocular • No Ca++

Tl WI: Usually hypo intense, resembles CSF T2WI: Hyperintense PDjIntermediate: May be slightly hyperintense FLAIR: Usually suppresses T2* GRE: No blooming DWI: Typically no diffusion restriction Tl C+: No enhancement

Arachnoid

low density cyst

DDx: Neuroglial

Porencephalic

cyst

• Extra-axial • Does not have epithelial lining

Cyst

Cyst

Cysticercosis

Ependymal Cyst

Primary Non-Neoplastic Cysts

Enlarged PVSs

cyst

NEUROGLIAL CYST Key Facts Top Differential

Terminology • Benign epithelial-lined

CNS cyst

• • • • • •

Imaging Findings • Best diagnostic clue: Nonenhancing CSF-like parenchymal cyst with minimal/no surrounding signal abnormality • May occur anywhere throughout neuraxis

Diagnoses

Porencephalic cyst Enlarged perivascular spaces (PVSs) Arachnoid cyst Ependymal cyst Epidermoid cyst Infectious cyst

Ependymal cyst

Demographics

• Intraventricular

• Age: Any age; adults> children • Gender: M = F

Epidermoid

cyst

Natural History & Prognosis

• Cyst contents don't suppress on FLAIR, do restrict on DWI • Lined by stratified squamous epithelium

• Varies with cyst size, location • May be stable over many years

Infectious cyst

Treatment

• Cysts usually in subarachnoid • Ca++, enhancement common • Cysts usually < 1 cm

space, ventricles

• Observation

vs fenestration/drainage

I DIAGN@STIC

of cyst

CHECKLIST

I PATH@l.(Uili¥

Consider

General Features

• Parenchymal cysts that don't communicate with the ventricular system and have minimal/no surrounding gliosis may be NGC

• General path comments: Fluid-containing cavity buried within cerebral white matter • Etiology o Intraparenchymal: Lining of embryonic neural tube becomes sequestered within developing WM • Evagination of neuroectoderm along choroidal fissure • May contain ependymal or choroid cells as cyst lining o Subarachnoid space • Leptomeningeal neuroglial heterotopia postulated • Epidemiology: Uncommon « 1% of intracranial cysts)

Image Interpretation

Pearls

• Use FLAIR, DWI to help distinguish types of intracranial cysts

between different

I SEl.ECTED REFERENCES 1.

2.

Ironside JW et al: Neuroglial cysts. In Diagnostic Pathology of Nervous System Tumours, pp 532-534. Churchill-Livingstone, London, 2002 Tsuchida T et al: Glioependymal cyst in the posterior fossa. Clin Neuropathol. 16(1):13-6, 1997

Gross Pathologic & Surgical Features • Rounded, smooth, unilocular clear fluid resembling CSF

Microscopic

cyst, usually containing

I IMAGE

GAl.l.ERY

Features

• Varies from columnar (ependymal type) epithelium low cuboidal cells resembling choroid plexus o Variable expression of GFAP o Cytokeratin, EMA expression absent

to

I CLINICAl. ISSUES Presentation • Most common signs/symptoms: Headache • Other signs/symptoms o Seizures o Neurologic deficit (depends on cyst size, location)

(Left) Axial T2WI MR shows a well-demarcated cyst (arrow) adjacent to the left temporal horn in a patient with epilepsy. The cyst does not

communicate with the ventricle. Epithelial-lined Nee at surgery. Axial FLAIR MR in the same case shows complete suppression, no surrounding gliosis.

(Right)

Primary Non-Neoplastic Cysts

7 21

Coronal graphic shows enlarged perivascular spaces in the midbrain, thalami causing mass effect on the third ventricle and aqueduct with resulUng hydrocephalus.

lilERMI.N(tlI.QC¥ Abbreviations

and Synonyms

• Perivascular spaces (PVSs); Virchow-Robin

spaces

Definitions • Pial-lined interstitial fluid (ISF)-filled structures that accompany penetrating arteries but do not communicate directly with subarachnoid space

IIN1ACINGP1NOINdS General Features

7 22

• Best diagnostic clue: Fluid-filled spaces that look like CSF, surround/accompany penetrating arteries • Location o Most common site for normal PVSs = basal ganglia (cluster around anterior commissure) o Other common locations • Midbrain • Deep white matter • Subinsular cortex, extreme capsule o Less common sites • Thalami • Dentate nuclei • Corpus callosum, cingulate gyrus

Axial T2WI MR shows clusters of variable-sized cysts in the midbrain and adjacent temporal lobe. Note expansion of the right cerebral peduncle by the cysts. Biopsy-proved giant PVSs.

o Most common location for expanded ("giant" or "tumefactive") PVSs = midbrain • Can be found almost anywhere • BUT almost never involve cortex (PVSs expand within subcortical white matter) • Size o PVSs usually 5 mm or less • Occasionally expand, attain large size (up to several cm) • May cause focal mass effect, hydrocephalus • Widespread dilatation of PVSs may look very bizarre • Morphology o Clusters of well-demarcated, variably-sized parenchymal cysts o Multiple> solitary cysts

CT Findings • NECT o Clusters of round/ovoid/linear/punctate lesions • Low density (attenuation = CSF) • No Ca++ • CECT: Don't enhance

MR Findings • TlWI o Multiple well-delineated cysts isointense with CSF o Focal mass effect common

DDx: Prominent PVSs

Lacunes

cyst-like

Cystic Astrocytoma

Primary Non-Neoplastic

Neurocysticercosis

Cysts

ENLARGED PERIVASCULAR SPACES Key Facts • Pial-lined interstitial fluid (ISF)-filled structures that accompany penetrating arteries but do not communicate directly with subarachnoid space

• • • •

Imaging Findings

Top Differential

Terminology

• Most common site for normal PVSs = basal ganglia (cluster around anterior commissure) • Most common location for expanded ("giant" or "tumefactive") PVSs = midbrain • PVSs usually 5 mm or less • Occasionally expand, attain large size (up to several

em) • Clusters of round/ovoid/linear/punctate cyst-like lesions • Multiple well-delineated cysts isointense with CSF • Focal mass effect common

•

• •

• • •

•

• Expand overlying gyri • Midbrain enlarged PVSs may compress aqueduct/3rd ventricle, cause hydrocephalus T2WI o Appear isointense with CSF • Signal intensity within PVSs actually measures slightly < CSF o No edema in adjacent brain, may have 1 SI PD/lntermediate: Isointense with CSF FLAIR o Suppress completely o 25% have minimal increased signal in brain surrounding enlarged PVSs T2* GRE: No blooming DWI: No restricted diffusion Tl C+ o No enhancement o +/- Visualization of penetrating arteries with contrast MRS: Spectra in adjacent brain typically normal

Angiographic

Findings

• Conventional: High-resolution DSA may depict penetrating arteries in area of enlarged PVSs

Nuclear Medicine

Findings

• Tc-99m HMPAO SPECT normal, shows no ischemic changes

Imaging Recommendations • Best imaging tool: Routine MR + FLAIR, DWI • Protocol advice: Contrast optional

I DIFFERENTIAL DIAGNOSIS Lacunar infarcts • Older patients • Common in basal ganglia, white matter • Adjacent parenchymal hyperintensity

Cystic neoplasm • Usually in pons, cerebellum, thalamus/hypothalamus • Single> multiple cysts

Suppress completely DWI: No restricted diffusion No enhancement Best imaging tool: Routine MR + FLAIR, DWI

Diagnoses

• Lacunar infarcts • Cystic neoplasm • Infectious/inflammatory

cysts

Clinical Issues • PVSs occur in alllocatiollS, at all ages and are easily seen in most patients on 3T imaging • "Leave me alone" lesion that should not be mistaken for serious disease

• Signal not quite like CSF • Parenchymal signal abnormalities • May enhance

Infectious/inflammatory

common

cysts

• Neurocysticercosis o Cysts often have scolex o Most are < 1 em o Can be multiple but don't typically occur in clusters o Cyst walls often enhance o Surrounding edema often present • Other parasites o Hydatid cysts often unilocular, almost all in children o Multilocular parasitic cysts typically enhance, mimic neoplasm more than PVSs

I PATHOLOGY General Features • General path comments o Enlarged cystic-appearing spaces o Actually contain interstitial fluid, not CSF • Genetics o Usually normal unless PVSs expanded by un degraded mucopolysaccharides (Hurler, Hunter disease) o PVSs expand in some congenital muscular dystrophies • Etiology o Theory = ISF accumulates between penetrating vessel, pia o Egress of ISF blocked, causing cystic enlargement of PVS • Epidemiology o Common nonneoplastic brain "cyst" o Common cause of multifocal hyperintensities on T2WI • Associated abnormalities o Hydrocephalus (midbrain expanding PVSs can obstruct aqueduct) o "Cysts" caused by enlarged/obstructed PVSs reported with pituitary adenomas, large aneurysms

Primary Non-Neoplastic Cysts

7 23

Gross Pathologic & Surgical Features • Smoothly demarcated,

Microscopic

fluid-filled cyst(s) 4.

Features

• Single or double layer of invaginated pia • Pia becomes fenestrated, disappears at capillary level • PVSs usually very small in cortex, often enlarge in subcortical white matter • Surrounding brain usually lacks gliosis, amyloid deposition

5.

6.

7.

8.

Presentation • Most common signs/symptoms o Usually normal, discovered incidentally at imaging/autopsy o Nonspecific symptoms (e.g., headache) • Clinical profile: Patient with nonspecific, nonlocalizing symptoms who has bizarre, alarming multi cystic-appearing brain mass initially diagnosed as "cystic neoplasm"

Demographics

9.

10.

11.

• Age

o PVSs occur in all locations, at all ages and are easily seen in most patients on 3T imaging o Present in 25-30% of children (benign normal variant) o Enlarged PVSs • Mean age = mid 40s • Gender: Giant PVSs: M:F = 1.8:1

12. 13.

perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol. 29(2):106-17,2003 Papayannis CE et al: Expanding Virchow Robin spaces in the midbrain causing hydrocephalus. A]NRAm] Neuroradiol. 24(7):1399-403, 2003 Kitajima M et al: Central nervous system lesions in adult T-cell leukaemia: MRI and pathology. Neuroradiology. 44(7):559-67, 2002 Ozturk MH et al: Comparison of MR signal intensities of cerebral perivascular (Virchow-Robin) and subarachnoid spaces.] Comput Assist Tomogr. 26(6):902-4, 2002 Weller RO: How well does the CSF inform upon pathology in the brain in Creutzfeldt-]akob and Alzheimer's diseases? ] Pathol. 194(1):1-3,2001 Seto T et al: Brain magnetic resonance imaging in 23 patients with mucopolysaccharidoses and the effect of bone marrow transplantation. Ann Neurol. 50(1):79-92, 2001 Song C] et al: MR imaging and histologic features of subinsular bright spots on T2-weighted MR images: Virchow-Robin spaces of the extreme capsule and insular cortex. Radiology. 214(3):671-7, 2000 Weller RO et al: Cerebral amyloid angiopathy: accumulation of A beta in interstitial fluid drainage pathways in Alzheimer's disease. Ann N Y Acad Sci. 903:110-7,2000 Laitinen LVet al: Dilated perivascular spaces in the putamen and pallidum in patients with Parkinson's disease scheduled for pallidotomy: a comparison between MRI findings and clinical symptoms and signs. Mov Disord. 15(6):1139-44, 2000 Masalchi M et al: Expanding lacunae causing triventricular hydrocephalus.] Neurosurg 91: 669-74, 1999 Adachi M et al: Dilated Virchow-Robin spaces: MRI pathological study. Neuroradiol40: 27-31, 1998

Natural History & Prognosis • Usually remain stable in size • Occasionally continue to expand

Treatment

7

• "Leave me alone" lesion that should not be mistaken for serious disease • Shunt ventricles if midbrain lesions cause obstructive hydrocephalus

24

Consider • Could a multi-cystic nonenhancing be a cluster of enlarged PVSs?

Image Interpretation

mass on MR or CT

Pearls

• Prominent but normal PVSs are identified in nearly all patients and in virtually every location at 3T imaging

1. 2.

3.

Salzman K et al: Giant "tumefactive" perivascular spaces. A]NR (in press), 2004 Nishi K et al: Histochemical characteristic of perivascular space in the brain with an advanced edema. Leg Med (Tokyo). 5 Suppl1:S280-4, 2003 Preston SD et al: Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the

Primary Non-Neoplastic

Cysts

Typical (Left) Coronal graphic shows normal PVSs as they

accompany penetrating arteries into the basal ganglia, subcortical white matter. Normal PVSs cluster around the anterior commissure but occur in all areas. (Right) Axial T2WI MR obtained on 3T scan in a 60 yo shows prominent but completely normal PVSs in the basal ganglia (open arrows), subinsular cortex (arrows) and white matter (curved arrows).

Variant (Left) Axial T2WI MR shows

multiple bizarre-appearing cysts in the centrum semiovale of both hemispheres. The cysts vary in size, expand but otherwise spare the overlying cortex (arrows). Enlarged PVSs. (Right) Coronal T1 C+ MR in a 7 y male shows a cluster of cysts in the dentate nuclei. The cysts are similar to CSF in signal and do not enhance. Note focal mass effect on 4th ventricle. Enlarged PVSs.

7

Variant (Left) Axial graphic shows

enlarged PVSs in the white matter of the occipital lobe, centrum semiovale, corpus callosum, and cingulate gyrus. Note focal expansion of overlying cortex. (Right) Axial FLAIRMR in an asymptomatic patient shows clusters of variable-sized CSF-intensity cysts with minimal surrounding gliosis, expansion of overlying gyri. Enlarged PVSs (Courtesy L. Valanne, MO).

Primary Non-Neoplastic

Cysts

25

Sagittal graphic shows a small cystic lesion within the pineal gland (arrows). Small benign pineal cysts (PCs) are often found incidentally at autopsy or imaging.

Abbreviations

o Sharply-demarcated, smooth cyst behind 3rd ventricle • Fluid iso-/slightly hyperdense to CSF • 25% Ca++ in cyst wall • Rare: Very hyperdense cyst with acute hemorrhage ("pineal apoplexy") • CECT: Rim or nodular enhancement

and Synonyms

• Pineal cyst (PC); glial cyst of pineal gland

Definitions • Nonneoplastic

intrapineal

Sagittal T1 C+ MR shows a classic benign pineal cyst (arrows) with rim enhancement, mild mass effect (note slight compression, displacement of tectal plate) (Courtesy L. Rudolf, MO).

glial-lined cyst

MR Findings

General Features

26

• Best diagnostic clue: Homogeneous fluid-filled mass above, clearly distinct from tectum • Location: Above tectum, below internal cerebral veins (ICVs) • Size: Most are small « 1 cm) but may be up to 2 cm or more • Morphology o Round/ovoid, relatively thin-walled cyst • May flatten tectum, occasionally compress aqueduct • Variable hydrocephalus (enlarged 3rd, lateral ventricles; normal 4th V) with large cysts

CT Findings • NECT

• TlWI o 55-60% slightly hyperintense to CSF on Tl WI o 40% isointense o 1-2%: Hemorrhage (heterogenous signal intensity) • T2WI: Iso/hyperintense to CSF • PD/Intermediate: 85-90% hyperintense to CSF • FLAIR: Doesn't suppress (moderately hyperintense) • T2* GRE

o Usually normal o Uncommon: Blooming caused by old or recent hemorrhage • DWI: Typically shows no restriction • Tl C+ o 60% enhance • Partial/complete rim, nodular • Cystic areas may fill in on delayed scans, resemble solid tumor • MRV: Internal cerebral veins (ICVs) may be elevated by large lesions

DDx: Pineal Cyst

..

~ .'

1 ..•

."

I~"\ '"'

,4

.

t .\\

~

' l_

.J~.--:'~~j ~'. ~ Pineocytoma

Epidermoid

Cyst

Arachnoid

Primary Non-Neoplastic

Cyst

Cysts

Cystic Pineal

PINEAL CYST Key Facts Clinical Issues

Terminology • Nonneoplastic

intrapineal

glial-lined cyst

Imaging Findings • Best diagnostic clue: Homogeneous fluid-filled mass above, clearly distinct from tectum • 55-60% slightly hyperintense to CSF on IIWI • PD/Intermediate: 85-90% hyperintense to CSF • FLAIR: Doesn't suppress (moderately hyperintense) • 60% enhance

Top Differential • • • •

Diagnoses

• MRS: None reported

Diagnostic Checklist

IPATHOlOG¥

Findings

• Conventional o Arterial phase almost always normal o Venous phase • May show elevation, displacement of ICVs if large PC present • Thalamostriate veins splayed, bowed if hydrocephalus present

Imaging Recommendations • Best imaging tool: MR without, with contrast • Protocol advice: Use thin sections (3 mm or less) for detecting, defining lesions in this anatomically complex region

I DIFFERENTIAL DIAGNOSIS Normal pineal gland (can be cystic) • Three anatomic appearances imaging o Nodule (52%) o Crescent (26%) o Ring-like (22%)

on contrast-enhanced

General Features • General path comments o Embryology • Primitive pineal diverticulum divides into pineal recess, cavum pineal • Cavum pineal usually obliterated by glial fibers • Incomplete obliteration may leave residual cavity • Genetics: None known • Etiology o Etiology-pathogenesis: 3 major theories • Enlargement of embryonic pineal cavity • Ischemic glial degeneration +/- hemorrhagic expansion • Small pre-existing cysts enlarge with hormonal influences • Epidemiology o 1-4% prevalence at imaging o 20-40% microscopic cysts within pineal gland found at autopsy • Assodated abnormalities: Hydrocephalus (uncommon)

Gross Pathologic & Surgical Features

Pineocytoma • Usually solid components present; purely cystic tumors occur but are less common • Cystic pineocytomas occur, may be indistinguishable on imaging studies, require histology for definitive diagnosis • Both pineal cyst, indolent pineocytoma may not change on serial imaging

Epidermoid cyst • Quadrigeminal dstern relatively rare location • "Cauliflower" configuration • Mild/moderate restriction on DWI

Arachnoid cyst • No Ca++, enhancement • Follows CSF attenuation,

=

• PCs are often asymptomatic, represent an incidental MRfinding • A heterogenous, nodular or ring-like enhancing pineal mass may be a benign cyst, not neoplasm!

Normal pineal gland (can be cystic) Pineocytoma Epidermoid cyst Arachnoid cyst

Angiographic

• Vast majority clinically silent, discovered inddentally • Incidence of pineal cysts among women between 21-30 y significantly higher than any other group • Gender: F:M 3:1 • Size generally remains unchanged in males • Cystic expansion of pineal in some females begins in adolescence, decreases with aging

• Smooth, soft, tan to yellow cyst wall • Fluid contents vary from clear yellow (most common) to hemorrhagic • 80% < 10 mm • Can be large (reported up to 4.5 cm)

Microscopic

Features

• Delicate (usually incomplete) outer leptomeningeal fibrous layer • Middle layer of attenuated pineal parenchyma, with/without Ca++ • Inner layer of glial tissue with variable granular bodies, hemosiderin -laden macrophages • Compare with pineocytoma o Pseudolobular arrangement of small, round cells with pleomorphic nuclei o "Pinocytic" rosettes

signal intensity

Primary Non-Neoplastic Cysts

7 27

o Neuronal differentiation positive cells)

(NSE-, synaptophysin 1.

Presentation • Most common signs/symptoms o Vast majority clinically silent, discovered incidentally o Large cysts (> 1 em) may become symptomatic • 50% headache (aqueduct compression, hydrocephalus) • 10% Parinaud syndrome (tectal compression) • Very rare: "Pineal apoplexy" with intracystic hemorrhage, acute hydrocephalus, sudden death • Clinical profile: Young female with nonfocal headache

Demographics • Age o Mean age == 28 years o Incidence of pineal cysts among women between 21-30 y significantly higher than any other group o Incidence in women decreases with age o No change in males • Gender: F:M == 3:1 • Ethnicity: None known

Natural History & Prognosis • Size generally remains unchanged in males • Cystic expansion of pineal in some females begins in adolescence, decreases with aging • Rare: Sudden expansion, hemorrhage ("pineal apoplexy")

Michielsen G et al: Symptomatic pineal cysts: clinical manifestations and management. Acta Neurochir (Wien). 144(3):233-42; discussion 242, 2002 2. Korogi Y et al: MRI of pineal region tumors. J Neurooncol. 54(3):251-61,2001 3. Barboriak DP et al: Serial MR imaging of pineal cysts: implications for natural history and follow-up. AJRAm J Roentgenol. 176(3):737-43,2001 4. Tartara F et al: Glial cyst of the pineal gland: case report and considerations about surgical management. J Neurosurg Sci. 44(2):89-93, 2000 5. Engel U et al: Cystic lesions of the pineal region--MRI and pathology. Neuroradiology. 42(6):399-402, 2000 6. Kang H-S et al: Large glial cyst of the pineal gland: a possible growth mechanism. J Neurosurg 88: 138-40, 1998 7. Lantos PL et al: Tumors of the nervous system. In Graham Dr, Lantos PL (eds): Greenfield's Neuropathology, 6th ed., pp 677-82, Arnold, London, 1997 8. Sawamura Y et al: Magnetic resonance images reveal a high incidence of asymptomatic pineal cysts in young women. Neurosurg 37: 11-16, 1995 9. Sener RN: The pineal gland: a comparative MR imaging study in children and adults with respect to normal anatomical variations and pineal cysts. Pediatr Radiol 25: 245-8,1995 10. FainJS et al: Symptomatic glial cysts of the pineal gland. J Neurosurg 80: 454-60, 1994 11. Fleege MA et al: Benign glial cysts of the pineal gland: Unusual imaging characteristics with histologic correlation. AJNR 15: 161-6, 1994 12. Di Constanzo A et al: Pineal cysts: an incidental MRI finding? J Neurol Neurosurg Psychiatr 56: 207-8, 1993

Treatment • Usually none • Atypical/symptomatic lesions may require stereotactic aspiration or biopsy/resection o Preferred approach == infra tentorial supra cerebellar

7 28

Consider • PCs are often asymptomatic, represent an incidental MRfinding • MR appearance of PCs varies from o Uncomplicated cystic mass to o Mass with hemorrhage, enhancement, or hydrocephalus • A heterogenous, nodular or ring-like enhancing pineal mass may be a benign cyst, not neoplasm!

Image Interpretation

Pearls

• Can't distinguish benign PC from neoplasm (pineocytoma) on basis of imaging studies alone • Histopathology required for definitive diagnosis o May be complicated by tissue fragmentation, cyst collapse, reactive changes in adjacent tissue

Primary Non-Neoplastic Cysts

Tvpical (Left) Sagittal Tl WI MR in a

young female with headaches shows a cystic-appearing pineal gland (arrow). Signal intensity is slightly greater than CSF in the adjacent 3rd ventricle, quadrigeminal cistern. (Right) Axial FLAIRMR (in the same patient) shows the pineal cyst (arrows) does not suppress, is moderately hyperintense. Serial imaging studies over 3 years showed no change. Presumed benign pineal cyst.

Variant (Left) Axial NECT in a young

female with sudden onset of headache, diplopia shows a 73 mm hyperdense mass in the pineal gland (open arrow). Note calcific foci (solid arrows). (Right) Axial T2WI MR in the same case shows a mixed, predominately hypointense lesion of the pineal (arrow). No enhancement was present. Hemorrhagic pineal cyst found at surgery (Courtesy P.Oedick, MO).

7

Variant (Left) Sagittal TlWI MR shows a pineal region mass (arrow) that is slightly hyperintense to CSF.This lesion was found incidentally in a patient scanned for followup of pituitary adenoma resection. (Right) Sagittal Tl C+ MR shows rim enhancement with a central enhancing nodule. This "target" appearance is atypical for a pineal cyst, found at surgery.

Primary Non-Neoplastic

Cysts

29

Axial graphic shows multiple cystic masses in the choroid plexus glomi (arrows), often seen incidentally on scans of middle-aged and older adults. Most are degenerative xanthogranulomas.

Abbreviations

and Synonyms

• Choroid plexus cyst (CPe); choroid plexus xanthogranuloma (CPX)

Definitions • Nonneoplastic, noninflammatory cysts of choroid plexus lined by compressed connective tissue found at both ends of age spectrum o Adult: CPC is common incidental finding on imaging studies in older patients (approximately 40% prevalence) o Fetus: CPCs seen in 1% of second trimester pregnancies

7

IIMA(jIN.G·.flNioIN<.JS General Features

30

• Best diagnostic clue o Older patient with "bright" choroid plexi on MRI o Fetus or newborn with large (> 2 mm) choroid plexus cyst(s) on US • Location o Atria of lateral ventricles most common site • Attached to or within choroid plexus • Usually bilateral

Axial CECT in a 60 year old male scanned for trauma shows cystic-appearing masses attached to the choroid plexus glomi (arrows). Classic xanthogranulomas (benign nonneoplastic cysts).

o Less common: 3rd ventricle • Size o Variable • Usually small (2-8 mm) • Often multiple • Rare: Large cysts (> 2 cm) • Morphology: Cystic or nodular/partially mass(es) in choroid plexus glomi

CT Findings • NECT o Iso- or slightly hyperdense compared to CSF o Irregular, peripheral Ca++ in majority of adult cases • CECT: Varies from none to rim or solid enhancement

MR Findings • • • • • • •

T1WI: Iso/slightly hyperintense compared to CSF T2WI: Hyperintense compared to CSF PD/lntermediate: Hyperintense FLAIR: 2/3rd iso-, 1/3rd hypointense on FLAIR T2* GRE: Blooms with intracystic hemorrhage (rare) DWI: 65% show restricted diffusion (high signal) Tl C+ o Enhancement varies from none to strong o Variable pattern (solid, ring, nodular) o Delayed scans may show filling in of contrast within cysts

DDx: Choroid Plexus Cyst

Ependymal

Cyst

Ch Plexus Papilloma

cystic

Epidermoid

Primary Non-Neoplastic

Cyst

Cysts

US Pseudolesion

CHOROID PLEXUS CYST Key Facts Terminology • Nonneoplastic, noninflammatory cysts of choroid plexus lined by compressed connective tissue found at both ends of age spectrum • Adult: CPC is common incidental finding on imaging studies in older patients (approximately 40% prevalence) • Fetus: CPCs seen in 1% of second trimester pregnancies

Imaging Findings • Older patient with "bright" choroid plexi on MRI • Fetus or newborn with large (> 2 mm) choroid plexus cyst(s) on US • Usually bilateral • Often multiple • Iso- or slightly hyperdense compared to CSF

Ultrasonographic

• • • •

T1WI: Iso/slightly hyperintense compared to CSF FLAIR: 2/3rd iSo-, 1/3rd hypointense on FLAIR DWI: 65% show restricted diffusion (high signal) Enhancement varies from none to strong

Top Differential Diagnoses • • • • • •

Ultrasound "pseudolesion" Ependymal cyst Neoplasm Infectious/inflammatory cysts Epidermoid cyst Villous hyperplasia of choroid plexus

Diagnostic Checklist • Most common cause of choroid plexus mass in adults is benign degenerative cyst (xanthogranuloma)

Sturge-Weber syndrome

Findings

• Real Time o Prenatal US • Cyst> 2 mm surrounded by echogenic choroid • In absence of other abnormalities, low risk for chromosomal abnormalities

Imaging Recommendations • Best imaging tool o Adults: MR without, with contrast o Fetus, newborn • Antenatal: Maternal US or MR • Postnatal: US of infant with anterior, posterior, mastoid fontanelles as acoustic windows • Protocol advice o MR without/with contrast, FLAIR o U/S transverse view of lateral ventricle at atrial level

• Enlarged "angiomatous" malformation

choroid plexus ipsilateral to

Infectious/inflammatory

cysts

• Neurocysticercosis (NCe) o Multiple cysts common (parenchyma, subarachnoid space, ventricles) o Not associated with choroid plexus o May be migratory o Look for scolex, other signs of NCC (e.g., parenchymal Ca++) • Other parasites less commonly intraventricular

Epidermoid cyst • Intraventricular location rare (4th> > lateral ventricle) • "Cauliflower", insinuating pattern

Villous hyperplasia of choroid plexus

I DIFFERENIIAl.

• Very rare • Often overproduces CSF • Causes hydrocephalus

DIAGNOSIS

Ultrasound "pseudolesion"

Choroid plexus infarct

• Tiny anechoic areas in fetal choroid are normal, not CPC • Normal fluid-filled atria can be confused with CPC on transverse view • "Split" or "truncated" choroid can mimic CPC

• Usually seen in choroid artery infarct • May cause t intraventricular signal on DWI

Ependymal cyst

I PAIHOl.OGY

• • • •

Doesn't enhance Usually unilateral Attenuation, signal more like CSF Histopathology shows + immunoreactivity S-100

General Features for GFAP,

Neoplasm • Choroid plexus papilloma (children < 10 y; strong relatively uniform enhancement; cystic variant reported but rare) • Meningioma (usually solid) • Metastasis (rarely cystic) • Cystic astrocytoma (rare in older patients)

• General path comments: CPC commonly found at autopsy or imaging in middle-aged, older adults • Genetics o Large fetal choroid plexus cysts associated with trisomy 21 or 18 in only 6% of cases o Presence of additional malformations increases risk factors for aneuploidy • Etiology o CPCs • Lipid from desquamating, degenerating choroid epithelium accumulates in choroid plexus • Lipid provokes xanthomatous response

Primary Non-Neoplastic

Cysts

7 31

• Epidemiology o Most common type of neuroepithelial cyst • 1% of all pregnancies on routine US • 50% of fetuses with T18 • Small asymptomatic CPCs found incidentally in > 1/3 of all autopsied adults • Associated abnormalities o Fetal CPC • Trisomy 18 (mildly increased risk < 2x baseline risk) • Trisomy 21 (only if other markers present) o Adult CPC: May cause obstructive hydrocephalus (rare)

o In absence of other markers, none o With other markers, amniocentesis warranted

Consider • Amniocentesis with karyotyping if CPCs + other anomalies (e.g., cardiac anomaly, clenched hands with overlapping fingers, clubfeet) present on fetal US

Image Interpretation

Pearls

• Most common cause of choroid plexus mass in adults is benign degenerative cyst (xanthogranuloma)

Gross Pathologic & Surgical Features • Nodular, partly cystic yellowish gray masses in choroid plexus glomus • Rare: Hemorrhage

1.

Microscopic

2.

Features

• • • • •

Neuroepithelial microcysts Trapped choroid plexus epithelium often associated Cysts contain nests of foamy, lipid-laden histiocytes Foreign body giant cells Chronic inflammatory infiltrates (lymphocytes, plasma cells) • Cholesterol clefts, hemosiderin • Peripheral psammomatous Ca++ common • Immunohistochemistry positive for prealbumin, cytokeratins, GFAP,EMA, S-100

3. 4. 5.

6.

7. 8.

Presentation • Most common signs/symptoms o Adult CPC • Typical: Asymptomatic, discovered incidentally at autopsy/imaging • Rare: Headache

Demographics 32

9.

10.

11.

• Age o Adult CPC: Prevalence increases with age o Fetal CPC: Prevalence decreases with age • Gender: None known • Ethnicity: None known

12.

13.

Natural History & Prognosis • Fetal CPCs o Transient finding; typically resolve in 3rd trimester regardless of whether isolated or with associated anomalies o CPC + minor markers = 20% risk for chromosome abnormality o CPC + major markers = 50% risk for chromosome abnormality • Adult CPCs o Usually remain asymptomatic, nonprogressive

Treatment

14.

15. 16.

17. 18.

Liebeskind DS et al: Infarction of the choroid plexus. A]NR 25:289-90, 2004 Enriquez G et al: Potential pitfalls in cranial sonography. Pediatr Radiol. 33(2):110-7, 2003 Ishiyama H et al: Diffusion-weighted MRI of choroid plexus cysts (abstr). Neuroradiol43: 107,2001 Pettenati M] et al: Prenatal diagnosis of complete sole trisomy 1q. Prenat Diagn. 21(6):435-40, 2001 Mendez-Martinez OE et al: Symptomatic bilateral xanthogranulomas of choroid plexus in a child. Br] Neurosurg. 14(1):62-4,2000 Boockvar ]A et al: Symptomatic lateral ventricular ependymal cysts: Criteria for distinguishing these rare cysts from other symptomatic cysts of the ventricles. Neurosurg 46: 1229-33, 2000 Morcos CL et al: The isolated choroid plexus cyst. Obstet Gynecol. 92(2):232-6, 1998 Peleg D et al: Choroid plexus cysts and aneuploidy. ] Med Genet. 35(7):554-7, 1998 Parizek] et al: Choroid plexus cyst of the left lateral ventricle with intermittent blockage of the foramen of Monro, and initial invagination into the III ventricle in a child. Childs Nerv Syst. 14(12):700-8, 1998 Muenchau A et al: Xanthogranuloma and xanthoma of the choroid plexus: evidence for different etiology and pathogenesis. Clin Neuropathol. 16(2):72-6, 1997 Kadota T et al: MR of xanthogranuloma of the choroid plexus. A]NR Am] Neuroradiol. 17(8):1595-7, 1996 Britz GW et al: Hydrocephalus secondary to diffuse villous hyperplasia of the choroid plexus.] Neurosurg 85: 689-91, 1996 Hicks M] et al: Symptomatic choroid plexus xanthogranuloma of the lateral ventricle. Case report and brief critical review of xanthogranulomatous lesions of the brain. Clin Neuropathol. 12(2):92-6, 1993 Sugar 0: Symptomatic xanthogranuloma of the choroid plexus of the third ventricle. A new case with ultrastructural study. Surg Neurol. 29(1):79, 1988 Hinshaw DB]r et al: The bright choroid plexus on MR: CT and pathologic correlation. A]NR 9: 483-6, 1988 Razavi-Encha F et al: Symptomatic xanthogranuloma of the choroid plexus of the third ventricle. A new case with ultrastructural study. Surg Neurol. 27(6):569-74, 1987 Handagoon P et al: Xanthogranulomas of choroid plexus. Neuroradiology. 29(2):172-3, 1987 Pear BL:Xanthogranuloma of the choroid plexus. A]RAm] Roentgenol. 143(2):401-2, 1984

• Adult CPC: Usually none o Rare: Shunt for obstructive hydrocephalus • Fetal CPC

Primary Non-Neoplastic Cysts

CHOROID

I IMAGE

PLEXUS CYST

GAllERY (Left) Axial PO/Intermediate

MR in an asymptomatic older male shows bilateral choroid plexus masses. The mass in the right atrium is larger, hyperintense; the left-sided mass is smaller and heterogeneous. (Right) Coronal T7 C+ MR shows some peripheral enhancement of the right atrial cyst, which is slightly hyperintense to CSF. The left cyst shows solid enhancement. Typical CPCs (Courtesy R. Sherry, MO).

(Left) Axial fetal ultrasound shows large bilateral choroid plexus cysts (arrows). Trisomy 18 (Courtesy A. Kennedy, MO). (Right) Sagittal US in another case shows small adjacent CPCs (arrows) within echogenic choroid plexus, normal fluid-filled atrium (open arrow). Isolated finding, normal outcome (Courtesy A. Kennedy, MO).

7

Other (Left) Axial T7 C+ MR shows

a lobulated mass in the atrium of the right lateral ventricle (arrow). The mass is isointense with CSF and is barely visible. Typical CPX. (Right) Axial gross pathology shows a choroid plexus xanthogranuloma (arrows) found incidentally at autopsy. Note lobulated contour, yellowish color (Courtesy R. Hewlett, MO).

Primary Non-Neoplastic

Cysts

33

EPENDYMAL CYST

Axial FLAIR MR shows a cyst within the left lateral ventricle with signal intensity isointense to CSF on all pulse sequences. 22 year old female with headaches. Presumed ependymal cyst.

TERMINOLOGY Abbreviations

and Synonyms

• Neuroepithelial

cyst, glioependymal

Coronal T7 C+ MR shows an intraventricular ependymal cyst. The thin cyst wall (white arrow) is seen. Note the lack of enhancement and lateral displacement of the choroid plexus.

MR Findings cyst

Definitions • Neuroepithelial cyst in the ventricle, supratentorial parenchyma, or subarachnoid space • Congenital, benign ependymal-lined cyst

• Tl WI: Isointense to CSF, cyst wall may be seen • T2WI: Isointense to hyperintense to CSF (protein content) • PD/Intermediate: Isointense to hyperintense to CSF • FLAIR: Isointense to CSF • DWI: No diffusion restriction • Tl C+: No enhancement

Imaging Recommendations

I IMAGING

• Best imaging tool: Multiplanar MR • Protocol advice: Multiplanar MR with DWI, contrast

FINDINGS

General Features

7 34

• Best diagnostic clue: Nonenhancing thin-walled cyst with CSF density/intensity • Location o Intraventricular common, typically lateral ventricle o Intraparenchymal, central white matter of temporoparietal and frontal lobes o Subarachnoid space, less common • Size: Variable, typically small, 2-3 mm up to 8-9 cm • Morphology: Smooth, thin-walled cyst

I DIFFERENTIAL DIAGNOSIS Choroid plexus

cyst

• May be indistinguishable • Typically bilateral and arise in choroid plexus glomus • Commonly DWI positive, enhance

Arachnoid

cyst

• May be indistinguishable;

CSF intensity

CT Findings

Epidermoid

• NECT: Cyst is isodense to CSF; Ca++ extremely rare • CECT: No enhancement

• Insinuating growth pattern • Heterogeneous on FLAIR, DWI positive • If intraventricular, usually fourth ventricle

DDx: Intraventricular

Choroid Plexus Cysts

Cystic-Appearing

Arachnoid Cyst

cyst

Lesions

Epidermoid Cyst

Primary Non-Neoplastic

Cysts

Asymmetric Ventricles

EPENDYMAL CYST Key Facts I maging Findings • Best diagnostic clue: Nonenhancing thin-walled cyst with CSF density/intensity • Intraventricular common, typically lateral ventricle

Top Differential • • • •

Diagnoses

ChorOid plexus cyst Arachnoid cyst Epidermoid cyst Neurenteric cyst

Neurenteric

• Asymmetric ventricles • Porencephalic cyst

Pathology • General path comments: Congenital, benign cyst lined with ependymal cells • Epidemiology: Uncommon, less than 25 symptomatic cases reported

Treatment

cyst

• Typically posterior fossa • Typically isointense to hyperintense

on T1WI

Asymmetric ventricles

• If symptomatic, surgical excision or decompression o Rapid resolution of symptoms after surgery • Conservative management if asymptomatic

• Lateral ventricle asymmetry, normal variant

I DIAGNOSTIC

Porencephalic cyst • Focal encephalomalacia, • Typically communicates

I PATH 0

+/- surrounding gliosis with the ventricle

1..0GY

CHECKI..IST

Consider • Ependymal cysts may be indistinguishable benign cysts

Image Interpretation

from other

Pearls

General Features

• Ependymal cysts follow CSF on all MR sequences, including DWI, and do not enhance

• General path comments: Congenital, benign cyst lined with ependymal cells • Etiology: Thought to arise from sequestration of developing neuroectoderm • Epidemiology: Uncommon, less than 25 symptomatic cases reported

I SEI..ECTED REFERENCES

Gross Pathologic & Surgical Features

2.

• Thin-walled

Microscopic

1.

cyst filled with clear serous liquid

Features

• Fluid-filled space lined by columnar or cuboidal cells, with or without cilia • No fibrous capsule or basement membrane • Immunohistochemistry: GFAP and S-100 positive

3.

Pawar SJ et al: Giant ependymal cyst of the temporal horn an unusual presentation: case report with review of the literature. Pediatr Neurosurg 34:306-10, 2001 Boockvar JA et al: Symptomatic lateral ventricular ependymal cysts: criteria for distinguishing these rare cysts from other symptomatic cysts of the ventricles: case report. Neurosurgery 46:1229-33, 2000 Numaguchi Y et al: Large asymptomatic noncolloid neuroepithlial cysts in the lateral ventricle: CT and MR features. Neuroradiology 31:98-101, 1989

I IMAGE GAI..I..ERY I CI..I N ICAI.. ISSUES Presentation • Most common signs/symptoms: Typically asymptomatic • Other signs/symptoms o Headache, seizure, gait disturbance, dementia o Symptoms often related to obstruction of CSF flow or increased intracranial pressure

Demographics • Age: Typically young adults, less than 40 years • Gender: Male predominance

Natural History & Prognosis • Uncommon so natural history is unknown • Interval follow-up typically shows no clinical or imaging changes in asymptomatic lesions • Recurrence after surgical intervention uncommon

(Left) Axial CECT shows a large cyst with mass effect, isodense to CSF in this 55 year old with headaches and papilledema. There is lack of

calcification and enhancement, typical of ependymal cyst. (Right) Cross pathology shows an intraventricular ependymal cyst in the lateral ventricle (black arrow). Note the thin, glistening cyst wall. Incidental finding at autopsy (Courtesy of j. Townsend, MO).

Primary Non-Neoplastic

Cysts

7 35

Coronal graphic shows an intraparenchymal CSF-filled cavity that communicates with the left lateral ventricle. Classic porencephalic cyst lined with gliotic white matter (arrows).

Abbreviations

and Synonyms

• Porencephaly

Definitions

7 36

• Various definitions available for porencephaly o Congenital/acquired cavity within cerebral hemisphere, filled with cerebrospinal fluid (CSF), that mayor may not communicate directly with ventricular system o Presence of cysts/cavities in brain parenchyma communicating by a "pore" with arachnoid space o Brain cavities developed in fetal life or early infancy, whether or not they communicate with arachnoid space o Deep, unilateral/bilateral cavities or excavations, frequently communicating with subarachnoid space or lateral ventricles, which occur following brain destruction during the end of fetal or beginning of newborn period

Coronal T2WI MR in a different patient shows porencephalic dilatauon of the left lateral ventricle present in an area of encephalomalacia.

• Location o Usually corresponds to territories supplied by cerebral arteries (ischemic injury in midgestation) o Cortical/subcortical cavity, unilateral/bilateral o Usually connected with one of the lateral ventricles • Size: Variable • Morphology: Rounded or oval

Radiographic Findings • Myelography: Contrast material injected into subarachnoid space in lumbar region mayor may not fill the cystic space

CT Findings • NECT o Intraparenchymal smooth-walled cavity, CSF-isointense o Communication with ventricle or separating membrane • CECT: No contrast enhancement of fluid-filled cavity • CTA: Absence of vessels at site of porencephaly

MR Findings

General Features • Best diagnostic clue: Cystic space in brain parenchyma, enlarged adjacent ventricle on CT, MRI

• Tl WI: Smooth-walled cavity within brain parenchyma, isointense to CSF • T2WI: Common adjacent brain atrophy, gliosis • PD/Intermediate o Reliable prediction of cyst contents

DDx: Intracranial Cysts

1\\

.

I

\

\

I

I

I

,/ Encephalomalacia

Schizencephaly

CC Agenesis

Primary Non-Neoplastic Cysts

Dandy-Walker Cyst

PORENCEPHALIC

CYST

Key Facts Terminology • Deep, unilateral/bilateral cavities or excavations, frequently communicating with subarachnoid space or lateral ventricles, which occur following brain destruction during the end of fetal or beginning of newborn period

Imaging Findings • Best diagnostic clue: Cystic space in brain parenchyma, enlarged adjacent ventricle on CT, MRI

Top Differential • • • • •

•

• • •

Diagnoses

• Assess hippocampal porencephaly-related

• CSF-isointense content of maldevelopmental/porencephalic cyst • Non-CSF-isointense appearance in neoplastic/inflammatory lesion FLAIR o Accurately depicts CSF content of cyst o More accurate than PD in differentiating neoplastic/inflammatory from porencephalic Tl C+: Nonenhancing cyst MRA: Absence of vessels at site of porencephaly MRS: Absence of normal brain metabolites

Ultrasonographic

Findings

• Prenatal ultrasound

for congenital

• CSF-filled space extending cephalad from 3rd ventricle • Parallel appearance of lateral ventricles • Colpocephaly: Dilatation of occipital horns and posterior portions of temporal horns cysts

porencephaly

Findings

• Conventional:

Seen as area of absent blood vessels

Findings

• PET: Area of absent glucose metabolism

Findings

• Air or contrast ventriculography mayor communication with cystic space

structures in patients with seizures

Agenesis of corpus callosum

Angiographic

Other Modality

Pathology • Amygdala-hippocampal atrophy often coexists with congenital porencephaly (95% in some reports) • Familial porencephaly may be associated with inherited thrombophilia • CSF-filled cavity with smooth walls, lined by white matter of cerebral hemisphere

Diagnostic Checklist

Arachnoid cyst Ependymal cyst Neoplastic/inflammatory cyst Agenesis of corpus callosum Encephalomalacia

Nuclear Medicine

• Schizencephaly • Dandy- Walker malformation • Hydranencephaly

may not show

Imaging Recommendations

Encephalomalacia • Late gestational, perinatal or postnatal injuries (thrombotic/embolic infarction, asphyxia, infection) • Slightly hyperdense/intense to CSF; cavity contains septations and is lined by astr6cytic proliferation

Schizencephaly • Intraparenchymal cavity lined by gray matter, extending from ventricular surface to brain surface

Dandy-Walker

malformation

• Large median posterior fossa cyst widely communicating with 4th ventricle • Rotated, raised, and small cerebellar vermis in contact with tentorium • Upward displacement of tentorium and lateral sinuses • Posterior bossing of posterior fossa • Antero-Iateral displacement of normal cerebellar hemispheres

• Best imaging tool: MR • Protocol advice: FLAIR

Hydranencephaly

I DIFFERE~JI~l DI~G~OSIS

• Early destructive process of developing brain caused by toxoplasmosis, CMV, or arterial occlusion • Cortex and white matter completely destroyed and replaced by thin-walled sacs of leptomeninges, containing CSF

Arachnoid cyst • CSF-isointense extra-axial cyst that exerts variable degrees of mass effect • Unlike porencephalic cyst, is extra-axial and displaces brain tissue away from adjacent skull

Ependymal cyst • Intraventricular • Brain usually normal

Neoplastic/inflammatory

cyst

• Mass effect, contrast enhancement

if neoplastic

Ip~JHOlOG¥ General Features • General path comments: Focal cavity (within brain parenchyma) with smooth walls • Genetics o Most cases are sporadic o Familial porencephaly is a rare condition

Primary Non-Neoplastic

Cysts

7 37

• Autosomal dominant trait with variable expression and incomplete penetrance • Involved genes not yet mapped - search for mutations leading to hypercoagulable state • Etiology o Congenital: In utero destructive process caused by cerebral vascular events or infectious injury (CMV) o Acquired: Injury later in life, following head trauma, vascular occlusion, or infection • Epidemiology: 2.5% incidence of porencephalic cysts among 1,000 congenital and acquired brain lesions • Associated abnormalities o Amygdala-hippocampal atrophy often coexists with congenital porencephaly (95% in some reports) • This atrophy may be bilateral despite unilateral porencephalic cysts o Familial porencephaly may be associated with inherited thrombophilia

38

porencephaly:

Lesions develop later

Presentation • Most common signs/symptoms o May be associated with severe neurological deficits (hemiplegic cerebral palsy most common feature) o Mental retardation, medically intractable epilepsy • Clinical profile o Microcephaly/macrocephaly o Cerebellar symptoms o Various forms of cerebral paralysis (spastic hemiparesis, diplegia and tetraplegia) o Various ophthalmological signs o Seizures, psychomotor retardation

Gross Pathologic & Surgical Features

Demographics

• CSF-filled cavity with smooth walls, lined by white matter of cerebral hemisphere • Overlying skull may be o Remodeled due to long-term transmission of CSF pulsations when dilated ventricle abuts inner cortex of skull without significant brain tissue superficially o Progressively expanding when synechiae within ventricle create a ball-valve effect with progressive ventricular enlargement o Thickened when intervening brain tissue precludes transmission of CSF pulsations to underlying structures

• Age: Pediatric age most common; also occurs in adults • Gender: Equal predominance

Microscopic Features

7

• Encephaloclastic in 2nd trimester

• Congenital porencephalic cyst o Fluid-filled, focal cavity with smooth walls and minimal surrounding glial reaction o Limited capacity for astrocytic reaction in fetal brain o Necrotic tissue is completely reabsorbed (liquefaction necrosis) • Acquired porencephalic cyst o Mature brain reacts to injury by significant astrocytic proliferation o Resulting cavity often has septations and irregular wall composed primarily of reactive astrocytes

Staging, Grading or Classification Criteria • True porencephalic cyst o Caused by defect in generative process or abnormal migration of neurons o Most commonly located in region of sylvian fissure o May communicate with ventricles, cerebral cortical surface, and subarachnoid space • Porencephalic pseudocyst o Arises by disruption of normal brain tissue (due to vascular event or infection) o Can be unilateral and enlarge without communicating with other structures • Agenetic porencephaly o Destruction of a portion of germinal matrix prior to 26th gestational week o Accompanied by anomalies of overlying cortex (polymicrogyria)

Natural History & Prognosis • Narrow communication with ventricular pressure in cyst ~ mass effect

system may t

Treatment • Usually no treatment is required • Indications for surgery: Mass effect (hemimacrocephaly, midline displacement), localized/generalized symptoms • Procedures o Cystoperitoneal shunt (preferred) o If no communication with ventricular system: Fenestration or partial resection of cyst wall • Children with intractable seizures and porencephaly benefit from uncapping and cyst fenestration to lateral ventricle

I DIAG.NOSTIC\CI-IE(D~tIS-r Consider • Arachnoid cyst simulating porencephalic

Image Interpretation

cyst

Pearls

• Assess hippocampal structures in patients with porencephaly-related seizures • Cerebral imaging (CT, MRI) is unreliable to identify asymptomatic carriers of familial porencephaly

I SELECTED REFERENCES 1.

2.

3.

Moinuddin A et al: Intracranial hemorrhage progressing to porencephaly as a result of congenitally acquired cytomegalovirus infection - an illustrative report. Prenat Diagn. 23:797-800, 2003 Vilain C et al: Neuroimaging fails to identify asymptomatic carriers of familial porencephaly. Am] Med Genet. 112:198-202,2002 Aprile I et al: Analysis of cystic intracranial lesions performed with fluid-attenuated inversion recovery MR imaging. Am] Neuroradiol. 20:1259-1267,1999

Primary Non-Neoplastic

Cysts

Typical (Left) Axial T2WI MR shows

a cystic space within the brain parenchyma, filled with CSF-isointense fluid, that causes a focally dilated ventricle and displays mass effect on the surrounding brain tissue. (Right) Axial Tl C+ MR in the same patient shows CSF-isointense cystic space within brain parenchyma that causes a focally dilated left lateral ventricle and exerts mass effect on surrounding brain tissue.

Typical (Left) Sagittal TlWI MR

shows occipital cavity, isointense to CSF,widely communicating with subarachnoid space. (Right) Axial FLAIRMR in the same patient shows occipital cavity, isointense to CSF, widely communicating with subarachnoid space.

7

Typical (Left) Axial NECT shows porencephalic dilatation of frontal horn of left ventricle in an adult brain. Periventricular area of decreased density suggests encephalomalacia. (Right) Coronal FLAIRMR in a different patient shows porencephalic dilatation of the left lateral ventricle present in an area of encephalomalacia.

Primary Non-Neoplastic Cysts

39

Sagittal graphic shows a classic neurenteric cyst (arrow). Intracranial NECs are most often found near the midline, anterior to the brainstem.

Sagittal TlWI MR shows a well-delineated, slightly hyperintense mass anterior to the medulla (arrows). The mass was hyperintense on PO, T2WI, did not enhance. Neurenteric cyst at surgery.

MR Findings Abbreviations • Neurenteric

and Synonyms

cyst (NEe); enterogenous

cyst

Definitions • Benign malformative

endodermal

CNS cyst

• • • • • •

T1WI: Iso-/slightly hyperintense to CSF T2WI: Hyperintense to CSF PD/Intermediate: Hyperintense to CSF FLAIR: Hyperintense to CSF T2* GRE: No blooming Tl C+: No enhancement

Imaging Recommendations General Features

7 40

• Best diagnostic clue: Round/lobulated nonenhancing, slightly hyperintense (to CSF) mass in front of medulla • Location o Spine> > brain o Most all intracranial NECs found in posterior fossa • Midline, anterior to brain stem • Other: CPA, clivus • Rare: Suprasellar, quadrigeminal cisterns; anterior fossa • Size: Variable; usually < 2 cm • Morphology: Smooth, lobulated, well-demarcated

• Best imaging tool: MR without, with contrast • Protocol advice: FLAIR useful in distinguishing intracranial cysts

Epidermoid or dermoid cyst • CPA most common site for epidermoid • "White" epidermoid (rare) is hyperintense can be difficult to distinguish if midline

on Tl WI,

Arachnoid cyst • Like CSF on all sequences

CT Findings

Other endodermal

• NECT: Hypo-/isodense mass anterior to brainstem • CECT: No enhancement

• Location (not posterior fossa)

cyst (Rathke, colloid)

Schwannoma • Enhances strongly; usually not midline

DDx: Intracranial

Ruptured Dermoid

Primary Non-Neoplastic Cysts

NEURENTERIC CYST Key Facts Imaging Findings • Best diagnostic clue: Round/lobulated nonenhancing, slightly hyperintense (to CSF) mass in front of medulla • Most all intracranial NECs found in posterior fossa • T1WI: Iso-/slightly hyperintense to CSF • FLAIR: Hyperintense to CSF • T1 C+: No enhancement

• Protocol advice: FLAIR useful in distinguishing intracranial cysts

Top Differential • • • •

Diagnoses

Epidermoid or dermoid cyst Arachnoid cyst Other endodermal cyst (Rathke, colloid) Schwannoma

I PA.'-H0t0G¥

I DIAGN0S'-IC

General Features

Consider

• General path comments o Considered part of the split spinal cord malformation spectrum o Congenital endodermal cyst (like Rathke cleft, colloid cyst) • Etiology: Persistent neurenteric canal (connection between embryonic foregut, developing neural tube) • Epidemiology o Only 35 intracranial cases reported o < 1% of all spinal masses • Associated abnormalities o Vertebral anomalies in 50% of spinal NECs • Anterior segmentation defects

• A midline mass in front of the brain stem that is slightly hyperdense/intense to CSF may be an NEC

Image Interpretation

Microscopic

Features

• Lining varies from nonciliated to ciliated, low cuboidal to columnar • Contains mucin-secreting goblet cells • Stains positively for EMA, CEA, vimentin, cytokeratins • Negative for 5-100

Pearls

• Not all spinal NECs are associated with vertebral anomalies

I SEtEC'-ED 1.

2.

Gross Pathologic & Surgical Features • Transparent, thin-walled smooth round/lobulated cyst • Contents vary from clear, colorless fluid (like CSF) to thicker, more viscous/mucoid

CHECKI..IS'-

3.

4. 5.

6. 7.

REFERENCES

Christov C et al: Giant supratentorial enterogenous cyst: Report of a case, literature review, and discussion of pathogenesis. Neurosurg 54:759-63, 2004 Evans A et al: Magnetic resonance imaging of intraspinal cystic lesions: a pictorial review. Curr Probl Diagn Radiol. 31(3):79-94,2002 Agrawal D et al: Intramedullary neurenteric cyst presenting as infantile paraplegia: a case and review. Pediatr Neurosurg. 37(2):93-6, 2002 Niesen CE: Malformations of the posterior fossa: current perspectives. Semin Pediatr Neurol. 9(4):320-34, 2002 Filho FL et al: Neurenteric cyst of the craniocervical junction. Report of three cases. J Neurosurg. 94(1 Suppl):129-32, 2001 Simon JA et al: Intracranial neurenteric cysts: A differential diagnosis and review. RadioGraphies 17: 1587-93, 1997 Gao P-Y et al: Neurenteric cysts: Pathology, imaging spectru, differential diagnosis. UNR 1: 17-27, 1995

7 41

I CI..INICAt ISSUES

I IMAGE GAttER¥

Presentation • Most common signs/symptoms o Spine = cord compression, myelopathy o Brain = asymptomatic or headache

Demographics • Age: Any age • Gender: M = F

Natural History & Prognosis • May be stable or enlarge slowly

Treatment • Total surgical excision Sagittal T1 C+ MR shows a large, lobulated cystic mass (arrows) anterior to the brainstem that is slightly hyperintense to CSF. The mass compresses and displaces the medulla posterosuperiorly. (Right) Sagittal T2WI MR shows the mass is well-delineated, very hyperintense. Neurenteric cyst was found at surgery.

(Left)

Primary Non-Neoplastic

Cysts

PART I SECTION 8 Infedlon and Delllfelinatlni Diseue Infection of the brain and it linings pose an ever-growing, worldwide public health problem. Age-old di eases such a tuberculo is and malaria are becoming more lethal with the development of multidrug-resi tant strain. HIV infection i rampant and presents a different face where highly effective antiretroviral therapy i available versus area where such treatments are unknown or unavailable. ew di ea es for which there i currentl no known vaccine and no known cure (biohazard level 4 agents such a viral hemorrhagic fevers like ebola) are emerging. Wide pread immigration mean that di ea e once relatively onfined to certain geographic areas are now literally "out ide the window" of practicing radiologists everywhere. The threat of a worldwide influenza pandemic i no longer the stuff of cience fiction. The eminent obellaureate, Dr.)o hua Lederberg, once informed RS A attendee that, "We are in an evolutionary footra e with our 10 est biological competitor, bacteria and viruse." nd gue who i winning that one ... In this section we focu on a number of infections and inflammatory di orders that affect the . We begin with three congenital infection cau ed by the o-called TOR H agent and follow with an exten ive di cu ion of acquired infections. The section conclude with three demylinating di order: Multiple c1erosi acute di eminated encephalomyeliti (ADEM), and the rare but important mea I s-related subacute c1ero i panencephalitis ( PE). I

SECTION 8: Infection and Demyelinating

Congenital/Neonatal Infections Congenital Congenital Congenital

CMV HIV Herpes

1-8-4 1-8-8 1-8-10

Acquired Infections Group B Streptococcal Meningitis Citrobacter Meningitis Meningitis Abscess Ventriculitis Empyema Herpes Encephalitis Encephalitis (Miscellaneous) Rasmussen Encephalitis Tuberculosis Neurocysticercosis Parasites, Miscellaneous Fungal Diseases Rickettsial Diseases Lyme Disease HIV Encephalitis Opportunistic Infection, AIDS

1-8-12 1-8-16 1-8-20 1-8-24 1-8-28 1-8-30 1-8-34 1-8-38 1-8-42 1-8-46 1-8-50 1-8-54 1-8-58 1-8-62 1-8-64 1-8-66 1-8-70

Demyelinating Disease Multiple Sclerosis ADEM Subacute Sclerosing Pan encephalitis

1-8-74 1-8-78 1-8-82

Disease

CONGENITAL CMV

Axial graphic shows periventricular & basal ganglia calcification, abnormal white matter, ventricular asymmetry, and diffuse cortical dysplasia with focal thickening of cortex.

ITERMINOlOGY Abbreviations and Synonyms • Congenital

cytomegalovirus

(CMV) encephalitis

Definitions • Congenital infectioJ;l caused by transplacental transmission of human herpes virus o The most common cause of intrauterine infection in the USA o A spectrum of brain injury is possible depending upon timing of the fetal infection

Radiographic Findings • Radiography:

!Cranial-to-facial

ratio

• NECT o Cerebral parenchymal Ca++ (40-70%) • Periventricular (subependymal) o Ventricular dilatation and WM volume loss o Focal regions of WM low attenuation o Cortical gyral abnormalities o Cerebellar hypoplasia

General Features

4

• Gestational age at time of infection determines pattern of CNS injury o Prior to 18 wks - reduction in neurons and glia, lissencephaly, small cerebellum, ventriculomegaly o 18-24 wks - cortical gyral abnormalities, frontal> temporal o Third trimester - myelin delay or destruction, periventricular cysts o Perinatal infection - delay in myelin maturation, focal white matter injury (astrogliosis)

CT Findings

IIMAGING FINDINGS

8

Axial NEeT shows extensive periventricular calcification and intraventricular hemorrhage (arrow).

• Best diagnostic clue o Microcephaly o Cerebral calcification (40-70%) • Periventricular (sub ependymal) o Cortical gyral abnormalities • Agyria ~ pachygyria ~ diffuse polymicrogyria focal cortical dysplasia o Cerebellar hypoplasia o Myelin delay or destruction • Location: Dystrophic periventricular Ca++ has predilection for germinal matrix zones

~

MR Findings • TIWI o Periventricular subependymal foci of Tl shortening due to Ca ++ o Ventricular dilatation and periventricular WM volume loss

DDx: Neonatal Periventricular Calcification

Infection and Demyelinating Disease

CONGENITAL CMV Key Facts Imaging Findings

Pathology

• • • • • •

Microcephaly Cerebral parenchymal Ca++ (40-70%) Cerebellar hypoplasia Cortical gyral abnormalities Echogenic periventricular foci (Ca++) Branching basal ganglia and thalamic echoes (lenticulostriate vasculopathy) • Cranial sonography for neonatal screening • NECT when clinically suspected • MR brain to completely characterize abnormalities

• Most common cause of intrauterine infection • CMV is a ubiquitous DNA virus of the herpes-virus family • Affects'" 1% of all newborns • Cytomegaly (25-40 microns) with viral nuclear and cytoplasmic inclusions

Top Differential Diagnoses

• Congenital CMV in the developmentally microcephalic infant with SNHL

• Congenital lymphocytic choriomeningitis • Toxoplasmosis • Pseudo-TORCH syndromes

(LCM)

o Cerebellar hypoplasia • T2WI o Cortical gyral abnormalities • Ranging from agyria to focal cortical dysplasia o Myelination delay or destruction o Periventricular pseudocysts o Focal WM lesions with 1 T2 (gliosis) predominately in parietal deep WM o Hippocampal dysplasia (vertical orientation) o Temporal tip cystic changes frequent o Late T2 signal changes affect white matter between juxta-cortical and periventricular layers • FLAIR: Focal,patchy, or confluent regions of increased signal due to gliosis • T2* GRE: Periventricular ~ signal due to Ca++ • MRS: ~ NAA/Cr ratio due to loss of neuronal elements, 1 myoinositol (gliosis)

Ultrasonographic Findings • Real Time o Ring-like regions of periventricular lucency may precede Ca++ o Echogenic periventricular foci (Ca++) o Branching basal ganglia and thalamic echoes (lenticulostriate vasculopathy) o Periventricular pseudocysts and ventricular adhesions o Cerebellar hypoplasia

Clinical Issues • Most infected newborns appear normal

Diagnostic Checklist delayed,

I IDIFFERIHSil1EI~f.IDI~~~~SIS Congenital lymphocytic choriomeningitis (lCM) • Rodent borne Arenavirus o Carried by the feral house mouse and hamster • Produces a necrotizing ependymitis leading to aqueductal obstruction o Macrocephaly (43%) > microcephaly (13%) • NECT may perfectly mimic CMV

Toxoplasmosis • Protozoan parasite o Maternal risk factors include • Exposure to cat excreta during pregnancy • Eating raw or undercooked meat • l/lOth as common as CMV • Macrocrania > microcephaly • Neuronal migration abnormalities less common • Cerebral calcifications are random

Pseudo-TORCH syndromes • Baraister-Reardon, Aicardi-Goutieres (CSF pleocytosis, 1 CSF alpha interferon) o Auto recessive o Progressive cerebral and cerebellar demyelination o Basal ganglia Ca++ o +/- Periventricular Ca++

Imaging Recommendations

8 5

• Best imaging tool o Cranial sonography for neonatal screening o NECT when clinically suspected o MR brain to completely characterize abnormalities • Protocol advice o NECT for detecting periventricular Ca++ o T2*GRE to detect subtle calcification or hemorrhage

I P~1EI7-I~L~~M General Features • General path comments o Most common cause of intrauterine infection o Mechanism of fetal infection • Mother has primary infection during pregnancy • Mother has reactivation of latent infection o Mechanism of neonatal infection • Mother infected at delivery • Transmission of virus in breast milk • Blood transfusion

Infection and Demyelinating Disease

• Etiology o CMV is a ubiquitous DNA virus of the herpes-virus family o Hematogenously seeds the choroid plexus o Replicates in ependyma, germinal matrix, and capillary endothelia o Capillary involvement leads to thrombosis and ischemia o Chronic ischemia from placentitis leading to secondary perfusion insufficiency • Epidemiology o Affects'" 1% of all newborns • 10% of these have CNS or systemic signs and symptoms o 40% of mothers who acquire infection during pregnancy transmit virus to fetus

o Newborns with CNS manifestations (microcephaly, periventricular Ca++) • Up to 95% have major neurodevelopmental sequelae o Newborns with only systemic manifestations (hepatosplenomegaly, petechiae, jaundice) • Have better prognosis but still significantly affected o Infected newborns with neither CNS or systemic manifestations • Have best prognosis • At risk for: Developmental delay, motor deficits, and SNHL (most common) o Mortality '" 5%

Treatment • Ganciclovir may benefit infected infants

Gross Pathologic & Surgical Features • Micrencephaly • Early gestational infection o Germinal zone necrosis o Diminished number of neurons and glial cells o White matter volume loss ~ ventriculomegaly

Microscopic

Features

• Hallmark of CMV infection o Cytomegaly (25-40 microns) with viral nuclear and cytoplasmic inclusions • Patchy and focal cellular necrosis (particularly germinal matrix cells) • Vascular inflammation and thrombosis • Vascular and subependymal dystrophic Ca++

Staging, Grading or Classification Criteria • Timing of gestational infection determines insult o Neuronal formation between 8-20 weeks o Neuron migration until 24-26 weeks o Astrocyte generation begins near end of neuronal production o Maximal size of germinal zones at 26 weeks o Oligodendrocytes produced during first half of third trimester

Presentation

6

Consider • Congenital CMV in the developmentally microcephalic infant with SNHL

Image Interpretation

1.

3. 4.

5.

6.

van der Knaap MS et al: Pattern of white matter abnormalities at MR imaging: Use of polymerase chain reaction testing of Gothrie cards to link pattern with congenital cytomegalovirus infection. Radiology 230:529-36, 2004 Modlin JF et al: Case 25-2003: A newborn with petechiae and thrombocytopenia. N Engl] Med. 349: 691-700, 2003 Bale JF et al: Congenital infections. Neurol Clin. 20(4): 1039-60, 2002 Wright R et al: Congenital lymphocytic choriomeningitis virus syndrome: A disease that mimics congenital toxoplasmosis or cytomegalovirus infection. Pediatrics 100:1-6, 1997 Barkovich AJ et al: Congenital cytomegalovirus Infections of the brain: imaging analysis and embryologic considerations. AJNR. 15:703-15, 1994 Boesch C et al: Magnetic resonance imaging of the brain in congenital cytomegalovirus infection. Pediatr Radiol. 19:91-3, 1989

Natural History & Prognosis • Three prognostic

Pearls

• Congenital CMV encephalitis should be considered when MR shows o Cerebellar hypoplasia o Cortical gyral abnormalities (particularly agyria with thin cortex) o Myelin delay or destruction o Microcephaly • When NECT is classic for CMV encephalitis but the work-up for (S) TORCH infection is negative, consider o Lymphocytic choriomeningitis (LCM) o Pseudo-TORCH syndromes (most are autosomal recessive)

2.

• Most common signs/symptoms o Most infected newborns appear normal o 10% have systemic signs of disease • Hepatosplenomegaly (52%), petechiae (51%), chorioretinitis, jaundice, and IUGR o 55% with systemic disease have CNS involvement • Microcephaly, parenchymal Ca++, SNHL, seizures, hypotonia or hypertonia • Clinical profile: Seronegative women are at greatest risk for vertical transmission • Methods of diagnosis o Shell-vial assay for CMV (urine) o Late diagnosis with PCR for CMV-DNA from neonatal Guthrie card

delayed,

groups

Infection and Demyelinating Disease

Typical (Left) Sagittal T7WI MR shows microcephaly cerebellar atrophy and thin corpus callosum (arrow). (Right) Axial T2WI MR shows extensive bilateral peri-sylvian polymicrogyria (arrow). Note the shallow opercular cisterns (curved arrow).

(Left) Sagittal T7WI MR shows thickened peri-sylvian cortex (polymicrogyria) (arrow). (Right) Coronal T2WI MR shows asymmetric peri ventricular WM T2 prolongation consistent with demyelination and gliosis (arrow).

Typical (Left) Axial T2WI MR shows bilateral posterior periventricular cysts (arrow) and confluent white matter regions of T2 prolongation consistent with demyelination and gliosis. (Right) Coronal cranial ultrasound shows periventricular foci of echogenicity consistent with calcification (arrow).

Infection and Demyelinating

Disease

8 7

Axial NECT shows bilateral and symmetrical calcificadons in the basal ganglia, mostly in the globi pa/lidi.

Coronal oblique catheter angiogram shows fusiform dilation of the ICA, proximal MCA consistent with HIV vasculopathy (Courtesy P. Lasjaunias, MOJ.

Abbreviations

• T2WI: High signal in frontal subcortical WM if progressive encephalopathy • T2* GRE: May accentuate Ca++ • T1 C+: Faint BG enhancement initially • MRA: Fusiform vasculopathy (late) • MRS: !NAA, 1 Cho/Cr, presence of amino acids

and Synonyms

• Congenital AIDS, maternally

transmitted

AIDS

Definitions • Vertical HIV 1 infection early in-utero/late at delivery or by breast-feeding

pregnancy,

Angiographic Findings • DSA: Ectasia of intracranial

arteries

Imaging Recommendations • Best imaging tool: CT • Protocol advice o Baseline NECT o MR in symptomatic patients

General Features • Best diagnostic clue: Basal ganglia Ca++, volume loss

CT Findings

8 8

• NECT o Atrophy (57-86%), frontal> BG > diffuse o Mineralizing micro angiopathy (> 8 wks of age) o BG Ca++ (30-85%) > frontal white matter (WM) > cerebellum o Lymphadenopathy, benign lymphoepithelial parotid cysts • CECT: May show faint enhancement of BG prior to appearance of Ca++

Cytomegalovirus • Periventricular Ca++ • Microcephaly • Neuronal migration anomalies, cortical dysplasias

Congenital toxoplasmosis • Scattered Ca++ • Hydrocephalus

MR Findings • T1WI: Atrophy

DDx: Childhood

Brain

Ca++

CMV

Toxoplasmosis

Infection and Demyelinating Disease

CONGENITAL HIV Key Facts • Congenital

Terminology • Vertical HlV 1 infection early in-utero/late pregnancy, at delivery or, by breast-feeding

Imaging Findings • Best diagnostic clue: Basal ganglia Ca++, volume loss • MRA: Fusiform vasculopathy (late)

Top Differential

toxoplasmosis

Pathology • HIV leukoencephalopathy,

calcific vasculopathy

Clinical Issues • Diagnosis: PCR, HlV blood culture, p24-antigen

essay

Diagnostic Checklist

Diagnoses

• Consider HIV if bilateral symmetrical calcifications BG are found in a child> than 2 months

• Cytomegalovirus

I PATHOI...(iJ)~~

in

I lffil...lrsJllffiAI...ISSl:..JE~

General Features

Presentation

• General path comments o HIV leukoencephalopathy, calcific vasculopathy o Intrauterine transmission risk increased with higher maternal HIV load o Most acquired at birth, 3rd trimester, via breast feeding • Genetics o Co-receptors allow virus into cell o Mutations in receptor gene ~ immunity in small % • No HIV infection despite significant exposure or non-progression to AIDS • Etiology o HIV in microglial cells and macrophages o Viral proteins/neurotoxins ~ inflammation • Epidemiology o 2.4 million children infected world-wide by 1997 • 2000 new infections x day • Risk: 15-25% without breast feeding, 25-45% with breast feeding o 90% of new cases are vertically acquired o Risk of HIV infection in infants of HIV-infected mothers ~ 15-60%

• Most common signs/symptoms o Respiratory infections, diarrhea, failure to thrive o Hepato-splenomegaly, lymphadenopathy o Encephalopathy • Developmental delay: Common in children • Opportunistic infections: Less common in children • Diagnosis: PCR, HIV blood culture, p24-antigen essay

Gross Pathologic & Surgical Features • Microcephaly • Hemorrhage ~ HIV-induced thrombocytopenia/clotting • Subacute necrotizing encephalopathy if dilated cardiomyopathy • Calcific vasculitis (90%) of medium/small arteries • Cerebrovascular disease 25% at autopsy « 3% on imaging) o Infarctions, fusiform aneurysms o Diffuse fibrosing/sclerosing vasculopathy

Microscopic

Demographics • Age: Symptoms begin at 12 wks of life, some asymptomatic until 10 yrs of age

Natural History & Prognosis • Infected children survive longer with therapy • If symptomatic in 1st year of life ~ 20% die in infancy

Treatment • Retroviral therapy (50% rebound in 1st yr)

I DIAGrsJ(iJ)~Tllffi lffiHElffiKU~T Image Interpretation

Pearls

• Consider HIV if bilateral symmetrical calcifications BG are found in a child> than 2 months

I SEI...ECTED 1.

in

REFERErsJlffiES

Meleski ME et al: HIV exposure: neonatal considerations. Obstet Gynecol Neonatal Nurs. 32: 109-16,2003

J

IIMA~E ~AI...I...ER~

9

Features

• HIV encephalitis: Microglial nodules, multinucleated giant cells, perivascular mononuclear cells • HIV leukoencephalopathy: Myelin loss, astrogliosis

Staging, Grading or Classification Criteria • Progressive encephalopathy intervening plateaus • Static encephalopathy

8

with or without

(Left) Axial CECT shows markedly dilated arteries. (Right) Axial CECT shows ectasia of cerebral arteries (Courtesy P. Lasjaunias M 0).

Infection and Demyelinating Disease

Axial T1WI MR shows diffuse cystic encephalomalacia and prominent CSF-containing spaces.

Abbreviations

o Atrophy, low signal in WM, cysts, hydrocephalus, bleeds o Dysplastic cortex • T2WI o High signal in WM - cyst formation o Cerebellar high signal in 50% of patients • Tl C+ o Patchy enhancement - in cortex o Meningeal enhancement • MRS o May show 1 Cho during acute period, I NAA o Chronic stage - all metabolites low

and Synonyms

• HSV-2, vertically transmitted HSV, maternally transmitted HSV, neonatal HSV

Definitions • HSV-2 acquired at vaginal delivery - multi organ involvement + meningoencephalitis

General Features

Ultrasonographic

• Best diagnostic clue: Ca++ in GM, hypodensities WM, cysts, cortical enhancement

• Fine, linear echogenicities in BG - perivascular spaces (lenticulostriate vasculopathy) o Due to hypercellularity + mineralization of arteries o Not pathognomonici seen in all TORCH • Late: Multicystic encephalomalacia

in

CT Findings

8 10

Axial T2WI MR in the same case shows diffuse hyperintensities throughout the cerebral hemispheres. Congenital herpes.

• NECT o Severe atrophy o Ca++ in basal ganglia (BG), thalami, cortex, subcortical WM • Occasional bleeds - same locations o Hydrocephalus, ± hydranencephaly, cysts • CECT: Enhancement of cortex

Findings

Imaging Recommendations • Protocol advice: NECT, MRI

MR Findings

Cytomegalovirus

• TlWI

• Periventricular

(CMV)

Ca++, microcephaly,

DDx: TORCH

CMV

Toxoplasma

+ CMV

Infection and Demyelinating

Toxoplasmosis

Disease

dysplasias

CONGENITAL HERPES Key Facts Terminology

Top Differential

• HSV-2 acquired at vaginal delivery involvement + meningoencephalitis

-+

multiorgan

• Cytomegalovirus • osis

Diagnoses (CMV)

Imaging Findings • Best diagnostic clue: Ca++ in GM, hypodensities WM, cysts, cortical enhancement • Severe atrophy • Hydrocephalus, ± hydranencephaly, cysts • Late: Multicystic ence halomalacia

in

Pathology • Diagnosis

-+

HSV detection by cell culture or PCR

• Clinical profile o CSF: Pleocytosis, i protein, I glucose o EEG: Focal or multifocal paroxysmal, periodic discharges -+ repetitive sharp wave complexes

Toxoplasmosis • Scattered Ca++, hydrocephalus

Rubella • Basal ganglia Ca++, infarctions

Demographics • Age: Generally neonates (1-14 days) • Ethnicity: More common in African-Americans

I PATI-Ufn.€HIi¥'

Natural History & Prognosis

General Features • General path comments o Diagnosis -+ HSV detection by cell culture or PCR o HSV -+ induces apoptosis in neurons/glia • Etiology o Maternal transmission • 2% of women acquire HSV per year without recognizable symptoms • 30% of women> 30 years -+ seropositive • Epidemiology o More common in children from mothers that are: African-American, low income, large number of sexual partners, early age at first intercourse, drugs • 1:2500 births; 40-45% are premature babies o 2% of mothers become HSV+ during pregnancy o More common if genital disease present at delivery o Transplacental infection rare • Associated abnormalities o Hemolytic anemia, bleeding o Conjunctivitis, keratitis, chorioretinitis o Hepatomegaly, hyperbilirubinemia o Pneumonitis, vesicular exanthem

Gross Pathologic & Surgical Features

• Most die in infancy • Survivors -+ cerebral palsy, seizures, mental retardation

Treatment • Acyclovir: No effects on brain damage • If active maternal infection -+ C-section is indicated • Avoid fluid overload, manage intravascular coagulation/bleeding, ventilation

'DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Consider HSV in newborn with scattered brain Ca++, encephalomalacia, hydrocephalus

'SELECTED REFERENCES 1.

Schleiss MR. Vertically transmitted herpesvirus infections. Herpes 10: 4-11, 2003

I IMAGE GALLER¥'

• Meningoencephalitis, necrosis, bleeds, swelling • Microcephaly, hydranencephaly

8

Microscopic

11

Features

• Cowdry a intranuclear inclusions in all CNS cells • Inflammation of endothelial cells -+ thrombosis • Reactive microglial/astroglial proliferation

'CLINICAL

ISSUES

Presentation • Most common signs/symptoms o Skin vesicles/scars, chorioretinitis, microcephaly, micro-ophthalmia o Fever, low birth weight, mucous membrane ulcerations, irritability, stupor

(Left) Axial T2WI MR shows areas of high signal in franta"obes

WM

due to acute H5V-2. (Right) Coronal gross pathology shows ventricular dilations, cystic malacia & lack of normal cortical sulcation.

Infection and Demyelinating

Disease

Axial T2WI MR shows hydrocephalus, deep (open arrows) and peripheral (arrows) arterial infarcts. Small, bifrontal subdural empyemas (curved arrows) are barely visible.

Abbreviations

o Multifocal involvement o Arterial distributions often affected • Acute manifestations: Meningitis, cerebritis, vasculitis, ventriculitis, subdural empyema, arterial and venous infarction o Occasional spinal cord involvement • Chronic sequelae: Loculated hydrocephalus, cystic encephalomalacia

and Synonyms

• GBS meningitis; Group B B-hemolytic streptococcal meningitis, Group B streptococcus agalactiae meningitis

Definitions • Leading cause of newborn meningitis in developed countries o Early onset disease (EOD): GBS sepsis presenting in 1st week of life • 80% GBS infections are EOD; meningitis complicates 10% o Late onset disease (LOD): GBS sepsis presenting between 1 and 4 weeks of life • 20% GBS infections are LOD; meningitis complicates 40-60%

General Features

8 12

Axial CECT in the same case shows hydrocephalus, and hypodense deep and peripheral infarcts. Bifrontal, thick, rim enhancing subdural empyemas (open arrows) are easily seen.

• Best diagnostic clue: Meningoencephalitis in a newborn • Location: Cerebral hemispheres and deep gray matter • Size: Extensive, panlobar involvement typical • Morphology

CT Findings • NECT o Hydrocephalus +/- dependent debris in ventricles o Hypodensities in arterial distributions, white matter (WM), basal ganglia o Occasional hyperdense foci = hemorrhagic venous infarcts, laminar necrosis o Hypodense subdural collections = subdural empyema • CECT o Variably present dural, leptomeningeal, parenchymal enhancement • Thick, rim-enhancement around subdural empyemas • Abscess formation unusual o Ependymal enhancement indicates ventriculitis

MR Findings • TlWI o Hypo- and hyperintense

DDx: Neonatal Meningoencephalitis

E. Coli

Citrobacter

HSV2

Infection and Demyelinating Disease

foci common

GROUP B STREPTOCOCCAL MENINGITIS Key Facts Terminology • Leading cause of newborn meningitis countries

in developed

• Best diagnostic clue: Meningoencephalitis newborn

• • • •

• • •

in a

Diagnoses

• Other neonatal meningitides • Congenital infections (TORCH) • Hypoxic ischemic encephalopathy

•

(HIE)

• Newborn with sepsis • Typical signs/symptoms of meningitis subtle or absent in neonate • Maternal risk factors EOD: GBS colonization, GBS chorioamnionitis/bacteruria, membrane rupture> 18 hrs, intrapartum fever ~ 380 C, previous newborn with EOD, delivery <: 37 wks gestation

Pathology

Diagnostic Checklist

• GBS agalactiae serotype III responsible for majority of GBS meningitis

• No imaging features distinguish other neonatal meningitides

• Multifocal hypointensities = edema, ischemia, infarction • Hyperintense foci cortex and WM = laminar necrosis, hemorrhagic venous infarction T2WI: Blurring/loss of gray/WM junction = ischemia, infarction FLAIR: Pus in ventricles, subdural space, sulci and cisterns is hyperintense T2* GRE: Blooming of hemorrhagic foci DWI: Restriction within infarcts and pus collections Tl C+ o Variably present dural, leptomeningeal, parenchymal enhancement o Ependymal enhancement indicates ventriculitis o Thick, rim-enhancement around subdural empyemas MRA: Arterial narrowings, occlusions MRV: Dural venous sinus/cortical vein thrombosis (up to 30%) MRS: 1 Choline, I NAA; (+) lactate in areas of ischemia/infarction

Ultrasonographic

GBS

Clinical Issues

Imaging Findings

Top Differential

• 10-30% pregnant women have asymptomatic colonization of genitallGI tract • Incidence EOD 0.5/1000 live births

Findings

• Real Time o Hydrocephalus +/- mobile, echogenic debris in ventricles o Variably present 1 echogenicity parenchyma and sulci

Angiographic

Findings

• Conventional:

Vasospasm; arterial/venous

thromboses

Imaging Recommendations • Best imaging tool: MR with DWI/MRA/MRV • Protocol advice: CT useful for rapid, initial assessment of hemodynamically unstable neonate

GBS meningitis

from

o Account for majority of early onset meningitis in developing countries o Higher mortality than GBS meningitis o Specific pathogens • E. Coli: Along with GBS meningitis, major cause newborn meningitis in developed countries • Enterobacter spp: Most common cause meningitis in first few months of life • Citrobacter spp: Rare; high morbidity/mortality 2° to frequent abscess formation • Other meningitides o Listeria monocytogenes: Gram (+) rod

Congenital infections (TORCH) • CMV, toxoplasmosis, rubella: Infection occurs in-utero with chronic sequelae present in neonate/infant o CMV: Periventricular Ca++, microcephaly, migrational abnormalities, encephalomalacia, cerebellar hypoplasia o Toxoplasmosis: Parenchymal Ca++, encephalomalacia, microphthalmia • Herpes simplex virus type 2 (HSV 2): Infection acquired during passage through birth canal; presents in first 2-4 wks of life o Meningoencephalitis with extensive edema, necrosis, cystic encephalomalacia

Hypoxic ischemic encephalopathy

(HIE)

• Preterm: Injury to periventricular WM (mild) or thalami, basal ganglia, brain stem (severe) • Term: Injury to mature vascular watershed (mild) or areas of early myelination/metabolic activity (severe)

I PATHOLOGY General Features

I DIFFERENTIAL DIAGNOSIS Other neonatal meningitides • Enteric, Gram (-) meningitis

• General path comments o GBS agalactiae serotype III responsible for majority of GBS meningitis o Embryology-anatomy • GBS is a potent activator of the neonatal immune/inflammatory response

Infection and Demyelinating Disease

8 13

• Etiology o EOD: Aspiration of infected amniotic fluid or secretions birth canal o LOD: As EOD or postnatal maternal contact, breast milk, nosocomial o Onset bacteremia facilitated by immature neonatal immune system o Development of meningitis related to magnitude/duration of bacteremia o Production of B-hemolysin facilitates access of GBS across blood brain barrier • Epidemiology o 10-30% pregnant women have asymptomatic GBS colonization of genital/GI tract • 1-2% newborns born to colonized women develop EOD o Incidence EOD 0.5/1000 live births • Incidence decreased by > 50% as result of maternal screening & intrapartum chemoprophylaxis • Reduction incidence of GBS EOD accompanied by increase incidence neonatal Gram (-) sepsis • Term infants account for 50% GBS EOD 2° preterm intrapartum chemoprophylaxis

Gross Pathologic & Surgical Features • Debris, exudates at subarachnoid space/ventricles; ventricular septations • Parenchymal infarction/encephalomalacia; luminal narrowing vessels

Microscopic

Features

• Inflammation

adventitia

and vaso vasorum

=

Natural History & Prognosis • Prognosis o Mortality of early onset disease • 2% in full-term newborns, 10% in 34-36 wks gestational age, 30% in < 33 wks gestational age o Morbidity meningitis: 12-30% neurological sequelae (cortical blindness, spasticity, global mental retardation)

Treatment • Maternal o GBS screen: Rectovaginal swab at 35-37 wks gestation o (+) Maternal GBS screen OR presence of other risk factors: Intrapartum IV penicillin at least 4 hrs prior to birth o Future strategies • GBS PCR assay and rapid strep screen at onset of labor • GBS vaccine: Ideal prevention strategy; would prevent development of antibiotic-resistant pathogens • Neonatal meningitis o High dose IV penicillin • Therapy continued for 2-3 wks following CSF sterilization o +/- Antiepileptics o Multiple shunts usually required for loculated ventricles & periventricular cysts

vasculitis

Image Interpretation Presentation

8 14

Pearls

• No imaging features distinguish other neonatal meningitides

• Most common signs/symptoms o Lethargy, poor feeding, irritability o Seizures (40%), and bulging fontanelle are typically late findings • Clinical profile o Newborn with sepsis o Typical signs/symptoms of meningitis subtle or absent in neonate • CSF analysis: t White blood cells, protein; !glucose • CSF/blood Gram stain: Gram (+) diplococci • Maternal risk factors EOD: GBS colonization, GBS chorioamnionitislbacteruria, membrane rupture> 18 hrs, intrapartum fever;::: 38° C, previous newborn with EOD, delivery < 37 wks gestation

1.

2. 3.

4. 5.

Demographics • Age o 90% newborns with GBS EOD present within first 24 hrs of life o GBS LOD presents between 1 to 4 weeks after birth; occasionally up to 6 months • Gender: Male, preterm in(ants « 37 weeks) most at risk for EOD • Ethnicity: Maternal GBS colonization rates highest in African-American women

6.

GBS meningitis

from

Stevens JP et al: Long term outcome of neonatal meningitis. Arch Dis Child Fetal Neonatal Ed. 88(3):F179-84, 2003 Heath PT et al: Neonatal meningitis. Arch Dis Child Fetal Neonatal Ed. 88(3):F173-8, 2003 American College of Nurse-Midwives. Related Articles et al: Early-onset group B strep infection in newborns: prevention and prophylaxis Number 2, April 2003 (replaces Clinical Bulletin number 2, January 1997). J Midwifery Womens Health. 48(5):375-81, 2003 Gotoff SP: Group B Streptococcal Infections. Pediatr Rev 23:381-6,2002 Doran KS et al: Perinatal/Neonatal Case Presentation: Late-Onset Group B Streptococcal Infection in Identical Twins: Insight to Disease Pathogenesis. J Perinatol 22:326-30, 2002 Barkovich AJ: Infections of the Nervous System. Pediatric Neuroimaging, Lippincott William & Wilkins, Philadelphia, 715-70,2000

Infection and Demyelinating Disease

Typical (Left) Axial TlWI MR shows ill-defined, dependent, hypointense debris within the posterior horns of the lateral ventricles (arrows). (Right) Axial OWl MR shows diffusion restriction within the dependent intraventricular inflammatory exudate (pus).

Typical (Left) Axial T2WI MR shows multiple, tiny, hyperintense foci within the basal ganglia (open arrows). There is blurring of the bi-frontal and bi-occipital gray/white matter junction (arrows). (Right) Axial OWl MR shows diffusion restriction within multiple tiny basal ganglia infarcts and peripheral bi-occipital and bifrontal lobe infarcts.

Typical

(Left) Circle of Willis MRA shows occlusion of the right middle cerebral artery (open arrow). There is irregularity of the right supraclinoid ICA and proximal right middle cerebral artery (arrows). (Right) Axial OWl MR shows diffusion restriction within the right middle cerebral artery territory and left peri-sylvian cortex in a patient with right middle cerebral artery occlusion.

Infection and Demyelinating Disease

8 15

Axial T2WI MR shows "square" cavitating lesions of the frontal white matter. Note internal septation (arrow) from coalescence of small cavities.

Axial T7 C+ MR shows liquefying cavity with focal "dot-like" septal enhancement (arrow).

• Morphology:

Abbreviations

CT Findings

and Synonyms

• Citrobacter meningitis • Citrobacter cerebritis

Definitions • Citrobacter is a gram-negative o Predilection for very young, o In newborns (NB) ~ sepsis, abscesses o In elderly ~ causes urinary, infections

(Gm-) enteric bacterium very old meningitis, and cerebral upper respiratory tract

General Features

8 16

Square abscesses

• Best diagnostic clue o Multiple, large, cystic ("square") brain lesions • Replace (not displace) white matter o "Square" abscesses • Square abscess that "rounds" more likely to have infected contents • Increasing mass effect/edema more likely to have infected contents • Location: Predilection for lobar white matter (WM) • Size: Multiple large WM cysts

• NECT o Early (cerebritis) • Patchy, multilobar WM lesions • Low attenuation compared to unmyelinated brain o Late (abscess) • Lobar WM cavities with septations • Square morphology of abscesses • "Dot-like" focus of septal Ca++ • CECT o Early (cerebritis) • Variable often subtle parenchymal enhancement o Late (abscess) • "Dot-like" foci of septal enhancement • Rim or marginal septal enhancement • Multiple large cavities (+/- septations), replace WM

MR Findings • TlWI o Early (cerebritis) • Patchy multilobar areas of diminished Tl signal o Late (abscess) • Multiple large cysts • Square morphology • Septations • Tl WM signal abnormality diminishes

DDx: Pediatric Cavitary White Matter lesions

Pyogenic Abcess

Encephalomalacia

NAHI and WM Tears

Infection and Demyelinating Disease

CITROBACTER MENINGITIS Key Facts Clinical Issues

Imaging Findings • • • •

Multiple, large, cystic ("square") brain lesions Location: Predilection for lobar white matter (WM) Best imaging tool: MR brain with contrast Reveals dot-like foci of septal enhancement of the "squared" abscesses

Top Differential

Diagnoses

• Other bacterial brain infections • Cystic encephalomalacia • White matter lacerations in non-accidental injury (NAHI)

head

Sick, septic newborn or preterm infant Bulging fontanel, apnea, and seizures Immunocompromised patients are at higher risk 30% of neonates and infants with Citrobacter CNS infection die • 80% of neonates with Citrobacter meningitis develop brain abscesses • 50% of Citrobacter meningitis/abscess survivors have significant CNS damage

Diagnostic Checklist • Not all rim-enhancing cavities are abscesses • Citrobacter species (spp) and Enterobacter sakazakii have similar imaging

Pathology • Citrobacter CNS infection

• T2WI o Early (cerebritis) • Patchy multilobar T2 prolongation o Late (abscess) • Multiple septated cavities • Usually bilateral • T2 prolongation within WM • Variable edema, mass effect • Eventually, cavities may contract, causing profound WM loss • FLAIR: Increased signal within lobar WM • T2* GRE: "Dot-like" Ca++ within septal walls shows diminished signal • Tl C+ o Early (cerebritis) • Subtle patchy WM enhancement o Late (abscess) • Patchy WM enhancement • Rim or septal wall enhancement • "Dot-like" focus of septal enhancement • MRS o Products of fermentation • Lactate, acetate, and succinate o Proteolysis end-products released from neutrophils • Valine and leucine

Ultrasonographic

• • • •

Findings

• Real Time o Early (cerebritis) • Patchy regions of increased echogenicity • Loss of normal internal WM echo architecture o Late (abscess) • Multiple septated WM anechoic or hypoechoic cavities • Color Doppler:. Subtle flow within abscess septal walls

Imaging Recommendations • Best imaging tool: MR brain with contrast • Protocol advice o MR brain with contrast • Shows early parenchymal enhancement cerebritis

of

• Reveals dot-like foci of septal enhancement of the "squared" abscesses • Detects complications of brain infection (vascular, extra-axial purulent collections)

I DIFFERENTIAL

DIAGNOSIS

Other bacterial brain infections • Usually with greater surrounding edema and mass effect • Possible sinus, mastoid, or embolic/hematogenous sources of infection

Cystic encephalomalacia • • • •

Cortical and deep gray matter involved Thalamic and basal ganglia Ca++ Cysts replaces WM Passive ventricular dilatation

White matter lacerations in non-accidental head injury (NAHI) • Frontal lobe WM • Fluid level may be seen dependently within laceration • Associated intracranial manifestations of NAHI o Parafalcine/convexity subdural hematoma, subarachnoid hemorrhage

IPATHOlOG~ General Features • General path comments o Citrobacter spp are (Gm-) bacilli in the enterobacteriaceae family o Infection acquired • Horizontally (nosocomial) • Vertically (maternal) o Colonization (skin, umbilical stump) ~ bacteremia ~ meningitis o Embryology-anatomy: Predominantly lobar WM involvement • Genetics: No particular genetic predisposition known

Infection and Demyelinating Disease

8 17

• Etiology o Neurovirulence factors of Citrobacter spp • Unique 32-kD outer membrane protein • Resistance to phagocytosis o Citrobacter spp invades/transcytoses microvascular endothelial cells • Leads to hemorrhagic necrosis and abscess o Intracellular replication of Citrobacter in microvascular endothelial cells • Contributes to persistence of brain infection • Epidemiology o Epidemiology of Citrobacter infection • 5% of NB (gram negative) meningitis • 80% of NB brain abscesses • Abscesses may only appear near completion of therapy o Citrobacter CNS infection • Most cases considered sporadic • NICU outbreaks do occur

Gross Pathologic & Surgical Features • Opaque leptomeninges • Purulent exudate • Diffuse ependymitis

Microscopic

• 50% of Citrobacter meningitis/abscess significant CNS damage

Treatment • Antibiotics are mainstay of therapy • Determining antibiotic susceptibility is critical • Two drug therapy is standard o Remember, late abscesses occur! o Prolonged therapy typically required • Adjunctive surgical drainage of abscesses o If size > 2 em o If poorly responsive to initial antibiotic therapy

Image Interpretation

Pearls

• Minimal edema surrounding abscesses • Square abscesses with focal septal enhancement • Not all rim-enhancing cavities are abscesses o Some are WM necrosis and liquefaction • Citrobacter species (spp) and Enterobacter sakazakii have similar imaging

Features

• No well-formed fibrotic capsule • Organisms in walls of congested vessels • Neutrophils plus necrotic cell debris

1.

2.

Staging, Grading or Classification Criteria • Necrotic cavity vs infected abscess: Differentiation be difficult o Increased "Rounding" of cavity suggests abscess

can 3. 4.

5.

Presentation • Most common signs/symptoms o Sick, septic newborn or preterm infant o Bulging fontanel, apnea, and seizures • Clinical profile o In VLBW neonates • Sepsis • Bulging fontanelle • Cavitary brain lesions at imaging • Immunocompromised patients are at higher risk o Remember, neonates & sick preterms are immunocompromised! 18

survivors have

6.

Praise 0 et al: Citrobacter koseri (diversus) meningitis in an otherwise healthy adolescent. Scan] Infect Dis 35: 202-4, 2003 Badger ]L et al: Citrobacter freundii invades and replicates in human brain microvascular endothelial cells. Infect Immun. (8):4208-15, 1999 Doran T: Role of Citrobacter in Clinical Disease of Children: Review. Clin Infect Dis 28:384-94, 1999 Meier A et al: Neonatal citrobacter meningitis: Neurosonographic observations.] Ultrasound Med. 17(6):399-401, ]un, 1998 Tse G et al: Neonatal meningitis and multiple brain abscesses due to Citrobacter diversus. Pediatr Pathol Lab Med. 17(6),977-82, Nov - Dee, 1997 Kline MW et al: Citrobacter Diversus and Neonatal Brain Abscess. Pediatric Neurology 3(3):178-80, 1987

Demographics • Age o Mean age of onset of sepsis 5 days o Preterm newborns of very low birth weight (VLBW) are most susceptible o Citrobacter eNS infection beyond one month is rare

Natural History & Prognosis • 30% of neonates and infants with Citrobacter CNS infection die • 80% of neonates with Citrobacter meningitis develop brain abscesses

Infection and Demyelinating

Disease

Typical (Left) Axial NECT shows bi-frontal and left temporal "square" white matter cavitations (Courtesy M. Halsted, MO). (Right) Axial NECT shows cavitation of frontal lobe white matter (arrows) and peri-frontal volume loss (Courtesy M. Halsted, MO).

Variant (Left) Axial T2WI MR shows intraaxial and extra-axial abscesses including a hemorrhagic right occipital cavitation (arrow) (Courtesy S. Blaser, MO). (Right) Axial T1 C+ MR shows ring enhancement (arrow) of several, but not all, of the cavities identified on T2WI (Courtesy S. Blaser; MO).

Variant (Left) Axial NECT in same case followup demonstrates retraction of cavities with a tiny residual "dot" of calcification (arrow) and significant local volume loss (Courtesy S. Blaser, MO). (Right) Axial T 7 WI M R in a different case shows asymmetric periventricular white matter volume loss and cavity retraction (arrow) at the conclusion of therapy (Courtesy S. Blaser; MO).

Infection and Demyelinating Disease

8 19

Axial graphic shows diffuse inflammatory exudate involving the leptomeninges, filling the basal cisterns and sulci. This results in increased density/signal intensity on imaging studies.

Axial T1 C+ MR shows extensive leptomeningeal enhancement of the sulci and cisterns (arrows) in this 56 year old male patient with Streptococcus pneumoniae meningitis.

CT Findings Abbreviations

and Synonyms

• Leptomeningitis

Definitions

8 20

• NECT o Normal study is most common o Mild ventricular enlargement o Subarachnoid space enlargement o Basal cisterns effaced • CECT o Enhancing exudate in sulci, cisterns may be seen o Low density areas related to perfusion alterations • CTA: Arterial narrowing, occlusion

• Inflammatory infiltration of the pia mater, arachnoid, and CSF • Commonly related to hematogenous dissemination from a distant infection • Can be divided into acute pyogenic (bacterial), lymphocytic (viral), and chronic (TB) meningitis

MR Findings

General Features

• • • •

• Best diagnostic clue: Positive CSF by lumbar puncture • Location: Subarachnoid space, pia enhance • Morphology o Smooth, intense leptomeningeal enhancement typical o TB, fungal meningitis often basilar and confluent; may be nodular • Imaging may be normal early • Imaging findings nonspecific • Imaging best delineates complications o Hydrocephalus often occurs as early complication

DDx: Leptomeningeal

Metastasis

Tl WI: Exudate is isointense T2WI: Exudate is hyperintense FLAIR: Hyperintense signal in sulci, cisterns DWI o Variable, may show restriction o Most useful for vascular complications • Tl C+: Exudate typically enhances • MRA: Arterial narrowing, occlusion • Complications o Extraventricular obstructive hydrocephalus (EVOH) o Ventriculitis, choroid plexitis o Abscess, empyema, effusion o Cerebrovascular (arteritis, infarct, venous thrombosis) • Cerebral edema, infarction • DWI useful in depicting perfusion alterations

Disease

Neurosarcoidosis

SAH

Infection and Demyelinating

Disease

MCA Infarct

MENINGITIS Key Facts Terminology

Pathology

• Inflammatory infiltration arachnoid, and CSF

• Most commonly related to hematogenous from a distant infection

of the pia mater,

spread

Imaging Findings

Clinical Issues

• Best diagnostic clue: Positive CSF by lumbar puncture • Imaging may be normal early • Imaging best delineates complications

• Adults: Headache, fever, nuchal rigidity, +/- altered mental status • Children: Fever, irritability, nuchal rigidity • Effective antimicrobial agents have reduced but not eliminated mortality, morbidity • Complications occur in 50% of adult patients • Infectious: Cerebritis/abscess, ventriculitis, empyema, effusion • Vascular: Ischemia related to arterial spasm or infectious arteritis, dural venous thrombosis • Mortality 20-25%

Top Differential • • • • •

Diagnoses

Carcinomatous meningitis Neurosarcoidosis Increased FLAIR signal in CSF Primary CNS oma Gadolinium in

Ultrasonographic

• Increased signal in CSF on T1WI and FLAIR

Findings

• In infants, sulcal enlargement, echogenic deposits in subarachnoid space • Abnormally thickened meninges

Angiographic

General Features

Findings

• Conventional o Arterial narrowing, occlusion related to spasm and infectious arteritis o Venous thrombosis may be seen

Imaging Recommendations • Best imaging tool: Contrast-enhanced MR to evaluate for possible complications of meningitis • Protocol advice: MR to include FLAIR, DWI, Tl C+

I DIFFERE~SJ"IJl\1:cDI~(jj~@5IS Carcinomatous

meningitis

• Breast, lung most common distant primary tumors • Primary CNS tumors include: GBM, medulloblastoma, pineal tumors, choroid plexus tumors • Primary tumor often known

Neurosarcoidosis • Lacy leptomeningeal enhancement typical • May have ventricular, dural based enhancing

masses

Increased FLAIR signal in CSF • Subarachnoid hemorrhage • High inspired oxygen • Acute stroke (parenchymal congestion) • Artifact

(SAH) edema, vascular

Primary CNS lymphoma • Typically periventricular parenchymal • Occasionally, lymphocytic meningitis

Gadolinium

disease

in CSF

• Dialysis-dependent disease

I PJl\SJ"f"I@I:c@(jj¥

patient with end-stage renal

Infection

• General path comments o Pathology generally same regardless of agent o Routes of entry to CNS • Hematogenous • Choroid plexus (lacks a blood-brain barrier) • Direct extension o Pia penetrated by inflammatory cells, BBB altered o Meningitis-associated brain injury • Cytokines, reactive nitrogen species, hippocampal apoptosis (cell death) o Basilar meningitis typical of pyogenic infections, TB, cryptococcus, neurosyphilis, sarcoid, lymphoma • Etiology o Most commonly related to hematogenous spread from a distant infection o Direct extension less common • Sinusitis, otitis media, orbital infection o Penetrating injury least common • Epidemiology o Bacterial meningitis has increased in last 30 years related to nosocomial infection • Approximately 3/100,000 population in US o Meningitis is the most common form of CNS infection in children o Incidence of bacteria based on age • Elderly: Listeria monocytogenes, streptococcus pneumoniae, neisseria meningitidis, gram (-) bacilli • Adults: S pneumoniae, N meningitidis, group B streptococcus • Children: N meningitidis • Infants: S pneumoniae, N meningitidis • Neonates: Group B streptococcus, escherichia coli o Vaccine has markedly decreased incidence of Haemophilus influenzae meningitis o Viral meningitis: Enteroviruses most common

and Demyelinating

Disease

8 21

o Chronic meningitis: Mycobacterium tuberculosis (TB) most common o Fungal meningitis: Cryptococcus neoformans (AIDS) and Coccidioides immitis most common

Gross Pathologic & Surgical Features

Treatment

• Cisterns, sulci filled with cloudy CSF, then purulent exudate • Pia-arachnoid congested, may mimic SAH • Cortex may be edematous

• Intravenous antibiotics o Empiric therapy is based on age • < 1 month, Ampicillin and Cefotaxime • > 1 month, Ceftriaxone or Cefotaxime + Vancomycin + Dexamethasone o Specific therapy is based on culture and sensitivity o Ceftriaxone or Cefotaxime +/- Vancomycin, treatment of choice for most bacterial meningitides o Penicillin or Ampicillin for N. meningitidis, L. monocytogenes, group B streptococcus o Amphotericin B +/- Fluconazole or Flucystosine for fungal meningitis o TB meningitis requires combination therapy: Isoniazid, Pyrazinamide, Rifampin o Viral meningitis is treated with supportive care; except herpes meningitis - Acyclovir • Dexamethasone is a useful adjuvant therapy • Surgical intervention usually required for complications

Microscopic

Features

• Meningeal exudate o Polymorphonuclear neutrophils (PMNs), fibrin, intracellular and extracellular bacteria • Vessels within exudate may show fibrinoid necrosis, thrombosis • Foci of cortical necrosis • Infection may extend into perivascular spaces, ventricles • Subpial microglial, astrocytic proliferation

Presentation • Most common signs/symptoms o Adults: Headache, fever, nuchal rigidity, +/- altered mental status • Brudzinski sign: Flex neck, hips and knees flex involuntarily • Kernig sign: Flex hips and knees, try to extend knees, pain in hamstrings and patient resists o Children: Fever, irritability, nuchal rigidity o Infants: Fever, lethargy, irritability o Seizures in 30% of patients • Clinical profile o CSF shows increased white blood cells (leukocytosis) • Elevated CSF protein, decreased glucose typical of infectious meningitis o Purpuric rash may develop in N meningitidis (meningococcal) meningitis, highly morbid • Meningitis is a clinical-laboratory diagnosis

Demographics • Age: Occurs at all ages • Gender: No gender predominance

8 22

• Infection reaches labyrinth via cochlear aqueduct from subarachnoid space • Results in bilateral hearing loss typically • Mortality 20-25%

Natural History & Prognosis • Effective antimicrobial agents have reduced but not eliminated mortality, morbidity • Impaired CSF resorption may cause EVOH • Elevated ICP, cerebral perfusion alterations may occur as early complications • Complications occur in 50% of adult patients o Infectious: Cerebritis/abscess, ventriculitis, empyema, effusion • Effusion may be difficult to differentiate from empyema o Vascular: Ischemia related to arterial spasm or infectious arteritis, dural venous thrombosis o Labyrinthine ossificans is an uncommon complication

Consider • Imaging may be normal, most useful for complications

Image Interpretation

Pearls

• T1 C+, FLAIR often complementary

1.

in diagnosis

Kamran S et al: Role of fluid-attennuated invasion recovery in the diagnosis of meningitis: comparison with contrast-enhanced magnetic resonance imaging.] Comput Assist Tomogr 28:68-72,2004 2. Anzai Y et al: Paramagnetic effect of supplemental oxygen on CSF hyperintensity of FLAIRMR images. A]NR 25:274-9, 2004 3. ]an W et al: Diffusion-weighted imaging in acute bacterial meningitis in infancy. Neuroradiology. 45(9):634-9, 2003 4. Winkler F et al: Discrepancies between brain CT imaging and severely raised intracranial pressure proven by ventriculostomy in adults with pneumococcal meningitis. ] Neurol. 249(9):1292-7, 2002 5. Wall RA:Meningococcal disease: treatment and prevention. Ann Med. 34(7-8):624-34, 2002 6. de Gans] et al: Dexamethasone in adults with bacterial meningitis. N Engl] Med. 347(20):1549-56, 2002 7. Kaplan SL:Management of pneumococcal meningitis. Pediatr Infect Dis]. 21(6):589-91, 2002 8. Rai AT et al: Persistence of gadolinium in CSF: A diagnostic pitfall in patients with end-stage renal disease. A]NR 22:1357-61,2001 9. Teixeira] et al: Diffusion imaging in pediatric central nervous system infections. Neuroradiology. 43(12):1031-9, 2001 10. Kanamalla US et al: Imaging of cranial meningitis and ventriculitis. Neuroimaging Clin N Am. 10(2):309-31,2000

Infection and Demyelinating Disease

MENINGITIS IIMAGE GALLERY Typical (Left) Axial FLAIRMR shows

diffuse abnormal signal throughout the sulci (arrows) related to pyogenic meningitis. Note the normal suppressed CSF signal intensity in the lateral ventricles. (Right) Axial T1 C+ MR shows subtle leptomeningeal enhancement (arrow) in this 48 year old with N meningitidis. Imaging may be normal and is most helpful to exclude complications of meningitis.

Variant (Left) Axial T2WI MR shows

the complications of Coccidioidomycosis meningitis including hydrocephalus with transependymal flow of CSF, vasculitis, and cerebritis (arrows). (Right) Axial T1 C+ MR shows intense, irregular enhancement in the areas of cerebritis (black arrows). Note also the left basal ganglia chronic infarct related to infectious arteritis (white arrow).

Other (Left) Sagittal T1 C+ MR

shows extensive enhancement obliterating the basal cisterns, filling the cisterna magna, granulomatous meningitis. Note the dilated fourth ventricle (Courtesy T. Swallow, MO). (Right) Cross pathology shows extensive purulent exudate coating the base of brain involving the leptomeninges. The sulci and cisterns were also involved. E. coli meningitis (Courtesy j. Townsend, MO).

Infection and Demyelinating

Disease

8 23

ABSCESS

Axial graphic shows early cerebritis (initial phase of abscess formation). A focal unencapsulated mass of petechial hemorrhage, inflammatory cells and edema is seen.

• Gas-containing

I TERMINOLOGY • Focal pyogenic infection of the brain parenchyma, typically bacterial; fungal or parasitic less common • Four pathologic stages: Early cerebritis, late cerebritis, early capsule, late capsule

IMAGING FINDINGS General Features

24

abscess rare

CT Findings

Definitions

8

Axial graphic shows early capsule formation with central liquified necrosis and inflammatory debris. Collagen and reticulin form the well-defined abscess wall. Note the surrounding edema.

• Best diagnostic clue o Imaging varies with stage of abscess development o Early capsule: Well-defined, thin-walled enhancing rim o Ring-enhancing lesion with • High signal (restricted diffusion) on DWI, low ADC o T2 hypointense abscess rim with surrounding edema • Location o Typically supratentorial, but may occur infratentorial (up to 14%) o Frontal and parietal lobes most common, gray-white junction (hematogenous) o Anterior and middle cerebral artery distributions • Size: Variable,S mm - several cm • Morphology: Smooth, ring-enhancing lesion

DDx: Ring-enhancing

Primary Tumor

• NECT o Early cerebritis: Ill-defined hypodense subcortical lesion with mass effect; may be normal early o Late cerebritis: Central low density area; peripheral edema, mass effect increase o Early capsule: Hypodense mass with moderate vasogenic edema and mass effect o Late capsule: Edema, mass effect diminish • CECT o Early cerebritis: +/- Mild patchy enhancement o Late cerebritis: Irregular peripheral rim enhancement o Early capsule: Low density center with thin, distinct enhancing capsule • Deep part of capsule is thinnest; thickest near cortex o Late capsule: Cavity shrinks, capsule thickens • May be multiloculated and have "daughter" abscesses

MR Findings • TlWI o Early cerebritis: Poorly marginated, mixed hypointense/isointense mass o Late cerebritis: Hypointense center, isointense/mildly hyperintense rim

lesions

Resolving Clot

Demyelination

Infection and Demyelinating Disease

Metastasis

ABSCESS Key Facts Terminology

• Subacute infarct

• Four pathologic stages: Early cerebritis, late cerebritis, early capsule, late capsule

Clinical Issues

Imaging Findings of abscess development • Imaging varies with s • Early capsule: Well , thin-walled enhancing rim • High signal (restricted diffusion) on DWI, low ADC • T2 hypointense abscess rim with surrounding edema • Late capsule: Cavity collapses, thickened enhancement of capsule

Top Differential

Diagnoses

• Primary or metastatic neoplasm • Resolving hematoma • Demyelination

•

•

•

•

•

o Early capsule: Rim isointense to hyperintense to WM; center hyperintense to CSF o Late capsule: Cavity shrinks, capsule thickens T2WI o Early cerebritis: Ill-defined hyperintense mass o Late cerebritis: Hyperintense center, hypointense rim; hyperintense edema o Early capsule: Hypointense rim • Related to collagen, hemorrhage, or paramagnetic free radicals o Late capsule: Edema and mass effect diminish DWI o Increased signal intensity in cerebritis and abscess o ADC map: Markedly decreased signal centrally within abscess Tl C+ o Early cerebritis: Patchy enhancement o Late cerebritis: Intense but irregular rim enhancement o Early capsule: Well-defined, thin-walled enhancing rim o Late capsule: Cavity collapses, thickened enhancement of capsule • Capsule is thinnest on the ventricular side MRS: Central necrotic area may show presence of acetate, lactate, alanine, succinate, pyruvate, and amino acids Resolving abscess o Hyperintense on T2WI, FLAIR; hypointense rim resolves o Small ring/punctate enhancing focus may persist for months

Nuclear Medicine

Findings

• PET: FDG and Carbon-ll-Methionine increased uptake in brain abscess

have shown

Imaging Recommendations • Best imaging tool: Contrast-enhanced MR • Protocol advice: Multiplanar MR without and with contrast, DWI; MRS may be helpful

• Headache most common symptom (up to 90%); fever in approximately 50% • Surgical drainage and/or excision primary therapy • Antibiotics only, if small « 2.5 em) or early phase of cerebritis

Diagnostic Checklist • DWI, MRS helpful in distinguishing abscess from mimics • Search for local cause such as sinusitis, otitis media, or mastoiditis • T2 hypointense abscess rim resolves in successfully treated patients before enhancement

I DIFFERENTIAL

DIAGNOSIS

Primary or metastatic neoplasm • Thick, nodular enhancing wall typical • Low signal on DWI (occasionally high, can mimic abscess)

Resolving hematoma • History of trauma or vascular lesion • Blood products present

Demyelination • Enhancement often incomplete ring • Characteristic lesions elsewhere in brain • Small amount of mass effect for size of lesion

Subacute infarct • History of stroke • Vascular distribution,

gyriform enhancement

I PATI--IOlOG¥ General Features • General path comments o Cerebritis: Unencapsulated zone of vessels, inflammatory cells, and edema; necrotic foci gradually coalesce o Capsule: Well-defined capsule develops around necrotic core; as abscess matures, edema/mass effect decrease • Etiology o Hematogenous from extracraniallocation (e.g., pulmonary infection, endocarditis, urinary tract infections) o Direct extension from a calvarial or meningeal infection • Paranasal sinus, middle ear, teeth infections (via valveless emissary veins) o Penetrating trauma (bone fragments> > metal) o Postoperative o Right-to-Ieft shunts (congenital cardiac malformations, pulmonary arteriovenous fistulas)

Infection and Demyelinating Disease

8 25

o 20-30% have no identifiable source (cryptogenic) • Often polymicrobial (streptococci, staphylococci, anaerobes) • Epidemiology o Uncommon, approximately 2500 cases/year in U.S. o Bacterial: Staphylococcus, Streptococcus, Pneumococcus o Diabetic: Klebsiella pneumoniae o Posttransplant: Nocardia, Aspergillus, Candida o AIDS: Toxoplasmosis, Mycobacterium Tuberculosis o Neonates: Citrobacter, Proteus, Pseudomonas, Serratia, Staphylococcus aureus

Gross Pathologic & Surgical Features • Early cerebritis (3-5 days) o Infection is focal but not localized o Unencapsulated mass of PMNs, edema, scattered foci of necrosis and petechial hemorrhage • Late cerebritis (4-5 days up to 2 weeks) o Necrotic foci coalesce o Rim of inflammatory cells, macrophages, granulation tissue, fibroblasts surrounds central necrotic core o Vascular proliferation, surrounding vasogenic edema • Early capsule (begins at around 2 weeks) o Well-delineated collagenous capsule o Liquified necrotic core, peripheral gliosis • Late capsule (weeks to months) o Central cavity shrinks o Thick wall (collagen, granulation tissue, macrophages, gliosis)

Microscopic

Features

• Early cerebritis: Hyperemic tissue with PMNs, necrotic blood vessels, microorganisms • Late cerebritis: Progressive necrosis of the neuropil, destruction of PMNs, and inflammatory cells • Early capsule: Proliferation of granulation tissue about necrotic core • Late capsule: Multiple layers of collagen and fibroblasts

Presentation

26

• Most common signs/symptoms o Headache most common symptom (up to 90%); fever in approximately 50% o Other signs/symptoms: Seizures, altered mental status, focal neurologic deficits • Increased erythrocyte sedimentation rate (ESR) (75%), elevated WBC count (50%) • Clinical profile: Potentially fatal but treatable lesion • Variable prognosis, depending on o Size, location of abscess, virulence of infecting organism(s) o Systemic conditions

Demographics • Age o May occur at any age o Most common during third and fourth decades, but 25% occur in patients < 15 years

• Gender: M:F

=

2:1

Natural History & Prognosis • Complications of inadequately or untreated abscesses o Intraventricular rupture, ventriculitis (may be fatal) • Ventricular debris with irregular fluid level • Hydrocephalus • Ependymal enhancement typical o Meningitis, "daughter" lesions o Mass effect, herniation • Stereotactic surgery + medical therapy have greatly reduced mortality • Mortality variable, 0-30%

Treatment • Surgical drainage and/or excision primary therapy • Antibiotics only, if small « 2.5 em) or early phase of cerebritis • Steroids to treat edema and mass effect • Lumbar puncture hazardous, pathogen often can't be determined from CSF

Consider • DWI, MRS helpful in distinguishing mimics

Image Interpretation

abscess from

Pearls

• Search for local cause such as sinusitis, otitis media, or mastoiditis • T2 hypointense abscess rim resolves in successfully treated patients before enhancement

1.

Gary M et al: Brain abscess: Etiologic catheterization with vivo proton MR spectroscopy. Radio1230:519-27, 2004 2. Kao PT et al: Brain abscess: clinical analysis of 53 cases. ] Microbiol Immunol Infect. 36(2):129-36, 2003 3. Tsuyuguchi N et al: Evaluation of treatment effects in brain abscess with positron emission tomography: comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine. Ann Nucl Med. 17(1):47-51,2003 4. Leuthardt EC et al: Diffusion-weighted MR imaging in the preoperative assessment of brain abscesses. Surg Neurol. 58(6):395-402; discussion 402, 2002 5. Guzman R et al: Use of diffusion-weighted magnetic resonance imaging in differentiating purulent brain processes from cystic brain tumors.] Neurosurg. 97(5):1101-7,2002 6. Lai PH et al: Brain abscess and necrotic brain tumor: discrimination with proton MR spectroscopy and diffusion-weighted imaging. A]NR Am] Neuroradiol. 23(8):1369-77, 2002 7. Hartmann M et al: Restricted diffusion within ring enhancement is not pathognomonic for brain abscess. A]NR Am] Neuroradiol. 22(9):1738-42, 2001 8. Verlicchi A et al: From diagnostic imaging to management of brain abscesses. Riv di Neuroradiol14: 267-74, 2001 9. Rushing E] et al: Infections of the nervous system. Neuroimaging Clin N Am. 11(1):1-13, 2001 10. Falcone S et al: Encephalitis, cerebritis, and brain abscess: pathophysiology and imaging findings. Neuroimaging Clin N Am. 10(2):333-53, 2000

Infection and Demyelinating Disease

Typical (Left) Axial T2WI MR shows an ill-defined hyperintense mass in the right frontal and parietal lobes of this 40 year old male with severe headaches and elevated ESR. Earlycerebritis. (Right) Coronal T1 C+ MR shows patchy enhancement, edema and mass effect. Patient was initially treated with intravenous antibiotics but progressed and eventually required surgical intervention.

Typical (Left) Axial T2WI MR shows

the typical hypointense rim with surrounding hyperintense edema in this 38 year old male with early capsule formation. (Right) Axial OWl MR shows characteristic restricted diffusion of the early capsule stage. The ADC map showed markedly decreased signal centrally within the abscess.

Typical (Left) Axial T2WI MR shows a hyperintense mass with a

hypointense rim at the gray-white junction in this 66 year old female with colon cancer and a liver abscess. Note the surrounding vasogenic edema. (Right) Axial T1 C+ MR shows a thick wall of enhancement of the late capsule stage abscess. Despite decreased edema after steroids, she underwent surgical drainage and Streptococcus was cultured.

Infection and Demyelinating Disease

8 27

Axial graphic shows a right frontal abscess which has ruptured into the ventricular system. Note the debris level within the ventricles and the inflammation along the ventricular margins.

Abbreviations • Ependymitis,

and Synonyms

ventricular

empyema, pyocephalus

Definitions • Ventricular ependyma infection related to meningitis, ruptured brain abscess, or ventricular catheter

General Features • Best diagnostic clue: Ventriculomegaly with debris level, enhancing ependyma, periventricular T2 hyperintensity

Axial CECT shows ventriculitis related to abscess rupture. Note ventriculomegaly, ependymal enhancement (curved arrow), & irregular debris levels (arrows) (Courtesy T. Swallow, MO).

o May see hypointense debris layering dependently • FLAIR o Hyperintensity along ventricular margins o May see hyperintense debris layering dependently • DWI: Diffusion restriction of layering debris, low ADC • Tl C+ o Marked ependymal enhancement with ventriculomegaly o May have associated choroid plexitis with enlarged, edematous choroid o May see inflammatory septations and loculations in chronic cases

Ultrasonographic

Findings

CT Findings

• In infants, increased of choroid • Echogenic

ventriculomegaly with irregular margins, periventricular echogenicity, poor definition plexus material may be seen layering in ventricles

• NECT o Ventriculomegaly with dependent debris level o Subtle areas of low density along ventricular margins • CECT: Diffuse enhancement of ventricular walls

• Best imaging tool: MR in adults, ultrasound in infants • Protocol advice: Multiplanar MR with contrast, DWI

Imaging Recommendations

MR Findings

8 28

• TlWI o Ventriculomegaly with hyperintense debris o Subtle periventricular hypointensity • T2WI o Hyperintensity along ventricular margins

Lymphoma • Ependymal enhancement, typically nodular • Parenchymal disease usually present

DDx: Ventricular Enhancement/Debris

Lymphoma

Ependymal Spread

Hemorrhage

Infection and Demyelinating Disease

Vase Malformation

VENTRICULITIS .Key Facts Terminology

Top Differential

• Ventricular ependyma infection related to meningitis, ruptured brain abscess, or ventricular catheter

• • • •

Imaging Findings • Best diagnostic clue: Ventriculomegaly with debris level, enhancing ependyma, periventricular T2 hyperintensity

hemorrhage

• Mortality rate 40-80%

Presentation • Most common signs/symptoms: Dependent on etiology; often indolent • Clinical profile: CSF cytology, cultures may be normal

Demographics

• History of trauma; other sequelae seen • Ventricles typically not enlarged

Prominent ependymal

Clinical Issues

IClINICAl.1lSSUES

Ependymal tumor spread • Primary brain tumors: GBM, medulloblastoma, pineal tumors, ependymoma, choroid plexus tumors • Metastatic tumor from extracranial primary (Le., breast)

Intraventricular

Diagnoses

Lymphoma Ependymal tumor spread Intraventricular hemorrhage Prominent ependymal veins

• Age: May occur at any age • Gender: M > F

veins

Natural History & Prognosis

• Vascular malformations: AVM, DVA, cav malf • Abnormal venous drainage (Le., Sturge-Weber)

• Mortality rate 40-80%

Treatment • Surgical irrigation and drainage, antibiotics

If'Al'~~I.1~~¥ General Features • General path comments o Pathogens include bacteria, fungus, virus, parasites o Associated choroid plexitis is rare • Etiology o Complication of meningitis or cerebral abscess which ruptures into ventricular system o Complication of neurosurgical procedure, most commonly intraventricular catheter o Common bacterial organisms: Staphylococcus, streptococcus, enterobacter • Epidemiology o Bacterial ventriculitis may occur in healthy individuals after trauma or neurosurgical procedure o Fungal or viral ventriculitis occurs most commonly in immunosuppressed patients o Ventriculitis occurs in 30% of meningitis patients; up to 80-90% in neonates/infants o Intrathecal chemotherapy, rarely associated

I SEI.1ECl'ED REFERENCES 1.

2.

Pezzullo JA et al: Diffusion-weighted MR imaging of pyogenic ventriculitis. AJR AmJ Roentgenol. 180(1):71-5, 2003 Lyke KE et al: Ventriculitis complicating use of intraventricular catheters in adult neurosurgical patients. Clin Infect Dis. 33(12):2028-33, 2001

I IMAGE

GAI.1LER¥

8 29

Gross Pathologic & Surgical Features • Intraventricular sedimentation levels with inflammation and proteinaceous debris

Microscopic

Features

• Ependymal and subependymal macrophages, lymphocytes

(Left) Axial T7 C+ MR shows ventriculitis and meningitis related to a

inflammation

with

right temporal lobe abscess rupture. Note ventriculomegaly and intense ventricular wall enhancement. (Right) Axial OWl MR shows diffusion restriction of the lateral ventricular debris and the temporal lobe abscess in this 49 year old male with multiple abscesses and ventriculitis related to tooth abscess.

Infection and Demyelinating Disease

J.lgittal graphic shows frontal sinusitis with purulent debris and direct extension to the epidural space, resulting in an empyema (EOE). Note the inflammation in the adjacent frontal lobe.

Sagittal T2WI MR shows an EOE with abnormal signal in the adjacent brain related to cerebritis. Note the inwardly displaced dura (curved arrow) and sinusitis (Courtesy C. Hedlund, DO).

CT Findings Abbreviations

and Synonyms

• Subdural empyema (SDE), epidural empyema (EDE), epidural abscess

Definitions • Loculated collection of pus in subdural or epidural space, or both

General Features

8 30

• Best diagnostic clue: Extra-axial collection with rim enhancement • Location o Supratentorial typical • SDE: Convexity in > 50%, parafalcine in 20% • EDE: Often adjacent to frontal sinus o lnfratentorial, up to 10% • Often associated with mastoiditis • Size: Variable • Morphology o SDE: Crescentic typical; may be lentiform on coronal images o EDE: Biconvex, lens-shaped (lentiform)

• NECT o Extra-axial collection, typically isodense to hyperdense to CSF o SDE: Crescentic iso/hyperdense collection, confined by falx (NB: Can be small, easily overlooked!) • Frequently bilateral o EDE: Biconvex low density collection between dura, calvarium, contained by cranial sutures • Often continuous across midline • CECT o Strong peripheral rim enhancement o Posterior fossa EDE • Typically at sino dural angle • Tegmen tympani eroded • Pus may extend into cerebellopontine angle

MR Findings • TlWI o Extra-axial collection, hyperintense to CSF o SDE: Crescentic extra-axial collection o EDE: Lens-shaped bifrontal or convexity collection • Inwardly displaced dura seen as hypointense line between collection and brain • May cross midline in frontal region • T2WI o Isointense to hyperintense to CSF

DDx: Extra-axial lesions

Chronic Hematoma

Subdural Effusions

Subdural Hygroma

Infection and Demyelinating Disease

Dural Metastases

EMPYEMA Key Facts Terminology • Loculated collection of pus in subdural or epidural space, or both

Imaging Findings • Best diagnostic clue: Extra-axial collection with rim enhancement • Supratentorial typical • Infratentorial, up to 10% • Extra-axial collection, typically isodense to hyperdense to CSF • Best imaging tool: MR best to demonstrate presence, nature, extent, and complications

Top Differential Diagnoses • Chronic subdural hematoma • Subdural effusion

• •

•

•

•

o SDE: Crescentic collection, underlying brain may be hyperintense o EDE: Lens-shaped bifrontal or convexity collection • Inwardly displaced dura seen as hypointense line between collection and brain • Underlying brain may be hyperintense PD/Intermediate: Isointense to hyperintense to CSF FLAIR o Hyperintense to CSF o SDE: Crescentic collection, underlying brain may be hyperintense o EDE: Lens-shaped bifrontal or convexity collection • Underlying brain may be hyperintense DWI o SDE: Restricted diffusion (increased signal intensity) typical o EDE: Variable signal, may be mixed Tl C+ o Prominent enhancement at margin related to granulomatous tissue and inflammation o SDE: Encapsulating membranes enhance strongly, may be loculated with internal fibrous strands o EDE: Strong enhancement of collection margins o May see enhancement of adjacent brain parenchyma (cerebritisl abscess) o Subgaleal phlegmon or abscess ("Pott's puffy tumor") MRV: Venous thrombosis may be seen as lack of flow

Ultrasonographic

Findings

• Useful in infants • Heterogenous echogenic convexity collection with mass effect o Hyperechoic fibrous strands o Thick hyperechoic inner membrane o Increased echogenicity of pia-arachnoid and exudates in the subarachnoid space

Imaging Recommendations • Best imaging tool: MR best to demonstrate presence, nature, extent, and complications • Protocol advice o Contrast-enhanced multiplanar MR with DWI o DWI helpful to evaluate extent and complications

• Subdural hygroma • Dural metastasis

Pathology • Subdural empyema is more common than EDE • 15% of cases have both EDE, SDE • Infants, young children: Meningitis effusion which becomes superinfected • Older children, adults: Related to paranasal sinus disease in > 2/3

Clinical Issues • Epidural, subdural empyemas are rare, yet highly lethal • May progress rapidly, considered neurosurgical emergencies • Mortality 10-15%

IIJIFFEREN1H~1.1J1~~Nm~l~ Chronic subdural hematoma • MR shows blood products, may be loculated • Often enhances along edge, typically thinner than SDE • May be indistinguishable; history may help

Subdural effusion • • • •

Sterile, CSF-like collection associated with meningitis Follows CSF on all MR sequences Usually nonenhancing; may enhance mildly Frontal and temporal regions common, often bilateral

Subdural hygroma • Nonenhancing

CSF collection, often trauma history

Dural metastasis • Primary tumor often known, typically breast, prostate • Often diffuse, nodular enhancement • May have associated bone metastases

I p~J'MmLm~¥ General Features • General path comments o Subdural empyema is more common than EDE o SDE are more commonly complicated by abscess and venous thrombosis, > 10% of patients o 15% of cases have both EDE, SDE • Etiology o Infants, young children: Meningitis effusion which becomes superinfected o Older children, adults: Related to paranasal sinus disease in > 2/3 • Direct spread through posterior wall of frontal sinus • Retrograde spread through valveless bridging emissary veins of extra-, intracranial spaces o Mastoiditis 20% o Complication of head trauma or neurosurgical procedure, rare

Infection and Demyelinating Disease

8 31

o Complication of meningitis in adults, extremely rare o Causative organism: Streptococci, H influenzae, S aureus, S epidermidis most common o Anaerobic or microaerophilic organisms (strep, bacteroides) common • Epidemiology o Uncommon, occur 1/4 to 1/2 as often as abscess o SDE and EDE account for approximately 30% of intracranial infections o SDE: Sinusitis in 67%, mastoiditis in 10%

Gross Pathologic & Surgical Features

• Surgical drainage through wide craniotomy is gold standard • Intravenous antibiotics • Conservative management may be effective in small sinus-related EDE with adequate sinus drainage, antibiotics

Consider

• Encapsulated, yellowish, purulent collection • Spreads widely but may be loculated • Osteitis in 35%

Microscopic

Treatment

• Chronic subdural hematoma may be difficult to differentiate from SDE, history may help! • If a patient has sinusitis and neurologic symptoms, look for empyema!

Features

• Inflammatory infiltrate surrounded by granulomatous tissue

Presentation • Most common signs/symptoms o Majority have fever, headaches o Meningismus common, may mimic meningitis o Sinusitis often present o If large, mass effect causes focal neurologic signs or seizures, up to 50% • Clinical profile o Sinus or ear infection in > 75% of cases o Frontal subgaleal abscess ("Pott's puffy tumor") in up to 1/3 • Typically adolescent males o Periorbital swelling may be seen • Clinical diagnosis often delayed, confused with meningitis • Epidural, subdural empyemas are rare, yet highly lethal

Image Interpretation

1.

2. 3.

4.

5.

Demographics

8 32

• Age: Can occur at any age • Gender: No gender predominance

6.

Natural History & Prognosis

7.

• May progress rapidly, considered neurosurgical emergencies • Rapidly evolving, fulminant course • EDE may occasionally have an indolent course as the dura mater functions as a barrier between infection and brain o Much better prognosis than SDE • Can be fatal unless recognized, treated o Imaging essential as lumbar puncture can be fatal o CSF can be normal • Complications common o Cerebritis and brain abscess, approximately 5% o Cortical vein, dural sinus thrombosis with secondary venous ischemia o Cerebral edema o Hydrocephalus (> 75% of infratentorial SDE) • Mortality 10-15%

Infection

Pearls

• MRI with contrast and DWI is most sensitive, CT may miss small collections • DWI can help differentiate SDE from subdural effusions • EDE can be diagnosed when dura is displaced from inner table of skull

8.

9.

10. 11.

12.

13.

Tsai YD et al: Intracranial suppuration: a clinical comparison of subdural empyemas and epidural abscesses. Surg Neurol. 59(3):191-6; discussion 196, 2003 Tsuchiya K et al: Diffusion-weighted MRI of subdural and epidural empyemas. Neuroradiology 45:220-3, 2003 Heran NS et al: Conservative neurosurgical management of intracranial epidural abscesses in children. Neurosurg 53:893-8, 2003 Rohde V et al: Complications of burr-hole craniostomy and closed-system drainage for chronic subdural hematomas: a retrospective analysis of 376 patients. Neurosurg Rev. 25(1-2):89-94, 2002 Ong YKet al: Bifrontal decompressive craniectomy for acute subdural empyema. Childs Nerv Syst. 18(6-7):340-3; discussion 344, 2002 Nathoo N et al: Craniotomy improves outcomes for cranial subdural empyemas: computed tomography-era experience with 699 patients. Neurosurg 49:872-8,2001 Bambakidis NC et al: Intracranial complications of frontal sinusitis in children: Pott's puffy tumor revisited. Pediatr Neurosurg. 35(2):82-9, 2001 Amar AP et al: Treatment of central nervous system infections: a neurosurgical perspective. Neuroimaging Clin N Am. 10(2):445-59, 2000 Nathoo N et al: Cranial extradural empyema in the era of computed tomography: a review of 82 cases. Neurosurg 44: 748-54, 1999 Campbell BG et al: Emergency magnetic resonance of the brain. Top Magn Reson Imaging 9(4):208-27,1998 Chen CY et al: Subdural empyema in 10 infants: US characteristics and clinical correlates. Radiology. 207(3):609-17,1998 Goldberg AN et al: Current concepts in the surgical management of frontal sinus disease. Otolaryngol Clin North Am 30:355-70, 1997 Chang YC et al: Risk factor of complications requiring neurosurgical intervention in infants with bacterial meningitis. Pediatr Neurol. 17(2):144-9, 1997

and Demyelinating

Disease

Typical (Left) Axial T1 C+ MR shows

a left frontal subdural empyema with extension along the falx (arrow), typical of 50E. Note enhancement along the deep margin. Adult patient with frontal sinusitis. (Right) Axial T1 C+ MR shows a right frontal subdural empyema with loculation and enhancement (arrow). Note the left frontal subdural effusion with no enhancement (Courtesy;. Provenzale, MO).

(Left) Axial T1 C+ MR shows an epidural abscess with a thick enhancing margin (curved arrow) complicated by cerebritis (arrow). A subtle 50E is present anteriorly. Patient with sinusitis and seizures. (Right) Axial OWl MR shows typical mixed signal in the left frontal epidural abscess (curved arrow). Note also the small 50E (open arrow) and venous ischemia (arrow) (Courtesy C. Hedlund, DO).

Variant

(Left) Axial CECT shows bilateral posterior fossa subdural empyemas with enhancing margins. Patient with mastoiditis further complicated by hydrocephalus & venous thrombosis (Courtesy j. Cure, MO). (Right) Axial T1 C+ MR shows frontal sinusitis complicated by a small epidural abscess (black arrow) and frontal soft tissue swelling with enhancing subgaleal phlegmon (white arrow), Pott's puffy tumor.

Infection and Demyelinating

Disease

8 33

Coronal graphic shows inflammation in the temporal lobes, left cingulate gyrus, and right insula, Bilateral, asymmetric involvement of gray & white matter, typical of herpes encephalitis.

Coronal T7 C + M R shows gyriform enhancement of the temporal lobes, insular cortices and minimally of the cingulate gyri (arrows) bilaterally. Enhancement is typically a late feature.

o Rarely, may affect midbrain and pons (mesenrhombencephali tis)

Abbreviations

and Synonyms

• Herpes simplex encephalitis

CT Findings

(HSE)

• NECT o CT often normal early • Low attenuation, mild mass effect in medial temporal lobes, insula • Hemorrhage is typically a late feature o Predilection for limbic system, basal ganglia spared o Earliest CT findings at 3 days after symptom onset • CECT: Patchy or gyriform enhancement of temporal lobes, a late feature

Definitions • Brain parenchyma infection caused by herpes simplex virus type 1 (HSV-l) • Typically reactivation in immunocompetent patients

General Features

8 34

MR Findings

• Best diagnostic clue o Abnormal signal and enhancement of medial temporal and inferior frontal lobes o Involvement of cingulate gyrus, contralateral temporal lobe highly suggestive • Location o Limbic system: Temporal lobes, insula, subfrontal area and cingulate gyri typical o Cerebral convexity and posterior occipital cortex may become involved o Typically bilateral disease, but asymmetric o Basal ganglia usually spared o Atypical patterns seen in infants, children • May affect cerebral hemispheres primarily

DDx:

• TlWI o Decreased signal in gray and white matter, loss of gray-white junction, mass effect o May see subacute hemorrhage as increased signal within edematous brain o Atrophy and encephalomalacia, in chronic cases • T2WI o Increased signal in gray, subcortical white matter o Typically bilateral, but asymmetric o May see subacute hemorrhage as increased signal within edematous brain • PD/Intermediate: Increased signal in affected areas • FLAIR: Hyperintense swollen cortex/subcortical white matter

,.~~.'~'

Temporal lobe lesions

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I

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~.

~~

0>

.'

\:

.

\ ~/1."~

"',

I

\" Gliomatosis Cerebri

)

\

MCA Ischemia

Infection and Demyelinating Disease

,

....

/~~. '. ::.-

! I

'~~' '(

,

Limbic Encephalitis

I ' ..' 'i!" "

.

~J

Status Epilepticus

HERPES ENCEPHALITIS Key Facts Imaging Findings • Abnormal signal and enhancement of medial temporal and inferior frontal lobes • Limbic system: Temporal lobes, insula, subfrontal area and cingulate gyri typical • Typically bilateral disease, but asymmetric • Basal ganglia usually spared

Top Differential • • • • •

• HSV-l reactivation may occur spontaneously or be precipitated by various factors • HSV-l causes 95% of all herpetic encephalitis • Most common cause of fatal sporadic encephalitis • Hemorrhagic, necrotizing encephalitis of gray and white matter (primarily limbic system)

Clinical Issues • Fever, headache, seizures, +/- viral prodrome • Altered mental status, focal or diffuse neurologic deficit « 30%) • Polymerase chain reaction (PCR) of CSF, most useful for diagnosis • Mortality ranges from 50-70% • Antiviral therapy with intravenous Acyclovir

Diagnoses

Limbic encephalitis Infiltrating neoplasm Ischemia Status epileptius Other encephalitides

Pathology • HSV-l in adults and children

• T2* GRE: If hemorrhagic, hypointensity "blooms" within edematous brain • DWI: May be hyperintense (restricted diffusion) • Tl C+ o May see mild, patchy enhancement early o Gyriform enhancement usually seen 1 week after initial symptoms o Meningeal enhancement occasionally seen o Enhancement seen in temporal lobes, insular cortex, subfrontal area and cingulate gyrus • MR findings may be seen within 2 days of symptoms

Imaging Recommendations • Best imaging tool: MR is most sensitive • Protocol advice: Multiplanar MR with coronal T2 and/or FLAIR, DWI, T2* GRE, contrast

I [)U;FER.E~,,[I~1.. [)1~G~OSIS limbic encephalitis • Rare paraneoplastic syndrome associated with a primary tumor, often lung • Predilection for limbic system, often bilateral • Hemorrhage is not present • Imaging may be indistinguishable • Symptom onset usually weeks to months (vs acute in HSE)

Infiltrating neoplasm • Low grade gliomas often involve medial temporal lobe and cause epilepsy • Gliomatosis cerebri may involve the frontal and temporal lobes, may be bilateral • Onset usually indolent

Ischemia • Typical vascular distribution • Acute onset

(MCA, ACA, PCA)

Status epileptius • Active seizures may disrupt BBB, cause signal abnormalities and enhancement

• Temporal lobe epilepsy hyperperfusion herpes encephalitis

may mimic

Other encephalitides • Limbic system not typically involved • Neurosyphilis can affect medial temporal lobes, mimic herpes encephalitis o May involve meninges, blood vessels (obliterative endarteritis)

I P~,,[HOI..OG~ General Features • General path comments o HSV-l in adults and children o Herpes simplex virus type 2 (HSV-2) more common in neonates o HSV-l is a DNA virus o Viruses are obligate intracellular pathogens o Herpes viruses include: HSV-l, HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella-zoster virus (VZV), B virus, HSV-6, HSV-7 • Etiology o Initial HSV-l infection usually occurs in oronasopharynx through contact with infected secretions o HSV-l invades along cranial nerves (via lingual nerve, a division of the trigeminal nerve) to ganglia o HSV-l remains dormant in the trigeminal ganglion o New infection with genetically distinct HSV > reactivation of dormant virus (enrty portal probably CNl) o HSV-l reactivation may occur spontaneously or be precipitated by various factors • Local trauma, immunosuppression, hormonal fluctuations, emotional stress o HSV-l causes acute hemorrhagic, necrotizing encephalitis (primarily involving limbic system) • Epidemiology o HSV-l causes 95% of all herpetic encephalitis o Most common cause of fatal sporadic encephalitis

Infection and Demyelinating Disease

8 35

o Most common nonepidemic cause of viral meningoencephalitis o In adults, typically related to viral reactivation o Incidence: 1-3 cases/million

• Antiviral therapy with intravenous

• Hemorrhagic, necrotizing encephalitis of gray and white matter (primarily limbic system) o Severe edema and massive tissue necrosis with hemorrhage typical o Involvement of temporal lobes, insular cortex, and orbital surface of frontal lobes o Less frequent involvement of cingulate gyrus and occipital cortex

Consider

Features

• Intense perivascular cuffing and interstitial lymphocytic inflammation • Intranuclear inclusion bodies in infected cells (neurons, glia, endothelial cells) o Typically eosinophilic Cowdry A nuclear inclusions • Immunohistochemistry shows viral antigens, antibodies to HSV-1 • Chronic cases, microglial nodules form

Presentation

36

Treatment

Gross Pathologic & Surgical Features

Microscopic

8

• Survival complicated by memory difficulties, hearing loss, medically intractable epilepsy, personality changes

• Most common signs/symptoms o Fever, headache, seizures, +/- viral prodrome o Other signs/symptoms • Altered mental status, focal or diffuse neurologic deficit « 30%) o Children often present with nonspecific symptoms • Behavioral changes, fever, headaches, seizures o May progress to coma and death o Patients typically immunocompetent • HSV-1 is uncommon in AIDS • Clinical profile o CSF studies show a lymphocytic pleocytosis and elevated protein o Polymerase chain reaction (PCR) of CSF, most useful for diagnosis • Sensitivity/specificity of approximately 95-100% in CSF o EEG shows temporal lobe activity o Brain biopsy may be required for diagnosis

Demographics • Age o Occurs at any age o Highest incidence in adolescents and young adults • Approximately 30% of patients are less than 20 years old • Gender: No gender predominance

Natural History & Prognosis • Rapid diagnosis, early treatment with antiviral agents can decrease mortality, may improve outcome • Mortality ranges from 50-70% • Despite Acyclovir therapy, approximately 50% of patients have neurological disabilities

Acyclovir

• IV Acyclovir therapy started immediately if herpes encephalitis is suspected! • Unilateral disease may mimic stroke or tumor, history often helpful! • Limbic encephalitis should be considered if all clinical tests for herpes encephalitis are negative and there is a subacute onset of symptoms • Herpes encephalitis has an acute onset which helps differentiate from other etiologies

Image Interpretation

Pearls

• MR is most sensitive for diagnosis • FLAIR and DWI are the most sensitive sequences • Imaging is often key in diagnosis!

1.

Kuker W et al: Diffusion-weighted MRIin herpes simplex encephalitis. Neuroradiology 46: 122-5, 2004 2. Kaga K et al: Auditory agnosia in children after herpes encephalitis. Acta Otolaryngol. 123(2):232-5, 2003 3. Cakirer S et al: MRimaging in epilepsy that is refractory to medical therapy. Eur Radiol. 12(3):549-58, 2002 4. Kleinschmidt-DeMasters BKet al: The expanding spectrum of herpesvirus infections of the nervous system. Brain Patholll: 440-51, 2001 5. Theil D et al: Prevalence of HSV-1LATin human trigeminal, geniculate, and vestibular ganglia and its implication for cranial nerve syndromes. Brain Patholll: 408-13, 2001 6. TeixeiraJ et al: Diffusion imaging in pediatric central nervous system infections. Neuroradiology. 43(12):1031-9, 2001 7. Bash S et al: Mesiotemporal T2-weighted hyperintensity: neurosyphilis mimicking herpes encephalitis. AJNRAm J Neuroradiol. 22(2):314-6, 2001 8. Leonard JR et al: MR imaging of herpes simplex type 1 encephalitis in infants and young children: a separate pattern of findings. AJRAm J Roentgenol. 174(6):1651-5, 2000 9. Tsuchiya K et al: Diffusion-weighted MR imaging of encephalitis. AJR173: 1097-9, 1999 10. Kato T et al: Early diagnosis of herpes encephalopathy using fluid-attenuated inversion recovery pulse sequence. Pediatr Neurol. 19(1):58-61, 1998 11. Domingues RBet al: Diagnosis of herpes simplex encephalitis by magnetic resonance imaging and polymerase chain reaction assay of cerebrospinal fluid. J of Neurological Sciences 157:148-53, 1998 12. Koskiniemi M et al: Herpes encephalitis is a disease of middle aged and elderly people: polymerase chain reaction for detection of herpes simplex virus in the CSFof 516 patients with encephalitis. The Study Group. J Neurol Neurosurg Psychiatry. 60(2):174-8, 1996

Infection and Demyelinating

Disease

Typical (Left) Axial FLAIR MR shows hyperintense signal in the right temporal lobe, right insula, and bilateral medial frontal lobes. 52 year old male with fever and seizures. PCR positive for H5V-]. (Right) Axial NECT shows hypodensity in the right temporal and inferior frontal lobes 2 days after the M R study. His initial CT was "normal". CT findings can often only be seen 3 days after symptom onset.

(Left) Coronal FLAIR MR shows classic bilateral, asymmetric involvement of the medial temporal lobes and right insula in this 46 year old female with herpes encephalitis. Basal ganglia sparing is typical. (Right) Axial TlWI MR shows Tl hyperintensity representing subacute blood products in the right insula (arrow) on this follow-up study. Hemorrhage is typically a late feature of herpes encephalitis.

(Left) Axial NECT shows hemorrhage in the left temporal lobe with surrounding edema and mass effect. 25 year old male with altered mental status and aphasia. Poor prognosis despite early Acyclovir therapy. (Right) Axial OWl MR shows diffusion restriction in the right temporal lobe and hippocampus. OWl is very sensitive for encephalitis. Unilateral disease is atypical. 50 year old with fever and confusion.

Infection and Demyelinating Disease

8 37

Axial FLAIR MR shows symmetric hyperintense signal in the thalami. Patient with EBV encephalitis and a history of infectious mononucleosis. Imaging of encephalitis is often nonspecific.

Definitions • Diffuse brain parenchymal inflammation caused by a variety of pathogens, most commonly viruses • Location dependent on etiology

Coronal T2WI MR shows an ill-defined mass involving the gray and white mater of the right temporal lobe in this patient with viral encephalitis (Courtesy C. Sutton, MOJ.

o o o o o o

General Features

8 38

• Best diagnostic clue o Abnormal T2 hyperintensity of gray matter (GM) +/white matter (WM), or deep gray nuclei o Large, poorly-delineated areas of involvement common, +/- patchy hemorrhage o Imaging is often nonspecific • Location o Herpes simplex virus, type l(HSV-l): Limbic system o Cytomegalovirus (CMV): Periventricular WM o Epstein-Barr virus (EBV): Symmetric basal ganglia (BG), thalami, cortex or brainstem o Varicella-zoster virus (VZV) • Varicella: May affect multifocal areas of cortex • Zoster: Brainstem/cortical GM, cranial nerves o Cerebellitis: Bilateral cerebellar hemispheres o Eastern equine encephalitis (EEE): BG and thalami o Enteroviral encephalomyelitis

o o o

• EV71: Posterior medulla, pons, midbrain, dentate nuclei, spinal cord • Polio, coxsackie: Midbrain, anterior spinal cord Hantavirus: Pituitary gland hemorrhage HIV-l: Cerebral WM, brainstem, thalamus, BG Japanese encephalitis: Bilateral thalami, brainstem, cerebellum, spinal cord, cerebral cortex Murray Valley Encephalitis (MVE): Bilateral thalami; may affect midbrain, cervical spinal cord Nipah viral encephalitis: Multifocal WM Rabies encephalitis: Brainstem, hippocampi, hypothalamus, WM, GM Rhombencephalitis: Brainstem and cerebellum St Louis encephalitis: Substantia nigra West Nile virus (like polio): Brainstem, substantia nigra, anterior horn (cord), cerebellum

CT Findings • NECT: Initial CT negative in vast majority of patients

MR Findings • TlWI o Japanese encephalitis: Low signal foci in WM, brainstem, BG, thalami bilaterally o Rabies encephalitis: Hyperintense bilateral BG, rare • T2WI o CMV: Patchy increased signal in periventricular WM o EBV: Hyperintensity in BG, thalamus, cortex o Varicella: Multifocal increased cortical signal

DDx: Diffuse Parenchymal lesions

I~ \ ACA, MCA Ischemia

Astrocytoma

Herpes Encephalitis

Infection and Demyelinating

Disease

Status Epilepticus

ENCEPHALITIS (MISCELLANEOUS) Key Facts Terminology • Diffuse brain parenchymal inflammation caused by a variety of pathogens, most commonly viruses • Location dependent on etiology

Imaging Findings • Abnormal T2 hyperintensity of gray matter (GM) +/white matter (WM), or deep gray nuclei • Large, poorly-delineated areas of involvement common, +/- patchy hemorrhage • NECT: Initial CT negative in vast majority of patients • Best imaging tool: MR is most sensitive

Top Differential Diagnoses • Ischemia • Infiltrating neoplasm • Herpes encephalitis

•

• • •

•

o Zoster: Increased signal in brains tern, cortex o Cerebellitis: Hyperintense cerebellar signal o EEE: Increased signal in BG & thalami; may involve brainstem, cortex, periventricular WM o Enteroviral encephalomyelitis (EV71): Hyperintense lesions in posterior medulla, pons, midbrain, dentate nuclei of cerebellum • Less common: Cervical spinal cord, thalamus and putamen o Japanese encephalitis: High signal foci in WM, brainstem, BG, thalami bilaterally o MVE: Hyperintensity in bilateral thalami; may involve midbrain, cerebral peduncles o Nipah viral encephalitis: Multifocal WM hyperintensities; may affect GM o Rabies encephalitis: Ill-defined mild hyperintensity in brainstem, hippocampi, thalami, WM, BG • Paralytic rabies: Medulla and spinal cord hyperintensity o Rhombencephalitis: Patchy hyperintensity in pons, medulla, midbrain o St Louis encephalitis: May see hyperintensity of substantia nigra; often normal FLAIR o Nipah encephalitis: Discrete high signal lesions in subcortical, deep WM +/- GM • Confluent cortical involvement in relapsed and late-onset encephalitis T2* GRE: Japanese encephalitis: Thalamic hemorrhage DWI: Diffusion restriction is commonly seen TI C+ o Variable enhancement: None to intense o Meningeal enhancement can be seen o Herpes zoster oticus (Ramsay Hunt syndrome): Enhancing CNs 7, 8, membranous labyrinth MRS: May help differentiate encephalitis from infarct

Imaging Recommendations • Best imaging tool: MR is most sensitive • Protocol advice: Multiplanar MR with TI, T2, FLAIR, DWI and contrast

• Status epilepticus • Toxic/metabolic lesions

Pathology • Most (but not all) are caused by viruses • Spread of virus to CNS is hematogenous or neural • Herpes: Most common cause of sporadic (nonepidemic) viral encephalitis

Clinical Issues • Varies widely: Slight meningeal to severe encephalitic symptoms, +/- fever, prodrome • Many encephalitides have high morbidity, mortality • Rapid diagnosis, early treatment with antiviral or antibacterial agents can decrease mortality, may improve outcome

I DIFFERENTIAL

DIAGNOSIS

Ischemia • Typical vascular distribution,

DWI positive

Infiltrating neoplasm • Typically unilateral disease • Subacute onset

Herpes encephalitis • Limbic system and temporal lobe involvement

Status epilepticus • Active seizures with cerebral hyperperfusion, BBB disruption may cause abnormal signal, enhancement

Toxic/metabolic

transient

lesions

• Symmetric BG involvement

common

IPATHOlOG~ General Features • General path comments o Herpes viruses include: HSV-I, HSV-2, CMV, EBV, VZv, B virus, HSV-6, HSV-7 o HSV-2 is major cause of neonatal encephalitis o Varicella: Meningoencephalitis, cerebellar ataxia, and aseptic meningitis « I % of patients) o Zoster infection: Encephalitis, neuritis, myelitis, or herpes ophthalmicus • Immunocompetent patients: Cranial and peripheral nerve palsies • Immunosuppressed patients: Diffuse encephalitis • Herpes zoster ophthalmicus can cause ICA necrotizing angiitis o EBV is the agent in infectious mononucleosis • Diffuse encephalitis seen in < I % of patients • Associated with meningoencephalitis, Guillian-Barre syndrome, transverse myelitis o Enteroviruses include: Coxsackie viruses A & B, poliovirus, echoviruses, enteroviruses 68 to 71

Infection and Demyelinating Disease

8 39

o Arboviruses (arthropod-borne viruses) include: Eastern, Western, & Venezuelan equine encephalitis, St Louis encephalitis, Japanese B encephalitis, California encephalitis, tick-borne encephalitis o Nipah encephalitis: Paramyxovirus related to close contact with infected pigs o Rhombencephalitis: Viruses most commonly (HSV), Listeria monocytogenes, Legionnaire's disease, mycoplasma, Lyme disease, TB • Etiology o Most (but not all) are caused by viruses o Arboviruses are transmitted by mosquitoes and ticks o Viruses are obligate intracellular parasites o Replicate in skin or mucous membranes of respiratory, GI tracts o Spread of virus to CNS is hematogenous or neural o Some invade along CNs (Le., HSV-l via lingual nerve to trigeminal ganglia) o Latent infections may reactivate, spread along meningeal branches o Zoster: Latent virus in ganglia of CNs (often 5 & 7) can reactivate, spread to brainstem o Nipah encephalitis: Inflammation of small blood vessels with thrombosis and microinfarction o Rabies: Reaches CNS by retrograde axoplasmic flow • Epidemiology o Herpes: Most common cause of sporadic (nonepidemic) viral encephalitis o Japanese encephalitis: Most common endemic encephalitis in Asia o CNS involvement in EBV is uncommon, occurs in less than 10% of cases o VZV: Less than 1% have CNS involvement o In US, marked seasonal variation in frequency of encephalitis

Gross Pathologic & Surgical Features • Vascular congestion, generalized or local edema, +/hemorrhage, necrosis

Microscopic

o Zoster: Immunosuppressed patient with fever, meningismus, altered mental status o Cerebellitis: Sudden onset of limb and/or gait ataxia after infectious prodrome o Enterovirus encephalitis (EV 71) • Hand-foot-and-mouth disease (HFMD): Fever, vesicles on hands, feet, elbows, knees, lips • Herpangina: Ulcers of palate and pharynx • Cranial neuropathies, ocular disturbance, dyspnea, tachycardia if brainstem involved o Nipah virus: Fever, headache, dizziness, vomiting; segmental myoclonus, areflexia, hypotonia, hypertension, tachycardia o MVE: Fever, headache, confusion, tremors; may progress to paralysis, coma, respiratory failure o Rabies • Encephalitic: Fever, malaise, altered mental status, limbic dysfunction, autonomic stimulation signs • Paralytic: Weakness of all extremities o Rhombencephalitis: Areflexia, ataxia, ophthalmoplegia o St Louis encephalitis: Tremors, fevers • Clinical profile o Variable o CSF studies often abnormal

Demographics • Age: Occurs at all ages • Gender: No gender predominance

Natural History & Prognosis • Many encephalitides have high morbidity, mortality • Rapid diagnosis, early treatment with antiviral or antibacterial agents can decrease mortality, may improve outcome

Treatment • Dependent

on etiology

Features

• Infiltration by polymorphonuclear cells (PMNs), lymphocytes, plasma cells, and mononuclear cells • Perivascular cuffing characteristic • May see inclusion bodies (Le., Negri bodies in rabies)

Consider • Imaging often nonspecific, mimics other etiologies • Clinical history often helpful

Image Interpretation

Pearls

• DWI may detect lesions earlier than conventional

8 40

MRI

Presentation • Most common signs/symptoms o Varies widely: Slight meningeal to severe encephalitic symptoms, +/- fever, prodrome o Varicella and herpes zoster: Different clinical manifestations of infection by same virus (VZV) o Varicella encephalitis: Fever, headache, vomiting, seizures, altered mental status days-weeks after onset of (chicken-pox) rash o Zoster: Immunocompetent - CN & peripheral nerve palsies in derma tomes involved by skin lesions • CN 5, Ophthalmic branch most affected (herpes zoster ophthalmicus) • Rare complication: Contralateral hemiplegia related to cerebral angiitis and mycotic aneurysms

1. 2.

3.

4.

Eming M et al: Severe West Nile virus disease in healthy adults. Clin Infect Dis 38:289-92, 2004 Kennedy PG: Viral encephalitis: causes, differential diagnosis, and management. J Neurol Neurosurg Psychiatry 75, suppll:l0-5, 2004 Calli C et al: Proton MR spectroscopy in the diagnosis and differentiation of encephalitis from other mimicking lesions. J Neuroradiol. 29(1):23-8, 2002 Kleinschmidt-DeMasters BKet al: The expanding spectrum of herpesvirus infections of the nervous system. Brain Patholll: 440-51, 2001

Infection and Demyelinating Disease

Typical (Left) Axial CECT shows enhancement of the cerebellar hemispheres bilaterally in this young adult male patient with cerebellitis. Cerebellitis is often a disease of children. (Right) Axial T2WI MR shows abnormal hyperintense signal in the cerebellar hemispheres. Patient with acute onset of gait ataxia after infectious prodrome, cerebellitis. (Courtesy C. Sutton, MO).

(Left) Axial FLAIRMRshows hyperintense signal in the posterior frontal lobes and right parietal lobe. Immunosuppressed patient with CMV meningoencephalitis. CMV typically involves peri ventricular WM. (Right) Axial OWl MR shows restricted diffusion in the frontal lobes bilaterally with involvement of the gray and white matter. OWl is often positive in encephalitis and may be the most sensitive sequence.

Variant (Left) Axial T2WI MR shows abnormal hyperintense signal in the left brachium pontis (arrow), in the region of CN 5 root entry zone. Immunocompetent patient with tongue numbness and trigeminal neuralgia. (Right) Axial T1 C+ MR shows enhancement of CN 5, cisternal segment (curved arrow), root entry zone, and brachium pontis. Ophthalmic branch is most affected in herpes zoster. VZV encephalitis is rare.

Infection and Demyelinating

Disease

8 41

Coronal T2WI MR shows mild atrophy of left cerebral hemisphere with subtle high signal in the temporal cortex.

Coronal PET shows decreased uptake of temporal lobe.

Foe

in left

• Rasmussen syndrome (RS) • Chronic focal encephalitis (new term)

• Size: Variable but usually lobar, occasionally entire hemisphere affected • Morphology o Focal abnormality "spreads across hemisphere" o Becomes progressively more diffuse, extensive

Definitions

CT Findings

• Chronic, progressive, relentless, unilateral inflammation of brain of uncertain etiology • Characterized by hemispheric volume loss and difficult to control focal seizure activity

• NECT: Atrophy • CECT o Usually no enhancement o RARE transient cortical enhancement

Abbreviations

and Synonyms

may occur

MR Findings

General Features

8 42

• Best diagnostic clue o Unilateral progressive cortical atrophy o CT/MRI often normal initially • Cortical swelling, then atrophy ensue • Most brain damage subsequently identified occurs in first 12 months of disease • Location o Cerebral hemisphere o Usually unilateral • Precentral, inferior frontal atrophy • Unilateral cerebellar progressive volume loss

• T1WI: Blurring of cortical ribbon during early swelling • T2WI o Early focal swelling of gyri • Gray, underlying white matter mildly hyperintense • +/- Basal ganglia, hippocampi involved o Late: Atrophy of involved cerebral hemisphere or lobe • PD/Intermediate: Same as T2WI • FLAIR o Small areas of hyperintensity that progressively increase over time o Late: Atrophic, encephalomalacic/gliotic residual brain • T2* GRE o Typically normal

DDx: Cerebral Hemiatrophy

Sturge Weber

Dyke Mason

MELAS

Infection and Demyelinating Disease

RASMUSSEN ENCEPHALITIS 'Key Facts Terminology

Pathology

• Chronic, progressive, relentless, unilateral inflammation of brain of uncertain etiology • Characterized by hemispheric volume loss and difficult to control focal seizure activity

• Three different, not mutually exclusive factors may initiate or perpetuate events leading to injury • Genetics: Possibly viral trigger of genetic predisposition to immunodysfunction • 50% preceded by inflammatory episode

Imaging Findings

Clinical Issues

• Unilateral progressive cortical atrophy

Top Differential

Diagnoses

• Sturge-Weber syndrome • Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) • Hemispheric infarction (Dyke-Davidoff-Masson)

o Nonhemorrhagic • DWI: Subtle high signal on trace images • Tl C+: Usually doesn't enhance • MRS: ~ N-acetyl-aspartate (NAA) and choline; 1 myo-inositol, 1 glutamine/glutamate

Nuclear Medicine

• Following in-utero or perinatal infarct

I P~[fHQI..QG'1' General Features

Findings

• 99mTc-HMPAO nuclear scintigraphy: Early ~ perfusion even if normal MRI • PET and SPECT o Decreased cerebral perfusion/metabolism o Crossed cerebellar diaschisis o Transient hypermetabolism may be related to recent seizures (rare) • 11C methionine shows increased multifocal uptake

Imaging Recommendations • Best imaging tool: MR PLUS appropriate EEG findings • Protocol advice: MRI with contrast, PET

I DIFFERErN[fI~1.. DI~GrNQSIS Sturge-Weber

syndrome

• Progressive hemispheric atrophy • Cortical Ca++ • Port wine facial nevus and enhancement angioma

of pial

• General path comments o Three different, not mutually exclusive factors may initiate or perpetuate events leading to injury • Viruses • Autoimmune antibodies • Autoimmune cytotoxic T lymphocytes • Genetics: Possibly viral trigger of genetic predisposition to immunodysfunction • Etiology o Autoimmune theory (one theory) • Glutamate is excitatory neurotransmitter • Glutamate antibodies cross damaged blood-brain barrier • Antibodies bind and activate glutamate receptors • Nerve cells stimulated • Seizures induced • Epidemiology o 50% preceded by inflammatory episode • Tonsillitis, upper respiratory infection, otitis media o Extremely rare

Gross Pathologic & Surgical Features

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) • Acute: May cause cortical hyperintensity (parieto-occipital most common) • Chronic: Cortical atrophy, lacunes (basal ganglia, thalami)

Hemispheric infarction (Dyke-Davidoff-Masson) • Unilateral brain atrophy • Compensatory calvarial thickening • Elevation of the petrous ridge and hyperaeration the paranasal sinuses

• EEG: Early: Slow focal activity; late: Epilepsia partialis continua • Age: Usually begins in childhood (6-8 years of age) • Refractory to anti epileptic medications

of

• Hemispheric

Microscopic

cortical atrophy

Features

• Robitaille classification o Group 1 (pathologically active): Ongoing inflammatory process • Microglial nodules, +/- neuronophagia, perivascular round cells o Group 2 (active and remote disease): Acute on chronic • Above plus at least one gyral segment of complete necrosis and cavitation including full-thickness cortex o Group 3 (less active "remote" disease)

Infection and Demyelinating Disease

8 43

• Neuronal loss/gliosis and fewer microglial nodules o Group 4 (burnt out) • Nonspecific scarring with little active inflammation

1. 2.

Staging, Grading or Classification Criteria • Classification and staging: MR (T2WI) o Stage 1: Swelling/hyperintense signal o Stage 2: Normal volume/hyperintense signal o Stage 3: Atrophy/hyperintense signal o Stage 4: Progressive atrophy and normal signal

3.

4.

5. 6.

Presentation • Most common signs/symptoms o Intractable epilepsy o Progresses to epilepsia partialis continua o Other symptoms: Visual and sensory deficits, dysarthria, dysphasia • Clinical profile: Young child with progressive partial epilepsy that is not responsive to medical therapy • Course characterized by definite onset of seizure (Sz) activity o 20% present in status epilepticus • Followed by onset hemiparesis/II in Sz, often requiring hospitalization • Subsequent stabilization of hemiparesis and decrease in Sz • EEG: Early: Slow focal activity; late: Epilepsia partialis continua • CSF: +/- Oligoc1onal bands • Other: +/- GluR3 antibodies (50%), but not specific

Cook 5W et al: Cerebral hemispherectomy in pediatric patients with epilepsy. J Neurosurg 100: 125-41, 2004 Maeda Y et al. Rasmussen syndrome: multifocal spread of inflammation suggested from MRI and PET findings. Epilepsia 44: 1118-21, 2003 Granata T et al: Experience with immunomodulatory treatments in Rasmussen's encephalitis. Neurology 61:1807-10,2003 Bien CG: Diagnosis and staging of Rasmussen's encephalitis by serial MRI and histopathology. Neurology 58:250-7, 2002 Kim 5J et al: A longitudinal MRI study in children with Rasmussen syndrome. Pediatr Neurol 27(4):282-8, 2002 Fiorella DJ et al: 18F-fluorodeoxyglucose positron emission tomography and MR imaging findings in Rasmussen encephalitis. AJNR22:1291-9,2001

Demographics • Age: Usually begins in childhood • Gender: M = F • Ethnicity: No predilection

(6-8 years of age)

Natural History & Prognosis • Hemiplegia and cognitive deterioration in most cases • Older age at onset have longer prodromal stage and protracted course • Prognosis is poor • Hemiplegia is inevitable with or without treatment

Treatment

8 44

• Refractory to antiepileptic medications • +/- Transient improvement with plasma exchange, gancic1ovir, steroids, immunoadsorption • Surgical options o Hemispherectomy o Functional hemispherectomy/central disconnection

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• In patient with progressive intractable epilepsy with progressive atrophy of one hemisphere and high T2 signal consider Rasmussen encephalitis

Infection and Demyelinating Disease

Typical (Left) Axial NECT shows right cerebral hemispheric atrophy. (Right) Axial NECT in same patient shows atrophy of the right hemisphere and dilatation of the lateral ventricle.

(Left) Axial T2WI MR shows atrophy of right hemisphere and high signal in the white matter. (Right) Axial T2WI MR in the same patient shows dilatation of the sulci in the right hemisphere.

Typical

(Left) Axial T2WI MR in a patient with end-stage Rasmussen encephalitis shows severe atrophy of the right hemisphere and high signal in the parenchyma. (Right) Axial T7 C+ MR in the same patient shows no contrast-enhancement.

Infection and Demyelinating

Disease

8 45

Sagittal graphic shows basi/ar T8 meningitis and tuberculomas (arrows) which often coexist. Note vessel irregularity and early basal ganglia ischemia related to arteritis.

o TB spondylitis (Pott's disease) • Spine is most frequent osseous site o Less common sites: Calvarium (+/- dura), otomastoid o TB cervical adenitis: Child/young adult with pulmonary disease, conglomerate nodal neck mass

Definitions • Infection acid-fast • Typically localized

by Mycobacterium tuberculosis (TB), an bacillus causes tuberculous meningitis (TBM) and/or CNS infection, tuberculoma

CT Findings • NECT o TBM: May be normal early (10-15%) • Isodense to hyperdense exudate effaces CSF spaces, fills basal cisterns, sulci o Tuberculoma • Hypodense to hyperdense round or lobulated nodule/mass with moderate to marked edema • Ca++ uncommon (approximately 20%) • CECT o TBM: Intense basilar meningeal enhancement o Tuberculoma: Solid or ring-enhancing • "Target sign": Central Ca++ or enhancement surrounded by enhancing rim (not pathognomonic for TB)

General Features

8 46

Coronal T1 C+ MR shows basilar meningitis surrounding the MCA (arrow) and enhancing tuberculomas (open arrows). Note subtle low signal in left basal ganglia related to arteritis/ischemia.

• Best diagnostic clue o Basilar meningitis + extracerebral TB (pulmonary) o Meningitis + parenchymal lesions highly suggestive • Location o TBM: Basal meningitis o Tuberculomas: Typically parenchymal, supratentorial (often parietal lobes) • Infratentoriallesions are less common, can involve brainstem (up to 8%) • Dural tuberculomas may occur • Size: Tuberculomas range from 1 mm to 6 cm • Morphology o TBM: Thick basilar exudate o Tuberculoma: Round or oval mass • Solitary or multiple (more common) • Associated findings

MR Findings • TlWI o TBM: Exudate isointense or hyperintense to CSF o Tuberculoma • Noncaseating granuloma: Hypointense to brain • Caseating granuloma with solid center: Hypointense or isointense to brain

DDx: Intracranial T8 (Meningeal, Parenchymal) ~ /' ~~

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Bacterial Meningitis

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~

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:lo.... • Neurosarcoidosis

Pyogenic Abscess

Infection and Demyelinating Disease

Primary Glioma (GBM)

TUBERCULOSIS Key Facts Pathology

Terminology • Typically causes tuberculous meningitis localized CNS infection, tuberculoma

(TBM) and/or

Imaging Findings • Basilar meningitis + extracerebral TB (pulmonary) • Meningitis + parenchymal lesions highly suggestive • Tuberculomas: Typically parenchymal, supratentorial (often parietal lobes) • Tuberculoma: Solid or ring-enhancing

Top Differential Diagnoses • • • •

•

•

•

•

• •

• Most TB CNS infections are secondary result of hematogenous spread (often pulmonary) • Meningitis is most frequent manifestation of CNS TB and is more common in children • Reemerging disease (immigration from endemic areas, AIDS, drug resistant strains) • In some countries, TB represents 10-30% of intracranial masses

Clinical Issues • Varies from mild meningitis with no neurologic deficit to comatose • Long term morbidity up to 80%: Mental retardation, paralysis, seizures, rigidity, speech or visual deficits • Mortality is 25-30% of patients; higher in AIDS

Meningitis Neurosarcoidosis Abscess Neoplasm

• Caseating granuloma with necrotic center: Hypointense or isointense to brain with central hypointensity • Caseating granulomas may have hyperintense rim (paramagnetic material) T2WI o TBM: Exudate is isointense or hyperintense to CSF; may see low signal nodules (rare) o Tuberculoma (noncaseating - caseating granulomas) • Noncaseating granuloma: Hyperintense to brain • Caseating granuloma with solid center: Iso- to hypointense with hypointense rim (hypointensity due to free radicals, solid caseation or increased cellular density) • Caseating granuloma with necrotic center: Central hyperintensity with hypointense rim • Hypointense rim + surrounding edema common FLAIR o TBM: Increased intensity in basal cisterns, sulci related to proteinaceous exudate o Tuberculoma: Similar to T2 characteristics DWI o May show hyperintense center of tuberculoma o Helpful for detecting complications (stroke, cerebritis) TI C+ o TBM: Marked meningeal enhancement, basilar prominence; may be nodular • Punctate/linear basal ganglia enhancement = vasculitis • Rare: Ventriculitis, choroid plexitis • Rare: Pachymeningitis with dural thickening, enhancement (may mimic meningioma) o Tuberculomas • Noncaseating granuloma: Nodular, homogeneous enhancement • Caseating granuloma with solid center: Peripheral rim enhancement • Caseating granuloma with necrotic center: Peripheral rim-enhancement, central low signal MRA: May see vessel narrowing, irregularity, occlusion MRS

o TB abscess has prominent lipid, lactate amino acid resonances • Lipids at 0.9 ppm, 1.3 ppm, 2.0 ppm, • Complications: Hydrocephalus, ischemia • Chronic changes: Atrophy, Ca++, chronic

but no 2.8 ppm common ischemia

Angiographic Findings • Conventional o Narrowing of major arteries at base of brain (supraclinoid ICA, MI, AI) o Narrowing and occlusion of small and/or medium sized arteries o Abnormal blush, early venous drainage

Imaging Recommendations • Best imaging tool: MRI is most sensitive to delineate extent and complications • Protocol advice: Contrast-enhanced MRI with FLAIR, DWI, +/- MRA

I [)IFFERE~l'IAI...[)IAG~(}$I$ Meningitis • Infectious meningitis (bacterial, fungal, viral, parasitic) o Coccidioidomycosis, cryptococcus often basilar • Carcinomatous meningitis (CNS or systemic primary) o Primary tumor often known

Neurosarcoidosis • Typically leptomeningeal and/or dural enhancement • Rarely causes parenchymal nodules

Abscess • Other granuloma, parasite (NCC), bacteria • Pyogenic abscess often has more edema • Classically T2 hypointense rim and DWI +

Neoplasm • Primary or metastatic tumors may be indistinguishable • Thick, nodular enhancing wall and DWI - typical • Typically more indolent onset, history may help

Infection and Demyelinating Disease

8 47

8 48

General Features

Presentation

• General path comments o Most TB CNS infections are secondary result of hematogenous spread (often pulmonary) o Meningitis is most frequent manifestation of CNS TB and is more common in children o Childhood TB is typically a primary infection o Adult TB is most often postprimary infection • Up to 30% due to primary infection o 10% of patients with tuberculomas also have TBM • Etiology o CNS TB almost always secondary to pulmonary TBi rarely GI or GU tract • Hyperemia, inflammation extend to meninges • May involve perivascular spaces, cause vasculitis o TBM pathophysiology • Penetration of meningeal vessel walls by hematogenous spread • Rupture of subependymal or subpial granulomata into the CSF o Tuberculoma pathophysiology • Hematogenous spread (GM-WM junction lesions) • Extension of meningitis into parenchyma via cortical veins or small penetrating arteries o Arteries directly involved by basilar exudate or indirectly by reactive arteritis (up to 40% of patients) • Infection causes arterial spasm resulting in thrombosis and infarct • Lenticulostriate arteries, MCA, thalamoperforators most often affected • Infarcts most common in basal ganglia, cerebral cortex, pons, cerebellum • Arteritis: More common in children, HIV+ • Epidemiology o Worldwide: 8-10 million cases annually o Reemerging disease (immigration from endemic areas, AIDS, drug resistant strains) o In some countries, TB represents 10-30% of intracranial masses o 5-10% of all TB patients have CNS involvement o 10-20% of AIDS patients have CNS TB o Approximately 30% of TB patients are HIV+

• Most common signs/symptoms o Varies from mild meningitis with no neurologic deficit to comatose o TBM: Fevers, confusion, headache, lethargy, meningismus o Tuberculoma: Seizures, increased intracranial pressure, papilledema • Clinical profile o LP: Increased protein, pleocytosis (lymphocytes), low glucose, negative for organisms • CSF positive on initial LP in < 40% • Mycobacteria grow slowly, culture 4-8 weeks • PCR for TB may help confirm diagnosis earlier o TB skin test may be negative, particularly early o Elevated erythrocyte sedimentation rate common

Gross Pathologic & Surgical Features • TBM: Thick, gelatinous cisternal exudate • Tuberculoma: Noncaseating, caseating with solid center, or caseating with necrotic center o Rarely progresses to TB abscess o Lobulated mass with thick rim, occurs in parenchyma, subarachnoid space, dura

Microscopic

Demographics • Age: Occurs at all ages, more often in first 3 decades • Gender: No gender predominance

Natural History & Prognosis • Long term morbidity up to 80%: Mental retardation, paralysis, seizures, rigidity, speech or visual deficits • Mortality is 25-30% of patients; higher in AIDS • Complications: Hydrocephalus (70%), stroke (up to 40%), cranial neuropathies (3, 4, 6 common), syrinx • Tuberculomas may take months to years to resolve o Size of lesion determines healing time

Treatment • Untreated TBM can be fatal in 4-8 weeks • Multidrug therapy required: Isoniazid, rifampin, pyrazinamide, +/- ethambutol or streptomycin • Despite therapy, lesions may develop or increase • Hydrocephalus typically requires CSF diversion

Consider • TB often mimics other diseases like neoplasm

Image Interpretation

1.

2.

Features

• TBM: Inflammatory cells, fragile neocapillaries o Caseous necrosis, chronic granulomas, endarteritis, perivascular inflammatory changes • Tuberculoma, o Early capsule: Peripheral fibroblasts, epithelioid cells, Langerhans' giant cells, lymphocytes o Late capsule: Thick collagen layer; central liquefied caseating material in mature tuberculoma

Pearls

• Combination of meningitis suggests TB!

3. 4.

and parenchymal

lesions

Poonnoose SI et al: Giant cerebellar tuberculoma mimicking a malignant tumor. Neuroradiology 46:136-9, 2004 Wasay M et al: Brain CT and MRI findings in 100 consecutive patients with intracranial tuberculoma. J Neuroimaging. 13(3):240-7,2003 Ranjan P et al: Serial study of clinical and CT changes in tuberculous meningitis. Neuroradiology 45:277-82,2003 Pui MH et al: Magnetic resonance imaging findings in tuberculous meningoencephalitis. Can Assoc Radiol. J 52:43-9, 2001

Infection and Demyelinating Disease

Typical (Left) Axial T1 C+ MR shows diffuse, basilar enhancement in this patient with tuberculous meningitis. The basal predominance can help differentiate TB from other causes of meningitis. (Right) Axial T1 C+ MR shows homogeneous, nodular enhancement typical of noncaseating tuberculoma (arrow) and peripheral rim enhancement with central necrosis typical of a caseating tuberculoma (open arrow).

Typical (Left) Axial T2WI MR shows a hypointense cerebellar mass (arrow), typical of caseating tuberculoma. Note the surrounding edema, mass effect and hydrocephalus. T2 hypointensity can help in diagnosis of TB. (Right) Axial T1 C+ MR in same case shows peripheral enhancement of typical caseating tuberculoma (open arrow). Note enhancement of CN 3 (arrow), EVOH (Courtesy R. Ramakantan, MO).

Variant (Left) Axial CECT shows an irregular, peripherally enhancing mass in the left frontal lobe with central necrosis and surrounding edema. Solitary tuberculoma mimics tumor (Courtesy R. Ramakantan, MO). (Right) Axial CECT shows an intracranial empyema (arrows) and a subgaleal abscess in this young adult with a history of IV drug use, TB. Bone windows showed osteomyelitis (Courtesy j. Cooper; MO).

Infection and Demyelinating Disease

49

Coronal graphic shows subarachnoid, ventricular cysts. The convexity cysts have a scolex and surrounding inflammation. Inflammation around largest "seals" sulcus and appears parenchymal.

Abbreviations

and Synonyms

Axial CECT shows a typical colloidal vesicular stage cyst with peripheral enhancement and surrounding edema. Note the eccentric scolex (arrow). Patient with seizures, neurocysticercosis.

•

• NCC, cysticercosis

Definitions • Intracranial parasitic infection caused by the pork tapeworm, Taenia solium • Four pathologic stages: Vesicular, colloidal vesicular, granular nodular, nodular calcified

• • •

o Parenchymal cysts lcm or less o Subarachnoid cysts may be larger, up to 9 cm reported Morphology o Rounded or ovoid cyst, solitary in 20-50% o When multiple, usually small number of cysts o Disseminated form ("miliary" NCe) rare Imaging varies with development stage, host response Lesions may be at different stages in same patient Inflammatory response around cyst may seal sulcus, make lesions appear intra-axial

CT Findings General Features

50

• Best diagnostic clue: Cyst with "dot" inside • Location o Convexity subarachnoid spaces most common o May involve cisterns> parenchyma> ventricles o Parenchymal cysts often hemispheric, at gray-white junction o Intraventricular cysts are often isolated • Fourth ventricle is most common o Basal cistern cysts may be racemose (grape-like) o Rare CNS locations: Sella, orbit, spinal cord • Size o Cysts variable, typically 1 cm, range from 5-20 mm and contain a scolex; scolex 1-4 mm

DDx: Ring-enhancing

Pyogenic Abscess

• NECT o Vesicular stage (viable larva): Smooth, thin-walled cyst, isodense to CSF, no edema • Hyperdense "dot" within cyst = proto scolex o Colloidal vesicular stage (degenerating larva): Hyperdense cyst fluid with surrounding edema o Granular nodular (healing) stage: Mild edema o Nodular calcified (healed) stage: Small, Ca++ nodule • CECT o Vesicular stage: No (or mild) wall enhancement o Colloidal vesicular stage: Thicker ring-enhancing fibrous capsule o Granular nodular stage: Involuting enhancing nodule o Nodular calcified stage: Shrunken, calcified nodule

Parenchymal lesions

Tuberculoma

Metastases

Infection and Demyelinating Disease

Amebic Encephalitis

NEUROCYSTICERCOSIS Key Facts Terminology • Intracranial parasitic infection caused by the pork tapeworm, Taenia solium • Four pathologic stages: Vesicular, colloidal vesicular, granular nodular, nodular calcified

Imaging Findings • • • • •

Best diagnostic clue: Cyst with "dot" inside Convexity subarachnoid spaces most common May involve cisterns> parenchyma> ventricles Intraventricular cysts are often isolated Imaging varies with development stage, host response

Top Differential

Diagnoses

• Abscess • Tuberculosis • Neoplasm

• Subarachnoid lesions: Multiple isodense cysts without scolex, may cause meningitis • Intraventricular cysts not well seen on CT, may see hydrocephalus

• Arachnoid cyst • Enlarged perivascular spaces • Other parasitic infection

Pathology • Cysticercosis is most common, most widely disseminated parasitic infection in the world • CNS infection found in 60-90% of cysticercosis cases

Clinical Issues • • • • • •

•

MR Findings

•

• TlWI o Vesicular stage: Cystic lesion isointense to CSF • May see discrete, eccentric scolex (hyperintense) o Colloidal vesicular stage: Cyst is mildly hyperintense to CSF o Granular nodular stage: Thickened, retracted cyst wall; edema decreases o Nodular calcified stage: Shrunken, Ca++ lesion o Useful to detect intraventricular cysts • T2WI o Vesicular stage: Cystic lesion isointense to CSF • May see discrete, eccentric scolex • No surrounding edema o Colloidal vesicular stage: Cyst is hyperintense to CSF • Surrounding edema, mild to marked o Granular nodular stage: Thickened, retracted cyst wall; edema decreases o Nodular calcified stage: Shrunken, Ca++ lesion • FLAIR o Vesicular stage: Cystic lesion isointense to CSF • May see discrete, eccentric scolex (hyperintense to CSF); no edema o Colloidal vesicular stage: Cyst is hyperintense to CSF • Surrounding edema, mild to marked o Useful to detect intraventricular cysts (hyperintense) o 100% inspired 02 increases conspicuity • T2* GRE: Useful to demonstrate calcified scolex • DWI: Cystic lesion typically isointense to CSF • TI C+ o Vesicular stage: No enhancement typical, may see mild enhancement • May see discrete, eccentric scolex enhancement o Colloidal vesicular stage: Thick cyst wall enhances • Enhancing marginal nodule (scolex) o Granular nodular stage: Thickened, retracted cyst wall; may have nodular or ring-enhancement

• •

Seizure, headaches, hydroc Diagnosis confirmed b serum or CSF Age: Any age, commonly young, middle-aged adults Most common cause of epilepsy in endemic areas Oral albendazole (reduces parasitIc burden, seizures) CSF diversion often required to treat hydrocephalus

o Nodular calcified stage: Small calcified lesion, rare minimal enhancement MRS: Few reports show elevated lactate, alanine, succinate, choline; decreased NAA and Cr In children, may see "encephalitic cysticercosis" with multiple small enhancing lesions and diffuse edema Intraventricular cysts may cause ventriculitis and/or hydrocephalus Cisternal NCC may appear racemose (multilobulated, grape-like), typically lacks scolex o Complications: Meningitis, hydrocephalus, vasculitis

Imaging Recommendations • Best imaging tool o MRI is most sensitive o Calcified lesions may be better seen on CT or GRE • Protocol advice: MR with TI, T2, FLAIR, GRE, contrast

I DIFFERENTIAL

DIAGNOSIS

Abscess • Typically T2 hypointense rim and DWI + • Multiple lesions may occur related to septic emboli

Tuberculosis • Tuberculomas often occur with meningitis • Typically not cystic

8

Neoplasm

51

• Primary or metastatic (primary often known) • Thick, irregular margin enhancement typical • May have cyst and mural nodule (I.e., pilocytic astrocytoma, hemangioblastoma)

Arachnoid cyst • Solitary lesion with CSF density/intensity • No enhancement

Enlarged perivascular spaces • Follow CSF on all MR sequences • No enhancement

Infection and Demyelinating Disease

Other parasitic infection • May be cystic, but no scolex seen

General Features • General path comments o Four pathologic stages • Vesicular, colloidal vesicular, granular nodular, nodular calcified o Vesicular stage: Larva is a small marginal nodule projecting into small cyst with clear fluid • Viable parasite with little or no inflammation • May remain in this stage for years or degenerate o Colloidal vesicular stage: Larva begins to degenerate • Scolex shows hyaline degeneration, slowly shrinks • Cyst fluid becomes turbid and capsule thickens • Surrounding edema and inflammation o Granular nodular stage: Cyst wall thickens and scolex is mineralized granule • Surrounding edema regresses o Nodular calcified stage: Lesion is completely mineralized and small; no edema • Etiology o Caused by larval form of pig tapeworm, T solium o Man is intermediate host in life cycle of tapeworm • Fecal-oral most common route of infection • Ingestion of eggs from contaminated water, food • From GI tract, primary larvae (oncospheres) disseminate into CNS and skeletal muscle • Once intracranial, primary develop into secondary larvae, cysticerci o Man can also be the definitive host (infected with tapeworm) • Typically from uncooked pork • Viable larvae ingested, attach in GI tract • Epidemiology o Cysticercosis is most common, most widely disseminated parasitic infection in the world o CNS infection found in 60-90% of cysticercosis cases o Endemic in many countries (Latin America, parts of Asia, India, Africa, Eastern Europe) • In US, on the rise in CA, AZ, NM, TX o Increased travel, immigration have spread disease

Gross Pathologic & Surgical Features

52

o Varies with organism, development stage, host immune response o NCC asymptomatic until larvae degenerate o Other signs/symptoms • Syncope, dementia, visual changes, focal neurologic deficits, stroke • Clinical profile o Diagnosis confirmed by ELISAof serum or CSF o Serologic tests may cross react with Echinococcus o CSF studies abnormal in 50%, lymphocytic pleocytosis

Demographics • Age: Any age, commonly young, middle-aged adults • Gender: Slight male predominance • Ethnicity: In US, Latin American patients most commonly seen

Natural History & Prognosis • Most common cause of epilepsy in endemic areas • Variable time from initial infection until symptoms, 6 months to 30 years, typically 5 years • Variable time to progress through pathologic stages, 1 to 9 years, mean 5 years • Subarachnoid disease may be complicated by meningitis, vasculitis and hydrocephalus • Intraventricular NCC has increased morbidity and mortality o Increased morbidity related to acute obstructive hydrocephalus

Treatment • Oral albendazole (reduces parasitic burden, seizures) • Steroids often required to decrease edema during medical therapy • Surgical excision or drainage of parenchymal lesions may be required • CSF diversion often required to treat hydrocephalus • Endoscopic resection of intraventricular lesions in selected cases • Antiparasitic agents contraindicated in patients with encephalitic cysticercosis

Consider • Complex parasitic cysts may mimic brain tumor!

• Usually small translucent cyst with invaginated scolex

Image Interpretation

Microscopic

• FLAIRand T1WI helpful to identify scolex and intraventricular lesions • GRE helpful in young adults presenting with seizures

Features

• Cyst wall has 3 distinct layers: Outer (cuticular) layer, middle cellular (pseudo epithelial) layer, inner reticular (fibrillary) layer • Scolex has rostellum with hooklets, muscular suckers • Variable inflammatory reaction, acute and chronic

1.

2.

Presentation • Most common signs/symptoms o Seizure, headaches, hydrocephalus

3.

Pearls

]ayakumar PN et al: MRI and in vivo proton MR spectroscopy in a racemose cysticercal cyst of the brain. Neuroradiology. 46: 72-4, 2004 Garcia HH et al: Taenia solium cysticercosis. Lancet. 362(9383):547 -56, 2003 Zee CS et al: Imaging of neurocysticercosis. Neuroimaging Clin N Am. 10(2):391-407,2000

Infection and Demyelinating

Disease

NEUROCYSTICERCOSIS IIMAGE GALLERY (Left) Axial CECT shows a ring-enhancing mass with surrounding edema in the frontal lobe. Patient with headaches and seizures. Ventricular lesion is not well seen (arrow). NCe, colloidal vesicular stage. (Right) Axial TlWI MR shows the frontal lesion and the intraventricular cyst. Note cyst wall (open arrow) and the hyperintense scolex (arrow). TlWI and FLAIR MR are helpful to identify ventricular lesions.

(Left) Axial CECT shows right external capsule cyst with central "dot" representing a scolex. No edema or enhancement is seen, NCC vesicular stage. Calcified left putamen nodule, granular nodular stage. (Right) Axial T2WI MR shows cysts in subarachnoid spaces (arrows), filling the Sylvian fissure and causing mild mass effect on the cerebral peduncle. Note the lack of a scolex, typical of cisternal NCe.

Variant (Left) Axial TlWI MR shows innumerable cysts, each with a hyperintense scolex in this patient from Mexico. This disseminated form of NCC is rare and only seen in patients from endemic areas. (Right) Cross pathology, section shows translucent cyst with a characteristic invaginated white scolex diagnostic of neurocysticercosis. Resected lesion from a seizure patient (Courtesy B. Cremin, MO).

Infection and Demyelinating Disease

8 53

PARASITES, MISCELLANEOUS

Axial CECT shows a unilocular cyst with no surrounding edema or enhancement, typical of echinococcus (hydatid disease). Note significant mass effect. Patient from Turkey.

Axial CECT shows multiple punctate foci and ring-enhancing lesions with nodules. Note surrounding edema and mass effect, particularly in the right frontal lobe. Amebic encephalitis.

I TERMINOLOGY

• In chronic stage, round and ovoid Ca++ in mass o Schistosomiasis: Granulomatous encephalitis, hyperintense mass, enhancing dots along linear area o Sparganosis: Conglomerate, multicystic mass with surrounding edema o Trichinosis: Eosinophilic meningoencephalitis, vascular thrombi, infarcts o Trypanosomiasis: Meningoencephalitis, organisms in VRSs cause brain edema, congestion, petechial hemorrhages

Definitions • Parasitic infection affecting the CNS

I IMAGING General

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FINDINGS

Features

• Best diagnostic clue: Enhancing supratentorial mass, may be multiloculated • Location o Majority of parasitic infections are supratentorial o Amebic encephalitis: Supratentorial, frontal lobes and basal ganglia o Echinococcus: Parietal lobe common; MCA territory o Malaria: Predilection for basal ganglia, cortex o Paragonimiasis: Hemispheric, commonly posterior • Morphology o Amebic encephalitis: Meningoencephalitis; single or multiple focal, nodular or ring-enhancing masses o Echinococcosis: Large uni- or multilocular cyst +/detached germinal membrane, daughter cysts, no edema o Malaria: Punctate and ring hemorrhages, infarcts, cerebral edema o Paragonimiasis: Acutely may cause hemorrhage or infarct followed by granuloma formation

DDx: Ring-enhancing

Cystic GBM

Parenchymal

Metastatic Disease'

CT Findings • NECT o Amebic encephalitis: Diffuse edema o Echinococcus: Unilocular or multilocular cyst, isodense to CSF,no edema; Ca++ rare, < 1% o Malaria: 4 patterns, correlate with disease severity • Normal • Diffuse cerebral edema • Focal infarct: Cortex, basal ganglia, thalamus, pOllS, cerebellum; +/- hemorrhage • Bilateral thalamic and cerebellar hypodensity o Paragonimiasis: Multiple conglomerated granulomas, +/- hemorrhage • Multiple round or oval calcifications, surrounding low density, cortical atrophy, ventriculomegaly o Schistosomiasis: Single or multiple hyperdense lesions with edema, mass effect

lesions

Pyogenic Abscess

Infection and Demyelinating Disease

Neurocysticercosis

PARASITES, MISCELLANEOUS Key Facts Imaging Findings • Majority of parasitic infections are supratentorial • Amebic encephalitis: Meningoencephalitis; single or multiple focal, nodular or ring-enhancing masses • Echinococcosis: Large uni- or multilocular cyst +/detached germinal membrane, daughter cysts, no edema • Malaria: Punctate and ring hemorrhages, infarcts, cerebral edema • Paragonimiasis: Acutely may cause hemorrhage or infarct followed by granuloma formation • Schistosomiasis: Granulomatous encephalitis, hyperintense mass, enhancing dots along linear area • Sparganosis: Conglomerate, multicystic mass with surrounding edema • Trichinosis: Eosinophilic meningoencephalitis, vascular thrombi infarcts o Sparganosis: Conglomerate, multicystic mass with surrounding edema; +/- Ca++ • Atrophy, ventricular dilatation in chronic cases o Trichinosis: Hypodense white matter lesions, cortical infarcts o Trypanosomiasis: Edema with scattered petechial hemorrhage • CECT o Amebic encephalitis: Single or multiple focal, punctate, nodular or ring-enhancing masses o Echinococcus: No enhancement typical o Paragonimiasis: Ring-enhancement o Trichinosis: Ring-enhancing lesions

• Trypanosomiasis: Meningoencephalitis, organisms in VRSs cause brain edema, congestion, petechial hemorrhages

Top Differential • • • •

Diagnoses

Neoplasm Abscess Neurocysticercosis Porencephalic cyst

Diagnostic Checklist • Complex conglomerated parasitic cysts of any etiology may mimic brain tumor! • Patient's travel history is often key to diagnosis

o Paragonimiasis: Conglomerated, multiple ring-enhancing lesions • Chronic: Atrophy and calcification o Schistosomiasis: Central linear enhancement surrounded by multiple punctate nodules, arborized appearance o Sparganosis: Variable; pattern may change on follow-up related to worm migration

Imaging Recommendations • Best imaging tool o Contrast MR is most sensitive for detection o CT may be helpful to identify associated Ca++ • Protocol advice: Contrast-enhanced MR

MR Findings • TlWI o Amebic encephalitis: Centrally hypointense mass o Echinococcus: Cyst isointense to CSF • T2WI o Amebic encephalitis: Hyperintense lesions, +/hemorrhage • May have hypointense rim o Echinococcus: Cyst isointense to CSF with hypointense rim; no perilesional edema o Paragonimiasis: Heterogeneous mass with surrounding edema, +/- hemorrhage • May have isointense or hypo intense rim o Malaria: Cortical and WM ischemia, hyperintense • Deep gray nuclei and cerebellar hyperintensity o Schistosomiasis: Hyperintense mass with surrounding edema o Sparganosis: Conglomerate, multicystic mass with surrounding edema, +/- hemorrhage • May see mixed signal lesion, central low signal and peripheral high signal • Unilateral white matter degeneration, cortical atrophy in chronic cases • Tl C+ o Amebic encephalitis: Heterogeneous or ring-enhancement o Echinococcus: No enhancement typical; may see fine peripheral enhancement

I DIFFERENTIAL DIAGNOSIS Neoplasm • Primary or metastatic (primary often known) • Thick, irregular margin enhancement typical

Abscess • T2 hypointense rim and DWI+ typical • Ring-enhancement, thinner on ventricular

margin

Neurocysticercosis • Cyst with marginal scolex • Multiple lesions common

8

Porencephalic cyst

55

• Encephalomalacia +/- surrounding gliosis • Typically communicates with ventricle

Arachnoid cyst • Nonenhancing solitary lesion with CSF density/intensity

I PATHOLOGY General Features • General path comments: size, stage of infection

Infection and Demyelinating Disease

Findings depend on number,

• Etiology o Amebic encephalitis: Entamoeba histolytica, Naegleria fowleri, Acanthamoeba most common • Infection from swimming in contaminated freshwater lake or inhaling dust or soil with amebic cysts • Ascends along olfactory tract to brain or hematogenous spread o Echinococcus (hydatid disease) is caused by E granulosis most commonly and E multilocularis • Dogs or other carnivores are definitive hosts • Sheep or cattle are intermediate hosts • Humans are secondarily infected by ingestion of food or water contaminated with parasite eggs • Parasite from GI tract to portal system, lymphatics • Infection usually occurs in liver and lungs o Malaria: Infection of erythrocytes by P falciparum • Vascular occlusion of capillaries by infected erythrocytes o Paragonimiasis: Ingestion of undercooked fresh water crabs or crayfish contaminated with Westermani flukes (lung fluke) • Worms penetrate skull base foramina and meninges and directly invade brain parenchyma o Schistosomiasis: Infestation from trematode (fluke) worms • Host is freshwater snail • Humans affected through skin • Migrate to lungs and liver, reach venous system o Sparganosis: Ingestion of contaminated water or food (snake, frogs) o Trichinosis: Ingestion of uncooked meat containing infective encysted larvae o Trypanosomiasis: African (sleeping sickness) and American (Chagas' disease) • African: Transmitted to humans by tsetse fly; invade meninges, subarachnoid, VRSs • American: Transmitted by reduviid bugs • Epidemiology o NCC most common parasitic infection worldwide o Increased travel, immigration have spread diseases o Amebic encephalitis: < 1% of amebiasis patients o Cerebral Echinococcus: 2% of intracranial masses o Malaria: Cerebral complications in 2% of cases o Paragonimiasis: Brain involvement in 2-27% of cases o Schistosomiasis: 2% of cases CNS complications o Sparganosis: Extremely rare o Trichinosis: CNS involvement in 10-24% of cases 56

Gross Pathologic & Surgical Features • Amebic encephalitis: Cerebral edema, hemorrhage, necrosis, meningeal exudate • Echinococcus: Cysts (4-10 cm) with thick, smooth wall o Cyst 3 layers: Host forms outer fibrous layer (pericyst), middle laminated membrane layer, inner germinal layer (produces scolex) • Malaria: Ischemia, edema, petechial hemorrhage • Paragonimiasis: Cystic lesions elaborate toxins that result in infarction, meningitis, adhesions • Sparganosis: Live worm or degenerated worm with surrounding granuloma found at surgery • Trichinosis: Eosinophilic meningoencephalitis, ischemic lesions, petechial hemorrhage, necrosis

• Trypanosomiasis:

Edema, congestion,

hemorrhage

Presentation • Most common signs/symptoms o Amebic encephalitis: Headache, fever, seizures, increased intracranial pressure, coma o Echinococcus: Mass effect related to lesion location o Malaria: Altered consciousness, seizures o Paragonimiasis: Headache, seizure, visual changes o Sparganosis: Headache, seizure, neurologic signs o Trichinosis: Fever, headache, delirium, seizures, focal neurologic deficits o Trypanosomiasis, African: Behavior change, indifference, daytime somnolence o Trypanosomiasis, American: Acute (fever, swollen face, conjunctivitis), Chronic (neurologic) o Schistosomiasis: Encephalopathy, seizures, paresis, headache, visual changes • Clinical profile o Varies with organism, development stage, host immune response o ELISA studies can be helpful in some diseases

Demographics • Age: Most parasitic infections occur at all ages but commonly affect children and young adults • Gender: Most parasitic infections, male predominance

Natural History & Prognosis • Some parasitic infections (e.g., echinococcosis) develop slowly over many years • Amebiasis: Second cause of death from parasites • Echinococcus complicated by rupture, hemorrhage, secondary infection • Malaria: Most common cause of death from parasites o 15-25% mortality despite appropriate therapy • Trichinosis: Mortality in 5-10% of affected individuals • Trypanosomiasis, American: Mortality 2-10% of meningoencephalitis patients

Treatment • Variable, ranges from oral therapy to lesion resection

Consider • Complex conglomerated parasitic cysts of any etiology may mimic brain tumor! • Patient's travel history is often key to diagnosis

1.

2. 3.

KHon AD et al: The role of eosinophils in host defense against helminth parasites. J Allergy Cin Immunol 113:30-7, 2004 Polat P et al: Hydatid disease from head to toe. Radio Graphics 23:475-94, 2003 Patankar TF et al: Adult cerebral malaria: prognostic importance of imaging findings and correlation with postmortem findings. Radiology 224:811-6,2002

Infection and Demyelinating Disease

Typical (Left) Axial T7 C+ MR shows posterior fossa masses with punctate enhancement (arrows) (Courtesy O. Kremens,5. Caletta, MO). (Right) Microscopic pathology from biopsy of case on left shows 5. mansoni with characteristic lateral spine (arrow).

(Left) Axial NECT shows symmetric, bilateral thalamic hypodensity in a young patient with malaria, severely altered consciousness (Courtesy R. Ramakantan, MO). (Right) Axial T2WI MR shows bilateral symmetric hyperintensity of the cerebellar hemispheres in the same patient. Patient expired despite maximal therapy. Adult cerebral malaria.

Typical (Left) Axial T2WI MR shows a heterogeneous lesion in the right frontal lobe with mass effect and surrounding edema in this patient from East Asia. Note the hypointense rim (arrow) typical of Paragonimiasis. (Right) Coronal T1 C+ MR shows conglomerated, ring-enhancing lesions with marked surrounding edema. Paragonimiasis. Lesion mimics a neoplasm. Chronically, calcifications and atrophy will develop.

Infection and Demyelinating Disease

57

Coronal T1 C+ MR shows small enhancing lesions (arrows) in the perivascular spaces along lenticulostriate arteries in the basal ganglia. Cryptococcus.

Axial T1 C+ MR shows multiple small enhancing foci due to nocardiosis in a patient post kidney transplantation.

Radiographic Findings Abbreviations • Blastomycosis, candidiasis

and Synonyms coccidiomycosis,

histoplasmosis,

Definitions • Blastomycosis: Rare, sporadic, caused by B dermatitidis, generally affecting lungs/skin • Coccidioidomycosis: Sporadic, relatively common, caused by C Immitis, generally affecting lungs • Histoplasmosis: Common, due to inhalation of H Capsulatum (found in animal/bird feces) • Candidiasis: Relatively common, opportunistic affects immunosuppressed patients

General Features

58

• Best diagnostic clue: Meningeal enhancement, multiple enhancing non-specific appearing lesions in brain and/or spinal cord in immunosuppressed patient • Location: Meninges, brain, spinal cord, vertebral bodies + discs • Size: Variable size of lesions • Morphology: Most lesions are ring-like and 'dot-like' and enhance

DDx: Multiple

TB

• Myelography o May present as in intramedullary spinal cord lesion producing 'block' of contrast flow o May present as adhesions and lesions in intradural/extramedullary space

CT Findings • NECT o Areas of low density ~ lacunar infarctions (infarcts may be larger) o Diffuse brain edema, herniations o Hemorrhages o Hydrocephalus o Vertebral body destruction (sclerotic lesions are rare = coccidioidomycosis) • CECT o Multiple foci of non-specific enhancement • Some are ring-like

MR Findings • T1WI: Ill-defined areas of I signal intensity • T2WI o Focal or diffuse areas of 1 signal o Spine: 1 Signal in vertebrae, disc and spinal cord • PD/Intermediate: Same as T2WI • FLAIR: Same as T2WI

Enhancing Brain lesions in Immunosuppressed

Cysticercosis

Metastases

Infection and Demyelinating

Disease

Patients

Septic Emboli

fUNGAL DISEASES Key Terminology • Blastomycosis, candidiasis

coccidiomycosis,

histoplasmosis,

Imaging Findings • Best diagnostic due: Meningeal enhancement, multiple enhancing non-specific appearing lesions in brain and/or spinal cord in immunosuppressed patient • Location: Meninges, brain, spinal cord, vertebral bodies + discs

Pathology • Blastomycosis: Endemic in Mississippi, Arkansas, Kentucky, Tennessee, Wisconsin, Africa (fungus lives in damp places, rotting wood)

• T2* GRE: May accentuate Ca++ or presence of blood products • DWI: Slightly bright on trace images but no restricted diffusion on ADC map • Tl C+ o Meningeal enhancement • Thick meningeal enhancement ...•thick acute exudates or meningeal fibrosis o Areas of non-specific appearing enhancement, may be ring-like, solitary-to-miliary • May be seen in spinal cord o Enhancement of disc, vertebrae and epidural space ...•discitis/osteomyelitis • MRA: Vessel irregularities (vasculitis), occlusions, mycotic aneurysms • MRV: Sinus thrombosis • MRS: Mildly t Cho, j NAA, t lactate

Angiographic

Findings

• Conventional:

Vasculitis, mycotic aneurysms

Nuclear Medicine • PET:

j

Metabolism

Findings and

j

blood flow to lesions

Imaging Recommendations • Best imaging tool: MRI • Protocol advice o Contrast-enhanced MRI needed in all patients o MRS may be helpful to differentiate infectious from neoplastic processes

I DIFFERENTIAL DIAGNOSIS locally invasive skull base neoplasm (e.g., SCCA) vs aggressive fungal infection • Look for soft tissue mass in nasopharynx • Fungal infection often angioinvasive with ICA occlusion (rare in SCCA)

Multiple ring-enhancing parenchymal lesions in immunocompetent patients

Facts • Coccidioidomycosis: Southwestern USA, Northern Mexico, South America (Argentina, Paraguay), t common in very young or old, pregnancy, immunosuppression (AIDS) ( fungus lives in damp places, rotting wood) • Histoplasmosis: Worldwide distribution, acquired by inhalation of fungus (in chicken, pigeon and bat feces) • Candidiasis: Worldwide distribution, t common in diabetes, lymphoma, leukemia, AIDS

Clinical Issues • In all: CFS shows pleocytosis, j glucose, t proteins • Delayed in treatment for> 2 weeks ...•poor prognosis

• Multiple pyogenic abscesses • TB

• Parasites (e.g., neurocysticercosis) • Fungal abscess (rare) • Septic emboli

Multiple ring-enhancing parenchymal lesions in immunocompromised patients • Fungal abscesses (common) • TB

• Toxoplasmosis

IpATaOlOG¥ General

Features

• General path comments: Focal or diffuse brain infection resulting in meningitis and solitary to miliary granuloma/abscess formation • Etiology o Blastomycosis: B dermatitidis, acquired by inhalation, may be secondary to pet bites o Coccidioidomycosis: C immitis, acquired by inhalation, then hematogenous spread o Histoplasmosis: H Capsulatum, acquired by inhalation, then hematogenous spread o Candidiasis: C Albicans, initially involves gastrointestinal or respiratory systems, then spreads hematogenously • Epidemiology o Blastomycosis: Endemic in Mississippi, Arkansas, Kentucky, Tennessee, Wisconsin, Africa (fungus lives in damp places, rotting wood) o Coccidioidomycosis: Southwestern USA, Northern Mexico, South America (Argentina, Paraguay), t common in very young or old, pregnancy, immunosuppression (AIDS) ( fungus lives in damp places, rotting wood) • 60,000-80,000 new cases/year in USA • 100 deaths/year in USA

• Metastases

Infection and Demyelinating

Disease

8 59

o Histoplasmosis: Worldwide distribution, acquired by inhalation of fungus (in chicken, pigeon and bat feces) • Approx 25% of USA population ~ infected • Histoplasmosis: Disseminated disease usually seen in infancy/childhood, immunosuppression o Candidiasis: Worldwide distribution, t common in diabetes, lymphoma, leukemia, AIDS • Occasionally seen in immunocompetent individuals • Most common nosocomial fungal infection • Associated abnormalities: Histoplasmosis: Calcified lung lesions and mediastinal nodes, cavitating lung lesions

Gross Pathologic & Surgical Features • In all: Congested meninges, swollen brain, focal granulomas and abscesses • Candidiasis: Hemorrhagic infarcts, abscess and granulomas w/o central necrosis (involvement may be miliary), minimal cellular reaction • Coccidioidomycosis: Involvement of CNS in 30% o Meningitis (most common site of CNS infection) o Vasculitis (40%) o Infarctions o Hemorrhages o Diffuse brain edema o Herniations • CNS involvement in 7%, meningitis with thick basilar exudates, vasculitis, foci of necrosis, granulomas, abscess

Microscopic Features • Granulomas or small abscesses with caseous necrosis, giant cells, neutrophils, lymphocytes • Identification of specific organism needed for diagnosis • Fibropurulent meningitis ~ may become meningeal fibrosis

Presentation

60

• Most common signs/symptoms o Initially for all: Weight loss, fever, malaise, fatigue o Blastomycosis: Pyoderma gangrenosum, keratoacanthoma, pneumonia, osteomyelitis, laryngeal masses, CNS involvement in 4-30% o Coccidioidomycosis: Pneumonia-like illness, meningitis which may be acute or chronic, sudden focal neurological deficits due to stroke/hemorrhage • Clinical profile o Blastomycosis: Lung lesions may simulate cancer/TB, immunocompetent patients o In all: CFS shows pleocytosis, !glucose, 1 proteins

• Ethnicity: No predilection

Natural History & Prognosis • Delayed in treatment

for > 2 weeks ~ poor prognosis

Treatment • Options, risks, complications o Blastomycosis: Itraconazole (first choice), voriconazole, amphotericin B (life-threatening o Candidiasis: Fluconazole may be helpful

Image Interpretation

cases)

Pearls

• Considered fungal infection with multiple enhancing brain lesions (particularly in a hematogenous distribution) in an immunocompromised patient

1.

Wong AM et al: Magnetic resonance imaging of carotid artery abnormalities in patients with sphenoid sinusitis. Neuroradiology. 46: 54-9, 2004 2. Revanku SG et al: Primary central nervous system phaeohyphomycosis: a review of 101 cases. Clin Infect Dis 38:206-16,2004 3. Komatsu H et al: Molecular diagnosis of cerebral aspergillosis by sequence analysis with panfungal polymerase chain reaction. ] Pediatr Hematol Oncol 26:40-4, 2004 4. Brant ME et al: Epidemiology, clinical manifestations, and therapy of infections caused by dematiaceous fungi. ] Chemother Is (SuppI2):36-47, 2003 5. Schelenz S et al: Candidemia in a London teaching hospital: analysis of 128 cases over a I-year period. Mycoses 46:390-6, 2003 6. Bradsher RW et al: Blastomycosis. Infect Dis Clin N Am 17: 21-40,2003 7. Chowfin A et al: Recurrent blastomycosis of the central nervous system: case report and review. Clin Infect Dis 30: 969-71, 2000 8. Erly WK et al: Disseminated coccidioidomycosis complicated by vasculitis: a cause of fatal subarachnoid hemorrhage in two cases. A]NR 20: 1605-8, 1999 9. Lai PH et al: Disseminated miliary cerebral candidiasis. A]NR 18: 1303-06, 1997 10. Desai SP et al: Disseminated CNS histoplasmosis. A]NR 12: 290-92, 1991

Demographics • Age o More common in young and older individuals o Also seen at any age if immunocompromised • Gender o More common in males (1 outdoor activities) • Blastomycosis: Agricultural workers

Infection and Demyelinating Disease

Typical (Left) Axial T1 C+ MR shows

ring enhancing lesion in left frontal lobe with surrounding edema and mass effect due to blastomycosis. (Right) Axial T1 C+ MR shows enhancement of the quadrigeminal plate cistern (arrow) due to blastomycosis.

(Left) Axial T1 C+ MR shows enhancing lesion in the right basal ganglia and thalamus and in the left occipital lobe due to coccidiomycosis. (Right) Axial T1 C+ MR shows multiple ring enhancing lesions due to nocardia.

Typical (Left) Axial FLAIRMR shows

high signal intensity in the basal ganglia, right greater than left. (Right) Coronal T1 C+ MR in the same patient shows enhancing lesions (arrow) along the perivascular spaces of the right neostriatum. Cocci vasculitis.

Infection and Demyelinating Disease

61

Axial OWl MR shows tiny white matter infarcts in the left hemisphere in a patient with Rocky Mountain spotted fever.

Abbreviations

and Synonyms

• Common: Rocky Mountain spotted (RMS) fever • Less common: Q fever, typhus, Mediterranean spotted fever

Definitions • Zoonotic infections of squirrels and other animals ~ ticks carrying rickettsia ~ men

Coronal T1 C+ MR shows non-specific pial enhancement in a patient with Rocky Mountain spotted fever.

o Increased signal in extra-ocular muscles ~ rare in Lyme disease • T2WI o Hyperintense WM lesions in distribution of peri-vascular spaces, deep gray nuclei, pons o Diffuse brain swelling • DWI: All lesions bright on trace images, some lesions show! ADC • Tl C+ o Some lesions and meninges enhance o Enhancement cauda equina nerve roots and lower thoracic spinal cord

Imaging Recommendations General Features • Best diagnostic clue: RMS: Ill-defined areas of low density on CT, high T2 signal in white matter (WM) with skin rash • Location: RMS: Deep, infarct-like lesions, cauda equina, low spinal cord

CT Findings

Multiple sclerosis (MS)

• NECT: Small Ill-defined WM low density foci • CECT: Lesions may enhance

• WM periventricular lesions, subcallosal lesions on sagittal T2WI and FLAIR, involvement of chiasm and/or optic nerves

MR Findings 62

• Best imaging tool: MRI, only 20% of patients with RMS have abnormal MRI • Protocol advice: Brain MRI with contrast

• TlWI o Slightly hypointense

Vasculitis

DDx: Multifocal

M.

• Segmental narrowing of arteries on angiography, multiple infarcts of different ages on T2WI/DWI

lesions

Sclerosis

White Matter lesions

Vasculitis

Sarcoidosis

Infection and Demyelinating Disease

Herpes

Simplex

1

RICKETTSIAL DISEASES Key Facts Terminology.

Pathology

• Common: Rocky Mountain spotted (RMS) fever • Zoonotic infections of squirrels and other animals ...• ticks carrying rickettsia ...•men

• RMS: Rickettsia rickettsii transmitted ticks, tick bites in 60% of patients

Imaging Findings

• RMS: Acute febrile illness, myalgias, headache, petechial rash (palms, soles, 90%)

• Best diagnostic clue: RMS: Ill-defined areas of low density on CT, high T2 signal in white matter (WM) with skin rash

Sarcoidosis • Non-specific WM lesions, enhancement in peri-vascular spaces/meninges, enhancing masses in suprasellar region/orbit

Clinical Issues

• RMS: 90% die if untreated, 20% of patients with MRI abnormalities die regardless of treatment • RMS: Complications in "" Vz of patients

Treatment • RMS: Doxycycline, tetracycline,

Viral illnesses • Herpes simplex encephalitis: Typically bilateral disease, but asymmetric, basal ganglia usually spared

IDIA'~~~~TI(})

chloramphenicol

(})HE(})KI..I~T

I PA'l"17n}JU.~~M

Consider

General Features

I~EI..E(})TEDREFERE~(})E~

• Remember normal MRI does not exclude diagnosis

• General path comments o RMS caused by Rickettsia rickettsii, most common rickettsial disease o Destruction of endothelial/vascular smooth muscle cells • Increased permeability ...•brain swelling • Thrombosis • Etiology: RMS: Rickettsia rickettsii transmitted by wood/dog ticks, tick bites in 60% of patients • Epidemiology: Increased incidence in Oklahoma, North Carolina, South Carolina, Tennessee, Arkansas

Microscopic

by wood/dog

1. 2. 3. 4.

5.

Singh-Behl D et al. Tick-borne infections. Dermatologic Clinics 21: 237-44, 2003 Walker DH et al: Pathogenic mechanisms of diseases caused by Rickettsia. Ann N Y Acad Sci 990: 1-11,2003 Warner RD et al: Rocky mountain spotted fever. JAVMA 221: 1413-17, 2002 Bonawitz C et al: Comparison of CT and MR features with clinical outcome in patients with Rocky Mountain Spotted fever. AJNR 18: 459-64, 1997 Baganz MD et al: Rocky Mountain Spotted fever encephalitis: MR findings. AJNR 16: 919-22, 1995

Features

• RMS: Diagnosis ...•identification of rickettsia on direct or indirect (> 1:64) immunofluorescence • RMS: Destructive systemic thrombovasculitis • Confirmation of RMS by histologic examination of skin biopsy

I'MA'GE GA'I..I..ERM

I (})1..1~I(})A'I.. 1~~l:1E~

8

Presentation • Most common signs/symptoms: RMS: Acute febrile illness, myalgias, headache, petechial rash (palms, soles, 90%) • Clinical profile: RMS: i or I WBC count, anemia, thrombocytopenia, coagulopathy, abnormal liver function tests, i BUN

Demographics • Age: No predilection

63

(Left) Sagittal T1 C+ MR shows enhancement

of ventral and dorsal (arrows) nerve roots in the distal spinal cord and conus medullaris regions. (Right) Axial T1 C+ MR shows the nerve roots enhancing. RMS often involves both brain, spine.

Natural History & Prognosis • RMS; Early antibiotics rapidly progressive

...•effective, if not treated ...•

Infection and Demyelinating Disease

Axial T2WI MR shows small bright lesion in the right posterior aspect of the white matter of the centrum semiova/e.

Abbreviations

and Synonyms

• Lyme borreliosis

Definitions • Multisystem inflammatory disorder ~ spirochete Borrelia burgdorferi, transmitted by deer tick

Axial T1 C+ MR shows enhancement of the facial nerves (black arrows) in the fundi of the internal auditory canals and of the geniculate ganglia (white arrows).

o High signal in periventricular WM, spinal cord o Occasionally gray matter involved o Size: 2-3 mm typical; large lesions rare • DWI: Some lesions have I ADC • Tl C+ o Some enhancement in WM lesions/meninges o Enhancement of CN 7 (including root entry zones) o Occasional enhancement of cauda equina

Imaging Recommendations • Protocol advice: Contrast-enhanced

brain MRI

General Features • Best diagnostic clue: Lesions simulate multiple sclerosis (MS) in patient with skin rash and influenza-like illness • Location o Periventricular white matter (WM) o CN 7, cauda equina, leptomeninges

CT Findings • NECT: Small hypodense periventricular lesions • CECT: Faint enhancement in some lesions

64

• WM lesions (may enhance); lesions in optic nerve, spinal cord, sub-callosal region common

Vasculitis • Lesions of 1 T2 signal and of different age, arterial narrowings on angiography

Sarcoidosis • Enhancement in peri-vascular spaces, enhancing lesions in brain, cord, suprasellar region, orbits

MR Findings • TlWI o Slightly low signal o Rare: Enlarged extra-ocular • T2WI

Multiple sclerosis (MS)

muscles

DDx: Common White Matter Hyperintensities

I

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"

~.

t .)~ ..~,(' '-1 I. ~;:

I

-"""

1

\.. ---r

, '.

,

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MS

Sarcoidosis

Vasculitis

Infection and Demyelinating Disease

JI

\,

Lacunar Infarct

LYME DISEASE Key Facts Terminology

Pathology

• Multisystemtnflammatory disorder •..•spirochete Borrelia burgdorferi, transmitted by deer tick.

• Most common tick-born (ixodes dammini)

lma

• Peak incidence: May-August

•

Findings al in periventricular WM, spinal cord cement of eN 7 (including root entry zones)

Chronic fatigue syndrome • Generally normal but may show subcortical areas of high T2 signal, t brain perfusion on SPECT

Infarctions • Lacunar infarcts + age-related WM changes

Iltlll-TI

disease in

USA

Clinical Issues • Standard Rx: Doxycycline, chlQramphenicol

tetracycline,

o Early localized: Fever, myalgias, headaches, petechial rash (palm, soles in 90%) o Early disseminated: Erythema migrans, arthralgias, myalgias, fever, adenopathy o Late: Arthritis, carditis, scleroderma-like lesions, CNS lesions, t intracranial pressure • Clinical profile: Confirmation of diagnosis: ELISA, PCR

Demographics

m E~till~

• Age: Transplacental

infection rarely reported

General Features

Natural History & Prognosis

• General path comments o Destruction of endothelial and vascular smooth muscle cells o B burgdorferi has t tropism for skin, CNS, joints, atrio-ventricular node • Etiology o Slow-growing motile spirochete • B burgdorferi is most common type • Transmitted to man by ixodid ticks • Epidemiology o Most common tick-born (ixodes dam mini) disease in USA o White tail deer/white footed mouse = most important reservoirs o Highest prevalence in: Connecticut, Rhode Island, New York, Pennsylvania, Delaware, New Jersey, Maryland, Massachusetts, Wisconsin o Also occurs in Europe o Approximately 10,000 new cases in USA o Peak incidence: May-August • Associated abnormalities: i IgM initially, then t IgG

• Progressive debilitating disorder if not treated early • Most recover with minimal or no residual deficits

Treatment • Standard Rx: Doxycycline, tetracycline, chloramphenicol • New: Ketolides (experimental studies) • Vaccination in endemic regions

ISELECIED 1.

REFERENCES

Ustymowicz A et a1: Proton MR spectroscopy in neuroborreliosis: a preliminary study. Neuroradio1ogy. 46: 26-30,2004

IIMAtillE GALLERY

Gross Pathologic & Surgical Features

8

• Pale-appearing periventricular lesions • Swelling of nerves ~ cauda equina, peripheral

65

Microscopic Features • Perivascular infiltrates of lymphocytes/plasma cells o Involving: Endoneurial, perineurial, epineurial blood vessels • Endarteritis obliterans • Axonal degeneration • Autonomic ganglia: Lymphocytes, plasma cells

(Left) Axial FLAIR MR shows focal area of high signal in posterior limb

of right internal capsule. (Right) Axial FLAIR MR shows tiny area of high signal in subcortical WM of medial left frontal lobe. Proven Lyme disease.

ICLINICAL

ISSUES

Presentation • Most common

signs/symptoms

Infection and Demyelinating

Disease

Axial CECT shows cortical atrophy and nonenhancing diffuse hypodensity in deep and periventricular white matter. Ventricles are slightly enlarged.

Axial CECT in the same HIV+ pauent, 6 months later, shows more severe cortical atrophy and diffuse hypodensity in deep and periventricular white matter. More pronounced ventriculomegaly.

CT Findings Abbreviations

and Synonyms

• HIV-l encephalitis/HIV-l

encephalopathy

(HIVE)

Definitions • Syndrome of cognitive, behavioral, and motor . abnormalities attributed to direct HIV effect on bram, in the absence of opportunistic brain infections o Most frequent neurological manifestation of HIV infection

General Features

66

• Best diagnostic clue: Combination of atrophy and symmetric, periventricular or diffuse white matter (WM) disease suggests HIVE • Location: Bilateral periventricular and centrum semiovale WM, basal ganglia, cerebellum, brainstem • Size: Variable • Morphology: Ends at gray-white matter junction • Pathology/imaging varies with patient age, acuity/chronicity • Clinical findings should guide imaging studies (not reverse)

DDx: Focal White Matter Abnormalities

PML

HSV Encephalitis

• NECT o Children: Atrophy and WM diffuse hypodensity • In utero HIV infection: Characteristic bilateral and symmetrical calcifications in basal ganglia and frontal WM with eventual contrast-enhancement o Adults: Normal or mild atrophy, WM hypodensity o No mass effect • CECT: Usually no contrast-enhancement

MR Findings • T1WI: WM abnormality may not be evident • T2WI o 2 imaging patterns • Focal abnormalities of high signal intensity • Diffuse moderate-high signal WM changes o Distribution and extent of WM lesions do not necessarily correlate with clinical picture • FLAIR o Same imaging patterns as T2WI o Allows early detection of small « 2 cm) lesions in cortical/subcortical and deep WM locations o Greater overall lesion conspicuity (when compared to T2 weighted fast spin-echo imaging) • Tl C+: No enhancement in involved regions • MRS o AIDS patients with CD4 < 200/mm3, neurologic evidence of AIDS dementia complex, and atrophy

in HIV+

Lymphoma

Infection and Demyelinating Disease

HHV6 Encephalitis

HIV ENCEPHALITIS Key Facts Imaging Findings

Pathology

• Best diagnostic clue: Combination of atrophy and symmetric, periventricular or diffuse white matter (WM) disease suggests HIVE • Pathology/imaging varies with patient age, acuity/chronicity • Clinical findings should guide imaging studies (not reverse) • MTR allows differentiation of HIVE from PML

• Hallmark of HIVE: Microglial nodules with multinucleated giant cells (MGCs) • Viral entry into brain occurs very early after systemic infection • 33-67% of adult AIDS patients and 30-50% of pediatric AIDS patients are affected by HIVE

Top Differential • • • • •

Diagnoses

Progressive multifocalleukoencephalopathy CMV-associated CNS disease Herpes virus encephalitis Toxoplasmosis Primary CNS lymphoma

• IH MRS in subcortical region shows IN-acetyl aspartate (neuronal loss) and 1 choline in WM (astrocytosis or microglial proliferation) o Cognitively normal and clinically asymptomatic patients • 1H MRS in subcortical region shows only 1 choline • Two major consequences of HIV migration to brain o Atrophy of brain parenchyma due to neuronal death o Alterations of deep WM (usually periventricular regions) ~ high signal intensity on T2WI • Magnetization transfer ratio (MTR) o Slightly lower than normal MTR values in areas of WM hyperintensities (WMHs) in HIVE (gliosis) o 1-2% t in MTR values of normal MR appearing WM in HIVE, indicating diffuse brain involvement o MTR allows differentiation of HIVE from PML • Dramatic t in MTR for PML lesions (as compared to HIVE lesions) likely due to demyelination o MTR may distinguish between severe and discrete WM involvement by HIVE o MTR may be useful in assessing drug effect on HIVE o Diffusion tensor imaging • May show early I fractional anisotropy in HIV-associated cognitive impairment

Imaging Recommendations • Best imaging tool o MRI better than CT for WM lesion detection o MRS may detect changes in WM even during asymptomatic stage (in patients with laboratory evidence of immunosuppression) o MRS may assess short-term response to intervention • Protocol advice o CT scan if • New seizurei depressed or altered orientation • Headache, different in quality (careful neurologic examination should precede neuroimaging) • CD4 count < 200 cells/mm3 o MR scan if • CT shows focal mass • Negative CT in patient with profound cognitive deficits or focal findings • If MR shows mass, obtain DWI, ADC maps

Clinical Issues • Most common signs/symptoms: Subcortical dementia with cognitive, motor and behavioral deficits • Highly active antiretroviral therapy (HAART) cannot prevent occurrence of HIVE, but t HIVE severity

I u)IFFERENIIAI.. U)IAGN@SIS Progressive multifocalleukoencephalopathy • Patchy, (usually) non enhancing WM lesions, may be unilateral but more often bilateral and asymmetric o Hypodense on CTi T2 hyper-IT 1 iso- and later hypointense areas on MR, usually without significant mass effect • Frontal and parieto-occipital locations most common • Characteristic involvement of subcortical U-fibers by ]C virus (unlike HIV or CMV)

CMV-associated

CNS disease

• Encephalitis (diffuse WMHs) • Ventriculitis (ependymal enhancement)

Herpes virus encephalitis • Herpes simplex virus (HSV), human herpes virus 6 (HHV6): Initially hippocampal and medial temporal lesions

Toxoplasmosis • Ring-enhancing mass(es) • Hyperintense lesions on T2WI/FLAIR, DWI • Predilection for hemorrhagei I MR perfusion

Primary CNS lymphoma • Solitary/multifocallesions, deep> subcortical lesions • Marked predilection for basal ganglia, cerebellar hemispheres, thalamus, brain stem, corpus callosum, and sub ependymal region • NECT: Iso-, hyper- or hypodense • CECT: Usually homogeneous enhancement • MR: T1 iso-/hypointensei variable on T2WI/FLAIR o Most lesions enhance in solid or ring fashion, but nonenhancing lymphoma also reported • Positive thallium-201 SPECTi 1 MR perfusion

Cryptococcosis • "Gelatinous" pseudo cysts within periventricular • Meningoencephalitis +1- vasculitis, infarction

Other CNS masses in HIV+ patients • Fungal infectioni TBi syphilisi astrocytoma

Infection and Demyelinating Disease

(rare)

spaces

8 67

General Features • General path comments o Hallmark of HIVE: Microglial nodules with multinucleated giant cells (MGCs) o Reactive gliosis, focal necrosis and demyelination o Mild neuronal loss; minor inflammatory changes o Viral entry into brain occurs very early after systemic infection • Genetics o HIV genomic =} more neurovirulent strains o Dementia affects only some patients depending on whether critical mutations occur in HIV strain • Etiology o During primary infection, HIV is transported into brain by monocyte/macrophage system o HIV has ability to cause neurologic disease, but does not replicate within neural/glial cells o Myelin destruction is not usual, and T2WI WMHs may be due to t water content o Inflammatory (T-cell) reaction with vasculitis, leptomeningitis o Immune activation of parenchyma (t microglial cells, cytokines, upregulation of antigens) • Epidemiology o 33-67% of adult AIDS patients and 30-50% of pediatric AIDS patients are affected by HIVE o HIVE occurs before opportunistic infections and neoplasms; prevalence unrelated to disease stage • Associated abnormalities o HIVE can occur in conjunction with other AIDS-related abnormalities (e.g., other infections) o Progressive encephalopathy (PE) in children is frequently associated with myelopathy

Gross Pathologic & Surgical Features

o HIV giant cells: PAS+ mono- or multinuclear macrophages • Mild HIVE: Finding 1 without MGCs • Moderate HIVE: Finding 1, 2 or 3 • Severe HIVE: Cerebral atrophy with finding 1 or 2

Presentation • Most common signs/symptoms: Subcortical dementia with cognitive, motor and behavioral deficits • Clinical profile o HIV cognitive syndrome: Minor or major (dementia) o Deficits of central motor function o Behavioral: Pseudodementia (depression), delirium and confusion o Pediatric PE: Microcephaly, cognitive defects, weakness, pyramidal signs, ataxia and seizures

Demographics • Age: Both pediatric and adult HIV+ patients • Gender: No gender preference; gender distribution HIVE reflects that of HIV infection

of

Natural History & Prognosis • Cognitive decline occurs once patients become immunocompromised • Slowly progressive impairment of fine motor control, verbal fluency and short-term memory • After few months: Severe deterioration and subcortical dementia with near vegetative state as final stage

Treatment • Highly active antiretroviral therapy (HAART) cannot prevent occurrence of HIVE, but I HIVE severity o HAART era: I Frequency of severe HIVE, but t frequency of mild-moderate HIVE

• Early: WM pallor • Late: Neocortical infection, atrophy

Microscopic Features

8 68

• HIVE o Infected cells: Mostly macrophages and microglia; few astroglia; rarely oligodendrocytes o Neurons undergo secondary damage o Minor inflammatory changes: Perivascular macrophage infiltrates and microglial nodules o In severe infections: MGCs with HIV antigen • PE in pediatric AIDS population o Inflammatory infiltrates with MGCs o Extensive calcific vasopathy primarily in small vessels of basal ganglia, also cerebral WM and pons o Atrophy from loss/arrested development of myelin

Consider

Staging, Grading or Classification Criteria

1.

• 3 Types of neuropathological findings o HIV encephalitis: Multiple disseminated foci of microglia, macrophages, and MGCs; if no MGCs found, HIV antigen/nucleic acids required o HIV leukoencephalopathy: Diffuse and symmetric WM damage (myelin loss, reactive astrogliosis, macrophages, and MGCs); if no MGCs found, HIV antigen/nucleic acids required

2.

• Evidence of "cerebral atrophy" by CT/MRI does not indicate AIDS dementia complex in HIV+ patient o Consider reversible causes first: Dehydration, malnutrition, protein depletion, or alcoholism

Image Interpretation

Pearls

• Characteristic parenchymal changes often missed by CT, but detected by MRI (T2WI)

Ragin AB et al: Whole brain DTI in HIV-associated cognitive impairment. AJNR25:195-200, 2004 Graham CB et al: Screening CT of the brain determined by CD4 count in HIV-positive patients presenting with headache. AmJ Neuroradio121:451-54, 2000

Infection and Demyelinating Disease

Typical (Left) Axial T2WI MR shows cortical atrophy, periventricular white matter hyperintensities and dilated ventricles. (Right) Axial T7 WI MR in the same patient shows volume loss in Sylvian fissures and compensatory dilation of ventricles secondary to atrophy. White matter abnormalities are less conspicuous on this image.

Typical (Left) Axial FLAIR MR in the same patient as above shows marked cortical atrophy (dilated sulci and Sylvian fissures), periventricular white matter hyperintensities and enlarged ventricles. (Right) Axial FLAIR MR in the same patient shows cortical atrophy, bilateral and symmetric periventricular white matter hyperintensities, and ventriculomegaly.

(Left) Axial CECT in HIV+ patient shows nonenhancing diffuse white matter hypodensity. Mild cortical atrophy also observed. (Right) Axial CECT in the same HIV+ patient shows nonenhancing diffuse white matter hypoden"sity and cortical atrophy.

Infection and Demyelinating Disease

8 69

Coronal graphic shows muluple toxoplasmosis abscesses in an HIV+ patient. Basal ganglia location is typical.

Abbreviations • Opportunistic

• Location o Toxo: BG in up to 75%, thalamus, cerebral hemispheres o Crypto: Virchow-Robin spaces(VRSs), mostly BG/subcortical WM o PML: Any lobe (frontal/parieto-occipital most common sites) • Posterior fossa may be involved • Size: Variable • Morphology o Crypto: Round (cryptococcomas, pseudocysts) o PML: Subcortical U-fiber involvement ~ "scalloped" appearance at gray-white (G-W) interface

and Synonyms infections

(OIs)

Definitions • CNS infections in patients with severely impaired cell-mediated immunity due to advanced AIDS • Cerebral toxoplasmosis (toxo) = encephalitis, abscesses • Cytomegalovirus (CMV) infection = encephalitis, ven triculoencephali tis • Progressive multifocalleukoencephalopathy (PML) = subacute demyelinating 01 • Cryptococcosis (crypto) = granulomatous meningitis/parenchymal CNS disease • Tuberculosis (TB) = meningitis, tuberculomas, tuberculous abscesses (TBA)

CT Findings • NECT o Toxo: Usually multiple hypo-/isodense lesions • Usually with surrounding edema and mass effect • Follow-up CT: Complete resolution of lesions or residuallucencies or hyperdense calcifications o PML: Multifocal, scalloping WM hypodensities without mass effect or edema • Rapid progression in size ~ confluence of lesions o TB meningitis: EVOH most common (50%) • Preferential involvement of basilar cisterns • Vasculitis and subsequent infarct o Tuberculomas/TBA: Edema, mass effect, Ca++ (chronic cases)

General Features

70

Axial T2WI MR shows lesions with hypointense rim and surrounding vasogenic edema, consistent with toxoplasmosis abscess.

• Best diagnostic clue o Toxo: Multiple ring-enhancing lesions of varying size with surrounding edema • Most common cause of focal lesion in HIV+ o Crypto: Multiple T2 hyperintense small areas in basal ganglia (BG) are characteristic

DDx: Focal Mass in HIV+

Primary Lymphoma

Taxa

Bacterial Abscesses

Infection and Demyelinating Disease

OPPORTUNISTIC INFECTION, AIDS Key Facts Terminology • CNS infections in patients with severely impaired cell-mediated immunity due to advanced AIDS

Imaging Findings • Toxo: Multiple ring-enhancing lesions of varying size with surrounding edema • Crypto: Multiple T2 hyperintense small areas in basal ganglia (BG) are characteristic • CMV encephalitis: Periventricular WM hyperintensities (WMHs) on T2WI • PML: Usually doesn't enhance • CMV encephalitis; Subependymal enhancement

Top Differential

• Focal/multifocal brain lesions in AIDS; Lymphoma vs Toxo, tuberculoma, TBA, cryptococcosis, bacterial abscesses • Meningeal involvement in AIDS (HIV or OJ > tumor)

Diagnostic Checklist • Contrast should be used in any CT/MR imaging in AIDS patients • Diffusion within lymphoma lesions is more restricted than in toxo lesions • Perfusion MRI: Regional blood volume is t in toxo, t in lymphoma

Diagnoses

• Diffuse/patchy WM abnormalities encephalitis vs PML, CMV

in AIDS: HIV

o CMV encephalitis: Periventricular hypodense lesions • CECT o Toxo: Thin, smooth rim or solid nodular enhancement o PML: Nonenhancing o TB meningitis: Often meningeal enhancement o Tuberculomas/TBA: Ring/nodular enhancing masses in cortex/G-W junction

MR Findings • TlWI o Toxo: Tl WI hypointense o PML: Tl WI hypointense lesions, confluent over time • As disease progresses: Lesions become more hypointense on Tl WI • T2WI o Toxo: T2WI hyperintense lesions (hypo-/isointense or mixed pattern also found) o PML: T2WI hyperintense WM lesions o CMV encephalitis: Periventricular WM hyperintensities (WMHs) on T2WI o Tuberculomas: T2WI hypo intense early (caseating necrosis), isointense later o TBA: T2WI hyperintense center (caseation necrosis) • OWl: Toxo: Hyperintense on OWl • Tl C+ o Toxo: Ring-enhancing lesions, often with surrounding hypointensity (edema) o PML: Usually doesn't enhance o Crypto: Most often normal, but 4 distinct patterns seen • Meningitis: Mild ventricular dilatation +/- nodular meningeal enhancement • Dilated VRSs => symmetric non enhancing cysts in BG/thalami • Cryptococcomas: Solid/ring-enhancing masses preferentially in choroid plexus • "Gelatinous pseudocysts": Nonenhancing cystic lesions, usually bilateral BG o CMV encephalitis: Subependymal enhancement o TB

• Basal meningitis: Thick cisternal enhancement and/or hydrocephalus

• Tuberculomas: Solitary or multiple ring/nodular enhancing lesions • PML: Characteristic if seen in more than one area; asymmetric pattern if bilateral lesions • TB may have different presentations o TBA: Unusual clinical presentation of CNS TB • Generally single lesions, larger than tuberculomas, mostly multiloculated o Cerebral infarction, most commonly in BG

Nuclear Medicine

Findings

• PET o Toxo lesions are hypometabolic o PML lesions usually hypo-, occasionally hypermetabolic

Imaging Recommendations • Best imaging tool: MR better than CT • Protocol advice: Tl C+, FLAIR, T2WI with OWl and ADC maps

I [)IFFER.EN'I'I~I.. [)1~GN@SIS Diffuse/patchy WM abnormalities HIV encephalitis vs PML, CMV

in AIDS:

• HIV encephalitis: Atrophy and symmetric, periventricular/diffuse WM disease o Magnetization transfer ratio (MTR) allows differentiation of HIV encephalitis from PML • Slightly lower than normal MTR values in areas of WMHs in HIV encephalitis due to gliosis • Dramatic I in MTR for PML lesions likely due to demyelination

Focal/multifocal brain lesions in AIDS: Lymphoma vs Toxo, tuberculoma, TBA, cryptococcosis, bacterial abscesses • Primary CNS lymphoma: Second cause of focal CNS mass in HIV+ o Intraparenchymal mass(es) +/leptomeningeal/intraventricular extension

Infection and Demyelinating Disease

8 71

o Solitary/multifocal, deep (BG, periventricular) > subcortical lesions • Signal like gray matter (± necrosis, hemorrhage) • Solid or ring-enhancing • T1WI iso/hypointense lesions; variable on T2WI o Positive 201 TI-SPECT (most solitary mass lesions in HIV+ are lymphoma, especially if subependymal) o PET: Hypermetabolic • Toxo: Often cannot be distinguished from lymphoma on CT, MRI o Toxo more commonly multiple (both can produce solitary or multiple lesions)

Meningeal involvement tumor) • • • •

in AIDS (HIV or 01 >

Acute aseptic HIV meningitis Cryptococcal or TB meningitis Lymphoma: Extension of parenchymal disease Fungal: Candidiasis, aspergillosis, coccidiosis

• TBA: Focal collection of pus with acid-fast bacilli, surrounded by vascular granulation tissue

Presentation • Most common signs/symptoms o Toxo: Encephalitis in 89%, chorioretinitis o Crypto: Headache, fever, mental status changes, meningismus, seizures o CMV: Chorioretinitis in 25% of AIDS patients, encephalitis or polyradiculopathy o PML: Headache, visual disturbance, dementia, hemiparesis, cognitive impairment, or seizure o TB meningitis: Fever, altered mental status, meningeal signs, and cranial neuropathy o TBA: Fever, headache, seizures, paresis

Demographics • Age o Ols are quite unusual in pediatric AIDS patients • PML most common in AIDS children

General Features

Natural History & Prognosis

• Etiology o Toxo: Obligate intracellular protozoan Toxo gondii (reactivation) o Crypto: Saprophytic fungus Crypto neoformans o PML:]C virus (polyoma) with tropism for oligodendrocytes (reactivation) o TB: Mycobacterium tuberculosis (mycobacterium avium intracellulare rarely involves CNS) • Epidemiology o 40 million AIDS patients worldwide o CNS toxo in 3-40% of AIDS patients • Most common CNS infection in AIDS population o Crypto in 5-10% of AIDS patients o PML in 2-5% of AIDS patients o Ols or lymphoma only in brain in 31% of persons with fully developed AIDS, brain + other in 13% o Multiple CNS Ols + lymphoma in 4%

• Highly active antiretroviral therapy improves prognosis • Toxo: 70-95% response to specific therapy • PML: Slowly progressive (death in 6-12 months), known therapy

Gross Pathologic & Surgical Features • Toxo: 3 morphological types of lesions o Necrotizing, organizing or chronic abscess • PML: Multifocal gray/brownish discoloration of WM (myelin loss)

Microscopic 72

no

Treatment • • • •

Toxo: Pyrimethamine + sulfadiazine; leucovorin CMV: Ganciclovir, foscarnet Crypto: Fluconazole, itraconazole TB: Prolonged anti-TB chemotherapy, at least 9 months for tuberculomas and at least 1 year for TBA

Image Interpretation

Pearls

• Contrast should be used in any CT/MR imaging in AIDS patients • Diffusion within lymphoma lesions is more restricted than in toxo lesions • Perfusion MRI: Regional blood volume is I in toxo, 1 in lymphoma

Features

• Toxo: Initial focus of encephalitis => parenchymal abscesses with necrosis and surrounding inflammation o Tachyzoites at periphery of lesion • PML: Enlarged astrocytes with lobulated hyperchromatic nuclei o Intranuclear]C inclusions within oligodendrocytes • CMV: Microglial nodules, microinfarctions, and giant cells with CMV inclusions o Concentrated in gray matter and widely distributed in cortex, BG, brain stem, and cerebellum • Crypto: Dilated Virchow-Robin spaces filled with fungi, without invasion of surrounding brain o Cryptococcoma: Fungi, mucoid material, and inflammatory cells • Tuberculoma: Granuloma

1.

Collazos J: Opportunistic infections of the CNS in patients with AIDS: diagnosis and management. CNS Drugs 17:869-87,2003

Infection and Demyelinating

Disease

Typical (Left) Coronal graphic shows gelatinous pseudocysts due to cryptococcus extending within the perivascular spaces adjacent to small perforating arteries. (Right) Coronal Tl C+ MR shows unenhancing hypointense gelatinous pseudocysts within the perivascular spaces, similar to the lesions shown in the diagram (left).

Typical (Left) Axial TlWI MR shows hypointense lesion infiltrating through white matter. On contrast-enhanced images (not shown), the lesion did not enhance, typical for PML. Note the absence of mass effect. (Right) ADC map corresponding to T2WI shown at beginning of this case shows restricted diffusion (dark signa/) within abscess. Note adjacent bright signal (increased diffusibility) within edema.

(Left) Coronal Tl C+ MR shows thick contrast-enhancing exudative dural thickening consistent with tuberculous meningitis. (Right) Axial Tl C+ MR in a different patient shows leptomeningeal and ependymal contrast-enhancement due to cryptococcal meningitis and ependymitis in an HIV+ patient.

Infection and Demyelinating Disease

73

Sagittal graphic illustrates multiple sclerosis plaques involving the corpus callosum, pons, & spine. Note perpendicular orientation at callososeptal interface along penetrating venules.

Sagittal FLAIR MR shows MS plaques with typical perpendicular orientation at callososeptal interface along penetrating venules ("Dawson fingers") as well as involving subcortical WM.

o Both solid and ring-like enhancement

Abbreviations

MR Findings

and Synonyms

• Multiple sclerosis (MS)

Definitions • Probable autoimmune-mediated demyelination genetically susceptible individuals

in

General Features • Best diagnostic clue: Multiple perpendicular callososeptal T2 hyperintensities • Location o > 85% periventricular/perivenous o 50-90% callososeptal interface o Infratentorial (10% adults, t in children) • Size o Linear to small, 5-10 mm o Tumefactive lesions can be large (several ems) • Morphology: Linear, round, or ovoid; "beveled", "target", "lesion-in-a-lesion" appearance

8

CT Findings

74

• CECT o Iso-/hypodense

+/- mild/moderate

enhancement

DDx: Periventricular T2 Hyperintense

,,.~-·i.~",.

(. I

• TlWI o Acute: Iso-/mildly hypointense o Chronic: Hypointense center, hyperintense rim o Variable atrophy; mostly loss of WM • T2WI o High convexity "sand-like" « 2 mm diameter) Virchow-Robin spaces in recent-onset MS o Hypointense basal ganglia 10-20% chronic MS • FLAIR o Bilateral, asymmetric linear/ovoid FLAIR hyperintensities o Perivenular extension; "Dawson finger" • Along path of deep medullary veins o Hyperintensities become confluent with severity • DWI o Acute lesions • Concentric ring pattern on diffusion-weighted images with hyperintense rim • Plaque rims: Variable ADC/anisotropic values, not statistically different from normal appearing white matter (NAWM) • Plaque centers: t ADC, !! anisotropy (cf rim, NAWM, chronic plaques) o Subacute/chronic lesions: Intermediate t ADC, moderate! anisotropy, cf NAWM

lesions

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patterns

Vasculitis

Lyme Disease

Infection and Demyelinating Disease

Susac Syndrome

MULTIPLE SCLEROSIS Key Facts Imaging Findings • Best diagnostic clue: Multiple perpendicular callososeptal T2 hyperintensities • Bilateral, asymmetric linear/ovoid FLAIR hyperintensities • Perivenular extension; "Dawson finger" • Transient enhancement during active demyelination (> 90% disappear within 6 months) • Rare: Large mass-like enhancing rings

Top Differential

Diagnoses

• ADEM • Lyme disease • Susac syndrome

• Most common disabling CNS disease of young adults; 1:1000 in Western world

Clinical Issues • • • • • • • •

Clinical profile: CSF positive for oligo clonal bands Age: 20-40; peak onset 30; 3-5% < IS, 9% > 50 Adults: M:F = 1:1.7-2 Children/adolescents: M:F = 1:5-10 All groups but Caucasian most common Most often occurs in temperate zones 45% patients not severely affected, nearly normal > 80% with "probable" MS, positive MR progress to clinically definite MS

=

Pathology • Estimated 2,500,000 people in world have MS

•

•

• • • •

•

o ADC/anisotropy abnormal in all WM, worse in periplaque regions o ADC + correlates with expanded disability status scale (EDSS)/disease duration Tl C+ o Transient enhancement during active demyelination (> 90% disappear within 6 months) • Nodular (68%) or ring (23%) • Semilunar, incomplete, "horseshoe-shaped" (9%) • Rare: Large mass-like enhancing rings o + Fat-saturation to assess for optic neuritis MRS o I NAA (NAA/Cr), 1 Choline (Cho/Cr) o MRS abnormalities found in NAWM o Only secondary progressive MS shows I NAA in normal appearing gray matter (NAGM) • May allow early distinction between relapsing-remitting & secondary-progressive Perfusion MRI (contrast-enhanced T2*): Low rCBV Magnetization transfer (MT): I MT ratio (MTR) in lesions/NAWM Functional MRI (fMRI): Significant I in activated voxels, 1 activation threshold, in visual cortex Functional connectivity MRI (fcMRI): I Functional connectivity between right/left hemisphere primary motor cortices MR measures of lesion load/disability o Tl lesion load correlates moderately with clinical disability (Tl > Tl/T2 > T2) o Proportion of T2 lesions hypointense on Tl (Tl/T2 ratio) important parameter for persistent deficit o MTR in lesions correlates moderately with disability o MTR histographic analysis (provides global index of whole brain MT abnormality) • Highest intrarater reproducibility, less observer-dependent, least time-consuming • Better than Tl or Tl/T2 lesion load but disregards lesion location/number • Histogram peak height (% residual "normal" white matter), mean MTR at 25th histogram percentile, show good EDSS correlation

o Caution: Use of different scanners significantly influences lesion load measurements; careful standardization recommended • 3.0 T vs 1.5 T: 21 % 1 number contrast-enhancing lesions, 30% 1 enhancing lesion volume, 10% 1 total lesion volume • MR diagnosis of MS requires o 2': 3 discrete lesions 2': 5 mm o Lesions in characteristic location o MS compatible clinical history

Nuclear Medicine

Findings

• PET: 1 Glucose utilization lesions and NAWM

correlates with I NAA in

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Contrast-enhanced FLAIR

I DIFFERENTIAL

MR with sagittal

DIAGNOSIS

ADEM • Viral prodrome,

monophasic

Autoimmune-mediated

illness

vasculitis

• Enhancing lesions spare callososeptal interface • "Beaded" angiogram appearance

8

Lyme disease

75

• Can be identical to MS (skin rash common)

Susac syndrome • Clinical presentation, course different from MS o Classic triad • Encephalopathy (HA in almost all +/- memory loss, confusion, etc) • Branch retinal artery occlusions • Hearing loss o Self-limited (2-4 y duration, then stabilizes), monophasic • Multifocal supratentorial WM lesions o Always involves CC

Infection and Demyelinating Disease

• Central> callososeptal interface • Central callosal "holes" in subacute/chronic • 70% basal ganglia, 50% posterior fossa lesions • 33% leptomeningeal enhancement

General Features • Genetics o Unknown; t incidence in first-order relatives o Gene transcripts present/increased in MS lesions • Osteopontin: Modulates T helper (TH) 1 cell-mediated autoimmunity • Leptin: Modulates THl- TH2 balance • Statin: Influences THI-cell-mediated autoimmunity • Etiology o Unknown; probably virus and/or autoimmune-mediated in genetically susceptible individuals o Activated T-cells attack myelinated axons o Cox-2, iNOS may cause excitotoxic death of oligodendrocytes • Epidemiology o Estimated 2,500,000 people in world have MS o Most common disabling CNS disease of young adults; 1:1000 in Western world

Gross Pathologic & Surgical Features • Acute: Poorly-delineated, yellowish-white periventricular plaques • Chronic: Gray, granular, well-demarcated generalized volume loss • Balo type of MS: Concentric rings of myelinated/ demyelinated WM

plaques ±

Microscopic Features

8 76

• Perivenous demyelination, oligodendrocyte destruction o Active: Foamy macrophages with myelin fragments, lipids; reactive astrocytes + perivascular inflammation; some hypercellular with atypical reactive astrocytes, mitoses (mimic tumor) o Chronic: Marked loss of myelin, oligodendrocytes; dense astrogliosis; minimal/no perivascular inflammation • Axonal transection

o Marburg type: Younger patients, febrile prodrome, clinically fulminant, death in months o Devic type ("neuromyelitis optica"): Simultaneous optic/spinal demyelination o Schilder type ("diffuse sclerosis"): Extensive, confluent, asymmetric demyelination bilateral supra-/infratentorial parenchyma o Balo type ("concentric sclerosis"): Large lesions with alternating zones of demyelinated/myelinated WM

Presentation • Most common signs/symptoms o Variable; initially impaired/double vision of acute optic neuritis (50% with positive MR develop MS) o Weakness, numbness, tingling, gait disturbances o t Sphincter control, blindness, paralysis, dementia o Cranial nerve palsy; usually multiple, 1-5% isolated (CNs 5, 6 most common) o Spinal cord symptoms in 80% • Clinical profile: CSF positive for oligoclonal bands

Demographics • Age: 20-40; peak onset = 30; 3-5% < 15, 9% > 50 • Gender o Adults: M:F = 1:1.7-2 o Children/adolescents: M:F = 1:5-10 • Ethnicity o All groups but Caucasian most common o Most often occurs in temperate zones

Natural History & Prognosis • 45% patients not severely affected, nearly normal • > 80% with "probable" MS, positive MR progress to clinically definite MS • In early RR, recovery often complete • Majority: Protracted course with progression of deficits • Late: Severe disability, cognitive impairment

Treatment • Immunomodulators

Image Interpretation

Pearls

• 95% of clinically definite MS patients have positive

Staging, Grading or Classification Criteria • Major clinical subtypes o Relapsing-remitting (RR) (85% initial presentation) o Secondary-progressive (SP) aka relapsing progressive • By 10 years 50%, and by 25 years 90% of RR patients enter SP progressive phase o Primary-progressive (PP) aka chronic progressive • 5-10% of MS population progressive from start o Progressive-relapsing (PR) • Rare, defined as progressive disease with clear acute relapses, with/without full recovery • Periods between relapses characterized by continuing disease progression • MS variants/subtypes

and/or immunosuppressant

MR

• "Tumefactive" MS can mimic neoplasm

1. 2. 3.

Do TH et al: Susac syndrome. AJNR 25:382-8, 2004 Rose JW et al: Inflammatory cell expression of Cox-2 in the MS lesion. J Immunol. 149:40-9, 2004 Fox RJ et al: Multiple sclerosis: disease markers accelerate progress. Lancet Neurol 3:10, 2004

Infection and Demyelinating Disease

Tvpical (Left) Sagittal FLAIR MR shows multiple sclerosis plaques with hyperintense rim & central hypointensity (latter also hypointense on T7 WI; not shown). Note characteristic posterior fossa lesion (arrow). (Right) Axial T7 C+ MR demonstrates nodular enhancing multiple sclerosis plaques. Note common periventricular location with perpendicular orientation as well as involving subcortical white matter.

Typical (Left) Axial FLAIR MR at 3.0 Tesla shows confluent multiple sclerosis plaques in commonly seen peri ventricular locations. (Right) Axial T2WI MR: Very hypointense bilateral basal ganglia, atrophy (evidenced by ventricular prominence), and confluent peri ven tric uIar! subcortical hyperintense plaques; advanced multiple sclerosis.

Other (Left) Axial T7 C+ MR shows irregular, thick, partial ring-enhancement about a mass-like lesion in a patient not previously diagnosed with MS; biopsy proven tumefactive MS (Courtesy M. Mirfakharee, MO). (Right) MR spectroscopy of lesion in patient with known multiple sclerosis (MS) yields abnormal spectrum: Elevated Choline (arrow) and depressed N-acetylaspartate (open arrow) consistent with MS.

Infection and Demyelinating Disease

8 77

Axial FLAIR MR shows bilateral muluple asymmetric flocculent hyperintense lesions of acute disseminated encephalomyeliUs.

Coronal T1 C+ MR demonstrates partial peripheral enhancement around multiple asymmetric flocculent lesions of acute disseminated encephalomyeliUs. Note supra- and infratentorial lesions.

• CECT: Multifocal punctate or ring-enhancing

Abbreviations

MR Findings

and Synonyms

• Acute disseminated

encephalomyelitis

(ADEM)

Definitions • Autoimmune-mediated white matter (WM) demyelination of brain and/or spinal cord, usually with remyelination

General Features • Best diagnostic clue: Multifocal WM/basal ganglia lesions 10-14 days following infection/vaccination • Location: May involve both brain and spinal cord; predominantly WM but also gray matter (GM) • Size: Tumefactive lesions may be large, but with less mass effect than that expected • Morphology o "Flocculent" to punctate o Tumefactive, mass-like lesions possible

CT Findings 78

• NECT o Initial CT normal in 40% o Low density, flocculent, asymmetric

lesions

• T2WI: T2 abnormalities better seen with FLAIR • FLAIR o Multifocal punctate to large flocculent FLAIR hyperintensities o Bilateral but asymmetric o Involve peripheral WM/GM junction o Can involve brain stem and posterior fossa o Do not usually involve callososeptal interface o Tumefactive, mass-like lesions possible, yet with less mass effect than expected for size • DWI o Variably restricted diffusion in acute lesions o Apparent diffusion coefficient (ADC): t In ADEM • Due to t extracellular water within demyelination • However, ADEM ADC normal within normal appearing white matter (NAWM), unlike MS • T1 C+

o Punctate, ring, incomplete ring, peripheral enhancement o Cranial nerve(s) may enhance o Absence does not exclude diagnosis • MRS o N-acetylaspartate (NAA) low within regions of prolonged T2 o Other metabolites usually normal

DDx: Multifocal White Matter lesions j/

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MS

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Aging WM Lesions

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lesions

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Fabry Disease

Infection and Demyelinating Disease

Behc;et

ADEM Key Facts Pathology

Terminology • Acute disseminated

encephalomyelitis

(ADEM)

Imaging Findings • Best diagnostic clue: Multifocal WM/basal ganglia lesions 10-14 days following infection/vaccination • Location: May involve both brain and spinal cordi predominantly WM but also gray matter (GM) • Initial CT normal in 40% • Multifocal punctate to large flocculent FLAIR hyperintensities • Do not usually involve callososeptal interface • Punctate, ring, incomplete ring, peripheral enhancement • May appear identical to MSi repeat MR necessary to distinguish with certainty

o NAA normalizes with resolution of symptoms/MRI abnormalities • Magnetization transfer ratio (MTR) o ADEM MTR normal within NAWM, unlike MS

• Following nonspecific upper respiratory tract infection, often viral • After specific viral illness: Epstein-Barr, influenza A, mumps, coronavirus • Especially after exanthematous diseases of childhood (chickenpox, measles) • After vaccination: Diphtheria, influenza, rabies, smallpox, tetanus, typhoid

Clinical Issues • Multifocal neurological symptomsi 5-14 days after viral illness/immunization • Usually monophasic, self-limited • Typically delay between symptom onset and imaging findings

Fabry disease

Imaging Recommendations • Best imaging tool o Contrast-enhanced MRI • Initial imaging often normal but more sensitive than CT • May appear identical to MSi repeat MR necessary to distinguish with certainty • Protocol advice: Limited rapid interval follow-up may be provided by FLAIR alone

I DIFFERENII}X[ DI}xGN~SIS

• Synonym: Angiokeratoma corporis diffusum universalis • X-linked recessivei incidence 1/40,000 • Deficiency (){-galactosidase Ai over-accumulate glycosphingolipids within lysosomes o Particularly within vascular epithelium o Causes multi-organ end-vessel failure • MRI: Scattered, asymmetric WM lesions, without enhancement o May involve brain stem and posterior fossa o Spares callososeptal interface and subcortical V-fibers o Cranial MRI sensitive to identify neurologic involvement in asymptomatic patients • Present with renal failure/heart disease

Multiple sclerosis (MS)

Beh<;et

• Predilection for periventricular WM (callososeptal interface), involves subcortical U-fibers, commonly posterior fossa • Lesions often more symmetric than ADEM • Relapsing-remitting course common • In children, MS has no sex predominance but in adolescent/young adults M:F = 1:2-3

• MRI: Scattered, asymmetric, subcortical WM lesions without cortical involvement o Nodular enhancement in acute phase o Predilection for midbrain • ADC t, similar to ADEM • Classic triad: Oral and genital ulcerations with uveitis

Autoimmune-mediated

in

vasculitis

• Multifocal GM/WM lesions o Bilateral, usually cortical/subcortical, basal ganglia/thalami o Ring-enhancing lesions may mimic infection

Aging brain with hyperintense

WM lesions

• Atherosclerotic brain changes in 50% patients> 50 yrs • Found in normotensive patientsi more common in hypertensives • Present in 10-30% cognitively normal elderly patients • MRI: Scattered, asymmetric WM lesions, without enhancement o Often periatriali posterior fossa uncommon o Spares callososeptal interface, subcortical V-fibers

Ip}xIH~[~G¥

8

General

79

Features

• General path comments: Autoimmune mediated severe acute demyelination • Genetics: ADEM associated with DRB1*01 and DRB1*017(03) in Russian population • Etiology o Following nonspecific upper respiratory tract infection, often viral o After specific viral illness: Epstein-Barr, influenza A, mumps, coronavirus o Especially after exanthematous diseases of childhood (chickenpox, measles) o After vaccination: Diphtheria, influenza, rabies, smallpox, tetanus, typhoid

Infection and Demyelinating Disease

o Spontaneously (no known cause) • Epidemiology o Rare, yet most common para/post-infectious disorder o Unknown, but increasingly reported • Associated abnormalities: Acute hemorrhagic leukoencephalopathy variant associated with ulcerative colitis and asthma

• Young patients with abrupt symptom onset • Fulminant often ending in death o Bilateral striatal necrosis (usually in infants, may be reversible)

Treatment • Immunomodulatory therapy (Tx) • MRI may show prompt regression in response to Tx

Gross Pathologic & Surgical Features • None, unless bleed or tumefactive

Microscopic • • • • • •

(focal) swelling

Features

Image Interpretation

Acute myelin breakdown Perivenous inflammation; lymphocytic infiltrates Relative axonal preservation Atypical astrogliosis Virus generally not found, unlike viral encephalitides Similar to experimental allergic encephalomyelitis, supporting autoimmune-related etiology

1.

2.

Presentation

3.

• Most common signs/symptoms o Usually preceded by prodromal phase: Fever, malaise, myalgia o Multifocal neurological symptoms; 5-14 days after viral illness/immunization • Initial symptoms: Headache, fever, drowsiness • Cranial nerve palsies, seizures, hemiparesis • Decreased consciousness (from lethargy to coma) • Behavioral changes • Clinical profile o CSF often abnormal (leukocytosis, elevated protein) • Usually lacks CSF oligoclonal bands

Demographics • Age o Children> adults o Peak age 3-5 y, but can occur at any age • Gender: Male predominance in some series

80

4. 5.

6.

7.

8.

9.

10. 11.

Natural History & Prognosis • Usually monophasic, self-limited • Variable prognosis o Complete recovery within one month: 50-60% o Neurologic sequelae (most commonly seizures): 20-30% o Mortality: 10-30% o Relapses are rare • "Relapsing disseminated encephalomyelitis" • May not be a separate entity from relapsing-remitting MS • Typically delay between symptom onset and imaging findings • Varicella and rubella ADEM have preferential patterns o Rubella ADEM characterized by acute explosive onset, seizures, coma and moderate pyramidal signs o Varicella ADEM characterized by cerebellar ataxia and mild pyramidal dysfunction • Rare manifestations of ADEM o Acute hemorrhagic leukoencephalopathy: 2%

Pearls

• Imaging findings often lag behind symptom onset, resolution

12.

13.

14.

15.

16. 17.

Yeh EA et al: Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics 113:7-6, 2004 Okamoto K et al: MR features of diseases involving bilateral middle cerebellar peduncles. A]NR Am] Neuroradiol. 24(10):1946-54,2003 Dale RC: Acute disseminated encephalomyelitis. Semin Pediatr Infect Dis. 14(2):90-5,2003 Garg RK:Acute disseminated encephalomyelitis. postgrad Med]. 79(927):11-7, 2003 Sener RN: Neuro-Behcet's disease: diffusion MR imaging and proton MR spectroscopy. A]NR Am] Neuroradiol. 24(8):1612-4, 2003 Stonehouse M et al: Acute disseminated encephalomyelitis: recognition in the hands of general paediatricians. Arch Dis Child. 88(2):122-4, 2003 Idrissova ZhR et al: Acute disseminated encephalomyelitis in children: clinical features and HLA-DRlinkage. Eur ] Neurol. 10(5):537-46, 2003 Tenembaum S: Acute disseminated encephalomyelitis: A long-term follow-up study of 84 pediatric patients. Neurology 59(8):1224-31,2002 Inglese M et al: Magnetization transfer and diffusion tensor MR imaging of acute disseminated encephalomyelitis. A]NR Am] Neuroradiol. 23(2):267-72, 2002 Murthy]M: Acute disseminated encephalomyelitis. Neurol India. 50(3):238-43, 2002 Honkaniemi] et al: Delayed MR imaging changes in acute disseminated encephalomyelitis. A]NRAm] Neuroradiol. 22(6):1117-24,2001 Bizzi A et al: Quantitative proton MR spectroscopic imaging in acute disseminated encephalomyelitis. A]NR 22:1125-30, 2001 Straussberg R et al: Improvement of atypical acute disseminated encephalomyelitis with steroids and intravenous immunoglobulins. Pediatr Neurol. 24(2):139-43, 2001 Dale RC et al: Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain 12:2407-22, 2000 Rust RS:Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions. Semin Pediatr Neurol. 7(2):66-90, 2000 Schaefer PW et al: Diffusion-weighted MR imaging of the brain. Radiology. 217(2):331-45, 2000 Kocer Net al: CNS involvement in neuro-Behcet syndrome: an MR study. A]NR Am] Neuroradiol. 20(6):1015-24, 1999

Infection and Demyelinating

Disease

Typical (Left) Axial FLAIR MR shows asymmetric flocculent, nearly confluent, hyperintense lesions of acute disseminated encephalomyelitis within posterior fossa structures. (Right) Axial FLAIR MR reveals multiple, asymmetric, primarily punctate hyperintense lesions of acute disseminated encephalomyelitis.

Variant (Left) Axial FLAIR MR demonstrates a large tumefactive hyperintense mass lesion. Lessmass effect is present than expected for lesion size. Smaller lesions were also present at other locations. (Right) Axial T1 C+ MR: Large tumefactive T1 hypointense mass lesion with minimal partial peripheral enhancement. Lessmass effect is present than expected for lesion size. More lesions were seen elsewhere.

Variant (Left) Axial FLAIR MR demonstrates rare manifestation of ADEM: Bilateral striatal necrosis, evidenced by asymmetric confluent hyperintensity involving gray and white matter of bilateral corpus striatum. (Right) Axial OWl MR exhibits rare manifestation of ADEM: Bilateral striatal necrosis, evidenced by asymmetric confluent restricted diffusion involving gray and white matter of bilateral corpus striatum.

Infection and Demyelinating

Disease

81

Axial T2WI MR shows hyperintensity in white matter of both hemispheres but predominantly in frontal and parietal regions. There is diffuse atrophy in young adult male with 55PE.

Abbreviations

Axial T1 C+ MR in same patient shows no enhancement in the zones of white matter signal abnormality.

• Involvement generally symmetric • Rare: Cystic temporal lobe lesions o Late: Diffuse atrophy o Involvement of basal ganglia/thalami (especially adults) o Rare: Resolution of findings • Tl C+: No enhancement

and Synonyms

• SSPE, Dawson encephalitis

Definitions • Rare, progressive measles virus-mediated encephalitis occurring after a clinically silent period (months-yrs)

is rare

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Routine brain MRI with contrast

General Features • Best diagnostic clue: Ill-defined T2 hyperintensities periventricular or subcortical white matter (WM) • Location: Parietal, occipital lobes

CT Findings • NECT o Often normal early o Diffuse brain swelling o No focal lesions, low density in WM • CECT: No enhancement

8 82

Acute post infectious measles encephalitis • Immune-mediated response during/shortly measles infection, acute presentation

after

Acute disseminated encephalomyelitis

(ADEM) • History of viral illness few days prior • Multifocal well-defined areas of t T2 signal without mass effect

MR Findings • Tl WI: Areas of I signal in WM, corpus callosum • T2WI o Diffuse t signal in WM, corpus callosum, no mass effect

DDx: Confluent T2 Hyperintense

ADEM

in

PML

Progressive multifocalleukoencephalopathy (PMl) • Areas of t T2 signal, no mass effect

White Matter lesions

MS

Infection and Demyelinating Disease

HIV

SUBACUTE SCLEROSING PANENCEPHALITIS Key Facts Terminology

Top Differential

• Rare, progressive measles virus-mediated encephalitis occurring after a clinically silent period (months-yrs)

• • • • •

Imaging Findings • Best diagnostic clue: Ill-defined T2 hyperintensities periventricular or subcortical white matter (WM) • Diffuse t signal in WM, corpus callosum, no mass effect

• Immunocompromised

Tumefactive

in

patients (AIDS, cancer)

Pathology • History of measles before 2 yrs of age in most patients

Demographics

multiple sclerosis (MS)

• Age: Childhood,

• Mass-like lesions in periventricular WM • Mass effect, peripheral enhancement (may look like brain tumor)

Human immunodeficiency

Diagnoses

Acute post infectious measles encephalitis Acute disseminated encephalomyelitis (ADEM) Progressive multifocalleukoencephalopathy (PML) Tumefactive multiple sclerosis (MS) Human immunodeficiency virus (HIV)

virus (HIV)

• Ill-defined areas of t T2 signal in WM, no mass effect

early adolescence; rare in adults

Natural History & Prognosis • Begins insidiously ~ subacute course ~ death • Duration: Generally 1-6 mos (can be as long as 2-4 yrs) • Rare: Remission followed by severe disease

Treatment • No treatment, some benefits from o Intraventricular interferon-alpha o Amantadine, Isoprinosine

I P~"f1Tlm E.m{)j¥

and ribavirin

General Features • General path comments: Measles virus induces apoptosis in neurons, oligodendrocytes, lymphocytes, microglia • Etiology: Measles virus (mutant form) (prevention is vaccination) • Epidemiology o History of measles before 2 yrs of age in most patients • 16x higher risk of developing SSPE

Gross Pathologic & Surgical Features • Diffuse swelling, atrophy • Cortical petechial bleeds • Subcortical encephaloclastic distributions

I DI~{)jNmS"fICCITIECKUS"f Consider • SSPE in an immigrant child with behavior changes and multifocal white matter disease

Image Interpretation

I SEE.EC"fED REFERENCES 1.

lesions in non-vascular 2.

Microscopic • • • • • •

Pearls

• Clinical stage of SSPE, MR findings correlate poorly

Features

Widespread myelin loss, gliosis Macrophagic infiltration, diffuse t microglial cells Perivascular lymphocytic cuffing (B, T cells) Diffuse neuronal loss Alzheimer-type neurofibrillary tangles Glial fibrillary tangles in oligodendrocytes

Sener RN: Subacute sclerosing panencephalitis with pontine involvement. J Comput Assist Tomogr 28:101-2, 2004 Schneider-Schaulies J et al: Measles infection of the central nervous system. J NeuroVirology 9: 247-52, 2003

IIM~{)jE{)j~llER¥

8 83

I CUNIC~E.ISSUES Presentation • Most common signs/symptoms: Progressive mental deterioration + motor impairment, myoclonus • Clinical profile o Positive CSF, plasma complement fixation test for measles o CSF: Oligoclonal bands o EEG: Periodic complexes with generalized polyspike, t voltage slow waves every 5-10 seconds

Infection

(Left) Axial NECT shows diffuse WM low density in both hemispheres and atrophy. (Right) Axial NECT in same patient shows extensive WM

hypodensity even involving internal capsules.

and Demyelinating

Disease

PART I SECTION 9 Metabollc/Deseneratiwe Disorders, Inherited The so-called "inborn errors of metabolism" form a very interesting, heterogeneous, ever-expanding group of disorders. Even the terminology is cause for confusion. Some call these "dysmyelinating" disorders, to contrast them with acquired "demyelinating" diseases. But not all inherited metabolic disorders affect primarily myelin. And some putatively "acquired" demyelinating diseases (such as multiple sclerosis) have a strong genetic predisposition. Inborn errors of metabolism can be-and have been-classified in a number of different ways. Some propose classifying them according to specific genetic criteria. Others suggest grouping them according to the cellular organelles that are predominately affected. Some prominent pediatric neuroradiologists take a pattern-based approach, dividing them into disorders that primarily affect white matter, gray matter, or both. Other options are to cite diseases by clinical syndrome, biochemical abnormality (e.g., in blood or urine), or histopathology (e.g., ragged red fibers in muscle biopsy). One thing is apparent: There is no "one size fits all" or a totally neat, internally consistent way to classify these diseases. We have chosen to group the inherited metabolic/degenerative diagnoses by affected organelles. We begin this section with a discussion of normal myelination and hypo myelination that lays the foundation for presenting a spectrum of disorders. Mitochondrial encephalopathies are followed by lysosomal and peroxisomal diseases. Organic and aminoacidopathies are next. At the end, because nothing ever fits a schema completely, we present some miscellaneous disorders such as Wilson disease.

SECTION9: MetaboIlclDepnerathe

Disorders, Inherited

Normal/Variant 1-9-4 1-9-8

Normal Myelination Hypomyelination

Mitochondrial

Disorders 1-9-12 1-9-16

Leigh Syndrome MELAS

lysosomal Disorders Mucopolysaccharidoses Gangliosidosis (GM2) Metachromatic Leukodystrophy Krabbe

(MLD)

1-9-20 1-9-24 1-9-28 1-9-32

Peroxisomal Disorders Zellweger X-Linked Adrenoleukodystrophy

1-9-36 1-9-38

Organic and Aminoacidopathies Maple Syrup Urine Disease Urea Cycle Disorders Glutaric Aciduria Type 1 Canavan Disease Alexander Disease

1-9-42 1-9-46 1-9-48 1-9-52 1-9-54

Miscellaneous van der Knaap Leukoencephalopathies Hallervorden-Spatz Syndrome Huntington Disease Wilson Disease

1-9-58 1-9-62 1-9-66 1-9-70

NORMAL MYELINATION

Axial TlWI MR shows bright signal of normal myelin in posterior limb of internal capsules in a newborn. Tl shortening correlates with presence of glycolipids and cholesterol in myelin.

ITERMINOlOGY Abbreviations

and Synonyms

• Myelin maturation,

white matter development

Definitions • Organized and predetermined pattern of development and distribution of myelin sheaths on axons • Begins in 5th fetal month and continues throughout life

IIMAGING FINDINGS General Features • Best diagnostic clue: Myelin development correlates with functional milestones • Location: Myelin maturation proceeds caudal to rostral, central to peripheral, dorsal to ventral • Size: White matter tracts increase in size with myelin formation, especially corpus callosum • Morphology: Diffusion tractography may provide insight on morphology of developing tracts

CT Findings • NECT o Unmyelinated white matter is hypodense relative to gray matter and to myelinated white matter

Axial T2WI MR in same neonate shows more limited hypointense signal (arrows). T2 shortening is thought to reflect tightening of myelin spiral and displacement of brain water protons.

o Gray-white differentiation is accentuated in neonate due to high water content of white matter o Density increase with myelination is relatively subtle, making CT insensitive in detecting delays in myelination

MR Findings • TlWI

o Tl WI is key sequence in assessing normal myelination in children < 1 year o Inversion recovery (IR) technique can accentuate Tl shortening of myelin o Detection of myelination progresses in a predictable fashion o Neonate has hyperintense signal in • Dorsal brain stem • Dentate nucleus • Optic tracts • Anterior commissure • Posterior limb internal capsule • Rolandic and perirolandic gyri • Pyramidal tracts 02 months • Splenium of corpus callosum • Anterior limb internal capsule • Early optic radiations 04 months • Genu of corpus callosum

DDx: Myelin on T1WI in the 1st Year of life

9 4

6 Weeks

4 Months

7 Months

Metabolic/Degenerative Disorders! Inherited

NORMAL MYELINATION Key Facts Terminology • Organized and predetermined pattern of development and distribution of myelin sheaths on axons • Begins in 5th fetal month and continues throughout life

Imaging Findings • Best diagnostic clue: Myelin development correlates with functional milestones • Location: Myelin maturation proceeds caudal to rostral, central to peripheral, dorsal to ventral • Tl WI is key sequence in assessing normal myelination in children < 1 year • T2WI is key sequence in assessing normal myelination in children 1-2 years

• Optic radiations become more apparent • Peripheral rami in pyramidal tracts (perirolandic gyri) o 6 months • Genu and splenium are equally hyperintense • Peripheral rami in parietal and occipital lobes become hyperintense 08 months • All but most peripheral rami of frontal gyri are hyperintense o 10-12 months • Adult appearance of myelin achieved on Tl WI • T2WI o T2WI is key sequence in assessing normal myelination in children 1-2 years o As myelin sheaths tighten peri-axonal water is displaced • Hypointense signal on T2WI o This process is delayed relative to changes seen on Tl WI, but follows same pattern o Neonate has hypointense signal in • Dorsal brainstem • Part of posterior limb of internal capsule • Perirolandic gyri 04 months • More hypo intense signal in rolandic and perirolandic gyri • Splenium of corpus callosum • More anterior extension in internal capsule 08 months • Genu and splenium of corpus callosum • Anterior limb of internal capsule • Decreasing signal in centrum semiovale and optic radiations • Decreasing signal in basal ganglia and thalamus o 12 months • External capsule hypointense signal becomes apparent • Expansion of centrum semiovale hypointensity • Clearly defined peripheral rami around central sulcus and in occipital poles o 16 months

• Diffusion tractography (DTI) has capability to identify fiber tracts as they become myelinated • May allow more specific identification of developing functional tracts • Use both TlWI and T2WI to assess myelination • Conventional double spin-echo sequences preferred forT2WI

Clinical Issues • Age: All children should achieve adult appearance WM by 36-40 months • Gender: No significant male/female difference • Myelination progresses throughout life

of

Diagnostic Checklist • Know gestational stage

•

•

•

•

age before assigning myelination

• Better definition of deep nuclei in brainstem and basal ganglia • Peripheral rami in parietal lobes become hypointense o 18 months • All but most peripheral frontal white matter rami are now hypointense • Some residual hyperintense signal around trigones of lateral ventricles; "terminal zones" 036 months • Adult appearance of myelin achieved on T2WI PD/Intermediate o Very helpful in distinguishing gliosis from lack of myelination • Gliosis appears more hyperintense on PD/Intermediate than normal unmyelinated white matter • Brighter than "terminal zones" FLAIR o FLAIRgenerates relatively "flat" images in immature brains o Signal changes associated with myelination (hyperintense to hypointense) similar to T2WI o Tend to occur 2-3 months after changes visible on T2WI • Smaller amounts of interaxonal water may exert greater influence on FLAIR sequences DWI o ADC values predate Tl and T2 weighted signal changes o Presence of myelin has significant affect on ability of water to diffuse • Fractional anisotropy increases with brain maturation • Diffusion perpendicular to myelin sheaths is restricted with decline in extra-axonal water • Diffusivity within the axon increases o Diffusion tractography (DTI) has capability to identify fiber tracts as they become myelinated • May allow more specific identification of developing functional tracts MRS

Metabolic/Degenerative Disorders, Inherited

9 5

NORMAL MYELINATION o Changes in relative metabolite concentrations in first two years of life may reflect myelination o Myoinositol and choline are high in neonate • Choline declines with myelination o NAA increases with myelination in the first year of life

Ultrasonographic

Findings

• Real Time: White matter becomes more echo genic as myelination progresses

Other Modality Findings • Magnetization myelination

transfer increases with brain

Imaging Recommendations • Use both T1WI and T2WI to assess myelination o IR may increase sensitivity to T1 shortening o Use T1WI to assess myelination up to 10-12 months o Use T2WI to assess myelination from 8 to 36 months o Conventional double spin-echo sequences preferred forT2WI • FSE sequences may minimize abnormal hyperintensity • PD/Intermediate echo images especially valuable < 24 months

I CLINICAL ISSUES Presentation • Most common signs/symptoms o MR demonstration of normal myelination closely parallels developmental functional milestones o Assessment of myelination is an essential aspect of MR in children • Analogous to documentation of developmental milestones by pediatrician

Demographics • Age: All children should achieve adult appearance WM by 36-40 months • Gender: No significant male/female difference

Natural History & Prognosis • Myelination

life

Treatment • Acquired disorders causing myelin delay can sometimes be treated

[DIAGNOSTIC

CHECKLIST

Consider

Image Interpretation

General Features • General path comments o Oligodendrocytes form, maintain axon myelin sheath o One oligodendrocyte may invest up to SO axons • Genetics o Two major structural proteins of myelin are myelin basic protein (MBP) and proteolipid protein (PLP) • MBP gene is encoded on chromosome 18q • PLP gene is encoded on chromosome Xq21-q22 • Etiology o Embryology • Oligodendrocyte precursors proliferate in germinal matrix • Neuron induces myelinization by electrical impulse

I SELECTED REFERENCES 1.

2.

3.

Gross Pathologic & Surgical Features

4.

• Pre-myelinated

5.

brain "soft" due to high water content

• Myelin sheath formed of multiple layers wrapped around axon o Form a protein-lipid-protein-lipid-protein stack

Staging, Grading or Classification Criteria • Myelination is assessed as "appropriate" for age or delayed • Delay in myelination should prompt investigation for possible causes

Pearls

• Use IR for T1WI < 10 months • Use conventional double spin-echo sequences for T2WI

Microscopic Features

6

progresses throughout

• Know gestational age before assigning myelination stage

I PATHOLOGY

9

of

6. 7.

Jellison BJ et al: Diffusion tensor imaging of cerebral white matter: A pictorial review of physics, fiber tract anatomy, and tumor imaging patterns. AJNR 25:356-69,2004 McGraw P et al: Evaluation of normal age-related changes in anisotropy during infancy and childhood as shown by diffusion tensor imaging. AJRAm J Roentgenol. 179(6):1515-22,2002 Mukherjee P et al: Diffusion-tensor MR imaging of gray and white matter development during normal human brain maturation. AJNRAm J Neuroradiol. 23(9):1445-56, 2002 Barkovich AJ: Concepts of myelin and myelination in neuroradiology. AJNR 21: 1099-1109,2000 Murakami JW et al: Normal myelination of the pediatric brain imaged with fluid-attenuated inversion-recovery (FLAIR)MR imaging. AJNRAm J Neuroradiol. 20(8):1406-11, 1999 Nakagawa H et al: Normal myelination of anatomic nerve fiber bundles: MR analysis. AJNR 19: 1129-36, 1998 Van der Knaap MS, ValkJ: Chapter 1 Myelin and white matter. In: Magnetic resonance of myelin, myelination, and myelin disorders, 2nd ed. Springer, Berlin, 1-17, 1995

Metabolic/Degenerative Disorders, Inherited

NORMAL MYELINATION

I IMAGE GALLERY Variant (Left) Axial fractional anisotropy map generated from on shows color coded white matter tracts in a 3 month old. AP oriented tracts are labeled green, transverse red, and cranial caudal blue. (Right) Tractography in same infant from ROI at proximal forceps minor (arrows) shows tracts projecting into left frontal lobe, up into pyramidal tract, and crossing corpus callosum into right parietal lobe.

(Left) Axial T2WI MR of 7 month old shows hypointense signal in anterior and posterior limbs of internal capsule (curved arrows) and in genu of corpus callosum, more than in splenium (open arrow). (Right) Axial T2WI MR at 72 months shows hypointense signal in forceps major and minor (open arrows) and in external capsule (curved arrow).

(Left) Axial T2WI MR of an 78 month old shows further myelination in frontal and occipital lobes, but most peripheral rami remain hyperintense (arrows). External capsule is better defined. (Right) Axial T2WI MR at 36 months shows adult pattern of myelin formation, with shortening in peripheral rami of white matter throughout brain (arrows) and definition of internal and external capsules.

Metabolic/Degenerative

Disorders, Inherited

9 7

HYPOMYELINATION

Axial T2WI MR shows marked and diffuse hypomyelination in a 73 yo with Pelizaeus Merzbacher disease. Degree of myelination would be appropriate for 6 months of age.

Axial T2WI MR in a normal 73 year old shows adult pattern of myelination, with hypointense signal from tightly packed myelinated axons extending to most peripheral aspect of gyri (arrows).

I TERMINOLOGY

CT Findings

Abbreviations

• NECT: Lack of myelin generally too subtle to identify onCT

and Synonyms

• Undermyelination,

delayed myelin maturation

MR Findings

Definitions • Diminished or absent degree of white matter (WM) myelination for age • Myelin "milestones" not achieved • May be primary hypomyelination syndrome or secondary to other pathology

I IMAGING

FINDINGS

General Features • Best diagnostic clue o Poor gray-white differentiation on Tl WI in children > 1 year o Poor gray-white differentiation on T2WI in children > 2 years • Location: Key areas to assess are internal capsule, pyramidal tracts, and peripheral frontal lobe WM rami • Size o Hypomyelination will result in reduced brain volume • Thin corpus callosum evident on sagittal images • Morphology: Typically normal

• TlWI o Myelinated WM is hyperintense on Tl WI o WM structures become hyperintense in predictable chronology o Myelination on Tl WI is complete by 1 year of age • T2WI o Myelinated WM is hypointense on T2WI o Hypointensity on T2WI lags hyperintensity on Tl WI by 4-8 months o Myelination on T2WI is complete by 3 years of age, usually by 2 years of age o "Terminal zones" • Regions of persistent hyperintense signal on T2WI in otherwise normal brains • Typically around trigones of lateral ventricles • Likely due to concentration of interstitial water migrating to ventricles in these areas • Must be distinguished from periventricular leukomalacia or perivascular spaces • PD/Intermediate: Key for distinguishing gliosis from undermyelination from terminal zones • FLAIR o Typically "bland" in children < 2 years

DDx: Causes of Hypomyelination

9 8

4 yo: 18q-syndrome

1 yo: AVF

Metabolic/Degenerative

Hunter Syndrome

Disorders, Inherited

8 mos:

He Defect

HYPOMYELINATION Key Facts Imaging Findings

Clinical Issues

• Location: Key areas to assess are internal capsule, pyramidal tracts, and peripheral frontal lobe WM rami • TlWI most helpful in children < 10 months

• Most common signs/symptoms: Developmental delay, hypotonia • Age: Primary hypomyelination syndromes typically present in infancy • No single group identified as at risk • No treatment yet for heritable disorders of hypomyelination

Top Differential • • • •

Diagnoses

Primary hypomyelination syndromes Prematurity External stresses Syndromes with hypomyelination and other findings

Pathology • Define degree of myelination by age at which it would be appropriate ~ "degree of myelination appropriate for x months of age"

o May help distinguish hypomyelination from gliosis like PD/lntermediate • DWI o ADC values predate Tl and T2 weighted signal changes • ADC drops as WM diffusivity decreases o Fractional anisotropy increases with brain maturation o Diffusion tractography (DTI) has capability to identify fiber tracts as they become myelinated • May show some myelination before changes on TlWlorT2WI • Tl C+: Some causes of hypomyelination have abnormal enhancement • MRS o Choline decreases as myelination progresses o Relative increases in myo-inositol, choline, and lipid resonances with hypomyelination o Significant increases in choline may indicate demyelination or dysmyelination

Imaging Recommendations • Best imaging tool: MR • Protocol advice o Tl WI most helpful in children < 10 months • Inversion recovery techniques can accentuate Tl shortening • DTI likely more sensitive o T2WI most helpful in children> 10 months

I

DIFFERENTIAL DIAGNOSIS

Primary hypomyelination • • • •

syndromes

Pelizaeus-Merzbacher disease (PMD) Spastic paraplegia type 2 (SPG2) 18q-syndrome Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC)

Prematurity • Use of normal milestones assumes full-term gestation • Adjust chronologic age for degree of prematurity

Diagnostic Checklist • It may not be possible to distinguish hypomyelination, dysmyelination, and demyelination • Remember to adjust chronologic age for degree of prematurity • Correlate imaging findings with clinical history and neurological exam to narrow scope of differential

External stresses • Chronic debilitating conditions in infancy o Congenital vascular malformations (AVF) o Malnutrition • Treatments for diseases in neonate o Organ transplantation o Chemotherapy • Myelination typically rebounds with treatment primary illness

Syndromes with hypo myelination findings

of

and other

• Typically cause dysmyelination, not hypomyelination • Mucopolysaccharidoses o Hunter, Hurler • Mitochondrial encephalopathies o Electron transport chain (ETC) defects o Mitochondrial membrane abnormalities • Leukodystrophies o Metachromatic leukodystrophy o Globoid leukodystrophy (Krabbe)

I PATHOLOGY General Features • General path comments: PMD and 18q-syndrome are prototypes of hypomyelination • Genetics o 10-30% of PMD and SPG2 caused by defects in proteolipid protein (PLP) gene (Xq21-q22) o 18q-syndrome causes hemizygous deletion (one copy of gene missing) of myelin basic protein gene • MBP gene on deleted segment of long arm of chromosome 18 • Etiology o Defects in PLP prevent normal myelin compaction • Compaction displaces water and accounts for T2 hypointensity • Myelin becomes unstable and breaks down without PLP

Metabolic/Degenerative Disorders, Inherited

9 9

HYPOMYELINATION o MBP is thought to stabilize myelin spiral at major dense line • Epidemiology: True primary hypomyelination syndromes (PMD, SPG2, 18q-, H-ABC) very rare • Associated abnormalities: Craniofacial-facial malformations associated with 18q-syndrome

Image Interpretation

Pearls

• Assess myelination prior to learning chronologic age of patient o Avoid predetermination bias • Correlate imaging findings with clinical history and neurological exam to narrow scope of differential

Gross Pathologic & Surgical Features • Smaller brain volume

Microscopic

I SELECTED REFERENCES

Features

• Pelizaeus-Merzbacher disease o Patchy myelin deficiency; no sparing of subcortical U-fibers o Islands of persistent perivascular myelin result in classic "tigroid" appearance o Absent or deficient compact myelin sheaths, "redundant myelin balls"

Staging, Grading or Classification Criteria • Define degree of myelination by age at which it would be appropriate ~ "degree of myelination appropriate for x months of age"

ICLINICAL ISSUES

1.

2.

3.

4.

5.

6.

Presentation • Most common signs/symptoms: Developmental delay, hypotonia • Classic PMD: Head titubation, hypotonia, only 50% able to sit • 18q-syndrome: Developmental delays, short stature, delayed bone age, limb anomalies

Demographics

7.

8.

9. 10.

• Age: Primary hypomyelination syndromes typically present in infancy • Gender o Classic PMD is X-linked recessive and thus exclusive to males o Other forms of PMD are autosomal recessive and equally distributed • Ethnicity o No single group identified as at risk o PMD may represent a group of phenotypically similar but genetically distinct entities

11.

12.

13. 14.

Natural History & Prognosis • Late progression

of symptoms may occur in some

Treatment

15. 16.

• No treatment yet for heritable disorders of hypomyelination 17.

9

I DIAGNOSTIC

10

Consider

CHECKLIST 18.

• It may not be possible to distinguish hypomyelination, dysmyelination, and demyelination • Remember to adjust chronologic age for degree of prematurity

Hudson LD: Pelizaeus-Merzbacher disease and spastic paraplegia type 2: two faces of myelin loss from mutations in the same gene.] Child Neurol. 18(9):616-24, 2003 Linnankivi IT et al: 18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images.] Magn Reson Imaging. 18(4):414-9, 2003 Pizzini F et al: Proton MR spectroscopic imaging in Pelizaeus-Merzbacher disease. A]NR Am] Neuroradiol. 24(8):1683-9, 2003 Plecko B et al: Degree of hypomyelination and magnetic resonance spectroscopy findings in patients with Pelizaeus Merzbacher phenotype. Neuropediatrics. 34(3):127-36, 2003 Battini R et al: Unusual clinical and magnetic resonance imaging findings in a family with proteolipid protein gene mutation. Arch Neurol. 60(2):268-72, 2003 van der Knaap MS et al: New syndrome characterized by hypomyelination with atrophy of the basal ganglia and cerebellum. A]NR Am] NeuroradioI23:1466-1474, 2002 Southwood CM et al: The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher disease. Neuron. 36(4):585-96, 2002 Hobson GM et al: A PLP splicing abnormality is associated with an unusual presentation of PMD. Ann Neurol. 52(4):477-88,2002 Koeppen AH et al: Pelizaeus-Merzbacher disease.] Neuropathol Exp Neurol. 61(9):747-59, 2002 Engelbrecht V et al: Diffusion-weighted MR imaging in the brain in children: findings in the normal brain and in the brain with white matter diseases. Radiology. 222(2):410-8, 2002 Takanashi] et al: Brain N-acetylaspartate is elevated in Pelizaeus-Merzbacher disease with PLP1 duplication. Neurology. 58(2):237-41, 2002 Cecil KM et al: Magnetic resonance spectroscopy of the pediatric brain. Topics in Magnetic Resonance Imaging 12(6):435-452, 2001 Woodward K et al: CNS myelination and PLP gene dosage. Pharmacogenomics. 2(3):263-72, 2001 Barkovich A]: Concepts of myelin and myelination in neuroradiology. A]NR Am] Neuroradiol 21: 1099-1109, 2000 Gabrielli 0 et al: 18q- syndrome and white matter alterations. A]NR Am] Neuroradiol. 19(2):398-9, 1998 Gay CT et al: Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency. Am] Med Genet. 74(4):422-31,1997 Loevner LA et al: White matter changes associated with deletions of the long arm of chromosome 18 (18qsyndrome): a dysmyelinating disorder? A]NR Am] Neuroradiol. 17(10):1843-8, 1996 Kolodny EH: Dysmyelinating and demyelinating conditions in infancy. Curr Opin Neurol Neurosurg. 6(3):379-86, 1993

Metabolic/Degenerative Disorders, Inherited

HYPOMYELINATION I IMAGE GALLERY Tvpical (Left) Axial T2WI MR in 4 yo with 18q-syndrome shows absence of myelination in all but genu and splenium (arrows); they normally myelinate after posterior limb of internal capsules (curved arrow). (Right) Axial T2WI MR in same child 5 years later shows some progression of myelination into peripheral rami of white matter (arrows), but white matter tracts are still very poorly defined.

(Left) Sagittal TlWI MR off mid-line shows absence of myelination in the frontal lobe in 13 yo with Pe/izaeus-Merzbacher. Faint myelination seen as hyperintense signal in corticospinal tract (arrows). (Right) Axial TlWI MR shows striking hypointense signal in white matter of this infant with Canavan disease, reflecting dysmyelination and demyelination, a different pathologic substrate than hypomyelination.

(Left) Sagittal TlWI MR in midline shows microcephaly with increased cranial-facial ratio in 13 yo with Pe/izaeus-Merzbacher. Thin corpus callosum (arrows) reflects decreased WM volume from hypomye/ination. (Right) Short echo (TE 35 msec) proton MRS shows only mild decrease in NAA for age, with some elevation of myoinositol (curved arrow). MRS is more sensitive for myelin turnover than myelin volume.

Metabolic/Degenerative Disorders, Inherited

9 11

LEIGH SYNDROME

Axial FLAIR MR shows symmetric signal abnormality in the dorsal putamina and caudate heads in Leigh syndrome.

ITERMINOlOGY Abbreviations

and Synonyms

• Leigh syndrome (LS) • Subacute necrotizing encephalomyelopathy

Definitions • Genetically heterogeneous mitochondrial disorder characterized by progressive neurodegeneration

IIMAGING FINDINGS General Features • Best diagnostic clue: Bilateral, symmetric t T2/FLAIR putamina and peri-aqueductal gray matter (PAG) • Location o Common • Basal ganglia (BG): Corpora striata (putamina> caudate heads) > globi pallidi (GP) • Brain stem (BS): PAG, substantia nigra/subthalamic nuclei, pons, medulla • Thalami, dentate nuclei o Infrequent: White matter (WM, cerebral> cerebellar), spine, cortical gray matter • Size o BS: Small, discrete foci « 1 cm) • Involvement central WM tracts typical

DDx: Childhood

Axial T2WI MR shows characteristic focal hyperintensity in the substantia nigra and peri-aqueductal gray matter (open arrow) in Leigh syndrome. The mamillary bodies are normal (arrows).

o BG: Involvement posterior putamina classic but variable o Thalami: Focal involvement dorsomedial nuclei classic but variable • Morphology o Except WM, lesions are bilaterally symmetric o Edema, expansion characteristic of early disease; volume loss characteristic of late disease • PAG edema may cause hydrocephalus o Involvement of lower BS (pons, medulla) and lack of BG involvement characteristic of LS 2° to SURFl mutation o Uncommon appearances • Mass-like BS involvement (esp PAG) • Predominant WM disease (simulates leukodystrophy)

CT Findings • NECT: Hypodense; occasionally normal • CECT: Enhancement uncommon

MR Findings • TlWI o Hypointense • Variable foci hyperintensity degradation products • T2WI: Hyperintense • FLAIR o Hyperintense

=

blood or myelin

Disorders with Bilateral Putamina T2 Hypenntenslty

9 12

Asphyxia

Asphyxia

MELAS

Metabolic/Degenerative Disorders, Inherited

CA-l

LEIGH SYNDROME Key Facts Terminology • Genetically heterogeneous mitochondrial disorder characterized by progressive neurodegeneration

Imaging Findings • Best diagnostic clue: Bilateral, symmetric t T2/FLAIR putamina and peri-aqueductal gray matter (PAG)

Top Differential

Diagnoses

• Profound perinatal asphyxia • Mitochondrial encephalopathy, stroke-like episodes (MELAS) • Glutaric aciduria type I (GA-1) • Wilson disease

Clinical Issues lactic acidosis,

Pathology • LS characterized by extreme genetic heterogeneity

• Resolution of signal abnormality or cystic encephalomalacia (hypointense) may be seen in chronic disease • DWI: Restricted diffusion in acute disease • T1 C+: Enhancement uncommon • MRS: t Choline, I NAA, (+) lactate

Ultrasonographic

Findings

• Hyperechoic deep gray structures, WM

Imaging Recommendations • Best imaging tool: MR with DWI/MRS • Protocol advice: MRS obtained in BG

I

DIFFERENTIAL DIAGNOSIS

Profound perinatal asphyxia • t T2 & T1 dorsolateral

putamina, lateral thalami, dorsal BS, peri-Rolandic cortex o T2 hyperintensity difficult to identify in the unmyelinated brain o T1 hyperintensity seen acutely • History of perinatal asphyxia

Mitochondrial encephalopathy, lactic acidosis, stroke-like episodes (ME LAS) • t T2/FLAIR putamina

(Ca++ in chronic disease) o May be asymmetric or unilateral • Stroke-like signal abnormality parietal-occipital lobes o Non-vascular distribution and (-) DWI typical

Glutaric aciduria type I (GA-1) • t T2/FLAIR corpora striata, GP, +/- WM disease • Characteristic opercular widening

Wilson disease • t T2/FLAIR putamina,

• Autosomal recessive (AR), X-linked, and maternal inheritance of mutated proteins involved in mitochondrial energy production underlie LS • Bioenergetic failure (ATP loss) and production reactive oxygen species likely key factors in mitochondria-mediated cell apoptosis • LS in children < 6 yrs of age = 1:32,000 (most common mitochondrial disease in this age group)

GP, midbrain, thalami o T2 changes evident older children, teens • t T1 GP 2° to hepatic failure o T1 changes identified in infants

• Presentation: Psychomotor delay/regression, hypotonia • Majority present by age 2 • Childhood & adult presentations uncommon • Natural history: Progressive neurodegeneration leading to respiratory failure and death in childhood • No curative treatment

[PATHOLOGY General Features • General path comments o 50-75% patients with LS have detectable biochemical or molecular abnormality o Embryology-anatomy • Main role mitochondria = production ATP via oxidative phosphorylation • Hundreds to thousands mitochondria/cell (t where t energy requirements) • Mitochondria contain own DNA (mtDNA, average of 5 mtDNA per mitochondrion) • mtDNA contribution to zygote exclusively from oocyte (maternal inheritance) • Mitochondria/mtDNA randomly distributed among daughter cells • mtDNA and nuclear DNA (nDNA) encode subunits of electron transport chain (ETe) complexes (COs) I, III-V (nDNA encodes subunits CO II) o Brain & striated muscle highly dependent on oxidative phosphorylation => most severely affected in mitochondrial disorders o Variable number of mitochondria/cell, and random distribution mitochondria/mtDNA into daughter cells account for phenotypic heterogeneity typical of all mitochondrial disorders • Genetics o LS characterized by extreme genetic heterogeneity o Autosomal recessive (AR), X-linked, and maternal inheritance of mutated proteins involved in mitochondrial energy production underlie LS • Mutations frequently involve ETC COs I-V leading to CO deficiencies • AR: Mutation SURFl gene (9q34) is most frequent cause LS due to CO IV (cytochrome C oxidase, COX) deficiency

Metabolic/Degenerative Disorders, Inherited

9 13

LEIGH SYNDROME • Other AR mutations: NDUFV1/NDUFS8 (llq13), NDUFS4 (5q11.1) NDUFS7 genes ~ CO I deficiency; NDUFS3 gene ~ NADH dehydrogenase deficiency; SDHA gene (5p15) ~ CO II deficiency; BCS1L gene (2q33) ~ CO III deficiency, and non-SURF1 mutations ~ COX deficiency • X-linked: PDHA1 gene (Xp22.2-p22.1) ~ pyruvate dehydrogenase CO deficiency • Maternally inherited (mtDNA mutations): MTATP6 gene ~ CO V deficiency (causes LS if mutation load> 90%, NARP {neuropathy, ataxia, retinitis pigmentosa} if load 70-90%); MTND5, MTND6 genes ~ CO I deficiency; MTC03 gene ~ COX deficiency; MTTK, MTTV tRNA genes • Etiology o Exact mechanistic relationship between mitochondrial dysfunction and neurodegeneration unknown o Bioenergetic failure (ATP loss) and production reactive oxygen species likely key factors in mitochondria-mediated cell apoptosis o Coenzyme Q10 deficiency and mitochondrial depletion have also been implicated in LS • Epidemiology o Mitochondrial disorders = 1:8,500 o LS in children < 6 yrs of age = 1:32,000 (most common mitochondrial disease in this age group) o Incidence LS increased in some population isolates: Saguenay-Lac-Saint-]ean (Quebec) = 1:2,063

Gross Pathologic & Surgical Features • Brownish-gray, gelatinous or cavitary foci corpora striata, GP, BS, dentate nuclei, thalami, spinal cord, WM

Microscopic

Features

• Biochemical defect identified by mitochondrial analysis of muscle biopsy or cultured skin fibroblasts • Ragged red fibers typically not present in LS o Prenatal diagnosis: Chorionic villus sampling (mutations and biochemical defects) • Clinical profile: Infant with psychomotor regression, hypotonia

Demographics • Age o Majority present by age 2 o Childhood & adult presentations • Gender: No gender predilection • Ethnicity: No ethnic predilection

uncommon

Natural History & Prognosis • Natural history: Progressive neurodegeneration to respiratory failure and death in childhood • Prognosis: Dismal (particularly SURF1); childhood/adult LS more slowly progressive

leading

Treatment • No curative treatment • Variable improvement with quinone derivatives, vitamins, dichloroacetate • Potential role antioxidants and inhibitors mtDNA replication

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Putaminal involvement classic but variable • Thalamic and PAG involvement simulates Wernicke encephalopathy; however, mamillary bodies spared in

LS

• Spongiform degeneration, gliosis, neuronal loss, demyelination, capillary proliferation

I SELECTED REFERENCES I CLINICAL ISSUES

1.

Presentation

9 14

• Most common signs/symptoms o Presentation: Psychomotor delay/regression, hypotonia o Other signs/symptoms • Progressive BS & BG dysfunction: Ataxia, ophthalmoplegia, ptosis, vomiting, swallowing and respiratory difficulties, dystonia • Variable seizures (generalized, focal, myoclonic and rarely infantile spasms), peripheral neuropathy o Early presentation, BS dysfunction, peripheral neuropathy & rapid neurologic deterioration typical of LS 2° SURF1 mutation o Metabolic stressors (e.g., infection) may unmask disease or cause deterioration o Elevated CSF, serum, urine lactate classic but not invariable o Clinical diagnosis: Progressive neurodegeneration; signs/symptoms BS & BG dysfunction; t lactate blood, CSF; characteristic BG or BS lesions MR

Metabolic/Degenerative

2. 3.

4.

5.

6. 7. 8. 9.

Benit P et al: Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome. J Med Genet. 41(1):14-7, 2004 Schon EA et al: Neuronal degeneration and mitochondrial dysfunction. J Clin Invest 111:303-12, 2003 Rossi A et al: Leigh Syndrome with COX deficiency and SURFl gene mutations: MR imaging findings. AJNR Am J Neuroradiol. 24(6):1188-91, 2003 Stickler DE et al: Juvenile-onset Leigh syndrome with an acute polyneuropathy at presentation. J Child Neurol. 18(8):574-6,2003 Farina L et al: MR Findings in Leigh Syndrome with COX Deficiency and SURF-1 Mutations. AJNR 23:1095-1100, 2002 Munich et al: Clinical Spectrum and Diagnosis of Mitochondrial Disorders. AmJ Med Genet 106:4-17, 2001 Tanji K et al: Neuropathological features of mitochondrial disorders. Semin Cell Dev BioI. 12(6):429-39, 2001 Arii J et al: Leigh syndrome: serial MR imaging and clinical follow-up. AJNR Am J Neuroradiol. 21(8):1502-9, 2000 Medina L et al: MR findings in patients with subacute necrotizing encephalomyelopathy (Leigh syndrome): correlation with biochemical defect. AJR Am J Roentgenol. 154(6):1269-74, 1990

Disorders, Inherited

LEIGH SYNDROME I IMAGE GALLERY Typical (Left) Axial T2WI MR shows symmetric hyperintensity and swelling in the putamina and thalami in early Leigh syndrome. Note signal abnormality in the peri ventricular white matter (Courtesy V. Mathews, MO). (Right) Single voxel, intermediate TE, MR spectroscopy obtained in the basal ganglia of a patient with Leigh syndrome demonstrates an inverted doublet at 1.3 ppm consistent with lactate.

Typical

(Left) Axial FLAIRMR

demonstrates focal, symmetric signal abnormality in the dorsomedial thalamic nuclei of a Leigh syndrome patient. (Right) Axial FLAIR MR in a Leigh syndrome patient with SURFI mutation shows symmetric hyperintensity in dorsal medulla and dentate nuclei. Involvement of the lower brainstem is typical of SURFl mutations.

(Left) Axial T2WI MR in

late-stage Leigh syndrome shows symmetric signal abnormality and volume loss in the corpora striata. (Right) Axial T1WI MR shows hypointensity and volume loss in the putamina in late stage Leigh syndrome.

9 15

Metabolic/Degenerative

Disorders, Inherited

MELAS

Axial graphic shows pathology of MEIAS. The acute onset of gyriform cortical swelling that crosses vascular territories is depicted (arrows). Note old lacunes, generalized/focal atrophy.

ITERMINOLOGY Abbreviations

and Synonyms

• Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) • Myoclonic epilepsy and ragged-red fibers (MERRF) • Mitochondrial encephalomyopathy (MEM) • Mitochondrial DNA (mtDNA); nuclear DNA (nDNA) • Lactate (Lac) • Cytochrome oxidase (COX)

Axial TlWI MR shows generalized atrophy + multifocal deep white matter lesions in a 9 yo male with muscle weakness. Note region of interest for single voxel MRS over the occipital lobes.

o Basal ganglia • Size o Variable o Multiple lesions common • Morphology o Acute: Gyriform swelling that often spares underlying WM o Chronic: Atrophy, deep WM and basal ganglia lacunar infarcts

CT Findings

• Inherited disorder of intracellular energy production caused by point mutation in mtDNA

• NECT o Acute: Swollen cortex o Chronic: Atrophy, lacunes • CECT: Variable gyriform enhancement • CTA: Usually normal

I IMAGING FINDINGS

MR Findings

Definitions

General Features • Best diagnostic clue o Acute: Stroke-like cortical lesions • "Shifting spread" (appearance, disappearance, reappearance elsewhere) is classic • Lesions cross typical vascular territories o Elevated lactate in CSF, "normal" brain on MRS • Correlates well with other MEM markers • Location o Parieto-occipital> temp oro-parietal region

DDx: Toxic-metabolic

• TlWI o Acute: Swollen gyri, compressed sulci o Subacute: Band of cortical hyperintensity consistent with laminar necrosis o Chronic: Progressive atrophy of basal ganglia, temporal-parietal-occipital cortex with preservation of hippocampal, entorhinal structures • T2WI o Acute: Hyperintense cortex/subcortical WM o Chronic: Multifocal hyperintensities in basal ganglia, deep WM

Basal Ganglia lesions

9 16

MERRF

Leigh Disease

Wilson Disease

Metabolic/Degenerative Disorders, Inherited

Cyanide Poisoning

MELAS Key Facts Terminology

• Best imaging tool: MR with multivoxel MRS

• Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) • Inherited disorder of intracellular energy production caused by point mutation in mtDNA

Top Differential Diagnoses

Imaging Findings • • • •

Acute: Stroke-like cortical lesions Elevated lactate in CSF, "normal" brain on MRS Lac ("doublet") peak at 1.3 ppm in 60-65% Presence/amount of lac at MRS varies with type of MEM as well as regional and temporal variations in involvement • Acute: 99mTc-HMPAO SPECT shows striking increase in tracer accumulation • Xenon CT shows focal hyperperfusion during acute strokelike episode, hypoperfusion later

• FLAIR:Acute: Cortical hyperintensity • T2* GRE: No hemorrhage • DWI o Acute: DWI positive • ADC variable but often normal or only slightly decreased (may help distinguish from acute ischemic stroke) • T1 C+: Acute: Gyriform enhancement • MRA: Normal without major vessel occlusion • MRS o Lac ("doublet") peak at 1.3 ppm in 60-65% • Lac peak inverts with intermediate TE (144mSec) due to J-coupling • Changes may precede DWI abnormalities o Cautions • Presence/amount of lac at MRS varies with type of MEM as well as regional and temporal variations in involvement • Lac not always elevated, especially in chronic lesions • Lac may be elevated in CSF but not brain (measure ventricular lac) • Multivoxel more sensitive than single voxel techniques • Failure to interrogate proper ROI reduces sensitivity • Abnormalities may appear later in disease course • Other causes of elevated CNS lac (e.g., hypoxia, ischemia, neoplasm, infection) must be excluded • If child is sedated with phenobarbital, resonance at 1.3 ppm may be present and mimic elevated lac (however doesn't invert)

Angiographic Findings • Conventional: Acute: Dilated cortical arteries, prominent capillary blush without arterial occlusion

Nuclear Medicine Findings • SPECT o Acute: 99mTc-HMPAO SPECT shows striking increase in tracer accumulation

• Myoclonic epilepsy with ragged-red fibers (MERRF) • Leigh disease • Other toxic/metabolic basal ganglia lesions

Pathology • A-to-G translation

at nucleotide

3243 of mtDNA

Clinical Issues • Acute onset: Headache, followed by hemianopsia, psychosis, aphasia • Progressive course with periodic acute exacerbation

Diagnostic Checklist • Think of MEM in patient with an acute "stroke-like" cortical lesion that crosses usual vascular territories

Other Modality Findings • Xenon CT shows focal hyperperfusion during acute strokelike episode, hypoperfusion later • Electromyographic findings consistent with myopathy found in majority of cases • EEG may show focal periodic epileptiform discharges

Imaging Recommendations • Best imaging tool: MR with multivoxel MRS • Protocol advice: Acquire spectra with TE of both 35, 144 mSec

I DIFFERENTIAL DIAGNOSIS Myoclonic epilepsy with ragged-red fibers (MERRF) • Propensity for basal ganglia, caudate nuclei • Watershed ischemia/infarcts common

leigh disease

• cox defect

+/- SURF1 gene mutation o Causes subacute necrotizing encephalomyopathy o Progressive impairment of cognitive, motor function • Imaging shows bilateral symmetric putaminallesions > globi pallidi • Other lesions in caudate nuclei, subthalamic nuclei, periaqueductal GM, brainstem

Other toxic/metabolic

basal ganglia lesions

• Pattern may give clue to etiology (e.g., putaminal involvement in Leigh disease; "eye of panda" in Wilson disease) • Cyanide, carbon monoxide poisoning

Kearns-Sayre syndrome (KSS) • Ataxia, ophthalmoplegia, retinitis pigmentosa • Diffuse symmetric Ca++ in basal ganglia, caudate nuclei, subcortical WM • Hyperintense basal ganglia on T1-, T2WI; cerebellar WM, posterior columns of medulla often involved

Metabolic/Degenerative Disorders, Inherited

9 17

MELAS

I PATHOLOGY

• Seizures • Muscle weakness (myopathy) • Sensorineural hearing loss • Chronic: Cognitive deficits, dementia • Clinical profile: Older child or young adult with muscle weakness and epilepsy or acute strokelike syndrome

General Features

Demographics

• General path comments o MEMs divided into somewhat ill-defined categories based on clinical, histopathologic, biochemical, genetic features • Many overlapping syndromes exist (e.g., Leigh-MELAS) • Genetics o Maternally-transmitted o A-to-G translation at nucleotide 3243 of mtDNA • Etiology o Respiratory chain is under dual genetic control • At least 13 proteins are encoded by mtDNA • Over 80 proteins encoded by nDNA o Defects in respiratory chain metabolism • Defective mitochondrial protein synthesis • NAD+ and NADP+ depletion occurs • Catabolic metabolism shifts from Krebs cycle to anaerobic glycolysis • Pyruvate, lactate accumulate • Result = cellular energy failure o May also cause hyperperfusion, vasogenic edema with BBB disruption during acute strokelike episodes o Caution: Relationship of phenotype to genotype complex, variable in most MEMs • Epidemiology o Overall prevalence of mitochondrial disorders = 5.7 per 100,000 in population> 14 y o Uncommon but important cause of stroke in pediatric cases • Associated abnormalities: Some cortical malformations associated with A3243G mutations

• Age o Onset of stroke-like episodes usually occurs in childhood/early adulthood • Mean age onset = 15 Y • 90%+ symptomatic by 40 Y • Gender: M:F ~ 2:1

Status epilepticus • May cause transient gyriform swelling, enhancement • No lac elevation in normal unaffected brain, CSF

Gross Pathologic & Surgical Features • • • •

Diffuse generalized atrophy Multiple focal cortical, deep WM/basal ganglia infarcts Prominent mineralization of basal ganglia Perivascular Ca++ in both GM, WM may occur

Microscopic Features

9 18

• Trichrome stain shows increased numbers of ragged-red fibers in skeletal muscle • Immunohistochemistry: COX-positive ragged-red fibers (may help distinguish from MERRF) • EM: Swelling, increase in number of dysfunctional mitochondria in smooth muscle, endothelial cells of small arteries and pial arterioles

I CLINICAL ISSUES Presentation • Most common signs/symptoms o Acute onset: Headache, followed by hemianopsia, psychosis, aphasia o Other signs/symptoms

Natural History & Prognosis • Recurrent strokelike events with either permanent or reversible neurologic deficits • Progressive course with periodic acute exacerbation

I DIAGNOSTIC

CHECKLIST

Consider • Think of MEM in patient with an acute "stroke-like" cortical lesion that crosses usual vascular territories

Image Interpretation

Pearls

• Obtain MRS in CSF, uninvolved brain

("normal"-appearing)

I SELECTED REFERENCES Abe K et al: Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events. Neuroradiology. 46(2):113-7,2004 2. Iizuka T et al: Slowly progressive spread of the stroke-like lesions in MELAS. Neurology. 61(9):1238-44, 2003 3. Keng WT et al: A3243G mitochondrial mutation associated with polymicrogyria. Dev Med Child Neurol. 45(10):704-8, 2003 4. Jeppesen TD et al: Late onset of stroke-like episode associated with a 3256C--> T point mutation of mitochondrial DNA. J Neurol Sci. 214(1-2):17-20, 2003 5. Sparaco M et al: MELAS: clinical phenotype and morphological brain abnormalities. Acta Neuropathol (Bed). 106(3):202-12, 2003 6. Wang XY et al: Serial diffusion-weighted imaging in a patient with MELAS and presumed cytotoxic oedema. Neuroradiology. 45(9):640-3, 2003 7. Chol M et al: The mitochondrial DNA G 135 13A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency. J Med Genet. 40(3):188-91, 2003 8. Carvalho KS et al: Arterial strokes in children. Neurol Clin. 20(4):1079-100, vii, 2002 9. Sakuta R et al: Atypical MELAS associated with mitochondrial tRNA(Lys) gene A8296G mutation. Pediatr Neurol. 27(5):397-400, 2002 10. Sartor H et al: MELAS: a neuropsychological and radiological follow-up study. Mitochondrial encephalomyopathy, lactic acidosis and stroke. Acta Neurol Scand. 106(5):309-13,2002 1.

Metabolic/Degenerative Disorders, Inherited

MELAS I IMAGE GALLERY Typical (Left) MR single voxel spectroscopy in patient suspected of MELASshows classic lactate "doublet" peak (arrow) at 1.3 ppm on this long TE (270 mSec) sequence. (Right) MRS in the same case obtained with intermediate TE (144 mSec) shows classic inversion of the lactate peak (arrow). MELAS confirmed at muscle biopsy.

Typical (Left) Axial T2WI MR shows

high signal intensity in the right temporal-parietal region with gyral swelling in this patient with first symptomatic episode of MELAS. (Right) Axial FLAIR MR (same case) shows hyperintensity in the cortex with limited involvement of the subcortical WM. No other lesions were present.

Typical (Left) Sagittal T1WI MR

(same case as above) shows the swollen gyri extend all the way to the tip of the temporal lobe. The involvement crosses the vascular distribution of the MCA and PCA. (Right) MR spectroscopy in the same case obtained with short TE (35 mSec) shows a lactate peak resonating at 1.3 ppm (arrow).

9 19

Metabolic/Degenerative Disorders, Inherited

MUCOPOLYSACCHARIDOSES

Axial graphic shows dilated Virchow-Robin spaces radially oriented in the white matter of the brain. There is a posterior predominance and the corpus callosum (arrow) is typically involved.

Axial TlWI MR shows similar dilated VR spaces with callosal involvement (arrow) and posterior predominance in a child with MPS 1 (Hurler).

ITERMINOLOGY

Radiographic Findings

Abbreviations

• Radiography: Dysostosis multiplex, broad ribs, trident hands, ]-shaped sella, "rosette" formation of multiple impacted teeth in a single follicle

and Synonyms

• Mucopolysaccharidoses (MPS); old term "gargoylism" o Prototype: MPS 1H (Hurler)

CT Findings

Definitions

I IMAGING FINDINGS

• NECT o Metopic beaking despite macrocrania o Macrocrania,{ density WM, dilated VRS are rarely visible on CT o Progressive hydrocephalus AND atrophy • MPS 1: Hydrocephalus an early finding in 25% • MPS 3B: Severe atrophy • CECT: Enhancing pannus associated with ligaments and dura at craniocervical junction (CVJ)

General Features

MR Findings

• Best diagnostic clue: Perivascular spaces (PVS), also known as Virchow-Robin spaces (VRS), dilated by accumulated GAG • Location: Favored sites of dilated VRS in MPS = corpus callosum (CC), peritrigonal white matter (WM), but can occur in other lobes • Size o Variably sized dilated VRS, usually under 5 mm, occasional large obstructed VRS occur o Range in number: One to too-many-to-count • Morphology: Round, oval, spindle, parallel to veins

• TlWI o Cribriform appearance WM, CC, basal ganglia (BG) • Dilated VRS filled with GAG: "Hurler holes" • Especially in severe MPS (MPS 1H, 2> > other MPS types) • Except MPS 4 (Morquio): CNS spared o Occasional arachnoid cysts (meningeal GAG deposition) • T2WI o i Signal of WM surrounding dilated VRS: Gliosis, edema, de- or dysmyelination

• Inherited disorder of metabolism characterized by enzyme deficiency and inability to break down glycosaminoglycan (GAG) o Failure to break down =} accumulation of toxic intracellular substrate

DDx: Cystic Spaces in White Matter

9 20

Velocardiofacial

Macrocephaly

VRS

Metabolic/Degenerative

Hypomelanosis of ito

Disorders,

Inherited

Neonatal HIE Cysts

MUCOPOLYSACCHARIDOSES Key Facts Terminology • Prototype: MPS 1H (Hurler) • Inherited disorder of metabolism characterized by enzyme deficiency and inability to break down glycosaminoglycan (GAG) • Failure to break down ~ accumulation of toxic intracellular substrate

Imaging Findings • Best diagnostic clue: Perivascular spaces (PVS), also known as Virchow-Robin spaces (VRS), dilated by accumulated GAG • Cribriform appearance WM, CC, basal ganglia (BG) • Except MPS 4 (Morquio): CNS spared • Occasional arachnoid cysts (meningeal GAG deposition) • Compression CVJ in majority MPS o +/- Additional patchy WM signal • FLAIR o VRS isointense with CSF o t Signal surrounds VRS • MRS o !NAA, t Ch/Creat ratio; t peak at 3.7 ppm contains signals from MPS • Improvement in presumptive MPS peaks following bone marrow transplant (BMT) • Spinal MRI o Compression CVJ in majority MPS • C2 meningeal hypertrophy • Progressive odontoid dysplasia ~ risk atlantoaxial subluxation if no BMT; some correction reported following BMT • Short C1 posterior arch o t T2 signal cord in 50% of those with radiographic CV] compression o Upper lumbar gibbus • MPS 1H (Hurler): Inferior beaking • MPS 4 (Morquio): Middle beaking

Nuclear Medicine Findings • 1231-IMP: ! Perfusion

Imaging Recommendations • Best imaging tool: MRI Brain • Protocol advice o Baseline MRI!MRS o F/U: Complications (CVJ compression, hydrocephalus); therapeutic response to BMT o Always visualize foramen magnum on any CNS study to seek CVJ compression, a treatable cause of morbidity

I DIFFERENTIAL DIAGNOSIS Velocardiofacial syndrome (microdeletion Chr 22) • Dilated VR spaces and plaques, typically frontal predominance; deviated carotid arteries in pharynx a clue

• Always visualize foramen magnum on any CNS study to seek CV] compression, a treatable cause of morbidity

Top Differential • • • • •

Diagnoses

Velocardiofacial syndrome (microdeletion Chr 22) Macrocephaly with dilated VRS Hypomelanosis of Ito Lack "beaked" metopic suture present in MPS Normal VR spaces

Pathology • Thick meninges • Honeycomb or cribriform appearance cut surface of brain

Diagnostic Checklist • Airway: Major sedation and anesthesia risk

Macrocephaly with dilated VRS • Lacks typical beaked metopic suture and foramen magnum compression

Hypomelanosis of Ito • Periventricular signal change (brighter and more persistent than MPS) with large VRS • May also have hemimegalencephaly • Typical whorled skin lesions • Lack "beaked" metopic suture present in MPS

Perinatal hypoxic ischemic encephalopathy • Transient phase of cystic change following hypoxic ischemic encephalopathy ~ atrophy

Normal VR spaces • Vary in number and prominence

I

PATHOLOGY

General Features • General path comments o GAG accumulates in most organs/ligaments • Hepatosplenomegaly (HSM), umbilical hernia • Skeletal dysostosis multiplex, joint contractures • Arterial wall (mid-aortic stenosis) and cardiac valve thickening • Dural thickening (cord compression at foramen magnum) • Coarse facies (formerly "gargoylism") • Upper airway obstruction (38%): Submucosal deposition ~ small, abnormal shape trachea (difficult intubation); abnormal configuration vocal cords o Embryology-anatomy • Dilated VR spaces may be seen in utero • Genetics: MPS: Autosomal recessive (exception: X-linked MPS 2) • Etiology: MPS: Ganglioside accumulation (toxic to neurons) • Epidemiology o 1:29,000 live births (series from Australia)

Metabolic/Degenerative Disorders, Inherited

9 21

MUCOPOLYSACCHARIDOSES • MPS 1H: 1 in 107,000 live births • MPS 2: 1 in 165,000 male live births • MPS 3: 1 in 58,000 live births • MPS 4A: 1 in 640,000 live births • MPS 6: 1 in 320,000 live births • Associated abnormalities o Dermal melanocytosis (mongolian-like spots) • Extensive, blue skin pigmentation differs from typical mongolian spots in persistence or progression

Gross Pathologic & Surgical Features • Thick meninges • Honeycomb or cribriform appearance brain

Microscopic

22

• BMT or IV recombinant human enzyme (e.g., MPS 1H: <x-L-iduronidase) o I Visceral accumulation MPS; ameliorate some manifestations • Murine embryonic stem cell models under evaluation for gene therapy

[DIAGNOSTIC in

CHECKLIST

Consider • Airway: Major sedation and anesthesia risk

Staging, Grading or Classification Criteria

Image Interpretation

• MPS 1-9, depends upon specific enzyme deficiency o MPS 1H, 1HS (Hurler/Hurler-Scheie): <x-L-iduronidase (4p16.3) o MPS 2 (Hunter): Iduronate 2-sulfatase (Xq28) o MPS 3A (Sanfilippo): Heparin N-sulfatase (17q25.3) o MPS 4A (Morquio): Galactose 6-sulfatase (16q24.3) o MPS 6 (Maroteaux-Lamy): Arylsulfatase B (5qll-q13)

• Not all MPS have typical facial features, dilated VRS may still signal one of the less common MPS • Not all dilated VRS are MPS • Always look for CVJ compression o Treatable cause of morbidity in MPS o Lack of CVJ compression suggests there may be a different etiology of dilated VRS than MPS

I CLINICAL ISSUES

I SELECTED REFERENCES

Presentation

Gabrielli 0 et al: Correlation between cerebral MRI abnormalities and mental retardation in patients with mucopolysaccharidoses. Am] Med Genet. 125A(3):224-31, 2004 2. Walker RW et al: Postobstructive pulmonary edema during anesthesia in children with mucopolysaccharidoses. Paediatr anaesth 13(5):441-7, 2003 3. Hanson M et al: Association of dermal melanocytosis with lysosomal storage disease: Clinical features and hypotheses regarding pathogenesis. Arch Dermatol139(7):916-20, 2003 in 4. Nelson et al: Incidence of the mucopolysaccharidoses Western Australia. Am] Med Genet 123A(3):31O-3, 2003 5. Shih SL et al: Airway changes in children with mucopolysaccharidoses. Acta Radiol 4391);40-3, 2002 7 (Sly disease) as a 6. Geipel A et al: Mucopolysaccharidosis cause of increased nuchal translucency and non-immune fetal hydrops: Study of a family and technical approach to prenatal diagnosis in early and late pregnancy. Prenat Diagn 22(6):493-5, 2002 Brooks DA: Alpha-L-iduronidase and enzyme replacement 7. therapy for mucopolysaccharidosis 1. Expert Opin BioI Ther 2(8):967-76,2002 8. Yukitoshi T et al: Evaluation of accumulated MPS in the brain. By 1H-MRS before and after BMT. Pediatr Res 49:349-55, 2001 9. van der Knaap MS et al: Ch 13 in: Magnetic Resonance of Myelin, Myelination, and Myelin Disorders, 2nd ed, PP.97-105, Springer-Verlag, Berlin, 1995 10. Nakamura T et al: Rosette formation of impacted molar teeth in mucopolysaccharidoses and related disorders. Dentomaxillofac Radiol 21(1):45-9, 1992 1.

• Most common signs/symptoms o Typical coarse facies develop (mild in MPS 3,6,7) • Macroglossia, bushy eyebrows, flat nasal bridge • Clinical profile o Prototype MPS 1H, appear normal at birth • Corneal clouding (except MPS 2): Proteoglycans in keratocytes • Mental retardation (significant except MPS 2b, 4, 1HS) • Joint contractures, dysostosis multiplex, short stubby fingers, carpal tunnel syndrome • Loses walking skills: Spinal claudication/myelopathy Cl-2 and vascular claudication from mid-aortic stenosis • Recurrent upper respiratory infection, nasal discharge, ear infections, sleep apnea, sensorineural deafness • Middle ear effusions (73%), otolaryngologist notes this pre-diagnosis MPS o MPS 7 may present with fetal nuchal translucency, hydrops fetalis or isolated ascites

9

Treatment

cut surface of

Features

• MPS: Glycosaminoglycans accumulate leptomeninges and V-R spaces

o MPS 1H death by 10 yrs, without therapy o MPS 2A death in late teens (cardiac) o Others variable • Significant correlation exists between WM alterations & mental retardation

Demographics • Age: MPS IH presents in infancy • Gender: MPS 2 (Hunter) is X-linked: Male • Ethnicity: Prevalence of specific MPS disorders varies with country

Natural History & Prognosis • Progressive deterioration without therapy • Rate of deterioration depends upon specific deficiency

Metabolic/Degenerative Disorders, Inherited

Pearls

MUCOPOLYSACCHARIDOSES I IMAGE GALLERY Typical (Left) Sagittal T2WI MR in a child with MPS I shows radially arrayed dilated VR spaces in the corona radiata and a larger loculated VR space (arrow) in the inferior basal ganglia. Both are typical of MPS. (Right) Axial T2WI MR shows dilated VR spaces in the corpus callosum and parietal lobes. Note that the margins of the VR spaces are less distinct on T2WI due to gliosis or adjacent dysmyelination.

Typical (Left) Axial NECT shows metopic beaking in a child with macrocephaly. The child has MPS 1. (Right) Coronal oblique 3D reconstruction shows metopic ridging (arrow), unusual in macrocephaly unless there is concomitant MPS.

Typical (Left) Sagittal T2WI MR in MPS I shows cord compression at craniocervical junction by a combination of short posterior arch of Cl (curved arrow) and ligament hypertrophy (arrow) due to MPS deposition. (Right) Sagittal TlWI MR in MPS I shows typical gibbus deformity with marked compression of the underlying conus medullaris (arrow).

9 23

Metabolic/Degenerative

Disorders, Inherited

GANGLIOSIDOSIS

Axial T2WI MR shows symmetric, diffuse thalamic hypointensity characteristic of Sandhoff disease. The corpora striata (putamina> caudate heads) and white matter are hyperintense.

• Gangliosidosis

Axial TlWI MR demonstrates symmetric hyperintensity within the thalami in Sandhoff disease. White matter is unmyelinated with the exception of the corpus callosum.

• Focal thalamic involvement in TS • Diffuse cerebral WM involvement with sparing of corpus callosum characteristic of all infantile GM2 • Morphology: Disease characterized by bilateral symmetric involvement of brain structures

ITERMINOLOGY Abbreviations

(GM2)

and Synonyms GM2 (GM2)

Definitions • Inherited glycosphingolipid lysosomal storage disorder characterized by GM2 ganglioside brain accumulation • Three major biochemically distinct, but clinically indistinguishable, types: Type B, type 0, and type AB o Type B infantile = Tay-Sachs disease (TS) o Type 0 infantile = Sandhoff disease (SD) o Type AB infantile = GM2 variant AB • Type Band 0 also exist in juvenile and adult forms • Type AB exists in infantile form only

I IMAGING FINDINGS

CT Findings • NECT o Hyperdense thalami classic but not invariable o +/- Hypodense CS, WM (CS occasionally hyperdense) o Late infantile GM2: CS swelling early; cortical atrophy (cerebral> > cerebellar) o Juvenile/adult GM2 • Cerebellar atrophy • Thalami, CS, WM normal • Rare, "mass-like", brain stem involvement • CECT: No abnormal enhancement

MR Findings

General Features • Best diagnostic clue: Bilateral, symmetric thalamic CT hyperdensity, T2 hypointensity, Tl hyperintensity (infantile GM2) • Location o Thalami, corpora striata (CS, putamina> caudate heads), cerebral> > cerebellar white matter (WM) (infantile GM2) • Diffuse thalamic involvement in SD

DDx: CT Hyperdense/T2

• TlWI o Hyperintense thalami +/- hypo intense WM o CS intensity variable o Cortical atrophy (cerebral> > cerebellar) o Juvenile/adult GM2: Cerebellar atrophy • T2WI o Hypointense thalami • SD: Diffusely hypointense

Hypointense Thalami

9 24

Status Marmoratus

NCL

Metabolic/Degenerative

Krabbe Disease

Disorders, Inherited

Krabbe Disease

GANGLIOSIDOSIS

(GM2)

Key Facts • Juvenile GMI gangliosidosis

Terminology • Inherited glycosphingolipid lysosomal storage disorder characterized by GM2 ganglioside brain accumulation

Imaging Findings • Best diagnostic clue: Bilateral, symmetric thalamic CT hyperdensity, T2 hypointensity, T1 hyperintensity (infantile GM2) • Morphology: Disease characterized by bilateral symmetric involvement of brain structures • Hyperdense thalami classic but not invariable

Top Differential

Diagnoses

• Status marmoratus • Neuronal ceroid lipofuscinosis • Krabbe disease

• TS: Focal, ventral hypo intensity; +/- focal, dorsal hyperintensity o Hyperintense WM (hypo- or demyelinated) o Hyperintense CS typical (occasionally iso-, or hypointense) • Hypointense CS more typical of late disease o Juvenile/adult GM2: Rare, hyperintense "mass-like" brainstem involvement • DWI: +/- Diffusion restriction ventral thalami TS • Tl C+: No abnormal enhancement

Ultrasonographic

Findings

• Echogenic thalami (infantile GM2)

Imaging Recommendations • MR (CT may confirm thalamic abnormality)

I DIFFERENTIAL DIAGNOSIS Status marmoratus • History of profound perinatal ischemia • Atrophy of the ventrolateral thalami, posterior putamina, dorsal brains tern, peri-Rolandic regions with CT hyperdensity, variable T2 hypo-, T1 hyperintensity of involved basal ganglia & thalami

Neuronal ceroid lipofuscinosis • Lysosomal storage disorder characterized by accumulation of autofluorescent lipofuscin in brain • CT hyperdense, T2 hypointense thalami, globi pallidi • Cerebral, cerebellar atrophy

Krabbe disease • Leukodystrophy with oligodendrocyte destruction • Hyperdense thalami, caudate and dentate nuclei o Thalamic T2 hypointensity is variable, late finding • T2 hyperintense cerebral, cerebellar WM with involvement of corpus callosum

Juvenile GM1 gangliosidosis • Rare lysosomal storage disorder characterized accumulation of GMI ganglioside/asialo-GAI • Imaging findings identical to SD

by in brain

Pathology • GM2 ganglioside normally resides in neuronal cell membranes; plays role in cell-cell recognition and synaptogenesis • Autosomal recessive inheritance • Deficient Hex A or GMAP causes accumulation GM2 ganglioside in neuronallysosomes

Clinical Issues • TS more common in Ashkenazi Jewish, French Canadians, Cajuns, and Druze • Infantile: Rapidly progressive psychomotor regression culminating in paralysis, blindness, deafness and death typically by 4 yrs of age • Supportive therapy, seizure control

I PATHOLOGY General Features • General path comments o GM2 ganglioside normally resides in neuronal cell membranes; plays role in cell-cell recognition and synaptogenesis o B-hexosaminidase A (Hex A) & GM2 activator protein (GMAP) required for lysosomal GM2 ganglioside catabolism o Hex A is one of 3 isoenzymes of B-hexosaminidase (Hex) formed by dimerization of ()(and B polypeptide subunits • Hex A = ()(Bdimer; Hex B = BB dimer; Hex S = ()(()( dimer • Hex A and Hex B are major forms; Hex S is minor form with unclear physiologic function • Genetics o Autosomal recessive inheritance • Type B: > 75 different mutations ()(subunit, Chr 15q23-q24; causes deficient Hex A • Type 0: > 20 different mutations B subunit, Chr 5q13; causes deficient Hex A and Hex B • Type AB: - 4 different mutations GMAP, Chr 5q31.3-q33.1 • GM2 variant Bl (rare) caused by ()(subunit mutation ~ normal ()(subunit production but creates catalytically inactive Hex A with GM2 ganglioside • Mutations allowing residual Hex A activity (0.5-4% of normal activity) account for milder juvenile/adult phenotypes • Etiology o Deficient Hex A or GMAP causes accumulation GM2 ganglioside in neuronal lysosomes o Increase in size & number of neuronal lysosomes leads to neuronal degeneration/apoptosis with secondary hypomyelination/demyelination • GM2 ganglioside accumulation in myelin membrane may also contribute to demyelination o Exact mechanism by which GM2 ganglioside accumulation causes neuronal apoptosis is unknown

Metabolic/Degenerative Disorders, Inherited

9 25

GANGLIOSIDOSIS • Activated microglia, macrophages, and astrocytes suggest an inflammatory component • Identification of autoantibodies in mouse models SD suggest autoimmune component • Epidemiology o TS: 1:300 carrier frequency in Sephardic, Oriental, Jewish and non-Jewish • 1:30 AshkenaziJewish, French Canadians • 1 Incidence Cajuns, Druze o SD, GM2 variant AB, and juvenile/adult type GM2 = pan-ethnic (I in small gene pools) • 1:1,000 Jewish, 1:600 non-Jewish, 1:16-29 Creole population of Cordoba, Argentina, 1:7 Maronite Christian Cypriots o Incidence TS US and Canada ! by > than 90% since 19702° to carrier screening and prenatal diagnosis

Natural History & Prognosis

• Infantile GM2: Early megalencephaly; late atrophy o Gelatinous, hemispheric white matter, +/- cavitation • Juvenile/adult: Cerebellar atrophy

Microscopic

Treatment

Features

• GM2 ganglioside accumulation in cerebral neurons o Less severe GM2 ganglioside accumulation in glial, Purkinje, anterior horn, and retinal ganglion cells oEM: GM2 ganglioside contained in "membranous cytoplasmic bodies" (MCBs) in neuronal cytoplasm, proximal nerve processes, axons • MCBs in cytoplasm cause distortion and ballooning; MCBs in proximal nerve processes form meganeurites • Hypomyelination, demyelination and Wallerian degeneration • Juvenile/adult GM2: Ganglioside accumulation in anterior horn cells, cerebellar neurons, basal ganglia, brain stem o MCBs occasionally absent • SD: Additional storage GM2 (and globoside) in viscera

I CLINICAL ISSUES Presentation

26

o Infantile: Symptom onset first year of life o Juvenile/adult: Symptom onset by 2-6 yrs of age/lst-3rd decades • Gender: No gender predilection • Ethnicity o TS more common in AshkenaziJewish, French Canadians, Cajuns, and Druze o SD, GM2 variant AB, juvenile/adult GM2: Pan-ethnic but 1 in small gene pools • Infantile: Rapidly progressive psychomotor regression culminating in paralysis, blindness, deafness and death typically by 4 yrs of age • Late infantile subacute variant form: Progression is aggressive leading to death within 2-4 years of onset • Juvenile: More slowly progressive with death between 5 and 15 years of age o Often 2° to infection, preceded by several years decerebrate rigidity in a vegetative state • Adult: Prolonged survival to age 60-80 years

Gross Pathologic & Surgical Features

9

(GM2)

• Most common signs/symptoms o Infantile GM2: Exaggerated startle response to noise; psychomotor retardation/regression o Juvenile/adult GM2: Atypical spinocerebellar ataxia; lower motor neuron disease o Other signs/symptoms • Infantile: Macrocranium, seizures, blindness (90% with cherry-red spot macula) • Juvenile/adult: Psychosis/depression (30%), early stuttering, dementia, extrapyramidal dysfunction • Clinical profile o Diagnosis: Documentation Hex A deficiency in serum leukocytes, cultured skin fibroblasts, amniotic fluid, or a chorionic villus sample o Abnormal results should be followed by DNA analysis to detect mutation and/or exclude a pseudo deficiency allele

• Supportive therapy, seizure control • Future therapies: Enzyme replacement, substrate deprivation, bone marrow transplantation, CNS stem cell transplantation, and retroviral-vector-mediated gene therapy

I SELECTED REFERENCES 1.

Yamaguchi A et al: Possible role of autoantibodies in the pathophysiology of GM2 gangliosidoses. J Clin Invest. 113 (2):200-8,2004 2. Jeyakumar M et al: Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain. 126(Pt 4):974-87,2003 3. Pelled D et al: Reduced rates of axonal and dendritic growth in embryonic hippocampal neurones cultured from a mouse model of Sandhoff disease. Neuropathol Appl Neurobiol. 29(4):341-9, 2003 4. Nassogne MC et al: Unusual presentation of GM2 gangliosidosis mimicking a brain stem tumor in a 3-year-old girl. AJNR Am J Neuroradiol. 24(5):840-2, 2003 5. Myerowitz R et al: Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling. Hum Mol Genet. 11(11):1343-50,2002 6. Yuksel A et al: Neuroimaging findings of four patients with Sandhoff disease. Pediatr Neurol. 21(2):562-5, 1999 7. Chavany C et al: Biology and potential strategies for the treatment of GM2 gangliosidoses. Mol Med Today 4:158-65, 1998 8. Hund E et al: Progressive cerebellar ataxia, proximal neurogenic weakness and ocular motor disturbances: hexosaminidase A deficiency with late clinical onset in four siblings. J Neurol Sci. 145(1):25-31, 1997 9. Myerowitz R: Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A Gene. Human Mutat 9:195-208, 1997 10. Van der Knaap et al: GM2 Gangliosidosis. In MR of Myelin, Myelination, and Myelin Disorders, 2nd ed, Springer 81-9, 1995 11. Brismar J et al: Increased density of the thalamus on CT scans in patients with GM2 gangliosidoses. AJNR Am J Neuroradiol. 11(1):125-30, 1990

Demographics • Age

Metabolic/Degenerative Disorders, Inherited

GANGLIOSIDOSIS

I IMAGE

(GM2)

GALLERY

Typical (Left) Axial PO in early

Tay-Sachs disease shows focal, symmetric hypointensity in ventral thalami (arrows), and symmetric hyperintensity in corpora striata, and, to a lesser extent, in the dorsal thalami. (Right) Axial T2WI MR in late stage Tay-Sachs disease shows symmetric hypointensity in ventral thalami & dorsal putamina. The brain is atrophic with diffuse white matter hyperintensity (hypomyelination).

Typical (Left) Axial NECT in infantile

eM2 demonstrates bilateral thalamic hyperdensity as well as hypoattenuation in the periventricular white matter. (Right) Sagittal T1WI MR nicely depicts vermian atrophy in a child with juvenile eM2.

Typical (Left) Axial T2WI MR in an adult with eM2 reveals atrophy of the cerebellar vermis and hemispheres. (Right) Axial T2WI MR shows normal basal ganglia, thalami, and white matter in a patient with juvenile eM2.

9 27

Metabolic/Degenerative

Disorders, Inherited

METACHROMATIC LEUKODYSTROPHY .

Axial FlAIR MR demonstrates symmetric periventricular white matter T2 prolongation. Also note the sparing of subcortical Ufibers (arrows) (Courtesy 5. Blaser, MO).

Axial FlAIR MR shows confluent periventricular white matter hyperintensity from metachromatic leukodystrophy in a "butterfly pattern" (arrows) (Courtesy 5. Blaser, MO).

o Late: Cerebral atrophy, progressive I periventricular WM attenuation • CECT: No WM enhancement (lacks inflammation) • CT Perfusion: I Perfusion to hemispheric WM

ITERMINOlOGY Abbreviations

and Synonyms

• Metachromatic leukodystrophy • Synonym: Sulfa tide lipoidosis

(MLD)

MR Findings • TlWI o Early: I Tl signal within periventricular WM o Late: Progressive I WM signal & cerebral atrophy • T2WI o Early in disease • Confluent periventricular hyperintensity ("butterfly pattern") • Early sparing of perivascular WM ("tigroid or leopard pattern") • Early sparing of subcortical U-fibers o Later in disease progression • Late progressive peripheral extension of T2 hyperintensity (demyelination) • Late involvement of U-fibers, corpus callosum, descending pyramidal tracts, internal capsules • Late progressive cerebral atrophy • PDjlntermediate: 1 Signal within periventricular WM • FLAIR: "Butterfly pattern" of periventricular hyperintensity • T2* GRE: No petechial hemorrhage • DWI o Restriction at margin of active demyelination

Definitions • Progressive neurodegenerative lysosomal storage disorder due to I arylsulfatase A (ARSA) o Manifests in a variety of forms: Late infantile (most common), juvenile, adult

I IMAGING FINDINGS General Features • Best diagnostic clue: Confluent "butterfly-shaped" cerebral hemispheric white matter (WM) T2 signal 1 • Location o Subcortical cerebral hemispheric WM • Early: Spares subcortical U-fibers, internal capsules • Late: Involvement of subcortical U-fibers • Morphology: Symmetric, confluent periventricular high T2 signal

CT Findings • NECT o Early: Symmetric

I periventricular

WM attenuation

DDx: Metachromatic

9

leukodystrophy

J

t

y

.

Pelizaeus Merzbacher

.' ':

"

look-alikes

\,

t J)'\i. , •.... "

28

(MLD)

t

"

Congenital CMV

,

Pseudo-TORCH

Metabolic/Degenerative Disorders, Inherited

PVL

METACHROMATIC LEUKODYSTROPHY

(MLD)

Key Facts Terminology • Progressive neurodegenerative lysosomal storage disorder due to I arylsulfatase A (ARSA)

Imaging Findings • Best diagnostic clue: Confluent "butterfly-shaped" cerebral hemispheric white matter (WM) T2 signal t • Early sparing of perivascular WM ("tigroid or leopard pattern") • Early sparing of subcortical U-fibers • Late progressive peripheral extension of T2 hyperintensity (demyelination) • Late involvement of U-fibers, corpus callosum, descending pyramidal tracts, internal capsules • Late progressive cerebral atrophy • Restriction at margin of active demyelination • MRS: t Choline, lactate, lipids, myo-inositol; I NAA o I ADC within demyelinated WM • T1 C+: No WM enhancement • MRS: t Choline, lactate, lipids, myo-inositol;

Ultrasonographic

• MRI: Include FLAIR • MRS: Sample central hemispheric

Top Differential • • • •

WM

Diagnoses

Pelizaeus-Merzbacher disease TORCH Pseudo-TORCH Periventricular leukomalacia (PVL)

Pathology • Associated abnormalities: disease

Symptomatic

gallbladder

Clinical Issues • Late infantile form (most common) • Manifests between 1 and 2 years • Strabismus, gait disturbance, ataxia, weakness, hypotonia • ASRA pseudodeficiency • Confirmed by skin biopsy

I NAA

Findings

• Thick gallbladder wall, ± sludge or polypoid ingrowths

Krabbe disease • Early involvement of cerebellar WM • CT shows t attenuation of thalami

• PET: 123I-IMP shows cerebral hypoperfusion

Vacuolating megaloencephalic leukoencephaly with subcortical cysts

Imaging Recommendations

• Slowly progressive, sparing of cognition

Nuclear Medicine

Findings

• Best imaging tool: Early MRI & MRS in pre-symptomatic enzyme deficient siblings • Protocol advice o MRI: Include FLAIR o MRS: Sample central hemispheric WM

I DIFFERENTIAL DIAGNOSIS Pelizaeus-Merzbacher

disease

• Usually manifests in the neonate and infant • Lack of myelination without myelin destruction • Cerebellum may be markedly atrophic

TORCH • Variable WM hyperintensity (demyelination & gliosis) • Non-progressive • Varied patterns of Ca++ depending on etiology

Pseudo-TORCH • Progressive cerebral and cerebellar demyelination • Brainstem, basal ganglia and periventricular Ca++ • Elevated CSF neurotransmitters

Periventricular

leukomalacia

(PVL)

• Usually symmetric periventricular bright T2 signal • Periventricular volume loss (non-progressive) • Static spastic diplegia or quadriplegia

Sneddon syndrome (arylsulfatase A pseudodeficiency) • Demyelination • Periventricular

may be precipitated by hypoxic event WM bright T2 signal

I PATHOLOGY General Features • General path comments o Systemic storage of sulfatide due to deficient ARSA • Symptomatic storage: CNS, peripheral nerves and gallbladder • Asymptomatic storage: Kidneys, pancreas, adrenals, and liver o Diagnosis confirmed by • Detecting excessive urine sulfatide • Absent or deficient ARSA activity in leukocytes • Genetics o Autosomal recessive trait • ARSA gene located at 22q13.31 • Considerable genotype-phenotype variability • > 40 different mutations documented (459+1G>A; P426L) o Compound heterozygosity with missense mutations associated with very late onset • Etiology o Absent or deficient activity of ARSA =:> sulfatide accumulation • Sulfa tide not able to be degraded ... t storage in lysosomes =:> lethal demyelination • Epidemiology o Pan-ethnic frequency of 1:40,000 • tIn Habbanite]ewish (1:75 live births) • t In Navajo Indians (1:2,500 live births) • Associated abnormalities: Symptomatic gallbladder disease

Metabolic/Degenerative Disorders, Inherited

9 29

METACHROMATIC LEUKODYSTROPHY Gross Pathologic & Surgical Features

Natural History & Prognosis

• Early o Enlarged brain & demyelination o Lack of inflammatory component to WM • Late o Progressive cerebral hemispheric demyelination o Cerebral atrophy

• Variable depending

Microscopic

Features

• CNS o PAS-positive metachromatic material accumulates within glial cells and neurons o Sulfatide deposition within plasma membranes o Sulfatide membrane-bound inclusions at the inner layer of myelin sheaths o Demyelination may be extensive yet inflammatory component is lacking • Biochemistry o Three isoenzymes of ARSA (A, B, & C) • Markedly ~ ARSA activity in late infantile, juvenile, and adult forms of MLD • Sulfatide content in WM is considerably higher in the late infantile form

I CLINICAL ISSUES Presentation

9 30

(MLD)

• Most common signs/symptoms o Late infantile form (most common) • Manifests between 1 and 2 years • Strabismus, gait disturbance, ataxia, weakness, hypotonia • ± Cherry-red macular spot • Bulbar signs ~ progressive hypotonia ~ decerebrate posturing ~ optic atrophy • Children frequently die by 8 to 10 years o Juvenile form • Appears between 5 and 10 years • Impaired school performance (nonverbal learning disability) • Spastic gait, ataxia, intellectual impairment • Brisk deep tendon reflexes • Progressive spasticity ~ progressive dementia ~ decerebrate posturing ~ seizures • Rare to survive longer than 20 years o Adult form • May present as MS • Dementia between third and fourth decades • Some adults present with schizophrenia • Progressive: Corticobulbar, corticospinal, and cerebellar changes • Clinical profile: Infant or young child with strabismus, hypotonia, ataxia, and weakness

Demographics • Age o Variable depending on form • Late infantile form presents between 1 & 2 yrs • Gender: Males and females affected equally • Ethnicity: t Incidence in Habbanite Jewish and Navajo Indians

on clinical form

Treatment • Bone marrow transplant o May arrest motor and intellectual deterioration • Attempts to promote ARSA enzymatic activity have shown poor results • Future role of retroviral-vector-mediated ARSA gene transfer

I DIAGNOSTIC

CHECKLIST

Consider • If WM involvement appears as "worst case MLD", involving internal capsule and brainstem ~ MLD look-alike, consider o Pseudo-TORCH o Vacuolating megaloencephalic leukoencephaly with subcortical cysts

Image Interpretation

Pearls

• "Butterfly pattern" of cerebral hemispheric WM • Early sparing of subcortical U-fibers • Lack of enhancement (no inflammatory component)

I SELECTED REFERENCES 1.

Gallo S et al: Late onset MLDwith normal nerve conduction associated with two novel missense mutations in the ASAgene. J Neurol Neurosurg Psychiatry. 75(4):655-7,2004 2. Sener RN:Metachromatic leukodystrophy: diffusion MRI findings. AJNRAmJ Neuroradiol. 23(8):1424-6, 2002 3. Engelbrecht V et al: Diffusion-weighted MRimaging in the brain in children: findings in the normal brain and in the brain with WM diseases. Radiology. 222(2):410-8, 2002 4. Weber ByarsAM et al: Metachromatic leukodystrophy and nonverbal learning disability: neuropsychological and neuroradiological findings in heterozygous carriers. Neuropsychol Dev Cogn Sct C Child Neuropsychol. 7(1):54-8, 2001 5. Johannsen P et al: Dementia with impaired temporal glucose metabolism in late-onset MLD. Dement Geriatr Cogn Disord. 12(2):85-8, 2001 6. Parmeggiani A et al: Sneddon syndrome, arylsulfatase A pseudodeficiency and impairment of cerebral white matter. Brain Dev. 22(6):390-3, 2000 7. Faerber EN et al: MRI appearances of metachromatic leukodystrophy. Pediatr RadioI29(9):669-72, 1999 8. Fukutani Y et al: Adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia. Psychiatry Clin Neurosci. 53(3):425-8, 1999 9. Kim TS et al: MR of childhood metachromatic leukodystrophy. AJNR18:733-8, 1997 10. Gieselmann V et al: Molecular genetics of metachromatic leukodystrophy. Hum Mut 4(4):233-42, 1994 11. Stillman AEet al: Serial MR after bone marrow transplantation in two patients with metachromatic leukodystrophy. AJNRAmJ Neuroradiol. 15(10):1929-32, 1994

Metabolic/Degenerative Disorders, Inherited

METACHROMATIC LEUKODYSTROPHY

I IMAGE

(MLD)

GALLERY

Typical (Left) Axial T2WI MR shows

linear hypointense "tigroid pattern" of preserved perivascular myelination (arrows) (Courtesy 5. Blaser, MO). (Right) Single voxel magnetic resonance spectroscopy (MRs) of left parietal white matter in a patient with metachromatic leukodystrophy shows elevation of choline (arrow). Note the maintained NAA.

Typical

(Left) Axial FLAIRMR early in the disease course of

metachromatic leukodystrophy shows predominantly posterior distribution of periventricular bright T2 signal (arrows). (Right) Coronal T2WI MR shows preserved subcortical U-fiber myelination (arrows). Also note the confluent peritrigonal demyelination (open arrows).

Typical

(Left) Axial T2WI MR shows the advanced stage of

metachromatic leukodystrophy. Note the bi-hemispheric atrophy including passive ventricular dilatation and confluent white matter hyperintensity (arrows). (Right) Coronal T2WI MR shows cerebral atrophy, ex-vacuo ventricular dilatation, and confluent periventricular hyperintensity (demyelination). Note the involvement of subcortical U-fibers (arrows).

Metabolic/Degenerative Disorders, Inherited

9 31

KRABBE

Axial NEeT in early infantile Krabbe disease shows symmetric thalamic hyperdensity likely calcification, There is ventricular enlargement & fissural prominence secondary to volume loss,

o Late infantile-juvenile: matter involvement • CECT: No enhancement

ITERMINOlOGY Abbreviations

Axial T2WI MR of advanced Krabbe disease shows atrophy hypointense Be & thalami, as well as hyperintense deep white matter (sparing subcortical U-fibers) & posterior limb internal capsule,

and Synonyms

No cerebellar WM, deep gray

• Globoid cell leukodystrophy

MR Findings

Definitions

• TlWI o Infantile (early) • Deep, periventricular WM hypointensity • Thalami, BG hyperintensity o Infantile (late) • Hyperintensity in thalamus, BG • Diffuse WM hypo intensity • Severe progressive atrophy ~ microcephaly o Late infantile-juvenile: No cerebellar WM, BG involvement • T2WI o Infantile (early) • Hypointensity in thalamus, BG • Confluent symmetric deep periventricular WM h yperin tensity • Spares subcortical U-fibers • Cerebellum affected to a lesser degree o Infantile (late): Diffuse WM hyperintensity, end stage resembles all other dysmyelinating disease o Late infantile-juvenile: May not have cerebellar WM, BG involvement o Adult • Frequently involves corpus callosum

• Progressive autosomal-recessive degenerative leukodystrophy of CNS & PNS

I IMAGING FINDINGS General Features • Best diagnostic clue: In very early stage thalamic, basal ganglia (BG) CT hyperdensity (MRI may be normal) • Location: Thalami, BG, white matter (WM), corticospinal & pyramidal tracts, PNS

CT Findings • NECT o Infantile (early) • Symmetric hyperdensity in thalami, basal ganglia (BG), corona radiata, cerebellum • Deep, periventricular WM hypodensity o Infantile (late) • Symmetric punctate WM calcifications • Diffuse low density in periventricular WM • Atrophy develops ~ microcephaly

DDx: CT Hyperdense/T2

Hypointense Thalami

9

• ..! -

u,·

-

••

r

1

-~

32 "

l NCL

GM2 Gangliosidosis

Metabolic/Degenerative

,f-' .. . '.. ,.

"c

," .-. ~ . a ""_'-..-. _~i "

.. ..

.

GM2 Gangliosidosis

Disorders, Inherited

Status Marmoratus

KRABBE Key Facts Terminology • Progressive autosomal-recessive degenerative leukodystrophy of CNS & PNS

Imaging Findings • Best diagnostic clue: In very early stage thalamic, basal ganglia (BG) CT hyperdensity (MRI may be normal)

Top Differential

Diagnoses

• Neuronal ceroid lipofuscinosis (NCL) • GM2 gangliosidoses (e.g., Tay-Sachs) • Status marmoratus

Pathology • Gene mapped to chromosome 14q32.1) & has been cloned

• •

• •

14 (14q24.3 to

• Posterior hemispheric WM hyperintensity along precentral (motor) gyri & corticospinal tracts • Optic nerve hypertrophy FLAIR: Better delineates abnormal T2 affects DWI o High ADC within affected WM which worsens with disease progression o Diffusion tensor-derived anisotropy maps ~ loss of diffusion anisotropy • Relative anisotropy (RA) differences found in BG, middle cerebellar peduncles, internal capsule, corpus callosum, periventricular WM • After stem cell transplantation, mean RA between RA of untreated patients & control subjects • May be a marker of treatment response T1 C+: Infantile (late): Enhancing rim between abnormal WM and unaffected U-fibers MRS o Infantile: Pronounced 1 choline, myo-inositol; moderate NAA reduction; mild lactate accumulation o Late infantile-juvenile: 1 Choline, myo-inositol; mild NAA reduction o Adult: Mild 1 choline & myo-inositol, may be close to normal

Imaging Recommendations • Best imaging tool: MRI + FLAIR • Protocol advice: Consider DWI + DTI

I DIFFERENTIAL DIAGNOSIS Neuronal ceroid lipofuscinosis (NCL) • Inherited neurodegenerative disorders associated with accumulation of abnormal pigment lipofuscin • Hypointense/hyperdense thalami & putamina; hyperintense periventricular WM

GM2 gangliosidoses

(e.g., Tay-Sachs)

• Lysosomal lipid storage disorders caused by mutations in at least 1 of 3 recessive genes: HEXA, HEXB, GM2A • Hypointense/hyperdense thalami; patchy hyperintense WM

Metabolic/Degenerative

• Gene defects result in deficiency of lysosomal galactosylceramidase I (aka gal acto cerebroside S-galactosidase) • Results in accumulation of psychosine 100x normal concentrations • Psychosine is toxic to brain, esp oligodendroglia ~ destruction of oligodendrocytes

Clinical Issues • Neonatal: Most common symptom is extreme irritability • Seizures result in medical attention • Diagnosis made from leukocyte or skin fibroblast S-galactosidase assay • Molecular assay available for genetic counseling, prenatal testing • Neonatal: Rapidly progressive, few live> 2 yrs

Status marmoratus • End result of acute near-total asphyxia • BG & thalami develop chronic pathologic lesion termed "status marmoratus" • Lesions have "marble-like" appearance 2° neuronal loss, gliosis, & hypermyelination

I PATHOLOGY General Features • General path comments: Deficiency of normal removal process of myelin breakdown products • Genetics o Autosomal recessive lysosomal disorder o Gene mapped to chromosome 14 (14q24.3 to 14q32.1) & has been cloned • Different mutations associated with differing severity for both age of onset & progression • Later onset (e.g., adult) has milder phenotype likely from a lesser degree of enzyme deficiency • Solitary mutation in 40-50% of infantile cases with European, Mexican ancestry • 65 mutations & polymorphic changes described • Majority of adult form mutations occur at 5' end of the gene; infantile cases cluster at 3' end • Gene polymorphisms I in vitro expression & may in part be responsible for pseudodeficiency states • Phenotype variation between homozygotes within same sibship has been reported • Sibship variation may not be a function of mutation alone but also from differing rates of psycho sine turnover o Sulfotransferase may also be deficient ~ suggests galactosylceramide degradation may be complex • Etiology o Gene defects result in deficiency of lysosomal galactosylceramidase I (aka galactocerebroside S-galactosidase) • Normally aids in cleavage of galactose from psychosine & galactosylceramide, leaving sphingosine & cerami de respectively

Disorders,

Inherited

9 33

KRABBE • Galactosylceramidase II & III can catalyze galactosylceramide but not psychosine • Results in accumulation of psychosine 100x normal concentrations • Psycho sine is toxic to brain, esp oligodendroglia ~ destruction of oligodendrocytes • Mechanism by which psychosine causes demyelination & dysmyelination is unclear o Accumulation of psycho sine causes: • Up-regulation of AP-1, a pro-apoptotic pathway • Down-regulation of NF-kappaB pathway, an antiapoptotic pathway • Epidemiology o 6:1,000 in the Druze community in Israel o 1:25-50,000 in Sweden; 1:100,000 US & Europe • Associated abnormalities o Protruding ears o Adult: Lumbosacral nerve root enhancement may accompany or precede intracranial findings

Gross Pathologic & Surgical Features • Small, atrophic brain

Microscopic

Features

• Myelin loss with astrogliosis & dysmyelination • Severe oligodendrocyte loss • Perivascular large multinucleated "globoid" and mononuclear epithelioid cells in demyelinated zones • "Globoid" cells = macrophages containing PAS-positive galactocerebrosides • Demyelination is marked within cerebrum, cerebellum, brain stem, spinal cord with segmental involvement of peripheral nerves • "Globoid" cells identified in enlarged optic nerves • "Globoid" cell inclusions in sweat gland epithelial cells

• Visual failure, cerebellar ataxia, spasticity, polyneuropathy, dementia, psychosis o Adult • Hemiparesis, spastic paraparesis, cerebellar ataxia, intellectual impairment, visual failure, peripheral polyneuropathy, talipes cavus • Clinical profile o Diagnosis made from leukocyte or skin fibroblast B-galactosidase assay o Molecular assay available for genetic counseling, prenatal testing

Demographics • Gender: M = F • Ethnicity: Most reported cases have European ancestry, but can affect all

Natural History & Prognosis • Neonatal: Rapidly progressive, few live> 2 yrs o Motor deterioration ~ quadriparesis, decerebrate o Hypertonicity becomes flaccidity as PNS involved o Blindness • Infantile-juvenile: More protracted course, slower rate of progression • Adult: Heterogeneous, progresses more slowly o MRI may remain normal for many years, even in presence of symptoms • Sequelae (e.g., infection) cause most deaths

Treatment • Hematopoietic stem cell transplantation o Halts disease progression in mild forms of Krabbe o Both clinical & radiologic manifestations may reverse or retard • Gene therapy for Krabbe (as well as all lysosomal storage disorders) holds promise

Staging, Grading or Classification Criteria • Infantile: Before age 2 o Most common & most severe o Onset 1st year of life, usually 3-6 mos o Variants: Irritative-hypertonic, neonatal feeding abnormality, hemiplegic, prolonged floppy • Late infantile-juvenile: After age 2 o Considerable biochemical, clinical variations o Variants: Visual failure, cerebellar ataxia, spastic-onset, acute polyneuropathy, dementia-psychosis • Adult: After age 10 o Corticospinal, pyramidal tract symptoms o Mimics a peripheral neuropathy o Often undiagnosed for many years

I SELECTED REFERENCES 1.

2. 3. 4.

5.

6.

I CLINICAL ISSUES

9 34

7.

Presentation • Most common signs/symptoms o Neonatal: Most common symptom is extreme irritability • Seizures result in medical attention • Hypersensitivity to sensory stimuli (e.g., hyperacusis), fevers, feeding problems, failure to thrive, optic atrophy, cortical blindness o Infantile-juvenile

Metabolic/Degenerative

8.

9.

Haq E et al: Molecular mechanism of psycho sine-induced cell death in human oligodendrocyte cell line. J Neurochem. 86(6):1428-40, 2003 Henderson RD et al: Adult onset Krabbe disease may mimic motor neurone disease. J Clin Neurosci. 10(5):638-9,2003 Suzuki K: Globoid cell leukodystrophy (Krabbe's disease): update. J Child Neurol. 18(9):595-603, 2003 Brockmann K et al: Proton MRS profile of cerebral metabolic abnormalities in Krabbe disease. Neurology. 60(5):819-25, 2003 Bajaj NP et al: Adult onset of Krabbe's disease resembling hereditary spastic paraplegia with normal neuroimaging. J Neurol Neurosurg Psychiatry. 72(5):635-8, 2002 Giri S et al: Galactosylsphingosine (psychosine)-induced expression of cytokine-mediated inducible nitric oxide synthases via AP-1 and C/EBP: implications for Krabbe disease. FASEBJ. 16(7):661-72, 2002 Jatana M et al: Apoptotic positive cells in Krabbe brain and induction of apoptosis in rat C6 glial cells by psychosine. Neurosci Lett. 330(2):183-7, 2002 Guo AC et al: Evaluation of white matter anisotropy in Krabbe disease with diffusion tensor MR imaging: initial experience. Radiology. 218(3):809-15, 2001 Farina L et al: MR imaging and proton MR spectroscopy in adult Krabbe disease. AJNR Am J Neuroradiol. 21(8):1478-82,2000

Disorders, Inherited

KRABBE

I IMAGE GALLERY Typical (Left) Coronal T2WI in late stage Krabbe shows atrophy plus hypointense Be, thalami, & dentate nuclei. Note hyperintense periventricular, temporal, & cerebellar white matter, sparing subcortical U-fibers. (Right) Axial OTi of Krabbe shows severe anisotropy loss (e.g., frontal white matter (arrows), splenium (open black)). Note some external capsule anisotropy (open white) & poor gray/white distinction.

Typical (Left) Axial FLAIR MR in juvenile-onset Krabbe disease demonstrates characteristic symmetric hyperintensity (demyelination) in parietal white matter, sparing subcortical U-fibers. (Right) Axial FLAIR MR in juvenile-onset Krabbe disease reveals symmetric hyperintensity of bilateral corticospinal tracts (arrows).

Typical (Left) Coronal T2WI MR in adult-onset Krabbe disease shows bilateral precentral (motor) gyri white matter hyperintensity sparing subcortical U-fibers with associated focal atrophy (arrows). (Right) Axial T2WI MR in adult-onset Krabbe disease shows bilateral precentral/deep frontal white matter hyperintensity with focal atrophy. This extended into corticospinal, pyramidal tracts (not shown).

9 35

Metabolic/Degenerative

Disorders, Inherited

ZELLWEGER

Axial T2WI MR shows patchy bi-hemispheric demyelination (arrows), hyperintense subependymal germinolytic cysts (open arrow), and abnormal left sylvian fissure operculization (curved arrow).

ITERMINOlOGY Abbreviations

and Synonyms

• Zellweger syndrome,

cerebrohepatorenal

syndrome

Definitions • Neonatal leukodystrophy failure

IIMAGING

resulting from peroxisome

Single voxel MRS using PRESS short TE (35 mSec) technique, reveals prominent peaks in the lipid and lactate range (arrows) in a patient with Zellweger syndrome (Courtesy C. Clasier, MO).

• T2WI o Cortical and cerebellar malformations • Microgyria, polymicrogyria, pachygyria o Hyperintense WM and germinolytic cysts • MRS: I NAA, 1 lipids and lactate

Imaging Recommendations • Best imaging tool: MRI, d-MRI, & MRS • Protocol advice: 3D SPGR for cortical malformations, FLAIR for germinolytic cysts

FINDINGS

General Features

IDIFFERENTIAL DIAGNOSIS

• Best diagnostic clue: Caudothalamic germinolytic cysts, demyelination, microgyria • Location: Microgyria more common in the frontal and temporal regions

• Cerebellar malformations

Radiographic Findings

• Heralds with hepatomegaly

• Radiography: High forehead, macrocephaly, anterior fontanel

large

CT Findings • NECT: Hypoplastic supraorbital cysts, simplified gyral pattern

ridges, subependymal

DDx: Zellweger

syndrome more common

Infantile Refsum disease and jaundice

Congenital CMV • Periventricular demyelination and Ca++ • ± Subependymal cysts, ± cortical malformation

Pseudo-TORCH • Progressive cerebral and cerebellar demyelination • Basal ganglia, thalamic and periventricular Ca++

MR Findings • Tl WI: Profound hypomyelination, subependymal cysts

Pseudo-Zellweger

hypointense

Neonatal adrenoleukodystrophy • Lacks facial dysmorphism

Mimics

9 36

Pseudo-Zellweger

Infantile Refsum

Metabolic/Degenerative

Congenital CMV

Disorders, Inherited

Pseudo-TORCH

ZELLWEGER Key Facts Imaging Findings

Top Differential

• Best diagnostic clue: Caudothalamic germinolytic cysts, demyelination, microgyria • Radiography: High forehead, macrocephaly, large anterior fontanel • Microgyria, polymicrogyria, pachygyria • MRS: ~ NAA, t lipids and lactate • Protocol advice: 3D SPGR for cortical malformations, FLAIRfor germinolytic cysts

• • • • •

Diagnoses

Pseudo-Zellweger syndrome Infantile Refsum disease Congenital CMV Pseudo-TORCH Neonatal adrenoleukodystrophy

Diagnostic Checklist • Consider Zellweger syndrome in floppy neonate with elongated forehead

I PATHOLOGY

Image Interpretation

General Features

• Germinolytic cysts, demyelination malformations

• General path comments: Peroxisomal failure: Defective transport of proteins into peroxisomal matrix - accumulation of very long chain fatty acids • Genetics: Autosomal-recessive, possible PEX 13 gene inactivation • Etiology: Peroxisomal failure • Associated abnormalities o Eye abnormalities: Brushfield spots, retinal pigment degeneration o Hepatomegaly (78%), renal cortical cysts (97%) o Skeletal: Stippled chondral calcification

1.

2. 3.

4.

Microscopic

cortical & cerebellar malformations

Features

5.

• Pachygyria, polymicrogyria, or microgyria • Sudanophilic leukodystrophy

6. 7.

[CLINICAL ISSUES Presentation • Most common signs/symptoms o Dysmorphism: High forehead, hypoplastic supraorbital ridges o Myopathic weakness, seizures, optic atrophy • Clinical profile: Low Apgar scores, very floppy, dysmorphic facies

and cortical

I SELECTED REFERENCES

Gross Pathologic & Surgical Features • Demyelination,

Pearls

Barth PG et al: Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival. Neurology. 62(3):439-44, 2004 Caceres-Marzal C et al: Zellweger syndrome. Reports on two new cases. Rev Neurol. 36(11):1030-4, 2003 Brosius U et al: Cellular and molecular aspects of Zellweger syndrome and other peroxisome biogenesis disorders. Cell Mol Life Sci. 59(6):1058-69, 2002 Groenendaal F et al: Proton magnetic resonance spectroscopy (lH-MRS) of the cerebrum in two young infants with Zellweger syndrome. Neuropediatrics. 32(1):23-7, 2001 Stone JA et al: MR in a patient with Zellweger syndrome presenting without cortical or myelination abnormalities. A]NR. 19(7):1378-9, 1998 Barkovich AJ et al: MR of Zellweger syndrome. AJNR 18(6):1163-70, 1997 Faust PL et al: Targeted deletion of the PEX2 peroxisome assembly gene in mice provides a model for Zellweger syndrome, a human neuronal migration disorder. J Cell BioI 139:1293, 1997

I IMAGE GALLERY

Demographics • Age: Onset shortly after birth • Gender: More common in males

Natural History & Prognosis • Average life span 12.5 weeks

Treatment • No proven definitive treatment • Early administration of docosahexaenoic

9

acid (DHA) (Left) Axial T2WI MR shows caudotha/amic groove cysts (arrows)

I DIAGNOSTIC

CHECKLIST

Consider

and demyelination in a Zellweger syndrome patient. Also note the perisylvian polymicrogyria (open arrows). (Right) Coronal T2WI MR of Zellweger syndrome demonstrates small germinolytic cysts (arrows).

• Consider Zellweger syndrome in floppy neonate with elongated forehead

Metabolic/Degenerative Disorders, Inherited

37

X-LINKED ADRENOLEUKODYSTROPHY

Axial graphic illustrates typical layers of involvement in classic childhood cerebral X-ALD. The intermediate zone of inflammaUon (arrows) enhances and moves peripherally with progression.

ITERMINOLOGY Abbreviations

and Synonyms

• X-linked adrenoleukodystrophy (X-ALD): Severe progressive form usually affecting pre-teen males • Adrenomyeloneuropathy (AMN): Mild adult form, occasionally called spino-cerebellar form, up to 50% have some cerebral involvement

• Pattern: Splenium ~ peri trigonal WM ~ corticospinal tracts/fornix/commisural fibers/visual and auditory pathways • Typically spares subcortical U-fibers • Morphology o Usually symmetrical, confluent, posterior involvement; rare frontal pattern occurs o Central (splenium) to peripheral gradient is usual

CT Findings

Definitions • Inherited disorder of peroxisome metabolism ~ impaired 0-oxidation of very long chain fatty acids (VLCFA) o X-ALD and AMN account for 80% of cases o At least 6 variants other than childhood cerebral X-ALD (CCALD) exist: Pre-symptomatic X-ALD; adolescent (AdoICALD); adult (ACALD); AMN; Addison only; symptomatic female carriers

I IMAGING FINDINGS General Features • Best diagnostic clue: Enhancing (CT or MRI) peritrigonal demyelination in CCALD • Location o Classic CCALD: Peri trigonal white matter (WM)

9

Axial T1 C+ MR demonstrates intermediate zone enhancement (arrow) in a child with advanced childhood cerebral X-linked adrenoleukodystrophy.

DDx: Causes of Abnormal

• NECT o I Density splenium/posterior WM o +/- Ca++ of involved WM • CECT: CCALD: Linear enhancement of intermediate zone typical

MR Findings • Tl WI: I Tl signal of involved WM • T2WI o t T2 signal of involved WM • CCALD: Splenium ~ peritrigonal WM ~ corticospinal tracts/fornix/ commisural fibers/visual and auditory pathways • AMN: Cerebellum, spinal cord, most common intracranial feature is corticospinal involvement, but may resemble CCALD • FLAIR: Same as T2WI • DWI o Restricted diffusion in involved WM

Periventricular White Matter Signal

38

PVL Follow-up

Hypoglycemia Late

WML No Enhancement

Metabolic/Degenerative Disorders, Inherited

MLD No Enhancement

X-LINKED ADRENOLEUKODYSTROPHY Key Facts Terminology • X-linked adrenoleukodystrophy (X-ALD): Severe progressive form usually affecting pre-teen males • Inherited disorder of peroxisome metabolism => impaired B-oxidation of very long chain fatty acids (VLCFA) • X-ALD and AMN account for 80% of cases • At least 6 variants other than childhood cerebral X-ALD (CCALD) exist: Pre-symptomatic X-ALD; adolescent (AdolCALD); adult (ACALD); AMN; Addison only; symptomatic female carriers

• Pattern: Splenium => peri trigonal WM => corticospinal tracts/fornix/commisural fibers/visual and auditory pathways • Typically spares subcortical U-fibers • X-ALD: ~ NAA even in normal-appearing WM predicts progression; 1 Cho, myo-inositol (ml), lactate • Best imaging tool: MRI + contrast

Pathology • Phenotypic variability: CCALD, AMN ~ pre-symptomatic presentations even within same family

Imaging Findings

Diagnostic Checklist

• Best diagnostic clue: Enhancing (CT or MRI) peritrigonal demyelination in CCALD • Classic CCALD: Peritrigonal white matter (WM)

• X-ALD presenting at atypical ages may have atypical appearances (lack of enhancement, asymmetry, and frontal rather than posterior predominance)

o DTl: Reduced brain "connectivity", 1 isotropic diffusion and loss of fractional anisotropy in obvious WM change AND in pre-symptomatic WM • Tl C+ o Contrast-enhancement: Leading edge (intermediate zone) enhances • Contrast-enhancement strongly linked to progression • MRS o X-ALD: ~ NAA even in normal-appearing WM predicts progression; 1 Cho, myo-inositol (ml), lactate • Peaks between 0.9 and 2.4 ppm probably represent VLCFA macromolecules o AMN: ~ NAA/Cho & ~NAA/Cr in internal capsule and corticospinal tracts; ~ NAA/Cho in parieto-occipital WM • Spinal MRI: Spinal atrophy in AMN

Nuclear Medicine

Findings

• PET: Hypometabolism of occipital lobes • SPECT: 99mTc-HMPAO shows 1 in regional cerebral blood flow in enhancing zone, but decrease elsewhere

Imaging Recommendations • Best imaging tool: MRI + contrast • Protocol advice o Enhanced MRI to show typical posterior, enhancing involvement of WM o DWljDTl and MRS may predict onset of pre-symptomatic disease

I DIFFERENTIAL DIAGNOSIS Periventricular leukodystrophy • Periventricular gliosis and volume loss following hypoxia of prematurity; doesn't enhance

Neonatal hypoglycemia follow-up)

(acute and

• May involve splenium, calcar avis, and posterior peri trigonal WM, but doesn't enhance

White matter disease with lactate (WML) • Involves splenium, peri trigonal WM and corticospinal tracts, but doesn't enhance

Metachromatic

leukodystrophy

• Involves splenium/peri trigonal WM, doesn't enhance

Alexander disease • Enhances, but frontal not peri trigonal WM

I PATHOLOGY General Features • General path comments o VLCFA accumulate in all tissues of body o Symptomatic accumulation: CNS myelin, adrenal cortex, Leydig cell testes • Adrenal failure: Skin bronzing • Testes: Early androgenetic alopecia in adults • Genetics o X-ALD: X-linked recessive, Xq28; mutations ABCDI gene (> 300 described!) o Phenotypic variability: CCALD, AMN ~ pre-symptomatic presentations even within same family • Etiology o Peroxisomes ubiquitous organelles involved in catabolic pathways • Involved with myelin formation/stabilization • Defect in VLCFA importer => impaired B-oxidation VLCFA • VLCFA accumulate in WM => brittle myelin o ABCDI is ATPase transporter protein: "Traffic" ATPase, required for transport hydrophilic molecules across peroxisomal membrane o Modifying/exacerbating factors affect phenotype • Down-regulation of gene • Inflammatory/traumatic triggers • Epidemiology: X-ALD and variants: 1 per 16,800 births in North America

Metabolic/Degenerative Disorders, Inherited

9 39

X-LINKED ADRENOLEUKODYSTROPHY Gross Pathologic & Surgical Features

Demographics

• Atrophy, WM softened

• Age: CCALD: Pre-teen males • Gender o Males in classic X-ALD o Female carries may show AMN-like symptoms • Ethnicity o CCALD predominates in North America and France o AMN predominates in Netherlands

Microscopic Features • Complete myelin loss (D-fibers preserved), astrogliosis • Ca++ (late), prominent inflammatory changes • Zone specific features o Innermost zone of necrosis, gliosis and +/- Ca++ o Intermediate zone of active demyelination and inflammation o Peripheral zone of demyelination without inflammation

Staging, Grading or Classification Criteria • Loes' MRI scoring system: Severity score based upon location and extent of disease and atrophy o Pattern 1: Parieto-occipital WM (rapid progression if contrast-enhancement present and very young) o Pattern 2: Frontal WM (same as pattern 1) o Pattern 3: Corticospinal tract (adults, slower progression) o Pattern 4: Corticospinal tract and cerebellar WM (adolescents, slower progression) o Pattern 5: Concomitant parieto-occipital and frontal WM (mainly childhood, extremely rapid)

ICLINICAl

40

Treatment • CCALD: Vegetative state, death in 2-5 years w/o BMT o Lorenzo oil doesn't work o Poor results: Cholesterol-lowering drugs, dietary VLCFA restriction, glycerol trioleate/trierucate intake, plasmapheresis, interferon, immuno-ablation o Early bone marrow transplantation (BMT) stabilizes demyelination: RARE reversal demyelination

I DIAGNOSTIC

CHECKLIST

Consider

ISSUES

Presentation

9

Natural History & Prognosis • CCALD: Progresses to spastic quadriparesis, blindness, deafness, vegetative state • AMN: Spasticity, weak legs and sphincter, sexual dysfunction

• Most common signs/symptoms: Skin bronzing, behavioral difficulties, hearing problems • Clinical profile: Phenotypes unpredictable even within one affected family • Classic childhood cerebral X-ALD (CCALD): 35-50%, but percentage ~ as new forms diagnosed o Pre-teen male (3-10 years): Behavioral, learning, gait, hearing, vision difficulties o Diagnose of "Addison/adrenal insufficiency" (skin bronzing, nausea & vomiting, fatigue) may predate diagnose of X-ADL • Adrenomyeloneuropathy (AMN) (25%) o 14-60 years o Spinal involvement> > brain involvement; peripheral nerve involvement o Brain inflammatory reaction eventually in 50% o Brain MRI: Variable pattern demyelination, enhancement (especially corticospinal tracts) • Pre symptomatic ALD (12%) o Abnormal genetic testing (due to known symptomatic brother or maternal uncle), but normal imaging, symptom free • 20-50% female carriers show AMN-like symptoms o Symptomatic due to skewed X-inactivation, but milder, late onset • Other presentations less common o AdolCALD: 10-20 years, symptoms and course similar to CCALD o ACALD: May be misdiagnosed as psychiatric disorder; very rapid progression; diffuse rather than posterior pattern

Metabolic/Degenerative

• X-ALD presenting at atypical ages may have atypical appearances (lack of enhancement, asymmetry, and frontal rather than posterior predominance)

Image Interpretation

Pearls

• Always enhance the unknown leukodystrophy/leukoencephalopathy

I SELECTED REFERENCES 1.

2.

3.

4.

5. 6.

7.

8.

Mo YH et al: Adrenomyeloneuropathy, a dynamic progressive disorder: brain magnetic resonance imaging of two cases. Neuroradiology, 2004 Fatemi A et al: MRI and proton MRSI in women heterozygous for X-linked adrenoleukodystrophy. Neurology 60(8):1301-7, 2003 Schneider JF et al: Diffusion tensor imaging in cases of adrenoleukodystrophy: Preliminary experience as a marker for early demyelination. 24(5):819-24, 2003 Loes DJ et al: Analysis of MRI patterns aids prediction of progression in X-linked adrenoleukodystrophy. Neurology 61(3):369-74,2003 Eichler FS et al: Proton MRS and DTI brain MRI in X-ADL: Initial experience. Radiology 225(1):245-52, 2002 Melhem ER et al: X-linked adrenoleukodystrophy: the role of contrast-enhanced MR imaging in predicting disease progression. AJNR 21(5):839-44, 2000 van Geel et al: X-linked adrenoleukodystrophy: Clinical presentation, diagnosis, and therapy. J of Neurol Neurosurg Psychiatry 63(1):4-14, 1997 Kumar AJ et al: MR findings in adult-onset adrenoleukodystrophy. AJNR 16(6):1227-37, 1995

Disorders, Inherited

X-LINKED ADRENOLEUKODYSTROPHY

I IMAGE

GALLERY

Typical (Left) Axial FLAIR MR in early X-linked adrenokukodysuophyshows focal demyelination of the splenium of the corpus callosum (arrow). (Right) Axial Tl C+ MR in the same child demonstrates intense focal enhancement (arrow) of the mid portion of the splenium of the corpus callosum.

Typical (Left) Axial FLAIR MR in a child with more advanced X-linked adrenokukodysuophyshows extension of abnormal signal from the splenium to the peritrigonal white matter (arrow). (Right) Sagittal TlWI MR in the same child demonstrates volume loss and low signal (arrow) of the involved splenium of the corpus callosum.

Typical (Left) Axial PO/Intermediate MR in another child shows classic advanced demyelination of splenium, peritrigonal WM, pulvinar (open arrow) and posterior aspects of the internal and external capsules (arrows). (Right) Axial T1WI MR in the same child shows increased signal of the leading edge of demyelination (arrows) and focal Ca++ (open arrow) of the peritrigonal white matter.

9 41

Metabolic/Degenerative Disorders, Inherited

MAPLE SYRUP URINE DISEASE

Axial T2WI MR in an encephalopathic one week old infant shows intense cerebellar and brainstem edema. The dentate nuclei (arrows) and cerebellar white matter are involved.

Axial OWl MR shows restricted diffusion of affected cerebellum and brainstem in the same infant diagnosed with maple syrup urine disease.

ITERMINOLOGY

CT Findings

Abbreviations

• NECT o Early: Diffuse edema NOT sparing brainstem and cerebellum • Recognize here for best neurocognitive outcome o Subacute: Rapid formation of typical (classic) MSUD edema pattern • Subacute: Cerebral peduncles, dorsal brainstem and cerebellar edema> supratentorial hemispheres • Margins become sharp during subacute phase

and Synonyms

• Maple syrup urine disease (MSUD) • Leucine encephalopathy

Definitions • MSUD is an inherited disorder of branched chain amino acid metabolism presenting in newborns with neurologic deterioration, ketoacidosis and hyperammonemia

MR Findings

I IMAGING FINDINGS General Features • Best diagnostic clue o The radiologist may be first to suggest diagnosis based on classic appearing MSUD edema • Cerebellar white matter, brain stem, globus pallidus • Thalamus, cerebral peduncles, corticospinal tracts (to cortex) • Location o Cerebellar and brainstem edema> supratentorial hemispheres o Edema of corticospinal tracts

DDx: Other Metabolic

• Tl WI: l Signal intensity, margins may be sharp • T2WI o Late: Generalized and MSUD edema disappear • Resolve to "pallor" and volume loss • FLAIR: Insensitive to fluid shifts in the newborn • DWI o Marked restriction (t intensity) and l ADC (MSUD edema = cytotoxic/intramyelinic) o DTI: l Anisotropy • MRS: Broad peak at chemical shift of 0.9 ppm

Ultrasonographic

Findings

• Real Time: t Echogenicity of globus pallidi, periventricular white matter, and areas typically involved by MSUD edema

Causes of Brainstem Swelling

9 42

Surf 7 Mutation

Mitochondrial

Alexander Enhances

Metabolic/Degenerative Disorders, Inherited

Vanishing WM

MAPLE SYRUP URINE DISEASE Key Facts Terminology

• Hexachlorophene

• Maple syrup urine disease (MSUD) • MSUD is an inherited disorder of branched chain amino acid metabolism presenting in newborns with neurologic deterioration, ketoacidosis and hyperammonemia

Clinical Issues

Imaging Findings • The radiologist may be first to suggest diagnosis based on classic appearing MSUD edema • Protocol advice: MRI with diffusion-weighted imaging best, but CT can make diagnosis in critically ill infant

Top Differential

Diagnoses

• Disorders causing brain stem and cerebellar swelling • Hypoxic-ischemic encephalopathy

• Patients in crisis often (but not always) smell like maple syrup (or burnt sugar) • MSUD has a potentially favorable outcome with strict dietary control and aggressive treatment of metabolic crises • May survive to adulthood if well controlled • Metabolic "intoxication" AT ANY AGE may be provoked by infection, injury, stress, fasting, or even pregnancy

Diagnostic Checklist • Neonatal testing for MSUD is NOT universal • Neonatal brain edema which includes the posterior fossa and brain stem is highly suggestive of MSUD

Imaging Recommendations • Best imaging tool: Diffusion-weighted imaging during the hyperacute phase • Protocol advice: MRI with diffusion-weighted imaging best, but CT can make diagnosis in critically ill infant

I DIFFERENTIAL DIAGNOSIS

•

•

Disorders causing brainstem and cerebellar swelling • Mitochondrial SURF1 mutations: Lactate may be seen in this AND in MSUD during crisis • Alexander disease: Abnormal signal and enhancement of brainstem and aqueduct • Vanishing white matter: Findings are persistent

Hypoxic-ischemic

encephalopathy

• No symptom free interval, usually positive history • Cerebellum, brain stem relatively spared (MSUD involves these areas)

Hexachlorophene

toxicity

• Myelin splitting disorder described in premature babies washed in hexachlorophene in 1960s & 70s • No imaging available

Machiafavi- Bignami • Myelin splitting disorder of adult red-wine drinkers • Splits corpus callosum

I PATHOLOGY General Features • General path comments o Maternal ingestion of fenugreek during labor gives false impression of MSUD • Shares a component, and smell, with urine of MSUD o Embryology-anatomy

toxicity

• •

• Involves early myelinated areas (myelin splitting disease, spares areas where myelin isn't present) Genetics o > 50 different mutations in genes governing enzyme components of branched-chain (){-ketoacid dehydrogenase complex (BCKD) • For example, E1(){(33%), Ell3 (38%), E2 (19%) o Autosomal recessive Etiology o Branched chain organic aciduria result from abnormalities of enzyme catabolism of branched chain amino acids (leucine, isoleucine, valine) o MSUD: i Activity BCKD ~ accumulation of branched-chain L-amino (BCAA) and metabolites (neurotoxic) o Accumulation of leucine in particular causes neurological symptoms o i Plasma isoleucine associated with maple syrup odor Epidemiology: 1:850,000 general population; but as frequent as 1:170 in population isolates Associated abnormalities: i Leucine impairs cell volume regulation ~ brain edema; muscle, liver and pancreatic edema

Gross Pathologic & Surgical Features • Brainstem edema • Spongy degeneration ganglia

of white matter and basal

Microscopic Features • i Oligodendrocytes and astrocytes • Alterations in neuronal migration, maturation o Aberrant orientation of neurons o Abnormal dendrites/dendritic spines

9

Staging, Grading or Classification Criteria

43

• Classical, intermediate, and intermittent MSUD; thiamine responsive MSUD

Metabolic/Degenerative Disorders, Inherited

forms of

MAPLE SYRUP URINE DISEASE

I CLINICAL

ISSUES

Presentation • Most common signs/symptoms o Initial symptoms of classic MSUD: Poor feeding, vomiting, poor weight gain, increasing lethargy • In neonates develop within 4-7 days o Patients in crisis often (but not always) smell like maple syrup (or burnt sugar) • Resuscitation with non-protein containing oral or IV hydrating fluids may "clear" the odor • Maple syrup odor may be difficult to identify in first days of life unless urine soaked diaper is allowed to dry • Maple syrup odor of cerumen said to be more predictable o Neonates in communities with known high risk of MSUD may be diagnosed within hours of blood sampling • If tested AND receive immediate results AND therapy is instituted => excellent outcome • Tandem mass spectrometry of whole blood filter paper shortens diagnosis time • Guthrie test insensitive before 24 hours, requires incubation period and has high false positive rate • Clinical profile o Normal at birth o Presents after disease free interval, usually within the first 48 hours to 2 weeks of life o Mimic of sepsis: Acute encephalopathy, vomiting, seizures, neurological distress, lethargy, coma, leukopenia/thrombopenia • Additionally free water retention, renal salt wasting and hyponatremia, dehydration o Plasma detection of alloisoleucine diagnostic for MSUD • May not appear until 6th day of life o Ketosis or ketoacidosis and hyperammonemia o Typical EEG: "Comb-like-rhythms" o Prenatal diagnosis can be performed on cultured amniocytes or chorion villus cells

Demographics

Natural History & Prognosis

44

Treatment • Acute "metabolic rescue" to reverse cerebral edema • May require hemodialysis during acute crisis to limit neurotoxicity/damage • Metabolically appropriate diet (protein-modified) minimizes severity o Inhibit endogenous protein catabolism while sustaining protein synthesis o Prevent deficiencies of essential amino acids o Maintain normal serum osmolarity o Dietary therapy must be lifelong o Commercially available formulas, foods are available without branched-chain amino acids or with reduced levels of branched-chain amino acids • Neonatal screening (tandem mass spectrometry) can diagnose • Orthotopic liver transplantation increases availability of BCKD (rarely used) • Gene therapy experimental

I DIAGNOSTIC

CHECKLIST

Consider • Neonatal testing for MSUD is NOT universal • Not all MSUD occurs in population isolates • Even if testing performed, results may be available only after 1 to 2 weeks in non-endemic areas

Image Interpretation

Pearls

• Neonatal brain edema which includes the posterior fossa and brainstem is highly suggestive of MSUD

• Age: May be diagnosed on day 1 of life if MSUD suspected • Ethnicity o 1/170 live births in certain population isolates (founder effect in old order Mennonites) o High carrier rate in Middle East and Ashkenazi Jewish decendents

9

o Pretreatment plasma leucine> 40 mg/100 mL OR encephalopathy> days associated with a poor cognitive outcome • May survive to adulthood if well controlled o Metabolic "intoxication" AT ANY AGE may be provoked by infection, injury, stress, fasting, or even pregnancy • Reports of late (adulthood) development peripheral neuropathy • Exfoliative skin and corneal lesions from inadequate amino-acid intake

• Breast feeding may delay onset of symptoms to second week of life • MSUD has a potentially favorable outcome with strict dietary control and aggressive treatment of metabolic crises o Response to therapy can be variable o Exposure to high levels branched chain amino acids (BCAA)and their metabolites neurotoxic o Uncontrolled BCAAlevels lead to profound cognitive impairment/death

Metabolic/Degenerative

I SELECTED REFERENCES 1.

2.

3.

4. 5.

6.

Parmar H et al: Maple syrup urine disease: Diffusion-weighted and diffusion-tensor magnetic resonance imaging findings. J Com put Assist Tomogr 28(1):93-7, 2004 Henneke M et al: Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease. Hum Mutat 22(5):417,2003 Morton DH et al: Diagnosis and treatment of maple syrup disease: A study of 36 patients. Pediatrics 109(6):999-1008, 2002 Fariello G et al: Cranial ultrasonography in maple syrup urine disease. ANR 17(2):311-5, 1996 van der Knaap MS et al: Maple syrup urine disease, Ch. 35 in Magnetic resonance of myelin, myelination, and myelin disorders, 2nd edition, 211-5; Springer-Verlag Berlin, 1995 Brismar J et al: Maple syrup urine disease: Findings on CT and MR. AJNR 11(6):1219-28, 1990

Disorders, Inherited

MAPLE SYRUP URINE DISEASE jlMAGE GALLERY Tvpical (Left) Axial NEeT shows sharply demarcated maple syrup urine disease pattern of edema in the cerebellar white matter and dorsal brainstem. (Right) Axial TlWI MR shows crisply demarcated low signal intensity in same distribution.

(Left) Axial NECT in the same infant shows expected involvement of mesencephalon and contiguous cerebral peduncles (arrow). There is supratentorial white matter edema, although to a much lesser degree. (Right) Axial T2WI MR in same infant shows dorsal mesencephalon involvement (arrow) in addition to involvement of the cerebral peduncle (open arrow).

Typical (Left) Axial T2WI MR shows globus pallidus, internal capsule, and ventral thalamic increased signal intensity of maple syrup urine disease. (Right) Axial TlWI MR in follow-up at 9 months of age shows delay in white matter myelination. Note the lack of myelin arborization of the frontal lobes (arrow).

9 45

Metabolic/Degenerative

Disorders, Inherited

UREA CYCLE DISORDERS

Axial TlWI MR shows high signal in lentiform nuclei and occipital cortex with underlying malacia compatible with infarctions and hemorrhage.

Axial T2WI MR shows infarctions in the lentiform nuclei, temporal and occipital lobes. Atrophy is also present.

ITERMINOlOGY

MR Findings

Abbreviations

• TlWI o CPSD/OTD: 1 Signal in deep gray nuclei and insular/perirolandic cortex o Ulegyria o Preservation of posterior fossa structures • T2WI o CPSD/OTD: 1 Signal in deep gray nuclei and insular/perirolandic cortex o Diffuse brain edema, infarctions o Chronic: Symmetric subcortical cysts • MRS o 1 Glutamine/glutamate o I Myoinositol on short TE o Presence of lipids/lactate

and Synonyms

• Carbamyl phosphate synthetase deficiency (CPSD), ornithine transcarbamylase deficiency (OTD), argininosuccinate synthetase/ligase deficiencies (ASD/ALD), arginase deficiency (AD, citrullinemia)

Definitions • Urea cycle incorporates nitrogen ~ urea (water soluble ~ excreted in urine) preventing accumulation of toxic nitrogen products • Each of 5 disorders represents an enzyme deficiency

I IMAGING FINDINGS

Imaging Recommendations

General Features • Best diagnostic clue: Neonatal encephalopathy with brain swelling, 1 urine ammonia, respiratory alkalosis, 1 plasma glutamine/alanine • Location: Deep gray nuclei, frontal and insular cortex

CT Findings • NECT o Subcortical hypodensities, o Atrophy

• Best imaging tool: MRI • Protocol advice: Noncontrast

brain MRI

IDIFFERENTIAL DIAGNOSIS Other causes of neonatal infarctions

infarctions,

edema

• Abruptio placenta, PRES, sagittal sinus thrombosis

Inherited disorders • Organic acidurias, disorders of fatty acid oxidation

9

DDx: Infarctions in Neonates

46

Abruptio Placenta

MELAS

PRES

Metabolic/Degenerative Disorders, Inherited

Sag Sinus Thrombi

UREA CYCLE DISORDERS Key Facts Terminology

• Diffuse brain edema, infarctions

• Carbamyl phosphate synthetase deficiency (CPSD), ornithine transcarbamylase deficiency (OTD), argininosuccinate synthetase/ligase deficiencies (ASD/ALD), arginase deficiency (AD, citrullinemia)

Top Differential

Imaging Findings

Clinical Issues

• Best diagnostic clue: Neonatal encephalopathy brain swelling, t urine ammonia, respiratory alkalosis, t plasma glutamine/alanine

Non-inherited

with

disorders

• Transient hyperammonemia, liver failure

• Progressive neurologic deterioration • 100% death if untreated (! mortality in older pts)

Demographics sepsis, herpes simplex,

• Age: Mostly neonates

Natural History & Prognosis • Progressive neurologic deterioration o 100% death if untreated (! mortality in older pts) • Severe neurological deficits in survivors

I PATHOLOGY General Features • General path comments: Assay for deficient enzyme from liver cells/erythrocytes • Genetics o All are autosomal recessive except OTD (X-linked) • CPSD: 2p, ASD: 9p, ALD: 7p, AD: 6p o Heterozygous OTD female ~ may have no symptoms • Etiology o Symptoms due to high levels of ammonia resulting in conversion of glutamate ~ glutamine in astrocytes o High osmolality ~ swelling, intracranial hypertension, cerebral hypoperfusion • Epidemiology o Types: Neonatal (t common), infancy, child, adult • Manifest in periods of diet with t protein content or t catabolism • Types determined by onset of symptoms not by prognosis o OTD is most common

Gross Pathologic & Surgical Features • Brain swelling, necrosis,. spongiform

Microscopic

Diagnoses

• Other causes of neonatal infarctions • Inherited disorders • Non-inherited disorders

Treatment • Liver transplant (uncertain benefit ), dialysis • Sodium benzoate/sodium phenylbutyrate • ! Protein intake, replace with essential amino acids

I

DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Consider urea cycle disorder in child with extensive temp oro-parietal and basal ganglia infarctions

I SELECTED REFERENCES L

2.

3. 4.

Kleppe S et al: Urea cycle disorders. Curr Treat Options Neurol5: 309-19, 2003 Takanashi J et al: Brain MR imaging in neonatal hyperammonemic encephalopathy resulting from proximal urea cycle disorders. AJNR, 24: 1184-87,2003 Leonard JV et al: Urea cycle disorders. Semin Neonatal, 7: 27-35,2002 Choi CG et al: Localized proton MR spectroscopy in infants with urea cycle defect. AJNR, 22: 834-37, 2001

changes in cortex

Features

• Alzheimer type II astrocytes • Splitting/vacuolation of myelin

I IMAGE GALLERY

I CLINICAL ISSUES Presentation • Most common signs/symptoms o May be normal at birth o Develop encephalopathy after 24-48 hours o Progressive lethargy, hypothermia, vomiting, apnea o Coarse/friable hair o All develop hepatic insufficiency • Clinical profile o t Ammonium blood levels o Neonatal screening with tandem mass spectrometry

9 47

(Left) Axial TlWI

MR shows symmetrical infarcts in posterior frontal and parietal regions. (Right) Axial T2WI MR shows chronic infarctions in the parietal lobes and abnormal high signal in the frontal white matter.

Metabolic/Degenerative Disorders, Inherited

GLUTARIC ACIDURIA TYPE 1

Axial TlWI MR demonstrates dilated Sylvian fissures in this patient with glutaric aciduria type 7.

ITERMINOLOGY Abbreviations

CT Findings

and Synonyms

• GA 1: Glutaric acidemia type Ii mitochondrial glutaryl-coenzyme A dehydrogenase (GCDH) deficiency

Definitions • Inborn error of metabolism characterized by encephalopathic crises and resultant severe dystonic-dyskinetic movement disorder

• NECT o > 95% "cyst-like" middle cranial fossa CSF spaces, opercular extension . • Sylvian fissure widening (93%), mesencephalIc cistern widening (86%) o Early macrocephaly, late atrophy (mostly ventricular enlargement) o SDH with minimal trauma o Lenticular nuclei hypodensity • CECT: No enhancement

MR Findings

I IMAGING FINDINGS General Features • Best diagnostic clue: Wide operculae and bright basal ganglia (BG) • Location: Sylvian fissures, basal ganglia • Size: Enlarged Sylvian fissures • Morphology o Wide opercula (frontotemporal atrophy) = "bat wing" dilatation of Sylvian fissures o Child abuse mimic: Easily torn bridging veins within enlarged cerebrospinal fluid (CSF) spaces =:> subdural hematomas (SDH)

9

Axial T2WI MR in same patient shows increased signal intensity in basal ganglia as well as diffusely throughout the white matter.

• TlWI o Sylvian fissure "cyst-like" spaces isointense to CSF o Subependymal pseudocysts (disappear by 6 months) o Fronto-temporal atrophy o Delayed myelination • T2WI o 1 Signal caudate/putamina> globus pallidusi BG atrophy over time o If severe: White matter (WM), thalami, dentate nuclei may be involved • PD/Intermediate: Same as T2WI • FLAIR: Same as T2WI but "cysts" in Sylvian fissures remain hypointense

DDx: Dilated Sylvian Fissures

48

Tuberous Sclerosis

Hurler

Arachnoid

Cyst

Metabolic/Degenerative Disorders, Inherited

Arachnoid

Cysts

GLUTARIC ACIDURIA TYPE 1 Key Facts Terminology • GA 1: Glutaric acidemia type 1; mitochondrial glutaryl-coenzyme A dehydrogenase (GCDH) deficiency • Inborn error of metabolism characterized by encephalopathic crises and resultant severe dystonic-dyskinetic movement disorder • Wide opercula (frontotemporal atrophy) = "bat wing" dilatation of Sylvian fissures • Child abuse mimic: Easily torn bridging veins within enlarged cerebrospinal fluid (CSF) spaces =? subdural hematomas (SDH) • Non-accidental

Diagnoses

injury (aka child abuse)

• DWI: Acute phase: Restricted diffusion in BG and selected WM tracts; may show more extensive disease than apparent by either CT or MR • T1 C+: No enhancement • MRS o I Chol/Cr ratio, I NAA o During crisis: +/- I Lactate

Nuclear Medicine

Findings

• PET: Fluoro-2-deoxyglucose (18FDG): Silent thalamic and cortical involvement manifesting as decreased uptake with normal MRI

Imaging Recommendations • Best imaging tool: MR • Protocol advice: MRS, DWI

I DIFFERENTIAL DIAGNOSIS Non-accidental

Pathology • Autosomal recessive • Epidemiology: 1:30,000 newborns

Clinical Issues

Imaging Findings

Top Differential

• Other disorders with bilateral middle cranial fossa "cyst-like" spaces • Causes of macrocephaly

injury (aka child abuse)

• GA 1 does not cause fractures • SDH in GA 1 from torn-bridging veins in presence of large CSF, atrophy • SDH in GA 1 do not occur w/o enlarged CSF spaces • Head trauma = most common cause of death o SDH most common finding, often interhemispheric o Skull fracture subarachnoid, epidural hemorrhage o Cerebral edema, contusion(s), shear injuries

Other disorders with bilateral middle cranial fossa "cyst-like" spaces • Tuberous sclerosis o Subependymal hamartomas, cortical tubers (56%) o Heterotopic gray matter (93%), giant cell astrocytoma (15%) • Mucopolysaccharidoses o Types I-VII: Hurler, Hunter, Sanfilippo, Morquio, Scheie, Maroteaux-Lamy, Sly o Hurler (MPS type IH) • (){-L-Iduronidase gene mutation (4p16.3) • Results in excess chondroitin sulfate B

• Initially normal development • Symptomatic: Most severely handicapped, 20% die before 5 yrs • Prognosis poor if has already presented with encephalopathic crisis • Intrauterine diagnosis available • Early treatment may prevent or ameliorate symptoms and imaging

• 1:100,000; healthy at birth, during 1st year of life features become course • "Gargoyle-like": Head enlarges with prominent forehead, enlarged eyes, flattened nasal bridge, thick lips, enlarged tongue • "Idiopathic" middle cranial fossae arachnoid cysts o 5% may be bilateral, usually asymptomatic o CSF intensity; may be slightly different on FLAIR o No DWI restriction

Causes of macrocephaly • Hydrocephalus o Congenital, post-traumatic, or obstructive o Ventricular prominence out of proportion to sulci o Enlarged temporal horns, rounded frontal horns, trans ependymal CSF flow • Canavan disease o Progressive autosomal-recessive leukodystrophy o Aspartoacyclase deficiency ~ I NAA in brain, urine o Early diffuse confluent demyelination, early V-fiber involvement o MRS: Marked i of NAA o Marked hypotonia, death by end of 1st decade • Benign familial macrocephaly: Family tendency toward large head size

I

PATHOLOGY

General Features • General path comments o Embryology: Toxic effects in utero impede operculization during 3rd trimester o Mild hepatocellular dysfunction during crisis • Genetics o Autosomal recessive o GCDH gene mutations (Chr 19p13.2) result in amino acid substitutions o Multiple mutations govern varied clinical presentation • European variant (most common): Arg402-to-trp • Amish variant, riboflavin sensitive: Ala421-to-val

Metabolic/Degenerative Disorders, Inherited

9 49

GLUTARIC ACIDURIA TYPE 1 • Severe, 1% residual enzyme, symptoms despite treatment (Tx): Glu365-to-Iys o Rare adult-onset: Compound heterozygosity with a deletion and novel missense mutation • Etiology o GCDH required for metabolism of lysine, hydroxylysine & tryptophan o !GCDH =} accumulation glutaric, glutaconic & 3-0H-glutaric acid o Accumulated substances likely toxic to striate cells and white matter • Epidemiology: 1:30,000 newborns

Gross Pathologic & Surgical Features • Macrocrania, frontotemporal CSF spaces, +/- SDH • Hypo- and de-myelination

atrophy/hypoplasia;

1

• Myelin vacuolation and splitting • Excess intramyelinic fluid • Spongiform changes, neuronal loss basal ganglia

Staging, Grading or Classification Criteria • Symptomatic: Fronto-temporal atrophy, BG signal changes • Pre symptomatic: Symptom-free; lack BG changes; but CSF spaces still enlarged

I CLINICAL ISSUES Presentation

50

Natural History & Prognosis • Symptomatic: Most severely handicapped, 20% die before 5 yrs • Pre symptomatic: Many (not all) remain asymptomatic with diagnosis and therapy • Treat before first encephalopathic crisis; avoid catabolic crises • Prognosis poor if has already presented with encephalopathic crisis

Treatment

Microscopic Features

9

Demographics • Age: Generally manifests during 1st year of life • Gender: No predilection • Ethnicity: 10% carrier rate in old order Amish

• Intrauterine diagnosis available o DNA analysis: Cultured amniotic fluid cells & chorionic villi biopsy o Fetal sonography: Dilated peri-Sylvian CSF in 3rd trimester • Early treatment may prevent or ameliorate symptoms and imaging o Low-protein diet (reduced tryptophan & lysine), synthetic protein drink o Riboflavin (Vit B2) to ensure cofactor supply for GCDH o Oral carnitine replacement; gamma aminobutyric acid (GABA) analog (baclofen)

I

• Most common signs/symptoms: Acute encephalopathy, seizures, dystonia, choreoathetosis, mental retardation • Initially normal development • Acute onset group: Majority o Episodic crises follow trigger (infection, immunization, surgery) • Acute Reye-like encephalopathy, ketoacidosis, NH4, vomiting • Dystonia, opisthotonus, seizures, excessive sweating • Follow-up: Alert child (intellect preserved> > motor); rapid infantile head growth =} frontal bossing; severe dystonia • Insidious onset 25%: No precipitating crisis, still =} dystonia • Presymptomatic may remain asymptomatic: Diagnose, treat, avoid catabolic stress • Rare asymptomatic without treatment: Still frontotemporal atrophy, but normal BG • Diagnosis: Frequent long interval between presentation and Dx o Tandem mass spectrometry of newborn filter-paper blood specimens • Chromatography-mass spectroscopy of urine o Deficient or absent GCDH activity in fibroblasts o Laboratory (may be relatively normal between crises) • Metabolic acidosis/ketosis, hypoglycemia, ! carnitine • Urinary organic acids: 1 Glutaric, glutaconic and 3-0H-glutaric acid

DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Consider GA in young children with "cysts" in Sylvian fissures and abnormal basal ganglia I SELECTED 1.

2. 3.

4.

5.

6. 7. 8.

9.

REFERENCES

Elster AW: Glutaric aciduria type I: value of diffusion-weighted magnetic resonance imaging for diagnosing acute striatal necrosis. J Comput Assist Tomogr. 28(1):98-100,2004 Twomey EL et al: Neuroimaging findings in glutaric aciduria type 1. Pediatr Radiol, 2003 Kolker S et al: Adult onset glutaric aciduria type I presenting with a leukoencephalopathy. Neurology. 60(8):1399, 2003 Strauss KA et al: Type I glutaric aciduria, part 2: a model of acute striatal necrosis. Am J Med Genet. 121C(1):53-70, 2003 Strauss KA et al: Type I glutaric aciduria, part 1: natural history of 77 patients. Am J Med Genet. 121C(1):38-52, 2003 Twomey EL et al: Neuroimaging findings in glutaric aciduria type 1. Pediatr Radiol. 33(12):823-30, 2003 Al-Essa M et al: 18FDG PET scan in GA type 1. Brain Dev 20(5):295-301, 1998 Hoffman GF et al: Clinical course, early diagnosis, treatment, and prevention of disease in glutaryl-Co A dehydrogenase deficiency. Neuropediatrics 27:115-23, 1996 Brismar Jet al: CT and MR of the brain in GA type 1: A review of 59 published cases and a report of 5 new patients. AJNR 16:675-83, 1995

Metabolic/Degenerative Disorders, Inherited

GLUTARIC ACIDURIA TYPE 1 I IMAGE GALLERY Typical (Left) Axial T2WI MR shows dilated Sylvian fissures and increased signal in the lentiform nuclei and heads of caudate nuclei in this patient with glutaric aciduria type 1. (Right) Axial OWl MR in the same patient demonstrates increased signal in basal ganglia and optic radiations.

(Left) Axial CECT shows dilated Sylvian fissures and low density in basal ganglia in a glutaric aciduria type 1 patient. (Right) Axial NEeT in the same patient shows large Sylvian fissures and lateral ventricles as well as low density in basal ganglia and diffusely throughout the white matter.

Variant (Left) Axial T2WI MR shows high signal intensity in only bilateral anterior lentiform nuclei and head of right caudate nucleus. Diagnosis = glutaric aciduria type 1. (Right) Axial T2WI MR in a glutaric aciduria type 1 patient reveals only mildly increased signal intensity in white mater as well as prominent lateral ventricles and cortical sulci.

9 51

Metabolic/Degenerative Disorders, Inherited

CANAVAN DISEASE

Axial T2WI MR shows diffuse cerebral hemispheric white matter hyperintensity. Also note the involvement of subcortical U-fibers (arrows) (Courtesy S. Blaser; MO).

o Late: Progressive cerebral atrophy and cerebellar dentate involvement • DWI: Restricted diffusion: At affected sites • Tl C+: Lack of enhancement • MRS: Marked 1 NAA

ITERMINOlOGY Abbreviations

and Synonyms

• Spongiform leukodystrophy

Definitions • Progressive autosomal-recessive

I

Single voxel, long TE (288), PRESS MRS of left hemispheric white matter shows marked elevation in NAA (arrow) (Courtesy K. Cecil, PhO).

leukodystrophy

Imaging Recommendations • Best imaging tool: MRI & MRS: 11 NAA is distinctive • Protocol advice: MRI brain, MRS, + contrast

IMAGING FINDINGS DIFFERENTIAL DIAGNOSIS

General Features

I

• Best diagnostic clue: Early: Diffuse confluent demyelination, early U-fiber involvement • Location o Subcortical U-fibers o Thalami and globi pallidi

Alexander disease (fibrinoid leukodystrophy)

CT Findings

• Butterfly pattern of hemispheric U-fibers

• Predilection for frontal WM

Metachromatic lipidosis)

• NECT o Diffuse I attenuation of cerebral white matter (WM) o I Attenuation globus pallidus and thalamus

leukodystrophy

(sulfatide

demyelination,

spares

Pseudo-TORCH

MR Findings

• Confluent cerebral and cerebellar demyelination • Basal ganglia, thalamic, and periventricular Ca++

• T1WI: Hypointense signal throughout cerebral WM • T2WI o Early: Subcortical U-fiber involvement, centripetal WM involvement o Early: Thalamic and globi pallidi hyperintensity

• Profound deficient myelin development

Pelizaeus-Merzbacher

disease

DDx: Canavan Disease Look-alikes

9 52

Alexander

MLD

Pseudo-TORCH

Metabolic/Degenerative Disorders, Inherited

Pelizaeus-Merzbacher

CANAVAN DISEASE Key Facts Terminology

Top Differential

• Progressive autosomal-recessive

leukodystrophy

• • • •

Imaging Findings • Early: Subcortical V-fiber involvement, centripetal WM involvement • Early: Thalamic and globi pallidi hyperintensity • MRS: Marked 1 NAA • Best imaging tool: MRI & MRS: 11 NAA is distinctive

Diagnoses

Alexander disease (fibrinoid leukodystrophy) Metachromatic leukodystrophy (sulfatide lipidosis) Pseudo-TORCH Pelizaeus-Merzbacher disease

Diagnostic Checklist • Perform MRS in all suspected leukodystrophies • MRS shows marked 1 NAA

I PATHOLOGY

Treatment

General Features

• No treatment currently available • Gene therapy and acetate supplementation evaluation

• General path comments: Vacuolization (spongy degeneration) of white matter • Genetics o Autosomal recessive ~ ASPA gene at 17 pter-p13 o Ashkenazi descent: Glu285Ala - non-Ashkenazi descent: Ala305Glu • Etiology: Deficiency of aspartoacyclase ~ N-acetyl aspartic acid 1 in brain and urine, NAA is neurotoxic

Gross Pathologic & Surgical Features • Edematous/gelatinous V-fibers

Microscopic

brain tissue,necrosis

subcortical

Features

• Spongiform degeneration of white matter • Loss of myelin sheath, sparing of axonal fibers

I

DIAGNOSTIC

• Perform MRS in all suspected leukodystrophies

Image Interpretation

Pearls

• MRS shows marked 1 NAA • Centripetal involvement of hemispheric

WM

I SELECTED REFERENCES 1.

• Age of onset predicts course

2.

I CLINICAL ISSUES

3.

Presentation

CHECKLIST

Consider

Staging, Grading or Classification Criteria

• Most common signs/symptoms o Three clinical variants: Infantile variant most common • Congenital (first few days of life): Early encephalopathy, rapid death • Infantile (3-6 months): Hypotonia, lethargy, head lag, macrocephaly ~ seizures, spasticity, optic atrophy • Juvenile: Onset at 4-5 years; slower progression • Clinical profile: Early severe hypotonia and macrocephaly

under

4. 5.

Kirmani BF: Developmental increase of aspartoacyclase in oligodendrocytes parallels CNS myelination. Brain Res Dev Brain Res 140(1): 105-15,2003 Matalon R et al: Knock-out mouse for Canavan disease: a model for gene transfer to the central nervous system. J Gene Med. 2(3): 165-75,2000 van der Knapp MS et al: Defining and categorizing leukoencephalopathies of unknown origin. MR imaging approach. Radiology 213:121-33, 1999 Gripp KW et al: Imaging studies in a unique familial dysmyelinating disorder. AJNR. 19(7):1368-72, 1998 Matalon R et al: Canavan disease: from spongy degeneration to molecular analysis. J Pediatr. 127(4): 511-7, 1995

I IMAGE GAllERY

Demographics • • • •

Age: Evident by four months Gender: No sex predilection Ethnicity: 1 Risk for Ashkenazi]ewish Epidemiology of lesion o Rare, high carrier state (1:37-58) among screened Ashkenazi Jewish

Natural History & Prognosis • Relentless, progressive neurodegenerative disorder o Chronic vegetative state with autonomic crises o Death by the end of the first decade

Metabolic/Degenerative

9 53

(Left) Axial T2WI MR shows early thalamic (arrow) and globi pallidi (open arrow) involvement. (Right) Axial T2WI MR shows advanced

confluent demyelination (arrows) and atrophy.

Disorders, Inherited

ALEXANDER DISEASE

Axial PO shows symmetrical white matter (WM) hyperintensity with frontal predominance. Hyperintensity is also seen in the basal ganglia. Note hypointense periventricularrim (arrows).

Axial T1 C+ MR shows intense enhancement of bifrontal periventricular WM, periventricular rim, caudate heads. Less intense, patchy enhancement is seen in the putamina and thalami.

ITERMINOLOGY Abbreviations

•

and Synonyms

• Alexander disease (AD) • Fibrinoid leukodystrophy; astrocytes

fibrinoid degeneration

of

Definitions • Rare leukoencephalopathy characterized by macrocephaly and psychomotor regression

• •

I IMAGING FINDINGS

•

General Features • Best diagnostic clue o Best diagnostic clue: Diffuse, symmetrical bifrontal white matter (WM) signal abnormality and enhancement o Other imaging clues • Thick enhancing periventricular rim (particularly around frontal horns) • Bilateral symmetrical signal abnormality of the corpus striatum (esp caudate head) > globus pallidus, thalamus, brain stem (BS) • Periventricular rim and basal ganglia (BG) involvement may precede frontal WM changes

DDx: Metabolic

• •

• Rostral caudal gradient and WM changes less pronounced in adult onset AD Location o Frontal WM • Frequent posterior progression WM changes • Subcortical U-fibers eventually involved o Periventricular rim o BG, thalami, BS > dentate, fornix, optic chiasm Size: Hemispheric WM, peripheral WM tracts (external and extreme capsules), deep gray structures Morphology: Red nuclei and claustrum "stand out on T2WI" 2° to sparing +/- Obstructive hydrocephalus (esp neonatal/infantile subtypes 2° to aqueduct obstruction from periaqueductal disease) Early disease characterized by swellingi late disease by atrophy and cystic encephalomalacia of frontal WM Atypical appearances AD o Isolated BS involvement in juvenile type (mimics Leigh disease) o Medullary and spinal cord atrophy in adult type

CT Findings • NECT o Dense periventricular rim surrounded by low density, esp frontal o BG may appear dense in early disease • CECT

Disease with White Matter Involvement

and Macrocephaly

9 54

Canavan Disease

MLC

GA-7

Metabolic/Degenerative Disorders, Inherited

MPS

ALEXANDER DISEASE Key Facts Terminology

Pathology

• Rare leukoencephalopathy characterized by macrocephaly and psychomotor regression

• AD characterized by Rosenthal fiber (RF) accumulation in astrocytes & hypo-/demyelination • De novo, heterozygous (dominant) mutations in GFAP (17q21) identified in > 90% cases AD • Infantile AD most common; adult AD least common

Imaging Findings • Best diagnostic clue: Diffuse, symmetrical bifrontal white matter (WM) signal abnormality and enhancement • Subcortical U-fibers eventually involved • Best imaging tool: MR C+/MRS

Top Differential

• Infantile AD: Macrocephaly, seizures, developmental delay/arrest • Most patients die within 10 yrs of disease onset (esp infantile/juvenile); rare long term survival

Diagnoses

• Canavan disease • Megaloencephalic leukoencephalopathy subcortical cysts (MLC) • Glutaric aciduria type 1 (GA-1) • Mucopolysaccharidoses (MPS)

Diagnostic Checklist

with

o Intense enhancement characteristic of early disease • Periventricular rim, frontal lobe WM, BG, thalami, BS (esp periaqueductal midbrain), dentate nuclei, fornix, optic chiasm

MR Findings • T1WI o Periventricular rim t • Remaining involved WM, deep gray structures I • T2WI o Periventricular rim variable, but frequently I • Remaining involved WM, deep gray structures t (early disease) • I Signal BG described in late disease o +/- Cystic cavum septum pellucidum et vergae • FLAIR: Cystic degeneration frontal WM (late disease) • T1 C+

o Intense enhancement characteristic of early disease • Periventricular rim, frontal lobe WM, BG, thalami, BS (esp periaqueductal midbrain), dentate nuclei, fornix, optic chiasm o Variable enhancement late disease • MRS o WM profile: I NAA/Cr, t myo-inositol/Cr, (+) lactate doublet (infantile AD) • t Myo-inositol reflects glial proliferation (astrocytosis) characteristic of AD • (+) Lactate indicates astrocytic oxidative stress

Nuclear Medicine

Clinical Issues

Findings

• 18F-fluorodeoxyglucose (FDG) PET o Hypometabolism in affected frontal white matter o Preserved overlying normal glucose metabolism

Imaging Recommendations • Best imaging tool: MR C+/MRS • Protocol advice o Perform MRS with short TE (20 ms) to identify myo-inositol at 3.5 ppm • Intermediate or long TE if needed to distinguish lactate from lipids o Enhance all"unknown" cases hydrocephalus and abnormal WM

Metabolic/Degenerative

• Diffuse, symmetrical bifrontal WM disease in macrocephalic infant highly characteristic of AD; blood DNA analysis confirmatory

DIFFERENTIAL DIAGNOSIS

I

Canavan disease • Clinical: Progressive neurodegeneration; macrocephaly • Diffuse WM disease with bilateral, symmetrical involvement of the globus pallidus and thalamus • Subcortical U-fibers involved early, then whole brain (peripheral ~ central) • No frontal lobe predominance; no enhancement • Characteristic t t NAA peak MRS

Megaloencephalic leukoencephalopathy with subcortical cysts (MlC) • Diffuse WM disease with involvement of the subcortical U-fiber and sparing of the basal ganglia • No frontal lobe predominance; no enhancement • Characteristic anterior temporal subcortical cysts • Clinical: Variable phenotype: Severe WM disease with discrepantly mild clinical course characteristic; macrocephaly

Glutaric aciduria type 1 (GA-1) • • • •

Bilateral, symmetrical basal ganglia signal abnormality Periventricular WM disease seen in severe disease No frontal lobe predominance; no enhancement Characteristic widened opercula 2° to extension of middle cranial fossa cysts into the opercula • Clinical: Encephalopathic crises progressing to dystonia-dyskinesis; macrocephaly

Mucopolysaccharidoses

(MPS)

• Cribriform appearance WM, corpus callosum 2° glycosaminoglycan-filled Virchow-Robin spaces • Patchy, mild periventricular WM signal abnormality without frontal predominance or enhancement • Clinical: Characteristic facies, mental retardation; macrocephaly

I PATHOLOGY General Features • General path comments

Disorders, Inherited

9 55

ALEXANDER DISEASE o AD characterized by Rosenthal fiber (RF) accumulation in astrocytes & hypo-/demyelination o Embryology-anatomy • Astrocytes play role in induction of blood-brain barrier (BBB) and formation of myelin by oligodendrocytes • Glial fibrillary acidic protein (GFAP) = major intermediate filament protein normally identified in astrocytes • Genetics o De novo, heterozygous (dominant) mutations in GFAP (17q21) identified in> 90% cases AD • ~ 21 different mutations identified; same mutation may be seen in all subtypes AD • Mutations cause gain in function o Theory: Gonadal mosaicism responsible for rare sibship and parent-child cases • Etiology o RFs: Abnormal intracellular protein aggregates containing GFAP, and small stress proteins <xB-crystalline, hsp27, and ubiquitin • Mechanism by which GFAP mutation induces RF formation in AD is uncertain • RFs also identified in astrocytomas, hamartomas, and glial scars o Theory: Accumulation RFs in astrocytes compromise astrocyte function and interaction with other cells leading to BBB dysfunction & hypo-/demyelination • Epidemiology o Rare; unknown incidence o Infantile AD most common; adult AD least common

Gross Pathologic & Surgical Features • Megaloencephalic, heavy brain with large ventricles • Swollen, transparent, gelatinous white matter with cortical thinning • Frontal white matter cavitation • BG swelling early; atrophy and cystic change later

Microscopic

Features

• Paucity of myelin/myelin loss in frontal lobes > caudal brain, +/- cerebellar white matter, dentate nucleus, BS • RFs identified as eosinophilic, electron-dense, cytoplasmic inclusions in fibrous astrocytes • Largest accumulation of RFs in subpial, subependymal and perivascular astrocytes o RFs found in deep and periventricular WM, BG, BS, thalami, optic nerve, and spinal WM • Generalized astrocytosis and variable neuraxonal degeneration also present

56

Demographics • Age o Infantile: Birth to 2 yrs o Juvenile: Late childhood/early • Gender: M = F • Ethnicity: No racial predilection

Treatment • Supportive; hydrocephalus in infantile type may respond to shunting • Potential future therapeutic role for agents causing down-regulation of GFAP expression

I

DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Diffuse, symmetrical bifrontal WM disease in macrocephalic infant highly characteristic of AD; blood DNA analysis confirmatory

I SELECTED REFERENCES 1.

2. 3.

5.

Metabolic/Degenerative

known

Natural History & Prognosis

Presentation • Most common signs/symptoms o Infantile AD: Macrocephaly, seizures, developmental delay/arrest o Other signs/symptoms • Infantile: Spasticity, quadriparesis in late disease • Juvenile: Asymptomatic to spasticity, psychomotor regression, and bulbar signs/symptoms (swallowing, breathing difficulties, vomiting); variable macrocephaly

teens

• Natural History o Variable rate of progression ultimately leading to death in all subtypes • Neonatal variant of infantile subtype is most rapidly fatal; infantile subtype is next most severe • Juvenile subtype is more slowly progressive • Adult subtype is mildest • Prognosis o Most patients die within 10 yrs of disease onset (esp infantile/juvenile); rare long term survival

4.

I CLINICAL ISSUES

9

• Adult: Asymptomatic to quadriparesis, ataxia, palatal myoclonus (can resemble multiple sclerosis) • Clinical profile: Infant with macrocephaly, seizures • Cerebrospinal fluid (CSF) analysis: Variable i protein, and presence of <xB-crystalline, hsp27, lactate • Diagnosis: Discovery GFAP mutation permits diagnosis by blood DNA analysis rather than brain biopsy

6. 7.

8.

Mignot C et al: Alexander disease: putative mechanisms of an astrocytic encephalopathy. Cell Mol Life Sci. 61(3):369-85, 2004 Johnson AB et al: Alexander's disease: clinical, pathologic, and genetic features. J Child Neurol. 18(9):625-32, 2003 Brockmann K et al: Cerebral proton magnetic resonance spectroscopy in infantile Alexander disease. J Neurol. 250(3):300-6, 2003 Gordon N: Alexander disease. Eur J Paediatr Neurol. 7(6):395-9, 2003 van der Knaap MS et al: Alexander Disease: Diagnosis with MR Imaging. AJNR 22:541-52,2001 Messing A et al: Alexander disease: new insights from genetics. J Neuropathol Exp Neurol. 60(6):563-73, 2001 Rodriguez D et al: Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation. Am J Hum Genet. 69(5):1134-40, 2001 Springer S et al: Alexander disease--classification revisited and isolation of a neonatal form. Neuropediatrics. 31(2):86-92,2000

Disorders, Inherited

ALEXANDER DISEASE I IMAGE GALLERY Typical (Left) Axial NECT shows

decreased density in the WM with a rosral caudal gradient. Note extension of WM hypodensity into the external/extreme capsules (arrows). The putamina are hyperdense. (Right) Axial CECT shows focal, symmetrical enhancement in the caudate heads, frontal WM, and frontal periventricular rim.

Typical (Left) Coronal T2WI MR shows diffuse, symmetrical WM hyperintensity with more focal hyperintensity and swelling in the frontal periventricular rim, caudate heads, superior putamina, and medial thalami. (Right) Axial FLAIRMR shows less severe disease with high signal intensity seen in the anterior and posterior periventricular rims and WM, with mild frontal predominance.

(Left) Sagittal T7 C+ MR shows swelling and enhancement of the midbrain tegmentum and tectum, compressing the cerebral aqueduct (arrows). Enhancement is also seen in the caudate head (open arrow). (Right) Axial CECT in severe disease shows cystic change in the bifrontal WM with enhancement in the basal ganglia.

9 57

Metabolic/Degenerative Disorders, Inherited

VAN DER KNAAP LEUKOENCEPHALOPATHIES

Axial T2WI MR in megaloencephalic leukoencephalopathy with cysts shows normal internal capsule and genu myelin maturation, but the remainder, including U-fibers, are abnormal.

ITERMINOLOGY Abbreviations

and Synonyms

• MLC: Megaloencephalic leukoencephalopathy with subcortical cysts o Formerly vacuolating megaloencephalic leukoencephalopathy with benign, slowly progressive course • VWM: Leukoencephalopathy with vanishing white matter (WM) o Alternatively CACH: Childhood ataxia central hypomyelination • WML: White matter disease with lactate • H-ABC: Hypomyelination with atrophy of the basal ganglia (BG) and cerebellum

Definitions • All are newly described neurodegenerative leukoencephalopathies with specific, recognizable neuroradiological features

I IMAGING FINDINGS General Features • Best diagnostic clue o MLC: Swollen WM; subcortical cysts o VWM: WM replaced by CSF signal

Sagittal T1WI MR in megaloencephalic leukoencephalopathy with cysts shows typical "cystic" areas involving frontoparietal white matter at vertex (arrow) & anterior temporal tip (open arrow).

o WML: Spinal involvement an important feature; brain lactate o H-ABC: Atrophy of BG (neostriatum) and cerebellum; hypomyelination • Location o MLC: Diffuse WM, includes subcortical U-fibers • Subcortical cysts (especially anterior temporal and frontoparietal) • Spares internal capsules, BG, thalami • Cerebellar WM involvement subtle o VWM: Diffuse WM, includes subcortical U-fibers • BG and thalami not involved • Trackt-like ventral trigeminothalamic and central tegmental tract demyelination in brain stem • Cerebellar WM involved o WML: Diffuse periventricular, deep cerebral WM; spared subcortical U-fibers; +/- temporal lobe WM • Posterior corpus callosum and posterior limb of internal capsule involved • Brainstem: Peduncles, pyramidal tracts, medial lemniscus, intraparenchymal trajectories of trigeminal nerves, anterior spinocerebellar tracts involved • Cerebellar WM involved later, but then notably abnormal • Spine: Dorsal columns; lateral corticospinal tracts o H-ABC: Diffuse hypomyelination of cerebral WM, subcortical U-fibers involved

DDx: Other Leukodystrophies

9 58

Metachromatic

LD

Pelizaeus-Merzbacher

Metabolic/Degenerative

Alexander (Frontal)

Disorders, Inherited

X-ALD (Posterior)

VAN DER KNAAP LEUKOENCEPHALOPATHIES Key Facts • H-ABC: Atrophy of BG (neostriatum) hypomyelination

Terminology • MLC: Megaloencephalic leukoencephalopathy with subcortical cysts • VWM: Leukoencephalopathy with vanishing white matter (WM) • WML: White matter disease with lactate • H-ABC: Hypomyelination with atrophy of the basal ganglia (BG) and cerebellum • All are newly described neurodegenerative leukoencephalopathies with specific, recognizable neuroradiological features

Top Differential

Nonenhancing Enhancing

Pathology • Etiology: All are due to inborn genetic errors • All are extremely rare

Diagnostic Checklist • Not all symmetrical leukodystrophies are metachromatic leukodystrophy • If U-fibers or specific features (cysts; tract, cerebellar, or spinal cord involved), consider one of the "new" leukoencephalopathies • Always enhance the unknown leukoencephalopathy

feature;

• Loss of volume of neostriatum • Myelin deficit of pyramidal tracts through posterior limb internal capsule to brain stem • Brachium pontis involved, cerebellar WM otherwise spared

I

DIFFERENTIAL DIAGNOSIS

Other leukodystrophies:

CT Findings • NECT: In all: Involved WM I attenuation • CECT: No contrast-enhancement

MR Findings • TlWI o In all: Involved WM I signal on Tl WI o H-ABC: If myelin present on initial study, stages of myelin maturation "lost" over time • T2WI o In all: Involved WM t signal on T2WI o H-ABC: Putamen small or not visible • FLAIR o In all: Involved WM t signal on FLAIR o MLC: Anterotemporal and frontoparietal subcortical cysts approximate CSF signal o VWM: Involved WM approximates CSF signal • DWI: MLC and WML: DTI shows I anisotropy, t ADC values • Tl C+: No contrast-enhancement • MRS o MLC: All metabolites I in cystic regions, INAA in WM, +/- lactate signal o VWM: All metabolites of affected WM disappear as the WM disappears; +/-lactate , glucose signals o WML: Positive lactate peak; normal to mildly t Cho, I NAA, t myo-inositol o H-ABC: t Myo-inositol and creatine (gliosis) in WM; I frontal NAA, but otherwise NAA relatively normal

Imaging Recommendations • Best imaging tool: MRI with MRS • Protocol advice: MRI, MRS, contrast administration exclude the enhancing leukodystrophies)

Diagnoses

• Other leukodystrophies: • Other leukodystrophies:

Imaging Findings • MLC: Swollen WM; subcortical cysts • VWM: WM replaced by CSF signal • WML: Spinal involvement an important brain lactate

and cerebellum;

(to

Metabolic/Degenerative

Nonenhancing

• Metachromatic leukodystrophy (MLD): Look for WM "stripes" on T2WI • Pelizaeus-Merzbacher: Lacks myelin maturation on T2WI, +/- minimal maturation on Tl WI • Canavan: Subcortical U-fibers involved early; markedly elevated NAA on MRS • Cree leukoencephalopathy: Involvement of WM, globus pallidus, thalami, medulla; spared olives, red nuclei and caudate nuclei

Other leukodystrophies:

Enhancing

• Alexander disease: Abnormal signal + enhancement of frontal WM & ependymal surfaces; basal nuclei involved • X-linked adrenoleukodystrophy: Abnormal signal and enhancement of peri trigonal WM and splenium

I PATHOLOGY General Features • General path comments: None have systemic or other organ involvement • Genetics o MLC: Autosomal recessive; gene localized on chr 22q(tel); 26 different mutations of MLCI gene • Encodes putative CNS membrane transporter o VWM: Recessive inheritance; gene on 3q27, mutations in genes that encode eIF2B subunits: EIF2Bl-S o WML: Autosomal recessive inheritance likely (2 affected sibling pairs) o H-ABC: Unknown, 7 cases in literature (no sibling pairs, so inheritance unknown) • Etiology: All are due to inborn genetic errors • Epidemiology o All are extremely rare • MLC: Rare, but carrier rate in some communities with high levels consanguinity as high as 1/40

Disorders, Inherited

9 59

VAN DER KNAAP LEUKOENCEPHALOPATHIES • H-ABC: 7 cases described in literature, 2 additional cases known

Gross Pathologic & Surgical Features • MLC: Spongiform leukoencephalopathy • VWM: WM rarefaction and cystic degeneration, WM progressively replaced by CSF, cortex preserved o Central tegmental pontine tract involvement • WML: No cases with pathology, however patterns suggest primary axonal degeneration and myelin loss • H-ABC: No cases with pathology, patterns suggest WM and deep gray matter atrophy

Microscopic Features • MLC: Vacuolization of outermost lamellae of myelin sheaths • VWM: Loss ofaxons and myelin sheaths; fibrillary gliosis and 1 number of oligodendroglial cells

Natural History & Prognosis • Imaging and clinical features progress in all cases

Treatment • Treat symptoms (seizures, spasticity) • Prenatal diagnosis is option in families with known mutations

I

DIAGNOSTIC

CHECKLIST

Consider • Not all symmetrical leukodystrophies are metachromatic leukodystrophy • If U-fibers or specific features (cysts; tract, cerebellar, or spinal cord involved), consider one of the "new" leukoencephalopathies

Image Interpretation

ICLINICAL ISSUES Presentation • Most common signs/symptoms o MLC: Delayed onset of slow motor deterioration (even slower cognitive decline), despite very abnormal MRI o VWM: Episodes of major deterioration and coma following infection or minor head trauma o WML: Slowly progressive pyramidal, cerebellar, and dorsal column dysfunction o H-ABC: Progressive extrapyramidal symptoms • Clinical profile o MLC: Macrocephaly, cerebellar ataxia and pyramidal tract involvement, motor deterioration, seizures • Vety slow cognitive decline, although learning problems in 50% o VWM: Episodic deterioration superimposed on progressive cerebellar ataxia, spasticity, +/- optic atrophy • Relatively preserved cognition o WML: Spasticity and ataxia • Learning problems in 50%, otherwise preserved cognition o H-ABC: Progressive extrapyramidal signs superimposed on variably disturbed motor development, progressive ataxia and spasticity • Relatively preserved cognition

Demographics

9 60

Pearls

• Always enhance the unknown leukoencephalopathy • Remember to assess myelin in the cervical spine on a sagittal view of brain

• Age o MLC: Macrocephaly before the age of 1 year o VWM: Young children (slower progression of older onset of symptoms) o WML: Older children, adolescents, young adults o H-ABC: 1-20 years • Ethnicity o MLC and VWM are increased in population isolates • Common MLC mutations in specific Indian community (Agarwal), Libyan Jewish, and Turkish populations due to founder effect • Common VWM mutations in certain regions of Netherlands

Metabolic/Degenerative

I SELECTED REFERENCES Schiffmann R et al: The latest on leukodystrophies. CUff Opin Neurol. 17(2):187-92,2004 2. Gallo A et al: Multiparametric MRI in a patient with adult-onset leukoencephalopathy with vanishing white matter. Neurology. 62(2):323-6, 2004 with 3. van der Knaap MS et al: A new leukoencephalopathy brainstem and spinal cord involvement and high lactate. Ann Neurol 53(2):252-8, 2003 Brockmann K et al: Megalencephalic leukoencephalopathy 4. with subcortical cysts in adult: Quantitative proton MRS and DTI MRI. 45(3):137-42, 2003 with vanishing 5. Leegwater PA et al: Leukoencephalopathy white matter: From magnetic resonance imaging pattern to five genes. J Child NeuroI18(9):639-45, 2003 6. van der Knaap MS et al: New syndrome characterized by hypomyelination with atrophy of the basal ganglia and cerebellum. 23(9):1466-74, 2002 Leegwater PA et al: Mutations of MLCI (KIAA0027), 7. encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts. AmJ Hum Genet 68:831-8, 2001 8. De Stefano N et al: Severe metabolic abnormalities in the white matter of patients with vacuolating megalencephalic leukoencephalopathy with subcortical cysts. A proton MR spectroscopic imaging study. J Neurol 248(5):403-9, 2001 9. van der Knaap MS et al: Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach. Radiology 213:121-33, 1999 10. van der Knaap MS et al: Phenotypic variation in leukoencephalopathy with vanshing white matter. Neurology 51(2):540-7, 1998 11. van der Knaap MS et al: A new leukoencephalopathy with vanishing white matter. Neurology 48(4):845-55, 1997 12. van der Knaap MS et al: Histopathology of an infantile-onset spongiform leukoencephalopathy with a discrepantly mild clinical course. Acta Neuropathol 92 (20):206-12, 1996 1.

Disorders, Inherited

VAN DER KNAAP LEUKOENCEPHALOPATHIES I IMAGE GALLERY Typical (Left) Axial T2WI MR in VWM shows abnormal signal of internal & external capsules (arrows), splenium (open arrow), periventricular & lobar white matter. There is no sparing of subcortical U-fibers. (Right) Axial T2WI MR in VWM demonstrates involvement of cerebellar hemispheric white matter (arrow).

(Left) Axial T2WI MR in WML shows involvement of periventricular white matter and sparing of the sub-cortical U-fibers. Note internal capsule, corticospinal tract (arrow) and corpus callosum involvement. (Right) Sagittal T2WI MR in WML shows focal involvement (open arrow) in the atrophied splenium of the corpus callosum. Note also the typical signal abnormality of an atrophied cervical spinal cord (arrows).

(Left) Axial TlWI MR in H-ABC shows caudate head, putamina, and globus pallidus atrophy (arrow), prominent sulci and bright thalami. There has been loss of previously attained myelin maturation milestones. (Right) Axial T2WI MR in H-ABC shows dark thalami standing out against unmyelinated white matter. There is symmetric loss of caudate heads, putamina, and globus pallidus. Also note diffuse volume loss.

Metabolic/Degenerative

Disorders,

Inherited

9 61

HALLERVORDEN-SPATZ

Axial T2WI MR demonstrates hypointense globus pallidi with symmetric hyperintense foci located anteromedially (arrows), the so-called "eye-of-the-tiger" sign typical of PKAN.

Axial T2WI MR shows symmetric hypointense globus pallidi without the "eye-of-the-tiger" sign in an older child; findings typical for neurodegeneration with brain iron accumulation (NBIA).

ITERMINOLOGY Abbreviations

and Synonyms

• HSS; pantothenate kinase-associated neurodegeneration (PKAN); neurodegeneration with brain iron accumulation type 1 (NBIA-l) • Neurodegeneration with brain iron accumulation (NBIA) = new umbrella term for disorders of focal brain iron accumulation o NBIA includes former HSS, aceruloplasminemia, neuroferritinopathy, and others o Former HSS with pantothenate kinase 2 gene (PANK2) mutation now called PKAN o Former HSS without PANK2 mutation now grouped under NBIA • PKAN and NBIA preferred terms due to 3rd Reich association of Julius Hallervorden

Definitions • Progressive neurodegenerative disorder characterized by extrapyramidal motor impairment and brain iron accumulation

I IMAGING FINDINGS General Features • Best diagnostic clue

9

SYNDROME

• •

• •

o "Eye-of-the-tiger" sign: Bilateral, symmetric foci T2 hyperintensity in globus pallidus (GP) surrounded by pallidal T2 hypointensity • One-to-one correlation of "eye-of-the-tiger" imaging appearance and PANK2 mutation • Symmetric T2 hypointense GP and substantia nigra (SN) in NBIA Location: GP, SN: "Eye" in "eye-of-the-tiger" is central or anteromedial GP Morphology o PKAN: Bilateral, focal GP hyperintensity surrounded by GP hypointensity has appearance of "tiger eyes" o NBlA: Uniform, bilateral, symmetric hypointensity Atrophy variably present, esp cerebellum in NBIA Iron deposition (ferritin-bound) responsible for T2 hypointense imaging appearance

CT Findings • NECT: Hyperdense GP foci or normal • CECT: No abnormal enhancement

MR Findings • Tl WI: Variable (ferritin-bound iron has greater Tl shortening than hemosiderin-bound) • T2WI o PKAN: "Eye-of-the-tiger"; +/- SN hypointensity • Hyperintense "eye" predates surrounding T2 hypointensity o NBIA: Uniform, hypointense GP, SN

DDx: Disorders with Increased Pallidal T2 Signal

62

MMA

Carbon Monoxide

Metabolic/Degenerative

Cyanide Poisoning

Disorders, Inherited

Kernicterus

HALLERVORDEN-SPATZ

SYNDROME

Key Facts Terminology • Neurodegeneration with brain iron accumulation (NBIA) = new umbrella term for disorders of focal brain iron accumulation • Former HSS with pantothenate kinase 2 gene (PANK2) mutation now called PKAN • Former HSS without PANK2 mutation now grouped under NBIA • Progressive neurodegenerative disorder characterized by extrapyramidal motor impairment and brain iron accumulation

Imaging Findings • "Eye-of-the-tiger" sign: Bilateral, symmetric foci T2 hyperintensity in globus pallidus (GP) surrounded by pallidal T2 hypointensity

• FLAIR: "Eye" in "eye-of-the-tiger" persists • T2* GRE: T2 hypointensities "bloom" due to paramagnetic effect iron • T1 C+: No abnormal enhancement • MRS: !NAA in GP (neuronal loss)

Nuclear Medicine

Findings

• PET: Hemispheric hypometabolism described in adult patient with dementia • Nuclear med: 123I-~-CIT / 123I-IBZM SPECT normal o Abnormal in Parkinson/multi-system atrophies

Imaging Recommendations • Best imaging tool: MR • Protocol advice o Include GRE sequence o T2 hypo intensity more conspicuous on spin echo (vs fast spin echo) and high field strength magnets

I DIFFERENTIAL DIAGNOSIS Metabolic

disorders with!

T2 signal GP

• Neuronal ceroid lipofuscinosis: ! T2 GP/thalami; cerebral and cerebellar atrophy • Fucosidosis: !T2 GP; 1 T2, atrophy white matter; cutaneous lesions; hepatosplenomegaly

Disorders with 1 T2 signal GP • Metabolic o Methylmalonic acidemia (MMA): 1 T2 GP, +/periventricular white matter (WM) o Kearns-Sayre/L-2-Hydroxyglutaric aciduria: 1 T2 GP (> than other deep gray) and peripheral WM o Canavan: 1 T2 GP (> than other deep gray) and peripheral WM; macrocephaly; 11 NAA • Ischemic/Toxic o Anoxic encephalopathy: 1 T2 GP (and other deep gray) and cortex o Carbon monoxide poisoning: 1 T2 GP (+/- other deep gray, cortex, WM) o Cyanide poisoning: 1 T2 BG followed by hemorrhagic necrosis

• One-to-one correlation of "eye-of-the-tiger" imaging appearance and PANK2 mutation

Top Differential

Diagnoses

• Disorders with 1 T2 signal GP • Metabolic • Ischemic/Toxic

Pathology • Iron accumulation

likely 2° phenomenon

in PKAN

Clinical Issues • Classic PKAN: Young child w/gait, postural deficits • Classic PKAN: Fatal; mean duration disease after symptom onset = 11 yrs • PKAN: MR imaging findings may precede symptoms • No curative treatment; iron chelation ineffective

o Kernicterus: 1 T2/T1 GP neonate

I PATHOLOGY General Features • General path comments o Iron accumulation likely 2° phenomenon in PKAN • Serial MRs in PKAN patients show hypertense foci GP predating surrounding hypo intensity o Embryology-anatomy • Normal progressive, physiologic brain iron accumulation GP, SN > red & dentate nuclei • !T2 signal GP identified in majority of normals by age ~ 25, but never before age 10 • Genetics o Autosomal recessive (50% sporadic) o PKAN: PANK2 mutation on chromosome 20p12.3-p13 • PANK2 encodes mitochondrial-targeted pantothenate kinase 2, key enzyme in biosynthesis of coenzyme A (CoA) • CoA essential to energy metabolism, fatty acid synthesis and degradation, among other functions • Null mutations more common in early-onset, rapidly progressive disease • Missense mutations more common in late-onset, more slowly progressive disease => suggests residual pantothenate kinase 2 activity in late-onset (less severe) disease o HARP: Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration • Allelic with PKAN • Same "eye-of-the-tiger" on MR • Prominent orofacial dystonia; early onset parkinsonism • Etiology o Leading theory • PANK2 mutation => CoA deficiency => energy and lipid dyshomeostasis => production oxygen free radicals => phospholipid membrane destruction

Metabolic/Degenerative Disorders, Inherited

9 63

HALLERVORDEN-SPATZ • Basal ganglia and retina esp prone to oxidative damage 2° to high metabolic demand o Contributing factors • Cysteine accumulation GP 2° to I phosphopantothenate causes iron chelation and peroxidative cell membrane damage • Lewy bodies, glial inclusions, and axonal spheroids further compromise glial and neuronal cell function • Epidemiology: Rare; incidence unknown

Gross Pathologic & Surgical Features • Symmetric rust-brown pigmentation GP (interna > externa) and pars reticulata SN o In addition to iron, intra- and extra neuronal ceroid lipofuscin and melanin contribute to pigmentation • Variable atrophy o Cerebellar atrophy more common in NBIA

Microscopic

Features

• Classic features o Neuronal loss, gliosis and glial inclusions primarily involving GP intern a and pars reticulata SN o Round or oval non-nucleated axonal swellings ("spheroids") in GP, SN, cortex, and brainstem o Abnormal iron accumulation GP interna and pars reticulata SN • Iron located in astrocytes, microglial cells, neurons and around vessels • Additional iron accumulation in red and dentate nuclei characteristic of NBIA • "Loose" tissue consisting of reactive astrocytes, dystrophic axons and vacuoles in anteromedial GP corresponds to "eye-of-the-tiger" on MR • Variably present neurofibrillary tangles, Lewy bodies, and acanthocytes (on blood smear) • Immunohistochemistry: (){-,S-, and ¥-synucleins are major constituents of spheroids

Staging, Grading or Classification Criteria • Clinical Classification o PKAN divided into classic and atypical disease • Classic PKAN: Early onset; more rapidly progressive disease; uniform phenotype • Atypical PKAN: Late onset; more slowly progressive disease; heterogeneous phenotype

o Classic PKAN: Young child w/gait, postural deficits o Atypical PKAN: Teenager w/speech, psychiatric disturbance • Normal serum and CSF iron levels

Demographics • Age o Classic PKAN: Majority present before 6 yrs of age; mean age = 3.5 yrs o Atypical PKAN: Mean age at presentation = 13 yrs o NBIA: Mean age at presentation = 7 yrs

Natural History & Prognosis • Natural History o Classic PKAN: Rapid, non-uniform progression with periods of deterioration interspersed with stability ultimately leading to death early adulthood o Atypical PKAN/NBIA: More slowly progressive with loss ambulation 15-40 yrs after disease onset • Prognosis o Classic PKAN: Fatal; mean duration disease after symptom onset = 11 yrs o Atypical PKAN/NBIA: Eventual severe impairment, +/- death, adulthood • PKAN: MR imaging findings may precede symptoms

Treatment • No curative treatment; iron chelation ineffective • Palliation of symptoms: Baclofen, trihexyphenidyl, stereotactic pallidotomy • Potential for pantothenate (vitamin B5) replacement therapy in PKAN

I

DIAGNOSTIC

• Physiologic GP hypointensity difficult to distinguish from pathologic hypointensity in an adult

Image Interpretation

9 64

Metabolic/Degenerative

Pearls

• If "Eye-of-the-tiger" on MR, then (+) PANK2 mutation • If no PANK2 mutation (NBIA) ~ no "eye-of-the-tiger" I SELECTED

I CLINICAL ISSUES • Most common signs/symptoms o Classic PKAN: Dystonia • Other extrapyramidal signs/symptoms: Dysarthria, rigidity, choreoathetosis • Upper motor neuron signs/symptoms and cognitive decline frequent • Pigmentary retinopathy 66% o Atypical PKAN: Psychiatric and speech disturbances • Other signs/symptoms: Pyramidal, extrapyramidal disturbances (including freezing), dementia o NBIA: Similar to atypical PKAN with exception of speech and psychiatric dysfunction • Clinical profile

CHECKLIST

Consider

1.

Presentation

SYNDROME

2.

3.

4.

5. 6.

REFERENCES

Thomas M et al: Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden-Spatz syndrome) and pantothenate kinase-associated neurodegeneration. Mov Disord. 19(1):36-42,2004 Hayflick SJ et al: Genetic, Clinical, and Radiographic Delineation of Hallervorden-Spatz Syndrome. N Eng J Med 348(1):33-40, 2003 Hayflick SJ. Related Articles et al: Unraveling the Hallervorden-Spatz syndrome: pantothenate kinase-associated neurodegeneration is the name. CUff Opin Pediatr. 15(6):572-7, 2003 Gordon N: Pantothenate kinase-associated neurodegeneration (Hallervorden-Spatz syndrome). Eur J Paediatr Neurol 6(5):243-7, 2002 Swaiman K: Hallervorden-Spatz Syndrome. Pediatr Neurol 25(2):102-8,2001 Dooling EC et al: Hallervorden-Spatz syndrome. Arch Neurol. 30(1):70-83, 1974

Disorders, Inherited

HALLERVORDEN-SPATZ

SYNDROME

jlMAGE GALLERY Typical (Left) Axial 12WI MR at the level of the substantia nigra demonstrates abnormal, symmetric nigral hypointensity (arrows). (Right) Coronal 12 WI MR captures all main findings in PKAN: "Eye-of-the-tiger" sign superiorly in globus pallidi, symmetric hypointensity inferiorly in bilateral substantia nigra (arrows).

(Left) Axial TlWI MR shows no apparent abnormal signal intensity in the substantia nigra in a patient with PKAN. (Right) Axial TlWI5PCR shows abnormal, hyperintense substantia nigra; the Tl WI appearance of H55 (both PKAN and NBIA) is variable.

Typical (Left) Axial 12* CRE MR shows paramagnetic "blooming" in the globus pallidi secondary to iron deposition. (Right) NECT shows hyperdense foci (mineralization) in the medial globus pallidus bilaterally.

9 65

Metabolic/Degenerative Disorders, Inherited

HUNTINGTON

Axial graphic shows bilateral caudate atrophy with convex margins of frontal horns (arrows).

ITERMINOlOGY Abbreviations • Huntington

and Synonyms

disease (HD), Huntington

chorea

Definitions • Autosomal dominant neurodegenerative disease with loss of GABAergic neurons of basal ganglia (BG) • Clinical triad: Early onset dementia, choreoathetosis, and psychosis

I IMAGING FINDINGS General Features • Best diagnostic clue: Atrophy of caudate nucleus (Cn) ~ enlargement of frontal horns of lateral ventricles • Location o Primarily striatum (especially Cn, putamen) o Cerebral cortex, globus pallidus (GP), thalamus o Substantia nigra (SN), brainstem • Size: Decreased (atrophy) • Morphology: Loss of convex surface of caudate head

CT Findings • NECT o Atrophy of Cn and putamen, also GP (less severe) o Enlargement of frontal horns of lateral ventricles

DISEASE

Coronal T2WI MR of a patient with Huntington disease demonstrates atrophy of caudate nuclei bilaterally, producing an increase in intercaudate distance.

o Diffuse cerebral atrophy (reported to be predominantly frontal in some studies) o Cn atrophy is measured on axial images at level of 3rd ventricle • Intercaudate distance (CC) between most medial aspects of Cn • CC compared with distance between most lateral aspects of frontal horns (FH) • CC compared with distance between inner tables (IT) of skull at level of CC measurement • 1 CC relative to FH or IT • !FH/CC ratio • 1 CC/IT ratio (bicaudate ratio): Most specific and sensitive measure for HD • CECT: No contrast-enhancement of affected structures

MR Findings • TlWI o Shrinkage of Cn and 1 CC o MR measurements: ! Volume in all BG structures • Also reported in pre symptomatic stage of HD o Diffuse cerebral atrophy • T2WI o Hyperintense signal in Cn, putamina in juvenile HD • Gliosis-related o Shrinkage of Cn and 1 CC o Striatum may have !signal due to iron deposition • MRS

DDx: Basal Ganglia Diseases

9 66

Leigh Syndrome

Wilson

Disease

H allervorden-

Spa tz

Metabolic/Degenerative Disorders, Inherited

CO

Poisoning

HUNTINGTON

DISEASE

Key Facts Imaging Findings • Best diagnostic clue: Atrophy of caudate nucleus (Cn) =} enlargement of frontal horns of lateral ventricles • 1 CC/IT ratio (bicaudate ratio): Most specific and sensitive measure for HD • Hyperechogenic lesions primarily in SN and Cn • t FDG uptake in BG before any detectable atrophy

Top Differential • • • •

Diagnoses

Leigh disease Wilson disease Hallervorden-Spatz Carbon monoxide poisoning

Pathology

o 1 Lactate concentration in occipital cortex of symptomatic HD, also in BG in some patients • Lactate level correlates with duration of illness o t N-acetylaspartate/creatine in BG (neuronal loss) o 11 Choline/creatine ratio in BG (gliosis) o Findings consistent with energy metabolism defect

Findings

• Transcranial real time sonography (TCS) o Hyperechogenic lesions primarily in SN and Cn • Hyperechogenic lesions in SN correlate with disease severity • Cn hyperechogenicity correlates with Cn hyperintensity on T2WI o Ventricular enlargement depicted by TCS correlates with CT findings • Functional transcranial Doppler ultrasonography o I Vasoreactivity in anterior cerebral artery during motor activation in early stage HD • Possibly due to brain peroxynitrite deposition

Nuclear Medicine

Clinical Issues • Pathognomonic feature of HD: Movement disorder • Mean age of onset: 35-44 y in adult-onset HD

Diagnostic Checklist

• CAG trinucleotide repeat disease affecting HD gene on chromosome 4p16.3

Ultrasonographic

• Polyglutamine expansion =} Huntington accumulates in nucleus and cytoplasm =} cytoplasmic huntington aggregates in axonal terminals • Juvenile HD: Involvement of GP and cerebellum • Severity grades (0-4) based on gross striatal pathology, neuronal loss and gliosis

Findings

• PET o t FDG uptake in BG before any detectable atrophy o ± Frontal lobe hypometabolism • SPECT: Perfusion defects in motor cortex, prefrontal cortex, and BG correlate with clinical disease

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: T2WI

I DIFFERENTIAL DIAGNOSIS leigh disease • Subacute necrotizing encephalomyelopathy • Onset usually < 2y , but juvenile/adult forms also exist • Changes in putamen, Cn, and tegmentum o Nonenhancing hypodensities (infarcts) on CT o Tl hypo-, T2 hyperintensities (infarcts) o No atrophy of Cn and putamina

• Rule out reversible dementi as and movement disorders • Caudate atrophy is main radiologic feature of HD • 1 Signal intensity in Cn and putamina on PD- and T2WI in children suggests HD

• Focal involvement of white matter, thalamus, brain stem and cerebellum

Wilson disease • Rigidity, tremor, dystonia, gait difficulty, dysarthria • CT: Low densities in BG, cerebellar nuclei, brain stem, and white matter • T2WI: Symmetrical signal hyperintensity in Cn, putamen, midbrain, and pons (gliosis and edema) o Asymmetrical hypointensity in frontal white matter o Characteristic irregular areas of hypointensity in Cn and putamen • Atrophy of Cn and brain stem on CT, MR

Hallervorden-Spatz • Involuntary movements (choreoathetosis), spasticity • Progressive dementia in young adults • Characteristic iron deposition in GP, red nuclei, SN o Diffuse hypointensity in these structures on T2WI o "Eye of the tiger" sign: Central spot of high signal in medial GP on T2WI • GP atrophy, ± cortical, Cn atrophy

Carbon monoxide poisoning • Bilateral CT hypodensity,

T2 hyperintensity

in GP

I PATHOLOGY General Features • General path comments o Gross atrophy of Cn and putamen • Selective neuronal loss and astrogliosis o Neuronal loss in deep layers of cerebral cortex o Varying degrees of atrophy (GP, thalamus, subthalamic nucleus, SN, cerebellum) depending on pathologic grade • Genetics o Autosomal dominant with complete penetrance o CAG trinucleotide repeat disease affecting HD gene on chromosome 4p16.3 • Toxic gain of function for mutant protein (Huntington)

Metabolic/Degenerative Disorders, Inherited

9 67

HUNTINGTON • Extra copies of glutamine in Huntington o Genetic anticipation: t Severity or ~ age of onset in successive generations • More commonly in paternal transmission of mutated allele o Homozygosity for HD mutation (very rare) • Associated with more severe clinical course • Etiology o Polyglutamine expansion ~ Huntington accumulates in nucleus and cytoplasm ~ cytoplasmic huntington aggregates in axonal terminals o Mutant Huntington abnormally associates with synaptic vesicles and impairs synaptic function • Epidemiology o Worldwide prevalence: 5-10/100,000 people o 3-7/100,000 in populations of W European descent

Natural History & Prognosis

• Diffuse cerebral atrophy, marked in Cn & putamen o Loss of convex bulge of Cn facing lateral ventricle • Juvenile HD: Involvement of GP and cerebellum o Not typically involved in adults

Microscopic Features

Treatment

• Neuropathological hallmarks of HD o Intranuclear inclusions of mutant Huntington o Perinuclear aggregates in cortex, striatum • Histochemical analysis may show t iron deposition in Cn, putamen

• Antidepressants, high-potency antipsychotics • Clozapine can suppress chorea • Ubiquinone (coenzyme Q10) ~ normalization of lactate levels in cortex and striatum • Bilateral neural transplantation • Trophic factors, grafting of trophic factor-producing cell lines under investigation

Staging, Grading or Classification Criteria • Severity grades (0-4) based on gross striatal pathology, neuronal loss and gliosis • Grade 0: No gross striatal atrophy o No detectable histologic neuropathology o Typical clinical picture and (+) family history of HD • Grade 1: No gross striatal atrophy o Microscopic neuropathologic changes • Grade 2: Striatal atrophy, convex Cn • Grade 3: More severe striatal atrophy, flat Cn • Grade 4: Most severe striatal atrophy o Concave medial surface of Cn I CLINICAL

ISSUES

Presentation

68

Demographics • Age o Mean age of onset: 35-44 y in adult-onset HD o Juvenile HD (5-10% of cases): Onset < 20 Y • Gender o M = Fi gender-related factor affecting disease onset • Earlier onset and faster progression of HD in offspring of male patients • 70% of juvenile cases have affected father • Ethnicity: Less common in African, Asian populations • Early symptoms: Personality changes and subtle movement disturbances • Progression to choreoathetosis and dementia • Behavioral disorganization, depression, suicidal behavior, psychotic features (visual hallucinations) • Adult HD: Progressive deterioration until death 15-20 y after onset • Higher degree of volume loss ¢> earlier age of onset • Juvenile HD: More progressive clinical course o Average survival: 7-8 y after onset

Gross Pathologic & Surgical Features

9

DISEASE

• Most common signs/symptoms o Triad: Movement disorder (choreoathetosis), dementia of subcortical type, behavioral changes/psychosis o Dysarthria, dysphagia, abnormal eye movements • Clinical profile o Pathognomonic feature of HD: Movement disorder • Chorea: Often facial twitching or twitching and writhing of distal extremitiesi ballism later on • Progressive ~ impaired gait ("dancing gait") • Rigidity and dystonia in later stages (adult HD) o Juvenile HD: Rigidity> chorea • Rigidity and dystonia may occur as initial symptoms • Cerebellar signs, dyslalia, rapid cognitive decline • Seizures, parkinsonism, dystonia, long-tract signs

I

DIAGNOSTIC

CHECKLIST

Consider • Rule out reversible dementias and movement disorders

Image Interpretation

Pearls

• Caudate atrophy is main radiologic feature of HD o Bicaudate diameter: Sensitive for Cn atrophy • Decline in size of GP and putamen correlates with disease progression • t Signal intensity in Cn and putamina on PD- and T2WI in children suggests HD I SELECTED 1. 2. 3.

4.

5.

REFERENCES

Alberch J et al: Neurotrophic factors in Huntington's disease. Prog Brain Res. 146:195-229,2004 MacDonald ME et al: Huntington's disease. Neuromolecular Med. 4(1-2):7-20, 2003 Postert T et al: Basal ganglia alterations and brain atrophy in Huntington's disease depicted by transcranial real time sonography. J Neurol Neurosurg Psychiatry 67:457-462, 1999 Ho VB et a1.Juvenile Huntington Disease: CT and MR features. AmJ Neuroradiol16:1405-1412, 1995 Jenkins BG et a1. Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurol 43:2689-2695, 1993

Metabolic/Degenerative Disorders, Inherited

HUNTINGTON

I IMAGE

DISEASE

GALLERY

Typical

I~

/

"-

,,

I

-

I

\'

J

j

)

\.

\ ...

~

.,

,

/

(Left) Axial T2WI MR shows decrease in caudate nuclei size, enlargement of frontal horns, and mild focal hypointensities in putamen and globus pallidus. Also note cortical atrophy. (Right) Axial PO/Intermediate MR in the same patient shows slight hyperintensity in caudate heads and putamina. Atrophy of caudate nuclei bilaterally causes frontal horn dilatation.

/

Typical (Left) Coronal T7 C+ MR demonstrates bilateral caudate atrophy with "ballooning" of frontal horns of lateral ventricles in a patient with Huntington disease. (Right) Axial T7 C+ MR in the same patient shows enlargement of sulci and Sylvian fissures consistent with cortical atrophy.

Typical (Left) Axial T2WI MR shows bilateral diffuse hypointensity in globus pallidus probably due to iron deposition in this patient with Huntington disease. (Right) Axial NECT in a young patient with family history of Huntington disease shows atrophy of caudate heads bilaterally and dilatation of lateral ventricle frontal horns.

9 69

Metabolic/Degenerative Disorders, Inherited

WILSON DISEASE

Axial T2WI MR at midbrain level shows the "face of the giant panda" sign, characteristic of Wilson disease (Courtesy M. Iwata, MD see reference 5).

Axial FLAIR MR demonstrates bilateral hypointense lesions in basal ganglia as well as hyperintense lesions in posterior portion of posterior limb of internal capsules (corticospinal tract).

ITERMINOLOGY

CT Findings

Abbreviations

• NECT o Copper deposition does not increase density on CT o Widening of frontal horns of lateral ventricles o Diffuse cerebral and cerebellar atrophy o ± Hypodensity in lenticular nuclei and thalami • CECT: Lesions do not contrast-enhance

and Synonyms

• Wilson disease (WD), hepatolenticular

degeneration

Definitions • Inborn error of copper metabolism characterized by o Liver cirrhosis, Kayser-Fleischer ring of cornea o Softening and degeneration of basal ganglia (BG)

I IMAGING FINDINGS General Features • Best diagnostic clue: Symmetrical T2 hyperintensity or mixed intensity in putamina (with hyperintense peripheral putaminal rim) and globi pallidi (GP), caudate nuclei, and thalami • Location o Most common: Putamen (predilection for outer rim) and pons (dorsal and central regions) o Caudate nuclei, GP, thalami (ventrolateral nuclei) o Midbrain, cerebellum (vermis and dentate nucleus) o Dentatorubrothalamic, pontocerebellar and corticospinal tracts o Cortical and subcortical lesions (mostly frontal lobe) • Size: Initially t (swelling of BG), then I (atrophy) • Morphology: No change in shape of affected structures

DDx: Hyperintense

MR Findings • TlWI o Tl signal generally reduced in BG o Signal intensity may be t in affected BG (paramagnetic effects of copper) • Detected only in untreated patients • t Signal in GP due to hepatic component of WD (portal-systemic encephalopathy) • T2WI o Generalized cerebral and cerebellar atrophy o Hyperintensity/hypointensity/mixed intensity in putamen, GP, caudate, thalamus • Concentric-laminar T2 putaminal hyperintensity • Hypointensity due to t iron content in BG or cavitations in aggressive WD o Characteristic "face of the giant panda" sign on axial sections at midbrain level • Hyperintensity in tegmentum (except for red nucleus) • Hypointensity of superior colliculus

T2 Basal Ganglia Changes

9 70

Leigh Syndrome

Acute CO Poisoning

Metabolic/Degenerative

CJD

Disorders, Inherited

Japanese Encephalitis

WILSON DISEASE Key Facts • !! Glucose metabolism

Imaging Findings • Best diagnostic clue: Symmetrical T2 hyperintensity or mixed intensity in putamina (with hyperintense peripheral putaminal rim) and globi pallidi (GP), caudate nuclei, and thalami • Most common: Putamen (predilection for outer rim) and pons (dorsal and central regions) • Hyperintensity/hypointensity/mixed intensity in putamen, GP, caudate, thalamus • Characteristic "face of the giant panda" sign on axial sections at midbrain level • Abnormally hyperintense tracts • DWI provides data on WD histopathologic stages • !N-acetyl aspartate/creatine (neuronal loss) in GP • In adults, BG lesions may differ from those in children

•

•

• •

•

• Preserved signal intensity of lateral portion of pars reticulata of substantia nigra o ± Hyperintensity in periaqueductal gray matter, pontine tegmentum o ± Involvement of dentate nucleus (1 intensity) o Abnormally hyperintense tracts • Dentatorubral if abnormal superior cerebellar peduncle (SCP) and dorsal mesencephalon • Dentatothalamic if abnormal SCP, dorsal mesencephalon, and thalamus • Pontocerebellar if abnormal base of pons, cerebellar hemispheres, and/or middle cerebellar peduncle • Corticospinal if abnormal posterior portion of posterior limb of internal capsule, middle division of cerebral peduncle and/or base of pons o 1 Signal intensity in cerebral, cerebellar white matter PD/Intermediate o Symmetrical high signal intensity in affected BG • +/- Swelling immediately after symptom onset • Subsequent diffuse cerebral atrophy DWI o Immediately after onset of neurologic symptoms • Hyperintense lesions and swelling of affected BG • Abnormally low ADC values • ! Diffusion (cell swelling and inflammation) o On subsequent imaging • Low signals in affected BG, high ADC values • 1 Diffusion (necrosis, spongiform degeneration and demyelination) o DWI provides data on WD histopathologic stages Tl C+: No contrast-enhancement MRS o !N-acetyl aspartate/creatine (neuronal loss) in GP o !Choline/creatine ratio in GP o ! Myoinositol/creatine ratio in WD with porto systemic shunting vs WD without shunting In adults, BG lesions may differ from those in children o Putaminallesions may not be present o GP and substantia nigra may show T2 hypointensity o ± Cortical, subcortical lesions (mainly frontal lobe)

in cerebellum, striatum and to lesser extent, in cortex and thalamus "

Top Differential • • • • • •

Diagnoses

Leigh disease Carbon monoxide poisoning Creutzfeldt-Jakob disease Japanese encephalitis OE) Striatonigral degeneration Organic aciduria

Pathology • Edema, necrosis and spongiform

degeneration

of BG

Diagnostic Checklist • Less severe changes in signal intensity with longer duration of disease

Nuclear Medicine

Findings

• PET o !! Glucose metabolism in cerebellum, striatum, and, to lesser extent, in cortex and thalamus o !! Dopa-decarboxylase activity (impaired nigrostriatal dopaminergic pathway) • SPECT o (123I)2B-carbomethoxy-3 B-( 4(123I)iodophenyl)tropane • Binds to presynaptic striatal dopamine carriers o (123I)iodobenzamide • Binds to postsynaptic striatal dopamine D2R o In WD patients without neurologic symptoms • Normal striatal binding ratios of both tracers o In symptomatic WD patients • !! Striatal binding ratios of both tracers o In all patients with WD • Highly correlated binding ratios of both tracers • SPECT parameters significantly correlate with severity of neurologic symptoms o Neurologic WD = secondary Parkinsonian syndrome • Altered pre- and postsynaptic dopaminergic tracts

Imaging Recommendations • Best imaging tool: MRI better than CT for early lesions • Protocol advice: T2WI, DWI

I DIFFERENTIAL DIAGNOSIS leigh disease • Subacute necrotizing encephalomyelopathy • Symmetrical spongiform brain lesions with onset in infancy/early childhood • Lesions predominantly in brainstem, BG (particularly putamen) and cerebral white matter (WM) • Focal, bilateral and symmetric T2 hyperintense lesions

Carbon monoxide poisoning • Bilateral GP hypodensity

Creutzfeldt-Jakob

on CT, hyperintensity

on T2

disease

• Progressively hyperintense changes in BG, thalamus and cerebral cortices on T2WI

Metabolic/Degenerative Disorders, Inherited

9 71

WILSON DISEASE Japanese encephalitis (JE) • Homogeneous T2 hyperintensities in BG and thalami o Symmetric or asymmetric • Posteromedial part of thalamus o Spared in WD, always involved in JE • Most characteristic finding in JE o Bilateral thalamic hyperintensities ± hemorrhage • JE is meningoencephalitis ~ meningeal enhancement

Striatonigral degeneration • Hypo- and hyperintense T2 changes in putamen o T2 hypointensity of dorsolateral putamen o T2 slit-like hyperintensity of putaminal outer rim o Highly specific of multiple system atrophy (parkinsonism)

Organic aciduria • Symmetrical diffuse WM changes, wide CSF spaces • BG changes (1 T2 signal ± volume loss in caudate and/or lentiform nuclei)

I PATHOLOGY General Features • General path comments o Excess copper throughout brain, with unexplained tendency for extensive BG damage o Brain lesions usually bilateral and often symmetrical o Abnormal WM in extrapyramidal + pyramidal tracts • WD considered an extrapyramidal disease • Genetics o Autosomal recessive o ATP7B gene on chromosome 13q14.3-q21.1 • Etiology o Defective incorporation of copper into ceruloplasmin and impaired biliary copper excretion o Brain lesions caused by accumulation of copper, chronic ischemia, vasculopathy, or demyelination • Epidemiology o Prevalence: 1 in 30,000 people o US carrier frequency: 1 per 90 individuals

Gross Pathologic & Surgical Features • Ventricular enlargement • Widening of cerebral and cerebellar sulci

Microscopic

9 72

Features

• Edema, necrosis and spongiform degeneration of BG • Opalski cells = PAS-positive altered glial cells • Involvement of supra- and infratentorial WM o Capillary endothelial swelling, gliosis o Spongiform degeneration, demyelination • Central pontine myelinolysis also found • Deep pyramidal cell layers of cerebral cortex involved

Staging, Grading or Classification Criteria • Stage 1: Initial period of accumulation of copper by hepatic binding sites • Stage 2: Acute redistribution of copper within liver and release into circulation • Stage 3: Chronic accumulation of copper in brain and other extrahepatic tissues

Metabolic/Degenerative

I CLINICAL ISSUES Presentation • Most common signs/symptoms o Neurologic: Asymmetric tremor, ataxia, dyskinesia, dysarthria, dystonia (mainly face), incoordination • Parkinsonian symptoms: Rigidity, bradykinesia o Psychiatric: Hyperkinetic behavior, irritability, emotional lability, difficulty in concentration, depression, psychosis, mania, personality change o Acute hepatitis, Kayser-Fleischer ring in cornea o Subtle pyramidal signs in up to 20% of cases • Clinical profile o 40-50% of patients present with liver disease o 35-50% with neurological or psychiatric symptoms o Corneal rings always present in neurologic WD

Demographics • Age o Onset of liver disease usually at age 8-16 yrs o Neurological symptoms are rare < 12 yrs o WD often recognized in 2nd-3rd decade • Gender o M = Fi M:F = 1:4 for fulminant WD presentation • Liver failure, encephalopathy, coagulopathy • Ethnicity: Higher prevalence in Japan (consanguinity)

Natural History & Prognosis • Children: Liver disease most common presentation • Older individuals: Neuropsychiatric symptoms o 1 Symptom severity with 1 brain copper deposition • Once symptomatic, WD is fatal if untreated • 70% mortality in patients with fulminant liver failure • Good prognosis with early chelation treatment • Best prognosis: Treated asymptomatic siblings

Treatment • Penicillamine, trientine, zinc, NH4 tetrathiomolybdate • Liver transplant (for severe hepatic decompensation)

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Less severe changes in signal intensity with longer duration of disease

I SELECTED REFERENCES 1. 2.

3. 4.

5.

Ferenci P: Review: diagnosis & current therapy of Wilson's disease. Aliment Pharmacol Ther. 19(2):157-65,2004 Barthel H et al: Concordant Pre- and Postsynaptic Deficits of Dopaminergic Neurotransmission in Neurologic Wilson Disease. Am] Neuroradiol 24:234-238, 2003 Sener RN: Diffusion MR Imaging Changes Associated with Wilson Disease. Am] NeuroradioI24:965-967, 2003 Van Wassenaer-van Hall HN et al: Cranial MR in Wilson Disease: Abnormal White Matter in Extrapyramidal and Pyramidal Tracts. Am] NeuroradioI16:2021-2027, 1995 Hitoshi S et al: Midbrain pathology of Wilson's disease: MRI analysis of three cases. ] Neurol Neurosurg Psych 54:624-626, 1991

Disorders, Inherited

WILSON DISEASE I IMAGE GALLERY Typical (Left) Axial T2WI MR in a young patient with Wilson disease shows bilateral symmetric laminar hyperintensity in basal ganglia and hyperintense signal in posterior limb of internal capsule (more on the left). (Right) Coronal T2WI MR in the same patient shows mixed intensities within putamina as hyperintense outer rims surrounding a central hypointensity. There is also symmetric hyperintensity of caudate nuclei.

Typical

(Left) Axial T2WI MR in a 19

yo male with Wilson disease shows laminar hyperintense signal in putamina as well as bilateral hyperintense corticospinal tracts (posterior limb of internal capsule) (arrows). (Right) Coronal T2WI MR in the same patient demonstrates hyperintense lesions in putamina.

(Left) Axial FLAIRMR in a patient with Wilson disease shows abnormal hyperintensity of the pontocerebellar tract (anterior pontine fibers, pontine tegmental reticular nucleus & middle cerebellar peduncles). (Right) Coronal T1 C+ MR in the same patient demonstrates symmetric, hypointense, nonenhancing lesions in putamina and caudate nuclei.

9 73

Metabolic/Degenerative

Disorders, Inherited

PART I SECTION 10 Toxlc/Metabollc/Deseneratiwe Acquired

DllOrden,

The spectrum of acquired toxic, metabolic, and degenerative brain diseases is almost dismayingly broad. The number of toxins that can affect the S is huge-and growing. Age-old agents such as alcohol are well-known. But who would have ever guessed the incredible number of common household agents that can be niffed, inhaled, or injected? Or the onslaught of sophisticated, laboratory-tailored "street" drugs that come into emergency rooms around the world? In this text we can only present a few of them. We divide this section into two general categories: The first section covers toxic, metabolic, nutritional and systemic diseases that may have C S manifestations. The second section, dementias and acquired degenerative diseases (some of which may in fact have a genetically-determined component), concludes our coverage of brain pathology. Specific diseases included in this section are a follows: Toxic, metabolic, nutritional and systemic diseases Hypoglycemia Kern icterus Drug abuse Hypothyroidi m Fahr disease Alcoholic encephalopathy Hepatic encephalopathy Acute hyperten ive encephalopathy (PRES) Chronic hypertensive encephalopathy Idiopathic intracranial hypertension (pseudotumor cerebri) CO p i oning Osmotic demyelination syndromes Radiation and chemotherapy Mesial temporal sclerosis Statu epilepticus Dementia and degenerative diseases ormal aging brain Alzheimer dementia Vascular (multi-infarct dementia) Fronto-temporal dementia (Pick disease) reutzfeld-jakob disease Parkinson disease Multisystem atrophy (including striatonigral degeneration, OPCD) Amyotrophic lateral sclerosis Wallerian degeneration Hypertrophic olivary degeneration

SECTION 10: Toxic/Metabolic/Degenerative Disorders, Acquired Toxic, Metabolic, Nutritional, Systemic Diseases with eNS Manifestations Hypoglycemia Kernicterus Drug Abuse Hypothyroidism Fahr Disease Alcoholic Encephalopathy Hepatic Encephalopathy Acute Hypertensive Encephalopathy, PRES Chronic Hypertensive Encephalopathy Idiopathic Intracranial Hypertension CO Poisoning Osmotic Demyelination Syndrome Radiation and Chemotherapy Mesial Temporal Sclerosis Status Epilepticus

1-10-4 1-10-6 1-10-8 1-10-12 1-10-16 1-10-20 1-10-24 1-10-28 1-10-32 1-10-36 1-10-38 1-10-42 1-10-46 1-10-50 1-10-54

Dementias and Degenerative Disorders Aging Brain, Normal Alzheimer Dementia Multi-infarct Dementia Frontotemporal Dementia Creutzfeldt-]akob Disease (C]D) Parkinson Disease Multiple System Atrophy Amyotrophic Lateral Sclerosis (ALS) Wallerian Degeneration Hypertrophic Olivary Degeneration

1-10-58 1-10-62 1-10-66 1-10-70 1-10-74 1-10-78 1-10-82 l-lOc86 1-10-90 1-10-94

HYPOGLYCEMIA

Axial OWl MR demonstrates increased occipital lobes of a hypoglycemic patient.

signal in the

Axial AOC map shows restricted diffusion in occipital lobes and splenium of corpus callosum.

Imaging Recommendations

ITERMINOLOGY Abbreviations

• Best imaging tool: MRI + DWI

and Synonyms

• Neonatal hypoglycemic

brain injury I

Definitions • Neonatal hypoglycemia ~ imbalance between supply and utilization of glucose (Glue); neonatal hypoglycemia ~ brain injury

DIFFERENTI

Venous thrombosis • May occur in neonates +/- neonatal hypoglycemia

Metabolic I

L DIAGNOSIS

IMAGING FINDINGS

stroke

• Lobar edema in urea cycle disorders

PRES

General Features • Best diagnostic clue: Severe occipita-parietal infarctions in a newborn with seizures

• Older children ~ history of immunosuppressant therapy

edema or

CT Findings • NECT: ! Occipita-parietal diffuse edema

density superimposed

on

I

PATHOLOGY General Features

MR Findings • Tl WI: Tl 1: Laminar necrosis, Ca++, petechial hemorrhage, myelin degradation • T2WI: T2 1: Infarcts (cortical/basal ganglia) • MRS: ! NAA, 1 lactate • DWI: Restricted diffusion, ! ADC (may be transient) o Commonly affected: Parietal, occipital, temporal, basal ganglia

• General path comments o Newborns with! capacity for mobilizing glucose from glycogenolysis/gluconeogenesis (GNG) OR for utilizing alternative substrates ~ hypoglycemia o Extreme Glue deprivation ~ 1 levels of excitatory amino acids (glutamate and aspartate) o Embryology-anatomy

DDx: Causes of Posterior Cerebral Infarctions

10 4

Sinus Thrombosis

Sinus Thrombosis

Toxic/Metabolic/Degenerative

Urea Cycle Disorder

Disorders, Acquired

PRES

HYPOGLYCEMIA Key Facts Terminology

Top Differential

• Neonatal hypoglycemia - imbalance between supply and utilization of glucose (Gluc); neonatal hypoglycemia - brain injury

• Venous thrombosis • Metabolic stroke

Imaging Findings • Best diagnostic clue: Severe occipito-parietal edema or infarctions in a newborn with seizures • DWI: Restricted diffusion, ! ADC (may be transient) • Best imaging tool: MRI + DWI • Fetal: Gluc crosses placenta, stored as hepatic glycogen • Neonate: Transition to extrauterine life requires t energy substrate • Genetics o Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) • Recessive> dominant o Beckwith-Wiedemann (BWS): BWS & PHHI genes both UplS region • Etiology o Inadequate substrate reserve (hepatic glycogen), muscle stores of amino acids (GNG substrates), or lipid stores • Seen with: IUGR, preeclampsia, maternal hypoglycemia or bleed o t Gluc utilization: Hypoxia, sepsis, heart disease, t bilirubinemia o Inborn errors of metabolism, midline anomalies + endocrine deficiencies o Hyperinsulinism: Uncontrolled maternal diabetes, PHHI, BWS • Epidemiology: 1.3-3 per 1,000 live births

Gross Pathologic & Surgical Features • Pale & edematous

brain, blurred gray/white boundary

Staging, Grading or Classification Criteria • Transitional-adaptive (new metabolic changes of extrauterine life) - mild, brief hypoglycemia, responds to Gluc • Secondary-associated (additional stresses of HIE, bleed, sepsis) - mild hypoglycemia, responds to Gluc • Classic-transient (IUGR and! glycogen/lipid stores, impaired GNG) - persistent late hypoglycemia, requires t amounts of Gluc • Severe recurrent hypoglycemia - variable onset, severe despite Gluc

I CLINICAL

Diagnoses

Clinical Issues • Most common signs/symptoms: Seizures/jitteriness, hypotonia, tachypnea, tachycardia, temperature instability, diaphoresis • Clinical profile: Risk factors: Small OR large babies, newborns with metabolic stress

Demographics • Ethnicity o PHHI: 1:40,000 Caucasian live births • t In population isolates

Natural History & Prognosis • Persistent uncontrolled neonatal hypoglycemia may cause irreversible brain damage - epilepsy, mental retardation

Treatment • Pre conceptual/gestational diabetic control to ! neonatal macrosomia • Blood Glue screening in newborns who are at risk or symptomatic • Intravenous glucose to restore normal blood glucose concentration • PHHI more difficult - diazoxide, octreotide, frequent feeding, subtotal pancreatectomy o Diazoxide or octreotide, frequent fee dings and raw cornstarch at night

I SELECTED REFERENCES 1. 2. 3.

Erbay CR et al: Case report: hypoglycemia and diffusion-weighted imaging. ]CAT 27: 420-223, 2003 Cornblath M et al: Hypoglycemia in the neonate. Seminars in Perinatology 24(2):136-49, 2000 Barkovich A] et al: Imaging patterns of neonatal hypoglycemia. A]NR 19:523-8, 1998

I IMAGE GALLERY

ISSUES

Presentation • Most common signs/symptoms: Seizures/jitteriness, hypotonia, tachypnea, tachycardia, temperature instability, diaphoresis • Clinical profile: Risk factors: Small OR large babies, newborns with metabolic stress

(Left) Axial OWl MR demonstrates high signal in the occipito-parietal regions and splenium of the corpus callosum of a patient with hypoglycemia. (Right) Intermediate TE (135 mSec) M RS shows low NAA (curved arrow) as well as the presence of lactate (arrow).

Toxic/Metabolic/Degenerative

Disorders, Acquired

10 5

Axial T2WI MR demonstrates increased signal intensity in the medial globi pallidi in a patient with kernicterus.

Axial T2WI MR of same case obtained 5 months later shows more pronounced increased signal in globi pallidi, diffuse delayed myelination and prominent CSF-containing spaces due to atrophy.

I TERMINOLOGY

Imaging Recommendations

Abbreviations

• Best imaging tool: MRI • Protocol advice: Noncontrast MRI for acute or chronic disease

and Synonyms

• Bilirubin or posticteric encephalopathy

Definitions • Encephalopathy due to deposition of toxic unconjugated bilirubin

IDIFfERENJIAUDIAGNOSI$ Globus

I IMAGING

FINDINGS

General Features • Best diagnostic clue o Acute: I Tl signal in globus pallidus (GP), hippocampi, substantia nigra (SN); subtle I T2 signal o Chronic: I T2 signal posteromedial border GP and dentate nucleus (DN); Tl normal

CT Findings

pallid us lesion look-alike

• Hyperalimentation (manganese): I Tl signal GP/SN • Hepatic failure: I Tl signal GP/SN, history known • Toxic/metabolic: Methyl-malonic acidemia, creatine deficiency, CO exposure

Profound hypoxic encephalopathy • I Tl, T2 signal posterior putamen, lateral thalamus, peri-Rolandic

• Not Useful in suspected cases of Kernicterus

I PATHOLOGY

MR Findings

General Features

• TlWI o Acute: I Tl signal in GP, hippocampi, SN, DN • Deposition unconjugated bilirubin or related to liver dysfunction (I manganese ?) • T2WI: I T2 signal/volume loss in posteromedial border GP, hippocampi; occasionally DN

• General path comments o Heme catabolism by-product ~ bilirubin (production is 2x greater than in adults) oLiver glucuronyl-transferase conjugates bilirubin ~ excreted by kidneys o Imbalance causes

DDx: Other Causes of Bilateral Basal Ganglia lesions

10 6

Anoxia

Anoxia

Toxic/Metabolic/Degenerative

MELAS

Hyperalimentation

Disorders, Acquired

KERNICTERUS

well appear

• Bilirubin production> bilirubin elimination • t Unconjugated bilirubin ~ immature blood-brain barrier ~ target neurons • Bilirubin;:: 20 mg/IOO dL neurotoxic in full term • Genetics: Non-hemolytic familial disorders with j glucuronyltransferase (Crigler-Najjar, Gilbert syndromes) • Etiology o Most common cause: Erythroblastosis fetalis o Bilirubin oxidized by inner mitochondrial membrane enzyme o Risk factors for t bilirubin • Breast feeding, > 10% loss birth weight, polycythemia, dehydration, hemolytic disorders o Risk factors t susceptibility to brain damage at near normal levels • Drugs compete for albumin binding of bilirubin • Sulphonamides, ceftriaxone, salicylates, Na-benzoate, hormones • Renal hypoalbuminemia, hepatic failure, j thyroidism • Prematurity, asphyxia, sepsis • t Cerebral blood flow; abnormal blood brain barrier • Epidemiology: Incidence increasing with early discharge, I breast feeding

Cross Pathologic & Surgical Features • Yellow staining> than seen on imaging o GP, "red-zone" of SN, subthalamic nuclei, mamillary bodies, lateral nuclei thalamus, hippocampi o Cranial nerve nuclei (3, 8) o Dentate nuclei, cerebellar flocculi

Microscopic

Natural History & Prognosis • Chronic: Choreoathetoid cerebral palsy, ataxia, cognitive delay, gaze paresis • Specific damage brains tern auditory nuclei ~ +/deafness • Prognosis poor once neurologic complications appear

Treatment • Early determination of hemolytic disease: Umbilical cord blood for blood type, Rh, Coombs and G6PD • Anti-D immunoglobulin prophylaxis • Phototherapy • Exchange transfusion for severe/urgent cases • SN-mesoporphyrin inhibits enzyme heme oxygenase (limits I bilirubin) • Hypothermia, feeding with milk may be beneficial

I SELECTED 1. 2. 3.

REFERENCES

Govaert P et al: Changes in globus pallidus with (pre)term kernicterus. Pediatrics. 112(6 Pt 1):1256-63, 2003 Rorke LB: Neuropathologic findings in bilirubin encephalopathy (kernicterus). I]NR 4(3):165-70, 1998 Erbetta A et al: Magnetic resonance imaging findings in bilirubin encephalopathy. I]NR 4(3):161-4, 1998

IIMA.GE GALtE.RY

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Features

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(~:l)'.'))

• Neuronal damage, neuropil spongiosis • Biluribin attach to and damage mitochondria

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ICLlNICA.L1SSUES

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Presentation • Acute, 2-5 days of life: Severe jaundice, somnolence, hypotonia, opisthotonus, rigidity, high-pitched cry, poor feeding

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(Left) Axial T1WI MR shows bright basal ganglia felt to be secondary to the patients liver dysfunction associated with kernicterus. (Right) Axial T2WI MR in chronic Kernicterus shows increased signal intensity in the medial globi pallid/.

Demographics • Age: Premature newborns,

infants not feeding well

10 7

Toxic/Metabolic/Degenerative

Disorders, Acquired

Axial NECT shows hyperdensity in the area of left basal ganglia corresponding to hemorrhage caused by extreme hypertension induced by cocaine overdose.

CTA in a different patient shows right ACA mycotic aneurysm (arrow) in a 27 yo drug abuser with bacterial endocarditis.

o Nonhemorrhagic ischemic stroke: MCA territory most common o Cocaine ~ infarctions in cerebrum, thalamus, brainstem, cerebellum, retina o Heroin, MDMA ~ globus pallidus (GP) ischemia o Amphetamines: Hemorrhage, vasculitis, pseudoaneurysm, infarcts (cortical/subcortical)

ITERM1NOL()(j¥ Definitions • Many drugs (prescription, "street") have adverse CNS effects o Major pathology generally vascular o Polydrug abuse (including EtOH) common • Cerebrovascular disease caused by illicit drug use o Cocaine: Intranasal, intravenous & intramuscular use, smoked, transplacental transfer • Cocaine hydrochloride (HCI) not smokable • Alkaloid form ("freebase", "crack") smokable o Amphetamines: Oral, intranasal, parenteral use • 3, 4-Methylenedioxymethamphetamine (MDMA, "ecstasy") o Heroin: Intravenous use, inhaled ("chasing the dragon")

• NECT o Cocaine: ICH, SAH, IVH o Heroin inhalation: Symmetric hypodensity in cerebellar white matter (WM), posterior cerebral WM and posterior limb of internal capsule • GP ischemic change (hypodensity) • CTA o May show segmental narrowing in vasculitis o CT Perfusion: May show perfusion defects

MR Findings

I·IMAGING.FINDINGS General Features • Best diagnostic clue: Young/middle-aged adult with ischemic or hemorrhagic stroke occurring in close temporal proximity to drug administration • Location o Hemorrhage: ICH, SAH, IVH

DDx: Spontaneous

CT Findings

• TIWI o Cocaine: Voxel-based morphometry • ~ Gray matter concentration in orbitofrontal, insular, cingulate and temporal cortex o Heroin vapor inhalation ~ leukoencephalopathy • T2WI o Cocaine users without cerebrovascular symptoms have 1 frequency of severe T2 hyperintense lesions • Cerebral and insular subcortex WM lesions

Intracranial Hemorrhage

in Young Adults

10 8

HTN Hemorrhage

Tumoral Hemorrhage

Toxic/Metabolic/Degenerative

Embolic Infarct

Dural Sinus Thromb

Disorders, Acquired

DRUG ABUSE Key Facts Pathology

Terminology • Cerebrovascular

disease caused by illicit drug use

Imaging Findings • Best diagnostic clue: Young/middle-aged adult with ischemic or hemorrhagic stroke occurring in close temporal proximity to drug administration • Heroin inhalation: Symmetric hypodensity in cerebellar white matter (WM), posterior cerebral WM and posterior limb of internal capsule • Cocaine users without cerebrovascular symptoms have t frequency of severe T2 hyperintense lesions • Cerebral and insular subcortex WM lesions • DWI: May show restricted diffusion • T1 C+: Subacute infarcts may enhance • MRA: Arterial spasm and/or vasculitis

• • • • •

• Incidence of WM lesions is strongly age-related • Transient occlusion of arteries in MCA territory ~ small infarctions o Heroin vapor inhalation • Hyperintense cerebral & cerebellar tracts • Involvement of cerebellar & posterior cerebral WM, posterior limb of internal capsule • Sparing of subcortical WM & dentate nuclei T2* GRE: Hemorrhagic lesions have j signal DWI: May show restricted diffusion T1 C+: Subacute infarcts may enhance MRA: Arterial spasm and/or vasculitis IH-MRS in heroin inhalation toxicity o j N-acetyl aspartate, t cerebral lactate

Angiographic

Findings

• PET o Chronic cocaine users: 150-H20-PET • Significant hypoperfusion in anterior cingulate and orbitofrontal cortex o Chronic cocaine users: FDG-PET • t Brain metabolism (global & regional in basal ganglia (BG) & orbitofrontal cortex) within 1 week of cocaine withdrawal • > 1 week: Time-dependent j metabolic activity • j Frontal metabolism in neurologically intact cocaine users persist> 6 months of abstinence o Chronic MDMA abusers: j rCBV in GP

Other Modality • 123I-R91150 SPECT

Cocaine HCl: Hemorrhagic (80%) > ischemic stroke Alkaloidal cocaine: Hemorrhagic = ischemic stroke Amphetamines: Hemorrhagic> ischemic strokes Heroin: Cerebral infarctions (MCA area, not watershed distribution), toxic leukoencephalopathy • Up to 30% of strokes in young patients (15-44 y) are drug-related • Drug-related ICH is frequently related to underlying vascular malformation (cerebral aneurysm, AVM)

Diagnostic Checklist • Drug-related hemorrhages may indicate an underlying vascular abnormality • Vasculitis can be very difficult to distinguish drug-related vasospasm

from

o Recent MDMA users: j Cortical ligand binding to serotonin (5-HT) 2A receptors (R) • Down-regulation of 5-HT2 R associated with j rCBV (vasoconstriction) in occipital cortex & GP o Ex-MDMA users: t Cortical ligand binding • Up-regulation of 5-HT2 R & t rCBV (vasodilation)

Imaging Recommendations • Best imaging tool: CT, MR • Protocol advice o NECT for suspected hemorrhage o If CT reveals hemorrhage ~ CTA/MRA/DSA o MR: Include T1 C+, GRE

I DIFFERENTIAL DIAGNOSIS

Findings

• Conventional o Cocaine-related strokes • Normal (unless predisposing lesion, e.g., AVM/aneurysm) • Intraluminal clot with normal vessels, vasospasm • Occlusion/narrowed arteries at base of brain or major branches of MCA o Heroin: Normal or beading in distal cerebral arteries • Stenosis/occlusion of internal carotid siphon/MCA

Nuclear Medicine

• • • •

Findings

Spontaneous intracranial hemorrhage young adults

in

• Hypertension (HTN): BG hemorrhages • Vascular malformations o Cavernous hemangiomas o Arteriovenous malformations (AVMs) • Intratumoral hemorrhage o Seen in "" 1% of brain tumors, usually malignant • Incomplete hemosiderin rings, enhancing nodule • (Persistent) mass effect out of proportion to amount of hemorrhage • Dural sinus thrombosis with hemorrhagic infarct o Underlying coagulable state often present (e.g., activated protein C deficiency) o Infarcts typically hemorrhagic and subcortical

I PATHOLOGY General Features • General path comments o Cocaine HCl: Hemorrhagic (80%) > ischemic stroke o Alkaloidal cocaine: Hemorrhagic = ischemic stroke o Amphetamines: Hemorrhagic> ischemic strokes

10 9

Toxic/Metabolic/Degenerative

Disorders, Acquired

o Heroin: Cerebral infarctions (MCA area, not watershed distribution), toxic leukoencephalopathy • Etiology o Cocaine, amphetamines • Systemic vasoconstriction ~ acute arterial HTN ~ hemorrhagic stroke (rupture of preexisting aneurysms, bleeding from AVM) • Cerebral vasoconstriction, vasculitis ~ infarction o Parenteral drugs • Infective endocarditis (IE) ~ emboli ~ cerebral infarction, hemorrhage, abscess, mycotic aneurysm • Bacteremia in absence of IE ~ brain abscess • Hepatitis ~ bleeding diathesis o Cocaine • t Platelet aggregation with thrombosis • Heart disease ~ source of emboli o MDMA abuse: Loss of serotoninergic neurons o Heroin ~ toxic leukoencephalopathy, hypoxic brain injury, ischemic stroke, brain abscess • Generalized hypoxia and hypotension • Possible immunologic mediated vasculitis • Nephropathy ~ severe HTN o Concomitant alcohol use may potentiate illicit drug effects by i hepatic metabolism • Epidemiology o 4% of all strokes occur in persons < 45 Y o Up to 30% of strokes in young patients (15-44 y) are drug-related o Estimated relative risk for stroke among drug abusers (after controlling for other stroke risk factors) is 6.5 • Associated abnormalities o Drug-related ICH is frequently related to underlying vascular malformation (cerebral aneurysm, AVM) o Drug-induced IE, vasculitis

Gross Pathologic & Surgical Features • Amphetamine, cocaine ~ arterial spasm/vasculitis • Cocaine in pregnancy ~ fetal infarctions in BG and t rate of neural tube closure defects • Amphetamine, cocaine and MDMA ~ ICH, SAH • MDMA ~ vasoconstriction in recent users and vasodilatation in ex-users o Bilateral GP necrosis (due to prolonged vasospasm)

Microscopic

Features

• Amphetamines ~ inflammatory vasculitis with vessel wall necrosis ("speed arteritis") similar to PAN • Cocaine ~ vasculitis affecting the CNS • Heroin ~ vasculitis (rare) probably related to contaminants used during preparation o Inhaled heroin vapors ~ symmetric spongiform degeneration in cerebral and cerebellar WM and corticospinal and solitary tracts

• Toxic leukoencephalopathy ~ cerebellar, pyramidal & pseudobulbar signs, spasms, death • Delayed post-anoxic encephalopathy ~ prolonged coma with extensor posturing • Clinical profile o Cerebral infarcts, TIAs, ICH, SAH • Temporal proximity of stroke to drug use

Demographics • Age o 85-90% of drug-related strokes: In 4th-5th decade • Age range: Perinatal to 63 y • Gender: M = F

Natural History & Prognosis • Time interval between drug use, stroke onset can be as long as one week o Risk for stroke is highest within first 6 hours after drug use and decreases with time • Strokes related to IE may be delayed o 20% mortality for IE-associated strokes of all kinds o 67% mortality for hemorrhagic strokes • Risk of stroke recurrence lessens during abstinence • Cocaine worsens presentation and outcome of patients with aneurysmal SAH • Very rare: Rapidly growing aneurysm in major intracranial vessels due to amphetamine abuse

Treatment • Management of drug-related stroke: Largely supportive • Antibiotics for embolic stroke due to IV drug-induced IE ~ i risk of recurrent infarction • Aggressive addiction rehabilitation • Experimentally, magnesium reverses cocaine-induced vasospasm

IDIACNOSTICCHECiKt.IST Consider • Drug abuse in young/middle-aged stroke

Image Interpretation

10 10

Pearls

• Drug-related hemorrhages may indicate an underlying vascular abnormality • Vasculitis can be very difficult to distinguish from drug-related vasospasm

I SELECTED REFERENCES 1. 2.

3.

Presentation

individual with

4.

• Most common signs/symptoms o Cocaine: Stroke, headache, seizures o Severe headache immediately after using cocaine, amphetamines, MDMA ~ think ICH o Heroin: BG damage ~ parkinsonism, hemiballism

Toxic/Metabolic/Degenerative

Keogh CF et al: Neuroimaging features of heroin inhalation toxicity: "Chasing the dragon". AJR 180: 847-850, 2003 Bartzokis G et al: The incidence of T2-weighted MR imaging signal abnormalities in the brain of cocaine-dependent patients Is age-related and region-specific. Am J Neuroradiol 20: 1628-1635, 1999 Kokkinos J et al: Illicit drugs and over-the-counter sympathomimetics. Neurol Clin 11: 577-590, 1993 WojackJC et al: Intracranial hemorrhage and cocaine use. Stroke 18: 712-715, 1987

Disorders, Acquired

Typical (Left) Axial PO/Intermediate

MR shows bilateral hyperintense globi pallidi (arrows) due to heroin abuse. (Right) Axial T2WI MR shows multiple areas of increased signal intensity in basal ganglia consistent with infarcts caused by amphetamine use.

Typical (Left) Axial T2WI MR shows bilateral periventricular hyperintensities likely related to vasculitis secondary to amphetamine use. (Right) Axial T2WI MR shows left temporal hyperintense infarct with areas of hemosiderin deposition from prior hemorrhage.

Typical (Left) Axial PO/Intermediate

MR in a patient who used MOMA ("ecstasy") shows hypointense rim consistent with hemorrhagic products. (Right) Axial FLAIRMR in the same patient shows right lentiform nucleus infarct.

10 11

Toxic/Metabolic/Degenerative

Disorders, Acquired

Coronal TIWI MR shows enlargement of pituitary gland consistent with clinical picture of primary hypothyroidism.

Sagittal T1 C+ MR shows enlargement of the pituitary gland consistent with the clinical picture of primary hypothyroidism.

MR Findings Abbreviations • Hashimoto

and Synonyms

thyroiditis

(HT), encephalopathy

(HE)

Definitions • Thyroid hormone deficiency ~ multiorgan signs/symptoms, including brain

IIMAGINGBNOINGS General Features • Best diagnostic clue: Symmetrical pituitary enlargement reversible with thyroid hormone replacement therapy (THRT) • Location: Pituitary enlarged, variable suprasellar extension/mass effect • Size: Increased (volume correlates with circulating thyrotropin levels) • Morphology: Hyperplasia of anterior pituitary

• TlWI o Enlarged pituitary isointense to cerebral WM o With THRT: Brain size t, ventricular size I o BG variably hyperintense (Ca++) o In endemic neurological cretinism • Bilateral globi pallidi, substantia nigra hyperintensity • Mild generalized atrophy • Enlargement of Sylvian fissures • T2WI o Homogeneous diffuse enlargement of pituitary gland, ± suprasellar extension, ± partial or complete obliteration of the infundibulum, ± compression of optic chiasm o Enlarged pituitary gland is isointense to cerebral white matter o In patients with HT-associated ataxia • Cerebellar vermis or olivopontocerebellar atrophy o Reported findings in Hashimoto encephalopathy

CT Findings • NECT o Sellar mass ± suprasellar extension o Basal ganglia (BG), variable cerebellar Ca++ • CECT: Enhancing intra/suprasellar mass

(HE)

• Cerebral atrophy • Diffuse/focal cortical, subcortical WM hyperintensity o In endemic neurological cretinism • Hypointensity in area of globus pallidus and substantia nigra bilaterally

DDx: Enlarged Pituitary Gland

10 12

Physiol Hyperpl

Hypophysitis

Toxic/Metabolic/Degenerative

Macroadenoma

Intracran Hypotens

Disorders, Acquired

HYPOTHYROIDISM Imaging Findings • Best diagnostic clue: Symmetrical pituitary enlargement reversible with thyroid hormone replacement therapy (THRT) • Basal ganglia (BG), variable cerebellar Ca++ • Enlarged pituitary isointense to cerebral WM • PET: Severe hypothyroidism (short duration): Generalized l regional CBF, glucose metabolism • Tc-99m HMPAO SPECT: Reversible cerebral hypoperfusion (25% l mean CBF) in reversible dementia caused by hypothyroidism • Best imaging tool: MR

Top Differential

Diagnoses

• Pituitary macroadenoma • Physiologic hyperplasia of pituitary • Hypophysitis

•

in

•

• Mild generalized atrophy • Enlarged Sylvian fissures • PD/lntermediate: Homogeneous hyperintense gland • Tl C+ o Enlarged pituitary enhances homogeneously, intensely, ~ cavernous sinuses o No focal hypointensities (suggestive of adenoma) • MRS: 1 Cho in untreated congenital hypothyroidism reflecting blocked myelin maturation

I PATHOl-O.GY

Nuclear Medicine

General Features

Findings

• PET: Severe hypothyroidism (short duration): Generalized l regional CBF, glucose metabolism

Other Modality

Findings

• Tc-99m HMPAO SPECT: Reversible cerebral hypoperfusion (25% l mean CBF) in reversible dementia caused by hypothyroidism

Imaging Recommendations • Best imaging tool: MR • Protocol advice: Coronal Tl C+

I DIFFERENTIAl-DIAGNOSIS Pituitary macroadenoma • Difficult to differentiate adenoma from pituitary hyperplasia • TlWI o Adenomas may be homogeneous or heterogeneous, typically with lower signal than normal pituitary gland o Isointense signal if hemorrhage or necrosis within adenoma • Tl C+: Focal hypointensity suggests macro- or micro adenoma

Physiologic hyperplasia of pituitary • Puberty, pregnancy, postpartum (first week) • Can be indistinguishable on imaging studies

Hypophysitis • Thick/bulbous

• Intense uniform enhancement

Enlargement of pituitary gland with spontaneous intracranial hypotension • Look for diffuse dural thickening, midbrain'" tonsillar herniation

"slumping

• General path comments o Diffuse hyperplasia of anterior pituitary o Cretinism • Malformed convolutions • Poor differentiation of cortical layers • Reduction in quantity of white matter • Nerve cell loss, delayed myelination • Etiology o Primary hypothyroidism • HT (most common cause in North America): Autoimmune disease • Iatrogenic hypothyroidism (second most common): Post-thyroidectomy, post-radioactive 1311 therapy • Congenital hypothyroidism: Aplasia/hypoplasia of thyroid gland, ectopic gland, enzymatic defects in thyroid hormone synthesis pathway • Goitrous hypothyroidism: In severe endemic iodine deficiency; extinct in USA, but major cause of mental deficiency worldwide o Secondary hypothyroidism: Uncommon cause • Hypothalamic-pituitary axis failure (l TRH/TSH) o Lack of inhibition of hypothalamic TRH, pituitary TSH caused by insufficient quantity of thyroid hormones o High TRH levels increase mainly TSH release, but also prolactin release from pituitary o Two mechanisms of cerebellar dysfunction in hypothyroidism • Endocrine disorder, reversible with THRT

stalk ± enlarged pituitary

Toxic/Metabolic/Degenerative

10 13

Disorders, Acquired

• Autoimmune mediated (HT), not reversed by THRT o Encephalopathy associated with HT • Likely autoimmune pathogenesis • Possible underlying cerebral vasculitis • Epidemiology o 8-9 million Americans have acquired hypothyroidism o Congenital hypothyroidism: Caucasian infants (1:4,000) affected more than African-American infants (1:30,000) • Associated abnormalities o HT is associated with other autoimmune diseases • Rheumatoid arthritis, SLE,IDDM, ulcerative colitis, myasthenia gravis, MS, pernicious anemia o Circulating antithyroid antibodies in 70-95% of patients with HT o Encephalopathy associated with subclinical HT with high titers of antithyroid antibodies

• 1 In brain size and I in ventricular size with treatment correlate with changes in levels of circulating thyroid hormones • In congenital hypothyroidism o Start treatment ASAP « 13 days) o Initial hormone replacement with levothyroxine should be ~ 10 Ilg/kg/day o Patients with early treated congenital hypothyroidism often develop subnormally and display subtle neurological defects • Endemic cretinism is determined in utero, is irreversible by postnatal treatment • Acquired cerebellar ataxia is typically reversible with THRT o In few patients: Ataxia persists despite THRT • HE: Steroid responsive in some patients

Gross Pathologic & Surgical Features

Consider

• Diffuse enlargement of pituitary gland • HT with cerebellar dysfunction: Atrophy of anterosuperior vermis

• Urgent thyroid function tests should be performed in all patients with pituitary enlargement prior to surgery to exclude hypothyroid induced pituitary swelling • Consider hypothyroidism in child (especially male) with diagnosis of "pituitary adenoma"!

Microscopic Features • Hyperplasia of thyrotrophs (thyrotropin-producing cells), +/- lactotrophs (prolactin-producing cells) in anterior lobe of otherwise normal pituitary gland • HT with cerebellar dysfunction: Loss of Purkinje cells o ± Gliosis of ventral pons

ICtlN ICALJSSIJES Presentation • Most common signs/symptoms o Hypothyroidism: Poor memory, psychomotor slowing, depression, reversible dementia o Acquired cerebellar ataxia o HE: Seizures, neuropsychiatric changes or focal neurological deficits o Other: Headache, visual impairment (bitemporal hemianopsia) if 11 pituitary

Demographics • Age o In acquired hypothyroidism, prevalence 1 with age o HE reported in pediatric and adult patients • Gender: Females commonly affected (in different epidemiologic surveys M:F ratio ranges from 1:2 to 1:8) by acquired hypothyroidism

Natural History & Prognosis • Rapid progression (3 weeks) of hyperplasia of anterior pituitary proven in acute development of hypothyroidism • In congenital hypothyroidism: Main developmental delay originates during first 3 months after birth

I.O.IACNioSTlcrCHECKI.ISJ

I SELECTED REFERENCES Oatridge A et al: Changes in brain size with treatment in patients with hyper- and hypothyroidism. Am J Neuroradiol 23:1539-1544, 2002 2. Selim M et al: Ataxia associated with Hashimoto's disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis. J Neurol Neurosurg Psychiatry 71: 81-87, 2001 3. Constant EL et al: Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study. J Clin Endocrinol Metab 86: 3864-3870, 2001 4. Bongers-Schokking JJ. Pre- and postnatal brain development in neonates with congenital hypothyroidism. J Pediatr Endocrinol Metab 14: 1463-1468,2001 5. Papakonstantinou 0 et al: MR imaging of pituitary hyperplasia in a child with growth arrest and primary hypothyroidism. Eur Radiol1O: 516-518, 2000 6. Kinuya S et al: Reversible cerebral hypoperfusion observed with Tc-99m HMPAO SPECT in reversible dementia caused by hypothyroidism. Clin Nucl Med 24: 666-668, 1999 7. Shimono T et al: Rapid progression of pituitary hyperplasia in humans with primary hypothyroidism: Demonstration with MR imaging. Radiology 213: 383-388, 1999 8. Desai MP et al: Pituitary enlargement on magnetic resonance imaging in congenital hypothyroidism. Arch Pediatr Adolesc Med 150: 623-628, 1996 9. Wolansky LJ et al: MRI of pituitary hyperplasia in hypothyroidism. Neuroradiology 38: SO-52, 1996 10. Gupta RK et al: Brain metabolite changes on in vivo proton magnetic resonance spectroscopy in children with congenital hypothyroidism. J Pediatr 126: 389-392, 1995 1.

Treatment • Prompt regression of pituitary enlargement with THRT

10 14

Toxic/Metabolic/Degenerative

Disorders! Acquired

HYPOTHYROIDISM

Variant (Left) Axial T2WI MR in a patient with Hashimoto encephalopathy shows diffuse confluent white matter hyperintensity with striking sparing of posterior aspects of cerebral hemispheres. (Right) Axial T2WI MR in the same patient shows symmetric involvement, edema in both external and internal capsules. Note sparing of corpus callosum.

Variant (Left) Axial FLAIRMR in the

same case shows hyperintensity extends into both temporal lobes. Diffuse brain swelling obliterates basal cisterns. (Right) Axial FLAIRMR shows hyperintensity extends to the subcortical U-fibers, involves the posterior pons and major cerebellar peduncles.

Variant (Left) Axial PO/Intermediate MR shows hyperintense putamen, globi pallidi, and caudate nuclei in a 77 year old female with longstanding hypothyroidism. (Right) Axial T7WI MR in the same shows focal hyperintensity in both globi pallidi. NEeT scan (not shown) disclosed dense calcifications in the basal ganglia, especially in the pallidi.

10 15

Toxic/Metabolic/Degenerative

Disorders, Acquired

Axial NECT shows bilateral heavy calcifications in basal ganglia and thalami.

• Cerebral white matter, internal capsule • Morphology: Variable extent; dense Ca++ often conforms to outline of BG

ITERMINOtQGY Abbreviations • • • • •

Coronal NECT in the same patient shows bilateral heavy calcifications in caudate nuclei and putamina. Cortical atrophy also observed.

and Synonyms

Fahr disease (FD) Cerebrovascular ferrocalcinosis Idiopathic non arteriosclerotic cerebral calcifications Bilateral striopallidodentate calcinosis (BSPDC) Idiopathic basal ganglia calcification (IBGC)

Definitions • Rare degenerative neurological disorder characterized by extensive bilateral basal ganglia (BG) calcifications that can lead to progressive dystonia, parkinsonism, and neuropsychiatric manifestations

I·IMAGINQFINDINCS General Features • Best diagnostic clue: Bilateral symmetric BG Ca++ on

CT • Location o Globus pallidus = most common site of Ca++ • Lateral pallidum more affected than medial pallidum o Additional areas of involvement may include • Putamen, caudate nuclei, thalami • Cerebellum (especially dentate nuclei)

Radiographic Findings • Radiography: Heavy bilateral/symmetrical BG Ca++ may be detectable on plain skull radiography

CT Findings • NECT: Bilateral, symmetrical Ca++ in BG, cerebral white matter, dentate nuclei, cerebellum • CECT: No enhancement

MR Findings • TlWI o Varying signal intensities of calcified lesions on MR related to • Stage of disease, volume of calcium deposit • Differences in calcium metabolism o Ca++ usually hyperintense on Tl WI o Hyperintense lesions in WM, especially centrum semiovale, may not be related to Ca++ • T2WI o T2 hyperintense areas in white matter • Mainly involve entire centrum semiovale • Do not correspond to any calcification • May reflect slowly progressive, metabolic or inflammatory brain process, which subsequently becomes calcified

DDx: Basal Ganglia Calcifications

"

I

\

l

I

\

16

~,

Physiological BCC

Aicardi-Coutieres

\

\

\

10

\

~)

Radiation + Cherno Rx

Toxic/Metabolic/Degenerative

Disorders, Acquired

Hyper PTH

FAHR DISEASE Key Facts Imaging Findings

Clinical Issues

• Best diagnostic

• • • • •

clue: Bilateral symmetric BG Ca++ on

CT • Functional abnormalities may precede morphological changes in FD process • ! Perfusion to calcified lesions

Top Differential

Diagnoses

Neuropsychiatric disturbance Cognitive impairment (subcortical dementia) Extrapyramidal movement disorders Early adulthood (schizophrenic-like psychosis) 6th decade (extrapyramidal syndrome, subcortical dementia)

Diagnostic Checklist

• Normal (symmetrical BG Ca++ in middle-aged, elderly) • Pathologic BGC (e.g., endocrinological, neuropsychiatric)

• FD in parkinsonian patients with dementia and cerebellar signs • Incidental discovery of BGC < 50 Y merits diagnostic investigation

Pathology • Calcium-phosphorus metabolism usually normal • Ca++ along capillary vessels, medial walls/adventitia of larger arteries, veins

o Dense Ca++ can appear hypo-/hyperintense T2WI • FLAIR: Same as T2WI

Angiographic

Findings

• Conventional:

Normal

Nuclear Medicine

on

Findings

• PET o May show ! bilateral FDG uptake in BG • Also seen in frontal and temp oro-parietal cortices and hippocampal area o Functional abnormalities may precede morphological changes in FD process

Other Modality

Findings

• SPECT with 99Tc-ethyl-cysteinate-dimer (ECD) o ! Perfusion to calcified lesions • Not associated with volume of calcium deposits o Correlates with clinical signs

Imaging Recommendations • Best imaging tool oCT: Higher diagnostic specificity for BGC than MR o CT is sensitive to small quantities of calcium o CT allows earlier diagnosis • Protocol advice: Axial NECT

I DIFFERENTIAl. DIAGNOSIS Normal (symmetrical BG middle-aged, elderly)

Ca++ in

• Localized in globus pallidus • Usually punctate, sometimes moderately heavy or quite heavy • Detected on CT scan, no clinical significance • Extremely common finding in older age group • If accompanied by other calcifications, consider pathologic condition

BGC in children • BCG in children/young adults can be inherited, acquired o Associated with Down syndrome, trisomy 5 o Mitochondrial encephalopathies • Kearns-Sayre, MELAS, MERRF • BGC can occur, but not prominent feature • T2 hyperintense lesions in BG o Aicardi-Goutieres syndrome • Autosomal recessive disorder • Encephalopathy shortly after birth =} developmental arrest o HIV encephalitis • Calcification in BG and cerebral atrophy o Cockayne syndrome • Autosomal recessive disorder of DNA repair • CT: Cortico-subcortical atrophy, BGC, and dentate nuclei calcification • T2WI: Hyperintensity of periventricular white matter and subcortical U-fibers • T2WI hypointense putamina and caudate nuclei • Atrophy of cerebellar vermis and brain stem • Dwarfism, microcephaly, mental retardation • Photosensitivity, ocular abnormalities • Gait disturbance, progeroid appearance o Long-term complications of radiation therapy for childhood brain tumors and intrathecal chemotherapy • Bilateral BGC, leukoencephalopathy

Pathologic BGC (e.g., endocrinological, neuropsychiatric) • Endocrinologic disorders o Hyperparathyroidism, hypoparathyroidism, pseudo hypoparathyroidism, post -thyroidectomy o Similar distribution of calcifications as in FD • Bilateral BG: Both globus pallidus and putamen • Dentate nuclei, thalami, subcortical areas o Hypoparathyroidism: t Ionic calcium in interstitial tissues with! levels of circulating calcium

10 17

Toxic/Metabolic/Degenerative

Disorders, Acquired

o Calcification in primary hypoparathyroidism is more diffuse than in other etiologies of calcification o Post-thyroidectomy hypoparathyroidism calcifications are more focal • Neuropsychiatric disorders (e.g., lupus, motor neuron disease)

• 6th decade (extrapyramidal syndrome, subcortical dementia) o Neurological manifestations vary, but movement disorders are most common • Parkinsonism most common, usually permanent and progressive • Childhood transient parkinsonism also reported • Paroxysmal dystonic choreoathetosis o Seizures

General Features

Demographics

• General path comments o Ca++ extracellular, extravascular space, often surrounding capillaries o Ca++ in areas of demyelination, lipid deposition • Genetics o IEGC (first gene locus mapped for lEGe) on chromosome 14q o FD is often familial but loci heterogeneous • Autosomal recessive or autosomal dominant • Autosomal dominant in most families with FD • Variable expressivity within same family, but most patients are symptomatic • "Genetic anticipation" (age of onset I with each transmission in a multigenerational family with dominantly inherited FD) • Etiology o Calcium-phosphorus metabolism usually normal o CNS Ca++ in FD could represent • Metastatic deposition secondary to local BBB disruption • Disorder of neuronal calcium metabolism o Defective iron transport and free radicals ~ tissue damage ~ calcification • Epidemiology: Rare • Associated abnormalities: Parkinsonism in autosomal dominant FD

• Age o Onset of clinical symptoms is typically 30-60 y o An infantile form also described • Gender: No gender predominance

Gross Pathologic & Surgical Features • Characteristic

pallidal calcification

Microscopic

Features

• Ca++ along capillary vessels, medial walls/adventitia of larger arteries, veins • Predominant element is calcium • Other elements (Zn, P, Fe, Mg, AI, K) also present • Calcium is incorporated into proteins or bound to polysaccharides during development and maturation of pathologic process

Natural History & Prognosis • Progressive mental deterioration and loss of motor accomplishments o Degenerative rather than developmental disorder • Adult-onset FD: Calcium deposition begins in 3rd decade, with neurological deterioration 2 decades later • Symmetrical spastic paralysis and sometimes athetosis appear, progressing to a decerebrate state

Treatment • Options, risks, complications o No specific treatment to limit progression of calcification o Theoretical improvement using chelators (xydifon, penicillamine, deferoxamine) o Antioxidants and calcium antagonists

Consider • FD in parkinsonian patients with dementia and cerebellar signs • Incidental discovery of BGC < 50 Y merits diagnostic investigation

Image Interpretation

1. 2.

Presentation

10

• Most common signs/symptoms o Neuropsychiatric disturbance o Cognitive impairment (subcortical dementia) o Extrapyramidal movement disorders • Clinical profile o Usually asymptomatic in first 2 decades of life, despite presence of multiple brain calcifications o Bimodal pattern of clinical onset • Early adulthood (schizophrenic-like psychosis)

3.

4.

Ogi S et al: Imaging of bilateral striopallidodentate calcinosis. Clin Nuc1 Med, 27:721-724, 2002 Hempel A et al: PET findings and neuropsychological deficits in a case of Fahr's disease. Psychiatry Research, 108:133-140, 2001 Geschwind DH et al: Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr's disease). AmJ Hum Genet, 65:764-772,1999 Avrahami E et al: MRI and CT correlation of the brain in patients with idiopathic intracranial calcification. J Neurol, 241:381-384, 1994

18

Toxic/Metabolic/Degenerative

Pearls

• MRI correlates better than CT with functional impairment • Symmetric BG Ca++ in middle-aged/older adults common, normal

Disorders, Acquired

Typical (Left) Axial NECT shows dense calcifications in both thalami and small irregular calcifications in left globus pallidus. (Right) Axial NECT in the same patient shows dense calcifications in the body of the caudate nuclei and periventricular regions.

(Left) Axial NECT shows dense calcifications in the head of caudate nucleus and lentiform nucleus bilaterally. Cortical atrophy also seen. (Right) Axial NECT in a different patient shows calcifications in globi pallidi and cerebellum.

Variant (Left) Axial NECT shows multiple foci of dense calcifications in the centrum semiovale and at the gray-white junction. (Right) Axial NECT in the same patient shows heavy calcifications in basal ganglia and cerebral white matter.

10 19

Toxic/Metabolic/Degenerative

Disorders, Acquired

Sagittal graphic shows generalized and superior vermian atrophy, necrosis in the corpus callosum related to EtOH toxicity. Mammillary body, periaqueductal gray necrosis is seen with WE.

Sagittal TlWI MR shows classic superior vermian atrophy in a 38 year old alcoholic. The mamillary bodies appear atrophic (arrow) which may be related to WE.

• Cerebellum, superior vermis • Corpus callosum (Marchiafava-Bignami disease) +/-lateral extension into adjacent white matter • Basal ganglia (associated liver disease) o MtOH: Putamen, hemispheric white matter oWE • Mamillary bodies, periaqueductal gray matter, hypothalamus • Thalami adjacent to 3rd ventricle

ITERMINOLOGY Abbreviations

and Synonyms

• Alcoholic (EtOH) encephalopathy; methanol (MtOH) encephalopathy; Wernicke encephalopathy (WE)

Definitions • Acute, subacute, or chronic toxic effects of EtOH or MtOH on the CNS • Primary (direct) effects of EtOH = neurotoxicity (cortical/ cerebellar degeneration, peripheral polyneuropathy) • Secondary (indirect) effects (Le., trauma, malnutrition) • Rare treatable complication = WE

IIMAGINGiFINDING$ General Features • Best diagnostic clue o EtOH: Disproportionate superior vermian atrophy o MtOH: Bilateral hemorrhagic putaminal necrosis oWE: Mamillary body, medial thalamus, hypothalamus, periaqueductal gray abnormal signal/enhancement • Location o EtOH • Cerebral hemispheres, especially frontal lobes

CT Findings • NECT o EtOH: Generalized atrophy; superior vermis atrophy o MtOH: Bilateral hemorrhagic putaminal necrosis o WE (acute): Often normal • May see hypodensity in periaqueductal gray matter, mamillary bodies and medial thalamus • CECT: Acute alcohol-induced demyelination may enhance

MR Findings • TlWI o EtOH (dose-dependent) • Symmetric enlargement of lateral ventricles, sulci with chronic EtOH • t Size of cerebral sulci, interhemispheric/Sylvian fissures • +/- Hyperintensity in basal ganglia (liver dysfunction)

DDx: Cerebellar Atrophy

10 20

Chronic Dilantin

Marie Ataxia

Toxic/Metabolic/Degenerative

OPCD

Alzheimer

Disorders, Acquired

Dementia

ALCOHOLIC

ENCEPHALOPATHY Key Facts

Terminology

Top Differential

• Acute, subacute, or chronic toxic effects of EtOH or MtOH on the CNS

• • • •

Imaging Findings • EtOH: Disproportionate superior vermian atrophy • MtOH: Bilateral hemorrhagic putaminal necrosis • WE: Mamillary body, medial thalamus, hypothalamus, periaqueductal gray abnormal signal! enhancement • Symmetric enlargement of lateral ventricles, sulci with chronic EtOH • Bilateral hemorrhagic putaminal necrosis characteristic for methanol toxicity • 18F-FDG-PET: Significant decrease in whole-brain metabolism with chronic EtOH • Protocol advice: Contrast-enhanced MR + DWI

•

• • • • •

o MtOH • Bilateral hemorrhagic putaminal necrosis characteristic for methanol toxicity • Hemorrhagic subcortical necrosis • White matter hypointense lesions (confluent hemispheric +/- optic nerves) o WE: May see hypointensity in periaqueductal gray matter, mamillary bodies, hypothalamus, and medial thalamus • Chronic: Atrophic mamillary bodies (sagittal scan) T2WI o EtOH • Nonspecific multifocal WM hyperintensities common • Marchiafava-Bignami disease: Hyperintense corpus callosum (middle layers) virtually pathognomonic o MtOH • Acute hemorrhagic necrosis may cause hypointense foci oWE • Hyperintensity around 3rd ventricle, mamillary bodies, hypothalamus, medial thalamus, midbrain (periaqueductal gray) FLAIR: Lesions all typically hyperintense DWI o MtOH: Restriction (high signal) in putamen o WE: Restriction in/around 3rd ventricle, midbrain T1 C+: WE: Enhancement of mamillary bodies, periaqueductal gray, medial thalamus MRS: EtOH: NAA/Cr, Cho/Cr decreased in frontal lobes, cerebellum; recovers after detoxification fMRI o EtOH-induced motor inefficiency, alterations of cortical-cerebellar circuits o Children prenatally exposed to EtOH have deficits in information processing, memory

Nuclear Medicine

Findings

• PET o EtOH • 18F-FDG-PET: Significant decrease in whole-brain metabolism with chronic EtOH • Magnitude of reduction greater in males

Diagnoses

Nonalcoholic atrophy Anoxic infarcts Carbon monoxide (CO) poisoning Acquired/inherited metabolic disorders

Pathology • Alcohol readily crosses BBB • Causes both direct/indirect neurotoxicity • Epidemiology: EtOH, brain atrophy = dose-dependent, independent of gender/ethnicity

Diagnostic Checklist • 50% of WE cases occur in nonalcoholic including children

population,

oWE: 18F-FDG-PET: Diencephalic, medial temporal, limbic and retrosplenial hypometabolism

Imaging Recommendations • Best imaging tool o NECT for complications such as subdural hematoma, coagulopathies o MR for possible Wernicke encephalopathy (NB: Lack of imaging abnormalities does not exclude WE) • Protocol advice: Contrast-enhanced MR + DWI

I DIFFERENTIAl. Nonalcoholic

DIAGNOSIS

atrophy

• Alzheimer dementia (AD) = hippocampal, temporal atrophy, hypometabolism • Multi-infarct dementia pattern = focal infarcts +/generalized atrophy • Malnutrition, eating disorders = generalized • Chronic trauma = atrophy + cortical/axonal hemorrhages common • Inherited cerebellar degeneration syndromes (Marie ataxia, OPCD, etc)

Anoxic infarcts • Most are nonhemorrhagic vs hemorrhagic MtOH • Basal ganglia typically affected • Symmetric T2 hyperintensities typical

necrosis in

Carbon monoxide (CO) poisoning • Globi pallidi > putamen • Symmetric T2 hyperintensities typical • May involve hemispheric WM

Acquired/inherited

metabolic disorders

• Osmotic demyelination syndrome = pontine> putamen, cortical involvement • Inherited metabolic disorders (e.g., Wilson, Leigh disease) often involve basal ganglia

Toxic/Metabolic/Degenerative

10 21

Disorders, Acquired

ALCOHOLIC

ENCEPHALOPATHY

Ip~l'l-f(I)tQ(jM

• Cognitive problems, impaired memory • Most common neurologic abnormality =: polyneuropathy • Gait abnormalities, nystagmus (cerebellar degeneration) o WE =: triad of ataxia, oculomotor abnormalities, confusion • 80% have polyneuropathy • 50% nonalcoholic (end-stage cancer, bone marrow transplant), intractable vomiting, prolonged hyperalimentation o Korsakoff's psychosis =: amnestic syndrome o Marchiafava-Bignami disease =: sudden onset of altered mental status, seizures, dysarthria, ataxia, hypertonia, pyramidal signs

General Features • General path comments o Chronic EtOH • Brain shrinkage, cortical atrophy reflect lifetime consumption • EtOH modulates GABAergic neurotransmission in males> females o MtOH: Pallidal necrosis o WE: Demyelination, neuronal loss in affected areas • Etiology o EtOH • Alcohol readily crosses BBB • Causes both direct/indirect neurotoxicity o MtOH toxicity • Methanol metabolized to formaldehyde, formic acid • Causes "anion gap acidosis" • Select toxic effect on putamen, optic nerves • Commercial products containing methanol include antifreeze, paint remover, photocopying fluid oWE • Thiamine deficiency impairs dependent enzymes results in glutamate accumulation/cell damage • Nonalcoholic WE has same pathophysiology but different etiology (e.g., malnutrition, hyperalimentation) • Epidemiology: EtOH, brain atrophy =: dose-dependent, independent of gender/ethnicity • Associated abnormalities o EtOH • May increase risk of ischemic stroke, especially in putamen and anterior cerebral artery territories • Hepatic encephalopathy o Korsakoff psychosis may complicate WE

Demographics • Age: Any age (NB: WE can occur in children)

Natural History & Prognosis • EtOH: Ventricular, sulcal enlargement often reversible • WE: Ocular palsies respond first to thiamine; ataxia, apathy, confusion clear more slowly o High mortality if untreated

Treatment • EtOH: Cessation, establishment of adequate nutrition • WE

o Immediate administration of IV thiamine ~ quick response o 50% left with slow shuffling gait • Only 25% of Korsakoff patients achieve full recovery

I

DIAGNOSTIC

CHECKLIST

Consider • 50% of WE cases occur in nonalcoholic population, including children

Gross Pathologic & Surgical Features • EtOH o Atrophy (especially frontal) with enlarged ventricles, sulci o Callosal necrosis, atrophy (Marchiafava-Bignami disease)

1.

2.

• WE

o Mamillary bodies; periventricular midbrain/brain stem • Petechial hemorrhage (acute) • Mamillary body atrophy (chronic) o Dorsal medial thalamic nuclei (may cause Korsakoff psychosis)

Microscopic

I SELECTED REFERENCES

3.

4.

Features

• Axonal degeneration, demyelination (alcoholic polyneuropathy) • Purkinje cell loss (alcoholic cerebellar degeneration)

5. 6.

7.

10

Presentation • Most common signs/symptoms o Chronic EtOH

Ding J et al: Alcohol intake and cerebral abnormalities on magnetic resonance imaging in a community-based population of middle-aged adults. Stroke 35: 16-21,2004 Volkow ND et al: Positron emission tomography and single-photon emission computed tomography in substance abuse research. Semin Nucl Med. 33(2):114-28, 2003 Wang GJ et al: Alcohol intoxication induces greater reductions in brain metabolism in male than in female subjects. Alcohol Clin Exp Res. 27(6):909-17, 2003 Obata A et al: Acute effects of alcohol on hemodynamic changes during visual stimulation assessed using 24-channel near-infrared spectroscopy. Psychiatry Res. 123(2):145-52,2003 Reed LJ et al: FDG-PET findings in the Wernicke-Korsakoff syndrome. Cortex. 39(4-5):1027-45, 2003 Arbelaez A et al: Acute Marchiafava-Bignami disease: MR findings in two patients. AJNR Am J Neuroradiol. 24(10):1955-7,2003 Halavaara Jet al: Neuroimaging supports the clinical diagnosis of methanol poisoning. Neuroradiology. 44(11):924-8, 2002

22

Toxic/Metabolic/Degenerative

Disorders, Acquired

ALCOHOLIC

ENCEPHALOPATHY

IIMAGE GALLERY Typical (Left) Sagittal T2WI MR shows a swollen corpus callosum splenium with high signal in the middle white matter layers (arrow) and peripheral sparing, classic for acute Marchiafava-Bignami disease. (Right) Axial FLAIR MR in the same case shows high signal in the corpus callosum splenium (arrows) without other identifiable abnormalities. Male patient with a history of alcohol abuse and seizures.

Typical (Left) Axial T2WI MR shows symmetric hyperintensities in the medial thalami (arrows). Patient also had hyperintensities in the periaqueductal gray matter (not shown), classic for WE. (Right) Coronal T1 C+ MR in the same case shows enhancement in the tectal plate bilaterally (arrows). Nonalcoholic WE seen in a patient who had had a bone marrow transplant and hyperalimentation.

Other (Left) Axial gross pathology shows hemorrhagic putaminal necrosis characteristic of methanol toxicity. Note more focal necrosis in the lateral aspect of the putamen (arrows) (Courtesy R Hewlett, MO). (Right) Axial OWl MR in a patient with acute methanol toxicity shows restricted diffusion in both putamen (arrows), indicating acute infarction.

10 23

Toxic/Metabolic/Degenerative

Disorders, Acquired

HEPATIC ENCEPHALOPATHY

Axial T1WI MR shows hyperintense globi pallidi. Classic imaging findings in a patient with hepatic encephalopathy.

Sagittal T1WI MR in the same patient with hepatic encephalopathy shows hyperintense signal within lentiform nucleus extending into midbrain.

ITERMINOLOGY

MR Findings

Abbreviations

• TIWI o Bilateral hyperintensity in BG, particularly GP • Reported in 80-90% of chronic liver failure cases • Probably caused by manganese accumulation • Blood-brain barrier permeability to manganese may be selectively increased in chronic condition o 1 Signal intensity in pituitary gland, hypothalamus, and mesencephalon surrounding red nuclei • Occasionally 1 signal only in pituitary gland o Atrophy, especially affecting cerebellum o Acute HE: Blurring of gray-white matter junction • T2WI o Acute HE: High signal in most of cerebral cortex, sparing perirolandic and occipital regions o Hyperintense dentate nucleus, periventricular white matter (WM) o Experimentally T2 shortening is present in GP • Not evident due to intrinsic low T2 signal of GP • FLAIR: Fast-FLAIR sequences: 1 Signal along hemispheric WM in/around corticospinal tract • DWI: Acute HE: Increased cortical signal • Tl C+: No contrast-enhancement • MRS o I Myoinositol (ml), 1 glutamine/glutamate (Glx), I choline (Cho)

and Synonyms

• Hepatic encephalopathy

(HE), hepatic coma

Definitions • Functional, potentially reversible clinical syndrome during acute or chronic liver disease, characterized by psychiatric, cognitive and motor components

I IMAGING FINDINGS General Features • Best diagnostic clue: Bilateral Tl WI hyperintensity in basal ganglia (BG), particularly globus pallidus (GP) • Location: BG, particularly GP • Size: Variable, depending on degree of extent • Morphology: General similar in shape to outline of lentiform nucleus

CT Findings • NECT o Acute HE: Severe diffuse cerebral edema o Chronic HE: Cerebral atrophy, mild brain edema o No signal abnormality in BG • CECT: No contrast-enhancement of affected BG

DDx: T1 Hyperintense

Basal Ganglia lesions

10 24

Hyperalimentation

CO Poisoning

Toxic/Metabolic/Degenerative

NF Type I

Disorders, Acquired

Hypothyroidism

HEPATIC ENCEPHALOPATHY Key Facts Terminology

Top Differential

• Functional, potentially reversible clinical syndrome during acute or chronic liver disease, characterized by psychiatric, cognitive and motor components

• • • • • • • •

Imaging Findings • Best diagnostic clue: Bilateral T1WI hyperintensity in basal ganglia (BG), particularly globus pallidus (GP) • t Signal intensity in pituitary gland, hypothalamus, and mesencephalon surrounding red nuclei • Atrophy, especially affecting cerebellum • Acute HE: High signal in most of cerebral cortex, sparing perirolandic and occipital regions • Hyperintense dentate nucleus, periventricular white matter (WM) • I mllCr and CholCr ratios and t Glx/Cr ratios

• Brain glutamine concentrations are t in direct correlation with severity of HE in patients with chronic liver failure • Brain ammonia removal relies primarily on formation of glutamine o I mllCr and Cho/Cr ratios and t Glx/Cr ratios • With correction of hepatic dysfunction, these ratios normalize or overshoot the other way • mllCr: Most sensitive (80-85%) indicator of HE o May play role in monitoring lactulose therapy • Magnetization transfer imaging o t Magnetization transfer ratios in GP and other regions that appear normal on Tl WI (putamen, thalamus, corona radiata)

Ultrasonographic

Findings

• Transcranial Doppler ultrasonography o Cerebral resistance indices closely correlate with severity of cirrhosis and HE o Cerebral pulsatility and resistive indices: Elevated in cirrhotic patients with HE • HE related to increased cerebral vascular resistance

Nuclear Medicine

Findings

• PET o 13NH3-PET in chronic liver failure with mild HE • t Cerebral metabolic rate for ammonia • t "Permeability-surface area" product (measure of blood-brain barrier permeability to ammonia) o Redistribution of cerebral blood flow from cortical to subcortical areas (including BG)

Imaging Recommendations • Best imaging tool: MR imaging • Protocol advice: Multiplanar MR with Tl WI

I DIFFERENTIAL DIAGNOSIS liver copper overload • Wilson disease o Symmetrical hyperintensity in putamina caudate nuclei, and thalami on T2WI

and GP,

Diagnoses

Liver copper overload Hyperalimentation Other causes of Tl hyperintense BG Chorea-ballism associated with hyperglycemia Endocrine disorders leading to BG calcifications Fahr disease (idiopathic calcification of BG) Hypoxic-ischemic encephalopathy Neurofibromatosis type I: Unusual bright lesions

Diagnostic Checklist • With therapy, MRS and clinical response return toward normal before reversal of bright BG sign, which is delayed 3-6 months

o Hyperintensity in dentatorubrothalamic, pontocerebellar and corticospinal tracts on T2WI o Lesions appear hypo intense (occasionally hyperintense) on Tl WI, without enhancement • Cholestatic diseases • Inefficient biliary excretion of copper in newborn

Hyperalimentation • Bilateral hyperintense signal in GP and subthalamic nuclei on Tl WI, without enhancement o Caused by manganese deposition, astrogliotic reaction to such deposition, or both o Abnormal manganese metabolism in patients undergoing long-term parenteral feeding • No corresponding abnormalities on T2WI or CT

Other causes of T1 hyperintense

BG

• Microangiopathy and infarcts in AIDS • Chorea-ballism associated with hyperglycemia o Tl hyperintense putamen, caudate nucleus or both • Due to presence of abundant gemistocytes (swollen reactive astrocytes that usually appear with acute injury) o No significant T2 signal alteration, no mass effect, no gadolinium enhancement • Endocrine disorders leading to BG calcifications o Hyperparathyroidism, hypothyroidism o Hypoparathyroidism, pseudohypoparathyroidism, pseudopseudohypoparathyroidism • Fahr disease (idiopathic calcification of BG) • Hypoxic-ischemic encephalopathy o BG, para sagittal cortical areas most frequently involved • Hyperintense BG lesions on TI/T2WI • Diffuse laminar cortical hyperintensity on Tl WI in subacute stage • Laminar cortical, BG enhancement o Carbon monoxide poisoning • Most specific findings: GP hypodensity on CT and hyperintensity on T2WI • Langerhans cell histiocytosis • Neurofibromatosis type I: Unusual bright lesions

10 25

Toxic/Metabolic/Degenerative

Disorders, Acquired

HEPATIC ENCEPHALOPATHY o Hyperintensities inBG (usually GP), internal capsule bilaterally on 1'1WI o Smaller foci of hyperintensity in brain stem, cerebellar WM, dentate nucleus, BG, and periventricular WM on T2WI o Resolve by adulthood; no mass effect, edema, or gadolinium enhancement

General Features • General path comments o Mostly degenerative changes of astrocytes, Alzheimer type II astrocytosis • In cerebral (deep layers) and cerebellar cortex • In thalamic and lenticular nuclei • In many other nuclear structures of brainstem o Neuronal damage occurs later • Etiology o Underlying cirrhosis, acute fulminant viral hepatitis o Drugs and toxins, shock and/or sepsis o Childhood hepatic diseases are associated with bright hypothalamus & pituitary gland • Crigler-Najjar syndrome, Alagille syndrome • Copper toxicosis, Byler disease, biliary atresia o Porto systemic shunting through collateral vessels o Brain accumulation of neurotoxic and/or neuroactive substances • Ammonia, manganese, aromatic amino acids • Mercaptans, phenols, short-chain fatty acids • Bilirubin, neuroactive medications prescribed as sedatives to patients with liver failure o Alterations in neurotransmission, blood-brain barrier permeability and energy metabolism o Pro inflammatory cytokines (TNF Ot, interleukin lOt) may affect brain by production of nitric oxide in endothelial or neural cells after crossing a defective blood-brain barrier o HE precipitated by ammoniagenic situations • Oral protein load, GI hemorrhage, constipation • Epidemiology: Occurs in > 50% of all cases of cirrhosis • Associated abnormalities: Parkinsonian signs

Demographics • Age: Both pediatric/adult patients with severe hepatic dysfunction • Gender: No gender preference

Natural History & Prognosis • Acute HE: Severe brain edema may 1 intracranial pressure =;> cerebral herniation =;> death • Neuropsychologic signs of HE follow IH-MRS rather than MRI changes

Treatment • Identify & remove/treat precipitating factors o Infections, diuretics, sedatives, trauma o Bleeding and high-protein intake • Non-absorbable disaccharides (lactulose, lactitol) • Antibiotics (neomycin) with oto-/nephrotoxicity • L-ornithine-L-aspartate • Molecular adsorbents recirculating system albumin dialysis: Improves encephalopathy grade

Gross Pathologic & Surgical Features

Image Interpretation

• Laminar and pseudolaminar necrosis of cerebral cortex • Polymicrocavitation at gray-white matter junction

• With therapy, MRS and clinical response return toward normal before reversal of bright BG sign, which is delayed 3-6 months • With liver transplantation, T1 hyperintense BG return to normal intensity within 1 year postoperatively

Microscopic

Features

• Acute HE: Severe cytotoxic edema in astrocytes with anoxic neuronal damage o No inflammatory infiltration or demyelination • HE in chronic liver failure o Astrocytosis: Alzheimer type II astrocytes • Large swollen nuclei, prominent nucleoli • Margination of normal chromatin pattern o Neuronal degeneration

10

Presentation • Most common signs/symptoms o Altered mental status leading to stupor and coma o Jaundice, palmar erythema, spider angiomata, ecchymosis, gynecomastia, abdominal ascites o Motor abnormalities: Tremor, bradykinesia, asterixis, ataxia, apraxia, hyperreflexia o Fetor hepaticus (sweet musty aroma of breath secondary to exhalation of mercaptans) o Seizures: Rare manifestation of HE • Clinical profile o HE can occur during acute liver failure of any cause o HE can complicate chronic liver disease • Latent or subclinical (psychometric, EEG abnormalities) • Recurrent, occurring after precipitating events • Stable or permanent

1. 2.

Staging, Grading or Classification Criteria

3.

• HE type A: Associated with acute liver failure • HE type B: Associated with portal-systemic bypass • HE type C: Associated with liver cirrhosis

4.

Pearls

Lai PH et al: Hyperintense basal ganglia on T1-weighted MR imaging. AJR 172:1109-1115, 1999 Bryan RN et al: A new clinical application of MR spectroscopy in hepatic encephalopathy Am J Neuroradiol 19:1593-1594, 1998 Lee J et al: Acquired hepatocerebral degeneration: MR and pathologic findings. AmJ NeuroradioI19:485-487, 1998 Vymazal J et al: T1 and T2 alterations in the brains of patients with hepatic cirrhosis. Am J Neuroradiol 17:333-336, 1996

26

Toxic/Metabolic/Degenerative

Disorders, Acquired

Typical (Left) Axial TlWI MR in a patient with chronic cirrhosis shows typical diffuse hyperintense signal in lentiform nucleus. (Right) Axial Tl WI MR in a different patient with chronic severe liver failure shows hyperintense signal mainly around borders of lentiform nucleus.

(Left) Coronal Tl C+ MR shows hyperintense signal within lentiform nucleus that was present on unenhanced images. (Right) Axial NECT in the same patient shows diffuse cerebral edema.

(Left) Axial PO/Intermediate MR in a patient with acute hepatic encephalopathy shows hyperintense signal abnormality in subcortical regions and cortex. (Right) Axial Tl WI MR in a different patient shows hyperintense signal within substantia nigra and cerebral peduncles.

10 27

Toxic/Metabolic/Degenerative

Disorders, Acquired

ACUTE HYPERTENSIVE ENCEPHALOPATHY, PRES

Axial graphic shows the classic posterior circulation cortical/subcortical vasogenic edema and petechial hemorrhages characteristic of PRES.

• Morphology:

I·TERMIN(J)L()G¥ Abbreviations

Axial FlAIR MR in a young female with HUS/TTP and severe hypertension shows bioccipital foci of high signal intensity involving the cortex and subcortical white matter. Classic PRES.

Patchy>

confluent

CT Findings

and Synonyms

• Hypertensive encephalopathy; posterior reversible encephalopathy syndrome (PRES); reversible posterior leukoencephalopathy syndrome (RPLS)

Definitions • Disorder of cerebrovascular autoregulation with multiple etiologies, most of which cause acute hypertension (HTN)

IIMAGIN(JFIN[)ING~

• NECT o Patchy bilateral nonconfluent hypodense foci • Posterior parietal, occipital lobes > basal ganglia, brainstem o Less common: Petechial cortical/subcortical or basal ganglionic hemorrhage • CECT: +/- Mild patchy/punctate enhancement • CTA o Usually normal o Rare: Vasospasm with multifocal areas of arterial narrowing

MR Findings

General Features • Best diagnostic clue: Patchy cortical/subcortical PCA territory lesions in a patient with severe acute/subacute HTN • Location o Most common: Cortex, subcortical white matter • Predilection for posterior circulation (parietal, occipital lobes, cerebellum) • At junctions of vascular watershed zones • Usually bilateral, often somewhat asymmetric o Less common: Basal ganglia o Rare: Predominate/exclusive brainstem involvement • Size: Extent of abnormalities highly variable

• Tl WI: Hypointense cortical/subcortical lesions • T2WI o Hyperintense cortical/subcortical lesions o Less common • Extensive brain stem hyperintensity • Generalized white matter edema • PD/Intermediate: Multifocal hyperintensities • FLAIR o Parieto-occipital hyperintense cortical lesions in 95% o +/- Symmetric lesions in basal ganglia o Does not discriminate between vasogenic, cytotoxic edema (both have increased signal intensity)

DDx: PRES

28

Acute PCA Infarct

Hypotensive Stroke

Severe Hypoglycemia

Toxic/Metabolic/Degenerative

Disorders, Acquired

PML

ACUTE HYPERTENSIVE ENCEPHALOPATHY, PRES Key Facts Imaging Findings

Pathology

• Best diagnostic clue: Patchy cortical/subcortical PCA territory lesions in a patient with severe acute/subacute HTN • Parieto-occipital hyperintense cortical lesions in 95% • DWl: Usually normal • ADC map: Markedly elevated (bright areas) • Tl C+: Variable patchy enhancement

• Diverse causes, clinical entities with HTN as common component • Acute HTN damages vascular endothelium • Breakthrough of autoregulation causes BBB disruption • Result = vasogenic (not cytotoxic) edema • Acute/subacute systemic HTN • Preeclampsia, eclampsia • Uremic encephalopathies • Drug toxicity

Top Differential • • • •

Diagnoses

Acute cerebral ischemia Acute cerebral hyperemia Metabolic derangement Progressive multifocalleukoencephalopathy

Clinical Issues (PML)

• Headache, seizure, altered mental status • Caution: Some patients, especially children, may even be normotensive or have minimally elevated BP!

• T2* GRE: Blooms if hemorrhage present • DWl o DWl: Usually normal • Most common: Normal (no restriction) • Less common: High signal on DWI with "pseudonormalized" ADC (may indicate irreversible infarction) o ADC map: Markedly elevated (bright areas) o DTI (diffusion tensor imaging) • Shows foci of increased diffusion representing anisotropy loss • Vasogenic edema due to cerebrovascular autoregulatory dysfunction o Perfusion scans may show increased microvascular CBF • Tl C+: Variable patchy enhancement • MRS o May show widespread metabolic abnormalities • Increased Cho, Cr • Mildly decreased NAA • Usually return to normal within 2 months

• Rapid decompression of chronic SDH o Generally localized to cortex under the SDH • Postcarotid endarterectomy, angioplasty or stenting o Hyperperfusion syndrome occurs in 5-9% of cases o Perfusion MR or CT scans show elevated rCBF o Aggressive control of BP associated with clinical, radiological improvement

Nuclear Medicine

• "Horseshoe" > patchy enhancement • No predilection for posterior circulation

Findings

• SPECT o Variable findings reported; some show hyper-, others hypoperfusion in affected areas

Imaging Recommendations • Best imaging tool: Contrast-enhanced MR + DWl • Protocol advice: Repeat scan after BP normalized

I DIFFERENTIAL DIAGNOSIS Acute cerebral ischemia • Clinical history (HTN, time of symptom onset) important • DWl usually shows restriction (high signal)

Acute cerebral hyperemia • Ictal/postictal o May cause transient gyral edema, enhancement o Can mimic PRES, stroke, infiltrating neoplasm

Metabolic

derangement

• History provides diagnostic clues (e.g., dialysis disequilibrium syndrome) • Locations somewhat different o Pons, basal ganglia, white matter in osmotic demyelination o Posterior circulation in PRES, porphyria

Progressive multifocalleukoencephalopathy

(PML) • Usually spares cortex, basal ganglia • lmmunocompromised patients

Acute demyelinating

disease

Gliomatosis cerebri • Entire lobe(s) involved rather than patchy cortical/subcortical • Can mimic brain stem PRES

I PATHOLOGY General Features • General path comments: Typically reversible with blood pressure normalization • Etiology o Diverse causes, clinical entities with HTN as common component o Acute HTN damages vascular endothelium o Breakthrough of autoregulation causes BBB disruption

10 29

Toxic/Metabolic/Degenerative

Disorders, Acquired

ACUTE HYPERTENSIVE ENCEPHALOPATHY, PRES • Primarily at arteriolar level with HTN, diabetic vasculopathy, etc o Result = vasogenic (not cytotoxic) edema • Arteriolar dilatation with cerebral hyperperfusion • Hydrostatic leakage (extravasation, transudation of fluid and macromolecules through arteriolar walls) • Interstitial fluid accumulates in cortex, subcortical white matter • Posterior circulation sparsely innervated by sympathetic nerves (predilection for parietal, occipital lobes) o Frank infarction with cytotoxic edema rare in PRES • Epidemiology o Pre-eclampsia in 5% of pregnancies o Eclampsia lower « 1%) • Associated abnormalities o Acute/subacute systemic HTN o Preeclampsia, eclampsia • Typically occurs after 20 weeks gestation • Rare: Headache, seizures up to several weeks postpartum o Uremic encephalopathies • Acute glomerulonephritis • HUS/TTP • Lupus nephropathy, etc o Drug toxicity • Cyclosporin or FK-506 • Tacrolimus • Cisplatin • Interferon-alpha • Erythropoietin

Natural History & Prognosis • Most cases resolve completely with blood pressure normalization • May be life-threatening • Permanent infarction rare

Treatment • Favorable outcome with prompt recognition, treatment of HTN

IDIACN(lSTICeHE
Image Interpretation

[.SElECtED.R.EF~~E~Cg~ 1. 2. 3.

4.

Gross Pathologic & Surgical Features • Common o Cortical/subcortical edema o +/- Petechial hemorrhage in parietal, occipital lobes • Less common: Lesions in basal ganglia, cerebellum, brain stem, anterior frontal lobes

Microscopic

Features

5.

6.

7.

• Usually no residual abnormalities after HTN corrected • Autopsy in severe cases shows microvascular fibrinoid necrosis, ischemic microinfarcts, variable hemorrhage • Chronic HTN associated with mural thickening, deposition of collagen, laminin, fibronectin in cerebral arterioles

8. 9.

10.

Presentation

11.

• Most common signs/symptoms o Headache, seizure, altered mental status o Caution: Some patients, especially children, may even be normotensive or have minimally elevated BPl • Clinical profile: Young female with acute/subacute systemic HTN, headache +/- seizure

10

• Age: Any age but young> • Gender: M < F

12.

13.

14.

Demographics

Pearls

• Major ddx of PRES is cerebral ischemia; DWI is positive in the latter, usually negative in the former

old

Neuwelt EA:Mechanisms of disease: The blood-brain barrier. Neurosurg 54: 131-42,2004 Coutts SB et al: Hyperperfusion syndrome. Neurosurg 53: 1053-60,2003 Kinoshita T et al: Diffusion-weighted MR imaging of posterior reversible leukoencephalopathy syndrome: a pictorial essay. Clin Imaging. 27(5): 307-15, 2003 Thambisetty M et al: Hypertensive brainstem encephalopathy: clinical and radiographic features. ] Neurol Sci. 208(1-2): 93-9, 2003 Celik M et al: MRI reveals reversible lesions resembling posterior reversible encephalopathy in porphyria. Neuroradiology. 44(10): 839-41, 2002 Kumai Y et al: Hypertensive encephalopathy extending into the whole brain stem and deep structures. Hypertens Res. 25(5): 797-800, 2002 Covarrubias D] et al: Posterior reversible encephalopathy syndrome: prognostic utility of quantitative diffusion-weighted MR images. A]NR Am] Neuroradiol. 23(6): 1038-48, 2002 Singhi P et al: Reversible brain lesions in childhood hypertension. Acta Pedatric. 91(9): 1005-7,2002 Schaefer PW et al: Diagnostic value of apparent diffusion coefficient hyperintensity in selected patients with acute neurologic deficits.] Neuroimaging. 11(4): 369-80, 2001 Provenzale]M et al: Quantitative assessment of diffusion abnormalities in posterior reversible encephalopathy syndrome. A]NR Am] Neuroradiol. 22(8): 1455-61,2001 Mukherjee P et al: Reversible posterior leukoencephalopathy syndrome: Evaluation with diffusion-tensor MR imaging. Radiol219: 756-65,2001 Provenzale]M et al: Quantitative assessment of diffusion abnormalities in posterior reversible encephalopathy syndrome. A]NR 22: 1455-61,2001 Schmidt S et al: Brain involvement in haemolytic-uraemic syndrome: MRI features of coagulative necrosis. Neuroradiology. 43(7): 581-5, 2001 Port]D et al: Reversible intracerebral pathologic entities mediated by vascular autoregulatory dysfunction. Radiographics 18: 353-67, 1998

30

Toxic/Metabolic/Degenerative

Disorders, Acquired

ACUTE HYPERTENSIVE ENCEPHALOPATHY, PRES

Typical

/ .. 1\ ..

,,

"~' . ~ .. \ f !

~

,

i' ..

...

,

' .••

~

.

,/

'.JC.-

..

j

(Left) Axial T2WI MR in a patient with eclampsia shows bilateral cortical/subcortical occipital hyperintensities (arrows) with more subtle lesions in the anterior watershed zones. (Right) Axial T7 C+ MR in the same case shows patchy enhancement in the posterior circulation lesions (arrows) as well as in the more anterior watershed zone (open arrows). Classic PRES.

'::_ ... ,,J/ Variant (Left) Axial FLAIRMR in a patient with acute severe systemic HTN shows high signal intensity in both occipital lobes and the . brainstem. (Right) Axial OWl MR in the same case shows no definite foci of restricted diffusion. OWl in most cases of PRESis negative. The pattern of predominant brainstem involvement is less typical.

Variant (Left) Axial T2WI MR in a 15

y old pregnant female with headaches, severe HTN and cortical blindness shows very large mixed signal lesions in both occipital lobes. (Right) Axial T7WI M R in the same case obtained 5 days after emergency delivery shows large, asymmetric hemorrhagic occipital infarcts (arrows). Frank ischemia/infarction are uncommon complications of PRES.

10 31

Toxic/Metabolic/Degenerative

Disorders, Acquired

I

CHRONIC HYPERTENSIVE ENCEPHALOPATHY

Axial T2* eRE MR in a patient with chronic HTN shows WM hyperintense lesions in centrum semiovale bilaterally, as well as multiple hypointense lesions consistent with hemorrhagic lacunae.

Abbreviations

and Synonyms

• Chronic hypertensive encephalopathy (CHE) • Subcortical arteriosclerotic encephalopathy (SAE) aka Binswanger disease

• Internal capsule, caudate nuclei o Cerebral hemorrhage especially in basal ganglia (BG) and thalamus o Leukoaraiosis especially in corona radiata • Size: Variable • Morphology: Rounded or patchy lesions

CT Findings

Definitions • Brain parenchymal changes due to long-standing effects of untreated or poorly treated systemic hypertension (HTN) o Lacunar infarction, parenchymal hemorrhage o Diffuse white matter (WM) lesions • CHE causes vascular dementia • CHE can be associated with o Subcortical arterial and arteriolar leukoencephalopathy o Leukoaraiosis, Binswanger disease

General Features • Best diagnostic clue: Diffuse WM hypodensity on CT, WM hyperintense lesions on T2WI • Location o Sites of lacunae in order of decreasing frequency • Lenticular nuclei, pons, thalamus

DDx: Multifocal

32

Axial NEeT in a different patient with chronic hypertension shows diffuse periventricular white matter hypodensity consistent with leukoaraiosis.

Amyloid Angiopathy

• NECT o Focal hypodense regions in BG, thalamus and brain stem due to lacunar infarcts (usually multiple) o Diffuse hypodensity in periventricular regions • Associated with more severe systemic HTN o Hyperdense lesions due to petechial hemorrhages (if confluent enough)

MR Findings • Tl WI: Petechial hemorrhages shown as early hyperintense lesions • T2WI o Frequently hyperintense lesions within • Deep central gray matter structures (BG and thalamus) • Corona radiata and centrum semiovale o Diffuse, confluent regions of periventricular hyperintense WM involvement (leukoaraiosis) • T2* GRE o Multifocal hypointense lesions • Predilection for BG and thalami

lesions

CADASIL

Toxic/Metabolic/Degenerative

NPSLE

Granulomatous Angiitis

Disorders, Acquired

CHRONIC HYPERTENSIVE ENCEPHALOPATHY Key Facts Terminology • Brain parenchymal changes due to long-standing effects of untreated or poorly treated systemic hypertension (HTN) • CHE causes vascular dementia

Imaging Findings • Best diagnostic clue: Diffuse WM hypodensity WM hyperintense lesions on T2WI • Multifocal hypointense lesions

•

• •

•

on CT,

• Neuropsychiatric (NPSLE)

systemic lupus erythematosus

Pathology • Chronic HTN => irreversible structural changes in small arterial vessels of cerebral parenchyma • HTN: One of most important risk factors for Binswanger disease • Degenerative changes of AD type

Clinical Issues

Top Differential Diagnoses

• Memory loss, various features of dementia

• • • • •

• T2* GRE imaging in patients with cerebrovascular disease may detect cerebral lesions due to HTN

Amyloid angiopathy CADASIL Dementias Pseudoxanthoma elasticum Antiphospholipid antibody syndrome

• May also be seen in corona radiata, brain stem, and cerebellum • More common in patients with chronic HTN than in those without HTN • Hemosiderin deposits, indicative of old microhemorrhages DWI o When acute, may show small discrete foci of restricted diffusion o ADC: Lower in acute and higher in chronic lesions Tl C+: Demonstrates blood brain barrier dysfunction secondary to permeability increase MRS: IH MRS: Hypertensive older patients have a higher myoinositol/creatine ratio than normal controls but similar to that of patients with Alzheimer disease (AD) PD/Intermediate and FLAIR: Same as T2WI

Ultrasonographic

Findings

• Transcranial Doppler studies show 1 cerebrovascular resistance in middle cerebral arteries of patients with chronic HTN compared to early-stage HTN patients

Angiographic Findings • Conventional o Helpful only if vasculitis exclusion desired clinically or to preoperatively evaluate carotids o Large vessel occlusion is rare

Nuclear Medicine Findings • PET o Aids in discriminating CHE from AD by comparing patterns of hypoperfusion and/or hypometabolism • Frontal lobe (particularly cingulate and superior frontal gyri) predominantly affected in CHE • Parietotemporal PET abnormalities in AD • Regional CBF determined with 99mTc-HMPAO SPECT o Patients with mild CHE show reduced frontal CBF o Severe CHE: Diffuse cerebral hypoperfusion

Imaging Recommendations • Best imaging tool: MR is most sensitive • Protocol advice: MR with T2WI, FLAIR, T2* GRE

Diagnostic Checklist

I DIFFERENTIAl.. DIAGNOSIS Amyloid angiopathy • Second most frequent cause of cerebral hemorrhage (next to atheromatosis), especially recurrent • Hemorrhages are most common in frontal and parietal lobes, involving cortex and subcortical WM • Deep central gray nuclei, corpus callosum, and cerebellum are sometimes affected • Rare putaminal, thalamic, or brainstem hemorrhage • Amyloid deposition within small and medium arteries of cerebral leptomeninges and cerebral cortex • Amyloidosis may also cause o Transient ischemic attacks (TIA), cerebral infarcts o Binswanger type leukoencephalopathy o Symptoms resembling cerebral pseudotumor

CADASll • Nonarteriosclerotic, amyloid-negative hereditary angiopathy primarily affecting leptomeningeal and long perforating arteries of brain • Characteristic subcortical lacunar infarcts and leukoencephalopathy in young adults • Circumscribed lesions found predominantly within centrum semiovale, thalamus, BG, and pons • Anterior temporal pole and external capsule lesions have high sensitivity and specificity for CADASIL • Subcortical hypodense lesions on CT • Large, coalescent lesions in WM, isointense on Tl WI and hyperintense on T2WI • Small, well-delineated lesions that spare cortex, hypointense on Tl WI and hyperintense on T2WI

Dementias • Alzheimer dementia o Parietal and temporal cortical atrophy o Volume loss in hippocampi, entorhinal cortex o Often co-existing microvascular disease, WM hyperintensities • Multi-infarct dementia o Hyperintense lesions on T2WI and focal atrophy suggestive of chronic infarcts

10 33

Toxic/Metabolic/Degenerative

Disorders, Acquired

Pseudoxanthoma

elasticum

• Subcortical leukoencephalopathy • Dementia with multiple strokes with hypertension

Antiphospholipid

antibody syndrome

• Alterations of small penetrating arteries leading to luminal stenosis o Adventitial fibrosis, lipohyalinosis of media o Interruption/destruction of inner elastic membrane o Collagen subintimal proliferation

• Early stroke, recurrent arterial & venous thromboses • Spontaneous fetal loss, thrombocytopenia • Infarcts of various sizes and T2 hyperintense WM foci

Presentation

Neuropsychiatric systemic lupus erythematosus (NPSLE) • • • •

Most common: Small multifocal WM lesions Cortical atrophy, ventricular dilation Periventricular and diffuse WM changes Infarcts, hemorrhage, multifocal gray matter lesions

Other vasculitides • Primary angiitis of CNS, granulomatous • Polyarteritis nodosa, Behcet disease • Syphilis, Sjogren syndrome

angiitis

• Most common signs/symptoms o Memory loss, various features of dementia o Motor disorders, pseudobulbar syndrome • Clinical profile o Stepwise or gradual progression of mental deterioration o Acute strokes, lacunar syndrome o Subacute onset of focal, pseudobulbar and extrapyramidal signs and seizures

Demographics • Age: Incidence increases with age • Gender: HTN more prevalent in men than women • Ethnicity: HTN more prevalent in African-Americans

General Features

Natural History & Prognosis

• General path comments o Chronic HTN ~ irreversible structural changes in small arterial vessels of cerebral parenchyma • ~ Chronic ischemia of WM ~ pale WM • ~ Small lacunar infarctions o Elevated blood pressure (BP) ~ hyalinosis and sclerosis in walls of small intraparenchymal arterioles ~ predisposition to thrombotic occlusion • Etiology o Hypertrophy of large cerebral arteries • i Distensibility of large cerebral arteries • Protects cerebral microvasculature by attenuating increases in pressure of downstream vessels o Hypertrophy of arteriolar wall • 1 Distensibility of cerebral arterioles o Alterations of endothelium-mediated dilatation • May impair vasodilator responses in chronic HTN and predispose to ischemia o Chronic HTN impairs dilatation of collateral vessels in cerebral circulation • 1 Susceptibility to cerebral infarction • Epidemiology: 60 million Americans affected by HTN • Associated abnormalities o HTN: One of most important risk factors for Binswanger disease o Degenerative changes of AD type

• Arteriolosclerosis associated with systemic HTN and increasing age o Primary factor in pathogenesis of hyperintense WM lesions on T2WI in elderly • WM lesions associated with cognitive decline • Periventricular hyperintense WM lesions o Increased in patients with untreated systemic HTN • Age, smoking and HTN are independent predictors of hyperintense lesions on T2WI • Untreated or poorly controlled systemic HTN ~ intracranial hemorrhages usually involving BG, thalamus, brain stem, or dentate nucleus of cerebellum • CHE eventually causes vascular-type dementia

Treatment • Options, risks, complications:

Image Interpretation

Long-term control of BP

Pearls

• T2* GRE has superior sensitivity in detecting old hemorrhages as compared with spin-echo sequences • T2* GRE imaging in patients with cerebrovascular disease may detect cerebral lesions due to HTN

Gross Pathologic & Surgical Features • Demyelination of periventricular • Multiple lacunae and infarctions • Parenchymal hemorrhage

Microscopic

10

and central WM

Features

1.

2.

• Multiple petechial microhemorrhages • Leukoaraiosis: Partial loss of myelin, axons, oligodendroglia, glial cells o Mild astrocytic gliosis, macrophagic infiltration

3.

Catani M et al: Proton magnetic resonance spectroscopy reveals similar white matter biochemical changes in patients with chronic hypertension and early Alzheimer's disease. J Am Geriatr Soc 50: 1707-1710, 2002 Nagata K et al: Can PET data differentiate Alzheimer's disease from vascular dementia? Ann N Y Acad Sci 903: 252-261, 2000 Chan S et al: Multifocal hypointense lesions on gradient-echo MR are associated with chronic hypertension. AJNR 17: 1821-1827, 1996

34

Toxic/Metabolic/Degenerative

Disorders, Acquired

CHRONIC HYPERTENSIVE ENCEPHALOPATHY

Typical (Left) Axial FLAIRMR in a patient with long-standing systemic hypertension shows hyperintense lesions in the external capsule and scattered throughout the white matter. (Right) Axial T2* eRE MR in the same patient shows multiple hypointense lesions within basal ganglia and thalami bilaterally, related to hemosiderin.

Typical (Left) Axial T2WI MR in a chronic hypertensive patient shows hyperintense white matter foci in basal ganglia and white matter. (Right) Axial PO/Intermediate MR in the same patient shows muttifocal hyperintense white matter lesions.

Typical (Left) Axial T2WI MR shows

diffuse pontine white matter hyperintense lesions in a patient with chronic hypertension. (Right) Axial T2WI MR in the same patient shows bilateral muttifocal, confluent hyperintense lesions in centrum semiovale.

10 35

Toxic/Metabolic/Degenerative

Disorders, Acquired

IDIOPATHIC INTRACRANIAL HYPERTENSION

Axial T2WI MR shows increased fluid in sheaths surrounding the optic nerves (curved arrows) associated with severe scleral flattening (open arrows).

Sagittal T1WI MR in another case of idiopathic intracranial hypertension ("pseudotumor cerebri") shows empty sella (arrow). Ventricular size is normal.

MR Findings Abbreviations

and Synonyms

• Idiopathic intracranial pseudotumor cerebri

hypertension

(IIH);

Definitions • t ICP without obvious underlying brain pathological condition • Multiple potential causes of intracranial hypertension (e.g., dural sinus thrombosis) excluded • Association of any medication or condition with IIH better termed "secondary pseudotumor syndrome"

General Features • Best diagnostic clue: Partial empty sella, dilation/tortuosity of optic nerve sheath, flattening of posterior sclera in patient with clinical findings of IIH

• TlWI o Partially empty sella turcica o Enlarged/tortuous optic nerve sheaths, posterior sclera flattened o Variable: Small ("pinched") ventricles • T2WI o Increased fluid around optic nerves +/- bulbous dilation of sheath behind globes o Optic nerve papilla may "protrude" into globe in severe cases • DWI o Normal brain water diffusion, proton longitudinal relaxation time o Suggests diffuse brain edema NOT associated with IIH • MRV: Use to exclude dural sinus thrombosis/stenosis

Imaging Recommendations • Best imaging tool: MR (include fat-saturated orbits, whole brain)

CT Findings • NECT o Usually normal o Enlarged optic nerve sheaths +/- empty sella in 40-50% o Less common: Slit ventricles (10%)

Secondary pseudotumor

syndromes

• Dural sinus stenosis/thrombosis

DDx: Empty Sella, Small CN 2

10 36

Empty Sella

Optic Atrophy

Toxic/Metabolic/Degenerative

Post MS Atrophy

Disorders, Acquired

Optic Atrophy

Tl C+ of

IDIOPATHIC INTRACRANIAL HYPERTENSION Key Facts Terminology

Imaging Findings

• t rep without obvious underlying brain pathological condition • Multiple potential causes of intracranial hypertension (e.g., dural sinus thrombosis) excluded • Association of any medication or condition with IIH better termed "secondary pseudotumor syndrome"

• Best diagnostic clue: Partial empty sella, dilation/tortuosity of optic nerve sheath, flattening of posterior sclera in patient with clinical findings of IIH

• Medications such as vitamin A/derivatives, some antibiotics (e.g., tetracycline), steroid withdrawal, hormones, lithium

Idiopathic or post inflammatory sclerosis) optic nerve atrophy

(multiple

• Small optic nerves without scleral flattening

Idiopathic empty sella (normal variant) • Normal optic nerve sheaths

I PATHOLOGY General Features • General path comments: 1 IC pressure of unknown etiology • Epidemiology: 1 Prevalence with obesity

Top Differential

Diagnoses

• Secondary pseudotumor syndromes • Idiopathic empty sella (normal variant)

• Gender: M:F

=

1:4-8

Natural History & Prognosis • Chief hazard: Vision loss from chronic papilledema

Treatment • Goal = prevent visual loss, improve associated symptoms • Options o Medical (e.g., weight loss, carbonic anhydrase inhibitors) o Surgical (e.g., LP shunt, optic nerve sheath fenestration)

I DIAGNOSTIC CHECKliST Image Interpretation

Pearls

• Must exclude venous stenosis/space-occupying

lesion

Gross Pathologic & Surgical Features • Bilateral papilledema

Microscopic

I SELECTED REFERENCES

Features

1.

• Normal CSF cytology, chemistry

Binder DK et al: Idiopathic intracranial hypertension. Neurosurgery 54: 538-552, 2004 Bastin ME et al: Diffuse brain oedema in idiopathic intracranial hypertension: a quantitative MRIstudy. J Neural Neurosurg Psychiatry 74: 1693-6,2003 Bandyopadhyay S. Pseudotumor cerebri. Arch Neurol 58:

Staging, Grading or Classification Criteria

2.

• Modified Dandy criteria must be met (e.g., symptoms of 1 ICP with> 250 mm H20, normal CT/MR without DST, etc)

3.

I CliNICAL

I IMAGE GAllERY

ISSUES

1699-1701,2001

Presentation • Most common signs/symptoms o Headache in 90-95% • Generalized, episodic, throbbing, aggravated by Valsalva o Papilledema (bilateral optic nerve head swelling) virtually universal o Progressive visual loss +1- CN 6 paresis, diplopia common o Occasional: Pituitary dysfunction o Uncommon: Vertigo, tinnitus o In children: Irritability, "sunset" sign, bulging anterior fontanelle • Clinical profile: Obese female age 20-44 y with HA, papilledema

Demographics • Age: Peak

=

15-40 years (occasionally

seen in children)

(Left) Axial T2WI MR shows increased fluid in bilateral optic nerve sheaths with mild flattening of the globes at optic nerve insertion.

Also note CSF filled, expanded, empty sella (arrow). (Right) Coronal TlWI MR in the same case shows unusually small lateral ventricles with a "pinched" appearance. Obese female with headaches, papilledema consistent with IIH.

Toxic/Metabolic/Degenerative

Disorders, Acquired

10 37

Axial T2WI MR shows hyperintense lesions within globi pallidi in a patient in the acute stage of CO poisoning.

1",,~R.MINOl()(j'\{ Abbreviations

Axial T2WI MR in the same patient a few months later shows mild decrease in size of globus pallidus lesions and development of a rim of hypointense signal.

CT Findings

and Synonyms

• Carbon monoxide (CO) poisoning (COP)

Definitions • Anoxic-ischemic encephalopathy, usually with bilateral lesions, caused by inhalation of CO gas

!IMt\G! IN(} i/FIiNi [)iINiG'S General Features • Best diagnostic clue: Globi pallidi (GP) hyperintensity on T2WI or hypodensity on CT • Location o GP: Most common site of abnormality o Cerebral white matter (WM): Second most common o Putamen, caudate nucleus, thalamus, substantia nigra, corpus callosum, fornix, hippocampus: Less common • Size: !(Hippocampal and generalized cerebral atrophy) • Morphology o Focal findings and diffuse lesions o Typically oval lesions confined to GP o Ventricles may be compressed due to edema o Severe changes show loss of gray/white differentiation due to diffuse edema

DDx: Hyperintense

• NECT o Symmetric hypodensity in GP o Symmetric diffuse hypodensity in cerebral WM • More advanced in centrum semiovale • CECT: Enhancement in GP has been reported

MR Findings • T1WI: Both T1 hypointensity in GP (probably due to necrosis) and T1 hyperintensity in GP (probably due to hemorrhage) have been reported • T2WI o Ischemia/infarct of basal ganglia (BG) • Bilateral T2 hyperintensities of GP surrounded by hypointense rim (probably due to hemosiderin) • Caudate nucleus and putamen may be affected, either alone or in addition to GP abnormality o Cerebral hemispheric WM: Bilateral confluent T2 hyperintense WM (periventricular, centrum semiovale) • Reflects diffuse demyelination • Reported in delayed encephalopathy of COP and patients with severe COP who became asymptomatic in chronic stage o Abnormal signal in cerebral cortex (less frequent) • Cortical hyperintensity: Most common pattern, with predilection for temporal lobe

Basal Ganglia Lesions

10 38

Wilson Disease

Japanese Enceph

Toxic/Metabolic/Degenerative

CjD

Disorders, Acquired

Chronic HTN

CO POISONING Key Facts Terminology • Anoxic-ischemic encephalopathy, usually with bilateral lesions, caused by inhalation of CO gas

Imaging Findings • Best diagnostic clue: Globi pallidi (GP) hyperintensity on T2WI or hypodensity on CT • T1WI: Both Tl hypointensity in GP (probably due to necrosis) and T1 hyperintensity in GP (probably due to hemorrhage) have been reported • Bilateral T2 hyperintensities of GP surrounded by hypointense rim (probably due to hemosiderin) • Cerebral hemispheric WM: Bilateral confluent T2 hyperintense WM (periventricular, centrum semiovale) • SPECT studies show cerebral hypoperfusion deficits

• •

•

• •

• Abnormalities in perisylvian cortex, anterior temporal lobe and insular cortex • Asymmetrical, diffuse cortical hyperintensity affecting parietal and occipital lobes also possible o Medial temporal lobe in region of hippocampus may show signal abnormality: Uncommon despite frequent pathological findings o Diffuse, bilateral high signal within cerebellar hemispheres, affecting cortex and WM • Not seen in acute setting; develops later o Delayed encephalopathy 2-3 weeks after recovery • Additional high intensity in corpus callosum, subcortical U-fibers, internal and external capsules • Associated with low intensity in thalamus and putamen due to iron deposition PD/Intermediate: High signal in affected BG FLAIR o Same as T2WI o Additional periventricular high signal in acute COP • May not be visible on conventional T2 FSE DWI o Early (acute) stage of COP • Diffuse symmetrical hyperintense changes on DWI in subcortical hemispheric WM (restricted diffusion due to cytotoxic edema) • WM may appear normal on FLAIR • Corresponding ADC maps: Low signal intensity and low ADC values in same regions • Subtle cortical lesions and unaffected BG, thalami, periventricular WM, or hippocampus o Delayed stage of COP (weeks post-exposure) • High signal area in cerebral WM • ± Abnormal WM findings on T2WI • Low ADC values persist at this stage o Chronic stage of COP • Gradual increase in ADC values, consistent with macrocystic encephalomalacia • Hyperintense WM areas on T2WI o Symmetric bright lesions in GP o WM and cortical hyperintensities Tl C+: Enhancement in GP has been reported MRS

• DWI best for lesion detection (and mathematical information with ADC maps) in acute stage of COP

Top Differential Diagnoses • • • •

Wilson disease Japanese encephalitis (jR) Small vessel ischemic disease Creutzfeldt-Jakob disease

Pathology • CO-induced parkinsonism • Demyelination, edema and hemorrhagic

necrosis

Clinical Issues • Persistent neurologic sequelae: Occur immediately following COP and persist over time • Delayed neurologic sequelae (10-30% of victims)

o SeriaI1H-MRS scans performed after appearance of delayed sequelae in COP • Persistently 1 Cho/Cr at DWI abnormal WM site • Progressively j NAAICr with time (j NAA is marker of neuron and axon degeneration) • Progressively 1 Lac/Cr with time o Reflects developmental process of WM lesions • Demyelination progresses to neuronal necrosis

Nuclear Medicine Findings • SPECT studies show cerebral hypoperfusion deficits o j Regional cerebral blood flow in frontal and temporal cortices and diffuse hypoperfusion defects have been reported

Imaging Recommendations • Best imaging tool o DWI best for lesion detection (and mathematical information with ADC maps) in acute stage of COP o MRI more sensitive than CT for detection of brain abnormalities following COP • Protocol advice: Multiplanar MR including DWI, T2WI

I DIFFERENTIAL DIAGNOSIS Wilson disease lesions, involving BG, dentate nucleus, pons, mesencephalon • Tl hypointense (occasionally hyperintense) lesions • Variably hyperintense/hypointense on T2WI

• WM/GM

Japanese encephalitis (JE) • Homogeneous T2 hyperintensities in BG and thalami, symmetric or asymmetric • Most characteristic finding in JE o Bilateral thalamic hyperintensities ± hemorrhage • JE is meningoencephalitis ~ meningeal enhancement

Small vessel ischemic disease • BG lacunae: Typically asymmetric, multifocal • Focal hyperintensities in corona radiata, centrum semiovale

10 39

Toxic/Metabolic/Degenerative

Disorders, Acquired

Creutzfeldt - Jakob

disease

• Progressively hyperintense cerebral cortex on T2WI

changes in BG, thalami,

Leigh disease • Symmetrical spongiform brain lesions with onset in infancy/early childhood • Lesions predominantly in brain stem, BG (particularly putamen), and cerebral WM • Focal, bilateral and symmetric T2 hyperintense lesions

IpA.tHOL()G~ General Features • General path comments o Bilateral necrosis of GP o Multifocal areas of demyelination in periventricular WM, sparing of subcortical arcuate U-fibers (so-called "Grinker myelinopathy") • Etiology o CO: Colorless, odorless, tasteless gas generated through incomplete combustion of virtually all carbon-containing products o Mechanisms of brain injury include • Hypoxia, reduced cellular oxygen metabolism • Lipid peroxidation leading to oxidative injury • Damage to vascular endothelium due to deposition of peroxynitrite • Excitotoxicity, apoptosis • Epidemiology o Most common cause of accidental poisoning in Europe and North America o Causes 2-6,000 deaths/year in USA, from both accidental and non-accidental overdoses o i Prevalence of COP during winter months • Associated abnormalities o CO-induced parkinsonism • GP lesions after COP or periventricular and deep WM hyperintensities without BG lesions • Extrapyramidal syndrome may be due to lesions of WM areas containing BG output and/or input • Improvement usually accompanied by !extent and signal intensity of WM abnormalities, especially in frontoparietal centrum semiovale

Gross Pathologic & Surgical Features • GP necrosis, WM pallor

Microscopic

Presentation • Most common signs/symptoms o Nonspecific symptoms; controversial association of specific symptoms with known COHb levels o Acute toxicity: Nausea, vomiting, headache • Confusion, cognitive impairment, loss of consciousness, seizures, coma, death o Neuropsychological sequelae • Dementia, memory deficits, decreased attention • Irritability, mood and personality disturbance • Gait disturbance, Parkinsonian-like symptoms, apraxia, convulsive disorders • Visual-spatial & speech impairment, cortical blindness • Clinical profile: Depends on duration and intensity of exposure

Demographics • Age o Equivalent age-specific fatality rates between 15-75 y o Death rates from COP: i > 75 yand ! < 15 Y o Neonates and in utero fetuses: Most vulnerable • Ethnicity o For unintentional COP, race-specific death rates for African-American are 20% higher than for Caucasians o Race-specific death rates for blacks and other minority racial groups are 87% lower than for Caucasians (cultural partiality to this form of suicide)

Natural History & Prognosis • Persistent neurologic sequelae: Occur immediately following COP and persist over time • Delayed neurologic sequelae (10-30% of victims) o Occur weeks after initial recovery from acute COP • Two categories with regard to outcome o Normal/mild functional impairment • No or minimal abnormality on brain MR o Death/severe functional impairment (coma) • Diffuse brain damage on MR

Treatment • Hyperbaric oxygen (HBO) therapy: Treatment of choice in acute COP (within 6 hrs for best effect) • Early administration of 100% oxygen or HBO may prevent long-term neuropsychiatric sequelae

Features

• Demyelination, edema and hemorrhagic necrosis o Necrotic lesions in GP, other BG, hippocampus, cortex and cerebellum o WM lesions: Foci of necrosis or demyelination

I DIAGNOSTIC

CHECKLIST

Consider • MRI to monitor progression/resolution

of lesions

Staging, Grading or Classification Criteria

10

• 4 main pathological types o GP lesions: Variable degree of necrosis o WM lesions: Scattered/focal areas of necrosis or confluent areas of demyelination o Cortical lesions: Spongy changes, intense capillary proliferation, degeneration & loss of neurons o Hippocampal lesions: Coagulation necrosis

I SELECTED REFERENCES 1. 2.

Sener RN et al: Acute carbon monoxide poisoning: Diffusion MR imaging findings. AJNR 24:1475-1477,2003 Parkinson A et al: White matter hyperintensities and neuropsychological outcome following carbon monoxide poisoning. Neurology 58: 1525-1532,2002

40

Toxic/Metabolic/Degenerative

Disorders, Acquired

CO POISONING

I IMAG

E GALLERY

Typical (Left) Cross autopsy that shows bilateral globi pallidi necrosis (arrows) secondary to CO inhalation (Courtesy R. Hewlett, MO). (Right) Axial FLAIR MR in a different patient with CO poisoning shows hyperintense lesions within globi pallidi.

Typical (Left) Axial T7WI MR in a patient with CO poisoning shows heterogeneous signal in both globi pallidi (arrows) with hypointense center and rim of hyperintensity. (Right) Axial T7 C+ MR in the same patient shows homogeneously enhancing lesions in both globi pallidi.

Typical (Left) Axial FLAIR MR in a patient with CO poisoning shows hyperintense signal in both insulae (arrows). (Right) Axial FLAIR MR in a different patient with CO poisoning shows bilateral diffuse hyperintensities in centrum semiovale with sparing of subcortical U-fibers.

10 41

Toxic/Metabolic/Degenerative

Disorders! Acquired

OSMOTIC DEMYELINATION SYNDROME

Axial graphic shows acute osmotic demyelination affecting the central pons (arrows). The pons is slightly swollen with mild mass effect on the 4th ventricle.

Axial T2WI MR in a hyponatremic, alcoholic patient with rapid correction of serum sodium shows central pons hyperintensity with sparing the peripheral pontine fibers. Classic CPM.

• Osmotic demyelination syndrome (ODMS); formerly called "central pontine myelinolysis" (CPM) and/or "extrapontine myelinolysis" (EPM)

• Size: Variable extent • Morphology o Round or triangular-shaped (pons) o Regardless of site, demyelination often bila teral/ symmetric o Rare: Gyriform (cortical involvement)

Definitions

CT Findings

• Acute demyelination caused by rapid shifts in serum osmolality • Classic setting = rapid correction of hyponatremia o ODMS may occur in normonatremic patients

• NECT o Low density in affected areas (pons, BG, etc) o Look for other abnormalities (e.g., vermian atrophy) o No hemorrhage • CECT o Classic: No enhancement o Early, acute/severe demyelination may enhance moderately strongly

I TERMINOLOGY Abbreviations

I IMAGING

and Synonyms

FINDINGS

General Features • Best diagnostic clue: Central pons T2 hyperintensity with sparing of periphery • Location o 50% in pons (CPM) • Central fibers involved; peripheral fibers spared o 50% extra-pontine sites (EPM) • Basal ganglia (BG) • Cerebral white matter (WM) • Uncommon: Peripheral cortex, hippocampi • Rare: Lateral geniculate bodies o CPM + EPM = almost pathognomonic for ODMS

DDx: Hyperintense

MR Findings • TlWI o Acute • Classic: Mildly/moderately hypointense • Less common: Can be isointense with surrounding normal brain • Findings may be transitory, resolve completely • Initial study may be normal o Subacute • May resolve completely • Less common: Hyperintensity at 1-4 months (coagulative necrosis)

Pontine Lesions

10 42

Pontine Infarct

Multiple Sclerosis

Tox ic/Metabo lie/Degenerative

Diabetes

Low Grade Astro

Disorders, Acq u ired

OSMOTIC DEMYELINATION SYNDROME Key Facts Terminology • Osmotic demyelination syndrome (ODMS)i formerly called "central pontine myelinolysis" (CPM) and/or "extrapontine myelinolysis" (EPM) • Acute demyelination caused by rapid shifts in serum osmolality • Classic setting = rapid correction of hyponatremia • ODMS may occur in normonatremic patients

Imaging Findings • Best diagnostic clue: Central pons T2 hyperintensity with sparing of periphery • 50% in pons (CPM) • 50% extra-pontine sites (EPM) • Basal ganglia (BG) • Cerebral white matter (WM) • CPM + EPM = almost pathognomonic for ODMS • T2WI o Acute: Confluent hyperintensity in central pons with sparing of periphery and corticospinal tracts • Symmetric hyperintensity in BG, WM (EPM) o Subacute: Hyperintensity often normalizes, may resolve completely • PD/Intermediate: Hyperintense • FLAIR: Hyperintense • T2* GRE: Hemorrhage, "blooming" rare • DWI o DWI: Restricted (mildly hyperintense) o ADC: Variablei normal to mildly hyperintense • Tl C+ o Common: Usually does not enhance o Less common: Moderate confluent enhancement

Nuclear Medicine

Top Differential • • • •

Diagnoses

Pontine ischemia/infarction Demyelinating disease Pontine neoplasm (astrocytoma, metastasis) Metabolic disease (Wilson, Leigh, diabetes, hypertensive encephalopathy)

Pathology • Heterogeneous disorder with common etiology osmotic stress

=

Pontine neoplasm (astrocytoma, metastasis) • Primary neoplasm (e.g., pontine "glioma") typically pediatric/young adult patients • Pons is a rare site for solitary metastasis

Metabolic disease (Wilson, Leigh, diabetes, hypertensive encephalopathy) • Basal ganglia > pons in Wilson disease • Basal ganglia, midbrain in Leigh disease • Parieto-occipital lobes = most common site in hypertensive encephalopathy • Pontine hypertensive encephalopathy o Typically does not spare peripheral fibers o Other lesions common

Findings

• PET o Early metabolic stress = variable hypermetabolism o Late = hypometabolic areas in affected sites

Imaging Recommendations • Best imaging tool: MR > > CT • Protocol advice o MR

• Include FLAIR, Tl C+, DWI • Repeat imaging

I DIFFERENTIAl.. DIAGNOSIS Pontine ischemia/infarction • Often asymmetric • Usually involves both central, peripheral pontine fibers • Caution: Perforating BA infarct(s) may involve central pons, mimic CPM (including DWI)

Demyelinating

• Acute: Confluent hyperintensity in central pons with sparing of periphery and corticospinal tracts • Subacute: Hyperintensity often normalizes, may resolve completely • Best imaging tool: MR > > CT

disease

• Look for typical lesions elsewhere • "Horseshoe" (incomplete ring) enhancement acute MS common

pattern in

IPATHOl..OG¥ General Features • General path comments o Demyelination without associated inflammation • Nonspecific (pattern, distribution suggests ODMS) • Etiology o Heterogeneous disorder with common etiology = osmotic stress o Osmotic stress = any change in osmotic gradient o Most common = iatrogenic correction of hyponatremia o Less common = osmotic derangement with azotemia, hyperglycemia, hypokalemia, ketoacidosis o Precise mechanism of osmotic stress-related myelinolysis unknown • Osmotic insult = change in serum osmolality • Relative intracellular hypotonicity • Serum osmolality change causes endothelial damage • Organic osmolyte deficiency predisposes to endothelial breakdown • Endothelial cells shrink, causing BBBbreakdown • Accumulation of hypertonic sodium-rich fluid in ECF

10 43

Toxic/Metabolic/Degenerative

Disorders, Acquired

OSMOTIC DEMYELINATION SYNDROME • Hypertonic ECF, release of myelin toxins damages WM • Cell death ensues o "Co-morbid" conditions that may exacerbate OM • Hepatic, renal, adrenal, pituitary, paraneoplastic disease • Nutritional (alcohol, malnutrition, vomiting) • Burn, transplantation, other surgical patients • Epidemiology: Autopsy prevalence in alcoholics varies from < 1% to 10% • Associated abnormalities: Chronic alcoholism most common underlying condition in patients with CPM

Gross Pathologic & Surgical Features • Bilateral/symmetrical,

Microscopic

soft, gray-tan discoloration

• Plasmapheresis, studied

I.OIAGNOST1C.·CHi~QI([IS'" Consider • Diagnosis of ODMS in alcoholic patient with basal ganglia, white matter disease (EPM)

Image Interpretation

Pearls

• Classic CPM spares peripheral pontine fibers • EPM can occur without CPM • Repeat MR may be necessary as initial study may be normal

Features

• Extensive demyelination, gliosis • Macrophages contain engulfed myelin bits and fragments • Axis cylinders, nerve cells preserved • No inflammation

I CLINICAL1SSUES

I SELECTED REFERENCES 1.

2.

3.

Presentation • Most common signs/symptoms o Seizures, altered mental status o Often biphasic when hyponatremia present • ODMS symptoms emerge 2-4 days (occasionally weeks) after correction of hyponatremia • Changing level of consciousness, disorientation • Pseudobulbar palsy, dysarthria, dysphagia (CPM) • Movement disorder (EPM) o Symptoms may resolve with serum osmolality increase • Clinical profile: Alcoholic, hyponatremic patient with rapid correction of serum sodium

4.

5.

6. 7. 8.

9.

Demographics • Age o Occurs at all ages • Most common = middle aged • Uncommon = pediatric patients (diabetes, anorexia common) • Gender: M > F

Natural History & Prognosis • Spectrum of outcomes o Complete recovery may occur o Minimal residual deficits • Memory, cognitive impairment • Ataxia, spasticity, diplopia o May progress to • Spastic quadriparesis • "Locked in"; may progress to coma, death • "Co-morbid" conditions common, poorer prognosis

Treatment

10

steroids, glucose infusions being

• No consensus; no "optimal" correction rate for hyponatremia • Self-correction (fluid restriction, discontinue diuretics) if possible

10.

11. 12.

13.

14.

15.

16.

17.

Rizek KAet al: Early diagnosis of central pontine myelinolysis with diffusion-weighted imaging. AJNR 25:210-3, 2004 Mochizuki H et al: Benign type of central pontine myelinolysis in alcoholism--clinical, neuroradiological and electrophysiological findings. J Neurol. 250(9): 1077-83, 2003 Sugimoto T et al: Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa. J Neurol Neurosurg Psychiatry. 74(3): 353-5, 2003 Kim JS et al: Decreased striatal dopamine transporter binding in a patient with extrapontine myelinolysis. Mov Disord. 18(3): 342-5, 2003 Bonkowsky JL et al: Extrapontine myelinolysis in a pediatric case of diabetic ketoacidosis and cerebral edema. J Child Neurol. 18(2): 144-7,2003 Chua GC et al: MRI findings in osmotic myelinolysis. Clin Radiol. 57(9): 800-6, 2002 Kilinc M et al: Osmotic myelinolysis in a normonatremic patient. Acta Neurol Belg. 102(2): 87-9, 2002 Un SH et al: Osmotic demyelination syndrome after correction of chronic hyponatremia with normal saline. Am J Med Sci. 323(5): 259-62, 2002 Lampl C et al: Central pontine myelinolysis. Eur Neurol. 47(1): 3-10, 2002 Niehaus L et al: Reversible central pontine and extrapontine myelinolysis in a 16-year-old girl. Childs Nerv Syst. 17(4-5): 294-6, 2001 Cramer SC et al: Decreased diffusion in central pontine myelinolysis. AJNR22: 1476-9, 2001 Ashrafian H et al: A review of the causes of central pontine myelinosis: yet another apoptotic illness? Eur J Neurol. 8(2): 103-9,2001 Agildere AM et al: MRI of neurologic complications in end-stage renal failure patients on hemodialysis: pictorial review. Eur Radiol. 11(6): 1063-9, 2001 Brown WD: Osmotic demyelination disorders: central pontine and extrapontine myelinolysis. Curr Opin Neurol. 13(6): 691-7, 2000 Calakos N et al: Cortical MRI findings associated with rapid correction of hyponatremia. Neurology. 55(7): 1048-51, 2000 Chan CY et al: Clinics in diagnostic imaging (45). Osmotic myelinolysis ( central potine myelinolysis). Singapore Med J. 41(1): 45-8, 2000 Waragai M, Satoh T: Serial MRI of extrapontine myelinolysis of the basal ganglia: a case report. J Neurol Sci 161: 173-5, 1998

44

Toxic/Metabolic/Degenerative

Disorders, Acquired

OSMOTIC DEMYELINATION SYNDROME

Typical (Left) Axial T2WI MR in a patient with CPM shows classic high signal in the central pons with peripheral sparing. Contrast-enhanced scans (not shown) demonstrated mild enhancement of the demyelinating area. (Right) Axial OWl MR in the same case shows acute restriction, with a pattern that precisely matches the hyperintensity on the T2WI shown on the left.

Variant (Left) Axial T2WI MR in a patient on a fad diet with daily coffee enemas shows central pontine high signal with peripheral sparing. (Right) Axial T2WI MR in the same case shows striking hyperintensity involving both caudate nuclei and the putamina (arrows). Patient was severely hyponatremic and became confused after sodium correction.

Variant (Left) Axial TlWI MR in a patient with EPM shows diffuse high signal in the cortex and putamina. (Right) Axial FLAIRMR in the same case shows extensive signal abnormality and edema in the cortical and deep gray matter. Frank cortical laminar necrosis is an atypical manifestation of OOMS.

10 45

Toxic/Metabolic/Degenerative

Disorders, Acquired

RADIATION AND CHEMOTHERAPY

Axial NECT shows Ca++ in the subcortical white matter and basal ganglia. Patient with a posterior fossa medulloblastoma treated with XRT and chemotherapy. Mineralizing microangiopathy.

2J

ITERMINOLOG¥ Abbreviations

and Synonyms

• Radiation-induced injury, radiation (XRT) changes, chemotherapy effects, treatment-related changes

Axial T2WI MR shows diffuse high signal in the centrum semiovale with sparing of the subcortical U-fibers, typical of treatment related leukoencephalopathy. Patient is sip whole brain XRT.

• Location o Radiation injury occurs in radiation port o Periventricular WM especially susceptible o Subcortical V-fibers and corpus callosum spared

CT Findings • NECT o Acute XRT: Confluent WM low density edema o Delayed XRT: Focal/multiple WM low density o Leukoencephalopathy: Symmetric WM hypodensity o Mineralizing micro angiopathy: BG, subcortical WM Ca++, atrophy o Necrotizing leukoencephalopathy: Extensive areas of WM necrosis, posterior Ca++ o PRES: Subcortical WM edema, posterior circulation

Definitions • Includes edema, arteritis, leukoencephalopathy, mineralizing microangiopathy, necrotizing leukoencephalopathy, posterior reversible encephalopathy syndrome (PRES), radiation injury, radiation-induced tumors • Radiation-induced injury may be divided into acute, early delayed injury, late delayed injury

MR Findings

I IMAGING FINDING5

• TlWI o Acute XRT: Periventricular WM hypointense edema o Delayed XRT: Focal or multiple WM hypointensities o Leukoencephalopathy: Diffuse, symmetric WM hypointensity; spares subcortical V-fibers o Mineralizing microangiopathy: Putamen hyperintensity, atrophy o Necrotizing diffuse leukoencephalopathy: Extensive areas of WM necrosis o PRES: Symmetric posterior WM hypointensity o Radiation-induced cryptic vascular malformations: Blood products

General Features • Best diagnostic clue o Radiation injury: Mild vasogenic edema to necrosis o Radiation necrosis: Irregular enhancing lesion(s) o Leukoencephalopathy: T2 WM hyperintensity, spares subcortical V-fibers o Mineralizing microangiopathy: Basal ganglia (BG), subcortical WM Ca++, atrophy o Necrotizing leukoencephalopathy: WM necrosis o PRES: Posterior circulation subcortical WM edema

DDx: Enhancing Supratentorial

Mass

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46

Recurrent GBM

Metastasis

Toxic/Metabolic/Degenerative

Abscess

Multiple Sclerosis

Disorders, Acquired

RADIATION AND CHEMOTHERAPY Key Facts Terminology

Top Differential

• Includes edema, arteritis, leukoencephalopathy, mineralizing microangiopathy, necrotizing leukoencephalopathy, posterior reversible encephalopathy syndrome (PRES), radiation injury, radiation-induced tumors

• • • • • •

Imaging Findings • Radiation injury: Mild vasogenic edema to necrosis • Radiation necrosis: Irregular enhancing lesion(s) • Leukoencephalopathy: T2 WM hyperintensity, spares subcortical V-fibers • Mineralizing microangiopathy: Basal ganglia (BG), subcortical WM Ca++, atrophy • Necrotizing leukoencephalopathy: WM necrosis • PRES: Posterior circulation subcortical WM edema

• T2WI o Acute XRT: Periventricular WM hyperintense edema o Early delayed XRT: Focal or multiple hyperintense WM lesions with edema, demyelination • Spares subcortical V-fibers and corpus callosum o Late delayed XRT: Diffuse WM injury or necrosis • Hyperintense WM lesion(s), +/- hypointense rim • Mass effect and edema o Leukoencephalopathy: Diffuse, symmetric involvement of central and periventricular WM, relative sparing of subcortical V-fibers o Mineralizing microangiopathy: Decreased signal o Necrotizing leukoencephalopathy: Extensive WM necrosis o PRES: Confluent, symmetric hyperintensity in subcortical WM, +/- cortex, posterior circulation • Occipital, parietal, posterior temporal lobes, cerebellum typical • May involve frontal lobes, BG, brainstem o Radiation-induced cryptic vascular malformations: Blood products • T2* GRE: Radiation-induced cryptic vascular malformations: "Blooming" related to blood products • Tl C+ o Acute XRT: No enhancement o Early delayed XRT: +/- Patchy enhancement o Late delayed XRT: Enhancement often resembles residual/recurrent tumor about resection cavity • May see nodular, linear, curvilinear, "soap bubble" or "Swiss cheese" enhancement • May have multiple lesions remote from tumor site o Necrotizing leukoencephalopathy: Marked enhancement, may ring-enhance o PRES: +/- Enhancement • MRS: Radiation necrosis: Markedly reduced metabolites (NAA, Cho, Cr), +/- lactate !lipid peaks • Perfusion MR: Decreased rCBV in radiation necrosis

Angiographic

Findings

• Radiation induced vasculopathy: Progressive narrowing of supraclinoid ICA and proximal anterior circulation vessels; may develop moyamoya pattern

Diagnoses

Recurrent glioblastoma multiforme (GBM) Metastasis Abscess Multiple sclerosis Vascular dementia Progressive multifocalleukoencephalopathy

Pathology • XRT: Spectrum from edema to cavitating WM necrosis

Diagnostic Checklist • Distinguishing residual/recurrent neoplasm from XRT necrosis difficult using morphology alone • MRS, PET or SPECT may help delineate recurrent tumor from radiation necrosis

Nuclear Medicine

Findings

• FDG-PET: Radiation necrosis is hypometabolic • Thallium 201 SPECT: Radiation necrosis is hypometabolic, decreased uptake

Imaging Recommendations • Best imaging tool: Contrast-enhanced MR • Protocol advice: PET, SPECT, MRS if question of XRT vs recurrent neoplasm

I DIFFERENTIAL DIAGNOSIS Recurrent glioblastoma multiforme

(GBM)

• Enhancing mass with central necrosis, mass effect • T2/FLAIR WM signal, often follows WM tracts • MRS shows increased Cho, decreased NAA, +/-lactate

Metastasis • Typically multiple lesions at GM & WM junctions, significant edema • MRS shows increased Cho, decreased NAA, +/-lactate • Ring-enhancing mass may mimic XRT necrosis

Abscess • Ring-enhancing mass, thinner margin along ventricle • T2 hypointense rim, diffusion restriction characteristic • MRS shows metabolites such as succinate, amino acids

Multiple sclerosis • Often open • Other • Often

incomplete, "horseshoe-shaped" enhancement, towards cortex lesions in typical locations, young patients lack significant mass effect

Vascular dementia • Large and small infarcts, WM disease • Typically older patients, clinical diagnosis

Progressive multifocalleukoencephalopathy • WM T2 hyperintensity, involves subcortical V-fibers • May cross corpus callosum; nonenhancing typical • Immunosuppressed patients

10 47

Toxic/Metabolic/Degenerative

Disorders, Acquired

RADIATION AND CHEMOTHERAPY Vasculitis

Microscopic Features

• Multiple small WM areas of T2 hyperintensity • Gray matter involvement, enhancement may be seen

• Acute XRT injury: WM edema from capillary damage • Early delayed injury: Vasogenic edema, demyelination o Demyelination: Macrophage infiltrates, loss of myelin, perivascular lymphocytic infiltrates, gliosis • Late delayed injury: WM necrosis, demyelination, astrocytosis, vasculopathy o Radiation necrosis: Confluent coagulative necrosis, Ca++, telangiectasias, hyaline thickening and fibrinoid necrosis of vessels, thrombosis • Mineralizing microangiopathy: Hyalinization & fibrinoid necrosis of small arteries & arterioles with endothelial proliferation, Ca++ deposition

Foreign body reaction • Granulomatous reaction to gelatin sponge, etc • Can mimic tumor recurrence, radiation necrosis

!PATHQLRGY General Features • General path comments o Neurotoxic reaction to radiation therapy divided into acute, early and late delayed injury • Acute: Mild and reversible, vasogenic edema • Early delayed injury: Edema & demyelination • Late delayed injury: More severe, irreversible o XRT variables include: Total dose, field size, fraction size, number/frequency of doses, adjuvant therapy, survival duration, patient age o Most XRT injury is delayed (months/years) o Second neoplasms: Meningiomas (70%), gliomas (20%), sarcomas (10%) • More aggressive tumors, highly refractory • Etiology o Radiation-induced vascular injury • Permeability alterations, endothelial and basement membrane damage, accelerated atherosclerosis, telangiectasia formation o Radiation-induced neurotoxicity • Glial and WM damage (sensitivity of oligodendrocytes > > neurons) • Miscellaneous (effects on fibrinolytic system, immune effects) o Radiation-induced tumor (Le., sarcoma) • Increased risk in patients with XRT ~ 5 years old, those with genetic predisposition (Nfl, retinoblastoma), BMT survivors o Radiation-induced cryptic vascular malformations: Predominantly capillary telangiectasias +/- CMs • Altered venous endothelium, veno-occlusive dz o Many chemotherapy agents cause CNS effects: Methotrexate, cytarabine, carmustine, cyclophosphamide, cisplatin o Mineralizing micro angiopathy: Common with chemotherapy & XRT, appears :2: 2 years after XRT o Necrotizing leukoencephalopathy: Combined XRT and chemotherapy, progressive disease o PRES: Related to elevated blood pressure which exceeds autoregulatory capacity of brain vasculature • Associated with cyclosporine, tacrolimus, FK506, I-asparaginase, cisplatin, OKT3 • Epidemiology o Overall incidence of radionecrosis 5-24% o Second neoplasms: 3-12%

I CtlNICALlSSl.JES Presentation • Most common signs/symptoms: Highly variable • Radiation injury to the brain is divided into 3 groups o Acute injury: 1-6 weeks after or during treatment o Early delayed injury: 3 weeks to several months o Late delayed injury: Months to years after treatment

Natural History & Prognosis • Younger patient at time of treatment: Worse prognosis • Radiation necrosis is a dynamic pathophysiological process; often progressive, irreversible

Treatment • Biopsy if imaging does not resolve tumor vs radionecrosis • Surgery if mass effect, edema • Acute radiation injury may respond to steroids

I DIAGNC)STICiCHI2
Image Interpretation

I SELECTED REFERENCES 1.

2.

3.

4.

Gross Pathologic & Surgical Features

10

• XRT: Spectrum from edema to cavitating WM necrosis • Demyelination: Sharp interface with normal brain • Radiation necrosis: Coagulation necrosis that favors WM, may extend to deep cortex

Pearls

• MRS, PET or SPECT may help delineate recurrent tumor from radiation necrosis

5.

Vazquez E et al: Neuroimaging in pediatric leukemia and lymphoma: differential diagnosis. Radiographies. 22:1411-28,2002 Kamingo T et al: Radiosurgery-induced microvascular alterations precede necrosis of the brain neuropil. Neurosurg. 49: 409-415, 2001 Chong VF-H et al: Temporal lobe changes following radiation therapy: imaging and proton MRS findings. Eur Radiol. 11: 317-24, 2001 Kumar AJ et al: Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiol. 217: 377-84, 2000 Keime-Guibert F et al: Neurological complications of radiotherapy and chemotherapy. J Neurol. 245(11):695-708, 1998

48

Toxic/Metabolic/Degenerative

Disorders, Acquired

RADIATION AND CHEMOTHERAPY

Typical (Left) Axial T2WI MR shows a hyperintense lesion in the left frontal lobe with a hypointense rim (arrow) and surrounding edema and mass effect. Imaging mimics recurrent tumor. Biopsy proven XRT necrosis. (Right) Axial T1 C+ MR shows an enhancing mass in the left frontal lobe with a "soap bubble" appearance suggesting radiation necrosis. Note mass effect and midline shift. XRT necrosis at repeat resection.

Typical (Left) Axial FLAIR MR shows confluent, symmetric hyperintensity in the posterior temporal and parietal lobes, typical of PRES. Patient with acute neurologic changes after Cyclosporine treatment. (Right) Axial FLAIR MR shows symmetric abnormal hyperintensity in the cerebellar hemispheres bilaterally, typical of PRES. Patient with acute neurologic changes and hypertension related to Cyclosporine.

Typical

(Left) Axial FLAIR MR shows abnormal hyperintensity in the cortical spinal tracts and thalami bilaterally. 46 year old female with demyelination related to chemotherapy for breast cancer treatment. (Right) Axial FLAIR MR shows abnormal hyperintensity in the pons, brachium pontis and cerebellar hemispheres bilaterally. Treatment related demyelination. 46 year old with ataxia following chemotherapy.

10 49

Toxic/Metabolic/Degenerative

Disorders, Acquired

MESIAL TEMPORAL SCLEROSIS

Coronal graphic shows atrophy and loss of internal architecture of the right hippocampus, related to neuronal loss and gliosis characteristic of MTS. Note atrophy of the fornix (arrow).

Coronal T2WI MR shows hyperintensity and atrophy of the right hippocampus (arrow). Loss of internal architecture is also seen, typical of MTS. 23 year old with complex partial seizures.

CT Findings Abbreviations

• NECT: Typically normal, insensitive to MTS

and Synonyms

• Mesial temporal sclerosis (MTS), hippocampal sclerosis, HS, Ammon horn sclerosis

Definitions • A seizure-associated neuronal loss with gliosis in hippocampus and adjacent structures

IIMAC$IN.GflNJOINiG$ General Features • Best diagnostic clue o T2 hyperintense signal & atrophy of hippocampus, loss of internal architecture o Secondary signs: Fornix, mamillary body atrophy, enlarged temporal horn of lateral ventricle o Additional signs: Loss of hippocampal head digitations, atrophy of white matter in parahippocampal gyrus, increased T2 signal in anterior temporal white matter • Location o Mesial temporal lobe o Hippocampus> amygdala> fornix> mamillary bodies o Bilateral in 20% of cases

DDx: Temporal lobe Hyperintense

MR Findings • TlWI o Decreased size of hippocampus o Loss of gray-white differentiation in hippocampus o May see fornix and/or mamillary body atrophy • T2WI o Hyperintense signal in the hippocampus o Atrophy of hippocampus o Loss of gray-white differentiation/internal architecture in hippocampus o May see fornix and/or mamillary body atrophy o May see dilatation of temporal horn o May see hyperintensity in anterior temporal lobe o Bilateral in 20% • FLAIR: Hyperintense signal in the hippocampus • DWI: Early reports show elevated ADC in MTS • Tl C+: No enhancement • MRS o Decreased NAA in hippocampus, temporal lobe o NAA/Cho ::; 0.8 & NAA/Cr ::; 1.0 suggests MTS o If scan patient within 24 hours of seizure, lactate/lipid peaks reported • Quantitative hippocampal volumetry may increase sensitivity of MTS detection, particularly in patients with bilateral MTS

lesions

10 50

Status Epilepticus

Astrocytoma

Choroidal Fissure Cyst

Toxic/Metabolic/Degenerative

Hipp Sulcus Remnant

Disorders, Acquired

MESIAL TEMPORAL SCLEROSIS Key Facts Imaging Findings

Pathology

• T2 hyperintense signal & atrophy of hippocampus, loss of internal architecture • Secondary signs: Fornix, mamillary body atrophy, enlarged temporal horn of lateral ventricle • Mesial temporal lobe • Hippocampus> amygdala> fornix> mamillary bodies • Bilateral in 20% of cases

• Controversial, may be acquired or developmental • MTS accounts for majority of patients undergoing temporal lobe surgery • Dual pathology occurs with MTS in 15% of cases • Cortical dysplasia is most common dual pathology

Top Differential • • • • • •

Diagnoses

Status epilepticus Low grade astrocytoma Cortical dysplasia Choroidal fissure cyst Hippocampal sulcus remnant Dysembryoplastic neuroepithelial

Clinical Issues • Anterior temporal lobectomy successful in 70-95% patients with MR findings of MTS

Diagnostic Checklist • MTS is most common cause of partial complex seizures • Coronal high-resolution T2WI is best to diagnose MTS tumor (DNET)

Angiographic Findings

Cortical dysplasia

• Wada testing, neuropsychological testing after intracarotid amy tal injection, may be performed prior to seizure surgery o Useful to lateralize memory and language functions o Helpful to predict post-operative memory loss, feasibility of surgery o May help lateralize seizure onset

• • • • •

Nuclear Medicine

Findings

• FDG-PET: Hypometabolism in affected mesial temporal lobe • SPECT: Hypoperfusion in epileptogenic zone o Ictal SPECT is more sensitive than interictal SPECT

Imaging Recommendations • Best imaging tool o High resolution MR of temporal lobes o MRS may help lateralize MTS in difficult cases • Protocol advice o Thin section coronal T2Wl (3-4 mm), angled perpendicular to long axis of hippocampus o Thin section coronal 3-D SPGR (1-2 mm), angled perpendicular to long axis of hippocampus o Coronal FLAIR through temporal lobes o Phased-array surface coils to improve resolution o No contrast necessary unless focal lesion seen

I DIFFERENTIAL DIAGNOSIS Status epilepticus • • • •

T2 hyperintensity in affected portion of brain Gyriform enhancement typical Clinical history of seizures, status epilepticus Follow-up imaging may be necessary

low grade astrocytoma • • • •

Focal or diffuse white matter mass Nonenhancing T2 hyperintense mass May involve temporal lobe, cause seizures Young adults typical

Most common dual pathology associated with MTS Abnormally thickened gray matter Abnormal sulcal orientation Gray matter in abnormal location Common cause of seizures

Choroidal fissure cyst • Cyst within choroidal fissure may distort normal hippocampus • Round cyst on axial, coronal images; follows CSF • Oval cyst parallels long axis of temporal lobe on sagittal imaging • No T2 hyperintensity of mesial temporal lobe • Asymptomatic patients

Hippocampal

sulcus remnant

• Normal variant, 10-15% of patients • Bilateral cysts along hippocampus, between dentate gyrus and cornu ammonis • Failure of normal involution of hippocampal sulcus • Asymptomatic patients

Dysembryoplastic (DNET) • • • •

neuroepithelial

tumor

Demarcated "bubbly" cortical mass Variable enhancement Often associated with cortical dysplasia Patients with partial complex seizures

Cavernous malformation • Heterogeneous hyperintense lesion, "popcorn-like" • Blood products, complete hemosiderin rim often seen • May occur in temporal lobe, cause seizures

I PATHOLOGY General Features • General path comments o MTS is primary cause of complex partial seizures o MTS associated with second lesion in 15%

10 51

Toxic/Metabolic/Degenerative

Disorders, Acquired

MESIAL TEMPORAL SCLEROSIS o Hippocampus portions: Head (pes), body, tail o Hippocampus has complex anatomy • Ammon horn, dentate gyrus, hippocampal sulcus, fimbria, alveus, subiculum, parahippocampal gyrus, collateral sulcus o Ammon horn, cornu ammonis (CA), contains 4 zones of granular cells: CA1, CA2, CA3, CA4 • CA1 most susceptible to ischemia • CA4 is also susceptible to ischemia • Entire Ammon horn may be involved • Genetics: Familial cases of mesial temporal lobe epilepsy reported • Etiology o Controversial, may be acquired or developmental • Acquired: Shown to be related to changes after prolonged febrile seizures, status epilepticus, complicated delivery, and ischemia • Developmental: 2nd developmental lesion in 15% o Likely that MTS represents a common outcome of both acquired and developmental processes o Multiple seizures in early childhood are associated with hippocampal atrophy • Epidemiology o MTS accounts for majority of patients undergoing temporal lobe surgery o Dual pathology occurs with MTS in 15% of cases o Cortical dysplasia is most common dual pathology o Causes for patients undergoing epilepsy surgery • MTS (50-70%) • Perinatal hypoxia, other insult (13-35%) • Tumors (15%) • Vascular malformations (3%), • Traumatic gliosis (2%), • Developmental abnormalities (2%)

Gross Pathologic & Surgical Features • Atrophy of mesial temporal lobe o Hippocampal body (88%) o Hippocampal tail (61 %) o Hippocampal head (51%) o Amygdala (12%) • No hemorrhage or necrosis

Microscopic • • • •

o Patients often have remote history of childhood febrile seizures, medically intractable seizures

Demographics • Age: Disease of childhood, young adults • Gender: No gender predominance

Natural History & Prognosis • Anterior temporal lobectomy successful in 70-95% patients with MR findings of MTS • If MR is normal, success of anterior temporal lobectomy is 40-55% • If amygdala involved, decreased success of surgery, approximately 50%

Treatment • Medical treatment successful in only 25% • Anterior temporal lobe resection for medically intractable disease o Resection includes anterior temporal lobe, majority of hippocampus, variable portions of amygdala • Surgical removal of MTS is approximately 90% effective in seizure control I DIAGNQSTICCHEIJl\l..fSr

Consider • MTS is most common cause of partial complex seizures • Imaging findings of MTS may occasionally be found in normal, seizure-free, patients

Image Interpretation

ISElECTrDii~Effi6.R.~.~i(Jj.E~ 1. 2.

Features

Decrease in hippocampal neurons and gliosis CA1, CA4, and CA3 are most affected May involve entire cornu ammonis and dentate gyrus Chronic astrogliosis with a fine fibrillary background containing bland nuclei of astrocytes and few remaining neurons

3. 4.

5.

6.

Presentation

10

7.

• Most common signs/symptoms o Partial complex seizures o Other signs/symptoms • May progress to tonic-clonic seizures • Clinical profile o EEG often helpful for localization (60-90%) o Intracranial EEG (subdural or depth electrodes) may be indicated if noninvasive studies discordant

Pearls

• Coronal high-resolution T2WI is best to diagnose MTS • Dual pathology occurs in 15% of cases • T2 hyperintensity and atrophy of hippocampus most sensitive signs of MTS

8.

9.

Bocti C et al: The pathological basis of temporal lobe epilepsy in childhood. Neurology. 60(2):191-5, 2003 Sokol OK et al: From swelling to sclerosis: acute change in mesial hippocampus after prolonged febrile seizure. Seizure. 12:237-40, 2003 Kumlien E et al: Treatment outcome in patients with mesial temporal sclerosis. Seizure. 11(7):413-7, 2002 Capizzano AA et al: Multisection proton MR spectroscopy for mesial temporal lobe epilepsy. AJNR Am J Neuroradiol. 23(8):1359-68, 2002 Benbadis SR et al: MRI evidence of mesial temporal sclerosis in subjects without seizures. Seizure. 11(5):340-3, 2002 Castillo M et al: Proton MR spectroscopy in patients with acute temporal lobe seizures. AJNRAm J Neuroradiol. 22(1):152-7, 2001 Ho SSet al: Temporal lobe developmental malformations and epilepsy: dual pathology and bilateral hippocampal abnormalities. Neurology. 50(3):748-54, 1998 Lee OH et al: MR in temporal lobe epilepsy: analysis with pathologic confirmation. AJNRAm J Neuroradiol. 19(1):19-27, 1998 Bronan RA et al: Regional distribution of MR findings in hippocampal sclerosis. AJNR Am J Neuroradiol. 16:1193-1200, 1995

52

Toxic/Metabolic/Degenerative

Disorders, Acquired

MESIAL TEMPORAL SCLEROSIS

Typical (Left) Coronal T2WI MR shows hyperintensity and atrophy of the left hippocampus (arrow), MTS. Secondary signs are seen including atrophy of the fornix and enlargement of the temporal horn (curved arrows). (Right) Axial FLAIR MR shows abnormal hyperintensity in the medial left temporal lobe in this patient with a history of encephalitis and MTS. 30 year old male with complex partial seizures.

Typical

(Left) Coronal T2WI MR shows marked atrophy and abnormal hyperintensity in the right hippocampus compatible with MTS. Secondary signs of fornix atrophy and temporal horn dilatation are seen (arrows). (Right) Coronal T2WI MR shows abnormal hyperintense signal and atrophy of the right anterior temporal lobe related to prior injury. These secondary signs of MTS are less commonly seen.

Variant

(Left) Coronal T2WI MR shows abnormal enlargement and hyperintensity of the right hippocampus (arrow). Patient with acute complex partial seizures. Follow-up imaging 9 months later showed right MTS. (Right) Coronal T2WI MR shows abnormal hyperintensity and atrophy of the hippocampi bilaterally related to bilateral MTS. Mesial temporal sclerosis is bilateral in 20% of cases.

10 53

Toxic/Metabolic/Degenerative

Disorders, Acquired

STATUS EPILEPTICUS

Coronal T7 c+ MR shows gyriform and meningeal enhancement. History of status epilepticus immediately prior to imaging. Patient's seizures were treated and repeat imaging was normal.

Coronal T2WI MR shows abnormal hyperintensity in the hippocampi bilaterally (arrows). Patient with temporal lobe status epilepticus. Imaging 7 year later showed mesial temporal sclerosis.

I TERMINOLOGY

CT Findings

Abbreviations

• NECT o Hypodensity in cortex and/or subcortical WM o Blurring of corticomedullary junction o Hippocampus, splenium of corpus callosum may be involved o No hemorrhage • CECT: Variable enhancement: None to marked

and Synonyms

• Transient seizure-related MR changes, reversible post-ictal cerebral edema

Definitions • Status epilepticus: > 30 minutes of continuous seizures or 2 or more without full recovery between seizures • MR changes associated with seizures likely related to transient cerebral edema

I IMAGING EfNDINGS General Features • Best diagnostic clue o T2 hyperintensity in gray matter (GM) and/or subcortical white matter (WM) with mild mass effect o May focally involve hippocampus, corpus callosum • Location o Supratentorial, related to epileptogenic focus • Typically cortex and/or subcortical white matter o May involve focal structures • Hippocampus (febrile or partial complex seizures) • Splenium of the corpus callosum o Occasionally cerebellar involvement

DDx: Supratentorial

MR Findings • TlWI o Hypointensity in cortex and/or subcortical WM • Swelling and increased volume of involved cortical gyri o Blurring of corticomedullary junction o Mild mass effect o Hippocampus, splenium of corpus callosum may be involved o Rarely cerebellar involvement seen • T2WI o Hyperintensity in cortex and/or subcortical WM • Swelling and increased volume of involved cortical gyri o Mild edema and mass effect o Hippocampus, corpus callosum splenium may be involved o Rarely cerebellar involvement seen o No hemorrhage

Cortical and Subcortical White Matter lesions

10 54

MCA Ischemia

MELAS

Toxic/Metabolic/Degenerative

Herpes Encephalitis

Astrocytoma (Grade II)

Disorders, Acquired

STATUS EPILEPTICUS Key Facts Imaging Findings • T2 hyperintensity in gray matter (GM) and/or subcortical white matter (WM) with mild mass effect • May focally involve hippocampus, corpus callosum • Supratentorial, related to epileptogenic focus

Top Differential • • • • • •

Diagnoses

Cerebritis Ischemia MELAS Herpes encephalitis Mesial temporal sclerosis (MTS) Astrocytoma

Pathology • MR signal abnormalities related to transient vasogenic and/or cytotoxic edema

• FLAIR o Hyperintensity in cortex and/or subcortical WM o Mild edema and mass effect o Hippocampus, splenium of corpus callosum may be involved • DWI o Restricted diffusion with a decrease in ADC map described acutely o ADC maps normal interictally, elevated in chronic seizures • Tl C+ o Variable enhancement: None to to marked o May see gyriform or leptomeningeal enhancement • MRS o Lipids and/or lactate shown in hippocampi of temporal lobe epilepsy (TLE) patients within 24 hours of last seizure o Follow-up MRS after seizures under control show no lipids/lactate • Perfusion imaging (PWI): Marked hyperemia on side of epileptic focus, elevated rCBF maps

Nuclear Medicine

Findings

• PET: Increased glucose metabolism and metabolic rate • HMPAO SPECT: High uptake in affected cerebral lobe during or immediately after a seizure • Seizures: Increased metabolism and increased perfusion

Imaging Recommendations • Best imaging tool: MR is most sensitive • Protocol advice o Contrast-enhanced MR with DWI o MRS may be helpful in TLE patients

I DIFFERENTIAl. DIAGNOSIS Cerebritis • T2 hyperintense "mass" with mass effect • Typically diffusion restriction positive • Patchy enhancement typical

• Hippocampus involvement by status epilepticus may result in mesial temporal sclerosis • Epidemiology: Rare, approximately 100 cases reported

Clinical Issues • • • •

Active seizures and/or status epilepticus Clinical profile: EEG shows seizure activity Age: Occurs at all ages, commonly young adults Typically complete resolution with treatment of seizures

Diagnostic Checklist • Acute seizures or status epilepticus may mimic other pathology such as tumor progression or cerebritis • Look for underlying mass which may have caused the seizures/status epilepticus

Ischemia • • • •

Typical vascular distribution (ACA, MCA, PCA) Acute/subacute positive diffusion restriction Wedge-shaped, involves GM and WM Gyriform enhancement in subacute ischemia

MELAS • Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes • Multifocal bilateral T2 hyperintensities, typically reversible • Predominantly GM involvement, may involve subcortical WM • Ischemia in more than one vascular territory • MRS shows lactate peak

Herpes encephalitis • • • •

Confined to limbic system, temporal lobes Blood products, enhancement typical Acute onset, often with fever May present with seizures

Mesial temporal sclerosis (MTS) • Abnormal T2 hyperintensity in mesial temporal lobe • Volume loss and architectural distortion of hippocampus

Astrocytoma • • • •

Infiltrating white matter mass May extend to involve cortex Variable enhancement in anaplastic (grade III) May cause epilepsy

Vasculitis • Multiple small areas of T2 hyperintensity subcortical WM, often bilateral • Gray matter involvement may be seen • Variable enhancement

in deep and

Demyelination • Multifocal white matter lesions, deep gray nuclei • Incomplete rim or "horseshoe" shaped enhancement • Lesions often in typical locations

10 55

Toxic/Metabolic/Degenerative

Disorders, Acquired

STATUS EPILEPTICUS [DIAGNostiICGI-IECKtIST General Features

Consider

• General path comments o Portions of brain most vulnerable to damage from status epilepticus • CAl, CA3 and hilus of hippocampus, amygdala, piriform cortex, cerebellar cortex, thalamus, cerebral cortex • Etiology o MR signal abnormalities related to transient vasogenic and/or cytotoxic edema • Redistribution of intracellular and extracellular water, related to alteration in cell membrane permeability or cytotoxic edema o Hippocampus involvement by status epilepticus may result in mesial temporal sclerosis o Involvement of corpus callosum splenium, 2 theories • Transient focal edema related to transhemispheric connection of seizure activity • Reversible demyelination related to anti epileptic drugs • Epidemiology: Rare, approximately 100 cases reported

• Acute seizures or status epilepticus may mimic other pathology such as tumor progression or cerebritis • Clinical information and follow-up imaging often differentiates seizure related MR changes from other etiologies

1. 2.

3.

4.

Gross Pathologic & Surgical Features • Acutely: Swelling of cortex and/or subcortical WM or hippocampus • Chronic: Atrophy of involved cortex and/or subcortical WM

Microscopic

Image Interpretation

5.

Features

• Acutely: Reactive astrocytes with swollen cytoplasm and neuropil, consistent with cytotoxic edema • Chronic: Marked neuronal loss with intense astrocytic reaction; reactive astrocytes replacing absent neurons • Gliosis and neuronal loss affecting GM/WM junction with extension to cortex

6.

7.

8.

9.

Presentation • Most common signs/symptoms o Active seizures and/or status epilepticus o Other signs/symptoms: Location dependent • Clinical profile: EEG shows seizure activity

10.

11.

Demographics • Age: Occurs at all ages, commonly • Gender: No gender predominance

young adults

• Typically complete resolution with treatment seizures • May be complicated by infarction related to hypoxemia

12. 13.

Natural History & Prognosis of

14.

Treatment

15.

• Treatment of underlying seizure disorder o Antiepileptic medicines primary therapy • Surgical resection in patients with intractable

Pearls

• Look for underlying mass which may have caused the seizures/status epilepticus • Seizure related changes will usually resolve within days to weeks on follow-up imaging

Oster] et al: Diffusion-weighted imaging abnormalities in the splenium after seizures. Epilepsia. 44(6):852-4, 2003 Calistri V et al: Visualization of evolving status epilepticus with diffusion and perfusion MR imaging. A]NRAm ] Neuroradiol. 24:671-3, 2003 Hicdonmez T et al: Reversible postictal MRI change mimicking structural lesion. Clin Neurol Neurosurg. 105(4):288-90, 2003 Cohen-Gadol AA et al: Transient postictal magnetic resonance imaging abnormality of the corpus callosum in a patient with epilepsy. Case report and review of the literature.] Neurosurg. 97(3):714-7, 2002 Polster T et al: Transient lesion in the splenium of the corpus callosum: three further cases in epileptic patients and a pathophysiological hypothesis. ] Neurol Neurosurg Psychiatry. 70(4):459-63, 2001 Kim]A et al: Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: periictal diffusion-weighted imaging. A]NR Am] Neuroradiol. 22:1149-60, 2001 Castillo M et al: Proton MR spectroscopy in patients with acute temporal lobe seizures. A]NR Am] Neuroradiol. 22:152-7,2001 Amato C et al: Transient MRI abnormalities associated with partial status epilepticus: a case report. Eur] Radiol. 38(1):50-4, 2001 Sagiuchi T et al: Transient seizure activity demonstrated by Tc-99m HMPAO SPECTand diffusion-weighted MR imaging. Ann Nucl Med. 15(3):267-70, 2001 Men S et al: Selective neuronal necrosis associated with status epilepticus: MR findings. A]NR Am] Neuroradiol. 21:1837-40,2000 Kim SSet al: Focal lesion in the splenium of the corpus callosum in epileptic patients: antiepileptic drug toxicity? A]NR Am] Neuroradiol. 20:125-9,1999 Aykut-Bingol C et al: Reversible MRI lesions after seizures. Seizure. 6(3):237-9, 1997 Chan et al: Reversible signal abnormalities in the hippocampus and neocortex after prolonged seizures. A]NR Am] Neuroradiol. 17:1725-31, 1996 Cox]E et al: Seizure-induced transient hippocampal abnormalities on MR: correlation with positron emission tomography and electroencephalography. A]NR Am] Neuroradiol. 16(8):1736-8, 1995 Wasterlain CG et al: Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia. 34:137-53, 1993

epilepsy

56

Toxic/Metabolic/Degenerative

Disorders, Acquired

STATUS EPILEPTICUS

Typical (Left) Axial FLAIRMR shows hyperintensity in the subcortical white matter with sulcal effacement. Patient with a history of brain tumor resection and new seizures. Complete resolution on repeat MRI. (Right) Axial T7 C+ MR shows meningeal and gyriform enhancement. Patient with a history of brain tumor resection and new seizures. Concern for tumor recurrence. Repeat MRI normal after seizures treated.

(Left) Axial T7WI MR shows abnormal hypointensity in the left mesial temporal lobe cortex (arrow) and subcortical white matter with mild mass effect. Patient with temporal lobe epilepsy, acute seizures. (Right) Axial T2WI MR shows hyperintensity in the mesial temporal lobe (arrows) that completely resolved on repeat MRI. 49 year old male with temporal lobe epilepsy, poorly controlled with medication.

Variant (Left) Axial T2WI MR shows

focal hyperintensity in the splenium of the corpus callosum (arrows). Lesion completely resolved after patient's seizures treated (Courtesy O. Mendelson, MO). (Right) Axial T2WI MR shows hyperintensity in the right temporal cortex with mild gyral expansion and sulcal effacement. 20 year old with status epilepticus, temporal lobe epilepsy. Repeat imaging normal.

10 57

Toxic/Metabolic/Degenerative

Disorders, Acquired

Axial graphic shows widening of sulci and ventricles in the absence of any brain parenchymal abnormalities.

Definitions • I Overall brain volume with advancing in relative t CSF spaces

age, reflected

Axial FlAIR MR shows dilated ventricles, wide cortical sulci and per/ventricular white matter hyperintensity in an elderly individual.

• Putamen increases linearly with age • Morphology o Brain tissue I, CSF volume t • Reflects overall WM volume loss> focal WM hyperintensities (WMHs) • Rounded appearance of dilated ventricles, sulci t

CT Findings General Features • Best diagnostic clue o "Successfully aging brain": Thin periventricular high signal rim without white matter (WM) hyperintensities (WMHs) • Associated with mild shrinkage of selected cerebellar regions • Location o Selective atrophy of WM, not gray matter (GM) predominates o Striatum (primarily caudate nucleus and putamen) • Size o Decreased total brain volume o Absolute striatal size • Caudate decreases linearly with age • Putamen remains relatively stable o Relative striatal size (ratio of absolute size to total brain volume) • Caudate remains relatively stable

DDx: Atrophy and T2 Hyperintense

• NECT o Enlarged ventricles, widened cortical sulci o Patchy/confluent periventricular low densities o ± Symmetrical, punctate calcifications in globi pallidi (GP) o ± Curvilinear vascular Ca++ • CECT: No contrast-enhancement

MR Findings • TlWI o Mild but significant age-related shrinkage of posterior vermis (lobules VI and VII, and VIII-X) and cerebellar hemispheres o Apparent age invariance of anterior vermis and ventral pons o Dilated perivascular Virchow-Robin spaces • Small foci isointense to CSF on all pulse sequences, conform to path of penetrating arteries • Round/oval/curvilinear with well-defined smooth margins • Bilateral and often symmetrical, lack mass effect

White Matter lesions

10 58

Alzheimer Disease

Vascular Dementia

Toxic/Metabolic/Degenerative

Chronic HTN

Disorders, Acquired

Pick Disease

AGING BRAIN, NORMAL Key Facts • Best imaging tool: MR • Include T2* GRE on all patients>

Terminology • ~ Overall brain volume with advancing age, reflected in relative 1 CSF spaces

Top Differential • • • • •

Imaging Findings • "Successfully aging brain": Thin periventricular high signal rim without white matter (WM) hyperintensities (WMHs) • Selective atrophy of WM, not gray matter (GM) predominates • Focal/confluent periventricular WMHs • FLAIR: Smooth, thin, periventricular hyperintense rim normal • "Black dots" > 60 Y is NOT normal! • Age-related shift from anterior to posterior cortical metabolism • With age, rGMR 1 in putamen and ~ in caudate

•

• • •

•

•

•

• Increase in number and size (> 2 mm) with age • In inferior 1/3 of putamen T2WI o Focal/confluent periventricular WMHs • Number/size i after SO y; "" universal after 65 y • Only rough correlation with cognitive function • Significant overlap with dementias o "Infarct-like" T2 hyperintense lesions • Seen in 1/3 of asymptomatic patients> 65 y • 70%< lOmm • Mostly in basal ganglia (BG), thalami • Probably represent clinically silent lacunar infarcts o T2 shortening • "Black line" in visual, motor/sensory cortex common, normal in older patients • Ferric iron deposition: Normal in GP, abnormal in thalamus • With aging, hypointensity in caudate and putamen progresses and may equal GP in 8th decade o PD/FLAIR: Smooth, thin hyperintense periventricular rim normal PD/lntermediate: Smooth, thin, hyperintense periventricular rim normal FLAIR: Smooth, thin, periventricular hyperintense rim normal T2* GRE o "Black dots" > 60 Y is NOT normal! • Long-standing hypertension • Amyloid angiopathy DWI o Small but significant increased water diffusibility • ADC increases • Decreased anisotropy on diffusion tensor imaging Tl C+ o WMHs don't enhance o If do enhance, consider acute lacunar infarct or metastases MRS o Metabolite distribution varies among different brain regions o Choline (Cho) content increases with aging

60 y

Diagnoses

Mild cognitive impairment Alzheimer dementia (AD) Sporadic subcortical arteriosclerotic encephalopathy Vascular dementia Frontotemporal dementia (Pick disease)

Pathology • Epidemiology: WMHs correlate with age, silent stroke, hypertension, female gender

Diagnostic Checklist • Broad spectrum of "normal" on imaging in elderly • Cannot predict cognitive function from CT/MR

o Creatine (Cr) increases with aging oN-acetyl aspartate (NAA) ratios: % NAA (signal intensity integral of NAA divided by sum of all metabolite signal intensity integrals), NAA/Cho, NAA/Cr • Decreased with aging in cortex, centrum semiovale, and temporal regions • Strong correlation between WM volume and CSF volume: Measure of overall brain atrophy

Nuclear Medicine

Findings

• PET o Metabolic alterations common • Global and regional changes in CBF o Gradual decline in regional cerebral blood flow (CBF) of GM and WM, particularly of frontal lobes o Age-related shift from anterior to posterior cortical metabolism • Putamen receives primarily posterior cortical input • Caudate receives relatively more anterior cortical input o Relative glucose metabolic rate (rGMR) measured by FDG PET • With age, rGMR i in putamen and ~ in caudate o ~ Pre-/postsynaptic dopamine markers in BG • 99mTc-HMPAO SPECT, Xe-133 inhalation show regional, global reduction in CBF

Imaging Recommendations • Best imaging tool: MR • Protocol advice o T2WI, PD, FLAIR o Include T2* GRE on all patients>

I

60 y

DIFFERENTIAL DIAGNOSIS

Mild cognitive impairment • Overlap with normal on standard imaging studies • Associated with ~ size and number of regions of brain activation in response to memory tasks despite normally appearing brain on conventional MRI

10 59

Toxic/Metabolic/Degenerative

Disorders, Acquired

AGING BRAIN, NORMAL • Higher calculated hippocampal ADCs (not visible) • Subtle hypoperfusion, hypometabolism in parahippocampal regions, cingulum, thalamus

Alzheimer • • • •

dementia

(AD)

Parietal and temporal cortical atrophy Striking volume loss in hippocampi, entorhinal cortex Often co-existing microvascular disease, WMHs Striking temporoparietal hypometabolism, hypoperfusion

Sporadic subcortical arteriosclerotic encephalopathy • Associated with hypertension • Numerous WMHs (overlap with normal) • Multiple lacunar infarcts in lenticular nuclei, pons, thalamus, internal capsule, and caudate nuclei • Diffuse, confluent regions of periventricular WM involvement (leukoariosis)

ICLINICAL1SSlJES Presentation

Vascular dementia • Hyperintense lesions on T2WI and focal atrophy suggestive of chronic infarcts

Frontotemporal

• Increased extracellular space, gliosis • Iron deposition in globus pallidus, putamen • WM capillaries lose pericytes, have thinner endothelium • Dilated perivascular spaces of Virchow-Robin o Extension of subarachnoid space that accompanies penetrating vessels into brain to level of capillaries • Minimal loss of cortical neurons with age • Neurofibrillary tangles (NFTs) o Tau phosphorylation, mitochondrial dysfunction may precede full NFT formation o NFTs appear in small numbers in entorhinal and transentorhinal cortices early in aging (around 60 y) o NFTs may induce neural dysfunction, destruction of synapses, and, eventually, neuronal death

dementia

• Most common signs/symptoms o Normal cognitive function o Mild cognitive impairment correlates with 1 risk of AD

(Pick disease)

• Asymmetric frontal, anterior temporal atrophy • T2 hyperintensity in frontotemporal WM • Dilated subarachnoid space over frontal lobes signifying atrophy • !Metabolic activity in frontotemporal cortices

General Features • General path comments o !Neuronal viability or function associated with accelerated membrane degradation and/or 1 glial cell numbers o Loss of synapses and dendritic pruning in selected areas rather than globally • Genetics o Genetic factors clearly affect aging of brain o Contribution of ApoE allotype to age-dependent cognitive decline • Etiology o Previous concepts of aging: Substantial cortical neuronal loss with age o New: Predominant neuroanatomic changes • White matter alterations, subcortical neuronal loss • Reduction in cell size> cell number o Neuronal dysfunction rather than loss of neurons/synapses o Accumulation of neurofibrillary tangles (NFTs) may be responsible for memory loss associated with aging • Epidemiology: WMHs correlate with age, silent stroke, hypertension, female gender

Demographics • Age: After 60 years of age • Gender o Differences in striatal size • Relatively constant size across lifespan in men • Variable size across lifespan in women: Smaller size in women aged 50-70 y than in men o Differences in rGMR • Caudate: Higher rGMR in women than men • Putamen: Equal rGMR of women and men o Greater dopamine transporters in caudate in women

Natural History & Prognosis • Parenchymal volume !, CSF spaces 1 progressively • WMHs progressively increase with age

Consider • Striatum may mediate age-associated cognitive decline because of decreasing volume and functional activity with age

Image Interpretation

I SELECTED 1.

2.

Gross Pathologic & Surgical Features • Widened sulci, large ventricles

Microscopic

Pearls

• Broad spectrum of "normal" on imaging in elderly • Cannot predict cognitive function from CT/MR

REfERENCES

Kbvari E et al: Cortical microinfarcts and demylination significantly affect cognition in brain aging. Stroke 35:410-4,2004 Brickman AM et al: Striatal size, glucose metabolic rate, and verbal learning in normal aging. Cognitive Brain Research 17:106-116, 2003

Features

• Decreased myelinated

fibers in subcortical WM

60

Toxic/Metabolic/Degenerative

Disorders, Acquired

AGING BRAIN, NORMAL

I IMAGE GALLERY Typical (Left) Coronal T2WI MR

shows marked hypointensity in both lenticular nuclei and wide cortical sulci in an elderly individual. (Right) Coronal T2WI MR in the same individual shows hypointense putamina and normal hippocampal size despite loss of brain cortex.

Variant (Left) Axial PO/Intermediate MR in a 79 yo individual

without cognitive impairment shows mild periventricular white matter hyperintensities. (Right) Axial NECT in an 85 year old subject without cognitive impairment shows wide sulci and lateral ventricles, as well as moderate periventricular hypo dense white matter.

Typical (Left) FOG PETin a normal

83 y shows normal metabolism in brain cortex, basal ganglia and thalami (Courtesy N. Foster, MO and the University of Michigan PET Center). (Right) FOG PETin the same individual shows essentially normal glucose metabolism (depicted in red and yellow) in cerebral cortex except for small regions of decreased metabolism.

10 61

Tox ic!Metabol ic!Degenerative Disorders, Acqu ired

ALZHEIMER DEMENTIA

Axial T2WI MR through the lateral ventricles depicts atrophy of the superior aspect of temporal lobes and parietal lobe atrophy (Courtesy}. Norfray, MOJ.

Coronal T2WI MR through the temporal lobes depicts marked atrophy of the hippocampi (Courtesy J. Norfray, MOJ.

o 1 Perihippocampal fissures due to atrophy of hippocampus and parahippocampal gyrus o Preferential volume loss in temporal & parietal lobes o Large temporal horns, medial temporal lobe atrophy

ITERMINOLOGY Abbreviations

and Synonyms

• Alzheimer dementia

(AD)

Definitions

MR Findings

• Progressive degenerative disease of brain due to abnormal accumulation of tau protein, which plays a key role in neuronal/glial dysfunction and cell death

• MRS o t NAA, 1 myoinositol, 1 phosphomonoester in medial temporal and, to lesser degree, parietal lobes o Useful to monitor progression of disease by measuring progressive I in NAA • TlWI, T2WI o Volume loss in entorhinal cortex, hippocampus o Often have co-existing microvascular disease, WMHs • Functional MRI: Initial studies show t activation in various brain regions following memory tasks • MR volumetric analysis of hippocampi and para hippocampal gyri may help in distinguishing patients with mild cognitive impairment (at risk for proceeding to AD) from normal elderly subjects • Perfusion MRI using dynamic susceptibility contrast-enhanced MRI demonstrates t rCBV in temporal and parietal regions o Correlates with t rCBF seen on PET and SPECT

IIMAGING FINDINGS General Features • Best diagnostic clue: Parietal and temporal cortical atrophy w/disproportionate hippocampal volume loss • Location: Predominates in medial temporal and parietal lobes • Size: Decreased (atrophy) • Morphology: Cortical atrophy • Current role of imaging in AD is to exclude "treatable" dementias, identify early-onset cases for possible innovative therapy

CT Findings • NECT o 1 CSF spaces surrounding

Nuclear Medicine medial temporal lobes

Findings

• PET, SPECT o Specificity/sensitivity of FDG PET limited (e.g., can't distinguish AD from PD dementia)

DDx: Causes of Dementia

10 62

CjD

B 72 Deficiency

Toxic/Metabolic/Degenerative

Meningioma

Disorders, Acquired

BilateralSDHs

ALZHEIMER DEMENTIA Key Facts Terminology

Top Differential

• Progressive degenerative disease of brain due to abnormal accumulation of tau protein, which plays a key role in neuronal/glial dysfunction and cell death

• • • • • •

Imaging Findings • Best diagnostic clue: Parietal and temporal cortical atrophy w/disproportionate hippocampal volume loss • Current role of imaging in AD is to exclude "treatable" dementias, identify early-onset cases for possible innovative therapy • Coronal MRI documents atrophy of hippocampus and entorhinal cortex early in disease process and helps exclude other causes of dementia • Identify early AD cases for possible therapy

Diagnoses

Creutzfeldt-]akob disease Causes of reversible dementia Vascular dementia Diffuse Lewy body disease Frontotemporal dementia (Pick disease) Corticobasal degeneration

Pathology • Neuritic plaques (NPs), NTs in hippocampus, neocortical/some subcortical areas

Clinical Issues • Age: Prevalence increases with age

Diagnostic Checklist • If no brain atrophy, patient unlikely to have AD

o Regional hypometabolic areas (I glucose, 02 utilization in temporal/parietal lobes) correlate with severity of cognitive impairment o Perfusion deficits (I rCBF) on PET using 015 H20 or SPECT in hippocampus and temporoparietal regions

Imaging Recommendations • Best imaging tool o Coronal MRI documents atrophy of hippocampus and entorhinal cortex early in disease process and helps exclude other causes of dementia o PET helps to differentiate AD from vascular or frontotemporal dementia when clinical diagnosis of AD uncertain • Preclinical AD diagnosed in patients with mild cognitive impairment + genetic risk factors (Apo~4 allele) + I metabolic rates • Protocol advice: Axial and coronal T2WI to assess specific regions of atrophy • Look for partially/fully reversible causes of dementia (detected in up to 10% of cases) • Identify early AD cases for possible therapy o Volumetric MR of hippocampus, entorhinal cortex o Functional neuroimaging allows diagnosis before neuronal death, but is currently "not cost-effective" o MR brain activation studies being investigated for role in diagnosis and following therapy o New diagnostic techniques, such as molecular imaging

• Depression ("pseudodementia") • NPH shows generalized ventricular enlargement without disproportionate hippocampal atrophy • Head trauma (e.g., chronic subdural hematoma) • Mass lesions (e.g., large sub frontal meningioma causes personality change, micturition problems before cognitive decline) • Infections (e.g., neurosyphilis, HIV)

Vascular dementia • 2nd most common dementia (15-30%) • Hyperintense lesions on T2WI and focal atrophy suggestive of chronic infarcts

Diffuse Lewy body disease • Hypometabolism of entire brain, including visual cortex/ cerebellum

Frontotemporal

dementia (Pick disease)

• Asymmetric frontal, anterior temporal atrophy • Volumetric studies differentiate from AD

Corticobasal degeneration • Prominent extrapyramidal, cortical symptoms • Severe frontoparietal atrophy

Other neurodegenerative • Huntington

disorders

disease, Parkinson disease

IPATHOI..OG¥

I DIFFERENTIAl.. DIAGNOSIS Creutzfeldt-Jakob

disease

• Dementia + myoclonus + EEG abnormalities • Hyperintense changes in basal ganglia, thalamus and cerebral cortex on T2WI

Causes of reversible dementia • Alcohol is 3rd most common cause of dementia • Endocrinopathies (e.g., hypothyroidism) • Vitamin B12 deficiency causing corticospinal tract + dorsal column lesions, peripheral neuropathy

General Features • General path comments: Degenerative process starts in medial temporal lobe, spreads to parahippocampal gyrus, temporal and frontal lobes, and finally involves motor and visual cortex • Genetics o Most cases spontaneous and 5-10% familial o Early-onset, familial, autosomal dominant AD • Mutations in amyloid precursor protein gene on chromosome 21

10 63

Toxic/Metabolic/Degenerative

Disorders, Acquired

• 55% have missense point mutations of presenilin-1 gene on chromosome 1 and presenilin-2 gene on chromosome 14 o The more common late-onset familial AD and sporadic AD: • Associated with apolipoprotein E (ApoE) E4 allele on chromosome 19 • 60-75% of all AD patients carry at least one copy • ApoE increases the susceptibility of patients subjected to head trauma to progress to AD o Spontaneous mitochondrial mutations after age 80 also contribute to formation of senile plaques • Etiology o B-amyloid precursor protein has pivotal role in AD o Independent development of neurofibrillary tangles (NTs) and senile plaques • Deposition of abnormal protein such as B-amyloid in senile/neuritic plaques and tau in NTs o Amyloid and tau deposited along course of cortical memory pathways cause neuronal damage o NTs are intraneuronal, fill cytoplasm, and impair glucose transport o Senile plaques are extraneuronal, promote an attack by microglia ("inflammatory cascade") • Epidemiology o 4 million Americans affected, > 30 million people worldwide • By 2050, > 14 million Americans affected by AD o Prevalence of "" 5.7% in people :2: 65 Y o AD is most common • Dementia/cause of cerebral atrophy in elderly • Neurodegenerative dementia (50-75%) • Associated abnormalities: Almost all patients with Down syndrome (trisomy 21) develop AD by age 40

Gross Pathologic & Surgical Features

• Clinical profile o Clinical subtypes • Mild cognitive impairment: Early, mild memory impairment; no deficits in cognitive domains other than memory • Possible AD: Dementia features in presence of second disease that could cause memory deficit but is not the likely cause • Probable AD: Memory deficits on neuropsychological testing, progressive worsening of memory and :2: 2 cognitive functions • Primarily a disease of old age but autosomal dominant familial AD can present as early as 4th decade • Initial symptom = memory impairment • Visual variant of AD may present with impaired visuospatial skills without memory complaints

Demographics • Age: Prevalence increases with age • Gender: Women more commonly affected (M:F

=

1:2)

Natural History & Prognosis • Chronic, progressive impairment of intellectual functions • 65 yo with mild cognitive impairment subsequently diagnosed as AD at 10-15% per year, > 50% at 5 years • Average patient lives 8-10 y after onset of symptoms

Treatment • Cholinesterase inhibitors delay the decline in memory + cognitive functions by 9-12 months • Disease modifying agents: Statius, NSAIDs, vitamin E • A wide variety of promising new drugs for early mild/moderate AD are under investigation • Amyloid vaccine is under investigation; t amyloid burden, but risk of encephalitis as side effect

• Shrunken gyri, widened sulci

Microscopic

Features

• Neuritic plaques (NPs), NTs in hippocampus, neocortical/some subcortical areas • Loss of synapses, neurons (greatest in layers 3 and 5) • Amyloid angiopathy (B-amyloid is major component of both NPs and blood vessels in AD) • Astrogliosis and microgliosis • t Fiber density primarily in temporal white matter • Disruption/loss of axonal membranes and myelin

Image Interpretation

1.

Staging, Grading or Classification Criteria 2.

• Transentorhinal stage: NTs develop in parahippocampal gyrus (clinically asymptomatic) • Limbic stage: NTs dramatically increase in parahippocampal gyrus, begin to develop in hippocampus (mild cognitive impairment) • Neocortical stage: NTs develop in temporal and parietal cortex, eventually spread to entire neocortex (severe dementia)

3.

4.

5. 6.

7.

Presentation • Most common signs/symptoms: Major dysfunction memory and cognition, and personality changes

Pearls

• If no brain atrophy, patient unlikely to have AD • FDG PET has prognostic value

in

Patwardhan MB et al: Alzheimer disease: Operating characteristics of PET-Ameta-analysis. Radiology 231:73-80,2004 Sair HI et al: In vivo amyloid imaging in Alzheimers disease. Neuroradiology 46:93-104, 2004 Norfray J et al: Alzheimer's disease: Neuropathological findings and recent advances in imaging. AJR 182:3-13, 2004 Petrella JR et al: Neuroimaging and early diagnosis of Alzheimer disease: a look to the future. RadioI226:315-336, 2003 Friedenberg RM: Dementia: one of the greatest fears of aging. Radiology. 229(3):632-5, 2003 Bayer TA et al: Key factors in Alzheimer's disease: amyloid precursor protein processing, metabolism and intraneuronal transport. Brain Pathol1l:1-11, 2001 Jack CRJr et al: Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease. Ann NeuroI43:303-31O, 1998

64

Toxic/Metabolic/Degenerative

Disorders, Acquired

ALZHEIMER DEMENTIA IIMAGE GALLERY Typical (Left) Axial TlWI MR image through the inferior temporal lobes shows marked atrophy of temporal lobes and enlargement of lateral ventricles. (Right) Axial FLAIR MR in a different patient shows marked atrophy of the temporal lobes and enlargement of the Sylvian fissures.

Typical (Left) Axial T2WI MR through the inferior temporal lobes shows marked atrophy of temporal lobes and enlargement of parahippocampal fissures (Courtesy j. Norfray, Mo). (Right) MRS spectrum in parietal lobe of patient with probable Alzheimer shows decreased N-acetyl aspartate level (neuronal loss) and elevated myoinositollevel (gliosis) (Courtesy}. Norfray, Mo).

Typical (Left) FOG PET in a patient with dementia depicts hypometabolism (green and blue regions in cortex) in both parietal lobes typical of AD (Courtesy N. Foster, Mo and the University of Michigan PET Center). (Right) FOG PET in the same patient shows decreased rate of glucose metabolism in posterior aspects of both temporal lobes, typical of AD (Courtesy N. Foster, Mo and the University of Michigan PET Center).

10 65

Toxic/Metabolic/Degenerative

Disorders, Acquired

MULTI-INFARCT

Axial graphic illustrates diffuse atrophy, right frontal & bilateral parietal chronic infarcts (arrows), acute left occipital infarct (open arrow), basal ganglia & thalamic lacunes.

DEMENTIA

Axial NECT demonstrates periventricular white matter hypodensity as well as bilateral MCA & right PCA vascular distribution cortical/subcortical infarcts in a patient with vascular dementia.

o BG lacunar infarcts o Atrophy • Diffuse with large ventricles and cortical sulci • Accompanied by focal lesion-associated atrophy

I TERMINOLOGY Abbreviations

and Synonyms

• Multi-infarct dementia (MID) • Vascular dementia (VaD)

MR Findings

Definitions • Stepwise progressive deterioration of cognitive function secondary to repeated cerebral infarctions

IMAGING FINDINGS General Features • Best diagnostic clue: Multifocal infarcts involving cortical gray matter, subcortical white matter (WM), basal ganglia (BG), pons • Location o Typically involve cerebral hemispheres and BG o Usually bilateral, but may be unilateral • Size: Decreased (Le., atrophy) • Morphology: Multiple small or large vessel as well as lacunar infarcts

CT Findings • NECT o Hypodensity in periventricular o Cortical, subcortical infarcts

WM

• T1WI: All MID have hypointense BG lacunar infarcts • T2WI o Central pontine infarcts o Atrophy • Diffuse with large ventricles and cortical sulci • Accompanied by focal lesion-associated atrophy • FLAIR o Periventricular hyperintensity o Focal cortical, deep and subcortical WM hyperintense foci from infarcts o Hyperintense BG lacunar infarcts • T2* GRE: Susceptibility aids in identifying hemorrhagic components • DWI o Diffusivity is increased within lesions and in normal appearing WM (NAWM) o Mean diffusivity of NAWM correlates with IQ & tests of executive function • No correlation identified with T2 lesion load o DTI may be useful in monitoring disease progression and a surrogate marker for treatment trials

DDx: Other Causes of Dementia ~

10 66

Alzheimer Disease

Alzheimer Disease

Frontotemp Dementia

Tox ic!Metabol ie/Degenerative

Disorders, Acqu ired

Pick Disease

MULTI-INFARCT DEMENTIA Key Facts Terminology • Stepwise progressive deterioration of cognitive function secondary to repeated cerebral infarctions

Imaging Findings • Best diagnostic clue: Multifocal infarcts involving cortical gray matter, subcortical white matter (WM), basal ganglia (BG), pons • Diffusivity is increased within lesions and in normal appearing WM (NAWM) • j NAA in both cortical and WM regions • PET: FDG-PET: Severity of MID neuropsychiatric symptoms correlates with extent of j cortical, WM metabolism

Top Differential

Diagnoses

• Alzheimer disease

• TI C+: Patients often present late, thus usually no enhancement • MRA: Circle of Willis, carotid, vertebral stenoses • MRS o j NAA in both cortical and WM regions o Frontal cortex NAA negatively correlated with volume of WM signal hyperintensity

Ultrasonographic

Findings

• Transcranial Doppler sonography o MCA & basilar pulsatility indices of MID are significantly 1 compared to AD & healthy age-matched subjects • Extracranial Doppler sonography may detect source of thromboembolism

Nuclear Medicine

Findings

• PET: FDG-PET: Severity of MID neuropsychiatric symptoms correlates with extent of j cortical, WM metabolism • SPECT o Iodine-I23 iodoamphetamine: j Frontal & BG CBFcorrelating with cognitive scores o Technetium-99m hexamethyl propylene amine oxime: CBF heterogeneity more posterior dominant for AD and anterior dominant for VaD

Imaging Recommendations • Best imaging tool o MRI + contrast o PET or SPECT may aid in diagnosis • Protocol advice: DTI may be useful for monitoring

I DIFFERENTIAL DIAGNOSIS Alzheimer

disease

• Often with more prominent atrophy of hippocampus & amygdala ~ temporal horn enlargement • PET: Bilateral temporoparietal hypoperfusion, hypometabolism sparing BG • Abnormal protein such as B-amyloid in senile/neuritic plaques and tau in neurofibrillary tangles

• Frontotemporal • Pick disease

dementia

Pathology • Approximately 10-30% of dementias • Second most common cause of dementia in elderly after AD in the US

Clinical

Issues

• • • • •

Infarcts with transient focal neurologic deficits Earlier age of onset than AD Incidence increases with age Gender: M > F Prognosis ultimately depends on underlying cerebrovascular status • 5-year survival rate is 39% for patients with VaD compared to 75% for age-matched controls

Frontotemporal

dementia

• Characterized by early onset of behavioral changes with intact visual, spatial skills • Frontal and temporal lobe atrophy

Pick disease • Preferential involvement of frontal lobes compared with temporal lobe involvement o May be striking ~ "knife-like" gyri • Distinctive cytoplasmic inclusions; "Pick bodies"

I PATI':IOlOG¥ General Features • General path comments: Combination between cerebrovascular lesions and Alzheimer-type pathology is most common neuropathological finding in elderly patients with dementia • Genetics o Apolipoprotein E (ApoE) • A serum protein involved in lipid metabolism • Encoded at a single gene locus on chromosome 19 by three alleles: E2, E3, E4 • Frequency of E4 allele significantly higher among cases of AD and VaD compared to controls • Odds of developing AD or VaD = 4.4 & 3.7x higher (respectively) in presence of even a single E4 allele • €3€3 and €2€3 genotypes are protective • That both dementi as share a common genetic influence supports a link between the pathogenesis of AD and VaD o Paraoxonase (PONI) • A component of high density lipoproteins with antioxidative potential • Two PONI polymorphisms (GlnI92Arg associated with enzyme activity and T-I07C associated with enzyme concentration) are independent risk factors for VaD particularly in ApoE (E4) • Subjects at risk have j plasma paraoxonase levels, less active enzyme ~ oxidative stress

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Toxic/Metabolic/Degenerative

Disorders, Acquired

MULTI-INFARCT DEMENTIA • Etiology o MID is usually due to multiple small infarctions • None involve an entire major vessel territory • Minority may be 2 to single or a few large infarctions o "" 75% of all MID patients exhibit small-vessel disease rather than thromboembolism o Growing evidence for involvement of cholinergic system in VaD • Cholinergic deficits well documented in VaD, independent of concomitant AD pathology • Cholinergic neuron loss 70% of AD, 40% of VaD • Epidemiology o Approximately 10-30% of dementi as o Second most common cause of dementia in elderly after AD in the US • Most common form in parts of Asia o 23-28% elderly stroke patients meet VaD criteria • Prevalence 9x higher in patients who have had a stroke than in controls 0

Gross Pathologic & Surgical Features • Multifocal infarctions with atrophy

Microscopic

Features

• Myelin and axonal loss with astrocytosis • Vessels display atheromata, lipohyalinosis, subintimal thickening, fibrinoid necrosis • Infarcted tissue undergoes necrosis ~ gliotic wall surrounding a CSF cavity

Staging, Grading or Classification Criteria • 8 subtypes of VaD o Multi-infarct dementias: Due to large cerebral emboli, usually readily identifiable o Strategically placed infarctions causing dementia o Multiple subcortical lacunar lesions: Develop VaD 5-25x more frequently than age-matched controls o Binswanger disease: Small-vessel disease ~ widespread incomplete infarction of WM o Mixtures of two or more of above VaD subtypes o Hemorrhagic lesions causing dementia o Subcortical dementias due to other causes of multiple subcortical lacunar lesions similar to Binswanger disease • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) • Familial amyloid angiopathies and coagulopathies o Mixtures of Alzheimer dementia (AD) and VaD

o Deterioration of executive function and attention, changes in personality rather than memory loss, are predominant • Clinical profile o Main risk factors • Advanced age, hypertension, diabetes, smoking • Hypercholesterolemia, hypercoagulable states • Hyperhomocysteinemia, hyperfibrinogenemia • Causes of brain hypoperfusion (e.g., obstructive sleep apnea, congestive heart failure, cardiac arrhythmias, and orthostatic hypotension)

Demographics • Age o Earlier age of onset than AD o Incidence increases with age • Gender: M > F

Natural History & Prognosis • Progressive, episodic, stepwise downward course • Intervals of clinical stabilization or even limited recovery • Prognosis ultimately depends on underlying cerebrovascular status • 5-year survival rate is 39% for patients with VaD compared to 75% for age-matched controls

Treatment • Goal is to prevent further vascular insult by controlling precipitating factors such as hypertension o Doing so may arrest, prevent further deterioration o Cognition can even improve • Three acetylcholinesterase inhibitors approved for use in AD are being tested in VaD (donepezil, rivastigmine, galantamine) o Donepezil has demonstrated significant improvement in cognition, global function, activities of daily living in comparison with placebo-treated patients with VaD

1.

2. 3.

4.

5.

Presentation

10

• Most common signs/symptoms o Infarcts with transient focal neurologic deficits • Most deficits persist o Discrete stepwise decline in cognitive skills, memory disturbance o Mood and behavioral changes o Severe depression is more common in VaD than AD o VaD frontal/subcortical intellectual impairment pattern contrasts typical AD cortical presentation

6.

Martinez-Bisbal MC et al: Cognitive impairment: classification by 1H magnetic resonance spectroscopy. Eur J Neurol. 11(3):187-93, 2004 Helbecque N et al: Paraoxonase 1 gene polymorphisms and dementia in humans. Neurosci Lett. 358(1):41-4, 2004 O'Sullivan M et al: DTI MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis. J Neurol Neurosurg Psychiatry. 75(3):441-7, 2004 Roman GC et al: Donepezil: a clinical review of current and emerging indications. Expert Opin Pharmacother. 5(1):161-80,2004 Luthra K et al: Apolipoprotein E Gene Polymorphism in Indian Patients with Alzheimer's Disease and Vascular Dementia. Dement Geriatr Cogn Disord. 17(3):132-135, 2004 Yoshikawa T et al: Heterogeneity of cerebral blood flow in Alzheimer disease and vascular dementia. AJNRAm J Neuroradiol. 24(7):1341-7, 2003

68

Toxic/Metabolic/Degenerative

Disorders, Acquired

MULTI-INFARCT DEMENTIA IIMAGE GALLERY Typical (Left) Sagittal T1 WI M R demonstrates frontal cortical thinning with white matter hypointensity (arrow) from infarction. Also note separate focus of white matter abnormality (open arrow). (Right) Axial FLAIR MR shows diffuse, confluent white matter hyperintensity in a patient with vascular dementia.

Typical (Left) Axial NECT demonstrates periventricular white matter hypodensity as well as bilateral MCA vascular territory evolving infarctions in a demented patient. Diagnosis = vascular dementia. (Right) Axial NECT shows white matter hypodensity as well as bilateral frontal & parietal evolving cortical infarctions. Note the associated focal biparietal cortical atrophy (arrows).

Typical (Left) Axial T2WI MR reveals bilateral thalamic lacunar infarctions (arrows) as well as confluent periventricular white matter hyperintensity. Note ventricular enlargement from associated atrophy. (Right) Axial FLAIR MR demonstrates only mild white matter hyperintensity as well as a very small cortical/subcortical infarct (arrow) in a patient with vascular dementia.

10 69

Toxic/Metabolic/Degenerative

Disorders, Acquired

FRONTOTEMPORAL DEMENTIA

Sagittal T7WI MR demonstrates marked atrophy of the frontal lobe in a patient with Pick disease.

I TERMINOLOGY Abbreviations

and Synonyms

• Pick disease (PiD), restricted to pathologic variant with Pick bodies; lobar cerebral atrophy • Frontotemporal dementia (FTD) = new name for clinical PiD

Definitions • Type of dementia caused by focal cortical atrophy involving frontal and/or temporal lobes

I IMAGING

FINDINGS

General Features • Best diagnostic clue: Anterior frontotemporal atrophy • Location o Anterior temporal and frontal lobes, orbital frontal lobe, and medial temporal lobes o Spared posterior aspect of superior temporal gyrus and pre- and postcentral gyri o Unremarkable parietal and occipital lobes • Size: ~ (Worse atrophy of dominant hemisphere) • Morphology: Marked asymmetry

CT Findings • NECT

Coronal T7WI MR in a patient with Pick disease shows prominent atrophy of both frontal lobes, more pronounced on the left side.

o May be greater involvement of frontal lobes • Represented as enlargement of frontal horns to greater extent than the rest of lateral ventricles o Concomitant caudate atrophy also reported • CECT: No contrast-enhancement

MR Findings • Tl WI: Normal signal in affected brain regions • T2WI o Hyperintensity in frontotemporal white matter o Dilated subarachnoid space over frontal lobes signifying atrophy • PD/Intermediate: Hyperintensity in frontotemporal white matter • FLAIR:Same as T2WI • Tl C+: No contrast-enhancement • MRS o ~ NAA and glutamate-plus-glutamine (neuronal loss) and t myo-inositol (t glial content) in frontal lobes • ~NAA in posterior cingulate gyri reported • Reflects ~ neuronal population and viability o Lactate peak in frontal lobes in some cases o t Phosphomonoester, phosphodiester

Nuclear Medicine

Findings

• PET: ~Metabolic activity in frontotemporal cortex • HMPAO-SPECT o Most sensitive technique for early detection of FTD • Hypoperfusion in ventromedial frontal region

DDx: Other Causes of Dementia

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Alzheimer Disease

Cortical Infarcts

Toxic/Metabolic/Degenerative

Subcortical Dementia

Disorders, Acquired

FRONTOTEMPORAL DEMENTIA Key Facts • Tauopathy: 3 and 4 microtubule-binding repeat tau pathology in both cortical gray and white matter • Etiology: Tau (hyperphosphorylated microtubular

protein)

,,~uJ_ ""bmtn,<Jil'ickipatlents

Clinical Issues • 3 major clinical syndromes reflect distribution of pathologic changes rather than histologic subtype • Frontal variant FTD (dementia of frontal type): 40% • Semantic dementia (progressive fluent aphasia): 40% • Progressive nonfluen taphaslOa(prlOmaryp rogressive aphasia)

Diagnostic Checklist

•

• Frontal atrophy should raise issue of PiD • Parieto-temporal atrophy: AD • Primarily white matter disease: Vascular dementia

lobar atrophy

• Occurs before atrophy is evident o Semantic dementia • Hypoperfusion of one or both temporal lobes • SPECT perfusion deficits predominantly frontal and anterior temporal with preserved perfusion posteriorly o Helps distinguishes FTD from AD • Reduced frontal perfusion is not specific to FTD o Occurs in schizophrenia, depression, HIV encephalopathy, Creutzfeldt-]akob, some AD cases

Imaging Recommendations • Best imaging tool: CT or MRI • Protocol advice: Routine Tl WI, T2WI

• Mild spontaneous extrapyramidal features with exaggerated adverse reactions to standard neuroleptics • Repeated unexplained falls and/or transient clouding or loss of consciousness

Head injury • Evident at an average of 11 months after trauma • Whole-brain atrophy occurs after mild/moderate traumatic brain injury • Injury with loss of consciousness ~ more atrophy

IPATHOl-OGY General Features

I DIFFERENTIALDIAGNOSrS Alzheimer

dementia

(AD)

• Parietal and temporal cortical atrophy with disproportionate hippocampal volume loss • Often co-existing microvascular disease, white matter hyperintensities • PET helps to differentiate AD from vascular/FTD when clinical diagnosis of AD uncertain

Corticobasal • • • • •

ganglionic degeneration

(CBD)

Prominent extrapyramidal, cortical symptoms Severe frontoparietal atrophy Atrophy of paracentral structures Superior parietal lobule knife blade atrophy Dilated central sulcus, asymmetry

Vascular dementia • • • •

2nd most common dementia (15-30%) White matter and deep gray lacunae Strokes of different ages, central pontine infarcts Hyperintense lesions on T2WI, hypodense areas on CT and focal atrophy suggestive of chronic infarcts

Diffuse Lewy body disease • Hypometabolism of entire brain, including visual cortex/ cere bellum • Visual & auditory hallucinations, paranoid delusions

• General path comments o Hallmark is circumscribed lobar atrophy o Nonspecific spongiform degeneration, with gliosis & neuronal loss, sometimes with Pick cells & bodies o Tauopathy: 3 and 4 microtubule-binding repeat tau pathology in both cortical gray and white matter • Genetics o 25-40% of FTD is familial o 10-30% of patients with positive family history have tau mutations • Tau gene located on chromosome 17 • FTD with parkinsonism linked to chromosome 17 o Many mutations occur in exon 10 of tau gene • One of most common tau mutations (P301L) is associated with classic FTD phenotype • Presymptomatic mutation carriers of P310L show frontal focal deficits decades prior to dementia • Potential developmental component related to mutant tau alters frontal lobe function in early life o Tau mutations: Three-repeat (3-R) tau • 2 6 different mutations described in classic PiD, usually outside exon 10 o Reported overlap between 3-R and 4-R tau in PiD • Etiology: Tau (hyperphosphorylated microtubular protein) accumulates in brains of Pick patients • Epidemiology o < 10% of primary degenerative dementias o 5% of all dementias

Toxic/Metabolic/Degenerative

Disorders, Acquired

10 71

FRONTOTEMPORAL DEMENTIA o 3rd most common neurodegenerative cortical dementia after AD and diffuse Lewy body disease o 4th most common if non-neurodegenerative (vascular) dementia is included • Associated abnormalities o Extrapyramidal signs, asymmetrical motor syndromes, degeneration of substantia nigra and other deep nuclei o Motor neuron disease (amyotrophic lateral sclerosis)

Gross Pathologic & Surgical Features • • • •

Thin cortex, indistinct gray-white matter junction Firm cortical gray matter (gliosis) Soft, retracted subcortical white matter Dilated frontal and temporal horns of lateral ventricles

Microscopic

Features

• In affected brain areas: Almost complete loss of large pyramidal neurons, diffuse spongiosis and gliosis • In middle & lower cortical layers of frontal & temporal regions: Swollen (ballooned) neurons (Pick cells) • In superficial layers of frontal & temporal neocortex and in dentate fascia of hippocampus o Homogeneous, ovoid, argentophilic inclusions (Pick bodies) • Tau-positive and ubiquitin-positive • Found only in "" 20% of cases with clinical FTD

Staging, Grading or Classification Criteria • Constantinidis' neuropathological classification based on presence of Pick bodies and Pick cells o Type A PiD ("classic" PiD) • Frontotemporal and limbic degeneration • Pick bodies and Pick cells o Type B PiD • Superior frontal and parietal atrophy • Pick cells and no Pick bodies o Type C PiD • Either circumscribed or diffuse cortical atrophy with varying involvement of deep gray matter • Neither Pick bodies nor Pick cells • Clinically and pathologically heterogeneous • Probably includes progressive subcortical gliosis

I.CUNICAlISSUE'S Presentation

10 72

• Most common signs/symptoms o Personality, behavior, and language changes o Memory loss, confusion, cognitive and speech dysfunction, apathy, and abulia • Clinical profile o 3 major clinical syndromes reflect distribution of pathologic changes rather than histologic subtype o Frontal variant FTD (dementia of frontal type): 40% • Changes in social behavior and personality predominate • Orbitobasal frontal lobe pathology o Semantic dementia (progressive fluent aphasia): 40% • Impaired language production & comprehension • Asymmetric anterolateral temporal atrophy • Relative sparing of hippocampal formation • Typically asymmetric (worse on left side)

o Progressive aphasia) • Affected language • Atrophy temporal

nonfluent phonologic

aphasia (primary progressive & syntactic components

of

of insula, inferior frontal lobes & superior lobes; wide Sylvian fissure

Demographics • Age o Younger age group than AD o Peak incidence at 55-65 y; onset usually < 70 Y • Gender: Affects both sexes equally • Ethnicity: Familial forms of Pick-complex dementi as particularly common in people of Scandinavian origin

Natural History & Prognosis • Insidious onset of behavioral & cognitive dysfunction • Memory problems less severe than speech & language disturbance • Slowly progressive, leading to increased vocational and personal disability • Eventual loss of verbal & problem-solving skills • Some patients develop artistic talents during course of dementia (disinhibition of "creative" brain areas)

Treatment • No effective therapy available

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Frontal atrophy should raise issue of PiD • Parieto-temporal atrophy: AD • Primarily white matter disease: Vascular dementia

I SELECTED

REFERENCES

Goedert M: Tau protein and neurodegeneration. 5emin Cell Dev BioI. 15(1):45-9,2004 2. Uchihara T et al: Pick body disease and Pick syndrome. Neuropathology. 23(4):318-26, 2003 3. Kertesz A: Pick Complex: an integrative approach to frontotemporal dementia: primary progressive aphasia, corticobasal degeneration, and progressive supranuclear palsy. Neurologist. 9(6):311-7, 2003 4. Bird T et al: Epidemiology and Genetics of Frontotemporal Dementia/Pick's Disease. Annals of neurology 54: 529-531, 2003 5. Tolnay M et al: Frontotemporal lobar degeneration--tau as a pied piper? Neurogenetics. 4(2):63-75, 2002 6. Kizu 0 et al: Proton chemical shift imaging in pick complex. A]NR Am] Neuroradiol. 23(8):1387-92, 2002 Dickson DW. Neuropathology of Pick's disease. Neurology 7. 56: 516-520, 2001 8. Hodges ]R. Frontotemporal dementia (Pick's disease): Clinical features and assessment. Neurology 56: 56-510, 2001 9. Growdin] et al: A 74-Year-Old Man with Memory Loss, Language Impairment, and Personality Changes. NE]M 342: 1110-1117,2000 10. Kitagaki H et al: Alteration of white matter MR signal intensity in frontotemporal dementia. A]NR 18: 367-378, 1997 1.

Toxic/Metabolic/Degenerative

Disorders, Acquired

FRONTOTEMPORAL

DEMENTIA

IIMAGE GALLERY Typical (Left) Axial NECT demonstrates predominantly frontal lobe volume loss from Pick disease. (Right) Axial T2WI MR in a Pick disease patient shows marked frontal lobe atrophy.

(Left) Axial FLAIR MR shows frontal lobe volume loss as well as associated hyperintense signal in white matter. (Right) Axial T2WI MR in a patient with Pick disease demonstrates marked volume loss as well as associated hyperintense signal within bilateral temporal lobes.

Typical (Left) FOG PET in a patient with Pick disease and dementia depicts glucose hypometabolism (green regions in cortex) in frontal lobes (Courtesy N. Foster, MO and the University of Michigan PET Center). (Right) FOG PET in same patient shows decreased rate of glucose metabolism in frontal and temporal lobes, consistent with Pick disease (Courtesy N. Foster; MO and the University of Michigan PET Center).

10 73

Toxic/Metabolic/Degenerative

Disorders, Acquired

CREUTZFELDT-JAKOB DISEASE (CJD)

Axial T2WI MR shows bilateral increased signal intensity in putamen and caudate nuclei in a patient with Creutzfeldt-Jakob disease.

Axial OWl shows bilateral restricted diffusion putamen, caudate nuclei with small foci in thalami.

in

ITERMINOLOGY

CT Findings

Abbreviations

• NECT o Usually normal (80%) o May show rapidly progressive atrophy and ventricular dilatation (20%) o Serial CT illustrates progression of atrophic process

and Synonyms

• Creutzfeldt-]akob disease (C]D) • Transmissible spongiform encephalopathy

(TSE)

Definitions • Rapidly progressing, fatal, potentially transmissible dementing disorder caused by a prion (proteinaceous infectious particle devoid of DNA and RNA)

IIMAGING FINDINGS General Features • Best diagnostic clue: Progressive T2 hyperintensity of basal ganglia (BG), thalamus, & cerebral cortex • Location o Predominantly gray matter (GM) • BG (caudate nuclei, putamina, and, to lesser extent, globi pallidi), thalami • Cerebral cortex (most commonly frontal and temporal lobes) o May involve only peripheral cortex o White matter (WM) usually not involved • Size: Slightly decreased (atrophy) • Morphology: Hyperintense T2 signal conforms well to outline of BG and gyriform pattern in cerebral cortex

MR Findings • TlWI o Normal o Hyperintensity on Tl WI in globus pallidus reported in sporadic C]D (sC]D) • T2WI o Hyperintense signal in BG and thalami o High signal intensity changes in cortical GM o Cerebral atrophy o With time, hyperintense foci may develop in WM • FLAIR o Two signs characteristic of new variant C]D (nvCJD) • "Pulvinar" sign: Bilateral symmetrical hyperintensity of pulvinar (posterior) nuclei of thalamus relative to anterior putamen • "Hockey-stick" sign: Symmetrical pulvinar and dorsomedial thalamic nuclear hyperintensity o Periaqueductal GM hyperintensity o Cortical signal intensity change on FLAIR images • Described in sC]D • Rarely identified in nvC]D

DDx: Entities with Abnormal Signal Intensity in Basal Ganglia

10 74

Acute Hypoxia

Leigh Syndrome

Toxic/Metabolic/Degenerative

Wilson Disease

HTN Encephalopathy

Disorders, Acquired

CREUTZFELDT-JAKOB DISEASE (CJD) Key Facts Terminology • Rapidly progressing, fatal, potentially transmissible dementing disorder caused by a prion (proteinaceous infectious particle devoid of DNA and RNA)

Imaging Findings • Best diagnostic clue: Progressive T2 hyperintensity of basal ganglia (BG), thalamus, & cerebral cortex • "Pulvinar" sign: Bilateral symmetrical hyperintensity of pulvinar (posterior) nuclei of thalamus relative to anterior putamen • PET: Regional hypometabolism of glucose correlates with sites of neuropathologic lesions • Best imaging tool: MR using FLAIR and DWI

Top Differential

Diagnoses

• Hypoxic-ischemic

encephalopathy

• DWI o Progressively hyperintense changes in striatum and cerebral cortex o Gyriform hyperintense areas in cerebral cortex • Correspond to localization of periodic sharp-wave complexes on EEG o DWI hyperintensity may disappear later in disease • Tl C+: No contrast-enhancement of lesions

Nuclear Medicine

Findings

• PET: Regional hypometabolism of glucose correlates with sites of neuropathologic lesions

Other Modality

Findings

• SPECT with N-isopropyl-p-(123I) iodoamphetamine o j Uptake of tracer and j absolute values of rCBF in various parts of cerebral cortex • Sometimes in asymmetrical pattern • Sensitive for diagnosis of early stage CJD

Imaging Recommendations • Best imaging tool: MR using FLAIR and DWI • Protocol advice: DWI (highest sensitivity for detection of signal intensity abnormalities), T2WI

I DIFFERENTIAL

DIAGNOSIS

Hypoxic-ischemic

encephalopathy

• BG and para sagittal cortical areas involved • Hyperintense BG lesions on T1WI and T2WI

Other causes of dementia • • • •

Alzheimer dementia Dementia in motor neuron disease Frontotemporal dementia Multiinfarct dementia

Bilateral T2 hyperintense

BG abnormalities

• Small vessel ischemic disease o BG involvement: Typically asymmetric and multifocal (rather than diffuse as in CJD) o Focal hyperintensities in corona radiata and centrum semiovale

• Other causes of dementia • Bilateral T2 hyperintense BG abnormalities • Cortical basal ganglionic degeneration

Pathology • General path comments: Definitive diagnosis of prion disease requires brain biopsy or necropsy • Associated abnormalities: EEG: Periodic high-voltage sharp waves on background of low-voltage activity • Spongiform encephalopathy: GM most affected

Clinical Issues • Rapidly progressive dementia associated with myoclonic jerks and akinetic mutism

Diagnostic Checklist • Lack of BG findings does not rule out C]D

• Wilson disease o WM and deep GM lesions, involving BG, dentate nucleus, pons, mesencephalon o T1 hypointense (occasionally hyperintense) lesions o Variably hyperintense/hypointense/both on T2WI • HIV-l encephalopathy and AIDS dementia complex o Similar lesions in putamen • Leigh disease o Primarily a childhood disease o BG lesions: CT hypodense, Tl hypointense

Cortical basal ganglionic degeneration • Neuronal loss in substantia nigra, frontoparietal cortex and striatum (BG atrophy may be subtle) • MR: Symmetric/asymmetric atrophy of pre- and post-central gyri; prominent parasagittal involvement • Subcortical gliosis: High intensity on T2WI

I J>ATHOlOG¥ General Features • General path comments: Definitive diagnosis of prion disease requires brain biopsy or necropsy • Genetics o Can be inherited, sporadic or acquired (infectious) o 10-15% of human prion disease cases associated with dominant mutations in autosomal prion protein (PrPc) gene (PRNP) on chromosome 20 o PrPc = normal host protein on surface of many cells, particularly neurons • Etiology o PrPSc = conformationally modified form of PrPc o PrPSc introduced into healthy cells => initiates self-perpetuating vicious cycle: PrPc - PrPSc o sC]D: Spontaneous PrPc - PrPSc or somatic mutation o Familial CJD: Mutations in PRNP o Iatrogenic C]D: Infection from prion-containing material • Surgical instruments, dura mater grafts • EEG electrodes, corneal transplants • Human pituitary-derived gonadotrophins

Toxic/Metabolic/Degenerative

Disorders, Acquired

10 75

CREUTZFELDT-JAKOB DISEASE (CJD) • 20% present with combination of both o nvC]D • Psychiatric abnormalities and sensory symptoms at presentation o Heidenhain variant of CJD • Isolated visual symptoms and signs (initially) • Predominantly occipital lobe degeneration • Normal conventional T1 and T2WI of brain • DWl/FLAIR may detect early cortical abnormalities o Extrapyramidal type of C]D • May show t signal intensity in BG o Pyramidal involvement with disease progression o BG dysfunction o Spinal cord involvement ~ muscle atrophy and fasciculations

• Human-derived growth hormone o nvC]D: Bovine TSE in cattle is transmitted to humans through infected beef products • Epidemiology o Most common TSE is sCJD o Incidence 1 per million (USA and internationally) • Associated abnormalities: EEG: Periodic high-voltage sharp waves on background of low-voltage activity

Gross Pathologic & Surgical Features • Mild cortical atrophy o Diffuse or confined to affected structures • Ventricular enlargement

Microscopic

Features

• Spongiform encephalopathy: GM most affected o Marked neuronal loss with reactive astrocytosis o Replacement gliosis o Neuronal vacuolation with spongiform changes • Spongiform pan encephalopathy (very rare) o Primary extensive involvement of WM o Loss of myelin and axons associated with generalized spongiform change in WM o ± Diffuse cerebral atrophy, loss of neurons and proliferation of astrocytes in cerebral cortex • 10% of patients with C]D have amyloid plaques in cerebellum or cerebral hemispheres o Apple-green birefringence using congo red staining when viewed under polarized light • Variable accumulation of PrPSc in brain tissue o PrPSc = abnormal, insoluble, protease-resistant amyloid form PrPc o Diffuse (common in sC]D) or discrete plaques

Demographics • Age: Young in nvC]D, older in sC]D (7th decade) • Gender: No gender preponderance • Ethnicity o sCJD occurs throughout world, in all races o nvC]D limited to Europe (almost all cases in UK)

Natural History & Prognosis • Long incubation period, but rapidly progressive once clinical symptoms begin • Rapidly progressing dementia, with death usually ensuing within months of onset o Mean duration of sC]D is 8 months o nvC]D has longer course (mean 16 months) o Familial CJD has mean duration of 26 months • 10% one year survival

Staging, Grading or Classification Criteria

Treatment

• Definite CJD o Characteristic neuropathology o Protease-resistant PrP by Western blot • Probable C]D o Progressive dementia; typical findings on EEG o :2: 2 of following: Myoclonus, visual impairment, cerebellar signs, pyramidal or extrapyramidal signs, or akinetic mutism • Possible CJD o Progressive dementia; atypical findings on EEG o :2: 2 of following: Myoclonus, visual impairment, cerebellar signs, pyramidal or extrapyramidal signs, or akinetic mutism o Duration less than 2 years

• No effective treatment

I DIAGNOSTICCHECKL.lST Consider • Heidenhain variant of C]D in patients with visual disorders of unclear origin and dementia

Image Interpretation

I SELECTED REFERENCES 1.

10

I CUNICALISSUES

2.

Presentation

3.

• Most common signs/symptoms o Rapidly progressive dementia associated with myoclonic jerks and akinetic mutism o Variable constellation of pyramidal, extrapyramidal, and cerebellar signs • Clinical profile o sCJD • 40% present with cerebellar dysfunction • 40% with rapidly progressive cognitive impairment

Pearls

• Lack of BG findings does not rule out C]D

4.

5.

Summers DM et al: The pulvinar sign in variant Creutzfeldt-Jakob disease. Arch Neurol. 61(3):446-7, 2004 Collins SJ et al: Transmissible spongiform encephalopathies. Lancet. 363(9402):51-61, 2004 Collie DA et al: Diagnosing Variant Creutzfeldt-Jakob Disease with the Pulvinar Sign: MR Imaging Findings in 86 Neuropathologically Confirmed Cases. AJNR, 24:1560-1569, 2003 Mao-Draayer Y et al: Emerging Patterns of Diffusion-Weighted MR Imaging in Creutzfeldt-Jakob Disease: Case Report and Review of the Literature. Am J Neuroradiol, 23:550-556, 2002 Barboriak DP et al: MR diagnosis of Creutzfeldt-Jakob disease: significance of high signal abnormality of the basal ganglia. AJR, 162:137-140, 1994

76

Toxic/Metabolic/Degenerative Disorde~, Acquired

C_R_E_UT_Z_f_E_LD_~_-J_A_K_O_B_D_IS_E_A_S_E_(C_J_D)

1

Typi~

_

__ ~ (Left) Coronal FLAIRMR shows hyperintense signal in caudate nuclei, lentiform nuclei and within temporal lobe cortices & hippocampi. (Right) Coronal FLAIRMR in the same patient with Creutzfeldt-jacob demonstrates hyperintense signal in both thalami.

Typical (Left) Axial FLAIRMR shows

bilateral hyperintense signal in putamina and thalami from Creutzfeldt-jacob disease. (Right) Axial OWl MR demonstrates bright signal of restricted diffusion in bodies of both caudate nuclei.

Typical (Left) Axial OWl MR shows hyperintense signal consistent with restricted diffusion within both amygdalae. (Right) Axial OWl MR in a different patient shows hyperintense signal consistent with restricted diffusion in right posterior temporal lobe and occipital lobe cortex.

10 77

Toxic/Metabolic/Degenerative

Disorders, Acquired

Axial midbrain diagram shows narrowing and depigmentation of substantia nigra (arrows) in Parkinson disease (upper) versus normal midbrain anatomy (lower).

Axial PO/Intermediate MR at upper midbrain level shows bilateral areas of hyperintense gray matter (substantia nigra) surrounded by hypointense red nuclei and crural fibers.

o SN = 2 layered gray matter (GM) structure on axial T2WI at upper midbrain level in normal subjects • Hypointense area in posterior region of crus cerebri = pars reticulata of SN (SNPr) • Relatively hyperintense area between SNPr, red nucleus (RN) = pars compacta of SN (SNPc) o Caution: Hypointense area normally seen on axial T2WI does not completely overlap anatomical location of SN • Corresponds to anterosuperior aspect of SN, adjacent crus cerebri at upper midbrain level • Corresponds to anteromedial part of peduncular fibers at lower midbrain level o Coronal & sagittal T2WI through RN in normal subjects: Hypointensity only at upper end of GM o Hypointensity of putamen • Associated with iron accumulation • Seen in parkinsonian syndromes, not in classic idiopathic L-dopa-responsive PD o T2 hyperintense foci in putamen and globus pallidus (GP) in some PD patients • PD/Intermediate o On axial PD weighted SE images in normal subjects: True anatomic location of SN (anteroinferolateral to RN) can be accurately identified • Area of hyperintense GM surrounded by hypointense RN and crural fibers at upper midbrain level

rtERMIN9l0CY Abbreviations

and Synonyms

• Idiopathic Parkinson disease (PD), paralysis agitans

Definitions • Progressive neurodegenerative disease predominantly caused by primary disorder of pars compacta of substantia nigra (SN)

IIMAGING ..FliN[)ING~ General Features • Best diagnostic clue: Narrowing or disappearance pars compacta of SN on T2WI • Location: SN, caudate nucleus and putamen • Size: Decreased (atrophy)

of

CT Findings • NECT: Nonspecific

cerebral atrophy

MR Findings • TlWI o Most common = generalized enlargement sulci, ventricles • Nonspecific (overlaps normal aging) o SN is not visible (normally present on Tl WI, PD) • T2WI

DDx: Parkinsonism-plus

Syndromes

10 78

PSP

MSA

Toxic/Metabolic/Degenerative

CBO

Disorders, Acquired

PARKINSON DISEASE Key Facts Imaging Findings

Top Differential

• Best diagnostic clue: Narrowing or disappearance of pars compacta of SN on T2WI • Most common = generalized enlargement sulci, ventricles • MSA-P: t Putaminal ADC values • PSP: t ADC in putamen, GP & caudate nucleus • Significantly t lactate/NAA ratio, especially in PD patients with dementia • Brain parenchyma sonography • Marked bilateral hyperechogenicity of SN in PD • FDG PET: Bilateral hypometabolism in temporal and parietal lobes in PD with dementia • Best imaging tool: MR • PD weighted SE, fast STIR images allow direct visualization of SN as a GM structure

• Multiple system atrophy (MSA) • Progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski syndrome) • Cortical-basal ganglionic degeneration (CBD) • Dementia with Lewy bodies • Parkinsonism-dementia-amyotrophic lateral sclerosis complex (PDALS) • St Louis encephalitis • Nigral degeneration due to striatal infarction

• SNPr and SNPc cannot be distinguished • Hyperintense GM between crural fibers and medial lemniscus at lower midbrain level o Axial PD/intermediate weighted SE images in PD • Indistinct border between SNPr, RN • Narrowing of SNPc or restoration of SNPr signal • Progressive loss of normal signal of SNPc from lateral to medial • Reflects neuronal loss, iron deposition • More prominent signal changes may predict poor response to drug therapy • Signal changes do not correlate with disease duration and severity o On coronal & sagittal images through RN in normal subjects: Tilted band with GM signal intensity found inferolateral & anteroinferior to RN • STIR o Fast STIR images: Same as PD/Intermediate o Quantitative evaluation of oblique coronal fast STIR images perpendicular to SN • No significant difference in size of SN between PD and normal subjects reported • DWI o Appear to differentiate PD from PSP and Parkinson variant of multiple system atrophy (MSA-P) • MSA-P: t Putaminal ADC values • PSP: t ADC in putamen, GP & caudate nucleus • MRS o Normal spectra or i NAA and t lactate o Significantly t lactate/NAA ratio, especially in PD patients with dementia • Impairment of oxidative energy metabolism

Ultrasonographic

Findings

• Brain parenchyma sonography o Marked bilateral hyperechogenicity of SN in PD • May reflect abnormal iron accumulation in SN (associated with degeneration of SN neurons) • PD: t SN iron is accompanied by i ferritin, forcing iron into alternative binding o Appears to discriminate between PD and atypical parkinsonian syndromes (PSP, MSA)

Diagnoses

Pathology • Recent pathologic studies in PD: Not significant i in size of SNPc, despite remarkable neuronal cell loss

• MSA, PSP: Normal SN echogenicity or only moderate SN hyperechogenicity • MSA, PSP: t SN iron bound by t ferritin

Nuclear Medicine

Findings

• PET o 18F-fluorodopa PET: i Striatal uptake proportional to number of dopaminergic neurons present & severity of clinical motor deficit o May diagnose early/relatively asymptomatic PD o FDG PET: Bilateral hypometabolism in temporal and parietal lobes in PD with dementia

Imaging Recommendations • Best imaging tool: MR • Protocol advice o PD weighted SE, fast STIR images allow direct visualization of SN as a GM structure • Cannot distinguish SNPr from SNPc (normally and in PD)

I DIFFERENTIAL DIAGNOSIS Multiple system atrophy (MSA) • Combination of cerebellar, pyramidal, extrapyramidal, and autonomic disorders • 85% of cases: Prominent T2 hypointensity in putamen & caudate nucleus (abnormal iron deposition) • Narrowing of SNPc (due to neuronal loss & iron deposition) • DWI: t Putaminal ADC values likely reflect ongoing striatal degeneration • "Hot cross buns sign" in pons on PD-/Tl-/T2WI • PET: i Metabolism in striatum, thalamus, cerebellum • PET: i 18F-fluorodopa uptake in striatum o MSA-P and Shy-Drager syndrome

Progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski syndrome) • Parkinsonism, supranuclear ophthalmoplegia (impaired downward gaze), pseudobulbar palsy, dementia

10 79

Toxic/Metabolic/Degenerative

Disorders, Acquired

• CT, MR: Dilatation of 3rd ventricle, atrophy of midbrain, enlargement of interpeduncular cistern • MR: t Width of SNPc, atrophy of superior colliculi, and high intensity to periaqueductal GM • Iron deposition in putamen, which appears more hypointense than GP on T2WI • DWI: 1 ADC in putamen, GP, and caudate nucleus

• LB (eosinophilic intracytoplasmic inclusions with peripheral halos and dense cores); gliosis o All LB stain for Ol-synuclein; most ubiquitin +

Cortical-basal (CBD)

• Most common signs/symptoms o Cogwheel rigidity, shuffling gate, masked facies, pill-rolling tremor, akinesia o Progressive subcortical dementia (parkinsonism typically precedes dementia by :2: 1 y)

ganglionic degeneration

• Neuronal loss in SN, frontoparietal cortex, striatum • Thinning of pre-/postcentral gyri + central sulcus dilatation • Prominent parasagittal involvement • Atrophy of basal ganglia may be subtle • Subcortical gliosis (high intensity on T2WI)

Dementia

with Lewy bodies

• Cortical dementia, parkinsonism, visual hallucinations, fluctuations in cognition and attention • Lewy bodies (LB) found diffusely in brain, including deep GM structures and cortex • Brainstem, SN and cortical atrophy • SPECT: Occipital hypoperfusion

Parkinsonism-dementia-amyotrophic sclerosis complex (PDALS) • Look for corticospinal

lateral

tract abnormalities

St Louis encephalitis • Abnormal signal in SN due to encephalitis

Nigral degeneration

due to striatal infarction

Presentation

Demographics • Age: Onset typically between 50-60 y • Gender: M:F = 1.5:1 • Ethnicity o Highest incidence in Caucasians o Lowest incidence in Asians and African-Americans

Natural History & Prognosis • Symptoms develop when 50% of dopaminergic neurons and 90% of striatal dopamine are lost • Onset of PD is typically asymmetric • Slowly progressive course of bradykinesia, rigidity & gait difficulty =} eventual disability after several years

Treatment • Levodopa, bromocriptine, amantadine • Selegiline (inhibitor of MAO-B), favored by some as initial treatment for younger patients • Stereotactic pallidotomy for medically refractive cases

• Abnormal signal intensity mainly beneath RN

Consider • Parkinson-plus

General Features • General path comments o SNPc degenerates from lateral to medial and in anterior to posterior direction o Most neuropathologic studies reveal intact striatum • Genetics: Sporadic (10-20% of cases familial) • Etiology o Genetic and environmental factors; MPTP o Mutations in parkinson gene gene on chromosome 6 • Early-onset autosomal recessive familial and juvenile-onset forms without LB in SN • Epidemiology o Idiopathic PD is most common movement disorder o 0.3% of general population o 1% of population> 50 y, 3% of population> 65 y

Image Interpretation

1.

2.

3.

4.

Microscopic

10

Pearls

• Role of imaging in parkinsonism: Exclude treatable bradykinesia (tumor, hematoma, hydrocephalus) • Minimal correlation between hypointense areas on T2WI and SN location on anatomical specimens/PD weighted/fast STIR images

Gross Pathologic & Surgical Features • Loss of pigmentation in SN and locus ceruleus • Recent pathologic studies in PD: Not significant t in size of SNPc, despite remarkable neuronal cell loss

syndromes

Features

• Loss of neurons in SN (especially SNPc), locus ceruleus, dorsal vagal nucleus, and substantia innominata

Richter EO et al: Determining the position and size of the subthalamic nucleus based on magnetic resonance imaging results in patients with advanced Parkin sons disease. J Neurosurg 100:541-6, 2004 Seppi K et al: Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the parkinson variant of multiple system atrophy. Neurology 60: 922-927, 2003 Walter U et al: Brain parenchyma sonography discriminates Parkinson's disease and atypical parkinsonian syndromes. Neurology 60: 74-77, 2003 Oikawa H et al: The substantia nigra in Parkinson disease: proton density-weighted spin-echo and fast short inversion time inversion-recovery MR findings. AJNRAm J Neuroradiol23: 1747-1756, 2002

80

Toxic/Metabolic/Degenerative

Disorders, Acquired

PARKINSON DISEASE

Typical (Left) Axial T2WI MR shows

hypointensity and narrowing of the substantia nigra. (Right) Axial T2WI MR in the same patient shows hypointensity of the substantia nigra and dilation of the lateral ventricles and third ventricle due to atrophy.

Typical

(Left) Axial T2WI MR shows hypointensity within the lentiform nuclei. (Right) Axial T2WI MR in the same patient shows hypointensity within the lentiform nuclei and cerebral atrophy.

Typical

(Left) Axial TlWI MR shows

that the SN is not visible on this pulse sequence. (Right) Axial PO/Intermediate MR in a different patient shows hypointensity within the lentiform nuclei.

10 81

Toxic/Metabolic/Degenerative

Disorders, Acquired

Sagittal T2WI MR shows flattening of ventral pons, marked cerebellar atrophy, as well as enlarged fourth ventricle and inferior cerebellar cistern.

Axial T2WI MR shows cerebellar and pontine atrophy, dilated fourth ventricle, as well as increased signal in transverse pontine fibers and middle cerebellar peduncles.

CT Findings Abbreviations

and Synonyms

• Multiple system atrophy (MSA) • Sporadic olivopontocerebellar atrophy (sOPCA) • Striatonigral degeneration (SND)

• NECT o Pontine atrophy, enlarged fourth ventricle (4th V) o Cerebellar atrophy (hemispheres> vermis) o Cortical atrophy (especially frontal & parietal lobes)

MR Findings

Definitions • MSA: Sporadic progressive neurodegenerative disorder of adult onset, unknown etiology with combination of cerebellar/pyramidal! extrapyramidal! autonomic disorders

General Features • Best diagnostic clue o sOPCA: Cruciform pontine hyperintensity on T2WI, atrophy of pons, inferior olives & cerebellum o SND: I T2 signal in dorsolateral putamen ± 1 T2 signal in lateral rim of putamen • Location o Striatum (mainly putamen), pontine base o Middle cerebellar peduncles (MCP) o Cerebellar white matter (WM), motor cortex • Size: Decreased (atrophy)

• TlWI o On sagittal images • Flat ventral pons, I pons/medulla (normal signal) • Cerebellar vermis/hemispheres atrophic o On axial images • I Anteroposterior diameter of pons & midbrain • I Width of superior and MCP • Enlargement of 4th V and cerebellopontine angle • Cerebellar atrophy (hemispheres> vermis) o MCP/cerebellum atrophy in sOPCA > other MSA subtypes o Linear hypointensity in putamen, especially SND o Frontal, parietal atrophy • T2WI o Brainstem, cerebellar atrophy o High T2 signal in base of pons and MCP o "Hot cross bun" sign: Cruciform pontine hyperintensity on T2WI • Reflects degeneration of pontine neurons and transverse pontocerebellar fibers (TPF) • Not pathognomonic for MSA

DDx: Cerebellar Atrophy

10 82

Hereditary

Hereditary

Toxic/Metabolic/Degenerative

Phenytoin Use

Disorders, Acquired

Alcohol Abuse

MULTIPLE SYSTEM ATROPHY Key Facts Terminology

Top Differential

• MSA: Sporadic progressive neurodegenerative disorder of adult onset, unknown etiology with combination of cerebellar/pyramidal! extrapyramidal! autonomic disorders

• Cerebello-olivary atrophy • Friedreich ataxia (spinocerebellar ataxia) • Progressive non-familial adult onset cerebellar degeneration • Hereditary OPCA • Hereditary cerebellar atrophy

Imaging Findings • Brainstem, cerebellar atrophy • High T2 signal in base of pons and MCP • "Hot cross bun" sign: Cruciform pontine hyperintensity on T2WI • ! Signal in dorsolateral putamen ± t signal in lateral rim of putamen • Atrophy of cerebral hemispheres • All MR findings observed in all MSA subtypes! • lH-MRS: Significantly! pontine/cerebellar NAA/Cr, Cho/Cr ratios in sOPCA

•

•

•

•

o ! Signal in dorsolateral putamen ± t signal in lateral rim of putamen • More frequent in SND than other MSA subtypes o Atrophy of putamen =} enlarged space between putamen and external capsule =} slit-like void on MR o Atrophy of cerebral hemispheres • Especially frontal and parietal lobes • Not significantly different in various subtypes • Related to higher cortical dysfunction in MSA o All MR findings observed in all MSA subtypes! PD/lntermediate o sOPCA: t Signal in TPF, MCP & cerebellum o SND: ! Signal in dorsolateral putamen ± hyperintense lateral rim of putamen DWI o DWI of pons with transverse diffusion gradient • Normal individuals: TPF seen as low intensity bundles in base of pons on axial multishot DWI • sOPCA: TPF not seen on DWI of pons o SND: t Putaminal ADC values MRS o lH-MRS: Significantly! pontine/cerebellar NAA/Cr, Cho/Cr ratios in sOPCA • Pontine NAA/Cr ratio (but not atrophy measurement) correlates with disability o Phosphorus MRS: ! Phosphocreatine, t phosphate Diffusion tensor MRI (DT-MRI) o sOPCA: ! FA in MCP, TPF & cerebellum

Ultrasonographic

Findings

• Brain parenchyma sonography in SND o Hyperechogenicity of lentiform nucleus o Normal echogenicity of substantia nigra (SN)

Nuclear Medicine

Findings

• PET o sOPCA: FDG uptake in cerebellar hemisphere, pons & thalamus is moderately t by walking • ! FDG uptake in cerebellar vermis during walking • PET activation ratio (FDG uptake during walking/FDG uptake during resting) demonstrates cerebellar dysfunction in early phase of sOPCA

Diagnoses

Pathology • Hallmark of MSA: Glial cytoplasmic containing (){-synuclein

inclusions

(GCls)

Diagnostic Checklist • MR features overlap in all MSA subtypes, independently of clinical presentation

o SND • FDG PET shows ! metabolism in putamen • llC-Raclopride PET shows! postsynaptic D2 receptor density in putamen • F-DOPA PET shows! putaminal F-DOPA influx constants (lower activity in posterior putamen) o llqR)-PK11195 PET in MSA • Microglia bind llqR)-PKl1195 when activated by neuronal injury • t llqR)-PKl1195 binding in dorsolateral prefrontal cortex, putamen, globus pallidus (GP), pons, SN

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Add sagittal T2WI or FLAIR

I DIFFERENFfIAt. DIAGNOSIS Cerebello-olivary

atrophy

• Cortical cerebellar degeneration • Selective atrophy of lateral cerebellum ("fish-mouth deformity" on parasagittal sections) & superior vermis (especially declive, folium and tuber) • 4th V may be greatly enlarged • Similar age of onset, slower progression

Friedreich ataxia (spinocerebellar

ataxia)

• Severe atrophy of spinal cord (flat posterior aspect) • Small medulla oblongata • Mild atrophy of vermian & paravermian structures

Progressive non-familial cerebellar degeneration

adult onset

• May occur in association with many conditions o Hashimoto thyroiditis (even in euthyroid state) o Paraneoplastic syndromes o Lithium intoxication, nutritional deficiency, EtOH o Prolonged phenytoin/phenobarbital use o Chronic vertebrobasilar insufficiency • Midline cerebellar atrophy on MR

Toxic/Metabolic/Degenerative

10 83

Disorders, Acquired

MULTIPLE SYSTEM ATROPHY Hereditary

• Loss of pigmented neurons & gliosis: Caudal lateral> rostral & ventromedial • Minimal astrogliosis in dorsolateral putamen • GCls in striatum & GP o SNC & posterior/dorsolateral putamen affected • SNC: Severe neuronal loss & gliosis in caudal SNC • Moderate neuronal loss & gliosis in putamen • Abundant GCls in SNC & putamen o SNC, putamen, CN & GP affected • SNC: Severe diffuse neuronal depletion • Putamen: Severe neuronal loss & gliosis (dorsolateral> ventromedial) • Mild-moderate degeneration of CN & GP • GCls infrequent in SNC & putamen

OPCA

• Dominant OPCA o "Fine comb" type of cerebellar atrophy o Hemispheres more involved than vermis o Atrophy of pons & MCP; enlarged 4th V • Recessive OPCA: Marked atrophy in lateral part of cerebellar hemispheres with "fish-mouth deformity"

Hereditary

cerebellar atrophy

• Middle-aged patients; severe superior vermian atrophy • Lesser involvement of rest of cerebellar cortex

I PATHOLOGY General Features • General path comments o Hallmark of MSA: Glial cytoplasmic inclusions (GCls) containing (){-synuclein • Described in 5 cellular sites: Oligodendroglial and neuronal cytoplasm and nuclei, and axons o SND = neuropathological substrate of L-Dopa unresponsive parkinsonism in MSA patients • Predominant degeneration of SN and striatum, with putamen> caudate nucleus (CN) o OPCA = pathological substrate of cerebellar dysfunction in MSA • Prominent degenerative changes in inferior olives, pontine nuclei, MCP, and cerebellar cortex o Variable degrees of OPCA in patients with SND and vice versa o Preganglionic sympathetic spinal cord lesions • Degenerative loss of preganglionic sympathetic cells in thoracic intermediolateral column • Loss of anterior horn cells in Onuf nucleus • Etiology: Unknown; ? environmental toxins • Epidemiology o Prevalence of MSA in US: 3-5/100,000 o Incidence rate of MSA: 3/100,000/year

Gross Pathologic & Surgical Features • • • •

Atrophy of ventral pons, MCP, cerebellar cortex Atrophy of inferior olive is secondary Depigmentation of SN; putaminal atrophy Frontal and parietal lobe atrophy

Microscopic

Features

• Majority of GCls are localized in WM o 1 Number of interfascicular oligodendroglial cells o Pallor or loss of myelin staining • Loss of cerebellar Purkinje cells (vermis> hemispheres) • Severe degeneration & gliosis in deep cerebellar WM • Neuronal loss and proliferation of astroglia in putamen o Iron deposition in extracellular space and remaining putaminal cells (especially in dorsolateral portion) • SN: Pigmented neuronal loss & astrocytosis • GCls reported in gray & WM of cerebral hemispheres

Staging, Grading or Classification Criteria

10

• 3 histological grades of severity of SND o SN pars compacta (SNC) affected

I Cli NICALISSUES Presentation • Most common signs/symptoms o Parkinsonian features predominate in 80% of patients (MSA-P subtype) • Bradykinesia, rigidity, postural & rest tremor, unsteady gait, dysequilibrium o Cerebellar symptoms predominate in 20% of patients (MSA-C subtype) • Gait ataxia, limb akinetic ataxia, dysarthria, cerebellar oculomotor disturbance o Autonomic failure in MSA • Symptomatic orthostatic hypotension • Erectile & urologic disturbance, constipation, hypo/anhydrosis o Neuropsychological dysfunction, particularly in memory & other higher order cognitive functions

Demographics • Age: Onset of MSA: Usually 6th decade • Gender: No gender preference

Natural History & Prognosis • Progressive neurodegenerative disease • Death occurs after approximately 9 y from onset

Treatment • Options, risks, complications o 90% of MSA-P patients are L-Dopa unresponsive o Symptomatic ther~py and supportive care

I DIAGNOSTIC CHECKLIST Image Interpretation

Pearls

• MR features overlap in all MSA subtypes, independently of clinical presentation

ISEtEC1EDi.REiFEi.~E!~~E~ 1.

2.

Mascalchi M et al: Proton MR spectroscopy of the cerebellum and pons in patients with degenerative ataxia. Radiology 223:371-378,2002 Naka H et al: Characteristic MRI findings in multiple system atrophy: comparison of the three subtypes. Neuroradiology 44:204-209,2002

84

Toxic/Metabolic/Degenerative

Disorders, Acquired

MULTIPLE SYSTEM ATROPHY

Typical (Left) Axial T2WI MR shows hypointense signal in basal ganglia and diffuse cortical atrophy. (Right) Axial T2WI MR in the same patient demonstrates bilateral putaminal hypointensity and diffuse cortical atrophy.

(Left) Axial T2WI MR shows atrophy of pons and cruciform pontine hyperintensity ("hot cross bun" sign). (Right) Axial T1WI MR shows loss of volume of pons and enlargement of prepontine cistern and fourth ventricle. Also observed is cerebellar atrophy.

(Left) Sagittal T1 WI M R shows marked pontine and cerebellar atrophy. (Right) Axial T2WI MR in the same patient shows pontine and cerebellar atrophy and hyperintense signal in dentate nuclei.

10 85

Toxic/Metabolic/Degenerative

Disorders, Acquired

AMYOTROPHIC LATERALSCLEROSIS (ALS)

Axial T2WI MR in a young man with ALS shows symmetric hyperintense corticospinal tracts (arrows) at the level of the internal capsule.

Axial T2WI MR in the same patient with ALS shows symmetric hyperintense corticospinal tracts (arrows) at the level of the cerebral peduncle.

ITE.RMINOLOGY

CT Findings

Abbreviations

• NECT o Serial CT exams may show progressive atrophy • First: Frontal, anterior temporal lobes • Next: Precentral gyrus • Later: Postcentral gyrus, anterior cingulate gyrus, corpus callosum (CC), tegmentum

and Synonyms

• Amyotrophic lateral sclerosis (ALS) • Lou Gehrig disease, motor neuron disease (MND)

Definitions • Selective degeneration of somatic motor neurons of brain stem/spinal cord (lower motor neurons (LMN)), large pyramidal neurons of motor cortex (upper motor neurons, UMN)i eventual loss of corticospinal tract (CST) fibers

11MAGING.· FINplNG$ General Features • Best diagnostic clue: Bilateral hyperintensities along CST extending from corona radiata to brain stem on T2WI/PD /FLAIR • Location o Both white matter (WM) and gray matter (GM) o Hallmark is CST, LMN degeneration • Size: Atrophy of motor system, particularly pyramidal tract, in advanced stages of ALS • Morphology: Signal abnormalities conforming to CST shape: Oval or thin curvilinear hyperintensities

DDx: T2 Hyperintense

Midbrain

MR Findings • TlWI o CST differs between ALS patients and normal subjects only at internal capsule (IC) o Different Tl appearances of CST have been reported • Tl isointense signal (most commonly): Could reflect 1 content of free radicals in CST in ALS • Tl hypointense or mild hyperintense signal • T2WI o Diffuse hyperintensity following pyramidal tract o Hypointense GM in precentral gyrus (motor cortex) • Not specific, may be due to iron and heavy metals accumulation in cortex of aged patients o Symmetric, rounded foci of high signal intensity on T2WI within caudal 1/3 of posterior limb of IC in about 50% of normal subjects • Never seen on PD images in normal subjects o T2 hyperintense CST may be specific for ALS when visible on corresponding PD images (most specific finding)

lesions

10 86

Glioma

Peduncle MS Plaque

Toxic/Metabolic/Degenerative

Wallerian Degen

Disorders, Acquired

Normal3T

AMYOTROPHIC LATERAL SCLEROSIS (ALS) . I

Terml~o ogy

Key Facts

• Wallerian

..•

• SelectIve degeneratIOn of somatIc motor neurons of brainstem/s?inal cord (lower motor neurons (LMN)), large pyramIdal neurons of motor cortex (ul?per .• motor neurons, UMN); eventual loss of cortIcospmal tract (CST) fibers

Imaging findings • Best diagnostic clue: Bilateral hyperintensities along CST extending from corona radiata to brainstem on T2WI/PD/FLAIR • Diffuse hyperintensity following pyramidal tract • Protocol advice: DTI, FLAIR, T2WI, PD

Top Differential

Diagnoses

• Primary lateral sclerosis and infantile-onset spastic paraplegia

lesions at

Pathology • Majority of ALS cases are sporadic (sALS) • 15-20% of ALS cases are familial (fALS)

Clinical Issues • UMN signs: Babinski sign, spasticity, hyperreflexia • LMN signs: Asymmetric muscle weakness, atrophy, fasciculations, hyporeflexia

Diagnostic Checklist hereditary

• FLAIR o More sensitive & less specific than FSE for detecting hypointensity in precentral gyrus GM o Hyperintense CST of ALS patients more frequently seen on FLAIR than on T2/Tl/PD weighted images • DWI: Hyperintensity (t diffusivity) in CST reported • Diffusion tensor imaging (DTI) o Fractional anisotropy (FA) in CST is lower in ALS compared with healthy subjects • Difference maintained from capsules to pyramids • t Fiber integrity in CST descending from motor and premotor cortex to IC and brainstem o t FA in posterior limb of IC, more caudal CST (pons), underneath motor & premotor cortex, extramotor regions in frontal lobe o t FA in thalamus and CC reported • Corresponds to atrophy of CC found in ALS • Severe atrophy in anterior 1/4 of CC associated with cognitive decline and psychiatric symptoms o FA correlates w/UMN involvement, disease severity o Mean diffusivity (MD) is higher in ALS at level of IC • MD positively correlates with disease duration • Difference lost caudally in CST • IH-MRS useful for assessing UMN involvement o t NAA/Cr, 1 choline & myoinositol, t glutamate in precentral gyrus & perirolandic region o Not sensitive enough to reveal early changes • Magnetization-transfer ratio (MTR) measurements o Significant t MTR in posterior limb of IC in ALS o May detect CST degeneration of ALS at early stage

Nuclear Medicine

degeneration Hypertrophic olivary degeneration • Other conditions with T2 hyperintense various levels of CST Normal individuals

Findings

• PET, 99mTc-HMPAO SPECT o ALS patients with impaired verbal fluency: t rCBF responses in anterior thalamic nuclear complex o Bilateral thalamic hypoperfusion, parietal and frontal hypoperfusion in familial ALS (fALS) o Hypoperfusion and oxygen hypometabolism in anterior cerebral hemispheres • Associated with progressive dementia in ALS o Metabolic and perfusion changes in cerebral cortex • Depend on UMN lesions, but not confined to CST o Sensorimotor: Very mild t rCBF, 02 metabolism

• DTI can assess CST lesions before pyramidal symptoms become apparent

Imaging Recommendations • Best imaging tool: MR • Protocol advice: DTI, FLAIR, T2WI, PD

I DIFFERENTIAl.. DIAGNOSIS Primary lateral sclerosis and infantile-onset hereditary spastic paraplegia • Neurodegeneration restricted to UMN o T2WI shows changes in motor pathways • ALS 2 mutations reported • Autosomal recessive disease with juvenile onset

Wallerian degeneration • Dynamic signal intensities change along CST in patients with various cortical/subcortical lesions

Hypertrophic

olivary degeneration

• Secondary degeneration of inferior olivary nucleus (ION), usually caused by primary lesions in dento-rubro-olivary pathway

Other conditions with T2 hyperintense lesions at various levels of CST • Metabolic diseases may involve CST bilaterally oX-linked adrenoleukodystrophy, Wilson disease o Hypoglycemic coma: Reversible CST changes • Demyelinating and inflammatory diseases o Multiple sclerosis, ADEM, Behcet disease, AIDS • Neoplasms: Brainstem glioma, malignant lymphoma • Intoxication: Heroin inhalation

Normal individuals • CST can appear hyperintense on 3T MR (normal fully myelinated brain at any age) and mimic ALS

I PATH 0 1..0GY General Features

10

• General path comments

Toxic/Metabolic/Degenerative

87

Disorders, Acquired

AMYOTROPHIC LATERAL SCLEROSIS (ALS) o o o o

•

•

•

•

ALS primarily involves anterior horn cells Affects both spinal cord and cranial motor nerves Wallerian degeneration of corticobulbar and CST Pathology of ALS is more severe in precentral gyrus than in postcentral gyrus Genetics o Majority of ALS cases are sporadic (sALS) o 15-20% of ALS cases are familial (fALS) o 10-20% of fALS cases are caused by mutations in copper/zinc superoxide dismutase 1 (SOD 1) gene (ALS1) on chromosome 21q • > 100 different mutations reported, majority are autosomal dominant • Toxic gain-of-function by mutant protein o Rare autosomal recessive juvenile-onset ALS • ALS2 gene on chromosome 2q encodes alsin Etiology o Etiology of sALS is largely unknown o Mutations in single gene can lead to selective degeneration of motor neurons o Increased expression of cyclooxygenase-2 in spinal cord, frontal cortex and hippocampus o Apoptosis, free radical-mediated oxidative stress, excessive glutamate-mediated excitotoxicity o Dopamine deficiency probably has important role Epidemiology o Incidence: 0.5-2 cases/100,OOO persons o Prevalence: 5/100,000 persons Associated abnormalities o ALS-plus syndrome: Typical ALS phenotype associated with dementia, parkinsonism or both • In patients from Southern Guam o ALS-like MND can occur as paraneoplastic syndrome

Gross Pathologic & Surgical Features • Atrophic precentral gyrus in longer disease duration • Degeneration of thalamus, CC atrophy

Microscopic

o Predominantly bulbar form usually leads to more rapid deterioration and death o fALS associated with SOD1 abnormality has mean age at 42 y, limb onset, slow evolution

Demographics • Age: Onset usually between 4th-7th decades of life • Gender: M:F = 2:1 • Ethnicity: Caucasian to non-Caucasian ratio is 1.6:1 in the US

Natural History & Prognosis • Progressive (distal to proximal) o Complete disability and death within a decade o 20% of patients survive> 5 y • Some patients with familial, juvenile-onset ALS survive for longer periods (2-3 decades)

Treatment • Riluzole (glutamate release inhibitor and insulin-like growth factor) may prolong survival o 1 NAA/Cr in precentral gyrus after riluzole therapy • Baclofen, dantrolene, or diazepam for spasticity

Consider • FLAIR in all patients with clinically suspected ALS

Image Interpretation

Features

• Loss of cortical pyramidal motor neurons and associated astrocytosis • Histologically uneven involvement of CST showing variable patterns of degeneration • "Senescent changes" with lipofuscin pigment atrophy • Various cytoplasmic inclusions with chromatolysis • Proximal and distal axonopathy with axonal spheroids • Surviving motor neurons are smaller and abnormal • Frequently undetected CST pathology in progressive muscular atrophy variant of ALS

1.

2.

3.

4.

5.

Presentation

10 88

Pearls

• High signal intensity in posterior limb of IC is highly suggestive for ALS when also visible on PD • T1 and PD weighted images differentiate real degeneration from normal areas • DTI can assess CST lesions before pyramidal symptoms become apparent

• Most common signs/symptoms o UMN signs: Babinski sign, spasticity, hyperreflexia o LMN signs: Asymmetric muscle weakness, atrophy, fasciculations, hyporeflexia o Bulbar signs: Slurred speech, dysphagia o Difficulty walking, unexplained weight loss o Hypoxia, cardiac arrhythmia • Clinical profile o Classic ALS: Both UMN and LMN affected o Solely UMN affected or solely LMN affected

6.

7.

Toxic/Metabolic/Degenerative

Sach M et al: Diffusion tensor MRI of early upper motor neuron involvement in amyotrophic lateral sclerosis. Brain 127:340-350, 2004 Kalra S et al: Neuroimaging in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 4(4):243-8, 2003 Strong M et al: Amyotrophic lateral sclerosis: a review of current concepts. Amyotroph Lateral Scler Other Motor Neuron Disord. 4(3):136-43, 2003 Bowen BC et al: MR imaging and localized proton spectroscopy of the precentral gyrus in amyotrophic lateral sclerosis. A]NR Am] Neuroradiol. 21(4):647-58, 2000 Chan S et al: Motor neuron diseases: comparison of single-voxel proton MR spectroscopy of the motor cortex with MR imaging of the brain. Radiology. 212(3):763-9, 1999 Kato Y et al: Detection of pyramidal tract lesions in amyotrophic lateral sclerosis with magnetization-transfer measurements. A]NRAm] Neuroradiol. 18(8):1541-7, 1997 Mascalchi M et al: Corticospinal tract degeneration in motor neuron disease. A]NR Am] Neuroradiol. 16(4 Suppl):878-80, 1995

Disorders, Acquired

AMYOTROPHIC LATERALSCLEROSIS (ALS)

Typical

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(Left) Axial T2WI MR in the same patient shown in images 7, 2 demonstrates bilateral low signal intensity in precentral (motor) cortex (arrows). (Right) Axial T2WI MR, in the same patient, shows symmetrical high signal intensity in corona radiata fibers corresponding to corticospinal tracts.

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(Left) Coronal T2WI MR shows hyperintense corticospinal tracts (arrows) in a patient with ALS (Courtesy O.Q. Castro, MO). (Right) Axial T2WI MR in the same patient shows hyperintense corticospinal tracts (arrows) at the level of the cerebral peduncle (Courtesy o.Q. Castro, MO).

(Left) Axial OWl MR shows

increased signal involving subcortical white matter of both precentral (motor) gyri, extending caudally into corticospinal tracts (not shown) typical for ALS. (Right) Axial AOC map in the same ALS patient appears normal.

10 89

Toxic/Metabolic/Degenerative

Disorders, Acquired

WALLERIAN DEGENERATION

Axial T2WI MR in a patient with left middle cerebral artery infarct (not shown) shows high signal intensity in left cerebral peduncle (arrow) consistent with Wallerian degeneration.

Abbreviations

o Acute stage: Normal size o Chronic stage: Decreased (atrophy) • Morphology o Signal changes conforming to WM tract shape • Oval regions in posterior limb of IC & cerebral peduncle; thin curvilinear regions in pons

and Synonyms

• Wallerian degeneration

Axial T2WI MR in the same patient shows hyperintense signal in corticospinal tract in left pons (arrow) from Wallerian degeneration.

(WaD)

Definitions • Secondary anterograde degeneration ofaxons and their myelin sheaths caused by proximal axonal or neuronal cell body lesions

rrMAGIN/G/FJN[)JNG~

CT Findings • NECT o Not sensitive for WaD in acute-subacute stages o Detects atrophy of pyramidal tracts in chronic stage • I Size of corresponding aspect of brain stem

MR Findings

General Features • Best diagnostic clue: Dynamic contiguous T2 hyperintensity along topographic distribution ~f pyramidal tract in internal capsule (IC) and bramstem in patients with various cerebral pathologies • Location o Primary lesion: Cortical or subcortical o WaD: Descending white matter (WM) tracts ipsilateral to neuronal injury • CST, corticobulbar, corti cop on tine tracts • Optic radiations o Center of cerebral peduncle may reveal WaD of CST o Lateral side of cerebral peduncle may show WaD of corticopontine tract • Size

DDx: Other T2 Hyperintense

• TlWI o Time-dependent changes in descending WM tracts o Stage 1 (first 4 weeks): No changes o Stage 2 (between 4-14 weeks): T1 hyperintense o Stage 3: Tl hypointense .. o Stage 4: Ipsilateral brain stem atrophy WIth/WIthout hypointensity • T2WI o Time-dependent changes in descending WM tracts o Stage 1 (first 4 weeks): No changes in adult CNS o Stage 2 (between 4-14 weeks): I Signal intensity o Stage 3: Increased signal intensity o Stage 4 (after months to years) • Atrophy, best seen in brain stem • Sometimes, T2 hyperintense signal may persist

lesions in Brainstem

10 90

ALS

Glioma

Toxic/Metabolic/Degenerative

MS Plaque

Hypertr Olivary Degen

Disorders, Acquired

WALLERIAN DEGENERATION Key Facts Terminology

Top Differential

• Secondary anterograde degeneration ofaxons and their myelin sheaths caused by proximal axonal or neuronal cell body lesions

• • • •

Imaging Findings • Best diagnostic clue: Dynamic contiguous T2 hyperintensity along topographic distribution of pyramidal tract in internal capsule (IC) and brainstem in patients with various cerebral pathologies • Oval regions in posterior limb of IC & cerebral pedunclei thin curvilinear regions in pons • Time-dependent changes in descending WM tracts • Atrophy, best seen in brainstem • Best imaging tool: MR • DWI allows early detection (stage 1) • T2WI detects changes after 4 weeks o Neonates and infants: Identification of WaD by T2WI is complicated by high water content and lack of myelination in immature WM o Adults: Strong correlation between T2WI detected WaD and long-term morbidity • PD/lntermediate: High intensity follows particular WMpathway • FLAIR: Same as T2WI • DWI o Identification of acute WM injury (stage 1) in neonates and infants • DWI findings precede development of WaD assessed by conventional MRI • May portend poor clinical outcome o t Signal intensity in descending WM tract ipsilateral to territorial infarct at level of IC or cerebral peduncle or both o Extent and severity of territorial ischemia is related to development of descending WM tract injury detectable by DWI o Adults: Correlation of DW changes in descending motor pathways at presentation with long-term neurologic disability • DW changes of acute CST injury may occur in only a small minority of territorial infarcts o ADC maps: I ADC values in involved WM tract compared with normal WM o Hyperintense DW signal intensity and I ADC values: Both within territorial infarct and ipsilateral CST o DW and ADC time courses in region of territorial injury and CST injury may be different • Relatively delayed development of diffusion abnormality in descending WM tracts o Subacute period after territorial infarction in adults • ADC reduction in WM is greater than that in gray matter within infarcts o DW signal intensity abnormality in descending WM tracts may persist, even as DW hyperintensity in ipsilateral cerebral hemisphere fades o WaD of inferior cerebellar peduncle (after lateral medullary infarction) depicted by thin slice DWI has been reported

Diagnoses

Neurodegenerative diseases Neoplasms Demyelinating and inflammatory diseases Hypertrophic olivary degeneration

Pathology • Degeneration follows fiber tracts through IC, midbrain, pons and medulla along pyramidal tract

Clinical Issues • Most common signs/symptoms: WaD in CST is associated with persistent hemiparesis • WaD may begin within 1 week of fiber tract damage • Demyelination can continue during next 6 months • WaD in CNS signifies irreversible loss of neuronal function

• Tl C+: No contrast-enhancement of degenerated tracts • MRS o IH-MRS enables in vivo assessment of axonal injury based on signal intensity of N-acetyl aspartate (NAA) o I NAA concentration « 3.0) in normal appearing WM in pons and cerebellar peduncles in early stages of relapsing-remitting multiple sclerosis (MS) • Evidence of early WaD outside MS plaques • Correlates best with disability, MS duration and relapse rate • Diffusion tensor imaging (DTI) o Myelin breakdown leads to I diffusion anisotropy o DTI may distinguish between primary lesion and associated WaD o Difference in diffusion properties between primary lesion and degenerated tract • Fractional anisotropy (FA) = measure of directionality of water diffusion • Mean diffusivity (MD) = measure of amount of water diffusion o Reduced FA with increased MD in infarct o Reduced FA with preserved MD in CST

Imaging Recommendations • Best imaging tool: MR • Protocol advice o DWI allows early detection (stage 1) o T2WI detects changes after 4 weeks

I DIFFERENTIAl.. DIAGNOSIS Neurodegenerative

diseases

• Amyotrophic lateral sclerosis (upper and/or lower motor neuron involvement) o Bilateral hyperintensities along CST extending from corona radiata to brain stem on T2WI/PD/FLAIR • Primary lateral sclerosis and infantile-onset hereditary spastic paraplegia o Upper motor neuron degeneration only

10

Neoplasms • Brainstem glioma, malignant

lymphoma 91

Toxic/Metabolic/Degenerative

Disorders, Acquired

WALLERIAN DEGENERATION • Multiple sclerosis, ADEM, Beh<;et disease, AIDS

• Stage 2: Decreased protein-lipid ratio • Stage 3: Increased edema and further lipid breakdown • Stage 4: Atrophy due to volume loss

Hypertrophic

Staging, Grading or Classification Criteria

Demyelinating

and inflammatory

diseases

olivary degeneration

• Secondary degeneration of inferior olivary nucleus (ION), usually caused by primary lesions in dento-rubro-olivary pathway • Time-dependent T2 changes of ION o Hyperintense signal without hypertrophy of ION: Within first 6 months of ictus o Both increased signal and hypertrophy of ION: Between 6 months and 3-4 years after ictus o Only increased signal in ION: Begins when hypertrophy resolves and can persist indefinitely

Metabolic

ICLINICALJSSlJES Presentation

diseases

• X-linked adrenoleukodystrophy, Wilson disease • Hypoglycemic coma: Reversible CST changes

• Most common signs/symptoms: WaD in CST is associated with persistent hemiparesis

Demographics

Intoxication

• Age: Reported in all ages • Gender: No gender preference

• Heroin inhalation

Normal individuals • CST can appear hyperintense on 3T MR (normal fully myelinated brain at any age)

I PATl-ta[(JG~ General Features • General path comments o Degeneration follows fiber tracts through IC, midbrain, pons and medulla along pyramidal tract o Axonal breakdown, myelin breakdown, and gliosis o Persistence of axonal and myelin debris in CNS WaD o Macrophage response during WaD ofaxons • Rapid and robust in peripheral nervous system (PNS), where axonal regeneration occurs • Delayed in central nervous system (CNS), where axonal regeneration is limited o Lack of adhesion molecule expression on CNS endothelium may explain poor leukocyte recruitment during WaD in CNS compared with PNS • Genetics: Process of axonal degeneration is genetically regulated • Etiology o Infarction, hemorrhage, neoplasm, encephalitis o Demyelinating disease, trauma, AV malformations o Reported also in patients with movement disorder • Epidemiology o WaD commonly follows CNS lesions • WaD in pyramidal tract reported in 78.6% cases of capsular infarct • Associated abnormalities: Primary lesion/disorder that caused secondary WM tract degeneration

Gross Pathologic & Surgical Features • Brainstem asymmetry

Microscopic

• Stage 1: First 4 weeks o Degradation of axon; mild changes in myelin • Stage 2: Between 4-14 weeks o Myelin protein breakdown without lipid breakdown • Stage 3: Myelin lipid breakdown and gliosis • Stage 4: Atrophy of ipsilateral brain stem

Natural History & Prognosis • WaD may begin within 1 week of fiber tract damage • Demyelination can continue during next 6 months • WaD in CNS signifies irreversible loss of neuronal function o Little evidence of axonal regeneration in CNS • Presence or absence of WaD may influence clinical outcome after stroke • Extent of WaD is related to severity of motor deficit

Treatment • No specific therapy

'.DIAGNOSrtccHECK[IS1 Image Interpretation

·SELEC1E()iRiEFEliENCES

1..

1.

2.

3.

4.

due to atrophy in chronic stage 5.

Features

Pearls

• In ischemic stroke: Important to differentiate DWI abnormality related to WaD from additional infarction • Time specific signal intensity changes of WaD ~ able to ascertain age of primary lesion

• Stage 1: Early degeneration o Beginning of myelin and axon breakdown o Myelin sheaths break up into ellipsoids and spheres, but retain myelin staining properties

Uchino A et al: Transient detection of early wallerian degeneration on diffusion MRI after acute cerebrovascular accident. Neuroradiology. 46(3):183-8, 2004 Mazumdar A et al: Diffusion-weighted imaging of acute corticospinal tract injury preceding wallerian degeneration in the maturing human brain. Am J Neuroradiol 24:1057-1066,2003 Casanova B et al: Evidence of Wallerian degeneration in normal appearing white matter in early stages of relapsing-remitting MS. J Neural 250:22-28, 2003 Pierpaoli C et al: Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture. Neuroimage 13: 1174-1185,2001 Werring DJ et al: Diffusion tensor imaging can detect and quantify corticospinal tract degeneration after stroke. J Neurol Neurosurg Psychiatry 69:269-272, 2000

92

Toxic/Metabolic/Degenerative

Disorders, Acquired

WALLERIAN DEGENERATION

I IMAGE GALLERY (Left) Axial T2WI MR shows large left middle cerebral artery infarct which resulted in ipsilateral Wallerian degeneration (not shown). (Right) Axial T2WI MR in the same patient illustrates the hyperintense signal within the left cerebral peduncle (arrow) from Wallerian degeneration.

Typical (Left) Axial T2WI MR in the same patient shows hyperintense signal in crossing corticospinal tracts in left side of pons (arrow) consistent with Wallerian degeneration. (Right) Axial T2WI MR in the same patient shows hyperintense signal in right side of medulla (arrow) consistent with Wallerian degeneration.

Typical (Left) Axial T2WI MR in a patient with a left middle cerebral artery infarct shows no abnormal signal in pons although diffusion revealed abnormality from Wallerian degeneration (not shown). (Right) Anisotropy map in which high anisotropy values are seen in red shows diminished anisotropy in left side of pons despite normal T2WI in the same patient.

10 93

Toxic/Metabolic/Degenerative

Disorders, Acquired

HYPERTROPHIC

OLIVARY DEGENERATION

Drawing of Cuillain-Mollaret triangle showing the inferior olivary nucleus (in green), contralateral dentate nucleus of cerebellum (in blue) and ipsilateral red nucleus (in red).

ITERMINOlOGY Abbreviations

and Synonyms

• Hypertrophic olivary degeneration

(HOD)

Definitions • Secondary degeneration of inferior olivary nucleus (ION), usually caused by primary lesions in dento-rubro-olivary pathway (anatomical triangle of Guillain and Mollaret)

I IMAGING

FINDINGS

General Features • Best diagnostic clue: T2 hyperintense, unenhancing enlargement of ION • Location o Triangle of Guillain and Mollaret defined by three anatomic structures • Dentate nucleus (DN) of cerebellum • Contralateral red nucleus (RN) • ION ipsilateral to RN o Central tegmental tract connects RN to ipsilateral ION o Superior cerebellar peduncle (dentatorubral tract) connects DN to contralateral RN

DDx: T2 Hyperintense

Axial T2WI MR demonstrates inferior olivary nuclei, which (arrows), secondary to degeneration.

hypertrophy of both are also hyperintense hypertrophic olivary

o Inferior cerebellar peduncle connects ION to contralateral cerebellar cortex and contralateral DN o Three patterns of HOD in relation to primary lesion • Ipsilateral HOD, when primary lesion is limited to brainstem (central tegmental tract) • Contralateral HOD, when primary lesion is in cerebellum (DN or superior cerebellar peduncle) • Bilateral HOD, when primary lesion involves both central tegmental tract and superior cerebellar peduncle • Size o Variable (time-dependent) size of affected ION • Normal in acute stage • Increased (hypertrophy) between 6 mos & 3-4 yrs • Decreased (atrophy) in advanced stage (> 3-4 yrs) • Morphology o Unique type of transneuronal degeneration • ION undergoes hypertrophy, rather than atrophy

CT Findings • NECT o May show acute primary injury (e.g., hemorrhage) o HOD typically not depicted on CT

MR Findings • TlWI o Acute phase: Normal ION • Shows primary lesion in brainstem o After HOD ensues

lesions of the Anterior Medulla

10 94

Brainstem MS

Brainstem Glioma

Toxic/Metabolic/Degenerative

Wallerian Degen

Disorders, Acquired

Medullary Infarct

HYPERTROPHIC OLIVARY DEGENERATION Key Facts Terminology • Secondary degeneration of inferior olivary nucleus (ION), usually caused by primary lesions in dento-rubro-olivary pathway (anatomical triangle of Guillain and Mollaret)

•

• • •

• MR images also detect primary lesion located in ipsilateral central tegmental tract • PET: Hypermetabolism of glucose in medulla in patients with HOD

Pathology

Imaging Findings

• There are six phases of pathologic

• Best diagnostic clue: T2 hyperintense, unenhancing enlargement of ION • Three patterns of HOD in relation to primary lesion • Variable (time-dependent) size of affected ION • Hyperintense signal without hypertrophy of ION: Within first 6 mas of ictus • Both increased signal and hypertrophy of ION: Between 6 mos and 3-4 yrs after ictus • Only increased signal in ION: Begins when hypertrophy resolves and can persist indefinitely

Clinical Issues

• Enlargement confined to ION, isointense to slightly hypointense to gray matter • Slightly increased olivary T1 signal also reported • ± Residual primary lesion T2WI o Three distinct MR stages in HOD • Hyperintense signal without hypertrophy of ION: Within first 6 mos of ictus • Both increased signal and hypertrophy of ION: Between 6 mos and 3-4 yrs after ictus • Only increased signal in ION: Begins when hypertrophy resolves and can persist indefinitely o On axial MR images: Disappearance of pre- and postolivary sulci in hypertrophic stage o MR images also detect primary lesion located in ipsilateral central tegmental tract • If old hematomas: Low signal areas on T2WI revealing hemosiderin deposition o ± Decreased size of contralateral ION, with higher than normal signal intensity o ± Mild to severe atrophic changes of cerebellar cortex contralateral to HOD PD/lntermediate: High signal intensity of ION better detected on PD images than on T2WI FLAIR: Similar to T2WI Tl C+: No contrast-enhancement of degenerated ION

Nuclear Medicine • PET: Hypermetabolism patients with HOD

Findings of glucose in medulla in

Imaging Recommendations • Best imaging tool: MR imaging • Protocol advice: T2WI (include coronal or sagittal sections)

I DIFFERENTltXl... DltXGNOSIS Other causes of high T2 signal intensity in anterior part of medulla • Demyelination related to multiple sclerosis • Tumor (astrocytoma, metastasis, lymphoma)

Toxic/Metabolic/Degenerative

• • • • •

change

Symptomatic palatal tremor/myoclonus ± Dentatorubral tremor (Holmes' tremor) Symptoms of cerebellar or brain stem dysfunction Clinical symptoms (tremors) rarely improve Medical treatment of palatal myoclonus is unsatisfactory

Diagnostic Checklist • Avoid misdiagnosis of tumor or multiple sclerosis • Lesions involving corticospinal tract o Wallerian degeneration, adrenoleukodystrophy o Amyotrophic lateral sclerosis • Infarction o Most medullary infarctions occur in posteroinferior cerebellar artery territory and involve posterolateral medulla (e.g., vertebral artery dissection) o Alternatively, medullary infarcts could be related to perforating branches of anterior spinal or vertebral arteries and have paramediallocation • Infectious/inflammatory processes o Tuberculosis, sarcoidosis o Acquired immunodeficiency syndrome o Rhombencephalitis

I PtXTHOI...OGY General Features • General path comments o Olivary enlargement: Histologically unusual vacuolar cytoplasmic degeneration ~ hypertrophy related in part to t number of astrocytes o After onset of primary lesion • Vacuolar cytoplasmic degeneration in 6-15 mos • Gliosis follows at 15-20 mos • Etiology o Transsynaptic degeneration caused by interruption of pathways composing Guillain-Mollaret triangle o Olivary de-afferentation thought to be source of ensuing HOD o Primary lesions usually located in contralateral DN or ipsilateral central tegmental tract o Focal brain stem insults that may lead to dentatorubral-olivary pathway interruption • Ischemic infarction, demyelination • Hemorrhage (related to hypertensive disease, occult cerebrovascular malformation, or diffuse axonal injury following severe head trauma) • Cavernous hemangioma • Epidemiology: Rare finding • Associated abnormalities

10 95

Disorders, Acquired

HYPERTROPHIC

OLIVARY DEGENERATION

o Primary brainstem insult • Most commonly pontine hemorrhage from trauma (including surgery), hypertension, tumor, and infarction

Gross Pathologic & Surgical Features • Focal swelling of ION • Unilateral HOD o Asymmetric enlargement of anterior medulla o "Pallor" in contralateral DN o Atrophy of contralateral cerebellar cortex • Bilateral HOD: More difficult to observe o No left-right asymmetry

Microscopic

Features

• Changes in hypertrophic degenerated ION o Neuronal cell body enlargement o Vacuolation of neurons o Fibrillary gliosis o Demyelination and astrocytic proliferation of WM • In contralateral cerebellar cortex o Decreased number of Purkinje cells • Contralateral DN reduced in size, possibly due to o Iron depletion 2 to axonal iron transport block o Loss of cells in nucleus 0

• May result from hypermetabolism

of ION

Demographics • Age: Reported in both children and adults • Gender: No gender preference

Natural History & Prognosis • After primary brainstem injury, olivary hypertrophy typically appears in delayed fashion o May occur between 3 weeks-II mos (usually within 4-6 mos) • Maximum hypertrophy at 5-15 mos • Olivary hypertrophy typically resolves in 10-16 mos • Olivary hyperintensity on T2WI may persist for yrs after resolution of hypertrophy • Finally ION undergoes atrophy • Clinical symptoms (tremors) rarely improve

Treatment • Medical treatment of palatal myoclonus is unsatisfactory o Patients may respond to tryptophan, carbamazepine, or trihexyphenidyl • Implantation of thalamic stimulator device may reduce tremor

Staging, Grading or Classification Criteria • There are six phases of pathologic change o No olivary changes within first 24 hours o Degeneration of olivary amiculum (white matter capsule at olive periphery), at 2-7 days or more o Olivary hypertrophy (mild enlargement w/neuronal hypertrophy & no glial reaction), at 3 wks o Maximal olivary enlargement (hypertrophy of neurons and astrocytes), at 8.5 mos o Olivary pseudohypertrophy (neuronal dissolution with gemistocytic astrocytes), after 9.5 mos o Olivary atrophy (neuronal disappearance with olivary atrophy and prominent degeneration of amiculum olivae), after few yrs

Image Interpretation

1. 2.

3.

Presentation • Most common signs/symptoms o Symptomatic palatal tremor/myoclonus • Rhythmic involuntary movement of soft palate, uvula, pharynx, and larynx o Severe myoclonus may also affect cervical muscles and diaphragm o ± Dentatorubral tremor (Holmes' tremor) • 2-5 Hz rest, postural, and kinetic tremor of an upper extremity • May occur before onset of palatal tremor o Symptoms of cerebellar or brain stem dysfunction • Associated with acute lesion within triangle of Guillain and Mollaret • Clinical profile o Palatal myoclonus (form of "segmental" myoclonus) • Usually develops 10-11 mos after 1 lesion • Virtually all patients who develop palatal myoclonus after brain insult will have HOD • Not all HOD patients develop palatal myoclonus

4.

5.

6.

7.

8. 9.

0

10

Pearls

• Avoid misdiagnosis of tumor or multiple sclerosis • Bilateral and symmetrical lesions in ION argue against subacute infarct and vertebral artery dissection

Harter DH et al: Hypertrophic olivary degeneration after resection of a pontine cavernoma. AJNR 100:717,2004 Rieder CR et al: Holmes tremor in association with bilateral hypertrophic olivary degeneration and palatal tremor: chronological considerations. Case report. Arq Neuropsiquiatr. 61(2B):473-7, 2003 Krings T et al: Hypertrophic olivary degeneration following pontine haemorrhage: hypertensive crisis or cavernous haemangioma bleeding? J Neurol Neurosurg Psychiatry. 74(6):797-9,2003 Conceicao C et al: Hypertrophic olivary degeneration. Semiology with magnetic resonance. Acta Med Port. 14(1):107-11,2001 Goyal M et al: Hypertrophic olivary degeneration: metaanalysis of the temporal evolution of MR findings. Am J Neuroradiol; 21:1073-1077, 2000 Salamon-Murayama N et al: Hypertrophic olivary degeneration secondary to pontine hemorrhage. Radiol; 213:814-817, 1999 Tsui EYKet al: Hypertrophic olivary degeneration following surgical excision of brainstem cavernous hemangioma: a case report. Clinical Imaging; 23:215-217, 1999 Kim SJ et al: Cerebellar MR changes in patients with olivary hypertrophic degeneration. AJNR; 15:1715-1719, 1994 Revel MP et al: MR appearance of hypertrophic olivary degeneration after contralateral cerebellar hemorrhage. Am J Neuroradiol; 12:71-72, 1991

96

Toxic/Metabolic/Degenerative

Disorders, Acquired

HYPERTROPHIC OLIVARY DEGENERATION I IMAGE GALLERY Typical (Left) Sagittal FLAIRMR shows abnormally increased signal intensity in an anterior medullary area (arrow) that corresponds to inferior olivary nucleus. (Right) Axial FLAIRMR in the same patient who suffered midbrain hemorrhage (not shown) depicts bilateral hyperintense and hypertrophied inferior olivary nuclei (arrows).

Typical (Left) Axial FLAIRMR shows high signal intensity and asymmetric enlargement of right anterior medulla corresponding to the region of hypertrophic degeneration of right inferior olivary nucleus (arrow). (Right) Axial T2WI MR in the same patient shows right pontine infarct, the primary lesion that led to right hypertrophic olivary degeneration.

Typical (Left) Axial T2WI MR shows

bilateral symmetric hypertrophy + increased signal intensity confined to inferior olivary nuclei, with loss of pre- and post-olivary sulci (arrows). (Right) Axial T2WI MR in the same patient shows the primary midbrain lesion that caused the occurrence of bilateral hypertrophic olivary degeneration.

10 97

Toxic/Metabolic/Degenerative

Disorders, Acquired

PART II

4

Anatomy-Based Diagnoses

Ventricles and Cisterns Sella and Pituitary CPA-lAC

[JJ

rn

[I]

Skull, Scalp, and Meninges [±]

PART II SECTION 1 Ventricles and Cisterns Approximately 10% of all intracranial neoplasms involve the cerebral ventricles, either primarily or by extension. In addition, the subarachnoid pa ar a common site of pathology that varie from benign, congenital lesions ( uch as arachnoid cysts) to infection (meningiti ) and neoplastic involvement ("carcinomatous meningitis"). We begin this relatively hort ection with an introduction to the gro and imaging anatomy of the cerebral ventricular system and subarachnoid pace. relatively compreh n ive list of di ord r involving the CSF spaces is shown, and a series of "custom" differential diagno is offered. Because the imaging characteristics of mass lesions in and around the ventricles are often non pecific, pr ci e location of the mass and the patient' ag are very helpful in offering an appropriate diagnosi . The pathologic entities discussed in this section include normal variants and hydrocephalus as follow: ormal variants avum epti pellucidi ( SP) avum velum interpositum ( VI) Enlarged subarachnoid spaces Hydrocephalu EVOH queductal tenosis ormal pre ure hydroc phalus F shunt and complications Other specific diagnoses are illu trated in their appropriate based section ( .g., neoplasms, and infection).

pathology-

SECTION 1: Ventricles and Cisterns

Introduction and Overview Ventricles, Cisterns Anatomy-Imaging

Issues

11-1-4

Normal Variants Cavum Septi Pellucidi (CSP) Cavum Velum Interpositum (CVI) Enlarged Subarachnoid Spaces

11-1-8 11-1-10 11-1-12

Hydrocephalus Obstructive Hydrocephalus Aqueductal.Stenosis Normal Pressure Hydrocephalus CSF Shunts and Complications

11-1-16 11-1-20 11-1-24 11-1-28

VENTRICLES, CISTERNS ANATOMY-IMAGING ISSUES

1 4

Sagittal oblique graphic shows the cerebral ventricles with foramen of Monro (open arrow), lateral recessesof 4th V with foramina of Luschka (arrows), foramen of Magendie (curved arrow).

Sagittal T2WI MR shows cerebral ventricles at 3T. lev in velum interpositum (arrow), frontal horn/body of lateral ventricle (open arrow), 4th V fastigium (curved arrow) are shown in detail.

ITERMINOLOGY Definitions • Two major intracranial CSF-containing compartments = ventricles, subarachnoid space (SAS)

IIMAGING ANATOMY • Lateral ventricles o Paired CSF-containing, ependymal-lined spaces curve from temporal horns around/above thalami o Frontal (anterior) horns • Triangle-shaped, indented by caudate heads (some asymmetry common) • Extend from genu/rostrum of corpus callosum posteriorly to pillars of fornix, F of M • Separated by septum pellucidum (may contain CSF) o Bodies • Axial: Course laterally as curve posteriorly • Coronal: Flattened triangles with inferomedial concavity formed by caudate, thalamus • Lateral: Roughly triangular shaped from CC to fornix in midline sectioni C-shaped with indentation from pulvinar of thalamus off-midline o Atria: Confluence of body, occipital and temporal horns; contains choroid plexus glomus o Occipital horns • Posterior extensions from atrium, bordered medially by forceps major of CC, laterally by tapetum and occipital radiations • Contain only CSF(when patient is supine, choroid plexus glomus may "dangle" into occipital horn) • Elevations on medial wall = upper (bulb), lower (calcar avis), accessory intraventricular prominence caused by hippocampal tail o Temporal (inferior) horns

•

•

•

•

• Axial: Curve laterally, then anteromedially into slit-like termination • Coronal: Slit-like, pial-lined choroid fissure appears to join ependymal-lined temporal horn as it curves over pes hippocampus • Sagittal: Finger-like CSFspace with medial indentation formed by collateral eminence of hippocampus Interventricular foramen (of Monro) o Y-shaped, with upper "arms" of Y into each lateral ventricle o Common stem opens into roof of 3rd V o Bounded anteriorly by fornices, posteriorly by choroid plexus and thalami Third ventricle o Axial: Single, midline; lies between thalami o Sagittal • Anterior border formed by lamina terminalis, anterior commissure • 75% show interthalamic adhesion (massa intermedia) • Bordered inferiorly by hypothalamus • Recesses:Optic (rounded; in front of optic chiasm); in.fundibular (points down towards center of pituitary stalk)i suprapineal (rounded posterior diverticulum above pineal gland); pineal (posterior diverticulum points into stalk of pineal gland, is bordered inferiorly by posterior commissure) o Coronal • Roof bordered by pial-lined tela choroidea of velum interpositum • CSFflow artifacts common, especially adjacent to FofM Aqueduct of Sylvius o Small, slender tube-like structure that joins 3rd and 4th ventricles o Traverses midbrain, surrounded by periaqueductal gray matter o Roof formed by tectal plate, flo.orby tegmentum 4th ventricle

VENTRICLES, CISTERNS ANATOMY-IMAGING

ISSUES

1 DIFFERENTIAL DIAGNOSIS • Colloid cyst (at foramen of Monro)

Congenital variants, malformations • • • •

CSP, CVI Septo-optic dysplasia, holoprosencephaly variants Callosal dysgenesis (high-riding 3rd V) Chiari II (elongated 4th V, fastigium usually absent)

Trauma • IVH +/- choroid plexus hematoma

Infection/i nflam mation • Ventriculitis +/- choroid plexitis • Pyocephalus (fluid-debris level; often fatal) • Sarcoid, histiocytosis

Nonneoplastic cysts • CSF-containing (arachnoid, ependymal) • Parasitic (e.g., neurocysticercosis)

cyst

o Complex configuration with rhomboid-shaped floor, tented roof o Sagittal • Funnel-shaped expansion from aqueduct into body of 4th V • Roof formed by superior medullary velum, a thin sheet of tissue stretching between the superior cerebellar penduncles • Triangular-shaped dorsal projection (fastigium) points towards vermis • Floor appears smooth, formed by dorsal surface of pons, medulla • Narrows inferiorly into obex at cranial end of central canal of spinal cord o Axial: Bean-shaped; posterior indentations formed by facial colliculi o Coronal • Diamond-shaped with upper point into aqueduct, lower into obex • Recesses: Posteriosuperior (blind wing-like pouches that curve over cerebellar tonsils) • Recesses: Lateral (curve around pons under major cerebellar penduncles) • Foramina: Luschka (opening of lateral recesses into cerebellopontine angle cisterns; contains choroid plexus that protrudes through lateral apertures into CPA) • Foramina: Magendie (medial aperture = midline opening into cisterna magna) • Foramina: Medial and lateral apertures of 4th ventricle are the ONLY normal connections between ventricular system, SAS • Choroid plexus and CSF production/resorption o Approximately 75% of CSF is produced by ventricular choroid plexus (remainder by other sites such as subcommissural organ) • Choroid plexus lacks BBB, enhances intensely • May contain cysts (xanthogranulomas) o Produced at rate of one-third to one-half mllminute or approximately 500 mllday o Total CSF volume in ventricles, SAS = approximately 125-150 ml

Benign neoplasm • • • •

Meningioma (atrium most common site) Astrocytoma (WHO grade I, e.g., giant cell, pilocytic) Central neurocytoma (body, lateral ventricle) Choroid plexus papilloma (atrium in children, 4th V in adults) • Subependymoma (F of Monro, 4th V obex) • Adenoma, craniopharyngioma (occasionally in 3rd V)

Malignant neoplasm • • • • •

Metastasis (choroid plexus, ependyma) Astrocytoma (WHO II-IV) Ependymoma (4th V most common site) Medulloblastoma Germinoma (hypothalamus, 3rd V)

o Bulk removal of CSF occurs through arachnoid granulations (AGs) in dural sinuses, venous lakes • If CSF resorption through AGs blocked, EVOH occurs • If cerebral aqueduct or 4th V outlet foramina occluded, IVOH ensues o Arachnoid granulations most prominent in transverse, superior sagittal sinuses o Variant: "Giant" arachnoid granulations • CSF attenuation/signal intensity • Seen as "filling defects" within intensely enhancing venous sinuses • Should not be mistaken for thrombus! • SAS and CSF cisterns o Numerous; most prominent are suprasellar and CPA cisterns (discussed in separate sections) o Variant: Can be prominent in newborns, infants

IANATOMY-BASED

IMAGING

ISSUES I

Key Concepts or Questions • Ventricles, cisterns contain CSF • Interstitial fluid (ISF) is found in brain parenchyma and within the perivascular (Virchow-Robin) spaces • CSF and ISF look grossly similar on imaging studies but are slightly different in chemical composition

Normal Measurements • Atrium of fetal lateral ventricles at 22 wks or later 10-12 mm

=

Imaging Pitfalls • Ventricular volume/size o Normal age-related increase after 60 y = approximately 1.2-1.4 mlly • Asymmetry o Asymmetry of the frontal, occipital horns is common, should not be mistaken for disease o Volume of right lateral, 3rd V larger in right-handed; left lateral ventricle in left-handed individuals o No gender differences

VENTRICLES, CISTERNS ANATOMY-IMAGING ISSUES

1

Sagittal graphic depicts the eSF-filled subarachnoid spaces in bright yellow, between arachnoid (green) and pia (red). Note contiguity between velum interpositum, quadrigeminal/superior cerebellar cisterns (arrows).

o Temporal horns are usually quite symmetric; asymmetry should prompt search for disease such as hippocampal sclerosis • CSF flow o Essentially one-way within ventricles o Pulsatile flow may cause bizarre artifacts on MR • "Flow voids" and/or signal inhomogeneities • Mass-like mimics may occur (e.g., flow at F of M can mimic colloid cyst)

ICLlNICALIMPLICATIONS

Subarachnoid spaces are shown in sagittal T2WI at 3T. Note velum interpositum (open arrow) contains lev (arrow), is· continuous with quadrigeminal/superior vermian cisterns. Suprasellar; interhemispheric, pontine cisterns are contiguous.

• Choroid plexus papilloma (children; rare location) • Pituitary adenoma, craniopharyngioma (intraventricular rare) • Chordoid glioma • Astrocytoma (hypothalamus, optic chiasm)

Mass in 4th V • • • • • •

Medulloblastoma (superior medullary velum) Ependymoma Dorsally exophytic brainstem glioma Choroid plexus papilloma (adults) Epidermoid cyst Subependymoma (obex; adults)

Clinical Importance • Significant variation, ventricular asymmetry is common • Actual size or change in size of ventricles is not reliable predictor of increased intracranial pressure • Ventricular volume increases in healthy aging adults>

ISELECTED REFERENCES 1. 2.

60y 3.

ICUSTOM DIFFERENTIAL DIAGNOSISI Mass in frontal horn of lateral ventricle

4.

• Subependymal giant cell astrocytoma tuberous sclerosis) • Astrocytoma (fibrillary) • Subependymoma

5.

(patients with

Mass in body of lateral ventricle

6.

• Central neurocytoma • Astrocytoma

7.

Mass in atrium of lateral ventricle

8.

• • • •

9.

Choroid plexus cysts (xanthogranulomas) Choroid plexus papilloma (children < 5 y) Meningioma Metastasis

Mass in 3rd V • Colloid cyst (rare in children)

Joseph VB et al: MR ventriculography for the study of CSF flow. AJNR AmJ Neuroradioi. 24(3):373-81, 2003 Jodicke A et al: Virtual endoscopy of the cerebral ventricles based on 3-D ultrasonography. Ultrasound Med BioI. 29(2):339-45, 2003 Karachi C et al: Hydrocephalus due to idiopathic stenosis of the foramina of Magendie and Luschka. Report of three cases. J Neurosurg. 98(4):897-902, 2003 Resnick SM et al: Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci. 23(8):3295-301, 2003 Jamous M et al: Frontal and occipital horn width ratio for the evaluation of small and asymmetrical ventricles. Pediatr Neurosurg. 39(1):17-21, 2003 Duffner F et al: Anatomy of the cerebral ventricular system for endoscopic neurosurgery: a magnetic resonance study. Acta Neurochir (Wien). 145(5):359-68,2003 Encha-Razavi F et al: Features of the developing brain. Childs Nerv Syst. 19(7-8):426-8, 2003 Vandewalle G et al: Accessory intraventricular prominence of the occipital horn of the lateral ventricle. J Neurosurg. 99(1):151-5,2003 Garel C et al: Ventricular dilatations. Childs Nerv Syst. 19(7-8):517-23,2003

VENTRICLES, CISTERNS ANATOMY-IMAGING ISSUES 1

I IMAGE GALLERY

7

Normal (Left) Axial graphic shows frontal horns of lateral ventricles (arrows), fornix (open white arrow), septum pellucidum (open black arrow), foramen of Monro (curved arrow) opening into 3rd ventricle. (Right) Axial T2WI MR shows ventricles at 3T. Frontal horns (arrows), third ventricle (open arrow) are indicated. Fornices are heavily myelinated tracts in front of foramen of Monro (curved arrow).

Normal (Left) Sagittal graphic shows close-up view of ventricular system. Rounded optic (arrow), pointed infundibular (curved arrow) recesses of 3rd ventricle, obex of 4th ventricle (open arrow) are indicated. (Right) Sagittal TlWI MR (3T) shows frontal horn at level of septum pellucidum as triangular-shaped space (open arrow) in front of fornix (arrow). Velum interpositum (curved arrow) lies above pineal.

Normal

(Left) Coronal graphic shows the septum pellucidum separating frontal horns of lateral ventricles. Foramen of Monro is Y-shaped, with common stem emptying into roof of 3rd ventricle (arrow). (Right) Coronal Tl C+ MR shows lateral, third ventricles at 3T. Foramen of Monro is filled with enhancing choroid plexus, thalamostriate veins (arrows). Pillars of fornix (open arrow) do not enhance.

CAVUM SEPTI PELLUCIDI (CSP)

1 8

Coronal graphic with axial insert shows classic cavum septi pellucidi (CSP) with cavum Vergae (CV) (arrows). Note finger-like CSF collection between lateral ventricles.

Axial TlWI MR in an asymptomatic patient shows incidental finding of a CSP + CII, seen here as a finger-like CSF collection (arrows) between frontal horns, bodies of lateral ventricles.

ITERMINOLOGY Abbreviations

and Synonyms

• Cavum septi pellucidi (CSP) +/- cavum Vergae (CV)

Definitions • Cystic CSF cavity of septum pellucidum posterior continuation (CV)

IIMAGING

(SP) +/-

• • • •

o Sagittal: Extends posteriorly from rostrum to splenium of corpus callosum above, ICVs below T2WI: Isointense with CSF FLAIR: Suppresses completely DWI: Doesn't restrict T1 C+: Doesn't enhance

Ultrasonographic

Findings

• Real Time o SP invariably cystic in fetus o Width of fetal CSP increases between 19-27 weeks o Plateaus, then gradually closes in rostral direction between 28 weeks and term

FINDINGS

General Features • Best diagnostic clue: Elongated finger-shaped CSF collection between lateral ventricles • Location o CSP = between frontal horns of lateral ventricles o CV = posterior extension between fornices • Size: From slit-like to several mm, occasionally> 1 cm • Morphology: Elongated, finger-like

Imaging Recommendations • Best imaging tool: U/S in fetus, newborn; MR in children, adults

I DIFFERENTIAL DIAGNOSIS

CT Findings

Asymmetric lateral ventricles

• NECT: CSF collection in septum pellucidum • CECT: Doesn't enhance

• Septum pellucidum

Cavum velum interpositum

MR Findings

• Triangular-shaped; of Monro

• TlWI o Axial: Finger-like CSF space between lateral ventricles

Ventricles and Cisterns

bowed but intact

(CVI)

doesn't extend anterior to foramen

CAVUM SEPTI PELLUCID' (CSP)

1

Key Facts Terminology • Cystic CSF cavity of septum pellucidum posterior continuation (CV)

(SP) +/.

• Cavum velum interpositum (CVI) • Ependymal cyst • Absent septum pellucidum (SP)

Imaging Findings

Pathology

• Best diagnostic clue: Elongated finger-shaped collection between lateral ventricles

• Present in 100% of premature,

Top Differential

CSF

Clinical Issues • Normally regresses but may persist as normal variant • Rare: Enlarges, may cause mass effect (+/- symptoms)

Diagnoses

• Asymmetric lateral ventricles

o May remain asymptomatic even if mass effect present o Headache = most common symptom (relationship to cyst unclear) . o Expanding CSP may have visual, behavioral, autonomic symptoms

Ependymal cyst • In body/atrium

of lateral ventricle

Absent septum pellucidum

(SP)

• Looks like CSP/CV on sagittal (coronal shows absent SP) • Congenital anomalies common

Natural History & Prognosis

General Features • General path comments: CSP is not the "5th ventricle" nor is CV a "6th ventricle" • Etiology o CSP forms if fetal SP fails to obliterate o Precise etiology of fluid accumulation unknown • Epidemiology o CSP • Present in 100% of premature, 85% term infants • 1% up to 15-20% of adults o CV

• Normally regresses but may persist as normal variant • Rare: Enlarges, may cause mass effect (+/- symptoms)

Treatment • Usually none (symptomatic cysts may be drained/shunted or fenestrated)

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• CV almost never occurs in absence of CSP

• 100% at fetal age 6 months, 30% term • < 1% of adults • Associated abnormalities o Rare: Hydrocephalus o Association with schizophrenia debated

I SELECTED REFERENCES 1.

Gross Pathologic & Surgical Features • CSP, CV may/may not communicate

Demographics • Age: CSP is universal in fetuses; decreases with age • Gender: M = F

I PATHOLOGY

Microscopic

85% term infants

Sencer A et al: Cerebrospinal fluid dynamics of the cava septi pellucidi and vergae. Case report. J Neurosurg. 94(1):127-9, 2001

with ventricles

Features

• CSP, CV may contain glial cells, scattered neurons

I IMAGE GAllERY

Staging, Grading or Classification Criteria • Shaw and Ellsworth classification for CSP, CV o Asymptomatic, incidental cavum (communicating or not) o Symptomatic, pathological, noncommunicating cavum • Simple and uncomplicated • Complicated by other lesions

I CLINICAL ISSUES Presentation

(Left) Sagittal T1 C+ MR shows a large CSP/CV that extends from just

• Most common signs/symptoms o Usually asymptomatic, incidental

behind the corpus callosum genu all the way posteriorly to the splenium. The fornices are not visible and the ICV is flattened (arrows). (Right) Coronal T1 C+ MR in the same case shows the large CSP bows the leaves of the septum pellucidum laterally (arrows).

Ventricles

and Cisterns

9

1 10

Sagittal graphic with axial insert shows a CVI. Note elevation, splaying of fornices (open arrows), inferior displacement of internal cerebral veins and 3rd ventricle (arrow).

Axial T2WI MR shows a small triangular-shaped CSF space, the CVI (open arrow), interposed between the fornices (arrows) and lateral ventricles. The CVI ends at the foramen of Monro.

• CECT: Doesn't enhance

Abbreviations

MR Findings

and Synonyms

• Cavum velum interpositum (CVI)i cavum velum triangularei cyst of the velum interpositum (VI)

Definitions • Cystic dilation of the cistern of the VI

General Features • Best diagnostic clue: Axial MR/CT shows triangular-shaped CSF space between bodies of lateral ventricles • Location o Midline between lateral ventricles, below fornices o Above tela choroidea of 3rd ventricle o Contains internal cerebral veins • Size: Fetal: Range = 10-30 mm; postnatal varies (few mm to several cm) • Morphology: Triangle (apex at foramen of Monro, base towards quadrigeminal cistern)

• TlWI o Axial: Triangle cavity of CSF between bodies of lateral ventricles o Sagittal: Varies from slit-like linear to round/ovoid CSF collection below fornices, above 3rd ventricle • T2WI: Isointense with CSF • FLAIR: Suppresses completely • DWI: Doesn't restrict • T1 C+: Doesn't enhance

Ultrasonographic

Findings

• Color Doppler o Hypoechoic midline interhemispheric cyst o Inverted "helmet shape" on sagittal sonograms o May show inferiorly displaced ICVs

Imaging Recommendations • Best imaging tool: MR without, with contrast • Protocol advice: Include FLAIR to distinguish between CVI, epidermoid cyst

CT Findings • NECT: Triangular cavity of CSF that doesn't extend anterior to foramen of Monro

Normal cistern of the velum interpositum • Usually small (slit-like or oval), doesn't elevate fornices

DDx: Cavum Velum Interpositum

Normal Cistern of VI

Arachnoid Cyst

Ventricles

Epidermoid Cyst

and Cisterns

Cavum Septi Pellucidi

CAVUM VELUM INTERPOSITUM (CVI)

1

Key Facts Terminology

Top Differential

• Cystic dilation of the cistern of the VI

• • • •

Imaging Findings • Best diagnostic clue: Axial MR/CT shows triangular-shaped CSF space between bodies of lateral ventricles • Size: Fetal: Range = 10-30 mm; postnatal varies (few mm to several cm)

Cavum septi pellucidi (CSP), Vergae (CV) • CSP + CV elongated, finger-like CSF space (CVI is triangular)

Arachnoid cyst • Lined with arachnoid

(may be indistinguishable)

Normal cistern of the velum interpositum Cavum septi pellucidi (CSP), Vergae (CV) Arachnoid cyst Epidermoid cyst

Clinical Issues • Usually asymptomatic,

• Gender: M

=

found incidentally

F

Natural History & Prognosis • Prenatal: Isolated CVI that is single, stable in size, not associated with other CNS anomalies has favorable postnatal outcome

Treatment

Epidermoid cyst • Lobulated, insinuating mass • Doesn't suppress with FLAIR; DWI shows restriction

I

Diagnoses

• Usually none (symptomatic shunted)

I DIAGNClSTIC

PA.THClI..ClGY

cysts may be fenestrated,

CHECKUST

Consider

General Features • General path comments: Normal cistern of VI is small to inapparent at autopsy • Genetics: No known association with trisomy • Etiology o As fetal cerebral hemispheres form and expand, a deep midline transverse cleft (the transverse fissure) is formed o Pia infolds along transverse fissure, forms CSF cistern (VI) o Cystic dilatation of VI may occur (precise etiology unknown) • Epidemiology: Common in early infancy, rare in adults • Associated abnormalities: Usually none (large CVIs may cause hydrocephalus)

Gross Pathologic & Surgical Features

• Could a CSF-appearing "cyst" be an epidermoid? • Use DWI, FLAIR to differentiate CSF-containing from other cysts

I SELECTED 1.

2.

3.

REFERENCES

Eisenberg VH et al: Prenatal diagnosis of cavum velum interpositum cysts: significance and outcome. Prenat Diagn. 23(10):779-83, 2003 Vergani P et al: Ultrasonographic differential diagnosis of fetal intracranial interhemispheric cysts. Am J Obstet Gynecol. 180(2 Pt 1):423-8, 1999 Chen CY et al: Sonographic characteristics of the cavum velum interpositum. AJNR Am J Neuroradiol. 19(9):1631-5, 1998

'IMAGE GA.I..I..ERY

• Pial-lined CSF-filled space

Microscopic

Features

• Occasionally cysts of midline CSF spaces contain glial cells, scattered neurons

I CLINICAL ISSUES Presentation • Most common signs/symptoms o Usually asymptomatic, found incidentally o Headache = most common but relationship unclear

to cyst

Demographics • Age: Can be found at any age (prevalence decreases with age)

(Left) Axial T!WI MR shows a very large CVI. Note splaying of fornices (arrows), anterior displacement of septum pellucidum (oRen arrow). Mild enlargement of lateral ventricles is seen. (Right) Sagittal' T! WI MR in same case shows anterior/superior displacement of fornix (curved arrow), inferior displacement of 3rd ventricle (open arrow). The corpus callosum is elevated, thinned.

Ventricles and Cisterns

11

ENLARGED SUBARACHNOID SPACES 12

Axial T2WI MR shows enlarged frontal, anterior interhemispheric pericerebral fluid spaces (curved arrow), mild ventriculomegaly, right-sided posterior plagiocephaly (arrow) in 7 month old.

I·TE~Mr~gl.g(jY Abbreviations

o Note normal maximum width peaks at 28 postnatal weeks (7 months) of life • Morphology o CSF space follows (not flattens) gyral contour o Right and left subarachnoid spaces symmetric

and Synonyms

• External hydrocephalus, physiologic extraventricular obstructive hydrocephalus (EVOH) • Physiologic subarachnoid space (SAS) enlargement, benign macrocephaly of infancy

Radiographic Findings

Definitions • Idiopathic

enlargement

Axial T2WI MR follow-up of same case as on the left at 17 months of age shows that the pericerebral and anterior interhemispheric fluid spaces have normalized.

of SAS during first year of life

• Radiography: Macrocephaly, frontal bossing • Myelography: Cisternography confirms communication of SAS, but not necessary

CT Findings

General Features • Best diagnostic clue: Enlarged SAS and increased head circumference (> 95%) • Location o SAS • Craniocortical: Widest vertical distance between brain and calvarium • Sinocortical: Widest distance between lateral wall of superior sagittal sinus and brain surface • Interhemispheric: Widest distance between hemispheres • Size o ::::5 mm widening bifrontal craniocortical/anterior interhemispheric SAS

• NECT o ::::5 mm widening bifrontal/anterior interhemispheric SAS o Enlarged cisterns (especially suprasellar/chiasmatic) o Mild enlarged ventricles (66%) o Sulci generally normal (especially posteriorly) o Postural unilateral lambdoid flattening common o Posterior fossa normal • CECT o Demonstrates veins traversing SAS o No abnormal enhancement of meninges

MR Findings • T1WI: Similar to NECT • T2WI o No abnormal brain tissue nor signal abnormalities o Single layer of fluid (SAS)with traversing vessels

~~ , tI

DDx: Enlarged Peri-cerebral

Spaces in Infants

..,.

, .'

~-

:.~ Atrophy, Small

He

--

.•..

"'0"

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Achondroplasia

NAT

Ventricles and Cisterns

NAT

ENLARGED SUBARACHNOID SPACES 1

Key Facts Terminology

• Acquired extraventricular

• External hydrocephalus, physiologic extraventricular o b st ruc t'lve h y d rocep h a Ius (EVOH) • Physiologic subarachnoid space (SAS) enlargement, benign macrocephaly of infancy • Idiopathic enlargement of SAS during first year of life

I(EVfl?H)d" 'd t 1"t (NAT) • n tete nonaCCl en a rauma

obstructive hydrocephalus

Pathology • Immature CSF drainage pathways

Clinical Issues Imaging Findings

• Macrocrania: Head circumference>

• Best diagnostic clue: Enlarged SAS and increased head circumference (> 95%) • z 5 mm widening bifrontal craniocorticaljanterior interhemispheric SAS • After diagnosis, best follow-up == tape measure, not imaging!

Top Differential

Diagnoses

95% • Family history of benign macrocephaly common • Age: 3 to 8 months usual • Self-limited; SAS enlargement resolves without therapy by 12-24 months • Macrocephaly often persists • Normal outcome (developmental delay resolves as prominent SAS resolves)

• Atrophy

• • • • •

o Flow void in aqueduct FLAIR: Homogeneous fluid T2* GRE: No blood products DWI: No restriction Tl C+: Enhancing veins traverse SAS Fetal MRI: Seen in fetus with distribution fluid/ventricular prominence related to positioning o Usually frontal prominence after birth due to position of child lying on back for scan

Ultrasonographic

Findings

• Real Time o Enlarged SAS z 5 mm o Veins as "dots" floating in SAS • Pulsed Doppler: Increased cerebral blood flow may identify "progressive" cases • Color Doppler: Veins traverse SAS

Angiographic

Atrophy • Atrophy: Small head circumference (He) o Forehead "pointed" due to metopic fusion • Benign SAS enlargement has large head o Forehead "flat" due to frontal bossing • Knowledge of HC critical for diagnosis

Acquired extraventricular hydrocephalus (EVOH)

• Conventional: Widened space between skull and arteries of brain surface

Findings

obstructive

• Often hemorrhagic/post inflammatory/neoplastic o Density of extra-axial collection does not = CSF • Also achondroplasia and other skull base anomalies o Coarctation of foramen magnum • Intermittent intracranial pressure waves

Inflicted "nonaccidental"

Findings

Nuclear Medicine

I DifFERENTIAl.. DIAGN(j)SIS

trauma (NAT)

• Predisposition to bleed with minor trauma controversial o Possible if SAS z than 6 mm o Venous "stretching" implicated

• Isotope cisternography o Accumulation of CSF in 4th and lateral ventricles similar to extraventricular hydrocephalus

I PATH(j)I..(j)G¥

Imaging Recommendations

General Features

• Best imaging tool: MRI to exclude chronic subdural collections • Protocol advice o Doppler sonography: Documents veins traversing SAS o MRI or CECT: To exclude underlying etiology o MRI: To exclude chronic subdural collections • SAS isointense with CSF on all sequences if benign o PC MRI shows normal intraventricular CSF flow o After diagnosis, best follow-up = tape measure, not imaging!

• General path comments: Clear CSF • Genetics o No documented genetic predisposition, although common in benign familial macro crania families • Family history of macrocephaly> 80% • Etiology o Immature CSF drainage pathways • CSF primarily drained via extracellular space ~ capillaries • Pacchionian granulations (PGs) don't mature until 18 months • PGs are then displaced into veins (as Starling-type resistors) • PGs regulate pulse pressure/venous drainage CSF when fontanels close

Ventricles

and Cisterns

13

ENLARGED SUBARACHNOID SPACES

1 14

• Benign SAS enlargement usually resolves at that time • Epidemiology: Reported on 2-65% of neuroimaging for macrocrania < 1 year old • Associated abnormalities: Anecdotal

• Always enhance CT (veins traverse SAS in benign enlarged SAS) and search for membranes (chronic subdural)

Gross Pathologic & Surgical Features • Deep/prominent but otherwise normal-appearing • No pathologic membranes

SAS

1.

Microscopic Features

2.

• Ependymal damage not seen in benign SAS enlargement

3.

Staging, Grading or Classification Criteria • Danger signs o Elevated ICP o Rapid enlargement of head circumference o > > > 6 mm width SAS o Onset or persistence> 1 year old

4.

5.

6.

Presentation • Most common signs/symptoms o Macrocrania: Head circumference> 95% o Frontal bossing o Mild developmental delay in 50% (motor > language) o No signs of elevated ICPi normal pressure on lumbar puncture • Clinical profile o Family history of benign macrocephaly common o Male infants, "late to walk"

7.

8.

9.

Lam WW et al: Ultrasonographic measurement of subarachnoid space in normal infants and children. Pediatr Neurol. 25(5):380-4, 2001 Girard NJ et al: Ventriculomegaly and pericerebral CSF collection in the fetus: early stage of benign external hydrocephalus? Childs Nerv Syst. 17(4-5):239-45,2001 Cosan TE et al: Cerebral blood flow alterations in progressive communicating hydrocephalus: transcranial Doppler ultrasonography assessment in an experimental model. J Neurosurg. 94(2):265-9, 2001 Papasian NC et al: A theoretical model of benign external hydrocephalus that predicts a predisposition towards extra-axial hemorrhage after minor head trauma. Pediatr Neurosurg. 33(4):188-93, 2000 Greitz D et al: The pathogenesis and hemodynamics of hydrocephalus: Proposal for a new understanding. I]NR 3:367-75, 1997 Chen CY et al: Pericerebral fluid collection: differentiation of enlarged subarachnoid spaces from subdural collections with color Doppler US. Radiology. 201(2):389-92, 1996 Prassopoulos P et al: The size of the intra-and extraventricular CSF compartments in children with idiopathic benign widening of the frontal subarachnoid space. Neuroradiology 37:418-21, 1995 Wilms Get al: CT and MR in infants with pericerebral collections and macrocephaly: benign enlargement of the subarachnoid spaces versus subdural collections. AJNRAm J Neuroradiol. 14(4):855-60, 1993 Mayta!] et al: External hydrocephalus: radiologic spectrum and differentiation from cerebral atrophy. AJRAm J Roentgenol. 148(6):1223-30, 1987

Demographics • Age: 3 to 8 months usual • Gender: 80% male

Natural History & Prognosis • Enlarged SAS ~ i suture/calvarial malleability/compliance ~ predisposes to posterior plagiocephaly • Self-limitedi SAS enlargement resolves without therapy by 12-24 months o Spontaneous resolution of spaces and symptoms • Calvarium "outgrows" brain, brain eventually "catches up" • Macrocephaly often persists

Treatment • No treatment necessary • Normal outcome (developmental prominent SAS resolves)

I

DIAGNOSTIC

delay resolves as

CHECKLIST

Consider • Nonaccidental way

injury if enlarged SAS atypical in any

Image Interpretation

Pearls

• Crucial: Know head circumference!

Ventricles and Cisterns

ENLARGED SUBARACHNOID

SPACES

1

I IMAGE GALLERY

15

Typical (Left) Axial CECT shows veins (arrows) traversing the enlarged subarachnoid space, (Right) Axial T2WI MR shows veins, represented by linear flow voids (arrows), traversing enlarged subarachnoid space,

Typical (Left) Sagittal T2WI MR shows enlarged 3rd ventricle, normal 4th ventricle, and a prominent flow void (curved arrow) across the aqueduct of Sylvius, (Right) Sagittal phase contrast flow sequence shows normal flow (arrow) across a non-obstructed aqueduct of Sylvius,

Typical

..

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... ···<''.~:

.••..

.-I, ." ~

'J ~

I.

,.

&.. ,I

•..

~ ~ . \;.•..

.'

,~"

I~

.f" .

I

~!.~

~"'-lti'

...'• ~

Ventricles

-

and Cisterns

-

(Left) Coronal sonogram shows dilated craniocortical SAS (note space between two markers) and veins (arrow) traversing subarachnoid space, (Right) Coronal color Doppler shows venous structure (arrow) traversing dilated subarachnoid space,

OBSTRUCTIVE HYDROCEPHALUS

1 16

Sagittal TlWI MR shows large mass within fourth ventricle (arrows) causing intraventricular obstructive hydrocephalus (lVOH), or non-communicating hydrocephalus.

ITERMINOLOGY Abbreviations

and Synonyms

• Two main types: IVOH and EVOH o IVOH (intraventricular obstructive hydrocephalus or "non-communicating" hydrocephalus) o EVOH (extraventricular obstructive hydrocephalus or "communicating" hydrocephalus) o Third type (rare) is overproduction of CSF (choroid plexus tumors) • Obstructive hydrocephalus can be acute (aOH) or chronic, i.e., "avulsed" or "compensated" (cOH)

Definitions • Enlarged ventricles due to absolute/relative CSF obstruction (mismatch between formation and absorption)

I IMAGING

FINDINGS

General Features • Best diagnostic clue o (aOH) = "ballooned" ventricles with indistinct ("blurred") margins o (cOH) = "ballooned" ventricles without periventricular halo • Location

DDx: Obstructive

NPH

Sagittal T2WI MR in the same case shows transependymal CSF flow, seen here as "fingers" extending into WM around the enlarged lateral ventricle. Medulloblastoma + acute IVOH.

o IVOH: Obstruction proximal to foramina of Luschka, Magendie o EVOH: Obstruction distal to 4th ventricle (4th V) outlet foramina • Size o Ratio between bifrontal horn diameter/intracranial diameter> .33 o Temporal horn width> 3 mm • Morphology o Varies with site and duration of blockage o Global/focally enlarged ventricle(s) +/- elevated ICP o Ventricles proximal to obstruction enlarge, appear more rounded

CT Findings • NECT o (aOH) = "ballooned" ventricles with periventricular low density "halo" o (cOH) = "ballooned" ventricles without periventricular halo o Basal cisterns, sulci compressed/obliterated • CECT: Typically no enhancement (if OH secondary to neoplasm, tumor may enhance)

MR Findings • TlWI o Lateral ventricles enlarged o Corpus callosum thinned, stretched upward o Fornix, ICV displaced downward

Hydrocephalus

NPH Ventricles

cpp

and Cisterns

Parenchvmal

Loss

OBSTRUCTIVE HYDROCEPHALUS

1

Key Facts Terminology

Top Differential

• Two main types: IVOH and EVOH • IVOH (intraventricular obstructive hydrocephalus or "non-communicating" hydrocephalus) • EVOH (extraventricular obstructive hydrocephalus or "communicating" hydrocephalus) • Enlarged ventricles due to absolute/relative CSF obstruction (mismatch between formation and absorption)

• Ventricular enlargement 2° parenchymal loss • Normal pressure hydrocephalus (NPH) • Long-standing overt ventriculomegaly in adults (LOVA) • Choroid plexus papilloma (CPP)

Imaging Findings • IVOH: Obstruction proximal to foramina of Luschka, Magendie • EVOH: Obstruction distal to 4th ventricle (4th V) outlet foramina • T1 C+: Hydrocephalus can induce leptomeningeal vascular stasis, mimic meningitis, metastases!

•

• • •

o 3rd ventricle often enlarged, herniated into expanded sella T2WI o aOH • "Fingers" of CSF-like hyperintensity extend into periventricular white matter, most striking around ventricular horns (periventricular "halos") • Disturbed/turbulent CSF flow in ventricles • Absent aqueductal "flow void" common • Corpus callosum may appear hyperintense o cOH • Large ventricles, normal CSF pressure • No periventricular halo Tl C+: Hydrocephalus can induce leptomeningeal vascular stasis, mimic meningitis, metastases! MRS: Small lactate resonances can be detected in up to 20% of CSF spaces even if no hydrocephalus Cardiac-gated cine-MR o May show no significant CSF flow in aqueduct

Other Modality

Findings

• Isotope cisternography may show ventricular reflux, stasis (EVOH) • Contrast enhanced-MR ventriculography has been used for assessing CSF flow, site of obstruction, status of 3rd ventriculostomies

Diagnoses

17

Pathology • Large ventricles without loss/dysgenesis tissue

of brain

Diagnostic Checklist • Size of ventricles generally correlates poorly with intracranial pressure

• Diffuse/focal enlargement of sulci, cisterns • Normal lateral ventricles can be asymmetric (related to handedness, not gender) • May correlate with some psychiatric disorders (e.g., schizophrenia)

Normal pressure hydrocephalus (NPH) • • • • •

Progressive dementia, gait disturbance, incontinence Ventricular dilation with normal CSF pressure Sulci normal/minimally enlarged Increased CSF displacement through aqueduct MRS shows lactate peak

Long-standing overt ventriculomegaly adults (LOVA)

in

• Early childhood onset or long-standing progression hydrocephalus into adulthood • Markedly enlarged ventricles, high ICP

of

Choroid plexus papilloma (CPP) • Account for 2-5% of childhood intracranial tumors • Typically present during infancy with signs of increased ICP • Usually located in the trigones of the lateral ventricles • May "over-produce" CSF • Hemorrhage, tumor spread may cause IVOH

Imaging Recommendations • Protocol advice o 3D constructive interference in steady state (CISS) decreases CSF flow artifact, allows better delineation of ventricular contour, septa o Cardiac-gated phase-contrast cine MR

I DIFFERENTIA[ DIAGNOSIS Ventricular enlargement

2° parenchymal

loss

• Old term = "ex vacuo" hydrocephalus (not used) • Age-related (ventricular volume t 1.2-1.4 ml/after 60 y)

o Ischemia/infarction; trauma; infection; toxic • Obtuse frontal angle (> 110°)

IPATHO[OG¥ General Features • General path comments o Large ventricles without loss/dysgenesis of brain tissue o Imbalance between CSF production, absorption • Genetics: Cell adhesion molecule Ll (LlCAM) only gene recognized to cause human hydrocephalus located on X chromosome (Xq28) • Etiology o Obstruction to CSF flow develops (may be intra or extraventricular); as CSF production continues, ventricular fluid pressure increases

Ventricles and Cisterns

OBSTRUCTIVE HYDROCEPHALUS 1 18

o Ventricles expand, compress adjacent parenchyma; stretching may rupture/open ependymal cell junctions o Periventricular interstitial fluid increases, leads to myelin destruction o Rare: More CSF produced than can be absorbed ("over-production" hydrocephalus; occurs with CPP, villous hyperplasia) o New: Overexpression of some growth factors (TGF), mutated Otx2 (head organizer during morphogenesis) reported o IVOH: Etiologies include tumors (most common cause in pediatric age group); AS; arachnoid cysts; aqueductal gliosis; congenital anomalies (Chiari malformations, Dandy-Walker malformations) o EVOH: Etiologies include thickened meninges (typically secondary to SAH, meningitis, CSF seeding of tumor, venous obstruction, NPH) • Epidemiology o Epidemiological data varies widely depending upon etiology and type of hydrocephalus o Most common neurosurgical procedure in children = CSF shunting for hydrocephalus

Image Interpretation

1. 2.

3.

4. 5.

6.

Gross Pathologic & Surgical Features

7.

• Focal/generalized ventricular enlargement • Ependyma and adjacent white matter are secondarily injured

8.

Microscopic

Features

9.

• Increased periventricular extracellular space • Ependymal lining damaged or lost; surrounding white matter becomes pale and rarefied

10.

11.

Presentation

12.

• Most common signs/symptoms: Headache, papilledema (aOH) • Clinical profile: Widely varies depending on etiology, severity, age of onset

13.

Wyldes M et al: Isolated mild fetal ventriculomegaly. Arch Dis Child Fetal neonatal Ed 89:F9-13, 2004 et al: Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex. Am] Psychiatry 161:15x-6, 2004 Erdogan AR et al: Sex and handedness differences in size of cerebral ventricles of normal subjects. Int] Neurosci 114:67-73,2004 Brown KP et al: IH MRS in human hydrocephalus. ] MRI 14:291-9,2003 Grunert P et al: The role of third ventriculostomy in the management of obstructive hydrocephalus. Minim Invasive Neurosurg. 46(1):16-21, 2003 Joseph VB et al: MR ventriculography for the study of CSF flow. A]NR Am] Neuroradiol. 24(3):373-81, 2003 Akhondi H et al: Hydrocephalus as a presenting manifestation of neurosarcoidosis. South Med]. 96(4):403-6,2003 Bhattacharyya KBet al: Bobble-head doll syndrome: some atypical features with a new lesion and review of the literature. Acta Neurol Scand. 108(3):216-20,2003 Davis GH: Fetal hydrocephalus. Clin Perinatol. 30(3):531-9, 2003 Papayannis CE et al: Expanding Virchow Robin spaces in the midbrain causing hydrocephalus. A]NR Am] Neuroradiol. 24(7):1399-403, 2003 Sener RN: Callosal changes in obstructive hydrocephalus: observations with FLAIRimaging, and diffusion MRI. Comput Med Imaging Graph. 26(5):333-7, 2002 Pen a A et al: Effects of brain ventricular shape on periventricular biomechanics: A finite-element analysis. Neurosurg 45: 107-18,2000 Oi S et al: Pathophysiology of long-standing overt ventriculomegaly in adults.] Neurosurg 92: 933-40, 2000

Demographics • Age: May be any age from in utero (congenital hydrocephalus) to adult • Gender: Both genders affected; epidemiological data varies widely and depends on type and etiology of hydrocephalus

Natural History & Prognosis • Usually progressive unless treated

Treatment • CSF diversion (shunt), endoscopic intervention ventriculostomy

and

Consider • Large-standing AS can be caused by slow-growing tectal tumor

Ventricles

Pearls

• Size of ventricles generally correlates poorly with intracranial pressure • Pulsatile CSF may create confusing signal intensity, even mimic intraventricular mass • Ventricular asymmetry can be normal variant

and Cisterns

OBSTRUCTIVE HYDROCEPHALUS 1 19

Typical (Left) Coronal T7 C+ MR shows IVOH with large enhancing intraventricular mass (black arrows) causing marked enlargement of the lateral ventricles (white arrows). (Right) Axial NECT shows same patient on left with large intraventricular mass (black arrow) within the fourth ventricle. Note dilated temporal horns (white arrows).

(Left) Sagittal T7 WI MR shows IVOH secondary to aqueductal stenosis. Distal stenosis of cerebral aqueduct (arrow). Note enlarged lateral and third ventricles. (Right) Axial FLAIR MR shows neurosarcoidosis and EVOH secondary to diffuse meningeal disease. Periventricular WM hyperintensities also present (arrows), as well as choroid involvement (open arrow).

(Left) Coronal T7 C+ MR shows neurocysticercosis involvement within third ventricle and aqueduct (arrow), causing IVOH. Lateral ventricles are dilated. (Right) Axial FLAIR MR shows neurocysticercosis resulting in IVOH. Large intraventricular cysts are present in the lateral vents (arrows), obstructing the foramina of Monroe.

Ventricles and Cisterns

20

Sagittal graphic shows obstructive hydrocephalus with massively enlarged ventricles, callosal thinning, "funnel" shaped aqueduct of Sylvius (arrow), herniation of floor of 3rd ventricle.

Abbreviations

o May see "aqueductal forking" or branching of aqueduct into channels o Aqueductal forking often accompanied by fusion of quadrigeminal bodies, third nerve nuclei or tectal beaking

and Synonyms

• Aqueductal stenosis (AS)

Definitions • Focal reduction in aqueduct size (diameter), congenital or benign acquired

General Features • Best diagnostic clue o Funnel-shaped aqueduct of Sylvius o "Ballooned" ventricles (lateral, third) and foramina of Monroe proximal to obstruction o Normal fourth ventricle and foramina (Luschka, Magendie) distal to obstruction o Interstitial edema with indistinct ("blurred") ventricular margins (absent if AS "arrested") • Location: Stenosis at cerebral aqueduct, either at level of the superior colliculi or at intercollicular sulcus • Size: Normal mean cross-sectional area of the aqueduct at birth is 0.2 to 1.8 mm2 • Morphology o Typically funnel-shaped aqueduct of Sylvius

DDx: Tectal/Tegmental/

Cyst in Aqueduct

Sagittal T2WI MR shows aqueductal stenosis with "funneled" aqueduct (curved arrow), hydrocephalus, thinning of the CC and inferior displacement of the third ventricle (open arrow).

CT Findings • NECT o Enlarged ventricles • Lateral and third disproportionately compared to fourth ventricle o No obstructing midbrain mass • CECT: No pathologic enhancement

enlarged

MR Findings • TlWI o Lateral ventricles enlarged o Corpus callosum (CC) thinned, stretched upward o Fornix, internal cerebral veins, 3rd ventricle floor displaced downward • T2WI o "Fingers" of CSF-like hyperintensity extend outwards from ventricles into brain (including CC) o Interstitial edema most striking around ventricular horns o Disturbed/turbulent CSF flow in ventricles o Absent aqueductal "flow void" common

Aqueductal

Pathology

Vasc Malformation

Ventricles and Cisterns

Tectal Glioma

AQUEDUCTAL STENOSIS

1

Key Facts Terminology • Focal reduction in aqueduct size (diameter), congenital or benign acquired

Pathology

Imaging Findings • Funnel-shaped aqueduct of Sylvius • "Ballooned" ventricles (lateral, third) and foramina of Monroe proximal to obstruction • Normal fourth ventricle and foramina (Luschka, Magendie) distal to obstruction • Corpus callosum (CC) thinned, stretched upward • Must carefully scrutinize posterior 3rd ventricle, tectum and tegmentum for presence of mass

Top Differential • Obstructing pathology

•

• • •

Diagnoses

extraventricular

midbrain

(tectal)

o Proximal stenosis generally show more severe hydrocephalus while distal stenosis generally show less Tl C+ o Helps to differentiate benign AS from neoplastic AS o Hydrocephalus can induce leptomeningeal vascular stasis, mimics meningitis or metastases! o Must carefully scrutinize posterior 3rd ventricle, tectum and tegmentum for presence of mass MRV: Downward displacement of internal cerebral veins Cardiac-gated cine-MR: Lack of significant CSF flow in aqueduct MRI findings more specific but nonetheless quite variable

Ultrasonographic

• Obstructing intraventricular (aqueductal) pathology • Post inflammatory gliosis (aqueductal gliosis) as etiology

Findings

• Real Time o Mastoid (posterolateral) fontanelle imaging in newborn may help differentiate AS from other pathologic conditions o Dilated lateral, third; normal fourth ventricles o In-utero shows same findings

Imaging Recommendations • Best imaging tool: Sagittal MRI • Protocol advice o 3D constructive interference in steady state (CISS) decreases CSF flow artifact, allows better delineation of ventricular contour, septa o Cardiac-gated phase-contrast cine MR

I DIFFERENIIAl. DIAGNOSIS Obstructing extraventricular (tectal) pathology

midbrain

• Neoplasm o Tectal astrocytoma, especially in neurofibromatosis o Pineal region tumors • Vascular malformation • Paracollicular arachnoid cyst

Ventricles

• AS obstructs CSF flow; CSF production continues, lateral/third ventricular fluid pressure increases • AS responsible for approximately 20% of congenital hydrocephalus

Clinical Issues • Insidious, may occur at any time from birth to adulthood • Headache, papilledema, 6th nerve palsy, bulging fontanelles • Sun-setting eyes (Parinaud syndrome & lid retraction & tonic downgaze)

Obstructing intraventricular pathology • Neurocysticercosis

with aqueductal

Post inflammatory as etiology

(aqueductal) cyst

gliosis (aqueductal gliosis)

• Post inflammatory process that is usually secondary to a perinatal infection or hemorrhage • Increasing in prevalence as newborns with bacterial meningitis or ICH survive at increasing rates • As in "benign" AS, the onset of symptoms (those of hydrocephalus) is insidious • Ependymal lining of aqueduct is destroyed; marked fibrillary gliosis of adjacent tissue is present • On imaging studies, differentiation of AS from aqueductal gliosis is not possible

I PAl'HOl.OG¥ General Features • General path comments o Congenital stenosis at level of aqueduct of Sylvius o The normal mean cross-sectional area of the aqueduct at birth is 0.5 mm2, ranging from 0.2-1.8 mm2

• Genetics o Cell adhesion molecule Ll (LlCAM) only gene recognized to cause human hydrocephalus, located on X chromosome (Xq28) o Overexpression of some growth factors (TGF), mutated Otx2 (head organizer during morphogenesis) reported • Etiology o Aqueductallumen normally decreases in size beginning 2nd week of fetal life until birth o This narrowing is caused by growth pressures upon the aqueduct from adjacent mesencephalic structures o AS obstructs CSF flow; CSF production continues, lateral/third ventricular fluid pressure increases

and Cisterns

21

1 22

o Ventricles expand, compress adjacent parenchyma, stretch corpus callosum which may rupture/open ependymal cell junctions o Periventricular interstitial fluid increases o Some postulate AS may be secondary to communicating hydrocephalus and secondary (external) compression of quadrigeminal plate by dilated cerebral hemispheres • Epidemiology o AS responsible for approximately 20% of congenital hydrocephalus o 0.5-1 per 1000 births, with recurrence rate in siblings of 1-4.5% • Associated abnormalities o CRASH: Callosal hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and X-linked Hydrocephalus o Bickers-Adams syndrome: X-linked hydrocephalus accounts for 7% cases in males • Stenosis of aqueduct, severe mental retardation, 50% with adduction-flexion deformity of thumb

Gross Pathologic & Surgical Features • Generalized

Microscopic

lateral and third ventricular

enlargement

Features

• Increased periventricular

extracellular

space

Presentation • Most common signs/symptoms o Symptoms depend upon age of patient at time of onset o Insidious, may occur at any time from birth to adulthood • Headache, papilledema, 6th nerve palsy, bulging fontanelles • Macrocrania, especially if sutures unfused • Sun-setting eyes (Parinaud syndrome & lid retraction & tonic downgaze)

• Most common cause of obstruction at level of Sylvian aqueduct in children is a pineal region tumor

Image Interpretation

1.

Tisell M et al: Neurological symptoms and signs in adult aqueductal stenosis. Acta Neurol Scand. 107(5):311-7,2003 2. Senat MV et al: Prenatal diagnosis of hydrocephalus-stenosis of the aqueduct of Sylvius by ultrasound in the first trimester of pregnancy. Report of two cases. Prenat Diagn. 21(13):1129-32, 2001 3. Partington MD: Congenital hydrocephalus. Neurosurg Clin N Am. 12(4):737-42, ix, 2001 4. Fukuhara T et al: Clinical features of late-onset idiopathic aqueductal stenosis. Surg Neurol. 55(3):132-6; discussion 136-7,2001 5. Schroeder HW et al: Endoscopic aqueductoplasty: technique and results. Neurosurgery. 45(3):508-15; discussion 515-8, 1999 6. Castro-Gago M et al: Autosomal recessive hydrocephalus with aqueductal stenosis. Childs Nerv Syst. 12(4):188-91, 1996 7. Blackmore CC et al: Aqueduct compression from venous angioma: MR findings. AJNRAm J Neuroradiol. 17(3):458-60, 1996 8. Villani R et al: Long-term outcome in aqueductal stenosis. Childs Nerv Syst. 11(3):180-5, 1995 9. Kadowaki C et al: Cine magnetic resonance imaging of aqueductal stenosis. Childs Nerv Syst. 11(2):107-11, 1995 10. Oka K et al: Flexible endoneurosurgical therapy for aqueductal stenosis. Neurosurgery. 33(2):236-42; discussion 242-3,1993

Demographics • Age: Congenital abnormality with presentation occurring anytime from birth to adulthood, depending on severity of stenosis • Gender: Males:Females = 2:1

Natural History & Prognosis • Usually progressive unless treated • May stabilize as "arrested hydrocephalus"

Treatment • CSF shunt diversion (most common neurosurgical procedure in children) • Endoscopic third ventriculostomy

Consider • Post inflammatory etiology

gliosis (aqueductal

gliosis) as

Ventricles

Pearls

• Tectal astrocytomas large enough to obstruct aqueduct can be missed on routine CT scanning • All patients with suspected AS should be carefully scrutinized for presence of an obstructing mass! • Patients with severe hydrocephalus generally have stenosis in proximal aqueduct, either at level of superior colliculi or at entrance to aqueduct immediately inferior to posterior commissure • In patients with mild hydrocephalus, level of obstruction is more often in distal portion of aqueduct

and Cisterns

1 23

Typical (Left) Sagittal T7WI MR shows aqueductal stenosis in distal portion of aqueduct. Note stretched corpus callosum (open arrow) and distended roof and floor of the third ventricles (arrows). (Right) Axial T2WI MR of same patient on left shows dilated lateral and third ventricles. Note "blurring" of margins.

Typical (Left) Coronal T2WI MR

shows "funneling" of the aqueduct in the coronal plane (white arrow), with markedly distended ventricular system proximal to the stenotic aqueduct. (Right) Axial FLAIRMR shows interstitial edema along ventricular margins (arrows), sometimes referred to as "blurring" of ventricles.

Typical (Left) Sagittal T2WI MR shows massively distended third and lateral ventricles with distal aqueductal stenosis (arrow). Note severe stretching of corpus callosum (open arrows). (Right) Axial NECT shows massively enlarged lateral and third ventricular system, tapering at the level of the cerebral aqueduct. This patient is 7 day old.

Ventricles and Cisterns

NORMAL PRESSURE HYDROCEPHALUS 24

Axial NEeT shows ventriculomegaly with rounded frontal horns, out of proportion to sulcal enlargement.

Abbreviations

and Synonyms

• Normal pressure hydrocephalus

(NPH)

Definitions • Ventriculomegaly CSF dynamics

with normal CSF pressure, altered

Axial T2WI MR in a different patient shows ventricles dilated out of proportion to sulcal enlargement. Periventricular, deep white matter lesions also present.

o Ventriculomegaly with rounded frontal horns, out of proportion to sulcal atrophy (ventriculosulcal disproportion) o Frontal and occipital periventricular hypodensities (representing transependymal CSF flow) may be present o Corpus callosal thinning (nonspecific)

MR Findings

General Features • Best diagnostic clue: Ventricles and Sylvian fissures symmetrically dilated out of proportion to sulcal enlargement, with normal hippocampus (which distinguishes NPH from atrophy) • Location: Ventriculomegaly is prominent in all 3 horns of lateral ventricles and 3rd ventricle, with relative sparing of 4th ventricle • Size: Increased ventricular volume • Morphology: Diffuse expansion of ventricles • Diagnostic challenge = identify shunt-responsive NPH

CT Findings • NECT

• TlWI o Lateral ventricles enlarge o +/- Aqueductal "flow void" • T2WI o Regions of moving CSF demonstrate no signal o Periventricular high signal, primarily anterior to frontal horns or posterior to occipital horns of lateral ventricles (transependymal CSF flow) o 50-60% have periventricular and deep white matter lesions • More frequent, severe compared to age-matched controls • Correlates with poor outcome after shunting, but should not exclude patients from surgery • MRS o Proton chemical shift imaging (lH-CSI): Lactate peaks in lateral ventricles in NPH patients, but not in patients with other types of dementia

DDx: NPH

Alzheimer

Binswanger

Ventricles

MID

and Cisterns

Microvascular

NORMAL PRESSURE HYDROCEPHALUS

1

Key Facts

•

• •

• •

•

Imaging Findings

Top Differential

• Best diagnostic clue: Ventricles and Sylvian fissures symmetrically dilated out of proportion to sulcal enlargement, with normal hippocampus (which distinguishes NPH from atrophy) • Diagnostic challenge = identify shunt-responsive NPH • Proton chemical shift imaging (1H-CSI): Lactate peaks in lateral ventricles in NPH patients, but not in patients with other types of dementia • Aqueductal"flow void" sign • CSF flow studies to detect increased velocity ("hyperdynamic" flow) • Indium-labeled CSF study with ventricular reflux, with no flow over convexities at 24-48 hours • Best imaging tool: MR with CSF flow studies preferred, CT also useful

• • • •

• Reflects ischemic changes in periventricular regions despite normal CSF pressure in patients with NPH • May be key factor in differentiating NPH from other dementias • May be useful as follow-up study after continuous spinal drainage Hypointense or absent signal in proximal 4th ventricle on T2WI, PD, FLAIR, with surrounding CSF appearing hyperintense Enlarged basal cisterns, Sylvian fissures; normal sulci Dilatation of optic and infundibular recesses of anterior 3rd ventricle and downward displacement of hypothalamus Corpus callosum bowed upwards (may be impinged by falx) Aqueductal"flow void" sign o Reflects increased CSF velocity through cerebral aqueduct o Present in some cases on PD, conventional SE sequences o May be reduced if flow-compensation, FSE techniques used o Correlated with favorable outcome after shunt surgery Cortical and subcortical lacunar infarctions (basal ganglia, internal capsule)

Nuclear Medicine

Findings

• PET o 18F-FDG PET shows decreased regional cerebral metabolism o 0(15) - water PET shows j CBF in cerebrum, cerebellum • SPECT: Cerebral blood flow (CBF) j in patients with NPH

Other Modality

Findings

• CSF flow studies to detect increased velocity ("hyperdynamic" flow) o Cardiac-gated 2D-FISP o Aqueduct stroke volume> 42 mL reported to correlate with good response to shunt

Ventricles

Diagnoses

25

Normal aging brain Alzheimer dementia Multi-infarct dementia (MID) Subcortical arteriosclerotic encephalopathy (Binswanger's disease)

Clinical Issues • Heterogeneous syndrome (classic clinical triad = dementia, gait apraxia, urinary incontinence)

Diagnostic Checklist • Intraventricular lactate level may be useful in differentiating NPH from other types of dementia

o Some patients with normal CSF flow values also improve • Indium-labeled CSF study with ventricular reflux, with no flow over convexities at 24-48 hours • ICP monitoring: Wave amplitude> 9 mm Hg correlates with post-shunt cognitive improvement

Imaging Recommendations • Best imaging tool: MR with CSF flow studies preferred, CT also useful • Protocol advice: T2WI with CSF flow study

I DIFFER.ENII~1.DI~6NQSIS Normal aging brain • Thin periventricular high signal rim without white matter hyperintensities ("successfully aging brain")

Alzheimer

dementia

• Dementia out of proportion to gait disturbance • Large parahippocampal fissures, small hippocampi, sulcal enlargement

Multi-infarct

dementia (MID)

• Multiple infarcts on imaging

Subcortical arteriosclerotic (Binswanger's disease)

encephalopathy

• Continuous, irreversible ischemic degeneration of periventricular and deep white matter • MR shows extensive periventricular and deep white matter hyperintensities, enlarged ventricles o Reflect microinfarctions and demyelination

I P~IHQI.Q6Y General Features • General path comments: understood • Etiology o 50% idiopathic

and Cisterns

Pathogenesis

of NPH poorly

NORMAL PRESSURE HYDROCEPHALUS 1 26

o 50% other (e.g., subarachnoid hemorrhage, meningitis, neurosurgery, or head trauma) o Age-related changes in CSF formation/absorption include increased resistance to CSF outflow • May be exacerbated in NPH o Dysfunctional CSF dynamics • Reduced absorption through arachnoid villi • Compensatory CSF flow into periventricular white matter • Transcapillary CSF resorption o NPH: Reduced CBF, altered CSF resorption without increased CSF pressure • Brain expands in systole, causes CSF displacement • Loss of parenchymal compliance, altered viscoelastic properties of ventricular wall • Increased interstitial fluid • Pulsation pressure directed toward ventricles • "Water-hammer" effect • May be further complicated by microangiopathy (including venous compromise), atrophy • Epidemiology: Accounts for approximately 0.5-5% of dementias

Natural History & Prognosis • Natural course: Continuing cognitive and motor decline, akinetic mutism, and eventual death • Potentially reversible cause of dementia when shunted

Treatment • Predictors of positive response to shunting o Absence of central atrophy or ischemia o Gait apraxia as dominant clinical symptom o Upward bowing of corpus callosum with flattened gyri and ballooned 3rd ventricular recesses o Prominent CSF flow void o Known history of intracranial infection or bleeding (nonidiopathic NPH) • After shunt surgery: o Variable outcome: 1/3 of patients improve, 1/3 display arrest of symptom progression, and 1/3 continue to deteriorate o Irregular periventricular hyperintensities seem to be key reversible white matter change at MR imaging

Gross Pathologic & Surgical Features

I DIAGNOSTIC CHECKLIST

• Enlarged ventricles, normal CSF pressure • Periventricular white matter is stretched and dysfunctional due to inadequate perfusion, without actually being infarcted

Consider

Microscopic Features

• Intraventricular lactate level may be useful in differentiating NPH from other types of dementia

• Arachnoid fibrosis in 50% • Periventricular tissue o Disruption of ependyma o Edema, neuronal degeneration and gliosis • Cerebral parenchyma o Almost 50% show no significant parenchymal pathology o 20% have neurofibrillary tangles, other changes of Alzheimer dementia o 10% arteriosclerosis, ischemic encephalomalacia

• Whether ventricular

Image Interpretation

1.

2.

3.

4.

Presentation • Most common signs/symptoms o Heterogeneous syndrome (classic clinical triad dementia, gait apraxia, urinary incontinence) o Symptom severity is related to CSF levels of neurofilament protein, a marker of neuronal degeneration • Clinical profile: Reversible cause of dementia

=

dilation is solely due to atrophy

5.

6.

Pearls

Owler BKet al: Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values. J Cereb Blood Flow Metab 24:17-23,2004 Czosnyka M et al: Age dependence of cerebrospinal pressure-volume compensation in patients with hydrocephalus. J Neurosurg 94:482-486, 2001 Kizu 0 et al: Proton chemical shift imaging in normal pressure hydrocephalus. Am J Neuroradiol 22:1659-1664, 2001 Tullberg M et al: Normal pressure hydrocephalus: vascular white matter changes on MR images must not exclude patients from shunt surgery. Am J Neuroradiol 22:1665-1673,2001 Parkkola RK et al: Cerebrospinal fluid flow in patients with dilated ventricles studied with MR imaging. Eur Radiol 10:1442-1446,2000 Bech RAet al: Frontal brain and leptomeningeal biopsy specimens correlated with CSF outflow resistance and B-wave activity in patients suspected of NPH. Neurosurg 40:497-502, 1997

Demographics • Age o Most common in patients> 60 y o Idiopathic form of NPH tends to present in elderly o Patients with chronic communicating hydrocephalus due to prior known insult tend to present at an earlier age • Gender: M > F • Ethnicity: No racial predilection

Ventricles and Cisterns

NORMAL PRESSURE HYDROCEPHALUS

1 27 (Left) Axial T2WI MR shows ventriculomegaly. (Right)

Sagittal TlWI MR in the same patient shows accentuated aqueductal flow void (arrow).

Typical

(Left) Axial T2WI MR shows

enlarged ventricles with rounded frontal horns. (Right) Axial FLAIRMR in the same patient shows ventriculomegaly out of proportion to sulcal enlargement.

(Left) Axial CECT shows symmetric dilatation of ventricles and Sylvian fissures out of proportion to sulcal enlargement. Frontal and occipital periventricular hypodensities suggest transependymal CSF flow. (Right) Axial CECT in the same patient shows symmetric dilatation of ventricles and Sylvian fissures out of proportion to sulcal enlargement. Frontal and occipital periventricular hypodensities also present.

Ventricles

and Cisterns

28

Axial T2WI MR shows reservoir (curved arrow), shunt tubing (arrow), collapsed left lateral ventricle and isolated right lateral ventricle with associated interstiUal edema (open arrow).

Abbreviations

Axial FlAIR MR shows the sequelae of overdrainage with bilateral subdural hematomas (arrows) and ventricular collapse following shunt (open arrow) placement.

o Distal shunt in peritoneal cavity (common), cardiac atrium or pleural cavity (rare) • Size: Distal tip long enough to allow for growth • Morphology: Usually constructed from silicone

and Synonyms

• Ventriculo-peritoneal (VP), ventriculo-atrial (VA), ventriculo-pleural (VPL), lumbo-peritoneal (LP)

Radiographic Findings

Definitions • CSF shunt establishes an accessory drainage pathway to bypass obstructed natural pathways • Many different pediatric disorders may necessitate CSF diversion • Shunting obstructed ventricles restores vascular compliance and normal trans-parenchymal drainage patterns

• Radiography o Plain films: Evaluate shunt continuity/integrity • Shunt fractures/separation (13%) • Shunt migration (rare = bowel perforation) • Fluoroscopy: Contrast shuntograms define site of obstructions (rarely performed) • Myelography: Myelography/cisternography rarely needed, but may define loculations

CT Findings

General Features • Best diagnostic clue: Dilated ventricles + fluid/edema "blurring" margin around valve/ventricles • Location o Proximal catheter in cerebral ventricles (common), intracranial subarachnoid space, or thecal sac (rare) o Unidirectional valve prevents reflux back into ventricles; reservoir attached to valve is optional o Catheter tunneled in subcutaneous tissue

• NECT o Ventricular dilatation (diffuse or loculated) • Isolated ventricles common following infection or hemorrhage o Note: Small, "slit" ventricles may occur with non-compliant ventricle syndrome, chronic overdrainage o Transependymal CSF egress ("blurred" ventricles) o Previous studies for comparison needed o +/- Subdural fluid or bleed (overdrainage in youngest) • CECT o +/- Ependymal enhancement

DDx: CSF Shunts and Complications

Peri-shunt Fluid

Acquired Chiari 7

Ventricles

and Cisterns

"S/it" Ventricles

CSF SHUNTS AND COMPLICATIONS

1

Key Facts

29

Terminology

Pathology

• Many different pediatric disorders may necessitate CSF diversion • Shunting obstructed ventricles restores vascular compliance and normal trans-parenchymal drainage patterns

• Common complications include shunt obstruction/breakage, infection, overdrainage • Each shunt, valve/device carries own set of complications

Imaging Findings

• 70% headache, vomiting, lethargy with shunt obstruction • Up to 30% shunts fail in first year, 80% fail by 10 years • Acute shunt obstruction may lead to death

• Best diagnostic clue: Dilated ventricles + fluid/edema "blurring" margin around valve/ventricles

Top Differential

Diagnoses

• Shunt failure with normal ventricles or lack of interstitial edema • Acquired Chiari l/tonsillar ectopia • Non-compliant ("slit") ventricle syndrome

o May identify other abnormalities neoplasm, etc)

Clinical Issues

Diagnostic Checklist • Not all shunt + headache = obstruction: Remember sinusitis, trauma, sinovenous thrombosisl • Previous comparison studies crucial!

o Always enhance the first imaging study of hydrocephalus (occult neoplasm) and fever (ventriculitis) o Baseline CT/MR following shunt insertion, follow-up at 1 y, then as needed o Plain films to identify shunt fracture or dislocation

(meningitis,

MR Findings • T1WI: Assess ventricular size • T2WI: Transependymal CSF egress • FLAIR: "Fingers" of CSF extending into periventricular WMcommon • T2* GRE: Assess hemorrhagic shunt tracts, shunt • DWI: No restriction for interstitial edema • T1 C+: Always enhance first time hydrocephalus to seek occult neoplasm • MRA: Stretched arteries with hydrocephalus • MRV: Venous thrombosis may precede hydrocephalus or follow shunting • MRS: Small lactate resonances can be detected in up to 20% of CSF, even if no hydrocephalus • 2D PC MR flow studies confirm obstruction (e.g., aqueduct) and patency of CSF pathways/ventriculostomy stoma

Ultrasonographic

Findings

• Real Time: Sonography for ventricular size possible with open fontanel • Pulsed Doppler: Resistive indices increase with shunt obstruction and raised ICP • Color Doppler: Research studies document flow within shunt tubing and aqueduct

Angiographic

Findings

• Conventional: hydrocephalus

Stretched and attenuated

Nuclear Medicine

I DIFFEREN"[I~EDI~(]NeSIS Shunt failure with normal ventricles or lack of interstitial edema • Look for fluid along shunt catheter or reservoir as only sign of malfunction

Acquired Chiari 1/tonsillar ectopia • Functioning

LP shunt causes tonsillar descent

Non-compliant

("slit") ventricle syndrome

• Older child (shunted in infancy), small ventricles + intermittent signs of shunt obstruction • Ventricles may appear normal/small even if shunt is malfunctioning! • Can be caused by shunt-induced sutural ossification

I

p~"[HeEe(]¥

General Features arteries with

Findings

• PET: Cerebral vascular reserve (CVR) measurement in selection of shunt candidates • Radionuclide studies o Can confirm distal obstruction, rarely needed

aids

Imaging Recommendations • Best imaging tool: CT easiest to obtain in setting of acute obstruction • Protocol advice o CT or MR to evaluate ventricles/CSF flow

• General path comments o Infected shunts 5-10%, especially younger than 6 months or within 3 months insertion o Ventricular loculation or isolation 6% o Overshunting 3% (leads to subdural effusions/hematomas and occasionally to parenchymal hemorrhage) o Shunt migration: Caudal> > > > cephalic • Etiology o CSF production 0.35mLjmin o 500 mL (adults), 250 mL (children) produced/absorbed in 24 hour period o Absorption requires> 6.8 mm H20 pressure to overcome sinovenous pressure

Ventricles and Cisterns

30

o Impaired CSF absorption allows accumulation and increased intraventricular/intracranial pressure o CSF diversion via shunt restores/maintains normal intracranial pressure • Epidemiology o CSF shunts in USA = 125,000 total • 33,000 per year (nearly half are revisions) o 160,000 shunts implanted each year worldwide • Associated abnormalities o Shunts in infants younger than 6 months carry increased risk of infection o Shunts in presence of blood or protein content> 19/dL prone to failure, early blockage

Gross Pathologic & Surgical Features • Transventricular ependymal adhesions • Ependymal "scar" restricts ventricular expansion • Extracranial shunt tubing calcifications

Microscopic

Features

• Gliosis along tract

Staging, Grading or Classification Criteria • Shunt complication rate 25-37% • Common complications include shunt obstruction/breakage, infection, overdrainage • Each shunt, valve/device carries own set of complications o VP (ventriculoperitoneal) abdominal complications: CSF pseudocyst/ascites, bowel perforation o VA (ventriculoatrial): Shunt nephritis, cor pulmonale, pulmonary embolus o LP (lumboperitoneal): Arachnoiditis, cerebellar tonsillar herniation, high migration rate o Internal 3rd ventricle to spinal SAS(Lapras catheter) no external access, no way to check flow o Shuntless CSF diversion: 3rd ventriculostomy, 4th ventricle outlet fenestration 70% patency o Anti-siphon devices: Obstruction by capsule formation o Flanged catheters: Increased risk of proximal occlusion o Programmable shunt: Reprogram after MRI! o One piece shunt decreased obstruction rate, but increased slit ventricle/SDH rate o Ventriculopleural (if peritoneum contaminated or cardiac complicated) can lead to pleural effusion o Pressure regulating shunts prone to overdrainage o Flow regulating valves prone to obstruction • Late complications o Child outgrows peritoneal tubing o Material degradation/fatigue, mechanical stress: Especially craniocervical junction, inferior ribs

o Infants: Bulging fontanel, increased head circumference • Clinical profile: Dependent upon diagnosis leading to CSF diversion and to number of complications

Demographics • Age o Peak age for shunt within first few weeks of life for myelomeningocele and congenital hydrocephalus o Later shunting follows trauma, meningitis, tumor

Natural History & Prognosis • Hydrocephalus: Mortality up to 80% without CSF diversion • Following shunting: 70% normal or relatively normal intelligence if no complications or associated anomalies • Incidence epilepsy up to 47% if shunt follows meningitis, hemorrhage • Most shunts eventually fail o Up to 30% shunts fail in first year, 80% fail by 10 years o 50% multiple revisions, progressively shorter intervals to next failure • Acute shunt obstruction may lead to death • Shunt related mortality: Malfunction (30%), infection (20%), pulmonary embolus (7%)

Treatment • Lengthen distal shunt as child grows • Change intraventricular component/valve if proximal obstruction • Alter pressure valve if over/under-draining • Subtemporal decompression/3rd ventriculostomy for non-compliant ventricle syndrome • Catheters impregnated with antimicrobial agents may decrease shunt infections

Consider • Not all shunt + headache = obstruction: Remember sinusitis, trauma, sinovenous thrombosis!

Image Interpretation

1.

2.

Presentation

3.

• Most common signs/symptoms o 70% headache, vomiting, lethargy with shunt obstruction o 30% neuropsychologic, cognitive or behavioral difficulties

4.

Ventricles

Pearls

• Previous comparison studies crucial! • Fluid tracking along shunt may be only sign of obstruction, even if normal or unchanged ventricles

5.

Fewel ME et al: Migration of distal ventriculoperitoneal shunt catheter into the heart. J Neurosurg 100:206-11, 2004 Braun KP et al. IH MRSin human hydrocephalus. J MRI 17(3):291-299,2003 Drake JM et al: CSF shunts 50 years on past, present and future. Childs Nerv Syst 16: 800-4, 2000 Tuli S et al: Risk factors for repeated CSF shunt failures in pediatric patients with hydrocephalus. J Neurosurg 92:31-38,2000 Lee IT et al: Unique clinical presentation of pediatric shunt malfunction. Pediatr Neurosurg 30: 122-6, 1999

and Cisterns

1 31

Typical (Left) Anteroposterior

radiography shows fractured (arrows) shunt tubing. (Right) Anteroposterior radiography shows large left pleural effusion in a child with a left ventriculopleural shunt (open arrows).

Typical (Left) Anteroposterior

radiography shows disconnected and caudally migrated peritoneal shunt looped in abdomen and pelvis. (Right) Anteroposterior radiography shows knotted abdominal shunt tubing. Tightly coiled appearance denotes an abnormal extraperitoneal placement of shunt. 2 shunts are present due to isolated ventricles.

Typical (Left) Axial NECT shows pelvic CSF ascites surrounding distal shunt tubing (arrow). (Right) Anteroposterior radiography shows dilated bowel loops floating in a large amount of intraabdominal and intrapelvic fluid. Child has VP shunt and peritonitis.

Ventricles and Cisterns

PART II SECTION 2 Sella and Pituitary The sella region is the mo t anatomically complex region within the calvarium. Lesions may arise from a variety of normal tructures and reflect di ea that spans the entire pathologic spectrum from congenital anomalies to numerou acquired disorders. We begin this section with an overview of normal gro and 3T imaging anatomy, then discuss imaging issues that focus on the pituitary gland and hypothalamu a well as their clinical implications. Ov r 30 separately identifiable diagnoses have been reported in the sella/ juxta ellar region. A list of the e entities is shown in the "Differential Diagnosis" box in the overview. Le ions of the central skull base and soft tissues of the upper head/neck are considered more pecifically in Diagnostic Imaging: Head and Neck. Here we have selected 10 diagno e that represent orne of the most common entitie en ountered within and above the sella as well a important but Ie s common di orders that may po e diagnostic dilemma. These are: Pituitary Microadenoma Pituitary Ma roadenoma Pituitary poplexy Pituitary Physiologic Hyperplasia raniopharyngioma Rathke left y t Tuber inereum Hamartoma Pituitary Stalk Anomalies Lymphocytic Hypophy itis Pituicytoma umerous other entities that may cau e disease in the suprasellar region are includ d in the" ustom Differential Diagnoses" hown in the overview. The e diagno es (such as aneurysm, low-grade astrocytoma of the optic chiasm/ hypothalamus, infections like tuberculosis and meningitis) are discussed fully in Part I under their pecific pathology category.

SECTION2: Sella and Pituitary

Introduction and Overview Sella, Parasellar Anatomy-Imaging

Issues

11-2-4

Congenital Pituitary Stalk Anomalies Tuber Cinereum Hamartoma Rathke Cleft Cyst

11-2-8 11-2-12 11-2-16

Neoplasms Pituitary Microadenoma Pituitary Macroadenoma Pituitary Apoplexy Craniopharyngioma Pituicytoma

11-2-20 11-2-24 11-2-28 11-2-32 11-2-36

Miscellaneous Pituitary Hyperplasia Lymphocytic Hypophysitis

11-2-38 11-2-40

SELLA, PARASELLAR ANATOMY-IMAGING ISSUES

2 4

,- - .. :

.' .,

Coronal graphic shows the sellar region. CNs 3 (solid arrow), 4 (open arrow), VI and V2 (curved arrow) are in the cavernous sinus wall; CN 6 is inside the sinus adjacent to the ICA. '

ITERMINOLOGY Abbreviations

and Synonyms

• Abbreviations o Pituitary gland (Pit) • Adenohypophysis (AH) • Neurohypophysis (NH) • Infundibulum (I), pars intermedia (PI) o Third ventricle (3rd V) o Optic chiasm (OC) o Hypothalamus (H), tuber cinereum (TC) o Mammillary bodies (MB) o Internal carotid artery (ICA) o Cranial nerve (CN) • Synonyms o Pituitary gland = hypophysis cerebri

IIMAGING ANATOMY Internal Structures-Critical

Contents

• Pituitary gland, AH (older term = anterior lobe) o Anatomy • 80% of Pit • Includes pars anterior (pars distalis or glandularis), pars intermedia, pars tuberalis • Wraps anterolaterally around NH o Origin = primitive stomodeum o Function • Acidophil cells: Secrete somato- (STH), lactogenic (LTH) hormones . • Basophil cells: ACTH, TSH, FSH, ICSH, LH, MH • Chromophobe cells: Unknown significance • Pituitary gland, pars intermedia (PI) o Small « 5% of Pit), between adeno", neurohypophysis o Origin = Rathke cleft (buccal ectoderm) o Function: Axons from hypothalamus pass through stalk, terminate, carry releasing hormones to AH • Pituitary gland, NH (older term = posterior lobe)

Coronal T1 C+ MR shows sella at 3T. Note filling defects in CS caused by CNs 3 (solid white arrow), 4 (open arrow), 6 (curved arrow). Meckel cave (black arrow) contains CSF,CN 5.

o Anatomy • Posteromedial 20% of Pit • Includes pars posterior (pars nervosa, posterior or neural lobe), infundibular stem and median eminence of tuber cinereum • Contains pituicytes, hypothalamohypophyseal tract o Origin = embryonic forebrain (diencephalon) o Function: Vasopressin, oxytocin pass from hypothalamus along hypothalamohypophyseal tract in PI, stored in NH

Adjacent Structures • Vessels, cavernous sinus (CS) o ICA, branches • Meningohypophyseal trunk (MHT) supplies CS, tentorium, pituitary • Inferolateral trunk (ILT) supplies tentorium, CNs 3/4/6, Gasserian ganglion, CN V3; extensive anastomoses with ECA • Inferior hypophyseal arteries supply NH • Vessels, suprasellar cistern o Supraclinoid ICA • Superior hypophyseal arteries supply median eminence, stalk, NH • Ophthalmic artery o Circle of Willis (COW); surrounds suprasellar cistern) • Posterior communicating artery • Nerves, CS o Oculomotor nerve (CN 3) = superior lateral dural wall o Trochlear nerve (CN 4) = dural wall below CN 3 o Abducens nerve (CN 6) = inside CS, adjacent to ICA o Trigeminal nerve (CN 5) . • CN Vl = lateral dural wall above CN V2, exits superior orbital fissure as ophthalmic nerve • CN V2 = lateral dural wall below CN 4, exits through foramen rotundum as maxillary nerve o Sympathetic plexus (surrounds cavernous ICA)

SELLA, PARASELLAR ANATOMY-IMAGING

ISSUES

DIFFERENTIAL DIAGNOSIS Pseudolesions

Infectious/inflammatory

• Physiologic hypertrophy (normal) • End-organ failure (e.g., hypothyroidism) • Pit enlargement secondary to venous congestion (intracranial hypotension, dAVF) • "Empty" sella

• • • • •

Congenital

Vascular

• • • • • • • •

• Aneury m • Hemachromatosis

Arachnoid cyst (intra- or suprasellar) Epidermoid cyst, dermoid cyst Rathke cleft cyst, pars intermedia cyst Ectopic H Duplicated stalk/gland Tuber cinereum (hypothalamic) hamartoma Lipoma Cephalocele

• CSF spaces, suprasellar cistern: Contiguous with interpeduncular, ambient cisterns, medial sylvian fissure • CSF spaces, 3rd ventricle: Optic recess (rounded, in front of infundibulum) • Bone, basisphenoid o Sphenoid sinus variably aerated, septated o Spenooccipital synchondrosis o Craniopharyngeal canal (midline, almost vertical conduit in basisphenoid contains dura, some vessels; 10% persist into childhood) • Mamillary bodies • Hypothalamus o Tuber cinereum (around, behind stalk; lacks BBB) o Supraoptic, paraventicular nuclei (secrete vasopressin, oxytocin) • Meninges o Dura (lines sellar floor, forms diaphragm a sellae) o Arachnoid (may protrude inferiorly through diaphragm a sallae)

IANATOMY-BASED

IMAGING

ISSUES I

Key Concepts or Questions • MR generally modality of choice in imaging Pit, hypothalamic disorders • Coronal plane minimizes volume averaging o Begin with 2 mm, small FOV pre contrast Tl-, T2WIs o Center of sella/hypothalamus • 20-30% of microadenomas seen only with "dynamic" MRC+ o Rapid bolus contrast infusion o Scans obtained q 10-12 seconds, sorted by slice

Normal Measurements • Size/height/configuration of normal Pit varies with gender, age o Children = 6 mm o Males, post-menopausal females = 8 mm o Young menstruating females = 10 mm (can bulge upwards) o Pregnant, lactating females = 12 mm

Meningitis (bacterial, fungal, TB) Hypophysitis (lymphocytic) Sarcoidosis, histiocytosis Pseudotumor Para itic cyst (neurocysticercosis)

(causes very hypointense

Pit)

Neoplasm • • • • •

Adenoma (macro-, microadenoma) Craniopharyngioma Astrocytoma Meningioma Metastasis, lymphoma, leukemia

Imaging Pitfalls • Normal variants o Physiologic hypertrophy o "Empty sella" • Protrusion of arachnoid, CSF into sella • Normal pituitary flattened against sellar floor • Rarely symptomatic (may be associated with pseudotumor cerebri) • Anatomic pitfalls o 15-20% of imaged Pits in asymptomatic patients have "filling defects" (pituitary "incidentaloma" cysts, nonfunctioning micro adenomas) o Paramedian ICAs ("kissing carotids") can mimic intra sellar aneurysm, cause mass effect on Pit

I CLINICAL

=

IMPLICATIONS

Clinical Importance • Pituitary dwarfism o Primary AH dysfunction (hypoplasia) o Ectopic NH ("bright spot" in hypothalamus) o Discontinuous or absent stalk • Precocious puberty o Secondary sexual development> 2.5 SD below mean o Central = premature activation of hypothalamic-pituitary-gonadal axis • Neoplasms of hypothalamus/optic chiasm • Tuber cinereum abnormalities (hamartoma) • Infundibulum deviated/foreshortened, thickened o Peripheral = gonadotropin-independent • Central diabetes insipidus o Hypothalamic-neurohypophyseal axis dysfunction • Trauma (post-op, transaction) • Infection/inflammation (meningitis, hypophysitis, granulomatous disease) • Neoplasm (germinoma, metastasis, lymphoma; large mass such as macroadenoma/craniopharyngioma with "stalk effect") • Hypersecretiol) syndromes: Named for hormones (e.g., prolactin with prolactinoma)

SELLA, PARASELLAR ANATOMY-IMAGING ISSUES

2 6

Sagittal graphic shows a normal sella and pituitary gland. Contributions from both anterior; posterior lobes form infundibulum (open arrow). Pars intermedia is indicated by arrow.

I CUSTOM

DIFFERENTIAL DIAGNOSIS

• • • •

Hyperplasia Microadenoma (rare in children) Nonneoplastic cyst (Rathke PI, occasionally colloid) Meningioma (usually extra sellar origin with secondary intra sellar extension) • Craniopharyngioma (truly intrasellar rare)

Suprasellar mass - adult Macroadenoma Meningioma Aneurysm (usually eccentric but can be midline) Metastasis Lymphoma Epidermoid, dermoid cyst (less common)

Suprasellar mass - child • • • • •

Craniopharyngioma (adamantinomatous type) Astrocytoma (optic chiasm, hypothalamus) Germinoma (can be primary but often with pineal) Arachnoid cyst Tuber cinereum hamartoma

Cystic-appearing • • • • •

Infundibular • • • •

intra- or suprasellar mass

Arachnoid cyst Epidermoid cyst Craniopharyngioma Dilated 3rd V (obstructive Pituitary abscess (rare)

Infundibular

• • • •

mass - child

aneurysm

• Infection (CS thrombophlebitis, fungal infection) • Inflammation (Tolosa-Hunt, inflammatory pseudotumor) • Vascular (ICA aneurysm, C-C fistula) • Neoplasm (meningioma, schwannoma, metastasis, lymphoma, hemangioma) • Abscess (rare)

I SELECTED REFERENCES 1.

2. 3. 4.

5.

mass - adult

Ectopic NH Lipoma Dermoid Thrombosed

Cavernous sinus syndrome

hydrocephalus)

Hypophysitis Sarcoidosis Metastasis, lymphoma Pituicytoma (rare)

• Pituitary dwarf • Histiocytosis • Germinoma

• Leukemia

Suprasellar "bright spot" (on T1WI)

Intrasellar mass - all

• • • • • •

I

Sagittal T2WI MR shows normal sella at 3T. Note top to bottom stalk tapering (straight arrow), pointed infundibular recess surrounded by tuber cinereum (curved arrow).

6.

Lee JH et al: Cavernous sinus syndrome: Clinical features and differential diagnosis with MR imaging. AJR 181: 583-90, 2003 Jaconetta G. et al: The spenopetrodival venous gulf: A microanatomical study. J Neurosurg 99: 336-75, 2003 Shin JH et al: MR imaging of central diabetes insipidus: A pictorial essay. Korean J Radiol 2:222-30, 2001 Robinson DH et al: Embolization of meningohypophyseal and inferolateral branches of the cavernous internal carotid artery. AJNR 20: 1061-7, 1999 Bronen RA et al: Magnetic resonance imaging of central precocious puberty. The importance of hypothalamic abnormalities. I]NR 1:145-53, 1995 Renn WH, et al: Microsurgical anatomy of the sellar region. J Neurosurg 43: 288-98, 1975

SELLA, PARASELLAR ANATOMY-IMAGING ISSUES

I IMAGE GALLERY Normal (Left) Sagittal TlWI MR shows normal sella at 3T. Note posterior pituitary "bright spot" (arrow), caused by vasopressin and oxytocin (neurosecretory granules in neurohypophysis). (Right) Sagittal TlWI MR shows 3T image (same case) performed with fat-saturated sequence. Note the clival marrow (curved arrow) suppresses but the posterior pituitary "bright spot" (open arrow) remains.

Normal (Left) Sagittal TI C+ MR shows normal pituitary, infundibulum at 3T with fat-saturation sequence. Note enhancement of the tuber cinereum (open arrow). The stalk normally tapers from top to bottom. (Right) Coronal T2WI MR shows optic chiasm (black arrow), CN 3 (curved arrow), and dot-like fascicles of CN V entering Meckel cave (open arrow). The pituitary gland is isointense with brain. 3T scan.

Normal (Left) Coronal TI C+ MR shows inferior hypophysis with "tuft" of contrast enhancement within the pars intermedia (arrow). The normal pituitary enhances but less strongly than the adjacent cavernous sinus. (Right) Axial T2WI MR shows suprasellar cistern at 3T. Optic recess of 3rd ventricle is round (black arrow) while infundibular recess is more pointed (curved arrow). Note mammillary bodies (open arrow).

2 7

PITUITARY STALK ANOMALIES

2 8

Sagittal Tl WI MR shows ectopic posterior pituitary gland located along tuber cinereum (arrow). Pituitary stalk is absent in this 2 year old with growth failure. Adenohypophysis is small.

o PPE: Anterior pituitary (adenohypophysis) small o DP: Each pituitary gland normal in size • Morphology o PPE: Adenohypophysis AND bony sella small o DP: Each pituitary gland AND bony sella normal in morphology, just laterally located

ITERMINOlOGY Abbreviations

Coronal TlWI MR shows two pituitary glands (arrows). The glands are bright in this newborn due to maternal hormonal influences.

and Synonyms

• Posterior pituitary ectopia (PPE) • Duplicated pituitary gland/stalk (DP)

Definitions • Congenital anomalies of pituitary stalk may indicate potential hypothalamic/pituitary axis malfunction

IIMAGING FINDINGS

Radiographic Findings • Radiography o PPE: Small sella turcica on lateral radiography o DP: Astute may find two fossae on AP view; craniofaciallcraniocervical anomalies common

CT Findings

General Features • Best diagnostic clue o PPE: NO (or tiny) pituitary stalk, ectopic posterior pituitary bright spot (EPPBS) on midline sagittal view o DP: 2 pituitary stalks on coronal view, thick tuber cinereum on midline sagittal view, tubo-mamillary fusion • Tuber cinereum/mamillary bodies fused into single mass • Location o PPE: EPPBS located along median eminence of tuber cinereum or truncated stalk o DP: Paired LATERALstalks, glands, bony fossae • Size

• NECT o PPE: Narrow pituitary fossa & skull base structures, clivus, +/- persistent sphenopharyngeal foramen o DP: Two widely separated pituitary fossae, +/midline basisphenoid cleft or frontonasal dysplasia • CTA o PPE: Medial deviation of juxtasellar/supraclinoid carotid arteries, "kissing carotids" o DP: Duplicated basilar artery, +/- widely separated juxtasellar/supraclinoid carotid arteries

MR Findings • TlWI o PPE: Absent, truncated or thread-like pituitary stalk (axial and coronal); small adenohypophysis

DDx: Pituitary Anomalies

Sella and Pituitary

PITUITARY STALK ANOMALIES Key Facts Terminology

Top Differential Diagnoses

• Posterior pituitary ectopia (PPE) • Duplicated pituitary gland/stalk (DP) • Congenital anomalies of pituitary stalk may indicate potential hypothalamic/pituitary axis malfunction

• PPE: Central Dr; stalk transection; lipoma • DP: Dilated infundibular recess of 3td ventricle ("pseudoduplication"); hamartoma tuber cinereum

Imaging Findings

• Midline CNS anomalies common in both

• PPE: NO (or tiny) pituitary stalk, ectopic posterior pituitary bright spot (EPPBS) on midline sagittal view • DP: 2 pituitary stalks on coronal view, thick tuber cinereum on midline sagittal view, tubo-mamillary fusion • PPE: Medial deviation of juxtasellar/supraclinoid carotid arteries, "kissing carotids" • DP: Duplicated basilar artery, +/- widely separated juxtasellar/supraclinoid carotid arteries

•

•

•

•

• EPPBS located along truncated stalk or median eminence of tuber cinereum • EPPBS USUALLY ton TlWI (phospholipids/secretory granules) • Bright spot may "dim over time" as patient outgrows available hormone levels • Chiari 1 (20%), +/- olfactory hypoplasia, frontal lobe dysgenesis/migration anomalies • +/- Absent septum pellucidum, ocular dysgenesis or hypoplastic optic nerves/chiasm o DP: Mass-like thickening tuber cinereum on sagittal view signals duplicated pituitary axis • Mamillary bodies fused with tuber cinereum into thickened 3rd ventricle (3rd V) floor • Two normal pituitary glands/stalks • Brain anomalies: Callosal dysgenesis, duplicated anterior 3rd V; cleft brain stem; Dandy-Walker • Cranial nerve anomalies: Olfactory nerve and optic nerve hypoplasia • Oral tumors: Epignathus (giant teratoma) or dermoid mixed signal; lipoma t Tl WI T2WI o PPE: Variable signal posterior pituitary bright spot o DP: Normal signal of glands, stalk, fusion mass Tl C+ o BOTH: Stalks & remnants enhance (absent blood-brain barrier) o PPE: Bright spot absent if multiple endocrine anomalies/diabetes insipidus (if so, enhance to find neurohypophysis) MRA o PPE: Supraclinoid carotid arteries medially deviated, "kiss" in midline; rare absent carotid artery/canal o DP: Partial split (common) or total duplication (rare) of basilar artery (BA); widely separated juxtasellar carotid arteries MRV: Defines torcular and straight sinus anomalies if midline posterior fossa anomaly present

Angiographic Findings • Conventional o PPE: Variable deviation "kissing carotids" 37% o DP: Split/duplicated BA, +/- lateral deviation carotids

2

Pathology

9

Clinical Issues • PPE: Short stature (growth hormone deficiency), +/multiple endocrine deficiencies • DP: +/- Facial midline anomalies; oral mass

Diagnostic Checklist • PPE: Assess optic and olfactory nerves, frontal cortex • DP: Oral tumors compromise airway

Imaging Recommendations • Best imaging tool: MRI, multi planar Tl WI • Protocol advice o BOTH: Sagittal and coronal Tl WI of hypothalamic/pituitary axis o PPE: Assess olfactory nerves, anterior frontal lobes with coronal FSE T2WI o DP: 3D CT of skull base & face in selected patients

1[;}IFFHRH~II~11. [;}1~~~1[)81$ PPE:Central 01; stalk transection; lipoma • Central diabetes insipidus (absent posterior pituitary bright spot, but normal location stalk & gland) • Surgical or traumatic stalk transection allows build-up of neurosecretory granules along stump • Bright spot doesn't "fat-sat"; lipoma does

DP: Dilated infundibular recess of 3rd ventricle (HpseudoduplicationH); hamartoma tuber cinereum • Dilated infundibular recess simulates but only one gland and one pituitary • Hamartoma tuber cinereum (TC) has 3rd V floor, but one midline pituitary

duplicated stalk, fossa round mass of stalk/gland

I R~IF'rII[)I1.~~~ General Features • General path comments o PPE: Disorder of midline prosencephalic development; multiple pituitary hormone deficiencies common o DP: Rarely symptomatic from pituitary causes o Embryology-anatomy: PPE • Adenohypophysis grows up from stomodeal ectoderm (Rathke pouch) • Neurohypophysis grows down from diencephalic neuroectoderm, should remain attached by stalk

Sella and Pituitary

10

•

•

•

•

• Antidiuretic hormone & oxytocin transported to posterior pituitary (neurohypophysis) via neurosecretory cells along infundibular stalk • Hypothalamic releasing hormones reach anterior pituitary (adenohypophysis) via infundibular portal system • Anterior pituitary dysfunction in PPE thought to be related to absent infundibulum o Embryology-anatomy: DP • Theory: Duplication prechordal plate and tip of rostral notochord leads to duplicated pituitary primordium Genetics o PPE: Mutations in genes encoding developmental transcription factors allow maldevelopment • HESXl(homeobox gene), PITl, PITX2, LHX3, LHX4, PROPl, SFl, and TPIT o DP: Gene mutation unknown Etiology o PPE: Genetic mutation leads to defective neuronal migration during embryogenesis o DP: Congenital anomaly, presumed genetic duplication of stomodeal origin structures Epidemiology o PPE: 1:4,000 to 1:20,000 o DP: Extremely rare (reported in 20+ patients) Associated abnormalities o Midline CNS anomalies common in both • PPE: +/- Lobar holoprosencephaly, septooptic dysplasia, Joubert syndrome • PPE: +/- Anomalies of structures formed at same time (pituitary, forebrain, eyes, olfactory bulbs) • DP: Callosal dysgenesis, Dandy-Walker spectrum, frontonasal dysplasia • DP: Craniofacial clefting and duplication anomalies: Frontonasal dysplasia; clefts/duplication of skull base, face, mandible, nose, palate o DP: Midline tumors: Oral, nasopharyngeal, palate • Epignathus, teratomas, dermoids, lipomas o DP: Spinal anomalies: Segmentation/fusion anomalies, schisms, hydromyelia, enteric cysts o DP: Rib & cardiac anomalies; Pierre-Robin anomalad

• Clinical profile o PPE: Short stature (growth hormone deficiency), +/multiple endocrine deficiencies • Peak growth hormone levels < 3 g/L more likely to have abnormal MRI • +/- Anosmia, poor vision, seizures (cortical malformations) • Neonatal hypoglycemia or jaundice, micropenis, single central incisor o DP: +/- Facial midline anomalies; oral mass • Face: +/- Hypertelorism or frontonasal dysplasia • Craniocervical segmentation and fusion anomalies • Airway or oral obstruction from pharyngeal tumor

Demographics • Age o PPE: Disorder becomes apparent in childhood with early growth failure o DP: Usually discovered in early infancy during imaging for complicated facial anomalies • Gender o PPE: M > F o DP: F > M • Ethnicity: None identified in either diagnosis

Natural History & Prognosis • PPE: Stable if no pituitary/hypothalamic crises; growth may be normal for a while o Severity and number of hormone deficiencies predicted by degree of hypoplasia of stalk and gland • DP: Usually significant intracranial, upper airway or cranio-cervical malformations, some lethal o Outcome unrelated to pituitary function

Treatment • Assess/treat endocrine malfunction PPE)

(more likely in

Consider • PPE: Assess optic and olfactory nerves, frontal cortex • DP: Oral tumors compromise airway

Gross Pathologic & Surgical Features

Image Interpretation

• PPE: Hypoplastic anterior lobe, truncation or aplasia of stalk; sella may be covered over with dura • DP: Tubo-mamillary fusion; 2 normal glands/stalks

• BOTH: Can miss findings/diagnosis if thick sections (MRI) or fail to evaluate bone algorithms (CT)

Microscopic

Pearls

Features

• PPE: Ectopic pituitary cells in stalk or sphenoid bone • DP o Normal, but duplicated, pituitary glands o Fused tuber cinereum, mamillary bodies and incompletely migrated hypothalamic nuclear cells

1.

2.

3.

Shroff et al: Basilar artery duplication associated with pituitary duplication: A new finding. AJNR24(5):956-61, 2003 Cushman LJ et al: Genetic defects in the development and function of the anterior pituitary gland. Ann Med 34(3):179-91,2002 Hamilton J et al: MR Imaging in idiopathic growth hormone deficiency. AlNR 19:1609-15,1998

Presentation • Most common signs/symptoms o PPE: Short stature o DP: Often unsuspected finding on craniofacial imaging

Sella and Pituitary

Typical (Left) Sagittal graphic shows ectopia of the posterior

pituitary bright spot (arrow) at the distal end of a truncated pituitary stalk. The sella turcica and adenohypophysis are small. (Right) Coronal T1WI MR shows location of posterior pituitary bright spot (arrow) along the median eminence (tuber cinereum). The pituitary stalk is absent.

(Left) Coronal MRA shows marked medial deviation of the juxtasellar/supraclinoid internal carotid arteries in PPE. (Arrow) marks right deviated internal carotid artery. Note dominant left ACA. (Right) Coronal MRA shows partial duplication of the upper basilar artery in an infant with pituitary duplication. Note that each superior cerebellar artery (arrows) arises from its own "basilar" artery.

Typical (Left) Sagittal T1WI MR shows a thickened floor of

sella and also fusion of the tuber cinereum and mamillary bodies, tubo-mamillary fusion. Note absence of a midline sella turcica (arrow). (Right) Coronal T2WI MR shows two pituitary stalks (arrows) in a newborn with midline skull base c1efting. The stalks are normal in size and project below the optic chiasm.

Sella and Pituitary

11

12

Sagittal T7 C+ MR shows nonenhancing sessile mass arising in the hypothalamus and projecting in the posterior suprasellar cistern.

Abbreviations • Hypothalamic

and Synonyms hamartoma,

diencephalic

hamartoma

Definitions • Non-neoplastic congenital heterotopia of gray matter located in region of tuber cinereum, characterized clinically by luteinizing hormone-releasing hormone (LHRH) dependent central precocious puberty at a very young age and/or gelastic seizures

General Features • Best diagnostic clue: Small (about 1 cm), round, nonenhancing mass contiguous with tuber cinereum • Location: Region of tuber cinereum • Size: Variable, few millimeters to giant (3-5 cm) • Morphology: Sessile or pedunculated round mass, similar in density/intensity to gray matter

Radiographic Findings • Radiography: Occasional suprasellar calcifications, eroded dorsum, enlarged sella

CT Findings

Sagittal T2WI MR shows that the lesion (arrow) is slightly bright.

o Homogeneous suprasellar mass • Between the pons/mamillary bodies and posterior aspect of optic chiasm on axial views • Isodense or slightly ~ density to brain • Less common: Cysts, Ca++ • Associated patent craniopharyngeal canal is very rare • CECT: Nonenhancing

MR Findings • TIWI o Isointense or slightly hypointense to gray matter • B/T mammillary bodies and infundibular stalk on coronal and sagittal • Anecdotal cases contain fat or cysts (RARE, look for other diagnosis) • T2WI: Iso or slightly i signal intensity (occasionally i i due to fibrillary gliosis) • PD/Intermediate: Hyperintense to CSF, slightly i signal than gray matter • FLAIR: +/- Bright • Tl C+: Nonenhancing (if enhances, look for other diagnosis) • MRS: (long TE): ~ NAA, minimally i choline; i myoinositol (short TE)

Angiographic Findings • Conventional:

Avascular lesion

• NECT

DDx: Hypothalamic

Astrocytoma

Masses

Chiasm Glioma

Sella

Lipoma

and Pituitary

Craniopharyngioma

TUBER CINEREUM HAMARTOMA Key Facts Terminology

Top Differential

• Non-neoplastic congenital heterotopia of gray matter located in region of tuber cinereum, characterized clinically by luteinizing hormone-releasing hormone (LHRH) dependent central precocious puberty at a very young age and/or gelastic seizures

• Craniopharyngioma • Chiasmatic astrocytoma • Lipoma

Imaging Findings • Best diagnostic clue: Small (about 1 em), round, nonenhancing mass contiguous with tuber cinereum • Isointense or slightly hypointense to gray matter • T2WI: Iso or slightly t signal intensity (occasionally t t due to fibrillary gliosis) • Tl C+: Nonenhancing (if enhances, look for other diagnosis)

Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Thin (3 mm) sagittal and coronal T2 and T1 C+ MR

[DIFFERENTIAL DIAGNOSIS Craniopharyngioma • Most common suprasellar mass in children • Contains increased or decreased signal cysts (90%), Ca++ (90%), enhancement (90%)

Chiasmatic astrocytoma • 2nd most common pediatric suprasellar mass (+/- NFl) • Enhancement heterogeneous and often vigorous; +/optic tract extension

Lipoma • Contains fat

Germinoma • Often multicentric masses: Suprasellar, pineal, thalamus, basal ganglia • Early leptomeningeal metastatic dissemination; precocious puberty

langerhans

lack

cell histiocytosis

• Enhances • Often causes diabetes insipidus

I PATffilOI:.OG¥

Diagnoses

Pathology • Shape and size of lesion reported to predict symptoms • Of histologically verified lesions: 3/4 precocious puberty, 1/2 seizures • Found in up to 33% of patients with precocious puberty

Clinical Issues • Infant with gelastic seizures, precocious puberty

o Embryology: Disturbed embryogenesis between gestational days 33-41 • Genetics o Pallister-Hall syndrome (GLI3 frameshift mutations, chromosome 7p13) • Hamartoma or hamartoblastoma of tuber cinereum • Digital malformations (short metacarpals, syndactyly, polydactyly) • Other midline (epiglottis/larynx) and cardiac/renal/anal anomalies o Often reported with facial or congenital cerebral midline anomalies o Other CNS plus skeletal/visceral syndromes: Cerebroacrovisceral-early lethality, Smith-Lemli-Opitz, Meckel, oro-facial-digital, holoprosencephaly -polydactyly, hydrolethalis, Laurence- Moon- Biedl • Etiology o Neuronal migration anomaly o Pathogenesis of precocious puberty-induced sexual precocity • +/- LHRH granules in hamartoma/connecting axons in some • Activating astroglial-derived factors in tumors may stimulate endogenous LHRH secretion if no intra-tumoral LHRH granules • Epidemiology o Of histologically verified lesions: 3/4 precocious puberty, 1/2 seizures o Found in up to 33% of patients with precocious puberty

Gross Pathologic & Surgical Features

General Features • General path comments o Shape and size of lesion reported to predict symptoms • Large sessile lesions => seizures • Small pedunculated lesions => central precocious puberty (CPP) • In fact, presentation with both seizures and CPP common

• Mature neuronal ganglionic tissue project from hypothalamus, tuber cinereum or mamillary bodies; rarely lie free in interpeduncular fossa • Pedunculated or sessile, rounded or nodular; lack invasion

Microscopic Features • May be considered as heterotopia

Sella and Pituitary

2 13

• Resembles gray matter with neurons similar to hypothalamus • Myelinated/unmyelinated axons and variable amounts of fibrillary gliosis • Rare reports of cysts, necrosis, calcifications and fat • Hamartoblastomas include more primitive undifferentiated cells

Staging, Grading or Classification Criteria 14

• Valdueza classification o Pedunculated, central precocious puberty or asymptomatic • Originates tuber cinereum • Originates mamillary bodies o Sessile, hypothalamus displaced, seizures • More hypothalamic dysfunction and abnormal behavior

• Surgery if failure of medical therapy or rapid growth of lesion o Stereotatic thermocoagulation o Gamma knife surgery • Microsurgical approach with total resection o Good response expected if seizures originate in or near mass o Location of lesion has significant risk of hypothalamic complications

Consider • Hypothalamic astrocytoma, histiocytosis, germ cell tumor (all show some contrast enhancement)

Image Interpretation

Pearls

• Nonenhancing mass in hypothalamus, isointense to gray matter on Tl, slightly 1 signal on T2 images

Presentation • Most common signs/symptoms o Gelastic seizures at onset in majority of patients • Gelastic seizures may also occur in hypothalamic astrocytoma! • Clinical profile o Infant with gelastic seizures, precocious puberty o Precocious puberty, tall, overweight, and advanced bone age o May result in acromegaly • Seizures (gelastic type: Laughing/crying spells) with larger hamartomas • Other seizure types frequent, but only gelastic originate in or near hamartoma and thalamus o Gelastic seizures may progress to partial epilepsy, partial complex seizures, generalized tonic clonic seizures • Patients with seizures have deterioration in behavior (aggression, psychiatric comorbidity) and cognition (speech and learning impairment) • As high as 33% in young patients with central precocious puberty • Rare: May secrete releasing hormone

1.

2.

3.

4.

5.

6.

7.

8.

Demographics • Age: Usually present between 1 and 3 years of age • Gender: No predilection, some report M > F • Ethnicity: No predilection

9.

Voyadzis J M et al: Hypothalamic hamartoma secreting corticotropin-releaing hormone. Case report J Neurosurg 100:212-6, 2004 Kremer S et al. Epilepsy and hypothalamic hamartoma: look at the hand Pallister-Hall syndrome. Epileptic Disord 5:27-30,2003 Martin DD et al. MR imaging and spectroscopy of a tuber cinereum hamartoma in a patient with growth hormone deficiency and hypo gonadotropic hypogonadism. AJNR 24:1177-80,2003 Mullatti N et al. The clinical spectrum of epilepsy in children and adults with hypothalamic hamartoma. Epilepsia 44:1310-19,2003 Luo s et al. Microsurgical treatment for hypothalamic hamartoma in children with precocious puberty. Surg Neurol 57:356-62, 2002 Debeneix C et al. Hypothalamic hamartoma: comparison of clinical presentation and magnetic resonance images. Horm Res 56:12-18, 2001 Tsugo H et al: Hypothalamic hamartoma associated with multiple congenital abnormalities. Two patients and a review of reported cases. Pediatr Neurosurg 29(6):290-6, 1998 Valdueza JM et al: Hypothalamic hamartomas: With special reference to gelastic epilepsy and surgery. Neurosurgery 34(6):949-58, 1994 Boyko OB et al: Hamartomas of the tuber cinereum: CT, MR and pathologic findings. AJNR 12:309-14, 1991

Natural History & Prognosis • Lack of growth; if growth is detected, surgery/biopsy indicated • Pedunculated lesions are less likely to be symptomatic • Sessile lesions are almost always symptomatic • Syndromic patients do poorly, may not su~vive their other malformations

Treatment • Hormonal suppressive therapy (LHRH agonist therapy); treat seizures o Hormonal suppressive therapy is successful in most patients

Sella and Pituitary

Typical (Left) Axial TI C+ MR shows

nonenhancing hamartoma (arrow) in the suprasellar cistern. (Right) Sagittal graphic shows a pedunculated mass (arrow) interposed between the infundibulum anteriorly and the mammillary bodies posteriorly. Mass resembles gray matter. Classic tuber cinereum hamartoma.

Variant

(Left) Coronal TI C+ MR shows a left-sided nonenhancing hamartoma (arrows) in the substance of the hypothalamus. (Right) Axial T2WI MR shows that the mass (arrows) is isointense to gray matter.

Variant

(Left) Sagittal TlWI MR shows a huge tuber cinereum hamartoma. (Right) Axial NECT shows large tuber cinereum hamartoma containing a calcification.

Sella and Pituitary

2 .... 15

16

Coronal graphic shows a typical suprasellar Rathke cleft cyst interposed between the pituitary gland (below) and the optic chiasm (above).

Sagittal T7WI MR shows a well-delineated hyperintense suprasellar mass that is clearly distinct from the pItUitary gland. Rathke cleft cyst was documented at surgery.

• Rathke cleft cyst (RCC)

o Occasionally become very large • May cause expansile intra-/suprasellar • Rare: Erode skull base • Morphology: Well-defined round/ovoid

Definitions

CT Findings

Abbreviations

and Synonyms

• Nonneoplastic cyst arising from remnants embryonic Rathke cleft

• NECT o Well-delineated round/lobulated intra/suprasellar mass • 75% hypo-, 25% mixed iso/hypodense • 10-15% Ca++ (curvilinear, in cyst wall) o Rare: May cause sphenoid sinusitis • CECT: Doesn't enhance

of

General Features • Best diagnostic clue o Nonenhancing, noncalcified intra/suprasellar cyst with intracystic nodule o Uncommon but pathognomonic = "posterior ledge sign" • Upward extension through diaphragma sellae with ledge of tissue overlying posterior lobe • Location o 40% completely intrasellari 60% suprasellar extension o Most RCCs are limited to sella • Between anterior, intermediate lobes • Size

o Most symptomatic diameter

RCCs are between 5-15 mm in

DDx: Cystic Suprasellar/Sellar

Mass

MR Findings • T1WI o Varies with cyst content (serous vs mucoid) • T1 MR = 50% hyper-, 50% hypointense • 75% have hyperintense intracystic nodule • 5-10% mixed (may have fluid-fluid level) • T2WI o Varies with cyst content • T2WI = 70% hyper-, 30% iso-/hypointense • 75% have hypointense intracystic nodule • FLAIR: Hyperintense • T2* GRE: Rarely blooms • T1 C+ o No internal enhancement (+/- enhancing rim of compressed pituitary)

r-

..

-r

l(

.•...

"

K,:\ l..

'J~

·"4'

-

;-: l

Nonneoplastic Cyst

,

..

.!-..• : \

.(

#

Craniopharyngioma

mass

~.

,.

Cystic Microadenoma

Sella and Pituitary

.

1

Epidermoid Cyst

RATHKE CLEFT CYST Key

Facts Pathology

Terminology • Nonneoplastic cyst arising from remnants embryonic Rathke cleft

of

Imaging Findings • Nonenhancing, noncalcified intra/suprasellar cyst with intracystic nodule • Tl MR = 50% hyper-, 50% hypointense • T2WI = 70% hyper-, 30% iso-/hypointense • No internal enhancement (+1- enhancing rim of compressed pituitary) • 75% have small nonenhancing intracystic nodule

Top Differential Diagnoses

• Usually incidental, found in up to 1/3 of all autopsies • Smoothly lobulated, well-delineated intra/suprasellar cystic mass • Content varies from clear CSF-like fluid to thick mucoid material

2

Clinical Issues

17

• Clinical profile: Asymptomatic • Age: Mean age = 45 years

Diagnostic Checklist • Obtaining endocrine profile • Look for hypointense intracystic nodule on T2WI

• Craniopharyngioma (CP) • Cystic pituitary adenoma • Other nonneoplastic cyst

o 75% have small nonenhancing

intracystic nodule

Imaging Recommendations • Best imaging tool: MR • Protocol advice o Sagittal, coronal pre-contrast Tl-, T2WI o "Dynamic" contrast-enhanced coronal T1WIs through sella o Sagittal, coronal thin section T1 C+

I [)IFFERENTIAL

• • •

[)IAGNOSIS

Craniopharyngioma

•

(CP)

• Histologic continuum between RCC, craniopharyngioma • Floccular Ca++ common in craniopharyngioma, rare in RCC • Noncalcified RCC can be indistinguishable from CP on imaging • 90% enhance (nodular, rim) • Cytokeratin profile helps distinguish from RCC (RCCs express cytokeratins 8, 20)

Cystic pituitary adenoma • Ca++ rare • Signal intensity often heterogeneous • Rim or rim + nodular enhancement common

Other nonneoplastic

cyst

• Arachnoid cyst (signal identical to CSF, no intracystic nodule) • Epidermoid cyst (25% show mild irregular enhancement, Ca++) • Miscellaneous intra sellar cyst (pars intermedia, colloid, dermoid, epidermoid cysts occur) • Rare: Sellar/hypophyseal neurocysticercosis

I PATHOLOGY General Features • General path comments

o One of spectrum of midline sellar/juxtasellar ectodermal cysts o Embryology • Ectodermal origin (persistence of Rathke pouch) • Neuroepithelial or endodermal origin (less likely) Genetics: No known heritable conditions Etiology: Arises from embryonic remnants of Rathke pouch Epidemiology o Common intra/suprasellar nonneoplastic cyst o Usually incidental, found in up to 1/3 of all autopsies Associated abnormalities o Sphenoid sinusitis (rare) o Compression of optic chiasm, hypothalamus

Gross Pathologic & Surgical Features • Smoothly lobulated, well-delineated intra/suprasellar cystic mass o Content varies from clear CSF-like fluid to thick mucoid material

Microscopic Features • Wall = single layer of ciliated cuboidal/columnar epithelium +1- goblet cells o Changes of mixed acute, chronic inflammation may be present • Variable cyst content o Clear or serous, +1- hemorrhage, hemosiderin o Amorphous, inspissated eosinophilic mucicarmine-positive colloid +1- cholesterol clefts o Firm, waxy yellow, inspissated material • Immunohistochemical stains positive for cytokeratin o Express cytokeratins 8, 20

I CUNICAL ISSUES Presentation • Most common signs/symptoms o Most are asymptomatic, found incidentally imaging or autopsy o Symptomatic RCC

Sella and Pituitary

at

18

• 70% pituitary dysfunction (amenorrhea/galactorrhea, diabetes insipidus, panhypopituitarism, hyperprolactinemia) • 45-55% visual disturbances • 50% headache o Other signs/symptoms • Head pain, visual disturbance (less common) • Hypopituitarism, amenorrhea/galactorrhea • Central diabetes insipidus • Clinical profile: Asymptomatic

11.

12.

13. 14.

Demographics • Age: Mean age = 45 years • Gender: Slight female predominance

15.

ciliated craniopharyngioma. Noshuyo Byori. 12(2):97-103, 1995 Graziani N et al: Do the suprasellar neurenteric cyst, the Rathke cleft cyst and the colloid cyst constitute a same entity? Acta Neurochir (Wien). 133(3-4):174-80, 1995 Sumida M et al: Rathke cleft cysts: correlation of enhanced MR and surgical findings. AJNRAm J Neuroradiol. 15(3):525-32, 1994 Meyer JR et al: Giant Rathke cleft cyst. AJNRAm J Neuroradiol. 15(3):533-6, 1994 Lach B et al: Colloid cyst of the third ventricle: a comparative ultrastructural study of neuraxis cysts and choroid plexus epithelium. Ultrastruct Pathol. 16(3):331-49, 1992 Asari S et al: MR appearance and cyst content of Rathke cleft cysts. J Comput Assist Tomogr. 14(4):532-5, 1990

Natural History & Prognosis • Most are stable, don't change in size/signal intensity • Some cysts may shrink/disappear spontaneously • Iso-/hyperintense cysts on T1WI more often cause symptoms • RCCs don't undergo neoplastic degeneration

Treatment • Conservative if asymptomatic • Aspiration/partial excision if symptomatic o Persistent/recurrent cyst formation occurs in approximately 1/3 of patients o May occur many years after surgery

Consider • Obtaining endocrine

profile

Image Interpretation • Look for hypointense

Pearls intracystic nodule on T2WI

1.

Kim JE et al: Surgical treatment symptomatic Rathe cleft cysts: Clinical features and results with special attention to recurrence. JNeurosurg 100:33-40, 2004 2. Xin W et al: Differential expression of cytokeratins 8 and 20 distinguishes craniopharyngioma from rathke cleft cyst. Arch Pathol Lab Med. 126(10):1174-8,2002 3. Kasperbauer JL et al: Rathke cleft cyst: diagnostic and therapeutic considerations. Laryngoscope. 112(10):1836-9, 2002 4. Shin JH et al: MR imaging of central diabetes insipidus: a pictorial essay. Korean J Radiol. 2(4):222-30, 2001 5. Byun WM et al: MR imaging findings of Rathke's cleft cysts: Significance of intracystic nodules. AJNR 21:485-8, 2000 6. Hayashi Y et al: Rathke cleft cyst: MR and biomedical analysis of cyst content. J Comput Assist Tomogr. 23(1):34-8, 1999 7. Saeki N et al: MRI findings and clinical manifestations in Rathke's cleft cyst. Acta Neurochir (Wien) 141:1055-61, 1999 8. Kleinschmidt-DeMasters BK et al: The pathologic, surgical, and MR spectrum of Rathke cleft cysts. Surg Neurol. 44(1):19-26; discussion 26-7, 1995 9. Naylor MF et al: Rathke cleft cyst: CT, MR, and pathology of 23 cases. J Comput Assist Tomogr. 19(6):853-9, 1995 10. Oka H et al: Origin of ciliated craniopharyngioma: pathological relationship between Rathke cleft cyst and

Sella and Pituitary

RATHKE CLEFT CYST

I IMAG

E GALLERY

Typical (Left) Coronal TlWI MR shows a classic RCC that elevates and drapes the optic chiasm. The pituitary gland is normal. (Right) Coronal T2WI MR shows most of the suprasellar mass is isointense with gray matter. Note the focal hypointense nodule (curved arrow), virtually pathognomonic of a RCC.

Variant (Left) Coronal Tl C+ MR shows very large combined intra- & suprasellar cystic mass. Note rim enhancement (curved arrow) with nonenhancing layer of debris (open arrow) within cyst. RCC was found at surgery. (Right) Sagittal Tl C+ MR shows the third ventricle is elevated and draped over the mass.

Other (Left) Sagittal T2WI MR shows a well-delineated extremely hypointense mass (arrow) found incidentally in an asymptomatic patient. Presumed RCC. (Right) Axial gross pathology shows a mucinous-containing RCC (arrow) found incidentally at autopsy (Courtesy E. Tessa Hedley-Whyte, MO).

Sella and Pituitary

2 19

PITUITARY MICROADENOMA

2 20

Coronal graphic shows a small microadenoma (open arrow) that slightly enlarges the right side of the pituitary gland and deviates the infundibulum towards the left.

• CECT: 2/3 of microadenomas appear hypodense normal pituitary on dynamic scans

I TERMINOLOGY Abbreviations

and Synonyms

• Pituitary microadenoma;

I IMAGING

to

MR Findings

prolactinoma

• TlWI o Variable signal intensity • Usually isointense to normal pituitary gland • Can be hyperintense if hemorrhage, necrosis • T2WI: Typically isointense to normal pituitary gland • T2* GRE: May show blooming if hemorrhagic

Definitions • Microadenoma

Coronal T7 c+ MR shows a 3 mm mass (arrow) that exhibits less intense enhancement than the surrounding pituitary gland. Microadenoma in a patient with galactorrhea.

== < 10 mm in diameter

FINDINGS

• T1 C+

General Features • Best diagnostic clue: Intrapituitary lesion that enhances less rapidly than surrounding normal gland • Location o Intrasellar o Rare: Ectopic origin outside pituitary fossa • Sphenoid or cavernous sinus • Pituitary stalk, third ventricle • Size: By definition, microadenomas are < 10 mm in diameter • Morphology: Circumscribed, well-demarcated mass surrounded by crescentic rim of compressed anterior pituitary

CT Findings • NECT: If uncomplicated (no hemorrhage, microadenomas are isodense, invisible

cyst),

o Enhanced scans show 70-90% seen as relatively hypointense, more slowly enhancing than normal pituitary o Beware: 10-30% can be seen only on dynamic contrast-enhanced scans!

Other Modality • Cavernous/inferior negative)

Findings petrosal sinus sampling (10% false

Imaging Recommendations • Best imaging tool: Dynamic contrast-enhanced MR ("keyhole" technique samples central 25% of k-space) • Protocol advice o Coronal thin section Tl Wls obtained during contrast infusion • Scans obtained at 10-15 second intervals following rapid bolus injection

DDx: Intrasellar Mass

Nonneoplastic

Cyst

Nonneoplastic

Cyst

Sella and Pituitary

Pit Hyperplasia

PITUITARY MICROADENOMA Key Facts Top Differential Diagnoses

Terminology • Microadenoma

• Nonneoplastic cyst (Rathke cleft, pars intermedia) • Craniopharyngioma • Pituitary hyperplasia

= < 10 mm in diameter

Imaging Findings • Best diagnostic clue: Intrapituitary lesion that enhances less rapidly than surrounding normal gland • CECT: 2/3 of microadenomas appear hypodense to normal pituitary on dynamic scans • Enhanced scans show 70-90% seen as relatively hypointense, more slowly enhancing than normal pituitary • Beware: 10-30% can be seen only on dynamic contrast-enhanced scans! • Best imaging tool: Dynamic contrast-enhanced MR ("keyhole" technique samples central 25% of k-space)

• At least 3 sections (3 mm or less, no inters lice gap) through pituitary gland, sorted by slice o Time-signal intensity curves through normal, abnormal gland may be helpful

I DIFFERENTIAL

DIAGNOSIS

Nonneoplastic cyst (Rathke cleft, pars intermedia) • Hypo-/hyperintense • No enhancement

to normal gland on Tl-, T2WI

Craniopharyngioma • Completely intrasellar craniopharyngioma is uncommon • May have Ca++ • Displaces/compresses normal pituitary (micro adenoma is contained within gland)

Pituitary hyperplasia • Gland appears slightly, diffusely enlarged • May appear slightly inhomogeneous but usually no discrete foci of hypointensity seen on contrast-enhanced scans

I PATH0 LO~:r¥ General Features • General path comments: Common incidental finding at autopsy (10-20% of cases) • Genetics o No consistent allelic losses or point mutations identified • Two normal copies of POU transcription factor Pit-1 (POUIF1) gene necessary for normal anterior pituitary lobe function o Pituitary tumors can occur as part of MEN1, Carney complex • Etiology o One possible model of pituitary tumorigenesis

2

Pathology • General path comments: Common incidental finding at autopsy (10-20% of cases) • 10-15% of all intracranial tumors • Prolactin-secreting = 30-400/0 of symptomatic adenomas • "Pituitary incidentaloma" (seen in 6-27% of MR scans, common even in children)

Clinical Issues • Clinical profile: Young female with primary or secondary amenorrhea and infertility, galactorrhea

• Hypophysiotrophic hormone excess, suppressive hormone insufficiency, or growth factor excess leads to hyperplasia • Increased proliferation predisposes to genomic instability, adenoma forms o Five endocrine cell types in anterior pituitary (each secretes specific hormone, may develop into microor macro adenoma) • Lactotrophs: Prolactin (PRL) • Somatotrophs: Growth hormone (GH) • Corticotrophs: Adrenocorticotrophic hormone (ACTH) • Thyrotrophs: Thyroid-stimulating hormone (TSH) • Gonadotrophs: Gonadotropins, luteinizing hormone, follicle-stimulating hormone • Epidemiology o 10-15% of all intracranial tumors • 1% of microadenomas are multiple o Prolactin-secreting = 30-40% of symptomatic adenomas o Pathologically, micro adenoma > > > macroadenoma • Most micro adenomas found incidentally (autopsy or imaging) • "Pituitary incidentaloma" (seen in 6-27% of MR scans, common even in children) • 10-20% prevalence in general population (most are nonfunctioning) • Associated abnormalities o Growth hormone secreting adenoma • Acromegaly in adults • Gigantism in adolescents

Gross Pathologic & Surgical Features • Small reddish-pink

nodule

Microscopic Features • Monotonous sheets of uniform cells • Cell type varies, has variable trichrome specific immunohistochemical stains

staining,

Staging, Grading or Classification Criteria • Adenomas are almost always WHO grade 1 • Pituitary carcinoma exceedingly rare

Sella and Pituitary

21

22

• Modified Kovacs and Horvath classification (cell type with tinctorial characteristics and hormones produced) o Growth hormone cell adenoma (chromophobe or acidophil, growth hormone) o Prolactin cell adenoma (chromophobe or acidophil, prolactin) o Mixed GH, prolactin cell adenoma (variable with GH, prolactin) o Acidophil cell adenoma (chromophobe, GH and prolactin) o Mammosomatotroph cell adenoma (acidophil, GH and prolactin) o Corticotroph cell adenoma (basophilic or chromophobe, ACTH) o Thyrotroph cell adenoma (chromophobe, TSH) o Gonadotroph cell adenoma (chromophobe, FSH, LH, alpha subunit in varied combinations) o Nonfunctioning adenoma (chromophobe, scanty or no hormones) o Plurihormonal adenoma (variable, two or three hormones in variable combinations)

Consider • An intra pituitary "filling defect" may be a benign, nonneoplastic cyst as well as an incidental micro adenoma

Image Interpretation

1.

2.

3.

4. 5.

Presentation • Most common signs/symptoms o Asymptomatic/nonfunctioning o Symptoms of secreting tumors vary according to type • Hyperprolactinemia (most common micro adenoma) • Clinical profile: Young female with primary or secondary amenorrhea and infertility, galactorrhea • Noninvasive laboratory tests (dexamethasone suppression, metyrapone stimulation, peripheral ovarian corticotropin-releasing hormone (CRH) stimulation)

6.

Demographics

11.

• Age: Prolactin om a = 20-35 y, GH-secreting adenoma = 30-50 Y • Gender o Prolactinomas typically in females but can occur in males with delayed puberty, primary hypogonadism o Prolactinomas in men usually larger, more often cystic/hemorrhagic

7.

8.

9. 10.

12.

13.

Natural History & Prognosis

14.

• Benign, slow-growing; many never become symptomatic

15.

Treatment

Pearls

• Microadenomas DO enhance, but more slowly than normal pituitary so dynamic studies are very helpful

Sarlis NJ et al: MR imaging features of thyrotropin-secreting pituitary adenomas at initial presentation. AJRAm J Roentgenol. 181(2):577-82,2003 Simard MF: Pituitary tumor endocrinopathies and their endocrine evaluation. Neurosurg Clin N Am. 14(1):41-54, vi, 2003 Kim LJ et al: Ectopic intracavernous sinus adrenocorticotropic hormone-secreting microadenoma. J Neurosurg 98:1312-7,2003 Hashimotoet al: A novel nonsense mutation in the Pit-1 gene. J Clin Endocrinol Metab 88:1241-7, 2003 Hirsch W et al: Microadenomas of the pituitary gland in children with and without hypophyseal dysfunction in magnetic resonance imaging. J Pediatr Endocrinol Metab. 15(2):157-62,2002 Abe T et al: Evaluation of pituitary adenomas by multidirectional multislice dynamic CT. Acta Radiol. 43(6):556-9,2002 Hirsch W et al: Microadenomas of the pituitary gland in children with and without hypophyseal dysfunction in magnetic resonance imaging. J Pediatr Endocrinol Metab 15:157-62,2002 Ironside JW et al: Pituitary fossa tumors. In: Diagnostic Pathology of Nervous System Tumours, Churchill-Livingstone, London. 465-507, 2002 Rand T et al: Evaluation of pituitary micro adenomas with dynamic MR imaging. Eur J RadioI41:131-135, 2002 Passos VQ et al: Long-term follow-up of prolactinomas. J Clin Endocrin Metab 87:3578-82,2002 Nishioka H et al: Gender-related differences in prolactin secretion in pituitary prolactinomas. Neuroradiol 44:407-10,2002 Ezzat S: The role of hormones, growth factors and their receptors in pituitary tumorigenesis. Brain Patholll: 356-70,2001 Smallridge RC et al: Corticotropin- and thyrotropin-secreting pituitary microadenomas: detection by dynamic magnetic resonance imaging. Mayo Clin Proc. 75(5):521-8, 2000 Nishizawa S et al: Therapeutic strategy for incidentally found pituitary tumors ("pituitary incidentalomas"). Neurosurg 43:1344-50, 1998 Bartynski WS et al: Dynamic and conventional spin-echo MR of pituitary microlesions. AJNR 18:965-72, 1997

• "Incidentaloma": Conservative (clinical, imaging follow-up unless change in size, oph thalmological/ endocrinological evaluation) • Functioning micro adenomas o Medical (bromocriptine, other dopamine agonists such as cabergoline) reduces PRL secretion to normal in 80% o Surgical (rhino septal) curative in 60-90%

Sella and Pituitary

Typical (Left) Coronal T1 C+ MR shows no definite abnormality in this 22 year old female with galactorrhea. The stalk is tilted slightly to the left but no intrapituitary mass can be identified. (Right) Coronal T1 C+ MR shows images from a "dynamic" MR obtained in the same patient. Note area that enhances less rapidly than the normal adjacent gland (arrow). Microadenoma found at surgery.

Typical (Left) Coronal T2WI MR shows a 5 mm isointense intrapituitary mass (arrow). (Right) Coronal T1 C+ MR shows the mass enhances strongly, uniformly. Microadenoma was found at surgery.

Other

.r

:.

lr

~,

'A-

~'e-, f

•

(Left) Coronal T2WI MR shows a well-delineated, cystic-appearing high signal intensity intrapituitary mass. Preoperative diagnosis was Rathke cleft cyst. Mostly cystic microadenoma was found at surgery. (Right) Coronal micropathology shows a normal pituitary gland surrounding a small non functioning microadenoma (curved arrows) that was found incidentally at autopsy (Courtesy j. Townsend, MO).

-

~

j

,,;. ~-'

\

'M

Sella and Pituitary

23

24

Coronal graphic shows pituitary macroadenoma (open arrow). Indentation from diaphragma sella causes "snowman" appearance (curved arrows). Some cystic degeneration & hemorrhage is depicted.

Abbreviations

and Synonyms

• Macroadenoma;

pituitary adenoma; prolactinoma

Definitions • Benign neoplasm of pituicytes in adenohypophysis

Coronal TlWI MR shows a classic pituitary macroadenoma with "snowman" shaped suprasellar extension (arrows). The pituitary gland cannot be identified as separate from the mass.

o "Giant" adenoma = > 4 cm in diameter « 0.5% of adenomas) • Morphology o Most common = "figure-of-eight" or "snowman" • Indentation = dural constriction caused by diaphragm a sellae o Less common = multilobulated margins

CT Findings

General Features • Best diagnostic clue: Sellar mass without separate identifiable pituitary gland; mass IS the gland • Location o Most common = intra- or combined intra/suprasellar • Upward extension of macroadenoma = most common suprasellar mass in adults o Uncommon = giant adenoma • May invade skull base, extend into anterior/middle/posterior fossae • Can mimic metastasis or other malignant neoplasm o Rare = "ectopic" pituitary adenoma • Sphenoid or cavernous sinus, stalk, third ventricle, clivus • Size 0> 10 mm

DDx: Sellar/Suprasellar

Metastasis

• NECT o Variable attenuation • Typical = usually isodense with gray matter (GM) • Cyst formation, necrosis common • Hemorrhage 10%; Ca++ 1-2% o Large adenomas expand sella, may erode floor o Aggressive adenomas extend inferiorly, invade sphenoid, may destroy upper clivus • CECT: Moderate, somewhat inhomogeneous enhancement

MR Findings • TlWI o Usually isointense with GM • Subacute hemorrhage has short T1 • Fluid-fluid levels may occur, especially with pituitary apoplexy o Posterior pituitary "bright spot" (PPBS) displaced into supradiaphragmatic level in 80% of cases o PPBS absent in 20% of large adenomas

Mass

Meningioma

Craniopharyngioma

Sella and Pitu itary

Hypophysitis

PITUITARY MACROADENOMA Key Facts Terminology • Benign neoplasm of pituicytes in adenohypophysis • Best diagnostic clue: Sellar mass without separate identifiable pituitary gland; mass IS the gland • Most common = "figure-of-eight" or "snowman" • Aggressive adenomas extend inferiorly, invade sphenoid, may destroy upper clivus • Usually isointense with GM • Most show early, intense but heterogeneous enhancement

Top Differential Diagnoses

•

• • •

•

• Gross cavernous sinus invasion at autopsy in 5-10%, microscopic in 45%

Clinical Issues • 75% are endocrinologically with type)

active (symptoms vary

Diagnostic Checklist • Check PRL levels in male with giant invasive skull base mass; it may be a giant adenoma! • No matter how aggressive/invasive it looks, pituitary tumors are almost never malignant

sellae)

o Cavernous sinus (CS) invasion difficult to determine (medial wall is thin, weak) o Cannot distinguish invasive benign adenoma from pituitary carcinoma (exceedingly rare) T2WI o Most common = isointense with gray matter o Less common • Cysts (hyperintense), hemorrhage (signal varies with age) • Densely-granulated GH-producing adenomas are often hypointense o Uncommon = high signal along optic tracts • Seen with 15-20% of adenomas that touch/compres's optic pathway FLAIR: Hyperintense to brain, gray matter T2* GRE: Blooms if hemorrhage present T1 C+ o Almost all macroadenomas enhance • Most show early, intense but heterogeneous enhancement • Some macro adenomas (thyrotropin-secreting adenomas; necrotic adenomas) are hypo enhancing • Subtle/mild dural thickening ("tail") present in some cases MRA: ICAs often displaced, encased (20%) but rarely occluded

Angiographic Findings • Conventional o Cavernous ICA may be displaced laterally, narrowed; occlusion rare o Suprasellar extension splays supraclinoid ICAs, anterior choroidal arteries laterally

Other Modality Findings • Cavernous/inferior petrosal sinus sampling may be helpful in evaluating ACTH-dependent Cushing syndrome

Imaging Recommendations • Best imaging tool o Thin-section MR

hypophysitis

Pathology

Imaging Findings

• Pituitary hyperplasia • Aneurysm • Meningioma (diaphragma

• Metastasis • Lymphocytic

o Multislice multidetector-row dynamic CT useful for patients in whom MR imaging is not available • Protocol advice: MR without, with dynamic contrast-enhanced sequences

I ~IFFERIHsIHI0I~E ~I~~~~BIB Pituitary hyperplasia • 25-50% of females 18-35 years have upwardly convex pituitary o Usually < 10 mm unless pregnant, lactating o Homogeneous enhancement o Normal pituitary function • Can occur with end-organ failure (e.g., ovarian, thyroid) • If prepubescent female or young male has "adenoma-looking" pituitary, do endocrine workup!

Aneurysm • • • •

Usually eccentric, not directly suprasellar Pituitary gland visible, identified separate from mass "Flow void" common on MR Ca++ more common (rare in adenoma)

Meningioma

(diaphragma sellae)

• Pituitary gland visible, can be identified SEPARATE from mass o Diaphragma sellae identifiable as thin, dark line between mass (above) and pituitary gland (below) • Dural thickening more extensive than with adenoma

Metastasis • Diffuse skull base invasion by adenoma may mimic more ominous disease • Occasionally can see systemic metastases to stalk, pituitary gland

Lymphocytic hypophysitis • Can mimic adenoma clinically, on imaging studies • Most common in peripartum female

Craniopharyngioma • Ca++, cysts more common

Sella and Pituitary

2 25

• Children> adults • Rim/nodular> solid enhancement

General Features

26

• General path comments o Usual growth pattern = bulges upward into suprasellar cistern o Gross cavernous sinus invasion at autopsy in 5-10%, microscopic in 45% o "Capsule" of macro adenoma is normal compressed pituitary gland • Genetics o Allelic loss of chromosome llq in MEN1 region o MEN1 gene (probably tumor suppressor) involved in adenoma formation • Etiology: Same as micro adenoma • Epidemiology o 10-15% of intracranial neoplasms o PRL-secreting = most common (prevalence approximately 500 cases per million) • Associated abnormalities o Acromegaly, gigantism (GH-secreting macro adenomas ) o MEN type 1 (parathyroid, pancreatic tumors with multicentric pituitary adenomas in 50%)

• Pituitary adenomas account for < 6% of intracranial tumors in adolescents, even rarer in children • Approximately 60% are macro-, 40% are micro adenomas • Beware! "Adenoma-like" mass in adolescent/prepubescent males may represent hyperplasia secondary to end-organ failure • Gender: Varies with secretory type; PRL-secreting tumors much more common in females

Natural History & Prognosis • Benign, usually slow but highly variable growth rate o Malignant transformation exceedingly rare • "Giant" adenoma o PRL often> 1000 ng/ml • Metastasizing pituitary adenoma o Occurs but is very rare (both CSF, extra-CNS) • Some adenomas (e.g., clinically silent corticotroph adenomas) behave in more aggressive manner with high recurrence rate o Apoptosis-related proteins (BAcl-2, Bax, p53) related to local control, recurrence

Treatment • Resection (15% recurrence at 8 years, 35% at 20 years) • Other: Medical, stereotaxic radiosurgery, conventional XRT

Gross Pathologic & Surgical Features • Reddish-brown,

lobulated mass

Staging, Grading or Classification Criteria

Consider

• WHO grade I • MIB > 1% suggests early recurrence, rapid regrowth

• Could sellar mass be nonneoplastic (e.g., hyperplasia, hypophysitis, etc)? • Check PRL levels in male with giant invasive skull base mass; it may be a giant adenoma!

Presentation

• No matter how aggressive/invasive it looks, pituitary tumors are almost never malignant

Image Interpretation • Most common signs/symptoms o Endocrine abnormalities • 75% are endocrinologically active (symptoms vary with type) o Visual field defect • 20-25% visual defect/cranial nerve palsy • Bitemporal hemianopsia o Rare = Nelson syndrome • Macroadenoma with elevated ACTH, MSH develops after bilateral adrenalectomy • Clinical profile o Middle-aged female with bitemporal hemianopsia o Less common: Male with impotence, decreased libido, visual disturbance o Rare: Pituitary apoplexy (can be acute, life- threatening)

1.

2. 3. 4.

5. 6.

Demographics • Age o Peak age = 20-40 years o Uncommon = presentation childhood/ adolescence

7.

in

Pearls

Chacko AG et al: The "capsule" of pituitary macroadenomas represents normal pituitary gland, a histopathological study. Br] Neurosurg 17:213-8, 2003 Ironside]W et al: Best practice No 172. Pituitary gland pathology.] Clin Pathol 56:561-8, 2003 Melmed S: Mechanisms for pituitary tumorigenesis: the plastic pituitary.] Clin Invest 112:1603-18, 2003 Bonneville F et al: Preoperative location of the pituitary bright spot in patients with pituitary macroadenomas. A]NRAm] Neuroradiol. 23(4):528-32, 2002 Cattin F et al: Dural enhancement in pituitary macroadenomas. Neuroradiology. 42(7):505-8, 2000 Cappabianca P et al: Pituitary macroadenoma and diaphragma sellae meningioma: differential diagnosis on MRI. Neuroradiology. 41(1):22-6, 1999 Abe T et al: Clinically non secreting pituitary adenomas in childhood and adolescence. Neurosurgery. 42(4):744-50; discussion 750-1, 1998

Sella and Pituitary

PITUITARY MACROADENOMA IIMAGE GALLERY Typical (Left) Coronal T1 c+ MR shows a macroadenoma that enhances strongly, invades the left cavernous sinus, and erodes the sellar floor. An area of lesser enhancement may represent cystic degeneration (arrow). (Right) Coronal NECT shows eroded sella caused by the adenoma (same case as shown on left).

Variant (Left) Sagittal T2WI MR shows an enormous invasive tumor in a middle-aged male. Initial preoperative diagnosis was chordoma but endocrine evaluation disclosed PRL > 1000 ng/ml. Giant macroadenoma. (Right) Coronal T1 C+ MR shows a large macroadenoma with associated cysts (arrows). Enlarged perivascular spaces obstructed by tumor were found at surgery.

Typical (Left) Coronal CECT shows an invasive macroadenoma that contains floccular calcification (arrows). (Right) Coronal gross pathology shows a pituitary macroadenoma discovered incidentally at autopsy. Note "figure-of-eight" configuration (Courtesy E. Tessa Hedley-Whyte, MO).

Sella and Pituitary

2 27

PITUITARY APOPLEXY

2 28

Coronal graphic shows a macroadenoma hemorrhage causing pituitary apoplexy.

with acute

IITERMINOLOGY Abbreviations and Synonyms • Pituitary apoplexy (PA);pituitary necrosis

Definitions • Acute clinical syndrome with headache, visual defects/ophthalmoplegia, altered mental status, variable endocrine deficiencies o Caused by either hemorrhage or infarction of pituitary gland o Pre-existing pituitary macroadenoma common

IMAGING FINDINGS General Features • Best diagnostic clue: Pituitary mass with peripheral enhancement, +/- hemorrhage • Location: Intra- or combined intra- and suprasellar • Size: Variable but typically> 1 cm • Morphology: "Snowman" or "figure-of-eight" intra- and suprasellar mass

CT Findings • NECT o Acute

Coronal T7 c+ MR shows a rim-enhancing intra- and suprasellar mass (arrow) in a patient with pituitary macroadenoma and sudden onset of visual symptoms (Courtesy R. Shin, MO).

• Sellar/suprasellar mass with patchy or confluent hyperdensity • May be associated with subarachnoid hemorrhage o Chronic: "Empty" sella • CECT o Minimal or no enhancement • Rim pattern suggestive but not diagnostic of PA

MR Findings • TIWI o Early acute: Enlarged gland, iso/hypointense with brain o Late acute/subacute: Hyperintense o Chronic: Hypointense • "Empty" sella (filled with CSF) • Small isointense pituitary remnant • T2WI o Acute • Enlarged, hypointense (hemorrhagic) or hyperintense (nonhemorrhagic) pituitary • Acute compression of hypothalamus, optic chiasm may cause hyperintensity along optic tracts o Subacute: Hyperintense o Chronic: Hyperintense ("empty" sella filled with CSF) • FLAIR o Acute: Hyperintense

DDx: Sellar/Suprasellar Mass

Pituitary Hemorrhage

Thrombosed Aneurysm

Rathke Cleft Cyst

Sella and Pituitary

Craniopharyngioma

PITUITARY APOPLEXY Key Facts Terminology • Acute clinical syndrome with headache, visual defects/ophthalmoplegia, altered mental status, variable endocrine deficiencies

Imaging Findings • Pituitary mass with peripheral enhancement, +/hemorrhage • Sellar/suprasellar mass with patchy or confluent hyperdensity • May be associated with subarachnoid hemorrhage • Early acute: Enlarged gland, iso/hypointense with brain • Late acute/subacute: Hyperintense • Enlarged, hypointense (hemorrhagic) or hyperintense (nonhemorrhagic) pituitary

o Chronic: Hypointense (CSF in "empty" sella suppresses) • T2* GRE: Blooming if blood products present • DWI o Restricted diffusion within adenoma may be early sign of apoplexy o ADC map: Markedly decreased signal intensity • TI C+ o Rim enhancement common o Adjacent dural thickening, enhancement in 50% of cases o Thickening of sphenoid sinus mucosa in 80% of cases

Angiographic

Findings

• Conventional:

Avascular or hypovascular

mass effect

Imaging Recommendations • Best imaging tool: MR • Protocol advice: MR without, with dynamic contrast-enhanced sequences; add GRE sequence, DWI

(non hemorrhagic)

• Clinical course usually subacute/chronic • Predominately supra-, rather than intrasellar • Cysts, small hemorrhagic foci may occur without necrosis

Craniopharyngioma • Ca++, multiple cysts with variable contents and mixed signal intensity common • Can usually identify normal/compressed pituitary distinct from mass

Rathke cleft

2

Top Differential

29

Diagnoses

• Pituitary macroadenoma (nonhemorrhagic) • Primary intrapituitary hemorrhage • Giant thrombosed intrasellar aneurysm

Pathology • Hemorrhagic sellar/suprasellar mass • Nonhemorrhagic (bland) pituitary infarction = swollen, edematous pituitary gland

Pituitary abscess • Rare • May be difficult to distinguish from bland (ischemic) infarction on imaging studies • Clinical signs of infection may be absent

Primary intrapituitary

hemorrhage

• Hemorrhage into nonadenomatous tissue is rare • Has been reported with infection (hantavirus), other neoplasms (germinoma)

Giant thrombosed

intrasellar aneurysm

• Acute thrombosis can present with panhypopituitarism, SAH • Patent aneurysm shows typical "flow void" on MR • Partially/completely thrombosed aneurysm may show mixed age laminated clot • Rare

I PATl-Uj) lOG~ General Features

I DIFFERENTIAL DIAGNOSIS Pituitary macroadenoma

• Acute compression of hypothalamus, optic chiasm may cause hyperintensity along optic tracts • Chronic: Hyperintense ("empty" sella filled with CSF) • Restricted diffusion within adenoma may be early sign of apoplexy • Rim enhancement common

cyst

• Proteinaceous fluid may be hyperintense, mimic hemorrhage • Cyst usually identifiable as separate from pituitary gland • Minimal/no enhancement • Clinical symptoms subacute/chronic

• General path comments: Both hemorrhagic and ischemic pituitary apoplexy typically occur in pre-existing macro adenoma • Genetics: Rare - MENI syndrome • Etiology o Hemorrhagic or ischemic pituitary infarction o Pre-existing macroadenoma common but PA can occur with normal pituitary gland • Epidemiology o PA occurs in approximately 1% of macro adenomas o Other reported clinical risk factors • Anticoagulation • Endocrinologic testing (dynamic pituitary function tests) • Radiation, bromocriptine therapy for existing macroadenoma • Trauma, surgery (especially cardiac) • Peri- or postpartum state

Sella and Pituitary

• Elevated estrogen levels (pregnancy, exogenous hormones) • Diabetes • Associated abnormalities o Pre-existing macroadenoma in 65-90% of PA cases o Multiple acute endocrine insufficiencies (pituitary, adrenal)

Gross Pathologic & Surgical Features 30

• Hemorrhagic sellar/suprasellar mass • Nonhemorrhagic (bland) pituitary infarction swollen, edematous pituitary gland

Microscopic

o Giant intra sellar aneurysm o Craniopharyngioma or Rathke cleft cyst with high protein content

Image Interpretation

Pearls

• Look for pituitary gland separate/distinct from mass (PA unlikely) • Rim-enhancement in a "snowman" shaped sellar/suprasellar mass may represent PA

=

1.

Features

• Pituicytes uniform but shrunken with dark pyknotic nuclei • Most common adenoma = null-cell type

2. 3.

4.

Presentation • Most common signs/symptoms o Headache • 80% have panhypopituitarism • Visual impairment, ophthalmoplegia common o Other signs/symptoms • Life-threatening pituitary insufficiency, acute adrenal crisis • Hypovolemia, shock, disseminated intravascular coagulation o Rare: Sheehan syndrome • Common: Loss of anterior pituitary hormone function long after index pregnancy (up to 15-20 years later) • Less common: Acute (peripartum) presentation • Clinical profile: Male with pituitary adenoma or post-/peripartum female with hypovolemia, shock

5. 6.

7.

8.

9. 10. 11. 12. 13.

Demographics • Age o Mean age = 57 years o Rare < 15 years • Gender: M:F = 2:1

14. 15.

Natural History & Prognosis • Varies from clinically benign event to catastrophic presentation with permanent neurologic deficits or death • Long-term pituitary insufficiency common in survivors

16. 17.

Chen Z et al: Pituitary apoplexy presenting as unilateral third cranial nerve palsy. Anesth Analg 98:46-8, 2004 Rogg]M et al: Pituitary apoplexy: Early detection with diffusion-weighted MR imaging. A]NR 23:1240-5,2002 Lust K et al: Sheehan's syndrome: Acute presentation with hyponatraemia and headache. Aust NZ] Obstet Gynaecol 41:348-351,2001 Arita K et al: Thickening of sphenoid sinus mucosa during the acute stage of pituitary apoplexy.] Neurosurg 95:897-901,2001 Scully RE et al: Case records of the Massachusetts General Hospital: Pituitary apoplexy. NE]M 344:1536-42, 2001 Lange M et al: A rare fatal course of disease in a patient with spontaneous pituitary apoplexy. Case report and literature review. Neurosurg Rev 22:163-9, 1999 Otsuka F et al: Pituitary apoplexy induced by a combined anterior pituitary test: Case report and literature review. Endocr]. 45:393-8, 1998 Pliam MB et al: Pituitary adenomas complicating cardiac surgery: summary and review of 11 cases.] Card Surg 10:125-32, 1995 Sugita S et al: A case of pituitary apoplexy in a child. Surg Neurol 43:154-7, 1995 Suh DC et al: Pituitary hemorrhage as a complication of hantaviral disease. A]NR 16:175-8, 1995 Fernandez-Real]-M et al: Pituitary apoplexy into nonadenomatous tissue. Am] Med Sci 310:68-70,1995 Lavallee G et al: MR of nonhemorrhagic postpartum pituitary apoplexy. A]NR 16:1939-41, 1995 Fernandez-Real]M et al: Giant intrasellar aneurysm presenting with panhypopituitarism and subarachnoid hemorrhage: case report and literature review. Clin Investig 72:302-6, 1994 Bills DC et al: A retrospective analysis of pituitary apoplexy. Neurosurg 33:602-9, 1993 Saito K et al: Primary chronic intra sellar hematoma. Acta Neurochir (Wien) 114:147-50, 1992 Vidal E et al: Twelve cases of pituitary apoplexy. Arch Intern Med 152:1893-9, 1992 Kyle CA et al: Subacute pituitary apoplexy: MR and CT appearance.] Comp Asst Tomogr 14:40-4, 1990

Treatment • Options, risks, complications o Early diagnosis, treatment of acute PA necessary to prevent morbidity/mortality • Best results with surgical decompression • Steroids, fluid/electrolyte replacement

Consider • Could a high density/hyperintense intra sellar mass represent something other than PAl

Sella and Pituitary

PITUITARY APOPLEXY IIMAGE GALLERY Typical (Left) Coronal T2WI MR shows a large hypointense pituitary mass in a 56 year old male who presented with acute visual problems. Nonhemorrhagic pituitary necrosis was found at surgery. (Right) Coronal T7 C+ MR shows only a small enhancing focus (arrow), characteristic of a largely necrotic macroadenoma.

(Left) Coronal T2W/ MR shows mixed iso-/hyperintense pituitary mass extending into the cavernous sinus. Partially cystic, necrotic adenoma with scattered hemorrhagic foci was found at surgery. (Right) Coronal T7 C+ MR shows patchy, inhomogeneous enhancement.

Other (Left) Coronal T2WI MR shows a largely "empty" sella (open arrow). Patient had a remote history of Sheehan syndrome with acute pituitary necrosis while pregnant. (Right) Axia/ gross pathology shows a large hemorrhagic macroadenoma (curved arrows) in a patient who presented with acute visual/oss and panhypopituitarism.

Sella and Pituitary

2 31

CRANIOPHARYNGIOMA

2 32

Sagittal graphic shows a predominantly cystic, partially solid, suprasellar mass with focal rim calcifications. Note small intrasellar component and fluid-fluid level.

I TERMINOLOGY Abbreviations

and Synonyms

• Craniopharyngioma (CP), craniopharyngeal tumor, Rathke pouch tumor, adamantinoma

duct

Definitions • Benign dysontogenetic epithelial tumor derived from Rathke pouch epithelium o Two types: Adamantinomatous and papillary

Sagittal T7 C+ MR shows a complex partially cystic suprasellar mass with enhancing rim (curved arrow) and solid components (open arrow). Classic craniopharyngioma.

• Entirely intra sellar (4%) • Often extends into multiple cranial fossae: Anterior (30%), middle (23%), posterior and/or retroclival (20%) o Rare ectopic locations • Optic chiasm, third ventricle • Other: Nasopharynx, pineal gland, sphenoid (sinus, clivus) • Size: Variable; often large at presentation (> 5 cm), occasionally giant • Morphology: Multilobulated and multicystic

Radiographic Findings

IMAGING FINDINGS General Features • Best diagnostic clue o CT Finding: Partially Ca++, partially solid, cystic suprasellar mass in a child o MR Finding: High signal intensity suprasellar mass on pre-contrast Tl WI • Location o Surgical division of CPs into three groups • Sellar • Pre chiasmatic • Retrochiasmatic o Imaging locations of CPs (adamantinomatous type) • Suprasellar (75%) • Suprasellar + intrasellar component (21 %)

• Radiography: Lateral skull: Amorphous sellar and suprasellar Ca++ , sellar enlargement, dorsum sella and clinoid erosion

CT Findings • NECT o Adamantinomatous type • 90% mixed solid (iso-), cystic (hypodense) • 90% calcify o Papillary type: Often solid, isodense, rarely calcifies • CECT: 90% enhance (solid = nodule + rim = capsule) • CTA: Displacement and encasement of circle of Willis

MR Findings • TlWI o Signal varies with cyst contents

DDx: Pediatric Suprasellar Mass

Rathke Cleft Cyst

Arachnoid Cyst

Astrocytoma

Sella and Pituitary

Macroadenoma

CRANIOPHARYNGIOMA Key Facts Terminology

Pathology

• Benign dysontogenetic epithelial tumor derived from Rathke pouch epithelium

• Most common pediatric intracranial tumor of non-glial origin • Approximately 54% of all pediatric sellar/chiasmatic region tumors are CPs

Imaging Findings • CT Finding: Partially Ca++, partially solid, cystic suprasellar mass in a child • MR Finding: High signal intensity suprasellar mass on pre-contrast T1WI • Tl C+: Solid portions enhance heterogeneously, cyst walls enhance strongly

Top Differential Diagnoses • • • •

•

• • • • • • •

Clinical Issues • Clinical profile: Pediatric patient with morning headache, visual defect, short stature • Age: Bimodal age distribution (peak 5-15 Yi papillary CP > SOy) • 64-96% overall 10 year survival

Diagnostic Checklist

Rathke cleft cyst (RCe) Suprasellar arachnoid cyst Hypothalamic/chiasmatic astrocytoma Pituitary adenoma

• Use NECT to detect Ca++ if MR diagnosis is in question

• Short Tl relaxation is the result of high protein content • Classic (adamantinomatous type) = hyperintense cyst + heterogeneous nodule • Less common (papillary type) = isointense solid component T2WI o Cysts = predominately hyperintense o Solid component = heterogeneous (iso/hyperintense, Ca++ portions hypointense) o Hyperintense signal in brain parenchyma adjacent to tumor may indicate • Gliosis, tumor invasion, irritation from leaking cyst fluid • Edema from compression of optic chiasm/tracts PD/lntermediate: Hyperintense cyst contents, heterogeneous soft tissue signal, ~ signal from Ca++ FLAIR: Cyst contents typically hyperintense T2* GRE: Susceptibility effect from calcified components DWI: Variable depending upon the character of cyst fluid Tl C+: Solid portions enhance heterogeneously, cyst walls enhance strongly MRA: Vascular displacement and/or encasement MRS: Cyst contents show broad lipid spectrum (0.9-1.5 ppm)

Angiographic Findings • Conventional: DSA: Avascular, encasing, ICAs displaced laterally, ACAs displaced anteriorly, BA displaced posteriorly

Imaging Recommendations • Best imaging tool: MR, particularly thin sagittal and coronal sequences • Protocol advice: MR without and with contrast, supplement with: FLAIR, GRE, diffusion weighted imaging and MRS

I DIFFERENTIAL DIAGNOSIS Rathke cleft cyst (RCC) • Noncalcified, usually doesn't enhance, less heterogeneous, no solid components • Small RCC may be indistinguishable from the rare intra sellar CP • RCCs express cytokeratin 8,20 (CPs generally don't)

Suprasellar arachnoid cyst • No Ca++, enhancement

Hypothalamic/chiasmatic

astrocytoma

• Solid, or with small cystic/necrotic components • Ca++ rarei robust enhancement common

Pituitary adenoma • Rare in prepubescent children • Isointense with brain, enhances strongly • When cystic and hemorrhagic can mimic CP

(Epi)dermoid tumors • Minimal/no

enhancement

Thrombosed aneurysm • Contains blood products • Look for residual patent lumen, phase artifact

I ~AtTHOlOG¥ General Features • General path comments o Cyst fluid contents are variable • Straw-colored ~ "crankcase" like oily material (blood, protein, cholesterol) o Histopathologic classification according to microscopic pattern of epithelium • Adamantinomatous (usually pediatric), papillary (adult), and mixed o Embryology • Rathke pouch (hypophyseal duct) is an invagination of the primitive stomatodeum

Sella and Pituitary

2 33

34

• Rathke pouch forms the pars tuberalis and adenohypophysis • When Rathke pouch fails to develop normally, it may differentiate into tooth primordia (adamantinomatous CP) or oral mucosa (squamous papillary CP) • Genetics o No known genetic susceptibility (rare reports occur in siblings) o Small subset of CPs are monoclonal tumors, arise from oncogenes at specific loci o Beta-catenin gene mutations found in adamantinomatous CP (genetically distinctive) • Etiology o Two proposed theories • CPs arise from remnants of the craniopharyngeal duct • CPs arise from squamous epithelial cells in the pars tuberalis of the adenohypophysis • Epidemiology o Most common pediatric intracranial tumor of non-glial origin o Comprise 1.2 to 4% of all intracranial tumors across all ages • 6 to 9% of all pediatric intracranial tumors • 0.5 to 2.5 new cases per million per year o Approximately 54% of all pediatric sellar/chiasmatic region tumors are CPs

Gross Pathologic & Surgical Features • Solid tumor with variable cysts • Adamantinomatous cysts often contain thick "machine oil-like" fluid • Epithelial fronds penetrate adjacent hypothalamus/ chiasm

Microscopic

Demographics • Age: Bimodal age distribution (peak 5-15 y; papillary CP> 50 y) • Gender: M = F • Ethnicity: More common in Japanese children

Natural History & Prognosis • Typically a slow growing benign neoplasm • Prognosis based upon o Size of tumor at presentation • > 5 cm, recurrence rate 83% • < 5 cm, recurrence rate 20% o Method of treatment (gross total vs subtotal resection vs biopsy and radiation) o Tumor cell type • 64-96% overall 10 year survival

Treatment • Methods of primary treatment o Radical surgery = gross total resection • Complications = hypothalamic injury, endocrine symptoms, vasa va sorum injury and pseudoaneurysm o Limited surgery = subtotal resection, plus radiation therapy o Biopsy, cyst drainage, and radiation therapy • Treatment for residual or recurrent tumor o Surgery, radiation therapy, or cyst aspiration o Cyst instillation with intracavitary radioisotopes, bleomycin, or other sclerosing agents

Consider

Features

• Adamantinomatous o Multistratified squamous epithelium with nuclear palisading o Nodules of "wet" keratin o Dystrophic Ca++ • Papillary o Sheets of squamous epithelium form pseudopapilla o Villous fibrovascular stroma

• Preoperative ophthalmologic evaluations

Image Interpretation

1.

2.

7% predicts recurrence

3.

Presentation • Most common signs/symptoms: Symptoms vary with location, size of tumor, and age of patient • Clinical profile: Pediatric patient with morning headache, visual defect, short stature • Visual disturbances o Bitemporal hemianopsia • Endocrine disturbances o Growth hormone (GH) deficiency> hypothyroidism > adrenal failure> diabetes insipidus • Hydrocephalus

Pearls

• Use NECT to detect Ca++ if MR diagnosis is in question

Staging, Grading or Classification Criteria • WHO grade I • MIB-1 labeling index>

and endocrine

4.

5.

6.

Srinivasan S et al: Features of the metabolic syndrome after childhood craniopharyngioma. J Clin Endocrinol Metab 89:81-6,2004 Behari S et al: Intrinsic third ventricular craniopharyngiomas: report on six cases and a review of the literature. Surg Neurol. 60(3):245-52; discussion 252-3, 2003 Saeki N et al: MR imaging study of edema-like change along the optic tract in patients with pituitary region tumors. AJNRAm J Neuroradiol. 24(3):336-42, 2003 Barajas MA et al: Multimodal management of craniopharyngiomas: neuroendoscopy, microsurgery, and radiosurgery. J Neurosurg. 97(5 Suppl):607-9, 2002 Fujimoto Y et al: Craniopharyngioma involving the infrasellar region: a case report and review of the literature. Pediatr Neurosurg. 37(4):210-6, 2002 Van Effenterre R et al: Craniopharyngioma in adults and children: a study of 122 surgical cases. J Neurosurg. 97(1):3-11,2002

Sella and Pituitary

CRANIOPHARYNGIOMA IIMAGE GALLERY Typical (Left) Sagittal gross pathology shows classic adamantinomatous craniopharyngioma with mixed solid, cystic components. Note intrasellar extension (curved arrow) (Courtesy R. Hewlett, MO). (Right) Axial NECT shows a low attenuation suprasellar mass with rim (arrow) and globular (curved arrow) CaH. Note fluid-fluid level formed by intracystic keratinaceous debris (open arrow).

(Left) Sagittal TlWI MR shows a complex predominantly cystic suprasellar mass. Tl shortening within the cyst due to machine oi/-like proteinaceous fluid (arrow). (Right) Coronal T2WI MR shows a mixed signal, cystic suprasellar mass with internal hypointense elements representing calcification (arrow).

Variant (Left) Axial NECT shows a predominantly solid, minimally calcified (arrow), suprasellar craniopharyngioma. (Right) Sagittal Tl C+ MR shows a principally cystic, sellar/suprasellar mass with rim-enhancement (arrow).

Sella and Pituitary

35

PITUICYTOMA

2 36

Sagittal graphic shows a pituicytoma involving the infundibular stalk and neurohypophysis. Lobular suprasellar mass without significant compression of the adjacent structures is typical.

• T2WI: Heterogeneously hypointense to isointense • T1 C+: Variable enhancement, typically diffuse

TERMINOLOGY Abbreviations

and Synonyms

Imaging Recommendations

• Granular cell tumor, granular pituicytoma, choristoma, myoblastoma, infundibuloma

• Best imaging tool: High-resolution MR of the sella • Protocol advice: Sag and cor T1, cor T2, post-contrast sag and cor Tl with FS, 3-4 mm slice thickness

Definitions • Rare tumor arising from pituicyte, a specialized glial cell in neurohypophysis and infundibulum

I

• May be indistinguishable;

General Features • Best diagnostic clue: Enhancing sellar or suprasellar mass arising from neurohypophysis or stalk • Location: Typically suprasellar (infundibular); pure intrasellar less common • Size: Variable (1-2 mm to 4 cm) • Morphology: Well-demarcated round or oval mass

CT Findings

Lymphocytic hypophysitis • May involve gland (anterior> posterior) or stalk • Typically pregnant or postpartum females

Pituitary hyperplasia • Typically diffuse gland enlargement

Metastasis • Primary tumor often known; multiple lesions common

I PATHOLOGY General Features

• TlWI o Isointense to hypointense solid mass o Posterior pituitary "bright spot" often absent

Pituitary Adenoma

typically anterior gland

mass; Ca++ rare

MR Findings

DDx: Sellar/Suprasellar

I DIFFERENTIAL DIAGNOSIS Pituitary adenoma

IMAGING FINDINGS

• NECT: Hyperdense sellar/suprasellar • CECT: Homogeneously enhancing

Sagittal T1 C+ MR shows a diffusely enhancing infundibular mass in this 22 year old female with delayed growth and hypopituitarism. Stable imaging over five years, presumed pituicytoma.

• General path comments: Some consider pituicytoma glial tumor separate from granular cell tumors

Mass

Hypophysitis

Pit Hyperplasia

Sella and Pituitary

Metastasis

a

PITUICYTOMA Key Facts Terminology

Top Differential

• Granular cell tumor, granular pituicytoma, choristoma, myoblastoma, infundibuloma • Rare tumor arising from pituicyte, a specialized glial cell in neurohypophysis and infundibulum

• • • •

Imaging Findings

Clinical Issues

• Best diagnostic clue: E.qhancing sellar or suprasellar mass arising from neurohypophysis or stalk

• Visual and endocrine dysfunction • Peak incidence: 5th decade

• Etiology: Arises from pituicytes in the neurohypophysis or infundibulum • Epidemiology o Rare (only 47 symptomatic cases have been reported in literature) o Autopsy series found incidental granular cell aggregates in up to 17% of un selected autopsy cases

I DIAGNOSTIC

2 common

CHECKLIST

Consider • If mass present posteriorly within the gland or involves stalk, consider pituicytoma

I SEl.ECTED REFERENCES

Gross Pathologic & Surgical Features • Well circumscribed, soft to medium consistency with a gray to yellow homogeneous or granular cut surface o Necrosis and cystic degeneration are uncommon o Rarely, tumor infiltrates surrounding structures including optic chiasm and cavernous sinus • Hypervascular tumor at surgery

Microscopic

Diagnoses

Pituitary adenoma Lymphocytic hypophysitis Pituitary hyperplasia Metastasis

Features

• Densely packed polygonal cells with small nuclei and abundant eosinophilic, granular, PAS+ cytoplasm • Perivascular lymphocytic aggregates common

Staging, Grading or Classification Criteria

1.

2.

3. 4. 5.

Katsuta T et al: Distinctions between pituicytoma and ordinary pilocytic astrocytoma. Case report.] Neurosurg 98:404-6, 2003 Figarella-Branger 0 et al: Pituicytomas, a misdiagnosed benign tumor of the neurohypophysis: Report of three cases. Acta Neuropathol104:313-9, 2002 Buhl R et al: Granular-cell tumour: A rare suprasellar mass. Neuroradiology 43:309-12,2001 Brat 0] et al: Pituicytoma: a distinctive low-grade glioma of the neurohypophysis. Am] Surg PathoI24:362-8, 2000 Warzok RW et al: Granular cell tumour of the neurohypophysis. In Kleihues P, Cavenee WK (eds), Tumours of the Nervous System, 247-8, IARCPress, 2000

• WHO grade I

I IMAGE GAl.l.ERY I CLINICAl. ISSUES Presentation • Most common signs/symptoms o Visual and endocrine dysfunction common • Headache, amenorrhea, galactorrhea, decreased libido, infertility, diabetes insipidus, hypopituitarism o May be asymptomatic

Demographics • Age o Peak incidence: 5th decade o No cases reported in a patient less than 20 years old • Gender: M:F = 1:2

Natural History & Prognosis • Benign, slow growing tumor • Regrowth after subtotal resection not uncommon

(Left) Sagittal T7WI MR shows a suprasellar mass in a 35 year old

with visual changes. The hyperintensity is atypical. Note the lack of normal posterior "bright spot." (Right) Sagittal T7 C+ MR shows diffuse enhancement of the suprasellar mass, similar to the adjacent pituitary gland. Biopsy proven pituicytoma (Courtesy B. Chong, MOJ.

Treatment • Surgical resection: Primary therapy; trans sphenoidal approach difficult given tumor vascularity • Inconsistent data regarding radiation therapy

Sella and Pituitary

37

38

Coronal CECT shows diffuse enlargement and enhancement of the pituitary gland with a convex margin in this 42 year old with ovarian failure.

Sagittal T1 C+ MR shows diffuse enlargement of the pituitary gland in this patient with hypothyroidism.

• CECT: Homogeneous pituitary gland

Abbreviations

and Synonyms

enhancement,

similar to normal

MR Findings

• Pituitary hypertrophy

Definitions • Physiologic enlargement of the pituitary gland most commonly related to hypothyroidism or other end-organ failure • May be associated with neuroendocrine neoplasms

• Tl WI: Isointense to remainder of pituitary gland • T2WI: Isointense to remainder of pituitary gland • T1 C+ o Diffusely enhancing gland typical o May cause focal nodular enlargement o Dynamic: Enhances similar to remainder of gland

Imaging Recommendations • Best imaging tool: High-resolution imaging of the sella • Protocol advice: Sag and cor Tl, cor T2, post-contrast sag and cor T1 with FS, 3-4 mm slice thickness

General Features • Best diagnostic clue o Enlarged homogeneously enhancing pituitary gland with convex superior margin o May be nodular, mimic pituitary adenoma • Location: Sella, may extend to suprasellar region and compress adjacent structures • Size: Greater than 10 mm up to 15 mm • Morphology: Enlarged gland with superiorly convex margin

CT Findings • NECT: Noncalcified

Pituitary macroadenoma • May be indistinguishable

Pituitary microadenoma • May be indistinguishable • Enhances slower than normal gland on dynamic study

Lymphocytic hypophysitis pituitary gland enlargement

• Enlarged gland and/or stalk • Pregnant or post-partum females

DDx: Sellar Mass

Macroadenoma

Microadenoma

Hypophysitis

Sella and Pituitary

Ie Hypotension

PITUITARY HYPERPLASIA Key Facts Terminology

Top Differential

• Physiologic enlargement of the pituitary gland most commonly related to hypothyroidism or other . end-organ failure • May be associated with neuroendocrine neoplasms

• • • •

Imaging Findings

Clinical Issues

• Enlarged homogeneously enhancing with convex superior margin

pituitary gland

• Untreated hyperplasia rarely transforms to adenoma • Treat end-organ failure or neuroendocrine tumor

(Ie) hypotension,

dAVFs

Natural History & Prognosis • Untreated hyperplasia

I PA'TH~I..@Cl¥

rarely transforms

to adenoma

Treatment

General Features • General path comments: May be nodular or diffuse • Etiology o Response to endocrinologic stimulation by orthotopic or ectopic production of hypothalamic releasing hormones • Orthotopic: Response to end-organ failure • Ectopic: Related to neuroendocrine tumors o Physiologic hyperplasia occurs in pregnancy and lactation • Epidemiology: Rare condition

Microscopic

2

• Gender: No gender predilection

Venous congestion • Can occur with intracranial

Diagnoses

Pituitary macroadenoma Pituitary microadenoma Lymphocytic hypophysitis Venous congestion

Features

• Nodular hyperplasia characterized by marked expansion of acini, architectural distortion • Diffuse hyperplasia requires formal cell count • Growth hormone (GH) cell hyperplasia usually diffuse, occurs with neuroendocrine tumors o Pancreatic islet cell tumor, pheochromocytoma, bronchial and thyroid carcinoid tumor • Prolactin (PRL) cell hyperplasia: Diffuse> nodular o May be seen with pregnancy & lactation, estrogen treatment, primary hypothyroidism, Cushing disease • Corticotroph hyperplasia: Nodular or diffuse o Associated with Cushing disease, neuroendocrine tumors, untreated Addison disease, idiopathic • Thyrotroph hyperplasia o Long-standing primary hypothyroidism, may have associated PRL hyperplasia • Gonadotroph hyperplasia o Primary hypogonadism at young age: Klinefelter and Turner syndrome

• If related to hypothyroidism, regression after thyroid hormone therapy common • Treat end-organ failure or neuroendocrine tumor

I DIAClN@STIC

CHECKLIST

Consider • Hyperplasia may mimic an adenoma, clinical info can help differentiate • If imaging looks like an adenoma in prepubescent male, consider end-organ failure! • Normal pituitary gland size: Pregnant/lactating females - up to 12 mm; males - up to 8 mm; young females - up to 10 mm

I SELECTED 1.

2.

3.

REFERENCES

Burger PC et al: Surgical Pathology of the Nervous System and Its Coverings. 4th ed. Philadelphia, Churchill Livingstone. 472-3, 2002 Young M et al: Pituitary hyperplasia resulting from primary hypothyroidism mimicking macro adenomas. Br J Neurosurg 13:138-42, 1999 Horvath E et al: Pituitary hyperplasia. Pituitary 1:169-79, 1999

IIMAClE ClALLER¥

I CLINICAL ISSUES Presentation • Most common signs/symptoms: Related to etiology (end-organ failure or neuroendocrine tumor)

Demographics

(Left) Coronal T7WI MR shows nodular hyperplasia and an upward

• Age: Typically adults, rarely occurs in children

convex margin of the pituitary gland in this Cushing disease patient. The mild hypointensity is atypical. (Right) Coronal T7 C+ MR shows diffuse enhancement of the hyperplasia, similar to the pituitary gland.

Sella and Pitu itary

39

40

Sagittal graphic shows lymphocytic hypophysitis. Note thickening of infundibulum as well as infiltration into the anterior lobe of the pituitary gland (open arrow).

Abbreviations

o Thick stalk (> 2 mm + loss of normal "top to bottom" tapering) o +/- Enlarged pituitary gland o 75% show loss of posterior pituitary "bright spot" • T2WI: Iso/hypointense • Tl C+ o Enhances intensely, uniformly o May have adjacent dural or sphenoid sinus mucosal thickening

and Synonyms

• Lymphocytic hypophysitis (LH); adenohypophysitis; primary hypophysitis; stalkitis

Definitions • Idiopathic gland

inflammation

Coronal T1 c+ MR shows an enlarged, uniformly enhancing infundibulum in a peripartum female with visual complaints and pituitary dysfunction. Classic lymphocytic hypophysitis.

of the anterior pituitary

Imaging Recommendations

I·.IMAGINC •••••. F1NOINCS

• Best imaging tool: MR • Protocol advice o Pre-contrast thin section « 3 mm) sagittal, coronal Tl- and T2WIs o Coronal "dynamic" Tl C+ (may show delayed pituitary enhancement)

General Features • Best diagnostic clue: Thick nontapered stalk, +/pituitary mass • Location: Supra-, intrasellar • Size: Usually < lOmm but may be up to 2-3 cms • Morphology: Rounded pituitary gland with infundibulum that appears thickened, nontapering bulbous

CT Findings • NECT: Thick/bulbous stalk, +/- enlarged pituitary gland • CECT: Intense uniform enhancement

MR Findings

or

I DIFFERENTIAL

DIAGNOSIS

Pituitary hyperplasia • Stalk usually normal • Can occur in later stages of pregnancy, post-partum, resembles LH

Macroadenoma

(prolactinoma)

• Diabetes insipidus (DI) is common in LH, rare with adenomas

• TlWI

DDx: Thick Pituitary Stalk

Pituitary Dwarf

Pit Hyperplasia

Sarcoid

Sella and Pituitary

Metastasis

LYMPHOCYTIC HYPOPHYSITIS Key Facts Terminology

Top Differential

• Lymphocytic hypophysitis (LH); adenohypophysitis; primary hypophysitis; stalkitis • Idiopathic inflammation of the anterior pituitary gland

• • • •

Imaging Findings

Clinical Issues

• Best diagnostic clue: Thick nontapered pituitary mass

stalk, +/-

• Posterior pituitary "bright spot" absent or displaced/deformed; sella enlarged/eroded

Diagnoses

Pituitary hyperplasia Macroadenoma (prolactinoma) Metastasis Sarcoid

• Most common impairment

signs/symptoms:

2 Headache, visual

Natural History & Prognosis • Unrecognized, untreated panhypopi tui tarism

Metastasis

LH can result in death from

• Usually known primary (lung, breast, etc)

Treatment

Sarcoid

• Biopsy plus endocrine replacement, corticosteroids • Subtotal surgical resection, chiasm decompression if mass effect but risk is impaired endocrine function

• Evidence for systemic disease often (but not invariably) present • Other granulomatous hypophysitis (Langerhans cell, Wegener) can mimic LH

Lymphocytic infundibula-neurohypophysitis

I DIAG~OSTIC

CHECKIiIST

Consider

• Involves infundibulum, neurohypophysis • Often affects males, presents with DI

• Other findings present (e.g., thickened

Pituitary "dwarf"

Image Interpretation

• Stalk may appear short and "stubby"

• LH can mimic adenoma

I PAIHOIiOG¥

I SELECTED REFERE~CES

General Features

1.

• General path comments: Rare idiopathic inflammatory disorder of anterior pituitary • Etiology: Unknown; no association with systemic autoimmune disorders • Epidemiology: Rare (1-2% of sellar lesions)

2.

3.

meninges)?

Pearls

Flanagan DE et al: Inflammatory hypophysitis - the spectrum of disease. Acta Neurochir (Wien). 144(1):47-56, 2002 Tashiro T et al: Spectrum of different types of hypophysitis: a clinicopathologic study of hypophysitis in 31 cases. Endocr Pathol. 13(3):183-95, 2002 Sato N et al: Hypophysitis: endocrinologic and dynamic MR findings. A]NR Am] Neuroradiol. 19(3):439-44, 1998

Gross Pathologic & Surgical Features • Diffusely enlarged stalk/pituitary

Microscopic

gland

I IMAGE GAIiIiERY

Features

• Acute o Dense infiltrate of B-, T-Iymphocytes, plasma cells, occasionally eosinophils; +/- lymphoid follicles o No granulomas, giant cells or organisms; no evidence for neoplasm • Chronic may demonstrate extensive fibrosis

I CIiI~ICAIi ISSUES Presentation • Most common signs/symptoms: Headache, visual impairment • Clinical profile: Peripartum female with headache, multiple endocrine deficiencies

Demographics • Age: Mean age at presentation • Gender: M:F = 1:8 or 9

for F = 3S y, M

=

4S Y

(Left) Coronal TlWI MR shows a sellar/suprasellar mass in a 42 year old male with diabetes insipidus. Note "figure of eight" configuration identical to macroadenoma. Biopsy was lymphocytic hypophysitis. (Right) Coronal Tl C+ MR shows LH. Note the mass enhances strongly and uniformly. Imaging appearance is indistinguishable from macroadenoma.

Sella and Pituitary

41

PART II SECTION 3 CPA-lAC For sheer anatomic complexity, the region of the cerebellopontine angle and internal auditory canal (CPA-lAC) is second only to the sella. Like the sella, the broad spectrum of normal anatomic structures in the region translates into a wide variety of corresponding pathology. We begin this section with a detailed discussion of normal CPA-lAC anatomy that focuses on the cisternal and intracanalicular segments of the vestibulocochlear nerve (CN 8) and anterior inferior cerebellar artery (AICA). Adjacent normal structures such as the flocculus and choroid plexus that may mimic a mass in the CPA cistern are described, along with anatomy-based imaging issues and potential diagnostic pitfalls. Because clinical symptoms of CN 7 or CN 8 dysfunction provide valuable input for focused imaging, these are also summarized with a brief overview of embryologic events along with the practical implications of their dysembryogenesis. While there are at least two dozen different lesions that have been reported in the CPA-lAC, only a handful are seen with any frequency. One lesion, vestibulocochlear (" acoustic ") schwannoma accounts for well over half of all the abnormalities encountered in this region. We have selected eight representative lesions for discussion, either because of frequency or diagnostic difficulty. These are: Congenital anomalies Lipoma Epidermoid cyst Arachnoid cyst Infectious/inflammatory lesions Ramsay Hunt syndrome Vascular Vascular loop compression Neoplasm Acoustic schwannoma Meningioma Metastases A special custom differential diagnosis, cystic CPA lesions, is presented the anatomic introduction and imaging overview.

in

SECTION 3: CPA-lAC

Introduction and Overview CPA-lAC Anatomy and Imaging Issues

11-3-4

Congenital Lipoma, CPA-lAC Epidermoid Cyst, CPA-lAC Arachnoid Cyst, CPA-lAC

11-3-8 11-3-12 11-3-16

Inflammatory Ramsay Hunt Syndrome

11-3-20

Vascular Vascular Loop Compression,

CPA-lAC

11-3-24

Neoplasms Acoustic Schwannoma Meningioma, CPA-lAC Metastases, CPA-lAC

11-3-28 11-3-32 11-3-36

CPA-lAC ANATOMY AND IMAGING ISSUES

3 4

Axial graphic shows normal dorsal (arrow) & ventral (open arrow) cochlear nuclei in lateral inferior cerebellar peduncle margin. Note cochlear nerve (curved arrow) in anterior CPA cistern.

Axial T2WI MR through inferior lAC shows normal inferior cerebellar peduncle-cochlear nuclei (arrow) cochlear nerve (open arrow) & inferior vestibular nerve (curved arrow). I

ITERMINOLOGY Abbreviations • • • • • • •

and Synonyms

Cerebellopontine angle (CPA) Internal auditory canal (lAC) Cranial nerve 7 & 8 (CN 7 & CN 8) Superior vestibular nerve (SVN) Inferior vestibular nerve (IVN) Anterior inferior cerebellar artery (AICA) CN 8 = vestibulocochlear nerve, acoustic nerve

Definitions • CPA-lAC cistern: CSF fluid space in cerebellopontine angle & internal auditory canal containing CN 7, CN 8 and AICA loop • lAC fundus: Lateral cap of lAC cistern filled with distal cranial nerves & CSF • Cochlear aperture: Bony opening between lAC fundus & cochlea • Modiolus: Hub of cochlea made up of spongy bone, spiral ganglia and proximal nerve fibers of cochlear nerve

•

•

I IMAGING ANATOMY Adjacent Structures • Vestibulocochlear nerve (CN 8): CPA-lAC cistern o Components • Vestibular portion (balance) • Cochlear portion (hearing) o Cochlear nuclei • Dorsal & ventral cochlear nuclei found on lateral surface of inferior cerebellar peduncle (restiform body) • Their location can be accurately determined by looking at high-resolution T2 axial images & identifying inferior cerebellar peduncle contour • These 2 nuclei receive axons from neurons with cell bodies in spiral ganglion in cochlear modiolus o Cochlear nerve portion, CN 8 course

•

•

• Leaves spiral ganglion of cochlea as auditory axons • Travels as cochlear nerve in anterior-inferior quadrant of lAC • Joins SVN & IVN at porus acusticus (opening to lAC) to become vestibulocochlear nerve bundle in CPA cistern • Crosses CPA cistern as posterior nerve bundle (facial nerve is anterior) to enter brainstem at junction of medulla & pons • Entering nerve fibers pierce brainstem, bifurcate, making synapses with both dorsal & ventral cochlear nuclei Nerves orientation in lAC cistern o "Seven-up, coke down" describes situation best o CN 7: Anterosuperior in lAC o Cochlear nerve: Anteroinferior in lAC o Superior vestibular nerve: Posterosuperior in lAC o Inferior vestibular nerve: Posteroinferior in lAC Arteries: CPA-lAC Cistern o Anterior inferior cerebellar artery (AICA loop) • Arises from basilar artery, rises superolaterally into lAC • Continues in lAC as internal auditory artery • May mimic cranial nerve on high-resolution T2 • Supplies inner ear including cochlea, flocculus of cerebellum, anterolateral pons in area of CN nuclei for CNs 5, 7 & 8 Other structures in CPA cistern o Flocculus: Lobule of cerebellum that projects into posterolateral CPA o Choroid plexus: May normally pass from 4th ventricle though foramen of Luschka into CPA cistern Other structures in lAC cistern o Crista falciformis: Horizontal bony projection from lAC fundus • Separates CN 7-SVN above from CN 8-IVN below o Bill's bar: Vertical bony ridge in superior portion lAC fundus • Separates CN 7 from SVN

CPA-lAC ANATOMY AND IMAGING ISSUES DIFFERENTIAL DIAGNOSIS Pseudolesions

• Intracranial

• Asymmetric cerebellar flocculus • Asymmetric choroid plexus • Marrow foci around lAC

Vascular • Aneurysm (vertebrobasilar, PICA, AICA) • Arteriovenous malformation

Congenital • Epidermoid cyst • Arachnoid cyst • Lipoma • eurofibromatosis

pseudotumor

Benign Tumor • • • •

Type 2

Infectious

3

Malignant Tumor

• Meningitis • Cysticercosis

• • • •

Inflammatory • Sarcoidosis

• Not seen normally on CT or MR of this area o Cochlear aperture: Small lAC outlet of CSF at base of cochlea o Meatal foramen: Opening from fundus for CN 7; leads to labyrinthine segment CN 7 o Macula cribrosa: Perforated bone between lAC & vestibule of inner ear

IANATOMY-BASED

Acoustic schwan noma Meningioma Facial nerve schwannoma Choroid plexus papilloma

IMAGING

ISSUES

I

Imaging Pitfalls • Vestibular portion, CN 8 o Seldom provides impetus for imaging CN 8 o When vertigo, dizziness, or imbalance imaged, MR usually normal • Cochlear portion, CN 8 o Principal impetus for imaging CN 8 o Global choice of imaging tool in hearing loss (CT vs MR)

• Bone CT used in trauma, otosclerosis & Paget disease • MR used for all other indications • MR imaging approach to UNCOMPLICATED unilateral sensorineural hearing loss (SNHL) o Screening MR involves high-resolution thin-section T2 MR imaging through CPA-lAC • MR imaging approach to COMPLEX SNHL (unilateral SNHL + other symptoms) o Whole brain & posterior fossa sequences • Begin with whole brain axial T2 ± FLAIR sequences • Conclude with axial & coronal Tl thin-section C+ MR of posterior fossa & CPA-lAC • Remember to visually interrogate following areas for lesions o Restiform body of medulla (area of cochlear nuclei): Look for stroke, tumor, cavernoma & multiple sclerosis o CN 8 in CPA-lAC cistern: Look for acoustic schwannoma, facial nerve schwannoma, meningioma, epidermoid & aneurysm

Metastasis, systemic or subarachnoid Brainstem glioma, pedunculated Ependymoma Melanotic schwan noma

spread

o Membranous labyrinth area of inner ear: Look for intralabyrinthine schwannoma & cochlear otosclerosis

Other Imaging Issues • Normal variants in CPA-lAC o Normal structures, when unusually prominent, trouble radiologist evaluating CPA-lAC o AICA loop flow void on high-resolution T2 MR • Will not prominently enhance on T1 C+ MR • Subtle enhancement in lAC on Tl C+ MR may be mistaken for small acoustic schwannoma o Choroid plexus protruding through lateral recess of 4th ventricle • T1 C+ MR shows enhancing bilateral tear-shaped masses of CPA cistern • Symmetry & characteristic appearance make diagnosis o Cerebellar flocculus is a lobule of cerebellum projecting into posterolateral aspect of CPA cistern • Signal follows intensity of cerebellum on all MR sequences o Marrow space foci in walls of lAC can mimic lAC tumor on Tl C+ MR images • Correlate location of foci with lAC cistern • Bone CT of T-bone may be necessary to identify this normal variant

ICLINICAL IMPLICATIONS Function-Dysfunction • CPA-lAC lesions most commonly present with SNHL o Uncomplicated unilateral SNHL: Patient otherwise healthy & presents with unilateral SNHL o Complicated SNHL: Patient has additional signs & symptoms in addition to unilateral SNHL • Including other cranial neuropathy, long tract signs & headache • Cochlear nerve injury o Hearing loss & tinnitus primary symptoms

CPA-lAC ANATOMY AND IMAGING ISSUES

3

••

6

Axial graphic shows fundal cochlear nerve (arrow) is made up of spiral ganglion axons (open arrows) in modiolus of cochlea. Spiral ganglion also sends axons to Organ of Corti (curved arrow).

Axial T2WI MR shows cochlear nerve in lAC heading to the fundus (arrow) where it goes through cochlear aperture on way to modiolus. Osseous spiral lamina of the cochlea (open arrow).

o If unilateral SNHL present, injury occurred between cochlear membranous labyrinth & cochlear nuclei of inferior cerebellar peduncle of brain stem • Facial nerve injury, CPA-lAC portion o Peripheral facial neuropathy: Including lacrimation, stapedial reflex, anterior 2/3 tongue taste loss & complete loss of muscles of facial expression on side of lesion • CN 7 rarely injured by lesion in CPA-lAC • If lesion in CPA-lAC and CN 7 is out, consider non-acoustic schwannoma causes such as facial nerve schwannoma or metastatic disease o Hemifacial spasm results from vascular loop compression of root exit zone of CN 7 • Rarely CPA mass can cause this symptom • AICA thrombosis o Unilateral SNHL, vestibular disturbances, ataxia, ipsilateral facial weakness & facial anesthesia

ICUSTOM DIFFERENTIAL DIAGNOSISI

IEMBRYOLOGY

I SELECTED REFERENCES

Cystic CPA lesions • Congenital o Epidermoid cyst o Arachnoid cyst • Infectious o Cysticercosis • Vascular o Aneurysm (vertebrobasilar, PICA, AICA) o Venous varix with dural AVF • Benign Tumor o Cystic acoustic schwannoma o Acoustic schwannoma + arachnoid cyst o Cystic meningioma (rare) • Malignant Tumor o Necrotic metastasis, systemic o Cystic ependymoma

Embryologic Events

1.

• lAC forms separately from inner ear & external ear • Forms in response to migration of CN 7 & CN 8 through this area

2.

Practical Implications

3.

• lAC may be absent or present independent of inner, middle or external ear developmental status • lAC size depends on number of nerve bundles migrating through this area at time of lAC formation o Fewer nerves, smaller lAC size o Any of 4 nerves in lAC may be missing o When only one nerve is seen, it is usually facial nerve & lAC is very small

4.

5.

6.

Nowe V et al: High-resolution virtual MR endoscopy of the cerebellopontine angle. AJR. 182:379-84,2004 Kocharian A et al: Hybrid phased array for improved internal auditory canal imaging at 3.0-T MR. J Magn Reson Imaging. 16(3):300-4,2002 Daniels RL et al: Causes of unilateral sensorineural hearing loss screened by high-resolution fast spin echo magnetic resonance imaging: review of 1,070 consecutive cases. Am J Otol. 21(2):173-80, 2000 Sartoretti-Schefer S et al: Spatial relationship between vestibular weighted fast spin-echo MR images. AJNR. 21(5):810-6,2000 Naganawa S et al: High-resolution MR cisternography of the cerebellopontine angle, obtained with a three-dimensional fast asymmetric spin-echo sequence in a 0.35-T open MR imaging unit. AJNR. 20(6):1143-7, 1999 Schmal brock P et al: Assessment of internal auditory canal tumors: a comparison of contrast-enhanced T1-weighted and steady-state T2-weighted gradient-echo MR imaging. AJNR. 20(7):1207-13, 1999

CPA-lAC ANATOMY AND IMAGING ISSUES

I IMAGE GALLERY Normal (Left) Axial T2WI MR through superior lAC reveals normal facial nerve (black arrow) & superior vestibular nerve (open arrow). Curved arrow: AICA loop. White arrow: Normal cerebellar flocculus. (Right) Axial bone CT through superior lAC shows labyrinthine segment of facial nerve canal exiting lAC (arrow) & superior vestibular nerve canal connecting lAC to anterior vestibule (open arrow).

Normal (Left) Axial T2WI MR through inferior lAC shows cochlear nerve (arrow) & inferior vestibular nerve (open arrow) course through high signal CSF. Notice margin of inferior cerebellar peduncle (curved arrow). (Right) Axial bone CT (inferior lAC). Arrow: Cochlear aperture. Open arrow: Inferior vestibular nerve canal leaves fundus. Curved arrow: Singular canal with posterior branch inferior vestibular nerve.

Normal (Left) Graphic of fundus of lAC shows all 4 nerves. Anterior superior is facial nerve (arrow). Anterior inferior is cochlear nerve (open arrow). Superior vestibular & inferior vestibular nerves also seen. (Right) Sagittal oblique T2WI MR through mid-lAC shows all four normal nerves. Arrow: Facial nerve. Open arrow: Cochlear nerve. Curved arrow: Inferior vestibular nerve. Superior vestibular nerve not labeled.

3 7

LIPOMA, CPA-lAC

3 8 Axial graphic of a CPA lipoma (arrow) illustrates the 7th & 8th cranial nerves as well as the AICA vessel (open arrow) passing through the lipoma on their way into the lAC.

Axial TlWI MR CPA lipoma is associated with an intravestibular lipoma (open arrow). Notice 8th cranial nerve (arrow) passing through the CPA lipoma on its way to the internal auditory canal.

• Linear along course of cranial nerves 7 & 8 in CPA • Ovoid with CPA cistern o Large lesions • Broad-based hemispherical shape adherent to lateral margin of pons

[TERMINOLOGY Abbreviations

and Synonyms

• Synonym: Hamartomatous angle (CPA)

lipoma of cerebellopontine

Definitions

CT Findings

• Lipoma, CPA-lAC: Benign, congenital fatty lesion of CPA o Facial & vestibulocochlear nerves pass through lesion on way to internal auditory canal (lAC)

• NECT o Low density CPA mass o Measure mass Hounsfield unit (HU) if uncertain • Hounsfield unit range: -20 to -60 HU • CECT: Lesion does not enhance

[IMAGING FINDINGS

MR Findings

General Features • Best diagnostic clue: Focal benign-appearing CPA mass which follows fat density (CT) & intensity (MR) • Location o Primary location = CPA cistern • lAC alone rarely seen • Concurrent intravestibular deposit may be seen in association with CPA or lAC primary lipoma • Size o 1-5 cm in maximum diameter • May be as small as few millimeters • Morphology o Small lesions

DDx: CPA Hyperintense

White Epidermoid

• TlWI o High signal CPA mass (parallels subcutaneous & marrow fat intensity) • Inner ear noncontiguous second fatty lesion may be present • Inner ear location = vestibule • T2WI o Intermediate "fat-intensity" lesion o Loses signal in parallel with subcutaneous and marrow fat o Chemical shift artifact along frequency encoding direction • STIR: Lesion "disappears" due to STIR inherent fat saturation • FLAIR: Fatty lesion remains high signal

Mass

Neurenteric Cyst

CPA-lAC

Hemo Acoustic

Ruptured Dermoid

LIPOMA, CPA-lAC Key Facts Terminology

Pathology

• Lipoma, CPA-lAC: Benign, congenital fatty lesion of CPA • Facial & vestibulocochlear nerves pass through lesion on way to internal auditory canal (lAC)

• Lipomas occur less frequently in CPA than epidermoid & arachnoid cysts • CPA lipoma is 10% of all intracranial lipomas • Associated abnormalities: Concurrent second fatty lesion may occur in inner ear vestibule

Imaging Findings • Best diagnostic clue: Focal benign-appearing CPA mass which follows fat density (CT) & intensity (MR)

Top Differential • • • • •

Diagnoses

"White" epidermoid cyst Neurenteric cyst Ruptured dermoid cyst Acoustic schwannoma, hemorrhagic Aneurysm

Clinical Issues • Clinical profile: Young adult presenting with slowly progressive unilateral sensorineural hearing loss • No treatment is best treatment • Surgical removal is no longer recommended in most cases

Diagnostic Checklist

9

• Once high signal lesion is seen in CPA on T1 C- MR, use fat saturation sequences to confirm diagnosis

• T1 C+

Ruptured dermoid cyst

o Lesion is already high signal on T1 precontrast images o Use fat saturated T1 C+ sequence • Lesion "disappears" secondary to fat saturation aspect of this MR sequence • No enhancement in region of lesion is present

• Ectodermal inclusion cyst • Original location usually midline • Rupture spreads fat droplets throughout subarachnoid space • Rupture may lead to chemical meningitis

Imaging Recommendations

Acoustic schwannoma,

• Best imaging tool o MR is 1st study ordered when symptoms suggest possibility of CPA mass o CT can easily confirm diagnoses by measuring Hounsfield units if some confusion on MR images persists • Protocol advice o When T1 C+ MR focused to CPA area is anticipated, need at least one precontrast T1 sequence • This T1 C- sequence helps distinguish fatty & hemorrhagic lesions from enhancing lesions • Fatty lesions include lipoma & dermoid • Hemorrhagic lesions with methemoglobin high signal include aneurysm & venous varix o Once high signal is seen on T1 C- sequences, fat saturated sequences distinguish fat from hemorrhage • This approach avoids mistaking lipoma for "enhancing CPA mass"

• Rare manifestation of common lesion • Patchy intraparenchymal signal on T1 C- MR • High signal areas persist even with fat saturated sequences

I DIFFERENTIAL DIAGNOSIS "White" epidermoid

cyst

• Rare imaging presentation of more common lesion • High T1 signal probably secondary to high protein content internal fluid • Shows restriction (high signal) on diffusion MR • Insinuates adjacent CSF spaces & structures

Neurenteric

cyst

• Most common in prepontine cistern • Contains proteinaceous fluid (high signal on T1 CMR)

hemorrhagic

Aneurysm • Ovoid CPA mass with calcified rim (CT) & complex layered signal (MR) • MR signal complex with high signal areas from methemoglobin in aneurysm lumen or wall • Does not enter lAC • CPA aneurysms from PICA> VA > AICA

I PATHOLOGY General Features • General path comments o Congenital lesion o Tendency to infiltrate & splay apart CPA cranial nerves (7, 8) o Embryology-anatomy • Lipomas may rarely be found within lAC or membranous labyrinth (vestibule) • Etiology o Best current hypothesis for lesion formation • Maldevelopment of meningeal precursor tissue (meninx primitiva) • Hyperplasia of fat cells normally within pia • Maldifferentiation of mesoderm into lipocytes rather than arachnoidal cells • Epidemiology o Lipomas occur less frequently in CPA than epidermoid & arachnoid cysts

CPA-lAC

3

LIPOMA, CPA-lAC o Fatty lesion: Lipoma or dermoid o Hemorrhagic lesion: Aneurysm lumen clot or clotted venous varix (dural arteriovenous fistula) o Highly proteinaceous fluid: Neurenteric cyst

o Epidermoid cyst> arachnoid cyst> > lipoma o CPA lipoma is 10% of all intracranial lipomas • Interhemispheric (45%), quadrigeminal/superior cerebellar (25%), suprasellar/interpeduncular (15%), sylvian cisterns (5%) • Associated abnormalities: Concurrent second fatty lesion may occur in inner ear vestibule

Image Interpretation

Pearls

• Once high signal lesion is seen in CPA on T1 C- MR, use fat saturation sequences to confirm diagnosis

Gross Pathologic & Surgical Features • Soft, yellowish mass • May incorporate cranial nerves 7 & 8 with dense adhesions • May be adherent to lateral brainstem

3 10

Microscopic

I SELECTED REFERENCES 1.

Features

• Highly vascularized lipomatous • Mature lipocytes

tissue

2. 3.

I CLINICAL ISSUES

4.

Presentation • Most common signs/symptoms: Mild, unilateral sensorineural hearing loss (60%) • Clinical profile: Young adult presenting with slowly progressive unilateral sensorineural hearing loss • Other signs/symptoms o May be found incidentally on brain CT or MR completed for unrelated reasons o Compression of cranial nerve 8: Tinnitus (40%), vertigo (45%) o Compression of trigeminal nerve root entry zone: Trigeminal neuralgia (15%) o Compression of facial nerve root exit zone: Hemifacial spasm, facial nerve weakness

5.

6.

7. 8.

9. 10.

Demographics

11.

• Age: Range at presentation: 10-40 years • Gender: No gender specificity

12.

Natural History & Prognosis • Usually does not grow over time • Stability confirmed with follow-up examinations • Attempts at complete excision of CPA lipomas may result in injury to cranial nerves 7 & 8 • Conservative symptom-based treatment yields excellent prognosis

13. 14. 15.

Treatment

16.

• No treatment is best treatment • Surgical removal is no longer recommended in most cases o "Cure was often worse than disease" because of entwined cranial nerves 7 & 8 o Historically, 70% of patients operated suffered new postoperative deficits • Surgical intervention only if cranial nerve decompression needed

I DIAGNOSTIC

17. 18.

CHECKLIST

Consider • When a high signal lesion is seen in CPA on T1 C- MR, 3 explanations to consider

CPA-lAC

Gaskin CM et al: Lipomas, lipoma variants, and well-differentiated liposarcomas (atypical lipomas): Results of MRI evaluations of 126 consecutive fatty masses. AJR 182: 733-9, 2004 Dahlen RT et al: CT and MR imaging characteristics of intravestibular lipoma. AJNR 23(8):1413-7,2002 Tankere F et al: Cerebellopontine angle lipomas: report of four cases and review of the literature. Neurosurgery 50(3):626-31,2002 Ruggieri RM et al: Therapeutic considerations in cerebellopontine angle lipomas inducing hemifacial spasm. Neurol Sci 21(5):329-31,2001 Alleyne CH Jr et al: Lipomatous glioneurocytoma of the posterior fossa with divergent differentiation: case report. Neurosurgery 42(3):639-43, 1998 Bigelow DC et al: Lipomas of the internal auditory canal and cerebellopontine angle. Laryngoscope 108(10):1459-69, 1998 Singh SP et al: Lipomas of the internal auditory canal. Arch Pathol Lab Med 120(7):681-3, 1996 Kato T et al: Trigeminal neuralgia caused by a cerebellopontine-angle lipoma: case report. Surg Neurol 44(1):33-5, 1995 Nishizawa S et al: Lipoma in the cerebellopontine angle--case report. Neurol Med Chir 30(2):137-42, 1990 Truwit CL et al: Pathogenesis of intracranial lipoma: an MR study in 42 patients. AJR 155(4):855-64, 1990 Yoshii K et al: Cerebellopontine angle lipoma with abnormal bony structures--case report. Neurol Med Chir 29(1):48-51,1989 Maiuri F et al: Intracranial lipomas. Diagnostic and therapeutic considerations. J Neurosurg Sci 32(4):161-7, 1988 LevinJM et al: Hemifacial spasm due to cerebellopontine angle lipoma: case report. Neurology 37(2):337-9, 1987 Pensak ML et al: Cerebellopontine angle lipomas. Arch Otolaryngol Head Neck Surg 112(1):99-101,1986 Dalley RW et al: Computed tomography of a cerebellopontine angle lipoma. J Com put Assist Tomogr 10(4):704-6, 1986 Rosenbloom SB et al: Cerebellopontine angle lipoma. Surg Neurol 23(2):134-8, 1985 Steimle R et al: Lipoma in the cerebellopontine angle. Surg Neurol 24(1):73-6, 1985 Leibrock LG et al: Cerebellopontine angle lipoma: a review. Neurosurgery 12(6):697-9, 1983

LIPOMA, CPA-lAC I IMAGE GAllERY Typical (Left) Axial TlWI MR shows an ovoid high signal CPA lipoma (arrow). If an enhanced Tl MR is done without fat saturation when lipoma is present, it is possible to mistake this lesion for acoustic schwannoma. (Right) Axial T2* eRE MR shows the lipoma as a dark ovoid mass (arrow). CPA-lAC lipoma can be isolated to the CPA as in this case. It is also possible for the lesion to involve both the lAC & CPA or the lAC alone.

Typical (Left) Coronal TlWI MR demonstrates a focal lipoma in the fundus of the internal auditory canal (arrow). There is no CPA or inner ear component in this case. (Right) Coronal T2WI MR shows the internal auditory canal fundal lipoma (arrow). It is critical for the radiologist to observe the black lines along the medial and lateral edge of the lipoma to avoid calling this lesion an acoustic schwannoma.

Variant (Left) Axial TlWI MR shows atypical CPA lipoma with CPA (arrow), posterior petrous apex (open arrow) & inner ear-vestibule (curved arrow) components. Notice direct connection of CPA, inner ear portions. (Right) Axial T2WI MR reveals all 3 components of a complex CPA lipoma that also involves the petrous apex (open arrow), inner ear (curved arrow). Black line along CPA component is chemical shift (arrow).

CPA-lAC

3 11

EPIDERMOID

CYST, CPA-lAC

3 12 Axial graphic shows large CPA epidermoid cyst in typical "bed of pearls" appearance. Notice 5th (open arrow) and 7th & 8th cranial nerves (arrow) are characteristically engulfed.

ITERMINOlOGY Abbreviations

and Synonyms

• Epidermoid cyst of CPA cistern (EpC-CPA) • Synonyms: Epidermoid tumor, primary cholesteatoma or epithelial inclusion cyst

Definitions • Congenital intradural lesion arising from inclusion of ectodermal epithelial elements during neural tube closure • "White epidermoid" o Epidermoid cyst with high protein content causing high signal on Tl, lower signal on T2 MR sequences

Axial T2WI MR shows the irregular margins (arrows) of a CPA epidermoid cyst. Notice also the 7th cranial nerve engulfed in the anterosuperior margin of the lesion (open arrow).

o Spread vector is cephalad into medial middle cranial fossa • Size o Wide range of sizes reported; 2-8 cm maximum diameter o Significantly larger than acoustic schwannoma at presentation • Morphology o Mass insinuates into cisterns, engulfs cranial nerves & vessels o Margins usually scalloped or irregular • Cauliflower-like margins possible o When large may invade adjacent brainstem ± cerebellum

CT Findings

IIMAGING FINDINGS General Features • Best diagnostic clue o CPA cisternal insinuating mass with high signal on diffusion MR • Engulfs cranial nerves (7th & 8th) and vessels (ArCA, vertebral artery) • Location o Posterior fossa most common site • CPA 75%, 4th ventricle 25%

• NECT o Resembles cerebral spinal fluid (CSF) on NECT o Calcification in 20% usually along EpC-CPA margins o Pressure erosion of adjacent T-bone may occur • CECT o No enhancement is rule • Sometimes margin of cyst minimally enhances • If nodular enhancement seen, consider rare squamous cell carcinoma arising from EpC-CPA o "Dense" epidermoid = rare variant

MR Findings • Tlwr

DDx: CPA Cystic Mass

Arachnoid Cyst

Neurenteric Cyst

CPA-lAC

Cystic Acoustic

EPIDERMOID

CYST, CPA-lAC

Key Facts Terminology • Synonyms: Epidermoid tumor, primary cholesteatoma or epithelial inclusion cyst • Congenital intradural lesion arising from inclusion of ectodermal epithelial elements during neural tube closure

• Neurenteric cyst • Cystic neoplasm

Pathology • 3rd most common CPA mass • 1% of all intracranial tumors • Pearly white mass in CPA

Imaging Findings

Clinical

• CPA cisternal insinuating mass with high signal on diffusion MR • Engulfs cranial nerves (7th & 8th) and vessels (AICA, vertebral artery) • Lack of any attenuation or "incomplete attenuation" on FLAIR is suggestive of EpC-CPA

• Clinical profile: 40 year old patient with minor symptoms has a large EpC-CPA discovered in CPA cistern on MR

Top Differential

Diagnoses

Issues

Diagnostic Checklist • Diffusion MR can also be used effectively to diagnose recurrent EpC-CPA

• Arachnoid cyst

• •

•

•

•

o Isointense or slightly hyperintense to CSF signal o When slightly hyperintense, term "dirty CSF" has been applied o "White epidermoid": High Tl signal T2WI o Isointense to hyperintense compared to CSF o "White epidermoid": Low T2 signal FLAIR o EpC-CPA does not null (attenuate) • Lack of any attenuation or "incomplete attenuation" on FLAIR is suggestive of EpC-CPA • "Incomplete attenuation" refers to a mixed signal lesion on FLAIRwhere part of lesion attenuates, part does not attenuate DWI o High signal on diffusion scans makes diagnosis o High signal on DWI indicates restricted diffusion is present o Foci in surgical bed indicates recurrence Tl C+ o No enhancement is rule o Mild peripheral enhancement occurs in approximately 25% of cases MRA o Vessels of CPA may be displaced or engulfed by EpC-CPA o Artery wall dimension not affected

Imaging Recommendations • Best imaging tool: Brain MR with FLAIR, DWI & enhanced Tl sequences • Protocol advice o Begin with routine enhanced MR imaging o FLAIR & diffusion sequences added to confirm diagnosis ' o Follow-up study looking for recurrence must include FLAIR & diffusion sequences

I DIFFERENTIAL DIAGNOSIS Arachnoid cyst • Pushes broadly on adjacent structures, does not insinuate • T1 & T2 signal follows CSF signal o May be higher signal on T2 because of no CSF pulsations • Fully attenuates on FLAIR sequence (low signal) • Shows no restriction on diffusion weighted imaging (low signal)

Neurenteric

cyst

• Most common pre-pontine cistern in location • Tl high signal (might mimic "white epidermoid") • T2 signal often low

Cystic neoplasm • Cystic meningioma and schwannoma both rare • Ependymoma and astrocytoma pedunculate from brain stem and 4th ventricle respectively • Will show some areas of enhancement on Tl C+ MR

I PATHOLOGY General Features • Etiology o From inclusion of ectodermal elements during neural tube closure • 3rd-5th week of embryogenesis • Results in migration abnormalities of epiblastic cells • Epidemiology o 3rd most common CPA mass o 1% of all intracranial tumors

Gross Pathologic & Surgical Features • • • •

CPA-lAC

Pearly white mass in CPA Surgeons refer to it as "the beautiful tumor" Lobulated, cauliflower-shaped surface features Insinuating growth pattern in cisterns o Engulfs cisternal vessels & nerves

3 13

EPIDERMOID • May become adherent • May cause hyperactive nerve (CN) 5 or 7

Microscopic

dysfunction

o Insinuating CPA cisternal lesion signal is low on Tl, high on T2 (similar to, but not identical to CSF) o Incomplete attenuation on FLAIR & restricted diffusion on DWI is present

of cranial

Features

• Cyst wall: Simple stratified cuboidal squamous epithelium • Cyst contents: Solid crystalline cholesterol, keratinaceous debris o Does not contain hair follicles, sebaceous glands or fat in contrast to dermoid • Grows in successive layers by desquamation from cyst wall

3 14

CYST, CPA-lAC

Image Interpretation

I SELECTED 1.

I CLINICAL

ISSUES 2.

Presentation • Most common signs/symptoms o Principal presenting symptom: Dizziness o Other symptoms: Depend on location, growth pattern • Trigeminal neuralgia (tic douloureux) • Sensorineural hearing loss • Facial neuralgia (hemifacial spasm) • Headache o Symptoms usually present for > 4 years before EpC-CPA is diagnosed • Clinical profile: 40 year old patient with minor symptoms has a large EpC-CPA discovered in CPA cistern on MR

3.

4.

5.

6.

7.

Demographics • Age o Although congenital, presents in adult life o Broad presentation from 20 to 60 years • Peak age = 40 years • Gender: No gender specificity

9.

Natural History & Prognosis

11.

8.

10.

• Slow growing congenital lesions that remains clinically silent for many years • Smaller cisternal lesions are readily cured with surgery • Larger lesions where upward supratentorial herniation has occurred are more difficult to completely remove

12.

13.

Treatment • Complete surgical removal is goal o Total removal possible in < 50% o Near-total removal often better surgical choice • Aggressive total removal may cause significant cranial neuropathy • Used when EpC-CPA capsule is adherent to brainstem & cranial nerves • If recurs, takes many years to grow o Diffusion MR sequence is the key in assessing for recurrence

I DIAGNOSTIC

Pearls

• Diffusion MR imaging sequence is the key to correct diagnosis • Diffusion MR can also be used effectively to diagnose recurrent EpC-CPA

14.

15.

16. 17.

CHECKLIST

Consider • MR diagnoses EpC-CPA when

CPA-lAC

REFERENCES

Lakhdar A et al: Epidermoid cyst of the cerebellopontine angle. A surgical series of 10 cases and review of the literature. Neurochirurgie 49(1):13-24, 2003 Dutt SN et al: Radiologic differentiation of intracranial epidermoids from arachnoid cysts. Otol Neurotol 23:84-92, 2002 Kobata H et al: Cerebellopontine angle epidermoids presenting with cranial nerve hyperactive dysfunction: pathogenesis and long-term surgical results in 30 patients. Neurosurgery 50:276-85,2002 Dechambre S et al: Diffusion-weighted MRI postoperative assessment of an epidermoid tumour in the cerebellopontine angle. Neuroradiology 41:829-31, 1999 Timmer FAet al: Chemical analysis of an epidermoid cyst with unusual CT and MR characteristics. AJNR 19:1111-2, 1998 Talacchi A et al: Assessment and surgical management of posterior fossa epidermoid tumors: report of 28 cases. Neurosurgery 42:242-51, 1998 Ochi M et al: Unusual CT and MR appearance of an epidermoid tumor of the cerebellopontine angle. AJNR 19:1113-5, 1998 Kallmes DF et al: Typical and atypical MR imaging features of intracranial epidermoid tumors. AJR 169:883-7, 1997 Kuzma et al: Epidermoid or arachnoid cyst? Surg Neurol 47:395-6, 1997 Mohanty A et al: Experience with cerebellopontine angle epidermoids. Neurosurgery 40:24-9, 1997 Ikushima I et al: MR of epidermoids with a variety of pulse sequences. AJNR 18:1359-63, 1997 Tien RD et al: Variable bandwidth steady-state free-precession MR imaging: a technique for improving characterization of epidermoid tumor and arachnoid cyst. AJR 164:689-92, 1995 Gao PY et al: Radiologic-pathologic correlation. Epidermoid tumor of the cerebellopontine angle. AJNR 13:863-72, 1992 Altschuler EM et al: Operative treatment of intracranial epidermoid cysts and cholesterol granulomas: report of 21 cases. Neurosurgery 26:606-13, 1990 Yamakawa K et al: Clinical course and surgical prognosis of 33 cases of intracranial epidermoid tumors. Neurosurgery 24:568-73, 1989 Tampieri D et al: MR imaging of epidermoid cysts. AJNR 10:351-6, 1989 DeSouza CE et al: Cerebellopontine angle epidermoid cysts: a report on 30 cases. J Neurol Neurosurg Psychiatry 52:986-90, 1989

EPIDERMOID

CYST, CPA-lAC

IIMAGE GALLERY (Left) Axial T2WI MR shows a high signal lesion with an irregular border along its margin with the brainstem and cerebellum (arrows). Mild penetration of the lAC is seen (open arrow). (Right) Axial FLAIR MR of EpC-CPA reveals "incomplete" fluid attenuation. Notice that the anterior portion has no fluid attenuation (arrow) while posterior portion shows partial attenuation (open arrow).

Variant (Left) Axial T2WI MR shows large Epe-CPA that illustrates the invasive nature of lesion. Notice lesion has invaded cerebellum along a broad front (arrows). AICA loop disappears into mass (open arrow). (Right) OWl MR image of large, invasive EpC-CPA reveals highly characteristic bright signal (arrows) indicating diffusion restriction. This conspicuously high signal signature easily differentiates EpC-CPA from arachnoid cyst and other CPA lesions.

Other (Left) Sagittal graphic of the brainstem shows a EpC-CPA that has involved the prepontine cistern. There it engulfs the basilar artery (arrow). (Right) Cross pathology of resected EpC-CPA. Close-up view shows the lobulated, pearly surface of the cyst.

CPA-lAC

3 15

ARACHNOID CYST, CPA-lAC

3 16 Axial graphic of arachnoid cyst in CPA shows its thin, translucent wall. Notice its "pushing" relationship to 7th & 8th cranial nerves (arrow) and brainstem-cerebellum (open arrows).

I TERMINOLOGY Abbreviations

and Synonyms

• Abbreviation: Arachnoid cyst (Ae) • Synonyms: Primary AC or congenital

AC

Definitions • Definition: Arachnoid or collagen-lined cavities that do not communicate directly with ventricular system or subarachnoid space

I IMAGING FINDINGS

Axial T2WI MR at level of the low CPA shows a high signal ovoid mass (open arrow) flattening the adjacent cerebellar hemisphere. Notice high signal of arachnoid cyst on T2WI similar to CSF.

• May spread into lAC (15%) • Size o Broad size range expected o Pushing lesion that may be very large but asymptomatic o When large, will exert mass effect on adjacent brainstem & cerebellum • Morphology o Sharply demarcated lesion with broad arching margins o Focal lesion that pushes cisternal structures but does not insinuate (d epidermoid cyst)

CT Findings

General Features • Best diagnostic clue o Cystic cisternal mass with imperceptible walls with CSF density (CT) or intensity (MR) o Lesion signal parallels signal of CSF on all MR sequences • Complete fluid attenuation on FLAIR MR imaging • No diffusion restriction on DWI MR Imaging • Location o 33% of all AC occur in posterior fossa • CPA = most common infra tentorial site o Spread patterns • Most remain confined to CPA (60%) • May spread dorsal to brainstem (25%)

• NECT o Density same as CSF o Rare high density from hemorrhage or proteinaceous fluid o Bone changes: Rarely causes pressure erosion of adjacent bone • CECT: No enhancement of cavity or wall

MR Findings • Tl WI: Low signal lesion isointense to CSF • T2WI o High signal lesion isointense to CSF • May have brighter signal than CSF • Fluid within cyst lacks CSF pulsations that decrease CSF signal

DDx: Cystic CPA Mass

Epidermoid Cyst

Neurenteric Cyst

CPA-lAC

Cystic Acoustic

ARACHNOID CYST, CPA-lAC Key Facts Terminology

• Neurenteric

• Abbreviation: Arachnoid cyst (Ae) • Synonyms: Primary AC or congenital AC • Definition: Arachnoid or collagen-lined cavities that do not communicate directly with ventricular system or subarachnoid space

• Embryonic meninges fail to merge • Noncommunicating fluid compartment surrounded by arachnoid is formed that contains CSF • Clinical profile: Adult undergoing unrelated symptoms • 75% of AC occur in children • Most cases require no treatment

• Cystic cisternal mass with imperceptible walls with CSF density (CT) or intensity (MR) • Lesion signal parallels signal of CSF on all MR sequences • 33% of all AC occur in posterior fossa • CPA = most common infratentorial site • Epidermoid

Pathology

Clinical Issues

Imaging Findings

Top Differential

cyst

brain MR for

Diagnostic Checklist • Differentiate AC from epidermoid cyst • Lack of restricted diffusion (high signal) on DWI MR sequence best clue

Diagnoses

cyst

o Well-circumscribed, pushing lesion compresses adjacent brainstem & cerebellum when large • Hydrocephalus seen with only larger CPA AC • Very rare associated finding • FLAIR: Suppresses completely (low signal) with FLAIR • DWI: No restriction (low signal) on diffusion MR • Tl C+ o No enhancement seen o AC wall imperceptible even on contrast-enhanced MR sequences

o Astrocytoma pedunculates from brainstem • Foci of enhancing tumor always present on Tl C+ MR

I PATHOLOGY General Features

I DIFFERENTIAL DIAGNOSIS

• General path comments o Split arachnoid contains CSF o Intracranial AC • Most common location for intracranial AC is middle cranial fossa (50%) • Posterior fossa AC second most common location (33%) • Suprasellar (10%) and other sporadic intracranial locations (7%) • Etiology o Embryonic meninges fail to merge o Noncommunicating fluid compartment surrounded by arachnoid is formed that contains CSF • Epidemiology: Accounts for 1% of intracranial masses • Associated abnormalities: Acoustic schwannoma has AC associated in 0.5%

Epidermoid cyst

Gross Pathologic & Surgical Features

• • • •

• Fluid-containing cyst with translucent membrane • May displace but does not engulf adjacent vessels or cranial nerves

Imaging Recommendations • Best imaging tool: Whole brain MR imaging • Protocol advice o Once AC is suspected on brain MR, add following sequences • FLAIR will show AC as low signal • Diffusion sequence will show low signal • Focused Tl C+ MR will show no enhancement with imperceptible cyst wall

Major lesion of differential concern in setting of AC FLAIR MR: Incomplete attenuation (mixed signal) Diffusion MR: Restriction (high signal) Morphology: Insinuates adjacent CSF spaces & vessels-cranial nerves

Neurenteric

cyst

• Very rare lesion • Usually pre-pontine cistern near midline • Often contains proteinaceous fluid (high signal on T1 MR sequences)

Cystic CPA tumor • Cystic meningioma or schwannoma both unusual variants • Cystic ependymoma or astrocytoma o Ependymoma pedunculates from 4th ventricle via foramen of Luschka

Microscopic Features • Thin wall of flattened but normal arachnoid cells • No glial limiting membrane or epithelial lining is present in AC wall • No inflammation or neoplastic change

I CLINICAL ISSUES Presentation • Most common signs/symptoms o Small AC: Asymptomatic, incidental finding on MR o Large AC: Symptoms from direct compression &/or raised intracranial pressure

CPA-lAC

3 17

ARACHNOID

CYST, CPA-lAC

• Clinical profile: Adult·undergoing brain MR for unrelated symptoms • Other symptoms: Defined by location & size o Vague, non-specific symptoms common o Headache o Dizziness, tinnitus and/or sensorineural hearing loss (SNHL) o Hemifacial spasm or trigeminal neuralgia

Demographics

3 18

5. 6. 7.

• Age o May be first seen at any age • 75% of AC occur in children • Gender: M:F = 3:1

8. 9.

Natural History & Prognosis • Most AC do not enlarge over time o Infrequently enlarge via CSF pulsation through ball-valve opening into AC o Hemorrhage with subsequent decrease in size has been reported • If surgery is limited to AC where symptoms are clearly related, prognosis is excellent • Radical cyst removal may result in cranial neuropathy and/or vascular compromise

Treatment

10. 11. 12. 13. 14.

• Most cases require no treatment • Surgical intervention is highly selective process o Reserved for cases where clear symptoms can be directly linked to AC anatomic location o Endoscopic cyst decompression via fenestration • Least invasive initial approach • Suboccipital retrosigmoid approach preferred

I DIAGNOSTIC

4.

15.

CHECKLIST

Consider • Differentiate AC from epidermoid cyst o Lack of restricted diffusion (high signal) on DWI MR sequence best clue • Determine if symptoms match location of AC before considering surgical treatment

Image Interpretation

Pearls

• AC signal parallels CSF on all MR sequences = key to radiologic diagnosis o Remember T2 signal may be higher than CSF from lack of CSF pulsation • DWI MR sequence will show AC as low signal (no diffusion restriction) lesion • FLAIR MR sequence will show AC as a low signal (fluid attenuated) lesion • No enhancement of AC, including wall, is expected

ISELECTED REFERENCES 1.

2.

3.

Dutt SN et al: Radiologic differentiation of intracranial epidermoids from arachnoid cysts. Otol Neurotol 23(1):84-92, 2002 Ottaviani F et al: Arachnoid cyst of the cranial posterior fossa causing sensorineural hearing loss and tinnitus: a case report. Eur Arch Otorhinolaryngol 259(6):306-8, 2002 Boltshauser E et al: Outcome in children with

CPA-lAC

space-occupying posterior fossa arachnoid cysts Neuropediatrics 33(3):118-21, 2002 Bonneville F et al: Unusual lesions of the cerebellopontine angle: a segmental approach. Radiographies 21(2):419-38, 2001 Gangemi M et al: Endoscopic surgery for large posterior fossa arachnoid cysts. Minim Invasive Neurosurg 44(1):21-4,2001 Ucar T et al: Bilateral cerebellopontine angle arachnoid cysts: case report. Neurosurgery (4):966-8, 2000 Samii M et al: Arachnoid cysts of the posterior fossa. Surg Neurol1999 Apr;51(4):376-82, 1999 Takano S et al: Facial spasm and paroxysmal tinnitus associated with an arachnoid cyst of the cerebellopontine angle--case report. Neurol Med Chir 38(2):100-3, 1998 Choi JU et al: Pathogenesis of arachnoid cyst: congenital or traumatic? Pediatr Neurosurg 29:260-6, 1998 Shukla R et al: Posterior fossa arachnoid cyst presenting as high cervical cord compression. BrJ Neurosurg 12(3):271-3, 1998 Jallo GI et al: Arachnoid cysts of the cerebellopontine angle: diagnosis and surgery. Neurosurgery 40(1):31-7, 1997 Flodmark 0: Neuroradiology of selected disorders of the meninges, calvarium and venous sinuses. AJNR13:483-91, 1992 Higashi S et al: Hemifacial spasm associated with a cerebellopontine angle arachnoid cyst in a young adult. Surg NeuroI37(4):289-92, 1992 Babu R et al: Arachnoid cyst of the cerebellopdntine angle manifesting as contralateral trigeminal neuralgia: case report. Neurosurgery 28(6):886-7, 1991 Weiner SN et al: MRimaging of intracranial arachnoid cysts. JCAT11:236-41,1987

ARACHNOID

I IMAGE

CYST, CPA-lAC

GALLERY

Typical (Left) Axial T2WI MR reveals

a medium size high signal arachnoid cyst in the low right CPA cistern. This lesion can be seen displacing the 9th cranial nerve anteromedially (arrow). Such "pushing" displacement is the rule in arachnoid cyst. (Right) Axial FLAIRMR image demonstrates complete fluid attenuation of this medium size arachnoid cyst (arrow), leaving this lesion devoid of signal. The 9th cranial nerve can be seen pushed anteromedially (open arrow) by the lesion.

Variant (Left) Large arachnoid cyst of posterior CPA cistern seen in an axial T2 MR image shows a smooth, pushing margin (arrows) in its interface with the subjacent cerebellum. The high signal fluid within the cyst parallels the signal of CSF. (Right) Axial OW MR image reveals no evidence for restricted diffusion in this large low signal arachnoid cyst (arrows). This absence of restriction on OWl MR sequence differentiates the arachnoid cyst from the epidermoid cyst of the CPA.

Other (Left) Coronal graphic of

CPA arachnoid cyst shows typical translucent cyst wall. CN 7 & 8 are pushed by cyst (arrow) without being engulfed by it. In epidermoid cyst, CNs are usually engulfed. (Right) Coronal gross pathology specimen views an arachnoid cyst in the left CPA cistern from below (arrows). Notice the gossamer-thin, translucent walls of the cyst itself (Courtesy E. T. Hedley-Whyte).

CPA-lAC

3 19

RAMSAY HUNT SYNDROME

3 20 Clinical photograph in a patient with active R/-IS reveals distinctive hemorrhagic vesicular rash of external ear (arrow) that is seen with acute onset 7th & 8th cranial neuropathy.

• When minimally involved, linear or no enhancement seen • Morphology: Linear or fusiform lAC enhancement rule

ITERMINOLOGY Abbreviations

and Synonyms

• Abbreviation: Ramsay Hunt syndrome (RHS) • Synonym: Herpes zoster oticus • Varicella zoster virus infection involving sensory fibers of cranial nerves 7, 8 & portion of external ear supplied by auriculotemporal nerve

IIMAGING FINDINGS General Features • Best diagnostic clue: Pathologic enhancement on Tl c+ MR of cranial nerves 7 ± 8 in lAC fundus along with all or part of membranous labyrinth • Location o 8th cranial nerve affected in fundal lAC o 7th cranial nerve affected in fundal lAC & within temporal bone o Membranous labyrinth also affected • Size o Only size variation relates to degree of cranial nerve involvement in lAC • When this area significantly involved, may mimic mass lesion

Bell Palsy

is

CT Findings

Definitions

DDx: linear CPA-lAC Meningeal

Axial T1 C+ MR in this patient with R/-IS & active vesicles on right external ear shows enhancement in the right lAC (arrow) and active inflammation of the right external ear (open arrows).

• NECT: Negative for bone changes or other findings • CECT: Negative for contrast enhancement in lAC

MR Findings • Tl WI: Liner intermediate signal seen in lAC fundus (represents inflamed cranial nerves) • T2WI o Thick section T2 (:? 4 mm) usually normal o High-resolution T2 • Fundal, 7th & 8th cranial nerves thickened • STIR:High signal in soft tissues of external ear • FLAIR o Parenchymal brain normal o High signal in soft tissues of external ear • Tl C+ o External ear • Fat saturated Tl C+ images may show enhancement of external ear vesicles & associated inflammation o Internal auditory canal • Linear to fusiform enhancement in lAC fundus (7th & 8th cranial nerves contribute)

Enhancement

Meningitis

Sarcoid, CPA

CPA-lAC

Metastasis,

lAC

RAMSAY HUNT SYNDROME Key Facts Terminology • Synonym: Herpes zoster oticus • Varicella zoster virus infection involving sensory fibers of cranial nerves 7, 8 & portion of external ear supplied by auriculotemporal nerve

Imaging Findings • Best diagnostic clue: Pathologic enhancement on Tl c+ MR of cranial nerves 7 ± 8 in lAC fundus along with all or part of membranous labyrinth • If external ear vesicular rash is clinically apparent, no imaging is necessary to investigate associated 7th & 8th nerve palsy

Top Differential

• Sarcoidosis • Meningeal metastasis

Pathology • Inflammatory infiltrates of lymphocytes & plasma cells • Found in geniculate ganglion, 7th & 8th cranial nerves and membranous labyrinth

Clinical Issues • Most common signs/symptoms: Facial palsy associated with external ear vesicles

Diagnostic Checklist • Combination of linear enhancement of fundal lAC, membranous labyrinth & intratemporal facial nerve suggest RHS

Diagnoses

• Bell palsy • Meningitis

• lAC enhancement not always present even with sensorineural hearing loss ± vertigo • Enhancement of facial nerve within temporal bone (labyrinthine, tympanic, mastoid segments all possible) • Enhancement of part or all of membranous labyrinth (cochlear portion enhances most commonly) o Intratemporal facial nerve • Entire intratemporal 7th cranial nerve enhancement typical • Labyrinthine segment involvement distinctive • Geniculate ganglion often also enhances • Rest of intra temporal 7th cranial nerve less frequently enhances o Membranous labyrinth • Pathologic enhancement often accompanies lAC & facial nerve enhancement • Fluid spaces of cochlea, vestibule & semicircular canals may all be variably affected • Membranous labyrinth enhancement may not be present even when hearing loss & vertigo present o Brainstem • Facial nucleus in brainstem enhances infrequently in RHS • Probably secondary to spread from lAC disease

Imaging Recommendations • Best imaging tool o Whole brain T2 MR with enhanced sequences focused on CPA-lAC & temporal bone o Findings best seen on fat saturated Tl C+ MR images o No role for CT in diagnosing RHS • Protocol advice o If external ear vesicular rash is clinically'apparent, no imaging is necessary to investigate associated 7th & 8th nerve palsy o If clinical presentation is atypical, MR imaging ordered • Include whole brain FLAIR sequence to exclude intra-axial cause of cranial neuropathy

• Include axial & coronal Tl C+ fat saturated thin section (3 mm) sequences through lAC & temporal bone

I DIFFERENTIAL DIAGNOSIS Bell palsy • Enhancement of 7th cranial nerve but not membranous labyrinth or 8th cranial nerve • Fundal 7th cranial nerve enhancing "tuft" • lAC enhancement usually less intense than RHS

Meningitis • Thickened, diffusely enhancing • CSF analysis may be revealing

meninges

Sarcoidosis • Multifocal meningeal enhancing foci • Spares inner ear & fundus of lAC • Increased erythrocyte sedimentation rate (ESR) & serum angiotensin converting enzyme (ACE)

Meningeal

metastasis

• Multifocal meningeal enhancing foci • Intraparenchymallesions may also be present

I

PATHOLOGY

General Features • General path comments o Varicella zoster virus can be cultured from vesicles or from saliva o Increased vascular permeability allows contrast to pass through blood-nerve barrier • Etiology o Classic hypothesis: Virus remains dormant within geniculate ganglion with periodic reactivation o Recent hypothesis: Primary polyneuritis with infection of 7th & 8th cranial nerve trunks with spread via interneural connections

CPA-lAC

3 21

RAMSAY HUNT SYNDROME Gross Pathologic

&. Surgical

• Edematous, hyperemic in fundus of lAC

Microscopic

• If imaging suggests RHS, contact referring clinician for history of external ear vesicular rash

Features

7th & 8th cranial nerves seen

Image Interpretation

Features

• Inflammatory infiltrates of lymphocytes & plasma cells • Found in geniculate ganglion, 7th & 8th cranial nerves and membranous labyrinth • Similar symptoms & MR findings have been described with human herpes virus 1 (HHV-1) infection

I SELECTED REFERENCES 1. 2.

3

I CLINICAL ISSUES

22

Presentation

3.

• Most common signs/symptoms: Facial palsy associated with external ear vesicles • Other signs/symptoms o Deep, burning pain in ear o Facial paralysis more severe than with Bell palsy o Painful erythematous vesicular rash of external ear o Sensorineural hearing loss (SNHL), tinnitus & vertigo due to 8th cranial nerve involvement • Interneural connections from 7th cranial nerve o Involvement of other cranial nerves, especially 5th cranial nerve possible (ophthalmic division) o Vertigo develops after onset of pain and either before or after vesicular eruption o Nausea & vomiting possible

4.

5.

6. 7.

8. 9.

Natural History & Prognosis • Ear pain followed in - 7 days by erythematous vesicular rash of external ear • Cranial neuropathies appear after onset of ear pain o Appear before or after vesicular eruption o When before, imaging may be done looking for etiology of 7th cranial nerve palsy • Multiple cranial nerve palsies & older age both are negative prognostic indicators • Facial palsy natural history o Major damage to 7th cranial nerve not until 2-3 weeks after onset o Compare to Bell Palsy where damage peaks at 10 days

Treatment

I DIAGNOSTIC

10.

11. 12.

13.

14.

15.

• Conservative management first o Warm compresses o Analgesics o Cornea care for facial paralysis • Pharmacologic treatment o Corticosteroids o Acyclovir reduces pain & is helpful in improving facial function

CHECKLIST

16. 17. 18.

19.

20.

Consider • MR imaging should only be done when clinical presentation is atypical

Pearls

• Combination of linear enhancement of fundal lAC, membranous labyrinth & intratemporal facial nerve suggest RHS

21.

CPA-lAC

Hu S et al: Acyclovir responsive brain stem disease after Ramsay Hunt syndrome.] Neurol Sci 217:111-3, 2004 Lu YC et al: Vertigo form herpes zoster oticus: superior or inferior vestibular nerve origin? Laryngoscope 113(2):307-11,2003 Kuhweide R et al: Ramsay Hunt syndrome: pathophysiology of cochleovestibular symptoms. ] Laryngol OtoI116(10):844-8, 2002 Grose C et al: Chickenpox and the geniculate ganglion: facial nerve palsy, Ramsay Hunt syndrome and acyclovir treatment. Pediatr Infect Dis] 21(7):615-7, 2002 Lavi ES et al: Enhancement of the eighth cranial nerve and labyrinth on MR imaging in sudden sensorineural hearing loss associated with human Herpesvirus 1 infection: Case report. A]NR 22:1380-2,2001 Sweeney C] et al: Ramsay Hunt syndrome. ] Neurol Neurosurg Psychiatry 71(2):149-54, 2001 Suzuki F et al: Herpes virus reactivation and gadolinium-enhanced magnetic resonance imaging in patients with facial palsy. Otol NeurotoI22(4):549-53, 2001 Steiner I et al: Bell's palsy and herpes viruses: to (acyclo)vir or not to (acyclo)vir? ] Neurol Sci 15i170(1):19-23, 1999 Sartoretti-Schefer S et al: Ramsay Hunt syndrome associated with brain stem enhancement. A]NR 20(2):278-80, 1999 Berrettini S et al: Herpes zoster oticus: correlations between clinical and MRI findings. Eur Neurol 39(1):26-31, 1998 Brandle P et al: Correlation of MRI, clinical, and electroneuronographic findings in acute facial nerve palsy. Am] OtoI17(1):154-61, 1996 Jonsson L et al: Gd-DPTA enhanced MRI in Bell's palsy and herpes zoster oticus: an overview and implications for future studies. Acta OtolaryngoI115(5):577-84, 1995 Kuo M] et al: Early diagnosis and treatment of Ramsay Hunt syndrome: the role of magnetic resonance imaging. ] Laryngol Otol109(8):777-80, 1995 Downie AC et al: Case report: prolonged contrast enhancement of the inner ear on magnetic resonance imaging in Ramsay Hunt syndrome. Br] Radiol 67(800):819-21, 1994 Sartoretti-Schefer S et al: Idiopathic, herpetic, and HIV-associated facial nerve palsies: abnormal MR enhancement patterns. A]NR 15(3):479-85, 1994 Tada Y et al: Gd-DTPA enhanced MRI in Ramsay Hunt syndrome. Acta Otolaryngol Suppl 511:170-4,1994 Adour KK: Otological complications of herpes zoster. Ann Neurol 35 Suppl:S62-4, 1994 Rovira Canellas A et al: Ramsay-Hunt syndrome and high-resolution 3DFT MRI. ] Com put Assist Tomogr 17(3):495-7, 1993 Yanagida M et al: Enhanced MRI in patients with Ramsay-Hunt's syndrome. Acta Otolaryngol Suppl 500:58-61, 1993 Korzec K et al: Gadolinium-enhanced magnetic resonance imaging of the facial nerve in herpes zoster oticus and Bell's palsy: clinical implications. Am] OtoI12(3):163-8, 1993 Osumi A et al: MR findings in a patient with Ramsay-Hunt syndrome.] Comput Assist Tomogr 14(6):991-3, 1990

RAMSAY HUNT SYNDROME I IMAGE GALLERY Typical (Left) Coronal T2WI MR shows typical MR appearance of RHS as a low signal area in right internal auditory canal (arrow). This "filling defect" is secondary to edematous 7th and 8th cranial nerves. (Right) Coronal T1 C+ MR in patient with RHS reveals typical MR appearance as mixture of linear & nodular enhancement in lateral internal auditory canal (arrow) on right.

Variant (Left) Axial T1 C+ MR magnified to right ear reveals typical MR appearance of RHS as linear enhancement within lAC (arrow) accompanied by more unusual enhancement of cochlear labyrinth (open arrow). (Right) Coronal T1 C+ MR magnified to right ear shows enhancement in lAC (arrow) and more laterally enhancement of inner ear (open arrow). This combination of lAC & inner ear enhancement is a well know variant MR appearance in RHS.

Variant (Left) Axial T1 C+ MR demonstrates focal, nodular enhancement in the fundus of the lAC on the left (arrow). Fortunately, this tumefactive appearance is rare as an MR manifestation of RHS. (Right) Coronal T1 C+ MR in patient with external ear vesicles and acute onset of 7th & 8th cranial neuropathies (RHS) shows solid enhancement of lAC fundus (arrow) in association with inner ear enhancement (open arrow).

CPA-lAC

3 23

VASCULAR LOOP COMPRESSION, CPA-lAC

3 24 Axial T2WI MR shows vertebral artery (arrow) in a very tortuous course impinging on deep cerebellopontine angle in area of root exit zone of facial nerve. Symptom: Hemifacial spasm.

ITERMINOlOGY Abbreviations

and Synonyms

• Synonyms o Trigeminal neuralgia (TN), tic douloureux, trigeminal nerve vascular loop syndrome, trigeminal nerve hyperactive dysfunction syndrome o Hemifacial spasm (HFS), facial nerve vascular loop syndrome, facial nerve hyperactive dysfunction syndrome

Definitions • Vascular loop compressing cranial nerves (CN) within CPA-lAC cistern causing spasmodic hyperfunction o Vascular loop compresses 5th CN at root entry zone (REnZ) results in trigeminal neuralgia o Vascular loop compresses 7th CN at root exit zone (RExZ) results in hemifacial spasm

I IMAGING FINDINGS General Features • Best diagnostic clue o High-resolution T2 MR shows serpiginous asymmetric signal void (vessel) in CPA • May impinge on proximal preganglionic or REnZ of 5th CN (causing TN)

• May impinge on proximal 7th CN or RExZ (causing HFS) • Location o Vascular loop is high, anterior CPA cistern along area of proximal preganglionic segment of 5th CN or at REnZ (TN) o Vascular loop is in mid-CPA cistern along proximal 7th CN or at RExZ (HFS) • Size o Offending vessels range from tiny to fusiform aneurysmal dilatation of vertebrobasilar system o Very small vessels may be sub-radiologic in size • Morphology o Asymmetric vascular loop flattens proximal CN 5 or 7

o When offending vessel is atherosclerotic, appears as serpiginous, irregular vessel • Offending vessels o Trigeminal neuralgia • Superior cerebellar artery> posterior inferior cerebellar artery> vertebrobasilar system o Hemifacial spasm • Anterior inferior cerebellar artery> posterior inferior cerebellar artery> vertebral artery

CT Findings segment

DDx: linear CPA-lAC Meningeal

Bell Palsy

Coronal T2WI MR in a patient with left hemifacial spasm reveals the left vertebral artery (arrow) compressing the proximal facial nerve (open arrow) at the root exit zone.

• NECT o Commonly

normal

Enhancement

Meningitis

Sarcoid, CPA

CPA-lAC

Metastasis, lAC

VASCULAR LOOP COMPRESSION, CPA-lAC Key Facts Terminology • Vascular loop (REnZ) results • Vascular loop (RExZ) results

compresses 5th CN at root entry zone in trigeminal neuralgia compresses 7th CN at root exit zone in hemifacial spasm

Imaging Findings • High-resolution T2 MR shows serpiginous signal void (vessel) in CPA • Vascular loop is high, anterior CPA cistern of proximal preganglionic segment of 5th REnZ(TN) • Vascular loop is in mid-CPA cistern along 7th CN or at RExZ (HFS)

Top Differential • Vertebrobasilar

asymmetric along area CN or at proximal

Clinical Issues • TN: Episodic lancinating pain following V2 &/or V3 distributions • HFS: Unilateral involuntary facial spasms • Negative MR does not preclude exploratory surgery

Diagnostic Checklist • There are many normal vessels in different parts of CPA cistern • Close correlation between symptomatic CN & asymmetric vascular loop imperative

Diagnoses

dolichoectasia

(VBD)

o Vertebrobasilar loop with high density, calcified vessels possible • CECT o Commonly normal o Vertebrobasilar loop with intravascular enhancement

• Protocol advice o Begin with whole brain T2 or FLAIR sequence to exclude multiple sclerosis o Follow with axial & coronal Tl C+ imaging of brain stem, CPA cistern including deep face • Look for asymmetric venous cause • Also look for cranial neuritis, perineural tumor and cisternal tumor o High-resolution thin-section imaging of brain stem & CPA cistern next • Best sequence to look for offending artery o MRA focused to posterior fossa • Remember to view source images before reprojection images

MR Findings • TlWI o Vessel usually not seen although contrast enhancement may help o Visibility dependent on size of vessel & flow rate • T2WI o High-resolution T2 or T2 images on 3T MR • Vessel best seen as low signal tube coursing through high signal CSF • FLAIR o Adjacent brain most commonly normal o Multiple sclerosis plaque in REnZ or RExZ may present with TN or HFS • DWI o High signal (restricted diffusion) in CPA cistern makes diagnosis of epidermoid • Cisternal masses may cause TN or HFS • Tl C+ o May elucidate rare venous cause of trigeminal neuralgia o Enhancing meningioma or schwannoma possible • Meningeal mass or adjacent schwannoma may cause TN or HFS • MRA o Source images most helpful o Reprojected images helpful for larger vessels

Angiographic

• Arteriovenous malformation, CPA • Venous angioma, posterior fossa • Aneurysm, CPA

I DIFFERENTIAL DIAGNOSIS Vertebrobasilar

dolichoectasia

(VBD)

• Common atherosclerotic finding in old patient • Tortuous, dilatated vertebrobasilar system • Rarely causes vascular loop syndrome

Arteriovenous

malformation,

CPA

• Much larger vessels (arteries & veins) with nidus • Rare in posterior fossa

Venous angioma, posterior fossa • Larger vessels (veins) • Posterior fossa location common but CPA rare as drainage route • Rarely can cause venous compression with HFS or TN resulting

Aneurysm, CPA

Findings

• Conventional: Not helpful; cannot assess relationship of vessel to 5th or 7th CN

Imaging Recommendations • Best imaging tool o Thin-section high-resolution T2 MR of CPA allows best vascular loop visualization o 3T MR will be best tool for this imaging problem

• PICA or vertebral artery aneurysm • Oval complex-signal mass

I PATHOLOGY General Features • General path comments

CPA-lAC

3 25

VASCULAR LOOP COMPRESSION, CPA-lAC

3 26

o 5th or 7th CN bundle experiences "irritation" from vessel ' o Brainstem nuclei secondarily affected • Abnormal brain stem response (ABR) • Etiology o Multiple sclerosis has been reported to cause TN or HFS o Cisternal masses such as epidermoid or meningioma may cause TN or HFS o "Kindling theory" • Vessel contact results in ectopic excitation • Antidromic impulses travel back to nucleus • Reorganization within nucleus results in increased discharge • Hyperactivity travels orthodromically down 7th nerve • Epidemiology: TN > HFS; TN incidence 1 per 100,000

Gross Pathologic & Surgical Features • Offending vessel compresses REnZ (TN) or RExZ (HFS)

Microscopic

Features

• These include multiple sclerosis, cistern tumor, neuritis & perineural tumor • Negative MR does not preclude exploratory surgery

I DIAGNOSTIC

CHECKLIST

Consider • There are many normal vessels in different parts of CPA cistern • Close correlation between symptomatic CN & asymmetric vascular loop imperative

Image Interpretation

Pearls

• First look for cisternal mass lesions such as epidermoid, meningioma or schwannoma • Next determine if source images for MRA or high-resolution T2 images identify offending vessel • Follow affected nerve (5th or 7th CN) distally into deep face to exclude neuritis & perineural tumor • Negative MR does not preclude surgical exploration in clear cut TN or HFS setting

• Myelin cover on affected cranial nerve is breached

I SELECTED REFERENCES

I CLINICAL ISSUES

1.

Presentation • Most common signs/symptoms o TN: Episodic lancinating pain following V2 &/or V3 distributions o HFS: Unilateral involuntary facial spasms • Other signs/symptoms o TN: Pain spontaneous or occurs in response to gentile tactile stimulation of trigger point o Hemifacial spasm • Begins with orbicularis oculi spasms • Tonic-clonic bursts which become constant over time

2.

3. 4. 5.

6.

Demographics • Age: Older patients (usually greater than 65 years) • Gender: No gender specificity

7. 8.

Natural History & Prognosis • Prognosis o Trigeminal neuralgia • 70% pain-free on no medications 10 years after microvascular decompression (MVD) • If recurrent TN, happens in 1st 2 years after MVD • 1% have permanent post-MVD complication (unilateral deafness most common) o Hemifacial spasm • 90% achieve> 5 year symptom relief with MVD • 10% have permanent postoperative complication (unilateral deafness)

9.

10. 11.

12.

13.

Treatment • Some patients can be managed conservatively with drug therapy • MVD used when symptoms are disabling in spite of drug therapy o Rarely other causes of TN & HFS are identified

14. 15.

CPA-lAC

Polo G et al: Brainstem auditory evoked potential monitoring during microvascular decompression for hemifacial spasm. Neurosurg 54:97-106,2004 Yoshino N et al: Trigeminal neuralgia: Evaluation of neuralgic manifestations and site of neurovascular compression with 3D CISS MR imaging and MR angiography. Radiology 228:539-45,2003 Zakrzewska JM: Diagnosis and differential diagnosis of trigeminal neuralgia. Clin J Pain 18(1):14-21, 2002 Tan NC et al: Hemifacial spasm and involuntary facial movements. QJM 95(8):493-500, 2002 Miwa H et al: Familial hemifacial spasm: report of cases and review of literature. J Neurol Sci 15;193(2):97-102, 2002 Jost WH et al: Botulinum toxin: evidence-based medicine criteria in blepharospasm and hemifacial spasm. J Neurol 248 1:21-4, 2001 Moller AR: Vascular compression of cranial nerves: II: pathophysiology. Neurol Res 21(5):439-43, 1999 Herzog JA et al: Vascular loops of the internal auditory canal: a diagnostic dilemma. Am J OtoI18(1):26-31, 1997 Illingworth RD et al: Hemifacial spasm: a prospective long-term follow up of 83 cases treated by microvascular decompression at two neurosurgical centres in the United Kingdom. J Neurol Neurosurg Psychiatry 60(1):72-7, 1996 Majoie CB et al: Trigeminal neuropathy: evaluation with MR imaging. Radiographics 15(4):795-811, 1995 Darlow LA et al: Magnetic resonance imaging in the diagnosis of trigeminal neuralgia. J Oral Maxillofac Surg 50(6):621-6, 1992 Ohashi N et al: Vascular cross-compression of the VIIth and VIIIth cranial nerves. J Laryngol Otol106(5):436-9, 1992 Parnes LS et al: Vascular relationships of the vestibulocochlear nerve on magnetic resonance imaging. AmJ OtoIJul;11(4):278-81, 1990 Haberman RS et al: False-positive MRI and CT findings of an acoustic neuroma. AmJ Otol10(4):301-3, 1989 Esfahani F et al: Air CT cisternography in the diagnosis of vascular loop causing vestibular nerve dysfunction. AJNR 10(5):1045-9, 1989

VASCULAR LOOP COMPRESSION, CPA-lAC I IMAGE GALLERY Typical (Left) Axial MRA shows asymmetrically large AICA loop (arrow) knuckling into the area of the root exit zone of the facial nerve. At surgery this loop was felt to be the cause of patient's hemifacial spasm. (Right) MRA reprojection reveals an asymmetrically large AICA loop (arrow) that has a sharp bend at approximately the area of the CPA. Source images showed the vessels impinged on the root exit zone of the facial nerve.

(Left) Axial MRA source image in patient with right HFS shows a tortuous right VA (arrow) & associated PICA (open arrow) pushing on root entry zone of facial nerve. Curved arrow: Facial nerve in CPA cistern. (Right) Anteroposterior MRA reprojection shows how a tortuous right VA (arrow) can elevate PICA loop (open arrow) in CPA cistern. In this case VA-PICA complex caused symptom of hemifacial spasm.

(Left) Axial T2WI MR in this patient with right trigeminal neuralgia shows the superior cerebellar artery (arrow) compressing the preganglionic segment of the trigeminal nerve (open arrow). (Right) Coronal T2WI MR shows flattened CN 5 root entry zone (open arrow). Patient's trigeminal neuralgia was secondary to compressing combination of superior cerebellar artery (arrow) & PICA (curved arrow).

CPA-lAC

3 27

ACOUSTIC SCHWAN NOMA

3 28 Axial graphic shows small intracanalicular acoustic schwannoma (open arrow) from superior vesubular nerve. Notice cochlear aperture is uninvolved (arrow).

ITERMINOLOGY Abbreviations

and Synonyms

• Common synonyms: Acoustic schwannoma (AS), acoustic neuroma, acoustic tumor, vestibular schwannoma • Uncommon: Neurinoma, neurilemmoma • Vestibular schwannoma is most accurate term o Since most lesions arise on the vestibular portion of 8th cranial nerve (CN)

Axial T2WI MR shows 5 mm intracanalicular acoustic schwannoma (open arrow). Cochlear aperture is spared (arrow). A 4 mm "fundal cap" of CSFis present.

• Screening MR done earlier o Larger lesions: Up to 5 cm in maximum diameter • Morphology o When small & intracanalicular, looks like ovoid to cylindrical mass o Larger lesions look like "ice cream (CPA) on cone (lAC)" o Seldom herniate cephalad into middle cranial fossa (cf CPA meningioma)

CT Findings

• Acoustic schwannoma = benign tumor arising from Schwann cells that wrap vestibulocochlear nerve in CPA-lAC

• CECT o Well-delineated, enhancing mass of CPA-lAC cistern o Calcification not present (cf CPA meningioma) o May flare lAC when larger o Smaller intracanalicular lesions « 6 mm) may be missed with CECT

I IMAGING FINDINGS

MR Findings

General Features

• TlWI o Intermediate signal most common o High signal patches if rare hemorrhagic lesion present (0.5%) • T2WI o High-resolution T2 MR: "Filling defect" in high signal CSF of CPA-lAC cistern • Small lesion: Ovoid filling defect in high signal CSF of lAC

Definitions

• Best diagnostic clue: Avidly enhancing cylindrical (lAC) or "ice cream on cone" (CPA-lAC) mass. • Location o Small lesions: Intracanalicular o Large lesions: Intracanalicular with CPA cistern extension • Size o Small lesions: 2-10 mm

DDx: CPA Mass

Arachnoid Cyst

Epidermoid Cyst

Meningioma, CPA

CPA-lAC

CN 7 Schwan noma

ACOUSTIC SCHWANNOMA Key Facts Terminology • Acoustic schwannoma = benign tumor arising from Schwann cells that wrap vestibulocochlear nerve in CPA-lAC

Imaging Findings • Best diagnostic clue: Avidly enhancing cylindrical (lAC) or "ice cream on cone" (CPA-lAC) mass • High-resolution T2 MR: "Filling defect" in high signal CSF of CPA-lAC cistern • Focal, enhancing mass of CPA-lAC cistern centered on porus acusticus • Best imaging tool: Gold standard is full brain T2 MR with axial & coronal T1 C+ MR imaging of CPA-lAC

Top Differential • Epidermoid

Diagnoses

Imaging Recommendations • Best imaging tool: Gold standard is full brain T2 MR with axial & coronal T1 C+ MR imaging of CPA-lAC • Protocol advice o High-resolution T2 MR imaging of CPA-lAC is only screening exam for AS • Used for uncomplicated unilateral sensorineural hearing loss (SNHL) in adult

I DIFFERENTIAL DIAGNOSIS Epidermoid

Pathology • Most common CPA-lAC mass (85-90%) • Second most common extra-axial neoplasm in adults

Clinical Issues • Most common signs/symptoms: unilateral SNHL

Adults with

Diagnostic Checklist • Unilateral well-circumscribed lAC or CPA-lAC mass should be considered AS until proven otherwise • Comment on AS involvement of cochlear aperture and/or lAC fundus in radiologic report

cyst

• Large lesion: "Ice cream in cone" shaped filling defect in CPA-lAC • T1 C+ o Focal, enhancing mass of CPA-lAC cistern centered on porus acusticus o 100% enhance strongly o 15% with intramural cysts (low signal foci) • Other MR findings o 0.5% associated arachnoid cyst o Dural tails are rarely present (cf meningioma)

• • • • •

• Meningioma • Facial nerve schwannoma

cyst

May mimic rare cystic AS Insinuating morphology T1 C+ MR: Nonenhancing CPA mass FLAIR: Partial or absent attenuation DWI: Diffusion restriction (high signal)

• Look for labyrinthine

segment "tail" to differentiate

Metastasis & lymphoma • May be bilateral; multifocal meningeal • Beware of "NF2" diagnosis in adult

involvement

Aneurysm • Ovoid to fusiform complex signal mass at CPA

I PATHOLOGY General Features • General path comments: Vestibular division of CN 8 far more common with AS than cochlear nerve • Genetics o Inactivating mutations of NF2 tumor suppressor gene in 60% of sporadic AS o Loss of chromosome 22q also seen o Multiple or bilateral schwannomas = NF2 • Etiology: Benign tumor arising from vestibular portion of CN 8 at glial-Schwann cell junction • Epidemiology o Most common lesion in patients with unilateral SNHL (> 90%) o Most common CPA-lAC mass (85-90%) o Second most common extra-axial neoplasm in adults • Associated abnormalities: Arachnoid cyst (0.5%)

Arachnoid cyst

Gross Pathologic & Surgical Features

• Pushing CPA lesion that does not enter lAC • Follows CSF signal on all MR sequences • T1 C+ shows no enhancement

• Tan, round-ovoid, encapsulated mass • Arises eccentrically from CN 8 at glial-Schwann cell junction o Glial-Schwann cell junction most commonly near porus acusticus

Meningioma • lntracanalicular meningioma may mimic AS (rare) • CECT: Calcified dural-based mass eccentric to porus acusticus • T1 C+ MR: Broad dural-base with associated dural "tails"

Facial nerve schwan noma • When confined to CPA-lAC, may exactly mimic AS

Microscopic

Features

• Differentiated neoplastic Schwann cells in a collagenous matrix • Areas of compact, elongated cells = Antoni A o Most AS comprised mostly of Antoni A cells • Areas less densely cellular with tumor loosely arranged, +/- clusters of lipid-laden cells = Antoni B

CPA-lAC

3 29

ACOUSTIC SCHWANNOMA • Strong, diffuse expression of S-100 protein • No necrosis but may have intramural cysts; rarely hemorrhagic

• Thin-section, T1 C+ axial & coronal MR is gold standard imaging approach

Staging, Grading or Classification Criteria

• Unilateral well-circumscribed lAC or CPA-lAC mass should be considered AS until proven otherwise • Comment on AS involvement of cochlear aperture and/or lAC fundus in radiologic report • Always make sure there is no "labyrinthine tail" on all AS to avoid misdiagnosing a facial nerve schwannoma

Image Interpretation

• WHO grade I lesion

I CLINICAL

ISSUES

Pearls

Presentation

3 30

• Most common signs/symptoms: Adults with unilateral SNHL • Clinical profile o Patient complains of slowly progressive SNHL o Laboratory • Brainstem electric response audiometry (BERA) most sensitive pre-imaging test for AS • BERA may be unnecessary if early, screening MR is employed • Other symptoms o Small AS: Tinnitus (ringing in ear); disequilibrium o Large AS: Trigeminal and/or facial neuropathy

Demographics

I SELECTED REFERENCES 1.

2.

3.

4. 5.

• Age o Adults (rare in children unless NF2) o Peak age = 40-60 years o Age range = 30-70 years • Gender: No gender specificity

6.

Natural History & Prognosis

8.

7.

• 75% of AS are slow growing; will grow at a gradual pace if left untreated • 10% of AS grow rapidly (:2: 1 em per year) • 15% of AS grow very slowly and can be left alone in older patients • If hearing is absent or very poor, successful surgical removal of AS will not restore any hearing already lost • Negative prognostic imaging findings for hearing preservation o Size> 2 em o AS involves lAC fundus and/or cochlear aperture

Treatment • Translabyrinthine resection if no hearing preservation possible • Middle cranial fossa approach for intracanalicular AS, especially lateral lAC location • Retrosigmoid approach when CPA or medial lAC component present • Radiation therapy o Gamma knife: Low-dose, sharply collimated, focused cobalt-60 treatment o Used when medical contraindications to surgery & residual post-operative AS

9.

10. 11.

12.

13. 14.

15.

16. 17.

18.

I DIAGNOSTIC

CHECKLIST 19.

Consider • Consider using high-resolution T2 unenhanced & coronal MR as "screening" for AS

axial

CPA-lAC

Yates PD et al: Is it worthwhile to attempt hearing preservation in larger acoustic neuromas? Otol Neurotol. 24(3):460-4, 2003 Rupa V et al: Cost-effective initial screening for vestibular schwannoma: auditory brainstem response or magnetic resonance imaging? Otolaryngol Head Neck Surg. 128(6):823-8,2003 Kobayashi M et al: Distance from acoustic neuroma to fundus and a postoperative facial palsy. Laryngoscope. 112(1):168-71,2002 Spickler EM et al: The vestibulocochlear nerve. Semin Ultrasound CT MR. 23(3):218-37, 2002 Nakashima K et al: Three-dimensional fast recovery fast spin-echo imaging of the inner ear and the vestibulocochlear nerve. Eur Radiol. 12(11):2776-80,2002 Natik SL et al: Determinants of tumor size and growth in vestibular schwannomas. J Neurosurg. 94:922-6, 2001 Komatsuzaki A: Nerve origin of the acoustic neuroma. J LaryngolOtol. 115:376-9,2001 Somers T et al: Prognostic value of magnetic resonance imaging findings in hearing preservation surgery for vestibular schwannoma. Otol Neurotol. 22:87-94, 2001 Salzman KL et al: Dumbbell schwannomas of the internal auditory canal. AJNR Am J Neuroradiol. 22(7): 1368-76, 2001 Hoistad DL et al: Update on conservative management of acoustic neuroma. Otol Neurotol. 22(5):682-5, 2001 Selesnick SH et al: Internal auditory canal involvement of acoustic neuromas: surgical correlates to magnetic resonance imaging findings. Otol Neurotol. 22(6):912-6, 2001 Zealley IA et: MRI screening for acoustic neuroma: a comparison of fast spin echo and contrast enhanced imaging in 1233 patients. Br J Radiol. 73:242-7, 2000 Gillespie JE: MRI screening for acoustic neuroma. Br J Radiol. 73:1129-30, 2000 O'Reilly B et al: The conservative management of acoustic neuroma: a review of forty-four patients with magnetic resonance imaging. Clin Otolaryngol. 25:93-7, 2000 Nakamura H et al: Serial follow-up MR imaging after gamma knife radiosurgery for vestibular schwannoma. AJNR. 21:1540-46, 2000 Rosenberg SI: Natural history of acoustic neuromas. Laryngoscope. 110:497-508, 2000 Dubrulle F et al: Cochlear fossa enhancement at MR evaluation of vestibular schwannoma: correlation with success at hearing-preservation surgery. Radiology. 215:458-2, 2000 Allen RW et al: Low-cost high-resolution fast spin-echo MR of acoustic schwannoma: an alternative to enhanced conventional spin-echo MR? AJNR. 17:1205-10, 1996 Jackler RK et al: Selection of surgical approach to acoustic neuroma. Otolaryngol Clin North Am. 25:361-87, 1992

ACOUSTIC SCHWANNOMA

I IMAGE GALLERY Typical (Left) Coronal T2WI MR demonstrates a small, intracanalicular-fundal acoustic schwan noma (arrow) that bows the crista falciformis cephalad (open arrow), indicating its origin from the inferior vestibular nerve. (Right) Axial T1 C+ MR shows an avidly enhancing large CPA-lAC acoustic schwan noma. In this case the tumor has completely filled the cochlear aperture (arrow). Surgical removal will most likely result in no residual hearing.

Variant (Left) Axial T1 C+ MR shows large enhancing acoustic schwan noma with only minimal penetration of lAC (arrow). Intramural cysts (open arrows) and a large associated arachnoid cyst (curved arrow) evident. (Right) Axial T2WI MR reveals the large CPA acoustic schwan noma has inhomogeneous signal. The 4th ventricle (arrow) can be distinguished from the associated arachnoid cyst (curved arrow) more readily with T2 imaging.

Other (Left) Axial graphic of a large acoustic schwan noma reveals the typical "ice cream on cone" CPA-lAC morphology. Mass effect on middle cerebellar peduncle (arrows) is evident. (Right) Axial T1 C+ MR demonstrates an enhancing intermediate to large acoustic schwan noma filling all but the most lateral lAC (open arrow), extending out into CPA to compress the lateral brachium pontis (arrows).

CPA-lAC

3 31

MENINGIOMA,

CPA-lAC

3 32 Axial graphic at level of lAC shows large CPA meningioma causing mass effect on brainstem & cerebellum. Notice broad dural base creates the shape of a mushroom head. Arrow: Dural "tail".

• Ovoid mass mimics acoustic schwannoma (5%) o CSF-vascular "cleft" between mass & brain o Frequently (50%) herniates cephalad into medial middle cranial fossa • Acoustic schwannoma rarely shows this vector of spread

I TERMINOLOGY Abbreviations

Axial gross pathologic section viewed from below shows a large CPA meningioma with a broad dural base compressing the cerebellum. The specimen demonstrates CSF-vascular cleft (arrows).

and Synonyms

• Posterior fossa meningioma

Definitions • Benign, unencapsulated neoplasm arising from meningothelial arachnoid cells of CPA-lAC dura

CT Findings

IMAGING FINDINGS General Features • Best diagnostic clue: CPA dural-based enhancing mass eccentric to lAC porus acusticus • Location o 10% occur in posterior fossa o When in CPA, asymmetric to lAC porus acusticus • Size o Broad range; may be large but most in 1-8 cm range o Generally significantly larger than acoustic schwannoma at presentation • Morphology o Three distinct morphologies • "Mushroom cap" (hemispherical) with broad base towards posterior petrous wall (75%) • Plaque-like (en plaque), +/- bone invasion with hyperostosis (20%)

• NECT o 30% isodense; 70% hyperdense o 25% calcified; 2 types seen • Homogeneous, sand-like • Dense chunks sprinkled throughout mass o Bone window findings • Hyperostotic or permeative-sclerotic bone changes possible (en plaque type) • lAC flaring rare (d acoustic schwannoma) • CECT: 90% strong, uniform enhancement; 10% inhomogeneous

MR Findings • TlWI o Isointense or minimally hyperintense to gray matter o When tumor has calcifications or is highly fibrous, hypointense areas are visible • T2WI o Wide range of possible signals on T2WI • Isointense or hypointense CPA mass (compared to gray matter) most likely meningioma

DDx: CPA Mass

Acoustic Schwan

Epidermoid Cyst

CPA-lAC

Arachnoid Cyst

FacialSchwannoma

MENINGIOMA,

CPA-lAC

Key Facts Terminology

Pathology

• Benign, unencapsulated neoplasm arising from meningothelial arachnoid cells of CPA-lAC dura

• Most common primary nonglial tumor • 2nd most common CPA-lAC mass (acoustic schwannoma = 1st most common) • Sharply circumscribed, unencapsulated

Imaging Findings • Best diagnostic clue: CPA dural-based enhancing eccentric to lAC porus acusticus • Enhancing dural-based mass with dural "tails" centered along posterior petrous wall

Top Differential • • • • •

mass

Clinical Issues • Adult female undergoing indication

Diagnoses

Diagnostic Checklist • Focal or diffuse hypointensity on T2WI in CPA mass suggests meningioma • Dural "tail" in lAC suggests meningioma with dural reaction, not acoustic schwannoma

Sarcoidosis Acoustic schwannoma (AS) Leptomeningeal metastasis Primary meningeal lymphoma Intracranial pseudotumor

• Focal or diffuse parenchymal low signal seen if calcified or highly fibrous o CSF-vascular cleft • Pial blood vessels seen as surface flow voids between tumor & brain o Arterial feeders to tumor seen as arborizing flow voids o High signal in adjacent brainstem or cerebellum • Represents peri tumoral brain edema • Correlates with pial blood supply • Its presence signals problems with safe removal & early recurrence • T2* GRE: May "bloom" parenchymal low signal • T1 C+

o Enhancing dural-based mass with dural "tails" centered along posterior petrous wall • 95% enhance strongly • Heterogeneous enhancement common especially in larger lesions o Dural thickening ("tail") in 60% • Represents reactive rather than neoplastic change in most cases • When extends into lAC may mimic lAC component of acoustic schwannoma

Angiographic

brain MR for unrelated

o Axial & coronal thin-section meningioma

T1 C+ MR best for

I DIFFERENTIAL DIAGNOSIS Sarcoidosis • Often multifocal, dural-based foci • Look for infundibular stalk involvement

Acoustic schwan noma (AS) • lntracanalicular • lntracanalicular

first, then CPA extension meningioma may mimic AS (rare)

Other schwannoma • Trigeminal, facial nerves • Round> flat dural based

Leptomeningeal

metastasis

• May be bilateral in CPA-lAC area • Multifocal meningeal involvement

Primary meningeal

lymphoma

• Rare intracranial lymphoma • Focal area enhancing, thickened

meninges

Intracranial pseudotumor

Findings

• Rare diffuse meningeal

• Conventional o Dural vessels supply tumor center, pial vessels supply tumor rim o "Sunburst" pattern of enlarged dural feeders common o Prolonged vascular "stain" into venous phase o Arteriovenous shunting may occur

Nonneoplastic

thickening

& enhancement

cyst

• Epidermoid cyst • Arachnoid cyst

I

Imaging Recommendations • Best imaging tool o Brain MR with focused posterior fossa imaging best approach o Bone only axial & coronal CT recommended if bone reaction or invasion suspected on MR • Protocol advice o Full brain T2 and/or FLAIR used to look for parenchymal brain edema

PATHOLOGY

General Features • General path comments: Multiple meningiomas occur in 10% of sporadic cases • Genetics o Long-arm deletions of chromosome 22 common o NF2 gene inactivated in 60% of sporadic cases o Angiogenic factors (FGF-2, VEGF, integrins) expressed

CPA-lAC

3 33

MENINGIOMA, CPA-lAC o May have progesterone, prolactin receptors; may express growth hormone • Etiology: Arises from meningothelial arachnoid cells (arachnoid "cap" cells), not dura • Epidemiology o Account for - 20% of primary intracranial tumors • Most common primary nonglial tumor o 1-1.5% prevalence at autopsy or imaging o 10% multiple (NF2; multiple meningiomatosis) o 2nd most common CPA-lAC mass (acoustic schwannoma = 1st most common) • Associated abnormalities: Meningioma + schwannoma =NF2

3 34

Gross Pathologic & Surgical Features • "Mushroom cap" (hemispherical) morphology most common (75%) • En plaque morphology (20%) also seen in CPA • Sharply circumscribed, unencapsulated • Distinct CSF-vascular "cleft" between mass & adjacent brain • Adjacent dural thickening (collar or "tail") is usually reactive, not neoplastic

Microscopic

Features

• Subtypes (wide range of histology with little bearing on imaging appearance or clinical outcome) o Meningothelial (lobules of meningothelial cells) o Fibrous (parallel, interlacing fascicles of spindle-shaped cells) o Transitional (mixed form; "onion-bulb" whorls and lobules) o Psammomatous (numerous small calcifications) o Angiomatous (abundant vascular channels), not equated with obsolete term "angioblastic meningioma" o Miscellaneous forms (microcystic, chordoid, clear cell, secretory, lymphoplasmocyte-rich, etc)

Staging, Grading or Classification Criteria

Natural History & Prognosis • Slow growing tumor that engulfs but does not typically destroy cranial nerves it encounters • Negative prognostic findings on MR o Peritumoral edema in adjacent brainstem o Loss of CSF-vascular cleft between tumor & brainstem o Significant subjacent bone invasion.

Treatment • Surgical removal if medically safe o Complete surgical removal possible in 95% when tumor does not invade skull base • Radiation therapy o Adjunctive therapy when surgical removal near complete o Alternative therapy when skull base invasion is extensive

I DIAGNOSTIC Consider

• Meningioma when imaging shows hemispherical, dural-based enhancing CPA mass with dural "tails" • Meningioma when CPA mass is large but relatively asymptomatic

Image Interpretation

I SELECTED REFERENCES 1.

3.

4.

5.

I CLINICAL ISSUES Presentation • Most common signs/symptoms: Most common to find incidentally • Clinical profile o Adult female undergoing brain MR for unrelated indication o Minimal symptoms often present even with larger, more invasive lesions

6.

7.

8.

Demographics • Age o Middle-aged, elderly patients; peak age = 60 years o If found in children, consider possibility of NF2 • Gender: F:M = 3:1

Pearls

• Focal or diffuse hypointensity on T2WI in CPA mass suggests meningioma • Dural "tail" in lAC suggests meningioma with dural reaction, not acoustic schwannoma

2.

• WHO grading classification o Meningioma (classic, benign) = 90% o Atypical meningioma = 9% o Anaplastic (malignant) meningioma = 1%

CHECKLIST

9.

CPA-lAC

Asaoka K et al: Intracanalicular meningioma mimicking vestibular schwannoma. AJNR 23:1493-6,2002 Roberti F et al: Posterior fossa meningiomas: surgical experience in 161 cases. Surg Neurol 56:8-20, 2001 Filippi CG et al: Appearance of meningiomas on diffusion-weighted images: correlating diffusion constants with histopathologic findings. AJNR 22:65-72, 2001 Kuratsu J et al: Incidence and clinical features of asymptomatic meningiomas. J Neurosurg 92:766-70,2000 Ildan F et al: Correlation of the relationships of brain-tumor interfaces, magnetic resonance imaging, and angiographic findings to predict cleavage of meningiomas. J Neurosurg 91:384-90, 1999 Yoshioka H et al: Peritumoral brain edema associated with meningioma: influence of vascular endothelial growth factor expression and vascular blood supply. Cancer 85:936-44, 1999 Haught K et al: Entirely intracanalicular meningioma: contrast-enhanced MR findings in a rare entity. AJNR 19:1831-3, 1998 Lalwani AK et al: Preoperative differentiation between meningioma of the cerebellopontine angle and acoustic neuroma using MRI. Otolaryngol Head Neck Surg 109:88-95, 1993 Buetow MP et al: Typical, atypical, and misleading features in meningioma. Radiographies 11:1087-106, 1991

MENINGIOMA,

CPA-lAC

IIMAGE GALLERY Typical (Left) Axial T7 C+ MR shows a smaller CPA meningioma as an enhancing, dural-based mass (arrow) asymmetrically oriented to porus acusticus of lAC (open arrow). There is minimal but definite penetration into medial lAC (curved arrow). (Right) Coronal T7 C+ MR reveals a smaller CPA meningioma (arrow) at level of lAC. Tumor penetrates porus acusticus (curved arrow). "Tell tale" dural "tail" (open arrow) helps make the meningioma diagnosis.

Variant (Left) Isolated intracanalicular meningioma is a rare lesion to encounter. This coronal CT through lAC shows a focal area of meningioma associated hyperostosis (arrow) that at first glance may suggest osteoma of lAC. (Right) Coronal T7 C+ MR demonstrates the area of hyperostotic bone (arrow) adjacent to the enhancing intracanalicular meningoma (open arrow). Black line separating 2 linear areas of enhancement (curved arrow) is crista falciform is.

Variant (Left) Axial T7 C+ MR shows a large CPA meningioma fills both CPA (arrow), lAC (open arrow). Notice lesion involves middle ear (curved arrow). Mastoid fluid enhances much less than meningioma. (Right) Axial T7 C+ MR reveals extensive low CPA meningioma (arrows) with en plaque morphology. Notice left vertebral artery (open arrow) & internal carotid artery in carotid space (curved arrow) are engulfed by tumor.

CPA-lAC

3 35

METASTASES, CPA-lAC

3 36 Axial gross pathologic specimen viewing CPA area from above shows nodular meningeal metastasis (arrow) protruding from porus acusticus of internal auditory canal (Courtesy R. I-Iewlett, MO).

I TERMINOLOGY Abbreviations

and Synonyms

• Synonyms: Leptomeningeal carcinomatosis, meningeal carcinomatosis, carcinomatous meningitis o All of these terms are misnomers • Neoplasms are not always carcinomas • Pachymeninges (dura) & leptomeninges (pia + arachnoid) are often both involved • Usually does not contain an inflammatory (-itis) component

Definitions • Diffuse infiltration cells metastasizing

I IMAGING

• NECT: Often normal • CECT o Unilateral or bilateral pathologic meningeal enhancement of meninges along CPA & lAC o CT shows lesions only when larger and/or multiple

FINDINGS

General Features • Best diagnostic clue: Bilateral linear or nodular meningeal enhancement in CPA-lAC on T1 C+ MR • Location o Common sites of origin • Primary tumors include breast, lung & melanoma • Meningeallymphoproliferative malignancy = lymphoma & leukemia

Meningitis

• Primary CNS tumor seed basal cisterns (drop metastases) o CPA and/or lAC meninges • Any other meningeal surface may be concurrently affected o Other CPA location • Metastatic focus in flocculus of cerebellum projects into CPA cistern o May extend into lACs & resemble bilateral acoustic tumors (NF2) • Size: Often small « 1 cm); causes symptoms early • Morphology: Infiltrating margins usually present

CT Findings

of leptomeninges by malignant from systemic neoplasia

DDx: linear-Multinodular

Patient with acute onset 7th & 8th nerve palsies. Axial T1 C+ MR shows nodular metastasis in right CPA centered anterior to lAC. Linear enhancement along meninges of lAC present (arrow).

MR Findings • T1WI: Focal meningeal thickening, isointense to gray matter • T2WI o High-resolution T2 MR • Tissue-intensity linear material along leptomeninges • 7th & 8th cranial nerves may be thickened • FLAIR

lesions of CPA-lAC

RHS

Sarcoid, CPA

CPA-lAC

NF2

METASTASES, CPA-lAC Key Facts Terminology

Top Differential

• Synonyms: Leptomeningeal carcinomatosis, meningeal carcinomatosis, carcinomatous meningitis • Diffuse infiltration of leptomeninges by malignant cells metastasizing from systemic neoplasia

• • • •

Imaging Findings

Pathology

• Best diagnostic clue: Bilateral linear or nodular meningeal enhancement in CPA-lAC on Tl C+ MR • Primary tumors include breast, lung & melanoma • Meningeallymphoproliferative malignancy = lymphoma & leukemia • Primary CNS tumor seed basal cisterns (drop metastases) • Tl C+ MR shows diffuse thickening & enhancement of leptomeninges (pia + arachnoid)

• Most commonly seeds meninges

o Larger lesions may cause high signal in adjacent brain stem and/or cerebellum o Associated parenchymal brain metastases seen as multiple high signal areas • Tl C+ o Tl C+ MR shows diffuse thickening & enhancement of leptomeninges (pia + arachnoid) o Enhancing mass centered in flocculus of cerebellum o Meningeal metastasis • Pathologic enhancement of meninges • Process typically diffuse & linear • Nodular masses have been described • Unilateral or bilateral • Associated other meningeal foci common • Multiple enhancing parenchymal brain metastases may be associated o Floccular metastasis • Enhancing mass centered in flocculus enlarging into CPA cistern

Imaging Recommendations • Best imaging tool: Tl C+ MR through posterior fossa is best imaging tool & sequence • Protocol advice o Axial & coronal planes recommended o Look for lAC enhancement but also evaluate meninges of the supra- & infratentorial brain

I DIFFERENTIAL DIAGNOSIS Meningitis • Bacterial, fungal or tuberculous meningitis • Tl C+ MR may be identical to CPA-lAC metastases • Clinical information & cerebrospinal fluid (CSF) evaluation keys

Ramsay Hunt syndrome (RHS) • External ear vesicular rash • Tl c+ MR shows enhancement 7th cranial nerve

in lAC & inner ear ±

Diagnoses

Meningitis Ramsay Hunt syndrome (RHS) Sarcoidosis, CPA-lAC Bilateral acoustic schwannoma (NF2) results when extracranial

neoplasm

Clinical Issues • Most common signs/symptoms: Rapidly progressive unilateral or bilateral 7th & 8th cranial nerve palsies • No curative treatments available • Therapies aimed at preserving neurologic function and improving quality of life

Sarcoidosis, CPA-lAC • Tl C+ MR may be identical when multifocal meningeal type • Look for infundibular stalk involvement • Increased erythrocyte sedimentation rate (ESR) & serum angiotensin converting enzyme (ACE)

Bilateral acoustic schwan noma (NF2) • Younger patients without history of malignancy • Focal CPA-lAC nodular masses • Remaining meninges spared

I PATHOLOGY General Features • General path comments o Leptomeningeal disease may arise de novo • Primary tumor may be undiagnosed or never found o Most commonly results when extra cranial neoplasm seeds meninges o Key anatomy: Meninges has 3 discrete layers • Dura (pachymeninges): Dense connective tissue attached to calvarium • Pia: Clear membrane firmly attaches to surface of brain; extends deeply into sulci • Arachnoid: Interposed between pia & dura; pia + arachnoid = leptomeninges • Etiology o Metastatic tumor involves leptomeninges of CPA and/or lAC o Leptomeninges follow 7th & 8th cranial nerves into lAC o Any leptomeningeal disease may manifest within lAC o Frequent association of CPA-lAC lesions with other meningeal lesions suggests following pathways of spread • Cerebrospinal fluid dissemination • Leptomeningeal extension • Epidemiology

CPA-lAC

3 37

METASTASES, CPA-lAC o Increasingly more common neurologic complication of systemic cancer • Due to increase in survival rate of cancer patients • Associated abnormalities o Multiple other leptomeningeal foci around brain o Parenchymal brain metastases may also be present

Gross Pathologic & Surgical Features • Diffuse, nodular &/or discrete

Microscopic

3 38

Features

• Common tissue types found o Solid tumors = breast, lung & melanoma • All involve both leptomeninges & pachymeninges o Lymphoproliferative malignancy = lymphoma & leukemia • Involve both leptomeninges & pachymeninges o "Drop" metastases from CNS tumors: Medulloblastoma, ependymoma, glioblastoma multiforme

Image Interpretation

I SELECTED REFERENCES 1. 2. 3.

4.

I CLINICAL ISSUES

5.

Presentation • Most common signs/symptoms: Rapidly progressive unilateral or bilateral 7th & 8th cranial nerve palsies • Clinical profile: Patient with past history of treated malignancy • Other symptoms o Vertigo & polycranial neuropathy

6.

7.

8. 9.

Demographics • Age: Older adults • Gender: No gender specificity

10.

Natural History & Prognosis • Meningeal metastases usually a late stage finding • Poor prognosis as patients have advanced, incurable disease by definition

11.

Treatment

12.

• No curative treatments available • Therapies aimed at preserving neurologic function and improving quality of life • Treatments are same as for underlying neoplasm o Radiotherapy ± chemotherapy depending on tissue type • Surgery rarely will playa role at this stage o Solitary melanoma met may be exception • If any question of diagnosis, excisional biopsy necessary

13.

I DIAGNOSTIC

Pearls

• If suspect CPA-lAC metastasis from Tl C+ MR appearance or history of known malignancy, make sure to review the following o Extracranial and calvarial structures for other lesions to confirm diagnosis o Look for involvement of other meningeal sites such as parasellar, other basal meninges o Parenchymal brain for abnormal FLAIR high signal and/or enhancing lesions on Tl C+ sequences

14.

15.

16.

CHECKLIST

Consider • Bilateral "acoustic schwannoma" in adult, consider metastatic tumor, not NF2 • Rapidly progressive 7th cranial nerve palsy + CPA mass suggests metastatic focus

CPA-lAC

Kesari S et al: Leptomeningeal metastases. Neurol Clin 21(1)25-66, 2003 Whinney D et al: Primary malignant melanoma of the cerebellopontine angle. Otol Neurotol 22:218-22, 2001 Schick B et al: Magnetic resonance imaging in patients with sudden hearing loss, tinnitus and vertigo. Otol NeurotoI22:808-12,2001 Krainik A et al: MRI of unusual lesions in the internal auditory canal. Neuroradiology 43:52-7, 2001 Zamani AA: Cerebellopontine angle tumors: role of magnetic resonance imaging. Top Magn Reson Imaging 11(2):98-107,2000 Shen TY et al: Meningeal carcinomatosis manifested as bilateral progressive sensorineural hearing loss. Am J Otol 21:510-2,2000 Cha ST et al: Cerebellopontine angle metastasis from papillary carcinoma of the thyroid: case report and literature review. Surg Neurol 54(4):320-6, 2000 SwartzJD: Meningeal metastases. AmJ OtoI20:683-5, 1999 Lewanski CR et al: Bilateral cerebellopontine metastases in a patient with an unknown primary. Clin Oncol 11(4):272-3, 1999 Arriaga MA et al: Metastatic melanoma to the cerebellopontine angle. Clinical and imaging characteristics. Arch Otolaryngol Head Neck Surg 121(9):1052-6, 1995 Yuh WT et al: Metastatic lesions involving the cerebellopontine angle. AJNR 14:99-106,1993 Mark AS et al: Sensorineural hearing loss: more than meets the eye? AJNR 14:37-45, 1993 Kingdom IT et al: Isolated metastatic melanoma of the cerebellopontine angle: case report. Neurosurgery 33(1):142-4, 1993 Lee YY et al: Loculated intracranial leptomeningeal metastases: CT and MR characteristics. AJR 154(2):351-9, 1990 Maiuri F et al: Cerebellar metastasis from prostatic carcinoma simulating, on CT-scan, a cerebellopontine angle tumor. Case report. Acta Neurol11(1):21-4, 1989 Gentry LR et al: Cerebellopontine angle-petromastoid mass lesions: comparative study of diagnosis with MR imaging and CT. Radiology 162(2):513-20, 1987

METASTASES, CPA-lAC I

IMAGE GALLERY

Typical (Left) Axial T1 C+ MR

reveals bilateral enhancing "plugs" of tissue filling both internal auditory canals (arrows). On 7stglance the diagnosis of NF2 might be considered. However; this older patient has bilateral lAC metastases. (Right) Axial T1 C+ MR shows en plaque meningeal thickening with enhancement (arrows). Inner ear (open arrows) enhancement bilaterally helps suggests diagnosis of multiple metastatic foci.

(Left) Axial T2WI MR demonstrates cochlear & vestibular nerves (arrow) in the lAC fundus thickened by pia-arachnoid metastatic disease. The modiolus is also enlarged (open arrow) as a result of metastatic involvement. (Right) Axial T1 C+ MR shows pia-arachnoid metastatic disease coating the cranial nerves in the distal lAC (arrow). Spread through the cochlear aperture into the cochlear labyrinth has also occurred (open arrow).

Variant (Left) Axial T1 C+ MR in patient with unilateral SNHL shows focal enhancing metastases centered in left flocculus (open arrow). Low signal within mass & irregular margins suggest this diagnosis. Arrow: Normal opposite flocculus. (Right) Axial T2WI MR acquired while screening a patient with unilateral SNHL reveals a low signal metastases within left flocculus (open arrow). Adjacent middle cerebellar peduncle & cerebellar hemisphere shows high signal edema (arrows).

CPA-lAC

3 39

PART II SECTION 4 Skull, Scalp, and MenlnBes The cov rings of the brain (skull, scalp, meninge ) are often overlooked, taking an imaging "back seat" to the more fascinating brain itself. evertheless, these structures are a source of pathology that should not be minimized in importance. For example, scalp masses are fairly common but rarely discussed in the imaging literature. Most are benign but may cause confusion on imaging studie. The differential diagnosis of focal calvarial masses, especially in children, can be challenging. There are rare but important lesions such as dural cavernous hemangiomas that can be imaging "dead ringers" for more common entitie uch as meningioma. We introduce this section by presenting the normal gross and imaging anatomy of the scalp, skull, and cranial meninges. This includes a detailed view of arachnoid granulations and the perivascular (Virchow-Robin) spaces. We follow with discussions of common malformations, trauma, and a spectrum of tumor and nonneoplastic disorders that involve the brain coverings. Lesions of the anterior, central, and posterior skull ba e are covered in Diagnostic Imaging: Head and eck. Congenital raniostenoses Atretic cephalocele Trauma

SECTION 4: Skull, Scalp, and Meninges

Introduction and Overview Skull, Scalp, Meninges Anatomy-Imaging

Issues

11-4-4

Congenital Craniostenoses Atretic Cephalocele

11-4-8 11-4-12

Trauma Calvarium Fracture Pneumocephalus Intracranial Hypotension

11-4-14 11-4-18 11-4-22

Nonneoplastic and Tumorlike Disorders Intracranial Pseudotumors Hypertrophic Pachymeningitis Fibrous Dysplasia Paget Disease Extramedullary Hematopoiesis Thick Skull Histiocytosis Neurosarcoid

11-4-26 11-4-30 11-4-34 11-4-38 11-4-42 11-4-44 11-4-48 11-4-52

Neoplasms Meningioma Atypical and Malignant Meningioma Benign Nonmeningothelial Tumors Malignant Nonmeningothelial Tumors Hemangioma Myeloma Skull and Meningeal Metastases

11-4-56 11-4-60 11-4-64 11-4-68 11-4-72 11-4-76 11-4-80

I

SKULL, SCALP, MENINGES ANATOMY-IMAGING

Coronal graphic shows the calvarial apex. 555 is formed by outer; inner dura. Arachnoid is indicated by open arrows. Arachnoid granulations extend from arachnoid into 555 (curved arrow).

4

ITERMINOLOGY Abbreviations

and Synonyms

• Pachymeninges = dura • Leptomeninges = arachnoid, pia • Galea aponeurotica = epicranial aponeurosis

Definitions • Dura = thick dense layer of fibrous connective tissue that is the most external layer of meninges o Epidural space = potential space between dura, inner table of calvarium o Subdural space = potential space between inner layer of dura, arachnoid • Arachnoid = thin, nearly transparent layer closely applied to inner dura o Subarachnoid space (SAS) = CSF-filled space between arachnoid, pia • Pia = thin, delicate membrane closely applied to brain (covers vessels, trabeculae in SAS), lines perivascular spaces o Subpial space = typically seen only when artificially detached from brain during fixation • Perivascular (Virchow-Robin) spaces = interstitial fluid (ISF)-filled, pial-lined spaces that accompany penetrating arteries

IIMAGING

ANATOMY

Anatomic Relationships • Scalp has 5 layers (first 3 firmly connected, act as single layer/flap) o Dermis (skin) o Subcutaneous fibro-adipose tissue • Fat density/signal intensity o Epicranium and muscles, aponeurosis • Occipitofrontalis • temporoparietalis o Subaponeurotic areolar tissue o Pericranium

surgically

ISSUES

Coronal gross pathology shows 555 is enclosed by dura, which folds inwards to form the falx cerebri (arrow). Note numerous accessory venous channels within falx (Courtesy S. Stensaas, PhD).

• Skull vault (calvarium) o Bones • Frontal • Parietal • Occipital (squamosa) • Temporal (squamosa) • Sphenoid (greater wing) o Sutures • Coronal • Sagittal • Lambdoid • Metopic (frontal; variable) o Inner table • Depressions for arachnoid granulations • Grooves for meningeal vessels • Parietal foramina (venous emissary channels, lakes) o Diploic space • Trabecular bone contains fat, red marrow • Inhomogeneously hyperintense on T1WI; hypointense with fat suppression • Cranial meninges o Pachymeninges (dura) • Dense fibrous connective tissue with layered collagen fascicles • Two layers: Outer (peri- or endosteal) and inner (meningeal) • Closely adherent, apposed except where separated (enclose venous sinuses) • Outer layer forms periosteum of calvarium, tightly attached to inner table (especially at sutures) • Inner layer folds (forms falx cerebri, tentorium, diaphragma sellae), divides cranial cavity into compartments • Dural capillaries lack endothelial tight junctions, therefore enhance strongly • Normal dura at imaging = smooth, < 2 mm, enhances less than cavernous sinus • On coronal Tl C+ MR appears most prominent near vertex, discontinuous as passes inferiorly and wraps under temporal lobes

I SKULL, SCAL~ MENINGES ANATOMY-IMAGING

ISSUES

DIFFERENTIAL DIAGNOSIS Congenital

Nonneoplastic masses

• phalocele • ranio ynostosis (syndromic, • Dermoid, epidermoid

• • • •

poradic)

Infection • Fa ciitis, osteomyelitis • Meningiti

Benign neoplasms

+/- ub-, epidural absce

• • • •

Trauma/hemorrhage/vascular malformations • • • • •

Ilematoma ( uperficial, sub-/epidural) Hemorrhage (subara hnoid; uperficial Fracture +/- pneumocephalus Intracranial hypoten ion dAVF, inus pericranii, etc

IMAGING

Normal Measurements • Normal dura generally < 2 mm

Imaging Pitfalls • Prominent

VRSs

ISSUES

Hemangioma (skull, dura) Plexiform neurofibroma ( Fl) Meningioma Benign nonmeningothelial tumors (e.g., osteoma)

Malignant neoplasms

idero is)

• teta tase • arcinoma (e.g., calp ba al cell, melanoma) • Myeloma, lymphoma • Hemangiopericytoma

o Should not be mistaken for lacunes (usually show no surrounding signal abnormality) o Can become very large, bizarre-looking; should not be mistaken for neoplasm

o Arachnoid • Thin, translucent; attached loosely to meningeal layer of dura • Forms outer margin of subarachnoid space (SAS) • Does not enter sulci or fissures (exception: dips into interhemispheric fissure along falx) • Trabeculae extend from arachnoid across SAS to pia (invested with thin pia-like layer) o Arachnoid granulations • Extension of SAS, arachnoid through dural wall and into venous sinus • Covered with arachnoid cap cells, venous sinus endothelium • CSF drains through endothelium into venous sinus • Most common sites: Superior sagittal, transverse sinuses • CSF density/signal intensity on imaging; do not enhance • Variant: Large ("giant") arachnoid granulations o Pia (covers glia limitans of cortex, extends into perivascular spaces) o Perivascular (Virchow-Robin) spaces (VRSs) • Pial-lined (single layer in cortex, double layer in basal ganglia/midbrain) • VRSs are filled with brain interstitial fluid (ISF), not CSF • Can be seen anywhere in brain, at all ages • Most prominent in/around anterior commissure and subcortical white matter • Imaging: Signal like CSF, suppresses on FLAIR • Variant: Giant ("tumefactive") VRSs should not be mistaken for neoplasm

IANATOMY-BASED

Fibrous dyspla ia, Paget di ease Langerhans cell histiocytosis, arcoido i Inflammatory p eudotumor Extramedullary hematopoiesis

Other Imaging Issues • Dura-arachnoid thickening o Follows inner table of skull o Can be smooth/linear or "lumpy-bumpy" o Nonspecific (can be caused by both benign and neoplastic disease) • Pia-subarachnoid space thickening o Follows pial surface of brain o Dips into sulci, cisterns o When severe, may fill SAS o Nonspecific (can be benign or malignant; infectious or neoplastic)

ICUSTOM DIFFERENTIAL DIAGNOSISI Scalp mass(es) • • • • • •

Dermoid Lipoma Contusion/laceration/hematoma (often subgaleal) Vascular malformation Plexiform neurofibroma Metastasis (extension from calvarium)

Generalized calvarial thickening

I

• Normal variant • Congenital anomaly (primary such as osteopetrosis secondary, Le., with microcephaly) • Shunted hydrocephalus • Long-term phenytoin (Dilantin) therapy • Acromegaly • Paget disease • Fibrous dysplasia • Chronic calcified subdural hematoma • Hematologic disorders o Thalassemia o Sickle cell disease o Iron deficiency anemia

vs

SKULL, SCAL~ MENINGES ANATOMY-IMAGING

I

Graphic depiction of arachnoid granulation projecting into dural venous sinus. Core of CSF (curved arrow) with covering of arachnoid cap cells (arrow), venous sinus endothelium (open arrows).

4 6

Focal or regional skull thickening • • • • • •

Normal variant (hyperostosis frontalis intema) Fibrous dysplasia Paget disease Meningioma Osteoblastic metastases (e.g., prostate, breast) Calcified cephalo- or subdural hematoma

ISSUES

CECT scan shows three discrete, round/ovoid filling defects in the transverse sinuses (arrows). All 3 measure CSF attenuation. Prominent arachnoid granulations, a normal variant.

• • • •

Eosinophilic granuloma Metastases (e.g., breast) Myeloma Multiple burr holes

Diffuse dural enhancement (abnormal, i.e., thick, continuous, nodular)

• Prominent convolutional markings (normal variant vs craniosynostosis) • Long-standing hydrocephalus • Osteogenesis imperfecta, achondrogenesis, hypophosphatasia, etc

• Postoperative • Infection • Inflammatory (sarcoid, histiocytosis, idiopathic hypertrophic cranial pachymeningitis) • Dural sinus thrombosis (collateral flow) • Intracranial hypotension (venous congestion) • Neoplasm (metastases> primary)

Regional/focal

I SELECTED REFERENCES

Generalized

calvarial thinning

skull thinning/defects

• Normal a Arachnoid granulations a Venous lakes • Lacunar skull (Chiari II) • Parietal foramina, large fontanelles, etc • Iatrogenic (burr holes) • Slow-growing intracranial mass o Arachnoid cyst o Low-grade cortically-based neoplasm like DNET • Leptomeningeal cyst ("growing" skull fracture) • NFl with sutural defects

1.

2. 3. 4. 5.

Solitary lytic calvarial lesions • Epidermoid (involves both inner, outer tableSi sclerotic rim) • Eosinophilic granuloma ("beveled" edges, no adjacent sclerosis) . • Metastasis (usually multiple), plasmacytoma • Lytic phase of Paget disease (well-circumscribed, sharply marginated) • Osteomyelitis • Cranial fasciitis of childhood

6.

I.

Multiple

lytic skull lesions

• Metabolic (hyperparathyroidism)

7. 8.

9.

de Divitiis 0 et al: Endoscopic transoral-transclival aproach to the brainstem and surrounding cisternal space: anatomic study. Neurosurgery 54: 125-30, 2004 Glass RBJet al: The infant skull: A vault of information. RadioGraphies 24: 507-22, 2004 Krmpotic-Nemanic J et al: The fate of the arachnoid villi in humans. Coil Antropol. 27(2):611-6, 2003 Riku S et al: Idiopathic hypertrophic pachymeningitis. Neuropathology. 23(4):335-44, 2003 Conegero CI et al: Tridimensional architecture of the collagen element in the arachnoid granulations in humans: a study on scanning electron microscopy. Arq Neuropsiquiatr. 61(3A):561-5, 2003 Rosso D et al: Dural cavernous angioma: a preoperative diagnostic challenge. CanJ Neurol Sci. 30(3):272-7, 2003 Nonaka H et al: Microvasculature of the human cerebral meninges. Neuropathology. 23(2):129-35, 2003 Rappard G et al: MR-guided catheter navigation of the intracranial subarachnoid space. AJNR Am J Neuroradiol. 24(4):626-9,2003 Hausler M et al: Inflammatory pseudotumors of the central nervous system: report of 3 cases and a literature review. Hum Pathol. 34(3):253-62, 2003

I

SKULL, SCAL~ MENINGES ANATOMY-IMAGING ISSUES

IIMAGE GALLERY

I

Normal (Left) Coronal graphic shows

the cranial meninges. Outer; inner dural layers form the SSS. The falx cerebri is an inward double fold of the meningeal dura. The cavernous sinus is an intradural structure. (Right) Coronal Tl C+ MR obtained at 3T shows SSS (open arrow) between outer; inner dural leaves. Dura curves down under the calvarium in a thin, smooth, somewhat discontinuous enhancing line (arrows).

4 7

Normal (Left) Sagittal graphic shows

the cranial leptomeninges enclosing CSF cisterns (in yellow). Green = arachnoid closely applied to inner dura (arachnoid along falx not shown), red = pia along brain surfaces. (Right) Sagittal T1 C+ MR at 3T shows enhancing falx cerebri (arrows), clival dura (open arrow), normal "flow voids" in SS, SSS. CSF-filled subarachnoid space lies between nonenhancing arachnoid and pia.

Normal (Left) Coronal graphic shows

cranial meninges. A thin pial layer covers brain, vessels/trabeculae in SAS (open arrows), invaginates along a penetrating cortical artery to form perivascular spaces (arrow). (Right) Axial T2WI MR at 3T shows numerous prominent but normal perivascular spaces in subcortical, deep WM (arrows). Note PVSs are invisible passing through cortex, are seen only when they enter the WM.

CRANIOSTENOSES

Coronal oblique NECT 3D reconstruction shows right frontal flattening, unilateral coronal synostosis (arrow) and an angled sagittal suture (open arrow).

4 8

o Plain films (extremity): Many anomalies described, certain are specific • Apert: Hand/foot syndactyly • Pfeiffer: Wide, "stub" thumbs • Saethre-Chotzen: Duplicated distal phalanx and cone shaped epiphysis of hallux • Muenke-type mutations: Calcaneo-cuboid fusion • Crouzon: Hands/feet normal

ITERMINOlOGY Abbreviations

and Synonyms

• Craniostenosis, sutural synostosis, craniosynostosis, cranial dysostosis

Definitions • Heterogeneous group of disorders with premature fusion (osseous obliteration) of cranial sutures o Non-syndromic craniosynostosis (more common) o Syndromic (> 150 syndromes)

CT Findings

IIMAGING FINDINGS General Features • Best diagnostic clue: Skull growth is !perpendicular & 1 parallel to fused suture • Location: Calvarium, +/- skeletal anomalies • Size: Single suture or universal synostosis • Morphology: Classic imaging appearance: Calvarial (and facial) distortion

Coronal oblique NECT 3D reconstruction shows hypotelorism and trigonocephaly with beaking of the fused metopic suture (arrow). The sagittal and coronal sutures are patent.

to

Radiographic Findings • Radiography o Skull: Dense suture; "bone bridge" on tangential view; digital markings; inner table scalloping

• NECT o Fibrous or bony "bridging"i may see bony "beaking" along suture o Scaphocephaly: ! Transverse, 1 AP ~ sagittal synostosis o Trigonocephaly: "Ax-head"i "pear-shaped" on axial ~ metopic o Plagiocephaly: Asymmetry ~ unilateral single or asymmetric multiple o Brachycephaly: 1 Transverse, ! AP ~ bicoronal or bilambdoid o Turricephaly: "Towering skull" ~ bicoronal or bilambdoid o Kleebattschadel: Bulging temporal, shallow orbits ~ bicoronal AND bilambdoid o Craniofacial dysostoses: "Towering skull", shallow orbits

DDx: Syndromic and Universal Stenoses

Skull, Scalp, and Meninges

CRANIOSTENOSES Key Facts Terminology • Heterogeneous group of disorders with premature fusion (osseous obliteration) of cranial sutures • Non-syndromic craniosynostosis (more common) • Syndromic (> 150 syndromes)

Imaging Findings • Best diagnostic clue: Skull growth is l perpendicular to & i parallel to fused suture • Size: Single suture or universal synostosis • Morphology: Classic imaging appearance: Calvarial (and facial) distortion • Fibrous or bony "bridging"; may see bony "beaking" along suture • Scaphocephaly: l Transverse, t AP ~ sagittal synostosis

• Trigonocephaly: "Ax-head"; "pear-shaped" on axial ~ metopic • Plagiocephaly: Asymmetry ~ unilateral single or asymmetric multiple • Brachycephaly: i Transverse, l AP ~ bicoronal or bilambdoid • Turricephaly: "Towering skull" ~ bicoronal or bilambdoid • Kleebattschadel: Bulging temporal, shallow orbits ~ bicoronal AND bilambdoid • Craniofacial dysostoses: "Towering skull", shallow orbits

Top Differential

Diagnoses

• Postural flattening • Secondary craniosynostosis

MR Findings

Secondary craniosynostosis

• Tl WI: Syndromic: See cerebellar tonsillar ectopia, hydrocephalus; agenesis corpus callosum (Apert craniofacial dysostosis) • T2WI: Non-syndromic, single synostoses: Brain normal • MRV: Postoperative dural venous occlusions occur

• Arrest of brain growth =} especially metopic or universal craniosynostosis

Ultrasonographic

Findings

• Fetal diagnosis of craniosynostosis defined by calvarial deformities and loss of normal sutural hypoechogenicity

Nuclear Medicine

Findings

• Bone Scan o Bone scintigraphy: Less accurate than PF or CT • Especially in the very young infant • Brain scintigraphy: Focall cerebral blood flow (CBF) subjacent to stenosed suture

Imaging Recommendations • Cephalometrics (plain skull radiographs): Optional • Low-dose 3D CT for surgical planning and follow-up • Common indication for imaging o Evaluate whether suture patent or fused o Assess brain anomalies, pre-operative ventricle size o Surgical planning and routine follow-up o Complications: Post-operative dural vein thrombosis, hydrocephalus, infection

I DIFFERENTIAL DIAGNOSIS Postural flattening • Hypotonic infant =} especially unilateral lambdoid ("sticky" suture) o Postural: Parallelogram skull, ipsilateral anterior ear displacement o Lambdoid synostosis: Trapezoid skull, ipsilateral posterior ear displacement • Premature infant =} especially sagittal

I PATItlO lOG'M General Features • General path comments o Embryology-anatomy • 13 weeks: Mineralization proceeds outwards from ossification centers • 18 weeks: Mineralizing bone fronts meet =} induce sutures • Skull enlarges by appositional growth at suture • Bone plates separated by osteogenic stem cell filled space • t Cell proliferation in sutures prior to onset of fusion =} i collagenous extracellular matrix =} subsequent ossification • Synostosis of one suture =} excessive growth at unfused sutures • Genetics o Syndromic synostoses usually autosomal dominant o Heterozygous gene mutations (FGFR: 1-3, TWIST and MSX2) • Fibroblastic growth factors (FGFs) bind to fibroblastic growth factor receptors (FGFRs) =} signal cell proliferation and differentiation • TWIST and MSX2 (transcription factors) determine the expression of target effector genes • Etiology o Up regulation of factors signaling sutural fusion: Transforming growth factor (TGF) and FGFs/FGFRs o Intact dura regulates overlying sutural activity • Acts as internal periosteum with osteogenic/ directional role • Regional differentiated dura mater induces fusion or allows patency in adjacent suture o Other craniosynostosis etiologies: Metabolic bone disease: t Thyroid, "l P04-vit D-resistant rickets," mucopolysaccharidoses/mucoli pidoses

Skull, Scalp, and Meninges

4 9

o Focal or generalized "copper-beaten" appearance & sclerotic hyperdense bands represent recurrence o As pediatric skull grows, evaluates for migration of fixation screws, plates, & wires • May end up buried within skull or even intracranially • Development of absorbable hardware may eradicate this problem

• Epidemiology o 1:2,500 o Sagittal 60%, coronal 20-30%, plagiocephaly 5-10%, metopic 1-2% • Associated abnormalities: Syndromic synostoses frequently associated with limb anomalies

Gross Pathologic & Surgical Features • Fibrous or bony "bridging"; focal synostotic foci or diffuse bony "beaking" along suture

Microscopic

Features

• 1 Osteoblastic

cell differentiation/maturation

Consider • Non-syndromic doesn't mean not genetic, single sutural synostoses also governed by genes

Image Interpretation

Presentation

10

• Most common signs/symptoms: Asymmetric face/cranium or t head growth • Clinical profile o Craniofacial asymmetry, with or without extremity malformations o Non-syndromic patients have normal cognitive and motor development o More common in twins, possibly mechanical forces

Demographics • Age o Infancy o At birth if severe or if extremity malformations • Gender o Scaphocephaly M:F = 3.5:1 o Trigonocephaly M:F = 2:1 o Apert M:F = 1:1 • Ethnicity: Apert population-based study: Asian highest prevalence, Hispanic lowest prevalence

Natural History & Prognosis • Abnormal skull growth =;> 1 ICP, impaired CBF, airway obstruction o Craniofacial deformity socially stigmatizing if severe • Single suture =;> 20 mandibular/maxillary deformities • Multiple suture =;> above and 1 ICP, t CBF; airway/aural/visual compromise • Syndromic: (+/-) Midline brain anomalies, (+/-) developmental delays

1.

2.

3. 4.

5.

6.

7.

8.

9.

Treatment • Mild deformity or positional o Aggressive physiotherapy and head repositioning o Orthotic head-band or helmet • Helmet therapy more effective with posterior plagiocephaly than with brachycephaly • Moderate to severe: Surgical cranial vault reshaping o Alternative: Distraction osteogenesis of cranial vault • Advantages: Less invasive, shorter operation time, easy care, minimal dural dissection • Disadvantages: Limited initial reshaping and necessity of a 2nd operation for device removal • Postoperative CT imaging very important o Establishes baseline o Rate of reossification can be assessed in regions where dura is left uncovered

Pearls

• In positional lambdoid flattening: Long-axis of skull is oblique (forehead to contralateral occiput) • In unilateral lambdoid synostosis: Long-axis of skull remains unilateral A-P (forehead to ipsilateral occiput)

10.

11.

12. 13. 14.

Cho BC et al: Distraction osteogenesis of the cranial vault for the treatment of craniofacial synostosis. J Craniofac Surg. 15(1):135-44,2004 Teichgraeber JF et al: Molding helmet therapy in the treatment of brachycephaly and plagiocephaly. J Craniofac Surg. 15(1):118-23, 2004 Glass RBJet al: The infant skull: A vault of information. Radiographies 24:507-22,2004 Trusen A et al: The pattern of skeletal anomalies in the cervical spine, hands and feet in patients with Saethre-Chotzen syndrome and Muenke-type mutation. Pediatr Radiol 33(3):168-72, 2003 Azimi C et al: Clinical and genetic aspects of trigonocephaly: A study of 25 cases. Am J Med Genet 117A(2):127-35,2003 Delahaye S et al: Prenatal ultrasound diagnosis of fetal craniosynostosis. Ultrasound Obstet GynecoI21(4):347-53, 2003 Rice DP et al. Molecular mechanisms in calvarial bone and suture development, and their relation to craniosynostosis. Eur J Orthod 25(2):139-48, 2003 Warren SM et al: Regional dura mater differentially regulates osteoblast gene expression. J Craniofac Surg 14(3):363-70, 2003 Panthaki ZJ et al: Hand abnormalities associated with craniofacial syndromes. J Craniofac Surg 14(5):709-12, 2003 Greenwald JA et al: Regional differentiation of cranial suture-associated dura mater in vivo and in vitro: Implications for suture fusion and patency. J Bone Miner Res 15(12):2413-30, 2000 Nah H: Suture biology: Lessons from molecular genetics of craniosynostosis syndromes. Clin Orthod Res 3(1):37-45, 2000 Alden TD et al: Mechanisms of premature closure of cranial sutures. Childs Nerv Syst 15:670-5, 1999 Wilkie AO: Craniosynostosis: Genes and mechanisms. Hum Mol Genet 6(10):1647-56, 1997 Tolarova MM et al: Birth prevalence, mutation rate, sex ratio, parent's age, and ethnicity in Apert Syndrome. Am J Med Genet 72(4):394-8, 1997

Skull, Scalp, and Meninges

Typical (Left) Lateral NECT 3D reconstruction shows brachyturricephaly following metopic and coronal synostosis. The child has Crouzon syndrome. (Right) Lateral NECT 3D reconsuucdonshows scaphocephaly from early sagittal synostosis. The remainder of the sutures are patent.

11 (Left) Coronal oblique NECT 3D reconstruction in the previous child shows a bony bridge (arrow) across the sagittal suture. Note frontal bossing. (Right) Coronal oblique NECT 3D reconstruction in another child with sagittal synostosis shows patent coronal sutures and "beaking" (arrow) of the fused posterior sagittal suture.

(Left) Axial NECT 3D reconstruction of lambdoid synostosis shows flattening of left brow ipsilateral to the fused left lambdoid suture (arrow); long-axis of skull is right A to right P & remains UNILATERAL. (Right) Axial NECT 3D reconstruction of positional plagiocephaly for comparison shows left lambdoid flattening & ipsilateral forehead prominence, not flattening; long-axis is OBLIQUE from right P to left A.

Skull, Scalp, and Meninges

Sagittal graphic shows midline sub-scalp atretic parietal cephalocele (arrow). Also note the persistent primitive falcine vein (open arrow).

12

Sagittal T2WI MR shows an atretic parietal cephalocele extending intracranially through a midline cranium bifidum (arrow). Also note the ascending primitive falcine vein (open arrow).

o Fenestration of superior sagittal sinus, primitive falcine vein

Abbreviations

and Synonyms

• Atretic parietal cephalocele encephalocele (IPC)

(APC), interparietal

Definitions • Sub scalp cephalocele bifidum

General

connected

to dura via cranium

Features

• Best diagnostic clue: CSF tract & vertical falcine vein "points to" subscalp mass • Location: Superior to lambda, midline, interparietal • Size: Usually < 15 mm • Morphology: Skin covered vertex sub scalp mass

Radiographic • Radiography:

Findings Cranium bifidum near the obelion

CT Findings • NECT o Cranium bifidum superior to lambda (small) o Sub scalp soft tissue mass • CECT o Extension of subscalp mass to or through dura

DDx: Midline Parietal Scalp/Subscalp

Epidermoid

Hemangioma

MR Findings • TIWI o Heterogeneous subscalp mass o Peaked tentorium (coronal) • T2WI o T2WI hyperintense subscalp mass extends through cranium o Persistent vertical falcine vein o Spinning-top configuration of incisura (axial) o Prominent: Superior cerebellar cistern and supra pineal recess • STIR: Fat suppression depicts sub scalp cephalocele • Tl C+: Shows primitive falcine vein • MRV: ± Bifid sagittal sinus

Ultrasonographic

Findings

• Real Time: Cranium bifidum often too small to detect

Imaging Recommendations • Best imaging tool: MRI & MRV • Protocol advice o MR: Thin, small FOV, sagittal T1 & T2 with fat-sat o Contrast to define sagittal sinus, and possible sinus pericranii (fat-sat best)

Masses

Sinus Pericranii

Skull, Scalp, and Meninges

Metastasis

ATRETIC CEPHALOCELE Key Facts Imaging Findings

Top Differential

• Cranium bifidum superior to lambda (small) • T2WI hyperintense subscalp mass extends through cranium • Tl C+: Shows primitive falcine vein • MR: Thin, small FOV; sagittal Tl & T2 with fat-sat • Contrast to define sagittal sinus, and possible sinus pericranii (fat-sat best)

• • • •

Diagnoses

(Rpi) Dermoid cyst Proliferating hemangioma Sinus pericranii Subgaleal tonvexity fluid collections

Clinical Issues • Clinical profile: Subscaip mass enlarges with crying

• Age: I

.

• Gender:

I DIFFERENTIAL DIAGNOSIS (Epi) Dermoid

Demographics • Age: Infants and young children • Gender: Girls slightly more common • Ethnicity: More common in Western hemisphere

cyst

• Scallops outer table, enhancing

wall

Proliferating hemangioma

Natural History & Prognosis

• Lobulated mass, vivid enhancement

• Outcome determined

Sinus pericranii

Treatment

• Internal venous flow, robust enhancement

• Treatment: Surgical

Subgaleal convexity fluid collections • Intact calvarium, fluid in subgaleal space

Metastasis

I DIAGNOSTIC

by associated anomalies

13

CHECKLIST·

• Destructive lesion of diploae

Consider

I PATHOU.OGN'

• Persistent fa1cine sinus points to cephalocele

• APC in child with midline parietal skin covered mass

Image Interpretation

Pearls

General Features • General path comments o Most APCs are involuted true meningoceles or encephaloceles o Embryology: Timing ~ 7-10 weeks of fetal life • Genetics: Typically sporadic, if syndromic ~ midline anomalies (holoprosencephaly, CC agenesis) • Etiology o Overdistended rhombencephalic vesicle o Folate deficiency, valproic acid exposure • Epidemiology o APCs ~ lOx more common than large IPC o IPCs = 10% of all cephaloceles

I SELECTED

Gross Pathologic & Surgical Features

I IMAGE GALlERN'

• Sub scalp mass, with o CSF tract to supracerebellar, suprapineal or quadrigeminal cistern, or o Fibrous tract terminating in falx or tentorium

Microscopic

1. 2.

3. 4.

REFERENCES

Aydin MD: Atretic cephalocele communicating with lateral ventricles. Childs Nerv Syst. 17(11):679-80, 2001 Yamazaki T et al: Atretic cephalocele-report of 2 cases with special reference to embryology. Childs Nerv System 17(11):674-8, 2001 Brunelle F et al: Intracranial venous anomalies associated with atretic cephaloceles. Pediatr RadioI30:743-7, 2000 Patterson R], et al:Atretic parietal cephaloceles revisited: an enlarging clinical and imaging spectrum? A]NR 19:791-5, 1998

Features

• Meningeal and vestigial neural tissue, CSF tract ependymal lined

I CLINICAL

ISSUES

Presentation • Most common signs/symptoms: Interparietal subscalp mass with cranium bifidum • Clinical profile: Sub scalp mass enlarges with crying

(Left) Axial T2WI MR shows superiorly dehiscent tentorial incisura (arrow). (Right) Coronal T2WI MR shows cigar-shaped CSF tract (arrow) on path to the subscalp parietal cephalocele.

Skull, Scalp, and Meninges

4

Axial NECT shows a comminuted depressed fracture near the vertex. A depressed fragment is evident (white arrow), and there is associated sagittal suture diastasis (black arrow).

Axial NECT demonstrates a nondisplaced linear fracture of the frontal bone (arrow).

14

o Skull base Fx: Insensitive; air-fluid (AF) levels o Growing Fx: Widening Fx lines over time

Abbreviations

and Synonyms

CT Findings

• Abbreviations: Fracture (Fx) • Calvarial, skull, skull base, basilar skull Fx

• NECT o Linear Fx: Sharply delineated lucent line with overlying soft tissue swelling o Depressed Fx: Fragment(s) displaced inwards o Diastatic Fx from spreading sutures • May tear underlying vessel causing EDH • Cranial "burst fracture" unique in infants: Wide diastasis (> 4 mm) ~ brain herniates through Fx, extrudes under scalp o Skull base Fx • Longitudinal, transverse, pneumocephalus common • AF level within adjacent air cell(s) • Nasal cavity fluid ~ CSF rhinorrhea • Ear cavity fluid from CSF otorrhea or blood density from hemotympanum • Air in TMJ glenoid fossa may be only CT sign of an inconspicuous skull base Fx o Longitudinal temporal bone Fx • Fx line parallel to long axis of petrous bone • Tympanic membrane disruption • Ossicular disruption; most commonly incudostapedial joint • AF levels in mastoid air cells

Definitions • Fx or break in the cranial (skull) bones

General Features • Best diagnostic clue: Linear calvarial lucency • Location o Fracture at thin squamous temporal/parietal bones, petrous ridge of temporal bone, sphenoid wings o Middle cranial fossa is weakest with thin bones & multiple foramina o Other sites: Cribriform plate, orbital roof, occipital condyles, region between mastoid & dural sinuses • Morphology: Fx can be linear, depressed, diastatic; also comminuted, overriding & closed or open

Radiographic Findings • Radiography o Linear Fx: Sharply defined, linear, lucent line o Depressed Fx: Bone-on-bone density

DDx: Calvariallucencies

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.' -',

~.. /,( ' .. ~~·1·'··· •

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.,

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T

Sutures & Grooves

'j

' .•

"

~

•

.:.

Vascular Grooves

-

,

' MMA Groove

Skllii. Sr;!ln. ;!ncl MpninQ"ps

Arachnoid Gran

CALVARIUM FRACTURE Key Facts Imaging Findings

Pathology

• Morphology: Fx can be linear, depressed, diastatic; also comminuted, overriding & closed or open • May tear underlying vessel causing EDH • AF level within adjacent air cell(s) • CTA: Quickly & easily evaluates for vascular injury • Best imaging tool: NECT; add MRI if depressed Fx or growing Fx • Plain films have no role • NECT scan for any high-risk

• Skull Fx in a child: If multiple, complex, bilateral, depressed & unexplained without trauma ~ RAISES SUSPICION OF CHILD ABUSE

Top Differential • • • •

Diagnoses

Suture line Vascular groove Arachnoid granulation Venous lake

Clinical Issues • • • • • •

Linear Fx: Often asymptomatic without LOC Fx present in majority of severe head injury cases "Raccoon eyes" periorbital ecchymosis "Battle sign" = mastoid ecchymosis Sequelae: CSF leak, delayed eN deficit(s), infarct Most skull Fx, even depressed, do not require surgery

=

Diagnostic Checklist • Sutures curvilinear, symmetric; fractures linear,asymmetric

o Transverse temporal bone Fx • Fx line perpendicular to long axis of petrous bone • Inner ear architecture commonly involved • Dense hemorrhage in mesotympanum o Mixed temporal bone Fx: Imaging elements of both longitudinal & transverse Fx o Occipital condylar fracture o Growing Fx: Herniation of CSF & soft tissue densities into epidural or subgaleal spaces • CTA: Quickly & easily evaluates for vascular injury

4

Vascular groove • Corticated margins, non-linear • Typical location (Le., MMA)

(branches like a tree)

Arachnoid granulation • Corticated margins; typical location (parasagittal, transverse sinus)

Venous lake • Corticated margins; typical location (Le., parasagittal)

MR Findings • • • • •

T2WI: Best to delineate dural injury FLAIR: Hyperintense cerebral contusion T2* GRE: Foci of hemorrhage susceptibility MRA: Assesses arterial injury MRV: Assesses venous injury

Angiographic

Findings

• Mostly supplanted

by CTA & MRA

Imaging Recommendations • Best imaging tool: NECT; add MRI if depressed Fx or growing Fx • Protocol advice o Thin-slice high-resolution NECT for skull base Fx • Sagittal/coronal reconstructions helpful o View/photograph using 3 window settings • Soft tissue: Levels = 40H, window = 75-100H • Bone: Levels = 500H, window = 3000H • Intermediate "blood": Levels = 75H, window = 150-200H • Trauma screen recommendations o Plain films have no role o NECT scan for any high-risk o Evaluate for vascular injury if carotid canal involved: CTA > > MRA > > > DSA

I DIFFERENTIAL

DIAGNOSIS

II?ATIHIOlOG¥ General Features • Etiology o Linear Fx: Low-energy blunt trauma over a wide surface area of skull o Depressed Fx: High-energy direct blow to a small surface area with a blunt object (e.g., baseball bat) o Occipital condylar fracture: High-energy trauma with axial load, lateral bending, or rotational injury • Epidemiology o Skull Fx present in 75% of fatal injuries at autopsy o 25-35% with severe brain injury don't have Fx o Skull base Fx = 19-21% of all skull fractures • Sphenoid Fx accounts for 15% of skull base Fx o 75-90% of depressed Fx are open Fx • Associated abnormalities o Linear Fx: Associated with epi-/subdural hematoma o Depressed Fx: Lacerated dura/arachnoid & parenchymal injury o Skull base Fx: CN injury, CSF leak, epistaxis, periorbital bruising o All: Pneumocephalus o 10-15% with severe head trauma have C1 or C2 Fx o Skull Fx in a child: If multiple, complex, bilateral, depressed & unexplained without trauma ~ RAISES SUSPICION OF CHILD ABUSE

Gross Pathologic & Surgical Features

Suture line • Suture less distinct, has dense sclerotic borders

• Open fractures o Skin laceration over fracture

Skull, Scalp, and Meninges

15

o Fx results in communication between external environment & intracranial cavity o May be clean or contaminated/dirty

Microscopic

Features

• Skull Fx: Extends through entire thickness of bone • Depressed Fx: Comminution of fragments starts at point of maximum impact & spreads centrifugally

Staging, Grading or Classification Criteria • Differentiation between skull Fx & normal sutures o Skull Fx • > 3 mm width, widest at center & narrow at ends • Involves outer/inner tables ~ appears darker than suture line or vascular groove • Can occur anywhere • Typically straight & has angular turns o ~ormal suture • < 2 mm width, same width throughout length • Lighter on x-rays compared to fracture lines • At specific anatomic sites • Does not run a straight line & appears curvilinear 16

Presentation • Most common signs/symptoms o Linear Fx: Often asymptomatic without LOC o Depressed Fx • Loss of consciousness (25% none, 25% < 1 hr) • Often symptoms referable to epidural hematoma o Skull base Fx: "Vernet"/"jugular foramen" syndrome • Foraminal involvement ~ CN 9, 10, & 11 deficits • Difficulty in phonation, aspiration • Ipsilateral paralysis: Vocal cord, soft palate, superior pharyngeal constrictor, sternocleidomastoid, & trapezius o Longitudinal temporal bone Fx • CO~DUCTIVE hearing loss • 10-20% C~ 7 palsy from facial canal involvement o Transverse temporal bone Fx • ~EUROSE~SORY hearing loss, vertigo • 50% C~ 7 palsy from lAC Fx o Mixed temporal bone Fx: Signs/symptoms of both longitudinal & transverse Fx o Occipital condylar Fx • Coma, associated cervical spinal injuries, lower C~ deficits, hemiplegia, quadriplegia • "Collet-Sicard" syndrome: C~ 9, 10, 11, & 12 deficits • Clinical profile o Fx present in majority of severe head injury cases o Linear Fx: Most common skull Fx; swelling at impact site, skin often intact o Depressed Fx: Often palpable; underlying brain, leptomeningeal injury o Skull base Fx • "Raccoon eyes" = periorbital ecchymosis • "Battle sign" = mastoid ecchymosis o Sphenoid bone Fx • CSF rhinorrhea/otorrhea, hemotympanum

Natural History & Prognosis • Sequelae: CSF leak, delayed C~ deficit(s), infarct • Patients who return to ED have a remarkable incidence of missed intracranial lesions, poor outcome • Healing process o Infants: Usually heals in 3-6 months without a trace o Children: Heals within 12 months o Adults: Heals 2-3 years, often residual lucency • Transverse temporal bone Fx o Permanent neurosensory hearing loss o Persistent vertigo, unrelenting C~ 7 palsy • Growing Fx ("post-traumatic encephalocele") can be a late complication o Herniation of CSF, brain, & vessels through lacerated dura/fracture into epidural/subgaleal space

Treatment • Most skull Fx, even depressed, do not require surgery • Contaminated open fractures: Broad spectrum antibiotics & tetanus vaccination • Type II & III occipital condylar Fx: Treated conservatively with neck stabilization via hard (Philadelphia) collar or halo traction • Indications for surgery o Depressed segment> 5 mm below inner table of adjacent bone or cosmesis o Gross contamination, dural tear with pneumocephalus, underlying hematoma o Correction of ossicle disarticulation o Occipital condylar Type III Fx (unstable) which requires atlantoaxial arthrodesis o Persistent CSF leak • Repeat NECT o Patients with contaminated open depressed skull fractures to check for infection/abscess o Dictated by complications; seizures, CSF leak

Consider • Child abuse when trauma undocumented

Image Interpretation

Pearls

• Sutures curvilinear, symmetric; fractures linear,asymmetric

1.

2.

3.

4.

Fabbri A et al: Prospective validation of a proposal for diagnosis and management of patients attending the emergency department for mild head injury. J Neurol Neurosurg Psychiatry 75:410-6, 2004 Legros B et al: Basal fracture of the skull and lower (IX, X, XI, XII) cranial nerves palsy: four case reports including two fractures of the occipital condyle--a literature review. J Trauma. 48(2): 342-8, 2000 Hofman PAM et al: Value of radiological diagnosis of skull fracture in the management of mild head injury. J Neurol Neurosurg Psychiatr 68: 416-22, 2000 Tuli S et al: Occipital condyle fractures. Neurosurgery. 41(2): 368-76; discussion 376-7, 1997

Skull, Scalp, and Meninges

Typical (Left) Sagittal T7WI MR shows a depressed calvarial fracture (black arrow) and its resultant venous epidural hematoma from superior sagittal sinus laceration (white arrow). (Right) Axial NECT demonstrates a nondisplaced linear skull fracture (white arrow). Associated subdural hematoma is barely visible (black arrows) although midline shift is readily seen (curved arrow).

4 17

Typical

(Left) Axial NECT demonstrates a longitudinal fracture of the temporal bone petrous ridge (arrow). Note disarticulation of the incudomallear joint (open arrow). (Right) Axial shows a transverse fracture of the temporal bone petro us ridge (arrow). It has involved both the vestibular apparatus and internal auditory canal.

Variant

(Left) Axial T2WI MR shows a "post-traumatic encephalocele" (arrow) within a calvarial fracture defect. (Right) Coronal T7 WI MR demonstrates a "post-traumatic encephalocele" (arrow) within a calvarial fracture defect.

Skull, Scalp, and Meninges

Anteroposterior pneumocephalus within sulci.

skull radiograph shows as mostly curvilinear collections

Axial NEeT demonstrates both subdural (arrow) as well as multifocalsubarachnoid pneumocephalus.

18

Abbreviations • Intracranial focal

o

and Synonyms

pneumocephalus,

pneumatocele

when

Definitions • Presence of air or gas within the skull o

General Features • Best diagnostic clue: Air within the cranial vault • Location o Can occur in any compartment o Extracerebral: Epidural, subdural, subarachnoid o Intracerebral: Brain parenchyma, cerebral ventricles o Intravascular • Size: Variable: Tiny collections to vast collections • Morphology o Diffuse o Focal: Sometimes referred to as "pneumatoceles"

o

o o

CT Findings • NECT o Very low density collections: -1000 HU o Epidural pneumocephalus

o o

• Remains localized • Does not move with changes of head position Subdural pneumocephalus • Often forms air-fluid level • Confluent • Moves with changes of head position • May see cortical veins stretched through subdural air Subarachnoid pneumocephalus • Multifocal • Non-confluent • Droplet-shaped • Often within sulci Intraventricular pneumocephalus • Rarely in isolation • Other findings of severe head trauma Intravascular air Tension pneumocephalus • "Mt Fuji sign": Subdural air separates/compresses frontal lobes, creating widened interhemispheric space between frontal lobe tips that mimics the silhouette of Mt Fuji • "Air bubble sign": Multiple small air bubbles scattered throughout several cisterns • Associated chronic subdural hematoma Skull, skull base, paranasal sinus, mastoid fractures Neoplasm invading sinus • Expansile or erosive

DDx: Various Locations of Pneumocephalus

Trauma: Sulcal

Fx: Skull base

Trauma: Cisternal

Skull, Scalp, and Meninges

Trauma: Sinus

PNEUMOCEPHALUS Key Facts • Pneumocephalus present in 3% of all skull fractures, 8% paranasal sinus fractures

Terminology • Presence of air or gas within the skull

Clinical Issues

Imaging. Findings • • • • •

Best diagnostic clue: Air within the cranial vault Can occur in any compartment Very low density collections: -1000 HU MRI: Foci of absent signal on all sequences Best imaging tool: NECT

Top Differential

Diagnoses

Diagnostic Checklist

• Traumatic • Iatrogenic • Infectious

• Pneumocephalus usually is not the problem: Find out what's causing it • Intravascular/cavernous sinus air with out trauma or intracranial/intrathecal procedure is of no clinical significance

Pathology • Most common

• Mortality: 15% • Most common complication: CSF leak (50%) • Infection (25%): Meningitis, epidural abscess, cerebritis, brain abscess • Most often resolves on its own after removal of etiology

etiology = trauma: 74%

• Solid or cystic o Sinusitis, mastoiditis o Post-surgical findings • Epidural, subdural, or subarachnoid air • Hyperdense hemorrhage • Craniotomy/-ectomy; sinus/sellar surgical defect • Overlying soft tissue swelling, air, blood o Ventriculostomy procedure • Focally at site of interval placement • May see scattered subarachnoid • Intraventricular common, especially after shunt manipulation o ICP monitor placement • Focally at site of interval placement • May have associated hyperdense hemorrhage • CECT o Enhancing paranasal sinus mass • May be associated with dural abnormality

I DIFFERENTIAl..

MR Findings

General Features

• T2WI: Sinusitis, mastoiditis

• General path comments o Acute pneumocephalus: Most patients present within 4-5 days of inciting event o Chronic pneumocephalus: Several year delay has been reported o Mechanism: Dural tear allows abnormal communication and air introduction via two possible events • Ball-valve mechanism from straining, coughing, sneezing, Valsalva • Vacuum phenomenon caused by CSF loss • Etiology o Most common etiology = trauma: 74% • Blunt: Present in 3% of all skull fractures, 8% paranasal sinus fractures • Air cell involvement: Frontal> ethmoid> sphenoid> mastoid • Penetrating: GSW, knife, penetrable foreign bodies o Neoplasm invading sinus: 13% • Osteoma: Frontal> ethmoid • Pituitary adenoma • Mucocele: Most often frontal • Epidermoid

• T1 C+

o Enhancing paranasal sinus mass • With erosive neoplasm often see dural involvement ~ thickening, occasionally breached • MRI: Foci of absent signal on all sequences o Epidural, subdural, subarachnoid, intraventricular, intravascular, tension pneumocephalus, neoplasm invading sinus, post-surgical findings • Same bullets as above for NECT o Ventriculostomy procedure • Air/hemorrhage at placement site or long tract • t FLAIR signal along tract • Artifact induced by hardware/tubing apparatus o Susceptibility from ICP monitor placement

Imaging Recommendations • Best imaging tool: NECT • Protocol advice o Evaluate variable windows at PACS workstation o From film ~ print trauma CT images with wide windows

DIAGN(,)$I$

19

Traumatic • Associated with other findings of trauma • May be found within any compartment

Iatrogenic • Most often after surgical procedure • Expected pneumocephalus seen in compartments manipulated & non-dependent subarachnoid space • May see intravascular, cavernous sinus following vascular access procedure; asymptomatic

Infectious • Rare sequela of gas-producing

infection

I PATH (')I..0GY

Skull, Scalp, and Meninges

4

20

• Paranasal sinus malignancy: Squamous cell carcinoma (51%), adenoid cystic carcinoma (12%) & adenocarcinoma (11%) o Infection from gas-forming organism: 9% • Extension from mastoiditis, sinusitis o Surgery: 4% • Hypophysectomy • Paranasal sinus surgery o Iatrogenic • Shunt placement/manipulation • ICP monitor placement o Tension pneumocephalus • Burr hole evacuation of subdural hematomas • Lumbar drain placement • Varius intracranial & facial surgeries • Use of nitrous oxide during anesthesia • Epidemiology o Pneumocephalus present in 3% of all skull fractures, 8% paranasal sinus fractures o 100% patients undergoing supratentorial surgery have pneumocephalus in first 48 hrs • Associated abnormalities o Cerebrospinal fluid (CSF) leak secondary to • Fracture: Cribriform plate, sphenoid sinus, mastoid air cells • Complication: Functional Endoscopic Sinus Surgery (FESS) ~ cribriform plate o Paranasal sinus neoplasm o Infection

Gross Pathologic & Surgical Features • Air within skull

Microscopic • • • •

Features

Most often from skull, skull base, or sinus Fx Concomitant dural tear Direct communication outside ~ inside established Air is transmitted forming pneumocephalus

• Patient will be asymptomatic • FREQUENT cause of consternation for on-call radiologists/residents • OF NO CLINICAL CONCERN • Tension pneumocephalus o Intracranial pressure rises as volume of air increases o Requires treatment • Complications o Most common complication: CSF leak (50%) o Infection (25%): Meningitis, epidural abscess, cerebritis, brain abscess

Treatment • Becomes an issue during air transport of trauma patients o Under normal flying conditions with! cabin pressure, intracranial air volume will t by approximately 30% at normal maximum cabin altitude of 8,000 ft o Causes t in ICP dependent upon both initial air volume & rate of change in cabin altitude o For an intracranial air volume of 30 cc, estimated worst-case increments of ICP from sea level to maximum altitude would be • 10 mmHg ~ 21.0 mmHg or 20 mmHg ~ 31.8 mmHg o Thus, sea-level pressure should be maintained during air transport of patients with suspected intracranial air • Most often resolves on its own after removal of etiology • Tension pneumocephalus o Bifrontal craniotomies, bifrontal subarachnoid screws, needle aspirations, ventriculostomies, administration of 100% oxygen, & closure of dural defects o Mixed success rates

Image Interpretation

Presentation • Most common signs/symptoms o Inciting event sequelae, most commonly trauma o Headache o Tension pneumocephalus: Headaches, ! level of consciousness, lateralizing deficits

Pearls

• Pneumocephalus usually is not the problem: Find out what's causing it • Intravascular/cavernous sinus air with out trauma or intracranial/intrathecal procedure is of no clinical significance

Demographics • Age: None; specific causes may have age prevalence • Gender: None; specific causes may have gender prevalence • Ethnicity: None; specific causes may have ethnic prevalence

Natural History & Prognosis • Mortality: 15% • Intravascular pneumocephalus o If trauma induced: Associated with mortal injury o If there is no history of trauma, or intracranial/intrathecal procedure • Secondary to intravenous catheterization • Often seen within cavernous sinus

1.

2.

3. 4.

5.

Andersson N et al: Air transport of patients with intracranial air: computer model of pressure effects. Aviat Space Environ Med. 74(2): 138-44,2003 Thompson TP et al: Iatrogenic pneumocephalus secondary to intravenous catheterization. Case report. J Neurosurg. 91(5): 878-80, 1999 Rubinstein D et al: Gas in the cavernous sinus. AJNRAm J Neuroradiol. 15(3): 561-6, 1994 Hudgins PA et al: Endoscopic paranasal sinus surgery: radiographic evaluation of severe complications. AJNRAm J Neuroradiol. 13(4): 1161-7, 1992 Ishiwata Y et al: Subdural tension pneumocephalus following surgery for chronic subdural hematoma. J Neurosurg. 68(1): 58-61, 1988

Skull, Scalp, and Meninges

PNEUMOCEPHALUS

(Left) Axial NECT shows

extensive intraventricular as well as multifocal subarachnoid pneumocephalus. (Right) Axial NECT shows multifocal subarachnoid and subdural pneumocephalus. Note cortical vein stretched through subdural air (arrow).

4 21 (Left) Axial NECT

demonstrates intravascular pneumocephalus within the superior sagittal sinus. (Right) Axial NECT shows subarachnoid pneumocephalus filling most left-sided sulci near the convexity.

Typical

(Left) Coronal NECT demonstrates a defect from

previous skull base surgery (white arrow) that was causing pneumocephalus. (Right) Axial NEeT shows "Mt. Fujisign" of tension pneumocephalus: Subdural air separates & flattens the frontal lobes, widening the interhemispheric space, mimicking the silhouette of Mt. Fujibilaterally.

Skull, Scalp, and Meninges

INTRACRANIAL

Sagittal graphic shows IH with dural venous engorgement (white arrows), "sagging midbrain" (open arrow), tonsil herniation (black arrow), hypothalamus displaced downwards (curved arrow).

4 22

and Synonyms

• Intracranial hypotension

Sagittal TlWI MR shows sagging midbrain, tonsillar herniation, optic chiasm draped over dorsum sellae. Tl C+ MR (not shown) demonstrated diffuse dural enhancement. Classic spontaneous IH.

• Size: Varies from none/minimal to striking (several mms) • Morphology: Dural enhancement smooth, not nodular or "lumpy-bumpy"

ITERMINOlOGY Abbreviations

HYPOTENSION

(IH)

Radiographic Findings

Definitions

I IMAGING FINDINGS

• Myelography o May demonstrate epidural contrast extravasation +/precise site • Dynamic CT myelo may show extradural contrast o Caution: Myelography may facilitate CSF leak, worsen symptoms

General Features

CT Findings

• Frequently misdiagnosed syndrome of headache caused by reduced intracranial CSF pressure

• Best diagnostic clue o Classic imaging triad = diffuse dural thickening/enhancement, downward displacement of brain through incisura ("slumping" midbrain), subdural hygromas/hematomas o Lack of one classic finding does not preclude diagnosis! • Location o Pachymeninges (dura) • Both supra-, infra tentorial • Primarily affects inner (meningeal) layer • May extend into lACs • Spinal dura, epidural venous plexi may be involved

• NECT o Relatively insensitive; may appear normal o +/- Thick dura o +/- Subdural fluid collections • Usually bilateral • Can be CSF (hygroma) or blood (hematoma) o Suprasellar cistern may appear obliterated o Atria of lateral ventricles may appear deviated medially, abnormally close ("tethered") to midline • CECT: Diffuse dural thickening, enhancement

MR Findings • TlWI o Sagittal shows brain descent in 40-50% of cases

DDx: Diffuse Dural Thickening

Meningitis

Dural Mets

Chronic SOH

Skull, Scalp, and Meninges

Dural Sinus Thrombus

INTRACRANIAL HYPOTENSION Key Facts Terminology

Pathology

• Frequently misdiagnosed syndrome of headache caused by reduced intracranial CSF pressure

• Dural thickening, enhancement due to venous engorgement • Common cause of IH = spontaneous spinal CSF leak

Imaging Findings • • • • •

Sagittal shows brain descent in 40-50% of cases Caudal displacement of tonsils in 25-75% Bilateral subdural fluid collections in 15% FLAIR: Hyperintense dura, subdural fluid Diffuse, intense dural enhancement in 85%

Top Differential • • • • •

•

• • • •

Diagnoses

Meningitis Metastases Chronic SDH Dural sinus thrombosis with venous engorgement Post-surgical dural thickening

• "Sagging" midbrain (midbrain displaced inferiorly below level of dorsum sellae; pons may be compressed against clivus) • Decreased angle between peduncles, pons • Caudal displacement of tonsils in 25-75% • Optic chiasm, hypothalamus draped over sella o Axial • Suprasellar cistern crowded/effaced • Midbrain, pons appear elongated ("fat midbrain") • Temporal lobes herniated over tentorium, into incisura • Lateral ventricles small, often distorted (atria pulled medially by downward displacement of midbrain) o Thickened dura usually isointense with brain o Bilateral subdural fluid collections in 15% • 70% have hygromas (clear fluid collects within dural border cell layer) • 10% have hematomas (blood of variable signal intensity) T2WI o Thickened dura usually hyperintense o Subdural fluid usually hyperintense (variable, depending on age of hematoma) PD/Intermediate: Thickened dura usually hyperintense FLAIR: Hyperintense dura, subdural fluid T2* GRE: May bloom if hemorrhage present T1 C+: Diffuse, intense dural enhancement in 85%

Ultrasonographic

Findings

• Color Doppler: Enlarged superior ophthalmic with higher mean maximum flow velocity

Angiographic

veins

Findings

• Conventional: Cortical, medullary veins may be diffusely enlarged

Nuclear Medicine

Findings

• Radionuclide cisternography (RNe) o Direct findings: Focal accumulation of radioactivity outside of subarachnoid space at leakage site o Indirect findings • Rapid washout from CSF space

Clinical Issues • Severe headache (can be orthostatic, persistent, pulsatile or even associated with nuchal rigidity) • Gender: M < F in patients with spontaneous IH • Most IH cases resolve spontaneously • Dural thickening, enhancement disappears; midline structures return (ascend) to normal position

Diagnostic Checklist • Not all findings must be present for diagnosis of IH

• Early appearance of activity in kidneys, urinary bladder • Poor migration of isotope over convexities

Imaging Recommendations • Best imaging tool o Contrast-enhanced cranial MR for diagnosis o RNC if localization required • Protocol advice o Search for actual leakage site only if • Two adequate blood patches have failed • Post-traumatic leak is suspected

I DIFFERENTIAt·DIAGNOSIS Meningitis • Dura-arachnoid enhancement than pia-subarachnoid space

pattern less common

Metastases • Usually thicker, more irregular ("lumpy-bumpy")

Chronic SDH • Enhancing membranes common • No "sagging midbrain"

enclosing blood products

Dural sinus thrombosis with venous engorgement • Look for thrombosed

sinus ("empty" delta sign, etc)

Post-surgical dural thickening • Look for other post-operative findings (e.g., burr holes) • May occur almost immediately after surgery, persist for months/years

Idiopathic hypertrophic pachymeningitis

cranial

• Headache usually not orthostatic • May cause bony invasion • Infratentoriallocation more common

Skull, Scalp, and Meninges

4 23

INTRACRANIAL HYPOTENSION ICLINICALISSUES

IPATH~L~(j¥

4 24

General Features

Presentation

• General path comments o Surgical specimen generally unremarkable with grossly normal-appearing dura o Skin biopsies typically normal (no identifiable connective tissue abnormalities) • Genetics: Abnormalities in COL5Al/2 in E-DII; FBNl usually normal in patients with isolated skeletal features of Marfan • Etiology o Dural thickening, enhancement due to venous engorgement o Common cause of IH = spontaneous spinal CSF leak • Weak dura +/- arachnoid diverticulae common • Aberrant extracellular matrix with abnormalities of fibrillin-containing microfibrils o Reduced CSF pressure precipitated by • Surgery (CSF overs hunting) or trauma (including trivial fall) • Vigorous exercise or violent coughing • Diagnostic lumbar puncture • Spontaneous dural tear, ruptured arachnoid diverticulum • Severe dehydration • Disc herniation or osteophyte (rare) o Pathophysiology = Monro-Kellie doctrine • CSF and intracranial blood volume vary inversely • In face of low CSF pressure, dural venous plexi dilate • Associated abnormalities o Dilated cervical epidural venous plexus, spinal hygromas, retrospinal fluid collections o Low opening pressure « 6 cm H20), pleocytosis, increased protein on lumbar puncture o Stigmata of systemic connective tissue disorder found in up to 2/3rds of patients • Marfan, Ehlers-Danlos type II • Clinical findings = minor skeletal features, small-joint hypermobility, etc; may be subtle

• Most common signs/symptoms o Severe headache (can be orthostatic, persistent, pulsatile or even associated with nuchal rigidity) o Uncommon: CN palsy (e.g., abducens), visual disturbances o Rare: Severe encephalopathy with disturbances of consciousness • Clinical profile: Young/middle-aged adult with orthostatic headache

Gross Pathologic & Surgical Features • Intracranial dura usually unremarkable • Spinal meningeal diverticula (often multiple), dural holes/rents common • No specific leakage site identified at surgery in at least 50%

Microscopic

Demographics • Age: Peak in third, fourth decades • Gender: M < F in patients with spontaneous IH

Natural History & Prognosis • Most IH cases resolve spontaneously o Dural thickening, enhancement disappears; midline structures return (ascend) to normal position • Rare: Coma, death from severe intracranial herniation

Treatment • Aimed at restoring CSF volume (fluid replacement, bedrest) o Initial: Lumbar or directed epidural blood patch o Emergent intrathecal saline infusion if patient severelyencephalopathic, obtunded • Surgery if blood patch fails (usually large dural tear) or SDHs with acute clinical deterioration o Dural suturing, packing with muscle pledget/Gelfoam, fribrin glue

I DIAGNOSTIC Consider

• Frequently misdiagnosed; imaging is key to diagnosis

Image Interpretation

Pearls

• Not all findings must be present for diagnosis of IH • Look for enlarged spinal epidural venous plexi • Retrospinal fluid at Cl-2 level does not necessarily indicate sit of CSF leak!

I SELECTED REFERENCES 1.

Features

• Meningeal surface normal o No evidence for inflammation or neoplasia • Inner surface o Layer of numerous delicate thin-walled dilated vessels often attached to inner surface o Nests of meningothelial cells may be prominent, should not be misinterpreted as meningioma o May show marked arachnoidal, dural fibrosis if longstanding

CHECKLIST

2.

3.

4.

Schievink WI et al: Connective tissue disorders with spontaneous spinal cerebral spinal fluid leaks and intracranial hypotension: A prospective study. Neurosurg 54: 65-71, 2004 Schievink WI et al: False localizing sign of Cl-2 cerebrospinal fluid leak in spontaaneous intracranial hypotension. J Neurosurg 100:639-44, 2004 de Noronha RJ et al: Subdural haematoma: a potentially serious consequence of spontaneous intracranial hypotension. J Neurol Neurosurg Psychiatry. 74(6):752-5, 2003 Koss SA et al: Angiographic features of spontaneous intracranial hypotension. AJNR AmJ Neuroradiol. 24(4):704-6, 2003

Skull, Scalp, and Meninges

INTRACRANIAL HYPOTENSION

Typical (Left) Sagittal T7 C+ MR in

severe IH shows obliteration of suprasellar cistern, "sagging" and "fat" midbrain with closed angle between peduncles/pons (arrow), dural enhancement, tonsillar descent. (Right) Axial T7 C+ MR (same case) shows diffuse dural enhancement, hypodense extra-axial fluid collections, small ventricles with medial deviation of choroid and ICVs (arrows) caused by midbrain descent.

4 25 (Left) Coronal T7 C+ MR

(same case as above) shows subdural fluid (open arrows) with diffuse dural thickening extending into both lACs (white arrows). Lateral ventricles are pulled towards the midline. (Right) Coronal T2WI MR shows the fluid collections are SDHs of different ages. Drainage of the SDHs without recognizing the underlying diagnosis of spontaneous IH caused worsening of the patient's symptoms.

Variant (Left) Axial T7 C+ MR at the C2 level in a patient with

spontaneous IH shows "draped curtain" appearance of markedly engorged epidural venous plexus (arrows). Brain MR showed only mild dural enhancement. (Right) Coronal T7 C+ MR in a 47 y old female with IH shows an enlarged pituitary gland (open arrow) with mild dural thickening (arrows). Sagittal T7WI (not shown) demonstrated sagging midbrain.

Skull, Scalp, and Meninges

INTRACRANIAL PSEUDOTUMORS

Axial T2WI MR at the level of the mid-medulla shows characteristically low signal area of thickened meninges (arrows) in this patient with intracranial pseudotumor.

4 26

I TERMINOLOGY Abbreviations

and Synonyms

• Idiopathic inflammatory syndrome, hypertrophic plasma cell granuloma

pseudotumor, Tolosa-Hunt cranial pachymeningitis,

Definitions

Axial T1 C+ MR shows enhancing rind of intracranial pseudotumor extending along surface of clivus (arrow), into jugular foramen (open arrow) & along surface of sigmoid sinus (curved arrow).

o Focal meningeal thickening may range in thickness from few millimeters to > 2 cm • Morphology o Infiltrating mass along meningeal surfaces • Mimics meningeal malignancy or en plaque meningioma • Classic imaging appearance o Enhancing mass thickens focal area of meninges

• Mixed inflammatory infiltrate involving meninges usually without associated orbital pseudotumor

CT Findings

I IMAGING FINDINGS

• NECT o Difficult to o Underlying • CECT o Enhancing, o Curvilinear

General Features • Best diagnostic clue: Enhancing, infiltrating meningeal mass • Location o May involve meningeal surface • Predilection for meninges of cavernous sinus area or basal meninges • Falx and tentorium are less often involved o Intracranial involvement in absence of orbital disease is rule (> 90%) • Size o May extensively involve meningeal surfaces & adjacent skull base

DDx: Meningeal Thickening

Meningitis

see without contrast-enhancement bone erosion unusual thickened meninges appearance in a single meningeal

MR Findings • Tl WI: Focal thickening of meninges isointense to gray matter • T2WI o Iso- to hypointense focal meningeal thickening • If fibrosis predominates, hypo intensity may be marked • FLAIR o Adjacent brain edema unusual o If present, best seen on FLAIR sequences • Tl C+

+/- Bone Invasion

Sarcoidosis

region

Meningioma

Skull, Scalp, and Meninges

Metastases

INTRACRANIALPSELJDOTUMORS Key Facts Terminology • Idiopathic inflammatory pseudotumor, Tolosa-Hunt syndrome, hypertrophic cranial pachymeningitis, plasma cell granuloma • Mixed inflammatory infiltrate involving meninges usually without associated orbital pseudotumor

Imaging Findings • Bestdiagl1osticdue: Enhancing, infiltrating meningeal mass • Intracranialinvolvement in absence of orbital disease is rule (> 90%) • Enhancing mass thickens focal area of meninges

Top Differential

Diagnoses

• Meningitis • Sarcoidosis

o Diffusely enhancing focal area of meningeal thickening o In more severe cases, meningeal "rind" may reach 2 cm in thickness o If underlying bone is invaded, fat saturated T1 C+ images show this best • MRA: When extensively involves meninges of cavernous sinus, internal carotid artery narrowing may occur

Imaging Recommendations • Best imaging tool: MR imaging best delineates meningeal disease • Protocol advice o Begin with MR including full brain FLAIR & enhanced T1 C+ with fat-saturation o Bone only unenhanced CT may help differentiate this lesion from en plaque meningioma

IDIFFERENTIAlDIACNOSIS Meningitis • TB, fungal or other in agent causes focal meningeal thickening • CSF analysis may not make diagnosis • Meningeal biopsy may be necessary

Sarcoidosis • Systemic manifestations abound • Increased erythrocyte sedimentation rate (ESR) & serum angiotensin converting enzyme (ACE) • Infundibular stalk involvement

En plaque meningioma • • • •

Enhancing meningeal mass Dural "tails" Permeative-sclerotic invasive bone changes typical May exactly mimic intracranial pseudotumor

Meningeal

metastases

• Nodular meningeal diffuse • Cranial neuropathy

carcinomatosis occurs early

less common than

• En plaque meningioma • Meningeal metastases • Meningeal non-Hodgkin

lymphoma

(NHL)

Pathology • Inflammatory pseudotumor is "quasineoplastic" lesion that most commonly affects lung and orbit • Has been reported to occur in nearly every site in human body • Chronic granulomatous disease of unknown origin

Clinical Issues • Intracranial lesion only: Chronic headaches • Clinical profile: Young adult presenting with chronic headaches & cranial nerve palsies • May respond Wsteroid therapy • Diagnosis of exclusioni.needs meningeal biopsy

• CSF cellular analysis usually provides diagnosis but meningeal biopsy may be necessary

Meningeal

non-Hodgkin

lymphoma (NHl)

• Usually more diffuse, multifocal with underlying bone involvement • The "great pretender" (can mimic many intracranial diseases) • May selectively affect meninges

I PATHOLOGY General Features • General path comments o Inflammatory pseudotumor is "quasineoplastic" lesion that most commonly affects lung and orbit • Has been reported to occur in nearly every site in human body o Can involve any of meninges, cavernous sinus or skull base o Spectrum of idiopathic inflammatory lesions • Etiology o Chronic granulomatous disease of unknown origin o Hypothesis 1: Low grade fibrosarcoma with inflammatory (lymphomatous) cells o Hypothesis 2: Immune-autoimmune pathophysiology • Epidemiology o Intracranial pseudotumor • Usually seen as isolated finding in absence of orbital pseudotumor o Orbital pseudotumor • 3rd most common ophthalmic disorder • 5-8% of all orbital masses

Gross Pathologic & Surgical Features • Surgical impression depends on histopathologic composition o Soft, compressible mass: Intracranial pseudo tumor or plasma cell granuloma o Hard, fibrotic mass: Hypertrophic cranial pachymeningitis

Skull, Scalp, and Meninges

4 27

INTRACRANIAL PSEUDOTUMORS Microscopic

o Steroid resistant cases and/or cases with extensive skull base involvement • Radiotherapy and/or chemotherapy • Surgical resection if in non-eloquent location also possible

Features

• Not a true lymphoid tumor • Histologic hallmarks o Mixed inflammatory infiltrate of lymphocytes (T & B cells) & plasma cells o Varying degrees of fibrosis present • Terminology depends on mix during histopathologic evaluation o Intracranial pseudotumor • Inflammatory meningeal mass with balanced mixture of lymphocytes, plasma cells & fibrous tissue o Plasma cell granuloma • Inflammatory meningeal mass with predominance of plasma cells o Hypertrophic cranial pachymeningitis • Inflammatory meningeal mass with predominance of dense fibrous tissue

4

I CLIN1CAL.ISSUES

28

Presentation

IOlAGNOSTICitctfE¢I<-tfST Consider • Intracranial pseudotumor is diagnosis of exclusion o First exclude infectious meningitis, en plaque meningioma & meningeal malignancy with biopsy o Realize that intracranial pseudotumor, plasma cell granuloma & hypertrophic cranial pachymeningitis are all part of same disease spectrum

Image Interpretation

Pearls

• Focal meningeal enhancing mass suggests includes pseudotumor in differential diagnosis • Diagnosed via meningeal biopsy only

I SELECTED REFERENCES

• Most common signs/symptoms o Intracranial lesion only: Chronic headaches o Orbital lesion: Painful proptosis • Clinical profile: Young adult presenting with chronic headaches & cranial nerve palsies • Other symptoms o Intracranial lesion only: Cranial nerve palsies o Orbital lesion: Visual loss, "red eye" & periorbital swelling

1.

2.

3.

4.

Demographics

5.

• Age o Intracranial pseudotumor: Young adults o Mean age at presentation of orbital pseudotumor 45 years • Gender: No gender propensity

6. =

Natural History & Prognosis

7.

8.

• Intracranial lesions o May respond to steroid therapy o When extensive meningeal-skull base involvement present, may be resistant to all forms of therapy • Such intractable disease may cause severe disability or death • Orbital lesions o 65% represented treatment successes o 35% treatment failures, with partial or no relief of symptoms • Treatment failures: Recurrence of inflammation after a period of quiescence or unremitting inflammation

Treatment

9.

10. 11.

12.

13.

14.

• Options, risks, complications o Diagnosis of exclusion; needs meningeal biopsy • Biopsy excludes infectious & neoplastic causes of focal meningeal thickening o High dose systemic steroids with slow taper is principal treatment option

15. 16.

Kupersmith MJ et al: Idiopathic hypertrophic pachymeningitis. Neurology. 62(5):686-94, 2004 Roche PH et al: Mixed meningeal and brain plasma-cell granuloma: an example of an unusual evolution. Acta Neurochir (Wien). 146(1):69-72,2004 Hausler M et al: Inflammatory pseudotumors of the central nervous system: report of 3 cases and a literature review. Hum Pathol. 34(3):253-62, 2003 Yuen SJ et al: Idiopathic orbital inflammation: distribution, clinical features, and treatment outcome. Arch Ophthalmol. 121(4):491-9, 2003 Narla LD et al: Inflammatory pseudotumor. Radiographies. 23(3):719-29, 2003 Wasmeier C et al: Idiopathic inflammatory pseudotumor of the orbit and Tolosa-Hunt syndrome--are they the same disease? J Neurol. 249(9):1237-41, 2002 Gollogly L et al: Meningeal inflammatory pseudotumour: a case report. Acta Neurol Belg. 101(2):116-20, 2001 Cho YSet al: Inflammatory pseudotumour involving the skull base and cervical spine. J Laryngol Otol. 115(7):580-4, 2001 Dehner LP: The enigmatic inflammatory pseudotumors: the current state of our understanding, or misunderstanding. J Pathol. 192:277-9,2000 Tekkok IH et al: Intracranial plasma cell granuloma. Brain Tumor Pathol. 17(3):97-103,2000 Lorberboym M et al: False-positive uptake of TI-201 by an intracranial inflammatory pseudotumor. Clin Nucl Med. 22(11):756-8, 1997 de Jesus 0 et al: Idiopathic orbital inflammation with intracranial extension. Case report. J Neurosurg. 85(3):510-3, 1996 Bencherif B et al: Intracranial extension of an idiopathic orbital inflammatory pseudotumor. AJNR. 14(1):181-4, 1993 Olmos PR et al: Fibrosing pseudotumor of the sella and para sellar area producing hypopituitarism and multiple cranial nerve palsies. Neurosurgery. 32(6):1015-21, 1993 Sitton JE et al: Intracranial inflammatory pseudotumor. Clin Neuropathol. 11(1):36-40, 1992 Clifton AG et al: Intracranial extension of orbital pseudotumour. Clin Radiol. 45(1):23-6, 1992

Skull, Scalp, and Meninges

INTRACRANIAL PSEUDOTUMORS

Typical (Left) Axial T7 C+ MR reveals intracranial pseudotumor thickening the meninges (arrows). Lesion also enters frontal sinus (open arrow) & invades into suprazygomatic masticator space (curved arrow). (Right) Coronal T7 C+ MR reveals intracranial pseudotumor affecting meninges on planum sphenoidale (arrows). Also notice intra-orbital involvement as enhancing tissue surrounding optic nerve (open arrow).

4 29 (Left) Axial T7 C+ MR reveals diffuse involvement of meninges by intracranial pseudotumor. Even the internal auditory canal (arrows) and the inner ear (open arrows) are involved in this case bilaterally. (Right) Axial T7 C+ MR (same case as left) shows disease spreading from orbital apex (arrow) to intracranial compartment (open arrow) (Courtesy N. Miller, MO).

Variant (Left) Coronal bone-only sinus CT reveals a focal area of bony destruction (arrow) just above the right orbital apex. (Right) Coronal T7 C+ MR with fat-saturation shows orbital pseudotumor in orbital apex surrounding optic nerve (arrow). Lesion spreads through orbital roof to involve the adjacent meninges (open arrow).

Skull, Scalp, and Meninges

HYPERTROPHIC PACHYMENINGITIS

Coronal graphic shows diffuse dura-arachnoid thickening (arrows). Note continuous pattern "turns the corner" under the temporal lobes and may involve the cavernous sinus.

4 30

ITERMINOLOGY Abbreviations

and Synonyms

• Idiopathic cranial hypertrophic pachymeningitis (ICHP); dural pseudotumor • Idiopathic invasive pachymeningitis (IIPM) can mimic neoplasm, aggressive infection (e.g., fungal)

Definitions • Diffuse dural thickening without known etiology (e.g., neoplasm or infection) • Involves at least 75% of dural surface

I IMAGING FIND.INGS

Coronal T1 c+ MR shows diffuse thickened dura extending from the vertex to the tentorial incisura. Biopsy disclosed meningeal fibrosis without inflammatory or neoplastic infiltration.

• Size: > 2 mm up to > 1 cm • Morphology o Usually smooth, linear, diffusely thickened dura o Less common: Nodular +/- focal mass-like lesions

CT Findings • NECT o Diffuse dural thickening • Usually isodense with brain • May be difficult to see without contrast o +/- Focal bone invasion • Jugular foramen, temporal bone, clivus most commonly affected • Less common: Orbit, cavernous sinus infiltration • CECT: Uniform, intense enhancement

MR Findings

General Features • Best diagnostic clue o Thickened enhancing meninges "turn the corner" under temporal lobes in continuous line from vertex (coronal scan) o Caution: Diffusely thickened dura is nonspecific and can be seen in a spectrum of identifiable disorders • Location o Follows inner calvarium o Extends along falx, tentorium o May extend into lACs, orbits, spine o Bilateral> unilateral

• TlWI o Crescentic thickened dura o Usually isointense with brain o Underlying CSF cisterns may be compressed but otherwise appear normal • T2WI o Common: Hyperintense to brain o Less common: Edema in adjacent brain (may be venous congestion) o Rare: Densely fibrosing pseudotumor may appear profoundly hypointense • PD/lntermediate: Hyperintense

DDx: Diffuse Dural Thickening

Chronic SOH

Prostate Mets

Sarcoid

Skull, Scalp, and Meninges

Intracran Hypotens

HYPERTROPHIC PACHYMENINGITIS Key Facts Terminology • Idiopathic invasive pachymeningitis (IIPM) can mimic neoplasm, aggressive infection (e.g., fungal) • Diffuse dural thickening without known etiology (e.g., neoplasm or infection) • Involves at least 75% of dural surface

• • • • •

Chronic subdural hematoma Neoplasm Infection/inflammation Intracranial hypotension Dural sinus occlusion

Pathology

Imaging Findings

• Diffuse dural thickening

• Thickened enhancing meninges "turn the corner" under temporal lobes in continuous line from vertex (coronal scan) • Caution: Diffusely thickened dura is nonspecific and can be seen in a spectrum of identifiable disorders • ;:::2 mm, continuous, can be smooth or nodular

Clinical Issues

Top Differential

Diagnoses

• FLAIR: Variablei usually hyperintense • Tl C+ o Intense, uniform enhancement o ;:::2 mm, continuous, can be smooth or nodular • MRV: May show jugular vein occlusion in IIPM

Findings

• Conventional: May show sigmoid sinus, jugular vein occlusion in IIPM

Nuclear Medicine

• Headache is most common symptom • Follow-up imaging helpful: 80% correlate with clinical state

Diagnostic Checklist • Look for "sagging midbrain" on sagittal T1WI to rule out intracranial hypotension as cause for thickened, enhancing dura

• Normal duralenhancement

Angiographic

has many causes

Findings

• Bone Scan: May be positive if bony invasion present • Fluorodeoxyglucose (FDG) PET o Hypermetabolism initially o t Activity correlates with therapeutic efficacy o Disappearance of uptake matches improved MR appearance and resolution of symptoms

Imaging Recommendations • Best imaging tool o Contrast-enhanced MR o Skull base CT if cranial neuropathy present, bone invasion suspected • Protocol advice: Use fat-suppression coronal Tl C+

Infection/inflam

mation

• Sarcoid often has other lesions, diffuse nonfocal dural thickening < focal dural-based masses • Most common finding in TB is meningitis (pia-arachnoid pattern) • Sinus disease common in Wegener • Systemic symptoms common with rheumatoid arthritis, SLE, Sjogren • Inflammatory pseudotumor +/- bone invasion (indolent infection like Pseudomonas sometimes present)

Intracranial hypotension • "Slumping" midbrain, tonsillar herniation • Dural venous engorgement

Dural sinus occlusion • Engorgement of collateral venous channels may thicken dura • Look for thrombus, "empty delta" sign

I PATHOLOGY General Features

I DIFFERENTIALDIAGNOS1S Normal dural enhancement • Thin « 2 mm), discontinuous, most prominent convexity, less intense than cavernous sinus

at

Chronic subdural hematoma • May contain loculated foci of old hemorrhage • May calcify

Neoplasm • Adjacent skull lesions common in metastasis • "En plaque" meningioma may invade bone, cause hyperostosis, have extensive nonneoplastic dural "tail" • Lymphoma often associated with systemic disease

• General path comments: Role of imaging, pathology is to exclude recognizable inflammatory or neoplastic cause of diffuse dural thickening • Etiology o Diffuse dural thickening has many causes • Congenital (mucopolysaccharidoses) • Iatrogenic (surgery, shunti post-LP meningeal enhancement rare & should be diagnosis of exclusion) • Trauma (chronic SDH) • Spontaneous intracranial hypotension • Infection (TB, HTLV-li indolent infections such as pseudomonas, syphilis, rhinoscleroma, fungal disorders may also invade bone) • Inflammatory (rheumatoid, sarcoid, Wegener, pseudotumor) • Neoplasm (meningiomatosis, lymphoma, mets)

Skull, Scalp, and Meninges

4 31

HYPERTROPHIC PACHYMENINGITIS • Hematologic (monoclonal plasma cell hyperplasia, extramedullary hematopoiesis) • Other (fibrosing inflammatory pseudotumors, fibrosclerosis) o ICHP may be idiopathic, invasive (rare)

Gross Pathologic & Surgical Features • Diffuse dural thickening

Microscopic • • • • • •

Features

Extensive meningeal fibrosis +/- Inflammatory cells (lymphocytes, plasma cells) May have multinucleated giant cells May show foci of necrosis No bacteria, fungi, neoplasia May have necrotizing vasculitis of dura/cerebral surface small arteries

liDIACNqST1C ..CFf[CK.lISI Consider • Ancillary tests (ANA, other serological markers)

Image Interpretation

I SELECTED REFERENCES 1.

2.

I CLINICAL ISSUES

4 32

3.

Presentation • Most common signs/symptoms o Headache is most common symptom o Cranial neuropathy: Progressive sensorineural hearing loss, hoarseness, optic neuropathy, Tolosa-Hunt syndrome o Ataxia, seizures o Diabetes insipidus • Clinical profile o Middle-aged patient with nonpostural headache o Sedimentation rate 1 o CSF may have 1 protein, lymphocytosis o Mild to moderate 1 of C-reactive protein o Has been associated with myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA) disease • MPO-ANCA titers elevated in silicosis workers with ICHP onset • ICHP may be a component of multisystem ANCA-associated vasculitis

4.

Demographics

11.

5. 6.

7.

8.

9.

10.

• Age: Any age; peak 3rd-5th decades

Natural History & Prognosis

12.

• Variable course o Some are benign, require no treatment o Others have sustained remission with steroids o Nearly 50% can relapse with or without steroid dependence

13.

14.

Treatment • Specific diagnosis may require biopsy • Corticosteroid therapy o Recurrence may occur with steroid tapering • Immunosuppressants (e.g., methotrexate, azathioprine) • Follow-up imaging helpful: 80% correlate with clinical state

Pearls

• Look for "sagging midbrain" on sagittal Tl WI to rule out intracranial hypotension as cause for thickened, enhancing dura

15.

16.

17.

D'Andrea G et al: Idiopathic intracranial hypertrophic pachymeningitis: two case reports and review of the literature. Neurosurg Rev. Epub, 2004 Saeki T et al: Two cases of hypertrophic pachymeningitis associated with myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA)-positive pulmonary silicosis in tunnel workers. Clin Rheumatol. 23(1):76-80, 2004 Kupersmith MJ et al: Idiopathic hypertrophic pachymeningitis. Neurology. 62(5):686-94, 2004 Lee YC et al: Idiopathic hypertrophic cranial pachymeningitis: case report with 7 years of imaging follow-up. AJNR Am J Neuroradiol. 24(1): 119-23, 2003 Riku S et al: Idiopathic hypertrophic pachymeningitis. Neuropathology. 23(4):335-44, 2003 Matsumoto K et al: Hypertrophic pachymeningitis as a result of a retropharyngeal inflammatory pseudotumor: case report. Neurosurgery. 51(4): 1061-4; discussion 1064-5, 2002 Sylaja PN et al: Idiopathic hypertrophic cranial pachymeningitis. Neurol India. 50(1): 53-9, 2002 Prabhakar S et al: Hypertrophic pachymeningitis: varied manifestations of a single disease entity. Neurol India. 50(1): 45-52, 2002 Manabe Y et al: Rheumatoid factor positive hypertrophic cranial pachymeningitis in association with hypopituitarism and multiple cranial nerve palsies. Intern Med. 40(9): 964-7, 2001 Holodny AI et al: Tumefactive fibroinflammatory lesion of the neck with progressive invasion of the meninges, skull base, orbit, and brain. AJNR Am J Neuroradiol. 22(5): 876-9,2001 Voller B et al: Hypertrophic chronic pachymeningitis as a localized immune process in the craniocervical region. Neurology. 56(1): 107-9, 2001 Voller B et al: Hypertrophic chronic pachymeningitis as a localized immune process in the craniocervical region. Neurology. 56(1):107-9, 2001 Dumont AS et al: Idiopathic hypertrophic pachymeningitis: a report of two patients and review of the literature. Can J Neurol Sci. 27(4): 333-40, 2000 Nakazaki H et al: Idiopathic hypertrophic cranial pachymeningitis with perifocal brain edema--case report. Neurol Med Chir (Tokyo). 40(4): 239-43, 2000 Nagashima T et al: P-ANCA-positive Wegener's granulomatosis presenting with hypertrophic pachymeningitis and multiple cranial neuropathies: case report and review of literature. Neuropathology. 20(1): 23-30,2000 Hatano N et al: Idiopathic hypertrophic cranial pachymeningitis: Clinicoradiological spectrum and therapeutic options. Neurosurg 45: 1336-44, 1999 Fukui MB et al: MR imaging of the meninges. Part II. Neoplastic disease. Radiol201: 605-12, 1996

Skull, Scalp, and Meninges

HYPERTROPHIC PACHYMENINGITIS

Typical (Left) Axial T2WI MR shows an elderly patient with nonpostural headache, no abnormalities on neurologic examination. The extracerebral CSF spaces appear enlarged but no other abnormalities are present. (Right) Axial T1 C+ MR in the same case shows diffuse dural enhancement. Biopsy showed dural fibrosis without evidence for granulomatous inflammation or neoplasm. Finaldiagnosis was IHPM.

4 Typical

33 (Left) Axial CECT in a patient

with non focal headache shows diffuse tentorial thickening (arrows). (Right) Axial T2WI MR in the same case shows bifrontal hyperintense extra-axial collections (arrows). Biopsy showed nonspecific dural fibrosis without evidence for tumor, infection, or inflammation.

Variant (Left) Axial T1 C+ MR in a patient with multiple lower cranial neuropathies shows markedly thickened dura (arrows) with invasion of the left temporal bone (open arrow). (Right) Axial T1 C+ MR in the same case shows more extensive dural thickening, invasion of clivus and temporal bones. Biopsy disclosed invasive pachymeningitis, etiology unknown (Courtesy N. Miller;MO).

Skull, Scalp, and Meninges

FIBROUS DYSPLASIA

Axial graphic shows expansion of lateral orbital rim, sphenoid wing and temporal squamosa by fibrous dysplasia. Note exophthalmos and stretching of the optic nerve on the ipsilateral side.

4 34

Coronal NECT in child with leontiasis ossea (diffuse craniofacial FD) shows extensive expansion of all bones. Inferior orbital nerve (arrow) is engulfed and the maxillary sinus encroached.

ITERMfNOIOiGY

Radiographic Findings

Abbreviations

• Radiography o Expanded bone with "ground-glass" appearance o CFD: Dental malocclusions in 20%

and Synonyms

• Fibrous dysplasia (FD); craniofacial fibrous dysplasia (CFD); osteitis fibrosa; osteodystrophie fibrosia • McCune-Albright syndrome (MAS): One of the most common FD syndromes • Jaffe-Lichtenstein dysplasia (monostotic FD)

Definitions • Congenital disorder characterized by expanding lesions with mixture of fibrous tissue and woven bone • Defect in osteoblastic differentiation and maturation • One of the most common of the fibro-osseous lesions

CT Findings • NECT o Imaging patterns relate to relative content of fibrous and osseous tissue o Expansile bone lesion, widened diploic space o CT shows "ground glass", sclerotic, cystic or mixed bone changes • If cystic may have thick sclerotic "rind"

MR Findings

I IMAGI NG FINDINGS General Features • Best diagnostic clue: "Ground-glass" matrix in a bone lesion on CT • Location o May involve any aspect of the skull o CFD: Majority have more than one bone involved • Maxilla, orbit, frontal bone most common in one series; ethmoids and sphenoids in another • Size: Small focal lesion to extensive skull involvement

• TlWI: Usual: !TlWI signal • T2WI o Usual: ! T2WI signal (if solid) or in rind (if "cystic") o t Clinical-pathologic activity =} t signal • Tl C+: Variable enhancement depends on lesion pattern (rim, diffuse, or none)

Nuclear Medicine

Findings

• Bone Scan o Radionuclide uptake: Perfusion/delayed phases o Nonspecific; sensitive to extent of skeletal lesions in polyostotic FD • PET: Accumulation (Ue) MET

,~ ,r' '

DDx: Craniofacial Fibrous Dysplasia Mimics

"";~:.")

,~

'

\~i

I

"\

(t/

Cherubism

Carre Osteomyelitis

Osteopetrosis

Skull, Scalp, and Meninges

Meningioma Ostosis

FIBROUS DYSPLASIA Key Facts Terminology

Top Differential Diagnoses

• Fibrous dysplasia (FD);craniafacial fibrous dysplasia (CFD); .osteitis fibrosa; asteadystrophie fibrosia • McCune·Albright syndrame (MAS): One of the mo~t camman FD syndromes • Cangenital disarder characterized by expanding lesians with mixture .offibrous tissue and waven bane • Defect inasteablasticdifferentiatianandmaturatian

• • • • •

Imaging Findings • Best diagnastic clue: "Ground·glass" matrix in a bane lesian an CT • Usual: j T2WI signal (if salid) or in rind (if "cystic") • Best imaging taal: Bane scan ta stage • CT .or MRI ta define lacal extent

Paget disease Garre~clerosing .oste.omyelitis Jaffe-Campanacci. (J-C) syndrome Crani.ometaphyseal dyspla~ia Meningiama

Clinical Issues • Mast camm.on signs/symptams: Painless swelling or deformity • RARE progressian ta fibro·, astea-, ch.ondro· and mesenchymal sarcama

Diagnostic Checklist • Manastatic and palyastatic FD likely an same spectrum .of phenatypic expressian, cansider checking far gene ta predict camplicatians

• Best imaging taal: Bane scan ta stage • Protacal advice o CT or MRI ta define lacal extent o Bane scan ta search far additianallesians

• Neurocutaneaus disorders: Osteitis fibrosa cystica in tuberous sclerosis and NFl • Chronic renal failure: Renal asteadystrophy may simulate leantiasis assea • Margagni syndrome .of hyperostasis frontalis interna: Past-menapausal wamen, limited ta frontal bane

I DIFFERENTIALDIAGNOSIS

I PATHOLOGY

Paget disease

General Features

• Pagetaid ground-glass FD mimics Paget disease • Paget: Calvarium, nat crania facial; "cattan waal" CT

• Hyperostasis and sclerosis .of craniafacial banes ~ facial distortian, cranial nerve campressian • Abnormal madelling .of lang bane metaphyses; paranasal "bas sing" • Mutatians in transmembrane protein ANK an Chr 5p

• General path camments: Any bane can be invalved • Genetics o GNAS1 gene mutatians in mana static, palyastatic and MAS o Cherubism: Autasamal daminant; mutatians in the c-Abl-binding protein SH3BP2 • Etialagy: Presence .of activating mutatian .of Gs-(){in asteablastic progenitor cells ~ i proliferatian; abnormal differentiatian • Epidemialagy o Actual incidence unknawn • Manastatic FD is 6 times more camman than palyastatic FD • Calvarial invalvement differs: Palyastatic FD (50%) > mana static FD (25%) • Manastatic FD (75%): Faund in skull & face 25% • Palyastatic FD (25%): Faund in skull & face 50% • Assaciated abnormalities: Syndromic specific features such as endacrinapathy, intramuscular myxama, failure ta thrive

Meningioma

Gross Pathologic & Surgical Features

• Resulting hyperostasis mimics FD • MRS: Characteristic alanine peak

• Tan-yellaw ta white Iesian; saft/rubbery ta gritty/firm • Variable cansistency depends upan fibrous vs asseaus make-up • Waven immature bane is structurally weak and prone ta fractures

Imaging Recommendations

Garre sclerosing osteomyelitis • Bany expansian, but inhamageneaus sclerotic pattern; +/- dehiscent bane cortex; +/- peri .osteal reactian

Jaffe-Campanacci (J-C) syndrome • Nan-assifying fibromas, axillary freckling and cafe-au-Iait (lacks neurafibromas) • Mimics palyastatic farms FD o J-C cafe-au-Iait: Caast .of Califarnia (like neurofibromatasis 1) o McCune-Albright cafe-au-Iait: Caast .of Maine

Craniometaphyseal

dysplasia

Other disorders with expanded bone and abnormal bony density • Thalassemia: Maxillary sinus invalvement typical; "hair-an-end" skull • Osteapetrosis: Invalvement .of all banes • Langerhans cell histiacytasis: Bany cartex frequently "disappears" during active phase

Microscopic Features • Fibrous stroma: Myxafibrous vascularity

Skull, Scalp, and Meninges

tissue .of mixed

4 35

FIBROUS DYSPLASIA • Osseous metaplasia: Bone trabeculae made up of immature, woven bone seen as peculiar shapes floating in fibrous stroma o Looks like "Chinese letters" or "alphabet soup"

Staging, Grading or Classification Criteria • Monostotic vs polyostotic • Specific lesion type (Pagetoid, sclerotic, cystic) relates to disease activity o Cystic, Pagetoid and sclerotic FD proposed to represent (in order) the most active to least active • Cystic FD (11-21%): Hypodense (CT) except rind • Pagetoid mixed FD (56%): "Ground-glass" plus cystic change • Homogeneous sclerotic FD (23-34%)

• FD of long bones in 25%

Demographics • Age: < 6 yrs (39%), 6-10 yrs (27%), > 10 yrs (39%) • Gender: MAS usually, but not exclusively, female

Natural History & Prognosis • RARE progression to fibro-, osteo-, chondro- and mesenchymal sarcoma o 0.5% (Netherlands Committee on Bone Tumors) o Usually polyostotic/syndromic forms o Nearly half arise following irradiation (marked increase in malignant potential) • Monostotic craniofacial FD has an excellent prognosis • Most spontaneously "burn out" in their teens and 20s • Polyostotic FD rarely life threatening, but poorer prognosis is present

Treatment Presentation

4 36

• Most common signs/symptoms: Painless swelling or deformity • Clinical profile o Proptosis, cranial neuropathy (diplopia, hearing loss, blindness), atypical facial pain or numbness, headache o Endocrinopathies if McCune-Albright • Presentations: Monostotic, polyostotic, craniofacial (CFD) and syndromic (many known syndromes) o Monostotic FD • 70% of all FD cases; single osseous site is affected • Older children and young adults (75% present before the age 30) • Skull and face involved in 25%; maxilla (especially zygomatic process) and mandible (molar area) > > frontal> ethmoid & sphenoid> temporal> occipital bones o Polyostotic FD • 25% of all FD cases; involves 2: 2 separate sites • Skull and face involved in 50% • Younger group, 2/3 have symptoms by 10 yrs o CFD • Autosomal dominant, stabilizes with skeletal maturity o McCune-Albright Syndrome (MAS) • Subtype of unilateral polyostotic FD: Clinical triad of polyostotic FD, hyperfunctioning endocrinopathies, cafe-au-lait spots • 5% of FD cases; appears earlier; affects more bones more severely • Renal phosphate wasting (50%) associated with elevation of circulating factor FGF-23; may result in rickets and osteomalacia o Mazabraud Syndrome • Polyostotic FD and intramuscular myxoma • 1 Risk malignant transformation FD lesions o Cherubism: Familial bilateral FD of jaw o "Mulibrey" nanism: Primarily Finland; severe, progressive growth failure; pericardial constriction • (MU)scle, (LI)ver, (BR)ain, (EY)e = triangular face; yellow ocular fundi pigment; hypoplastic tongue; peculiar high voice; nevae flammei 65% • Peroxisomal disorder with mutation TRIM37 gene

• Aggressive resection reserved for visual loss, severe deformity ("vault" more accessible than skull base) • No radiation therapy ~ malignant progression • Bisphosphonate ameliorates course (pain, fractures) in polyostotic and monostotic forms • Treat precocious puberty and renal phosphate wasting

IOIAGNostlC.CfIECKL.IST Consider • Monostotic and polyostotic FD likely on same spectrum of phenotypic expression, consider checking for gene to predict complications

Image Interpretation

Pearls

• "Ground glass" appearance on PF or CT and homogeneously decreased signal on T2WI characteristic

I SELECTED REFERENCES 1.

2. 3. 4. 5.

6.

7.

8.

Kos M et al: Treatment of monostotic fibrous dysplasia with pamidronate. J Craniomaxillofac Surg 32(1):10-5, 2004 Macdonald-Jankowski DS. Fibro-osseous lesions of the face and jaws. Clin Radiol 59(1):11-25, 2004 Karlberg N et al: Mulibrey nanism: Clinical features and diagnostic criteria. J Med Genet 41(2):92-8, 2004 MacDonald-Jankowski DS: Fibro-osseous lesion of the face and jaws. Clin Radiol 59:11-25, 2004 Chattopadhyay A et al: Hypophosphatemic rickets and osteomalacia in polyostotic fibrous dysplasia. J Pediatr Endocrinol Metab 16(6):893-6, 2003 Riminucci M et al: FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest 112:683-692, 2003 Lustig LR et al: FD involving the skull base and temporal bone. Arch Otolaryngol Head Neck Surg 127: 1239-47, 2001 Bianco P et al: Mutations of the GNASI gene, stronal cell dysfunction, and osteomalacic changes in non-McCune-Albright fibrous dysplasia of bone. J Bone Miner Res 15(1):120-8,2000

Skull, Scalp, and Meninges

FIBROUS DYSPLASIA

Typical (Left) Axial NECT shows benign-appearing bony expansion; medullary matrix has the classic "ground glass" appearance of fibrous dysplasia. (Right) Axial T1 C+ MR demonstrates benign-appearing bony expansion from fibrous dysplasia. The medullary matrix enhances diffusely.

4 Typical

37 (Left) Axial NECT shows cystic fibrous dysplasia of the superior orbital rim. There is a lucent cavity (arrow) and a thick sclerotic rind surrounded by a thin lucent rim (curved arrow). (Right) Axial T1 C+ MR with fat-saturation shows enhancement of the inner and outer margins of the sclerotic rind (arrows). There is subtle enhancement (open arrow) of the posterior sclerotic rind.

Typical (Left) Axial T2WI MR shows typical low signal intensity of the expanded, sclerotic rind (arrow) and high signal of the cystic center. (Right) Anteroposterior bone scan shows intense uptake of radiopharmaceutical by the right sided supra-orbital FD lesion.

Skull, Scalp, and Meninges

PAGET DISEASE

Coronal graphic illustrates diffuse Paget disease of the skull with severe diploic widening.

4 38

I TERMINOLOGY Abbreviations

and Synonyms

• Synonyms: Paget disease (PD), osteitis deformans

Definitions • Chronic metabolic skeletal DZ characterized by bony expansion with variable destruction and/or sclerosis

Coronal severe marrow marrow

TlWI MR shows diffuse Paget disease with diploic widening. Mosdy maintained yellow hyperintensity is seen within overail increased fat ("atrophic marrow").

• Both lytic & blastic lesions • Coarsening & thickening of trabeculae & cortices o Late sclerotic phase • Blastic lesions, often crossing sutures • "Tam-o'-shanter" skull: Marked t diploic space, particularly inner table • "Cotton wool" skull: Focal sclerosis within previous areas of "osteoporosis circumscripta" o Platybasia

CT Findings

IIMACING •• FINDI NGS General Features • Best diagnostic clue: Well-circumscribed sharply marginated defects &/or marked thickening + sclerosis • Location o Monostotic 10-35%: More commonly axial skeleton o Polyostotic 65-90%: More commonly right-sided o Skull in 25-65%: May be isolated to skull base

Radiographic Findings • Radiography o Diploic widening, coarse trabecula, thick cortices o Early destructive phase • Well-defined lysis; commonly frontal> occipital • "Osteoporosis/osteolysis circumscripta" • Inner & outer tables involved; inner usually more o Intermediate phase

• NECT o Bones: Three phases of PD same as radiography o Platybasia with basilar invagination (BI) o Sarcomatous transformation • Aggressive osteolysis, cortical destruction, soft tissue mass, with out periosteal reaction o Giant cell tumor (GCT) transformation • Lytic lesion without periosteal reaction or mass • Marrow replacement distinguishes from PD lysis • Cystic & hemorrhagic regions possible o PD pseudomass • "Soft tissue mass" 2° periosteal lifting by active PD • Significant absence of lysis • CECT o t Enhancement reflecting pathologic t vascularity o Sarcomatous transformation: Mass enhancement, often with central necrosis

DDx: Causes of Calvarial Thickening

/

,-

~

.

~\

Sclerotic Metastases

Diffuse Hyperostosis

Dilantin Therapy

Skull, Scalp, and Meninges

Fibrous Dysplasia

PAGET DISEASE Key Facts Terminology

Top Differential

• Chronic metabolic skeletal DZ characterized by bony expansion with variable destruction and/or sclerosis

• • • •

Imaging Findings • Best diagnostic clue: Well-circumscribed sharply marginated defects &/or marked thickening + sclerosis • Skull in 25-65%: May be isolated to skull base • "Cotton wool" skull: Focal sclerosis within previous areas of "osteoporosis circumscripta" • Platybasia with basilar invagination (BI) • t Enhancement reflecting pathologic t vascularity • Typically "hot" throughout all bone scan acquisitions (blood flow, blood pool & static) • Bone scans + radiographs abnormal in 56-86%

o GCT transformation:

Enhancing

solid tumor areas

Diagnoses

Osteosclerotic metastases Osteolytic metastases Fibrous dysplasia Causes of calvarial thickening

Pathology • Excessive & abnormal remodeling of bone, with both active & quiescent phases • Individual sites progress at variable rates, thus PD of differing phases may be seen within same patient

Clinical Issues • • • •

20% asymptomatic Fatigue, pain, tenderness, t hat size New pain/swelling"" malignant transformation Surgical indications: Cosmesis, nerve decompression

• Sulfur colloid scan: ~ Uptake

= marrow

replacement

MR Findings

Imaging Recommendations

• TlWI o Yellow marrow hyperintensity usually maintained • Occasionally have more fat than uninvolved bone o Early destructive to early intermediate phase • ~ Marrow intensity 2 to marrow replacement • Residual normal yellow marrow foci ...•excludes malignant transformation o Late sclerotic phase: Marrow hypointensity from sclerosis of coarse trabeculae & cortical thickening o PD pseudomass: Maintained areas of yellow marrow without replacement • T2WI: Marrow changes with marrow replacement • T1 C+ o t Enhancement reflecting pathologic t vascularity o Sarcomatous transformation: Mass enhancement, often with central necrosis o GCT transformation: Enhancing solid tumor areas • MRI findings of PD complications o Distortion & flattening of brain o Brainstem impingement from BI o Acquired Chiari 1 malformation o Sarcomatous transformation • Mass-like total marrow replacement • Focal bone destruction, soft tissue mass o GCT transformation • Lytic lesion with out periosteal reaction/mass • Marrow replacement allows it to be distinguished from the normal lytic phase of PD • Cystic & hemorrhagic regions possible

• Best imaging tool o Radiography + bone scan • Bone scans + radiographs abnormal in 56-86% • Bone scan alone abnormal in 2-23% • Radiographs alone abnormal in 11-20% o NECT defines detail/extent, esp PD of skull base o MRI for imaging PD complications • Protocol advice o NECT: High-resolution, thin-cuts through skull base o MRI: Coronal + sagittal sequences for BI; add contrast for malignant transformation workup

0

Nuclear Medicine

Findings

• Bone Scan o Marked uptake throughout all phases of PD • Typically "hot" throughout all bone scan acquisitions (blood flow, blood pool & static) • Findings may precede radiographic changes o Can be "cold" or normal in late sclerotic stage o Findings suggesting recurrence • New uptake, extension beyond initial boundaries • Cold foci in areas of t activity of bone destruction

I·DIFFERENtIAL.DIAGN!OSIS Osteosclerotic

metastases

• Classically prostate, breast, lymphoma

Osteolytic metastases • Most metastases; including lung, renal, thyroid

Fibrous dysplasia • "Ground-glass" appearance

Causes of calvarial thickening • There are many

I PATHOLOGY General Features • General path comments o Excessive & abnormal remodeling of bone, with both active & quiescent phases o Individual sites progress at variable rates, thus PD of differing phases may be seen within same patient • Genetics o Ashkenazi Jewish: t Prevalence of PD with assoc t frequency of HLA-DR2 o North New Jersey patients w/multifocal GCT & PD: Common ancestry to Avellino, Italy

Skull, Scalp, and Meninges

4 39

4 40

o "Hereditary hyperphosphatasia" aka "juvenile paget disease": Rare; patients of Puerto Rican descent o Unique Illinois family w/AD limb-girdle muscular dystrophy & PD: Linkage analysis ~ unique locus o 1 Expression of genes involved in inhibition of apoptosis, notably Bcl-2 o Mutations in p62 gene associated with PD • Etiology o Unknown o Viral theory • Probable chronic paramyxoviral infection, possibly Measles • Intranuclear inclusion bodies found in osteoclasts • In one report, canine distemper virus (closely related to Measles) found within Pagetic bone in 100% of 10 patients tested o Genetic theory supported by findings listed above o Familial as well as geographic "foci" clustering support both environmental & genetic factors o Others purported, including true neoplastic process • Epidemiology: 3-4% > 40 years; 10-11% > 80 years • Associated abnormalities: 1 Aortic stenosis, heart & bundle branch block; rarely Hashimoto thyroiditis

Gross Pathologic & Surgical Features • Abnormally soft new bone causing deformity

Microscopic

Features

• Early destructive phase: Giant osteoclasts w/numerous nuclei show intense activity & aggressive bone resorption; fibrovascular tissue w/large vascular channels replaces normal yellow marrow • Intermediate phase: I Osteoclastic & 1 osteoblastic activity; return of yellow marrow gradually occurs • Late sclerotic phase: I Osteoblastic activity, bone turnover, & vascularity • General histopathologic findings o Cement lines along coarsened/enlarged trabeculae characteristic; denotes bone resorption & formation o Trabecular thickening lacks normal interconnections & are weak; referred to as "pumice" bone o Cortices have most active bone turnover & repair o Areas of resorption & formation are hypervascular o Often t of marrow fat ("atrophic marrow")

o Ashkenazi Jewish have 1 prevalence • Geographic distribution o Overall 1 prevalence in Northern latitudes o t In Great Britain: Lands settled by British (Australia, New Zealand, US) share t prevalence o Rare in Asia & Africa (excluding South Africa)

Natural History & Prognosis • 10% develop secondary hyperparathyroidism from hypercalcemia related to aggressive bone remodeling • Skull base thickening ~ CN deficit(s), sensorineural hearing loss (cochlear involvement), mixed hearing loss (stapes fixation to oval window) • BI up to 30%; more common in women ~ brainstem compression, syrinx, obstructive hydrocephalus • Malignant transformation o Sarcomatous transformation (1% or less) • M:F = 2:1; 55-80 years • Osteosarc (50-60%), fibrosarc/malignant fibrous histiocytoma (20-25%), chondrosarc (10%) • Rarely lymphoma & angiosarc (1-3%) • < 10% 3 year survival • Metastasizes frequently, most commonly to lung o GCT • Skull/facial GCT almost always associated with PD • M:F = 1.6:1; 32-85 years • Solitary or multiple; 91% in polyostotic PD • Rarely cause mortality; generally don't metastasize

Treatment • Medical o Calcitonin, bisphosphonates, mithramycin o NSAIDs & acetaminophen for pain management o Goal: Control, reduction, & alleviation of pain, rather than return to normal bone o Radiography mayor may not improve/normalize • Biopsy with CT guidance needed to diagnose sarcomatous transformation • Surgical indications: Cosmesis, nerve decompression

I SELECTED REFERENCES 1.

2. 3.

I CLINICAL ISSUES Presentation • Most common signs/symptoms o 20% asymptomatic o Fatigue, pain, tenderness, t hat size o Hyperthermia from hypervascularity o CN deficit(s), pulsatile tinnitus o New pain/swelling ~ malignant transformation • Clinical profile o 2nd commonest DZ of older folks; osteoporosis 1st o 1 Serum alk phos & serum/urine hydroxyproline

Demographics • Age: > 40 years; unusual < 40 years • Gender: M:F = 2:1, onset slightly younger in men • Ethnicity o Caucasians> African-Americans> African-Africans

4.

5.

6.

7.

Donath J et al: Effect of bisphosphonate treatment in patients with Paget's disease of the skull. Rheumatology (Oxford). 43(1):89-94, 2004 Bender IE: Paget's disease. J Endod. 29(11):720-3, 2003 Lopez-Abente G et al: Identification of possible areas of high prevalence of Paget's disease of bone in Spain. Clin Exp Rheumatol. 21(5):635-8, 2003 Brandwood CP et al: Apoptotic gene expression in Paget's disease: a possible role for Bcl-2. J Pathol. 201(3):504-12, 2003 Ciani B et al: Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone. J BioI Chern. 278(39):37409-12,2003 Hoyland JA et al: A comparison of in situ hybridisation, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ-RT-PCR for the detection of canine distemper virus RNA in Paget's disease. J Virol Methods. 109(2):253-9, 2003 Smith SE et al: From the archives of the AFIP. Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. Radiographies. 22(5): 1191-216,2002

Skull, Scalp, and Meninges

(Left) Axial NECT demonstrates diffuse skull base Paget disease involvement with diploic widening, coarsened trabecula, & thick cortices. (Right) Axial T7 C+ MR shows diffuse skull base Paget disease with diploic widening, decreased intensity from marrow replacement (white arrows), & scattered enhancement of abnormal vascularity (black arrows).

4 Typical

41 (Left) Frontal bone scan

image demonstrates marked radiotracer uptake throughout the entire skull from Paget disease. (Right) Coronal NECT demonstrates diffuse periorbital & skull Paget disease involvement with diploic widening & coarsened trabeculae. The patient suffered from bilateral proptosis.

Typical (Left) Axial T2WI MR shows diffuse Paget disease involvement with diploic widening, & coarsened trabeculae. Marrow exhibits an increased quantity of hyperintense fat ("atrophic marrow"). (Right) Axial NECT demonstrates both lytic & blastic Paget disease, as evidenced by focal lysis (arrows) within a background of diffuse sclerotic diploic expansion and thickened cortices.

Skull, Scalp, and Meninges

EXTRAMEDULLARY HEMATOPOIESIS

Axial graphic shows striking extramedullary hematopoiesis. Note expansion of diploic space with red marrow, multiple lobulated dural-based collections of blood-forming elements.

4 42

• Also simulates meningioma o May show osseous findings of underlying o Soft tissue filling paranasal sinus(es) • CECT: Homogeneous enhancement

I TERM INiOlOCY Abbreviations

and Synonyms

• Extramedullary

hematopoiesis

Axial NEeT shows homogeneous hyperdense masses of extramedullary hematopoiesis along the falx (arrows).

(EMH)

disease

MR Findings

Definitions • Compensatory formation of blood elements due to decreased medullary hematopoiesis

IIMAGINCFtN[)ING~ General Features • Best diagnostic clue: Smooth homogeneous masses in patients w/chronic anemias or marrow depletion • Location: Epidural, dura matter, brain, skull, sinuses • Morphology: Smooth circumscribed masses

Radiographic Findings • Radiography o May show findings of underlying disease • Thalassemia ~ "hair-on-end" skull • Osteopetrosis ~ dense bone obliterating medullary space

• • • •

T1WI: Iso- to slightly hyperintense to cortex T2WI: Slightly hypointense to cortex FLAIR: No underlying parenchymal edema Tl C+ o Homogeneous enhancement o Simulates meningioma

Nuclear Medicine

Findings

• Uptake by 99mTc-sulfur colloid

Imaging Recommendations • Best imaging tool: Contrast-enhanced MRI • Protocol advice: Confirm with 99mTc-sulfur colloid

I DIFFERENTIAL DIAGNOSIS Meningioma • MRS: Characteristic

alanine peak

CT Findings

Metastases

• NECT o Smooth homogenous hyperdense masses • Mimics subdural hematoma on NECT

• Often multifocal, infiltrative,

DDx: Dural-based

Meningioma

Mimics of Extramedullary

Prostate Mets

skull invasion

Hematopoiesis

Subdural Hematoma

Skull, Scalp, and Meninges

Neurosarcoid

EXTRAMEDULLARY HEMATOPOIESIS Key Imaging Findings • Best diagnostic clue: Smooth homogeneous masses in patients w/chronic anemias or marrow depletion • Location: Epidural, dura matter, brain, skull, sinuses • Mimics subdural hematoma on NECT • Homogeneous enhancement • Simulates meningioma • Best imaging tool: Contrast-enhanced MRI • Protocol advice: Confirm with 99mTc-sulfur colloid

Natural History & Prognosis

Subdural hematoma • Trauma history, no enhancement

• Survival dependent

acutely

on primary underlying

disease

Neurosarcoid

Treatment

• Abnormal CXR, labs

• Treat primary disease • Low-dose radiotherapy treatment of choice given extreme sensitivity of hematopoietic tissue to XRT • Surgical resection

I PATHOLOGY

43

General Features • General path comments o Primarily in patients with congenital hemoglobinopathies • Thalassemia, sickle cell disease, hereditary spherocytosis, hemorrhagic thrombocytopenia o Also seen in: Leukemia, lymphoma, myelofibrosis, myelosclerosis, myeloid metaplasia • Etiology o Hematogenous stem cell spread to different organs o May be secondary to depleted, infiltrated or hyperactive bone marrow o Can be seen after granulocyte-colony stimulating factor therapy o Seen after exposure to ionizing radiation, benzene o Occasionally no etiology found • Epidemiology: Rare • Associated abnormalities: Secondary subdural hemorrhage from EMH involvement of dura reported

Microscopic

4

I DIAGNOSTICCHECDKl.TST Consider • What is the underlying

Image Interpretation

Pearls

• EMH is a subdural hematoma

I SEl.ECTED 1.

2.

3.

Features

• "Trilineage" Hyperplasia: Erythroid, myeloid and megakaryocytic elements

cause mimic

REFERENCES

Koch CA et al: Nonhepatosplenic extramedullary hematopoiesis: associated diseases, pathology, clinical course, and treatment. Mayo CUn Proc. 78(10):1223-33, 2003 Rizzo L et al. Extramedullary hematopoiesis: unusual meningeal and paranasal sinuses presentation in Paget disease. Radiol Med 105: 376-81, 2003 Aarabi B et al: Visual failure caused by suprasellar extramedullary hematopoiesis in beta thalassemia: case report. Neurosurgery. 42(4):922-5; discussion 925-6, 1998

I IMAGE GAllERY

I CLlNICAL.ISSlJES Presentation • Most common signs/symptoms o Asymptomatic; seizures o Cranial nerve deficit(s) at skull base o 1 Intracranial pressure if affects draining sinus(es) • Clinical profile o Generally older adults with myelofibrosis o Younger patients with hemolytic anemias

Demographics • Age: Generally older, may be seen in young individuals

Axial T1 C+ MR demonstrates homogeneously enhancing masses of extramedullary hematopoiesis along the falx (same case as previous image), (Right) Axial T2WI MR demonstrates homogeneous strikingly hypointense masses of extramedullary hematopoiesis along the falx (arrows). Same case as left and previous image. (Left)

Skull, Scalp, and Meninges

Sagittal T7WI MR demonstrates diffuse skull thickening secondary to chronic Oilantin therapy

4

Sagittal T7WI MR shows fairly focal skull thickening from benign hyperostosis interna; predominantly bifrontal in this patient.

44

Radiographic Findings Abbreviations

and Synonyms

• Skull thickening (ST) • Skull or calvarial thickening

Definitions • Diploic space expansion with/without cortical thickening

adjacent

• Radiography o Insensitive for diffuse, although may be apparent when ST is striking o Focal more easily appreciated as subtle but definite increased density without defined borders o Some etiologies have dramatic and unique findings which can quickly lead you to the cause; for example • Paget disease ~ "cotton wool" skull • B-thalassemia ~ "hair on end" skull

CT Findings

General Features • Best diagnostic clue: Widened skull width • Location o Parietal bones most commonly affected o Occipital squamae do not contain marrow and are usually spared o Can be any • Size o Diffuse involving nearly entire skull o Small focal/regional involvement at any skull location • Morphology o Generalized o Regional or focal • Highly dependent on underlying etiology

• NECT

o Thickened skull • Generalized or focal • Appearance can vary dependent on etiology • Inner table, outer table, diploic space involvement varies dependent on etiology o Findings may be classic/pathognomic • Dyke-Davidoff-Mason syndrome: Cerebral atrophy with ipsilateral compensatory osseous hypertrophy & hyperpneumatization of paranasal sinuses • B-thalassemia: "Hair on end" skull • Shunted hydrocephalus with cortical atrophy: Shunt presence with atrophy and ST

DDx: Diffusely Thick Skull

Normal Variation

Diffuse Hyperostosis

Diffuse Paget DZ

Skull, Scalp, and Meninges

Microcephaly

THICK SKULL Key Facts Clinical Issues

Terminology • Diploic space expansion cortical thickening

with/without

adjacent

Imaging Findings • Best diagnostic clue: Widened skull width • NECT for most causes of ST • MRI + contrast if cellular, aggressive causes are suspected (e.g., metastases) • Thin-section, high-resolution CT for pathology at skull base

Top Differential • • • •

Diagnostic Checklist

Diagnoses

• What is the underlying cause of the ST • Mnemonic "HIPFAM" to help remember some common causes of ST: Hyperostosis interna, idiopathic, paget disease, fibrous dysplasia, anemia, metastases/meningioma

Normal anatomic variation Hyperostosis interna Paget disease Microcephaly

• Fibrous dysplasia: Medullary expansion "ground glass" appearance • CECT: Some etiologies may show diploic enhancement

with a

MR Findings • Tl WI: May show alterations in normal diploic space signal ~ varies with etiology • T2WI: May show alterations in normal diploic space signal ~ varies with etiology • STIR: May show alterations in normal diploic space signal ~ varies with etiology • T1 C+: Some etiologies may show diploic enhancement • MRV: Focal etiologies may have dural sinus displacement

Angiographic

Findings

• Conventional: displacement

Focal etiologies may have dural sinus

Nuclear Medicine

• Most often asymptomatic • Patients with skull base ST may be symptomatic from foraminal or canal encroachment • Sino-orbital & auditive complications • Many tests can help discriminate between etiologies • ST itself not a cause of patient mortality • Usually no treatment required • Skull findings often harbinger of underlying disease • Therapy aimed at treating underlying etiology

I DIFFERENTIAl.. DIAGNOSIS Normal anatomic variation • Upper limits of normal • Normal appearing cortices & diploic space

Hyperostosis interna • Bone overgrowth occurs predominantly in inner table • Commonly predominant in frontal squama

Paget disease • Initial osteolytic change of skull is osteoporosis circum scripta • Later osteosclerotic phase thickens bone o Abnormal architecture of primitive or woven bone o Increased vascularity & pronounced connective tissue reaction o Bones are enlarged & show 1 radiodensity & accentuated trabeculae

Microcephaly

Findings

• Skull overgrowth occurs secondary to a small brain • Cause = developmental anomalies (e.g., lissencephaly) or a result of very early brain damage

• Bone Scan o Variable, dependent on cause of ST • May be cold or hot • Differences possible in early vascular vs later bone uptake phases • PET: 18F-fluoro-2-deoxyglucose (FDG) PET: May show uptake in aggressive etiologies

I PATHOI..OGY

Imaging Recommendations

General Features

• Best imaging tool o NECT for most causes of ST o MRI + contrast if cellular, aggressive causes are suspected (e.g., metastases) • Protocol advice. o Bone reconstruction algorithm o Thin-section, high-resolution CT for pathology at skull base • Both coronal and axial direct acquisition • Sagittal reformats can be helpful • Goal: Thoroughly evaluate foramina & canals

• General path comments: Skull thickening • Genetics: Some etiologies associated with genetic involvemen t/predisposi tion • Etiology o Etiologies more likely to cause generalized ST • Most commonly normal anatomic variation • Drug therapy e.g., Dilantin (phenytoin) • Microcephaly • Shunted hydrocephalus with cortical atrophy • Acromegaly • Chronic severe anemia: Sickle cell anemia, iron deficiency anemia, 0-thalassemia

Many others

Skull, Scalp, and Meninges

4 45

THICK SKULL

4 46

• Hyperparathyroidism • Osteopetrosis • Engelmann disease ("sclerosing diaphyseal dysplasia") at skull base o Etiologies more likely to cause regional or focal ST • Hyperostosis intern a = most common • Hyperostotic meningioma • Hyperostosing en plaque meningioma • Osteoma • Neuroblastoma • Calcifying cephalohematoma • Osteoblastic metastases (usually prostate or breast) • Dyke-Davidoff-Mason syndrome • Epidermal nevus syndrome o Etiologies causing both focal or generalized ST • Paget disease • Fibrous dysplasia • Calcified subdural hematoma • Epidemiology: Highly variable dependent on etiology • Associated abnormalities: Many causes are systemic & have a plethora of associated abnormalities

Gross Pathologic & Surgical Features • Skull thickening

Microscopic Feature,s • Inner/outer table cortical thickening with/without diploic space involvement • Specific histopathology varies greatly dependent on underlying cause

I CLINICAL ISSUES Presentation • Most common signs/symptoms o Most often asymptomatic o Without skull base disease: Most symptoms referable to disease affecting structures/systems outside skull o Patients with skull base ST may be symptomatic from foraminal or canal encroachment • Manifests as cranial nerve (CN) deficit(s) • Sino-orbital & auditive complications • Clinical profile o Many tests can help discriminate between etiologies • Dilantin (phenytoin) therapy: Dilantin levels • Acromegaly: 1 Growth hormone & IGF-l • Sickle cell anemia: Hemoglobin electrophoresis & Sickledex test abnormal • Iron deficiency anemia: ~ Hematocrit & hemoglobin; small red blood cells; ~ serum ferritin & iron; high iron binding capacity (TrBe) • B-thalassemia: Blood smear & hemoglobin electrophoresis abnormal • Hyperparathyroidism: 1 Serum calcium, 1 parathyroid hormone, ~ serum phosphorus, • Osteopetrosis: Radiographic skeletal series diagnostic for diffusely dense bones • Engelmann disease: Radiographic skeletal series show diaphyseal dysplasia • Neuroblastoma: Abdomen CT/MRI, MIBG scintigraphy reveal mass; 1 blood & urine catecholamines

• Prostate metastases: Abnormal prostate US; 1 prostate specific antigen & alkaline phosphatase • Breast metastases: Abnormal mammogram; axillary adenopathy • Dyke-Davidoff-Mason syndrome: Pathognomic NECT with contralateral paresis • Epidermal nevus syndrome: Nevi (linear comedonicus, inflammatory linear verrucous epidermal, linear sebaceous, linear epidermal) • Paget disease: 1 Serum alk phos & serum/urine hydroxyproline; abnormal radiography

Demographics • Age: Varies with etiology • Gender: Hyperostosis interna: Female

Natural History & Prognosis • Usually of no clinical concern • Aggressive lesions, especially those involving the skull base, have associated morbidity; usually CN deficit(s) • ST itself not a cause of patient mortality

Treatment • Usually no treatment required o Skull findings often harbinger of underlying disease o Therapy aimed at treating underlying etiology • Indications for partial or total surgical excision o Cosmesis (commonest) o Sino-orbital & auditive complications (less common) o Peripheral compressive cranial neuropathies (uncommon) o Compressive central neurological manifestations (rarest)

I DIAGNOSTIC

CHECKLIST

Consider • What is the underlying

Image Interpretation

cause of the ST

Pearls

• Mnemonic "HIPFAM" to help remember some common causes of ST: Hyperostosis interna, idiopathic, paget disease, fibrous dysplasia, anemia, metastases/meningioma

I SELECTED REFERENCES 1.

2.

3.

4.

5.

Lucey BP et al: Marked calvarial thickening and dural changes following chronic ventricular shunting for shaken baby syndrome. Arch Pathol Lab Med. 127(1): 94-7, 2003 Sharma RR et al: Symptomatic cranial fibrous dysplasias: dinico-radiological analysis in a series of eight operative cases with follow-up results. J Clin Neurosci. 9(4): 381-90, 2002 Smith SE et al: From the archives of the AFIP.Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. Radiographies. 22(5): 1191-216,2002 Ikedo D et al: Stimulatory effects of phenytoin on osteoblastic differentiation of fetal rat calvaria cells in culture. Bone. 25(6): 653-60, 1999 Lazzeri S et al: Epidermal nevus syndrome: MR of intracranial involvement. AJNR Am J Neuroradiol. 14(5): 1255-7, 1993

Skull, Scalp, and Meninges

THICK SKULL

Typical (Left) Sagittal TlWI MR shows diffuse skull thickening in this patient with microcephaly. (Right) Axial T2WI MR demonstrates chronic calcified bifrontal subdural hematomas (arrows) resulting in focal skull thickening.

4 47

Typical

(Left) Axial NECT demonstrates focal skull thickening from fibrous dysplasia. Note the characteristic "ground glass" appearance. (Right) Axial T 7 WI M R shows diffuse skull thickening in this patient with Paget disease.

Typical (Left) Axial NECT reveals focal skull thickening (arrows) associated with ipsilateral frontal sinus overgrowth in a patient with Dyke-Davidoff-Mason syndrome. (Right) Axial NECT demonstrates focal skull thickening with dense bone formation involving the outer table from a large skull osteoma.

Skull, Scalp, and Meninges

HISTIOCYTOSIS

Townes radiograph shows sharply circumscribed lytic defect of the occipital bone (arrow) (Courtesy L. Donnelly, MD).

4 48

!TERMINOLOGY Abbreviations

and Synonyms

• Langerhans cell histiocytosis (LCH) • Formerly called histiocytosis X

Definitions • Proliferation of Langerhans cell histiocytes forming granulomas within any organ system

• Rare: Choroid plexus, leptomeninges, basal ganglia, cerebellar WM, and brain parenchyma • Size o Skull and facial bones: Lesions grow fast, moderate soft tissue mass common o Pituitary infundibulum: Small lesions due to early endocrine dysfunction (DI) • Morphology o Variable patterns of bony lysis o Soft tissue masses vary from discrete ~ infiltrative

Radiographic Findings

IIMAGING.FINDINGS General Features • Best diagnostic clue o Skull ~ sharply marginated lytic skull defect with beveled margins o Mastoid ~ geographic destruction, soft tissue mass o Brain ~ thick enhancing infundibulum, absent posterior pituitary bright spot • Location o Skull • Calvarium is most common bony site involved, especially prevalent in frontal, parietal bones • Also mastoid portion of temporal bone, mandible, orbit, facial bones o Brain ~ pituitary infundibulum, hypothalamus

DDx: lytic

Sagittal T2WI MR in a patient with biopsy proven Langerhans cell histiocytosis shows heterogeneous slightly hyperintense occipital skull mass (arrow) (Courtesy L. Donnelly, MD).

• Radiography o Calvarium: Well defined lytic lesion, beveled edge, lack of marginal sclerosis • ± Button sequestra or sclerotic margins when healing o Mastoid: Geographic destruction, often bilateral, little regional adenopathy, o Facial/orbital: More variable patterns of bony lysis, discrete ~ permeative

CT Findings • NECT o Calvarium ~ lytic defect, beveled (inner table> outer table), small soft tissue mass o Mastoid ~ bone destruction, often bilateral, soft tissue mass o Brain ~ thickened pituitary stalk

Calvarial lesions

Burr Holes x2

Leptomeningeal Cyst

Metastases

Skull, Scalp, and Meninges

Multiple Myeloma

• CECT o Calvarium => enhancing soft tissue in lytic defect o Mastoid => soft tissue mass variably enhances o Brain => enhancing, thick pituitary stalk, ± hypothalamic mass or enhancement

MR Findings • TIWI o Soft tissue mass at site of bony lysis • Variable, T1 shortening if LCH lesion is proliferative (lipid laden macrophages) o Brain • Infundibulum: Hypointense ~ isointense to GM • Absence of posterior pituitary bright spot • T2WI o Skull, mastoid, orbital/facial lesions: Soft tissue masses show slight hyperintensity o Brain • Infundibulum/hypothalamus: Slightly hyperintense • ± Cerebellar white matter hyperintensity (autoimmune mediated demyelination) • FLAIR: Hyperintensity of the rare cerebellar white matter demyelination • DWI: Cerebellar demyelination with CNS LCH may show restricted diffusion • Tl C+ o Skull, mastoid, orbital/facial: Strongly enhancing soft tissue masses (defined or infiltrating) o Brain • Infundibulum: Vivid enhancement & stalk thickening • Rare => enhancing: Choroid plexus masses, nodules of the leptomeninges, and basal ganglia

Nuclear Medicine

Imaging Recommendations • Best imaging tool o Skull: NECT o Mastoid disease: CECT o Brain: MRI with contrast • Protocol advice o Skull: Bone algorithm o Suspected mastoid LCH: CECT, axial and coronal o Brain MR: Patient with diabetes insipidus • Pituitary: Small FOY, thin section, no gap, sagittal and coronal Tl imaging with contrast • If initial study is normal, repeat in 2-3 months

I D IFFERENTI}\LDIAGNgSIS Lytic calvarial lesions • • • •

Surgical (burr hole, shunt, surgical defect) Epidermoid, dermoid, leptomeningeal cyst TB, syphilis, sarcoid Metastases, multiple myeloma

Temporal bone destructive processes • Severe mastoiditis: Infection usually spares bony labyrinth • Fibrous dysplasia: Skull base lesions may be lytic • Rhabdomyosarcoma: Often with large ipsilateral cervical nodes

Pituitary infundibular/hypothalamic thickening or masses • Germinoma, glioma, PNET, lymphoma, metastasis • Lymphocytic hypophysitis, sarcoidosis, meningitis

Findings

• Bone Scan o Tc-Bone scan: Variable (cold ~ warm) • Calvarium: !Central uptake with halo of 1 activity • PET: 18-FDG: 1 Uptake in proliferating lesions, ! uptake for "burned-out" lesions

I·PAIHOlOGY General Features • General path comments: Masses of proliferating: Histiocytes, plasma cells, and eosinophilic inflammatory cells forming granulomas • Genetics

Skull, Scalp, and Meninges

4 49

HISTIOCYTOSIS o Familial cases documented o Monoclonality of pathologic Langerhans cell o T (7;12) translocation, involvement of the tel gene on chromosome 12 • Etiology: Uncertain: Inflammatory ~ neoplastic • Epidemiology o Affects 4 per 1 million o Peak age at onset 1 year (isolated), 2-5 years (multifocal disease) o Inverse relation between severity of involvement and age o 50% LCH cases are monostotic o Familial LCH < 2% o Bone lesions are most common manifestations of LCH ~ 80-95% of children with LCH • Associated abnormalities: t Risk of LCH: Family history of thyroid disease, underimmunization, penicillin use, solvent exposure

Gross Pathologic & Surgical Features

4 50

• Yellow, gray, or brown tumor mass

Microscopic

Features

• Monoclonality of Langerhans cells o Presence of CD1a and Birbeck granules needed to establish diagnosis

Staging, Grading or Classification Criteria • Formerly classified into one of 3 overlapping forms o Eosinophilic granuloma: Localized, calvarium most common, 70% o Hand Schueller Christian: Chronic disseminated form, multifocal, 20% o Letterer-Siwe: Acute disseminated form, onset < 2 years of age, ± skeletal involvement, 10% • Now classified according to risk factors o Young age, multifocal involvement, multiorgan dysfunction, relapse

I ClINICALISSUES

• Rarely, may spontaneously hemorrhage ~ epidural hematoma • Fascinating 22-year follow-up of an LCH patient revealed the following disease course o There were 5 relapsing infiltrations at different sites of the skull • Treated by surgery, radiotherapy, chemotherapy o During the last relapse, right temporal bone was infiltrated ~ bone destruction & spread to ICA o Eventually clinical remission was achieved o Authors concluded • Behavior of LCH may change with time, & assume an aggressive form • Chemotherapy is the treatment of choice for multifocal malignant form • Prognosis is unpredictable

Treatment • Therapeutic options depend upon symptoms, location, and extent of disease o Observation, excision/curettage, sclerotherapy/in j ection, radiation/chemotherapy • Solitary eosinophilic granuloma has best prognosis with spontaneous remission common o Curettage if painful, observe asymptomatic • LCH patients with DI: Oral or nasal vasopressin, ± chemotherapy and radiation

I D lAG NOSTIC0HECKuSl Consider • CNS LCH for ataxic patient with choroid plexus masses and cerebellar WM demyelination

Image Interpretation

Pearls

• Skull is most frequent bony site involved by LCH • Thick enhancing pituitary stalk is the most common CNS manifestation of LCH

I SELECTED REFERENCES

Presentation • Most common signs/symptoms o Calvarial: Pain, sub scalp mass, bony defect o Mastoid destruction: Pain, chronic otitis externa, retroauricular subscalp mass o Retroorbital mass: Exophthalmos, ± painful ophthalmoplegia o Pituitary infundibular involvement: DI, ± visual disturbance, ± hypothalamic dysfunction • Clinical profile: Child < 2 years with diabetes insipidus, ± lytic calvarial lesion

1.

2.

3.

4.

Demographics

5.

• Age: LCH typically presents under 2 years of age • Gender: M:F = 2:1 • Ethnicity: More common among Caucasians

6. 7.

Natural History & Prognosis • Variable depending on age of onset and extent of involvement o Multifocal and systemic LCH ~ mortality may approach 18%

8.

Kilborn TN et al: Paediatric manifestations of Langerhans cell histiocytosis: a review of the clinical and radiological findings. Clin Radiol. 58(4):269-78, 2003 Oliveira M et al: Spontaneous resolution of calvarial eosinophilic granuloma in children. Pediatr Neurosurg. 38(5):247-52,2003 Chen HC et al: Langerhans cell histiocytosis of the skull complicated with an epidural hematoma. AJNR Am J Neuroradiol. 23(3):493-5, 2002 Cho DY et al: Eosinophilic granuloma with acute epidural hematoma: a case report. Pediatr Neurosurg. 35(5):266-9, 2001 Gulam I et al: Langerhans' cell granulomatosis in an adult: a 22-year follow up. Eur Arch Otorhinolaryngol. 258(4):203-7,2001 Gizewski ER et al: Histiocytosis mimicking a pineal gland tumor. Neuroradiology. 43(8):644-6, 2001 Fernandez-Latorre F et al: Langerhans cell histiocytosis of the temporal bone in pediatric patients: imaging and follow-up. AJR 174(1):217-21, 2000 Shuper A et al: Cerebellar involvement in Langerhans' cell histiocytosis: a progressive neuropsychiatric disease. J Child Neurol. 15(12):824-6, 2000

Skull, Scalp, and Meninges

HISTIOCYTOSIS I IMAGE GALLERY Variant (Left) Axial NEeT shows a large geographic area of right temporal bone destruction and associated soft tissue mass (arrow). (Right) Coronal TI C+ MR shows a robustly enhancing destructive mass of the right lateral orbital wall (arrow). Also note the mass extending into the right suprazygomatic space (open arrow) LCH.

4 51

Variant (Left) Axial TI C+ MR shows

enhancing choroid plexus masses within the ventricular trigones (arrows). Also note the mottled enhancement (perivascular infiltration) within the basal ganglia (open arrows). (Right) Axial T2WI MR in a patient with systemic Langerhans cell histiocytosis shows hyperintense signal within the cerebellar white matter consistent with autoimmune mediated demyelination (arrows).

(Left) Sagittal TlWI MR shows thickening of the pituitary infundibulum (arrow) and absence of the normal posterior pituitary bright spot (open arrow). (Right) Sagittal TI C+ MR shows thickened vividly enhancing pituitary stalk (arrow) LCH.

Skull, Scalp, and Meninges

Coronal T1 C+ MR shows marked multHocal dural-based neurosarcoid.

enhancement

of

4 52

Axial T1 C+ MR demonstrates common basal cisternal location of neurosarcoid. Multifocal enhancing meningeal masses are evident in this patient who had extensive cranial nerve deficits.

• Mediastinal lymph node "eggshell calcification"

Abbreviations

CT Findings

and Synonyms

• Neurosarcoid, neurosarcoidosis • Boeck sarcoid

• CECT o May show basilar leptomeningeal o Osteolytic skull lesions

(NS)

Definitions • Multisystem inflammatory disease characterized non caseating epithelioid-cell granulomas

by

General Features • Best diagnostic clue: Solitary or multifocal CNS mass(es) + abnormal CXR • Location o Dura, leptomeninges, subarachnoid space • Esp basal cisterns involving optic chiasm, hypothalamus, infundibulum, cranial nerves (CN) o Brain parenchyma: Hypothalamus> brain stem> cerebral hemispheres> cerebellar hemispheres

Radiographic Findings • Radiography o Osteolytic skull lesions o Chest X-ray abnormal in most patients with NS • Hilar adenopathy +/- parenchymal involvement

DDx: Neurosarcoid

Cocci Meningitis

enhancement

MR Findings • TlWI o Hydrocephalus o Lacunar infarcts (brainstem, basal ganglia) o Isointense material within subarachnoid space/sulci, focally or diffuse o Isointense durallesion(s) • T2WI o Lacunar infarcts (brainstem, basal ganglia) o Hypointense material within subarachnoid space/sulci, focally or diffuse o Hypointense durallesion(s) o Sellar disease may appear cystic • FLAIR o ;:::;50% have periventricular T2 hyperintense lesions o Hyperintense vasogenic edema 2° to • Infiltrates perivascular (Virchow-Robin) spaces (PVS)

• May cause a small vessel vasculitis • DWI: Distinguish hyperintense acute ischemic cytotoxic edema from NS vasogenic edema • Tl C+

Mimics

Meningitis

Metastases

Skull, Scalp, and Meninges

Histiocytosis

NEUROSARCOID Key Terminology

1;::;~:;,"(rid:«1I • Multisystem

inflammatory

disease characterized

by

gmfiulomas

• Best diagnostic clue: Solitary or multifocal CNS mass(es) + abnormal CXR • "" 50% have periventricular T2 hyperintense lesions • Infiltrates perivascular (Virchow-Robin) spaces (PVS) • May cause a small vessel vasculitis • DWI: Distinguish hyperintense acute ischemic cytotoxic edema from NS vasogenic edema • Wide spectrum of MRI enhancement • Best imaging tool: MRI + contrast

Pathology • Etiology remains unknown

o Wide spectrum of MRI enhancement • Slightly> 1/3 have multiple parenchymal lesions • Slightly> 1/3 have leptomeningeal involvement, nodular and/or diffuse • 10% solitary intra-axial mass • 5-10% hypothalamus, infundibular thickening • 5% solitary dural-based extra-axial mass • Other: Vasculitic or ependymal enhancement o May coat CN, fill internal auditory canals (lAC)

Nuclear Medicine

Findings

• PET o 18-Fluorodeoxyglucose (FDG) PET ~ high pulmonary sarcoidosis uptake o Single reported NS case ~ hypometabolic temporal lobe lesion with hypermetabolic sarcoid elsewhere • Gallium Scan: 1 Uptake at systemic sites of inflammation, including NS (as high as 85%)

Imaging Recommendations • Best imaging tool: MRI + contrast • Protocol advice: Multiplanar, fat-saturation,

T1 C+

I DIFFER.ENTIj\[/oili\GNgS1S Dural, leptomeningeal, • • • •

subarachnoid

NS

Meningitis: CSF shows infection/organism Metastases: Labs different, negative CXR Meningioma: MRS ~ 1 alanine Infundibular histiocytosis: Age of onset 6-14 years

Brain parenchymal

NS

• Periventricular white matter disease: Different symptomatology & lab results, negative CXR

IPATHOLOGY General Features • General path comments: Focal or diffusely infiltrating granulomas involve parenchyma, leptomeninges, dura • Genetics

o Sarcoidosis may occur in families; still no genetic link proven o Genetic polymorphisms of MHC are associated with 1 risk of disease or affect disease presentation • HLA-DRB1 (*11 & *14), HLA-DQB1 *0201alleles • How many HLA genes are involved is unknown, but it is clear that HLA region is strongly implicated in sarcoidosis development o Genetic polymorphisms of cytokines are associated with 1 risk of disease or affect disease presentation (e.g., VEGF & TNF ) • Etiology o Etiology remains unknown • Possibly stimulation of immune system by one or more antigens &/or abnormal immune response o No clear familial pattern, occupation, environmental exposure links o DNA & RNA of mycobacterium, propionibacterium detected in some lesions suggesting a possible cause • Epidemiology o CNS involved in 5% (clinical) to 27% (autopsy) • Primary, isolated CNS sarcoidosis < 1% o 10-20 per 100,000 in North America o Lungs affected in > 90% NS patients • Associated abnormalities o Lofgren syndrome (aka acute pulmonary sarcoid) • All: Fever, malaise, bilateral hilar adenopathy • Erythema nodosum & large joint arthralgia • May have uveitis, parotitis o Heerfordt syndrome (aka salivary gland sarcoidosis) • Fever, parotitis, uveitis, & facial nerve paralysis

Gross Pathologic & Surgical Features • Granulomatous leptomeningitis dural-based solitary mass o Diffuse> nodular • Solitary or diffuse parenchymal • May infiltrate along PVS

(most common) or

lesion

Microscopic Features • Round/ovoid noncaseating granuloma composed of compact, radially arranged epithelioid cells with pale-staining nuclei

Skull, Scalp, and Meninges

4 53

NEUROSARCOID • Large multinucleated giant cells in arc/circle around central granular zone • Leptomeningeal granulomas extend into PVS, adjacent parenchyma • Arterial wall invasion by epithelioid cell granuloma causing disruption of media & internal elastica o Tissue may then cause luminal stenosis or occlusion • Fibrocollagenous tissue accumulates in dural lesions • Granulomatous infiltration of ventricular subependymallayers • CN perivascular/intraneural lymphocytic infiltration

Presentation

4 54

• Most common signs/symptoms o Most common symptom: CN deficit(s), most often facial nerve palsy • Bell palsy 14x t than general population o By imaging, optic nerve +/- chiasm most affected • Clinical & imaging CN findings often disparate o Symptoms vary with location, size of granulomas • Other CN: Hearing loss, diplopia/visual symptoms • HA, fatigue, seizures, encephalopathy, dementia • Weakness, paresthesias • Pituitary/hypothalamic dysfunction • Multiple sclerosis-type symptoms o Systemic involvement • Lung hilar nodes most often involved • Skin lesions second (up to 1/3) • Eye (Iritis, uveitis); polyarthritis o NS can occur without pulmonary or systemic sarcoid o Simultaneous expression of new & old granulomas suggest process may wax & wane • Clinical profile o Relatively common disease; can involve any organ o Kveim-Siltzbach skin test positive in 85% o Serum ACE levels elevated in < 50% of cases with NS o Hypercalcemia + hypercalciuria in up to 15% o Serum CD4:CD8 ratio often ~ o t CSF protein and/or cells insensitive, nonspecific

Demographics • Age: Onset in 3rd-4th decades; 3-5% children • Gender: M:F = 2:1 • Ethnicity o African-American: Caucasian-American = 10:1 • NS more common with West African heritage • Rare in other African/South American heritage o In Europe, Caucasians mostly affected • Geographic predilection o Temperate> tropical climates « 10/100,000) o Swedes & Danes commonly affected o Rare in Chinese, Southeast Asians, Inuits, Canadian Indians, New Zealand Maoris, & Spanish • Environmental factors: Nonsmokers> smokers

Natural History & Prognosis • Often indolent disease; up to 50% asymptomatic • 67% with NS have self-limited monophasic illness; remainder have chronic remitting-relapsing course o Most respond rapidly to steroids, others refractory • Obstructive communicating hydrocephalus

• • • •

o Most common complication o 2° to arachnoiditis, adhesions Vasculitis may cause small vessel ischemia, lacunes, cortical infarcts Poor prognostic indicators: Seizures, leptomeningeal, enhancing parenchymal, & spinal lesions Good prognostic indicators: Dural, CN, & nonenhancing parenchymal lesions Death in 5%: In USA most die from pulmonary complications, in Japan::::; 80% from cardiac DZ

Treatment • No known cure; goal is to alleviate symptoms • Corticosteroids useful in most cases; immunosuppressive drugs occasionally o Enhancement, even masses, may resolve o Optic nerve involvement often has residual symptoms or no response • A study specifically monitoring NS response showed that::::; 50% progressed despite corticosteroid & immunosuppressive therapy o Thus NS carries a poorer prognosis o 46% improve or have clinical symptom resolution, but only 26% do so on the basis of imaging • MR imaging resolution lags clinical symptom resolution

I DIAGNQSTICCHECKUST Consider • Look for an abnormal CXR

Image Interpretation

Pearls

• Protean manifestations make NS a "great mimicker" • CN deficit(s) & pituitary dysfunction often have normal MR + contrast imaging; conversely MR findings may be clinically silent

I SELECTED REFERENCES Kellinghaus C et al: Neurosarcoidosis: clinical experience and diagnostic pitfalls. Eur Neurol. 51(2):84-8, 2004 2. Koyama T et al: Radiologic manifestations of sarcoidosis in various organs. Radiographies. 24(1):87-104, 2004 3. Smith JK et al: Imaging manifestations of neurosarcoidosis. AJR Am J Roentgenol. 182(2):289-95, 2004 Baughman RP et al: Sarcoidosis. Lancet. 361(9363):1111-8, 4. 2003 5. Martinetti M et al: HLA and sarcoidosis: new pathogenetic insights. Sarcoidosis Vase Diffuse Lung Dis. 19(2):83-95, 2002 6. Dubey N et al: Role of fluorodeoxyglucose positron emission tomography in the diagnosis of neurosarcoidosis. J Neurol Sci. 205(1):77-81, 2002 Dumas JL et al: Central nervous system sarcoidosis: 7. follow-up at MR imaging during steroid therapy. Radiology. 214(2):411-20, 2000 8. Pickuth D et al: Role of radiology in the diagnosis of neurosarcoidosis. Eur Radioll0: 941-4, 2000 9. Zajicek JP et al: Central nervous system sarcoidosis--diagnosis and management. QJM. 92(2):103-17, 1999 1.

Skull, Scalp, and Meninges

NEUROSARCOID

(Left) Sagittal graphic illustrates neurosarcoid infiltration of the infundibulum. (Right) Sagittal T7 C+ MR demonstrates enhancing neurosarcoid infiltration thickening the infundibulum & hypothalamus (arrow).

4 Typical

55 (Left) Axial T2WI MR shows periventricular hyperintensity from brain infiltration. Note overlying hypointense dural sarcoid masses wrapping anterior frontal lobes & falx (arrows) (Courtesy B. Burton, MO). (Right) Axial T7 C+ & fat-saturation: Enhancing neurosarcoid lesions involve choroid (arrows), ependymal surfaces (open arrows), & infundibulum (curved arrow). Also note hydrocephalus.

Typical (Left) Axial T7 C+ & fat-saturation: Thick enhancing neurosarcoid envelops optic chiasm (open arrow) & extends along rectus gyri (arrows). Right optic nerve is involved out to globe (not shown). (Right) Histology: Noncaseating granulomas w/radially arranged epithelioid cells (white), peripheral lymphocytes (black), fibrocollagenous tissue (open black), & multinucleated giant cell (curved black).

Skull, Scalp, and Meninges

MENINGIOMA

Axial graphic illustrates dural-based mass w!calcifications (white foci), cortical buckling, trapped cortical vessels, & dural "tails". Intracranial arteries are becoming parasitized.

4 56

o Multiple meningiomas: at autopsy, M < F

I TERMINOLOGY Abbreviations

Axial T7 C+ MR demonstrates dural-based mostly homogeneously enhancing mass with cortical buckling. Note dural "tail" (arrow).

and Synonyms

Radiographic

1-9% all imaged cases, 16%

Findings

• Common meningioma (CM), atypical meningioma (AM), malignant meningioma (MM)

• Radiography: Hyperostosis, irregular cortex, tumoral calcifications, t vascular markings

Definitions

CT Findings

• Common

Meningioma

=

WHO grade 1 Meningioma

IIMAGINGflNOI NGS General

Features

• Best diagnostic clue: Dural-based enhancing mass w/cortical buckling & trapped CSF clefts/cortical vessels • Location o Supratentorial (90%): Para sagittal/convexity (45%), sphenoid ridge (15-20%), olfactory groove (5-10%), parasellar (5-10%) o Infratentorial (8-10%): CPA most common o Mise inside the dural: Intraventricular, optic nerve sheath, pineal region o Mise outside the dura: Paranasal sinus (most common), nasal cavity, parotid, skin, calvarium • Morphology o Extra-axial mass with broad-based dural attachment

• NECT o Hyperostosis, irregular cortex, tumoral calcifications, t vascular markings o Sharply circumscribed smooth mass abutting dura • Hyperdense (70-75%), iso- (25%), hypo- (1-5%) • Calcified (20-25%): Diffuse, focal, sandlike, sunburst, globular, rim • Necrosis, cysts, hemorrhage (8-23%) • Rare lipoblastic subtype ~ negative Hounsfield o Brain cysts & trapped pools of CSF common o Peritumoral hypodense vasogenic edema (60%) • CECT: > 90% enhance homogeneously & intensely • CTA: May complement DSA in defining vascular supply to tumor & normal tissues from each feeder artery before embolization

MR Findings • TlWI o Usually iso- to slightly hypointense with cortex o Necrosis, cysts, hemorrhage (8-23%) o Best to visualize gray matter "buckling"

DDx: Focal Dural Masses

/' f', .. ,~ Prostate Mets

Neurosarcoid

Pachymeningitis

Skull, Scalp, and Meninges

Extra Hematopoiesis

MENINGIOMA Facts

• • T2WI o Variable; sunburst pattern may be evident o Necrosis, cysts, hemorrhage (8-23%) o Best to visualize trapped hyperintense CSF clefts (80%) & vascular flow voids (80%) • FLAIR: Hyperintense peritumoral edema, dural "tail" • T2* GRE: Best sensitivity for calcification • DWI: DWI, ADC maps for CM variable in appearance • Tl C+ o > 95% enhance homogeneously & intensely o Dural "tail" (35-80% of cases ): Non-specific o En plaque: Sessile thickened enhancing dura • MRV: Evaluate possible sinus involvement • MRS o Elevated levels of Alanine at short TE • Reported peak ranges from 1.3-1.5 ppm • Perfusion MRI: Good correlation between volume transfer constant (K-trans) & histologic grade

Angiographic

• Conventional o "Sunburst or radial" appearance with prolonged vascular "stain" o DSA: "Mother-in-law" sign ~ comes early, stays late o Dural vessels supply lesion core & pial vessels (ACA, MCA, PCA) may supply periphery when parasitized o Venous phase vital to evaluate sinus involvement • Interventional: Preoperative embolization o Decreases operative time & blood loss o Particulate agents (e.g., polyvinyl alcohol) favored o Optimal interval between embolization & surgery is 7-9 days; allows for greatest tumor softening

Findings

• PET o CM often hypometabolizing compared to cortex o AM & MM have much higher glucose utilization o High glucose metabolic rate in radiation associated meningioma despite benign histology

Other Modality

Imaging Recommendations • Best imaging tool: MRI + contrast • Protocol advice: If extra-axial localization consider MRS ~ look for Alanine

Findings

• Imaging predictors of difficult, extra pial surgical cleavage plane

difficult,

I DIFFERENTIAt·DIAGNOSIS Dural metastasis • Skull often infiltrated;

Granuloma

multifocal

(sarcoid, TB)

• CXR & labs often abnormal

Idiopathic hypertrophic

Findings

Nuclear Medicine

o Peri tumoral edema on MR/CT ~ may obscure pial invasion by tumor o Tumor pial vascularization on DSA = pial invasion o Tumor/cortex interface is not a reliable predictor

pachymeningitis

• Dural biopsy essential to confirm diagnosis

Extramedullary

hematopoiesis

• Known hematologic disorders • Cavernous hemangioma of dura • Can be indistinguishable

I PATHOLOGY General Features • General path comments: Slow growing, benign • Genetics o Loss of one copy of chromosome 22 is most prevalent chromosomal change in meningioma • Deletion correlates with loss of NF2 gene product "Merlin" (aka schwannomin) o Second most frequent genetic abnormalities after 22q loss are 1p & 14q deletions • In 20% of CM, 77% of AM, & 100% of MM o Multiple meningiomas • Many display expected NF2 gene mutations • Some have normal NF2 genes suggests a second tumor-suppressor gene is also on chromosome 22

Skull, Scalp, and Meninges

4 57

MENINGIOMA

4 58

o Radiation associated meningiomas (RAM) • No significant differences between RAM & non-RAM in chromosome 1 & 22 losses o Genetic affects on location & histology • Strong correlation found between anterior skull base location, intact 22q, & meningothelial • Strong correlation found between convexity location, disrupted 22q, & transitional, fibrous • Alternative histogenesis & genetic pathway likely exists for meningiomas in anterior skull base o SUMMARY: There is significant correlation between # of chromosomal imbalances & tumor grade • CM: 47% 22q loss, 33% 1p deletion, 13% combined 1p/14q deletions • AM & MM incur additional genetic alteration(s) • Etiology o Arise from arachnoid meningothelial ("cap") cells o CM: 90% inactivation of NF2 gene product "Merlin" • 1st event is 22 chromosomal loss - monosomy • "Second hit theory": Remaining single NF2 copy is mutated; vast majority are null mutations • Results in truncated nonfunctional protein o May be related to female sex hormones: M < F, correlate + with breast cancer, may 1 in pregnancy, progesterone receptors identified o XRT predisposes: Most common radiation-induced tumor, latency 20-35 years • Epidemiology o Most common 1 adult intracranial tumor (13-20%) o '" 6/100,000 population; 1-1.5% autopsy prevalence • Associated abnormalities o Neurofibromatosis type 2 • MISME: Multiple inherited schwannomas, meningiomas, & ependymomas • 10% with multiple meningiomas have NF2 o Metastatic carcinoma to CM have been reported • CM are most common primary intracranial tumor to harbor metastases; majority are lung or breast 0

Gross Pathologic & Surgical Features • Two basic morphologies o Globose = globular, well-demarcated neoplasm with wide dural attachment o En plaque = sheet-like extension covering dura without parenchymal invagination • Homogeneous reddish-brown translucent pale surface • Soft to tough, occasionally gritty, dependent on fibrous tissue & calcium content • Invaginate into underlying brain without invading it

I CLINICAl Presentation

• Most common signs/symptoms o < 10% of all meningiomas ever cause symptoms o Highly dependent on tumor locale • Convexity/parasagittal = seizures & hemiparesis • Basisphenoid = visual field defects • Cavernous sinus = cranial nerve deficit(s) • Frontal = anosmia, although often become very large before becoming symptomatic

Demographics • • • •

• CM has wide range of subtypes o Meningothelial: Uniform tumor cells, collagenous septa, psammomatous calcifications (most common) o Fibrous: Interlacing fascicles of spindle-shaped cells, collagen/reticulin matrix o Transitional: Mixed; "onion-bulb" whorls, psammoma bodies o Lipoblastic: Metaplasia into adipocytes; large triglyceride fat droplets o Clear cell: Aggressive despite benign histology; metastasis & recurrence more than other subtypes o Others = angiomatous, micro cystic, secretory, chord aid, etc

Age: Middle decade of life Gender: M:F ranges 1:1.5 to 1:3 Ethnicity: More common in African-Americans Geographic predilection o In Africa nears 30% of adult 10 intracranial tumors

Natural History & Prognosis • Generally grow slowly, compress adjacent structures • Para sagittal often grow into & occlude SSS • Metastases rare (0.1-0.2%): Histology, location do NOT correlate with metastases

Treatment • Asymptomatic followed with serial imaging • Surgical goals o Resection of tumor & involved dura/dural "tail" (+ tumor-free margins) with duraplasty o Resection of involved or hyperostotic bone o CM recurrence = 9% • Radiotherapy infrequently utilized for CM

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Preoperatively define ENTIRE tumor extent • Could the patient be syndromic - MISME

ISELECTEO{REFEr{~;~(SES 1.

2.

3.

Microscopic Features

ISSUES

4.

Lopez-Gines C et al: Association of loss of 1p and alterations of chromo sones 14 in meningioma progression Cancer Genet cytogenet. 148:127-8, 2004 Alvernia JE et al: Preoperative neuroimaging findings as a predictor of the surgical plane of cleavage: prospective study of 100 consecutive cases of intracranial meningioma. J Neurosurg. 100:422-30, 2004 Takeguchi T et al: The dural tail of intracranial meningiomas on fluid-attenuated inversion-recovery images. Neuroradio146:130-5, 2004 Dezamis E et al: The molecular genetics of meningiomas and genotypic/phenotypic correlations Rev Neurol (Paris). 159(8-9):727-38,2003

Skull, Scalp, and Meninges

MENINGIOMA

/~\. \r•.,\ I . " ~ .

::

1

:1 /- ..' '1/ K: . .

, iiil

L·I

",

(Left) Axial Tl C+ MR shows

heterogeneous enhancing mass of cerebellopontine angle extending into the internal auditory canal but without obvious widening. Note dural "tail" (arrow). (Right) Axial Tl C+ MR shows meningioma arising from sphenoid ridge around anterior clinoid; it narrows cavernous internal carotid & extends through optic canal infiltrating optic nerve sheath (arrow).

4 59 (Left) Arterial phase digital

subtraction angiography during external carotid artery injection reveals a "radial" arterial feeder appearance. Prolonged vascular stain is not shown. (Right) Axial Tl C+ MR shows intense heterogeneous enhancement of an intraventricular meningioma. Obstruction is causing dilation of the temporal horn (arrow).

Variant (Left) Axial T2WI MR reveals

microcystic meningioma subtype containing numerous microcysts within large extracellular spaces containing edematous fluid. Bilateral white matter hyperintensity is unrelated. (Right) Sagittal TlWI MR shows lipoblastic metaplastic meningioma subtype. Metaplasia into adipocytes has occurred & the tumor contains large hyperintense triglyceride fat droplets (Courtesy C. Tubbs, MO).

Skull, Scalp, and Meninges

ATYPICAL AND MALIGNANT MENINGIOMA

Coronal graphic illustrates malignant menmgloma infiltrating scalp, skull, and underlying brain. Extensive vasogenic edema (in gray) is present as is mild right to left midline shift.

4 60

ITERMINOIO.(1jY Abbreviations

and Synonyms

• Common meningioma (CM), atypical meningioma (AM), malignant meningioma (MM) • Atypical = papillary; malignant = anaplastic

Definitions • Common meningioma = WHO grade 1 meningioma • Atypical meningioma = WHO grade 2 meningioma • Malignant meningioma = WHO grade 3 meningioma

IIMAGfNGiFINOINlG~

Coronal T7 C+ MR demonstrates enhancing tumor lobulations "mushrooming" both inwards deforming underlying brain as well as outwards into scalp.

• CECT o Enhancing tumor mass o Prominent pannus or tumor, extending mass termed "mushrooming"

away from

MR Findings • TlWI o Indistinct tumor margins o Extending tumor interdigitating with brain • FLAIR: Marked peritumoral edema • DWI o Markedly hyperintense on DWI o Marked decrease in ADC o Correlates with histopathology • T1 C+

General Features • Best diagnostic clue: Dural based lesion locally invasive with areas of necrosis & marked brain edema • Location o Occur anywhere along neuraxis o AM: Para sagittal (44%), cerebral convexities (16%)

CT Findings • NECT o Hyperdense w/minimal or no calcification o Marked perifocal edema & bone destruction o CT "Triad" of MM: Extracranial mass, osteolysis, & intracranial tumor

o Enhancing tumor mass o Plaque like & may extend into brain, skull, scalp • MRV: Evaluate possible sinus involvement • MRS o Elevated levels of Alanine at short TE • Reported peak ranges from 1.3-1.5 ppm • Perfusion MRI: Good correlation between volume transfer constant (K-trans) & histologic grade

Angiographic Findings • Conventional o External circulation ~ sunburst or radial appearance o DSA: "Mother-in-law" sign ~ comes early, stays late o Venous phase vital to evaluate sinus involvement

DDx: lesions Appearing Similar to Atypical or Malignant Meningioma

Skull Metastases

Osteosarcoma

Ewing Sarcoma

Skull, Scalp, and Meninges

Meningeal Sarcoma

ATYPICAL AND MALIGNANT MENINGIOMA Key Facts Terminology • Atypical meningioma

= WHO grade 2 meningioma

• Ewing sarcoma • Primary meningeal

sarcoma

• Malignant meru~gioma " WHQ grad, 3 meningioma

Pathology

Imaging Findings

• Loss of one copy of chromosome 22 is most prevalent chromosomal change in meningioma • SUMMARY: There is a significant correlation between number of chromosomal imbalances & tumor grade • AM = 7.2% of meningiomas • MM· 2.4%of me".nglo ••••

• Best diagnostic clue: Dural based lesion locally invasive with areas of necrosis & marked brain edema • Prominent pannus or tumor, extending away from mass termed "mushrooming" • Indistinct tumor margins • Elevated levels of Alanine at short TE • DSA: "Mother-in-law" sign - comes early, stays late • Best imaging tool: MRI + contrast

Top Differential

Diagnoses

• Metastasis • Osteosarcoma

['''''I

Clinical Issues • Ethnicity: More common in African-Americans • Resection of tumor & involved dura/dural "tail" (+ tumor-free margins) with duraplasty • Complication: CSF seeding • Radiotherapy: Frequently used for AM & MM

• Interventional: Preoperative embolization o !Operative time & blood loss o Particulate agents (e.g., polyvinyl alcohol) favored

Nuclear Medicine

Findings

• PET: 18-Fluorodeoxyglucose: AM & MM have much higher glucose utilization rates than CM

o

Imaging Recommendations • Best imaging tool: MRI + contrast • Protocol advice: Lack of distinct margins make extra-axial location difficult: Consider MRS

o

1.[)IFFERE~TI}\L()lAG.NOS1S Metastasis • Often known extracranial 1 neoplasm • Osteolytic & destructive or osteoblastic 0

& sclerotic

o

Osteosarcoma • Osteolytic + soft tissue mass & poorly defined margins • Tumoral calcification may be "sunburst" o

Ewing sarcoma • Affects children • CT: Laminated periosteal "onion skin appearance"

Primary meningeal sarcoma • Extremely rare non-meningothelial

tumor of meninges

o

I PATHOLOGY General Features • Genetics o Loss of one copy of chromosome 22 is most prevalent chromosomal change in meningioma • 22q 12 contains gene for NF2 & meningioma • Deletion correlates with loss of NF2 gene product "Merlin" (aka Schwannomin) o Second most frequent genetic abnormalities after 22q loss are 1p & 14q deletions

o

• Prominent in AM & MM: 1p loss found in 20% of CM, 77% of AM, & 100% of MM • Correlates with more aggressive behavior • 87.5% of AM & MM also have a 14q alteration • 1p & 14q deletions highly associated with 1 histologic grade & progression Chromosome 10 abnormalities shared with non-meningioma tumors • Incidence & complexity 1 with meningioma grade • Chromosome 10 deletions shared by other cancers Chromosome 9p losses important in AM & MM • Three genes at 9p21 are known tumor suppressor genes inactivated in many human tumors • Homozygous deletions of all three genes occurs in 0% of CM, 3% of AM, 46% of MM • CDKN2A gene product regulates G l/S-phase transition - cell-cycle inactivation important aberration in MM Multiple meningiomas • Many display expected NF2 gene mutations • Some have normal NF2 genes suggests a second tumor-suppressor gene is also on chromosome 22 Radiation associated meningiomas (RAM) • No significant differences between RAM & non-RAM in chromosome 1 & 22 losses • Suggests both tumorigenic pathways are similar regardless of previous skull irradiation Genetic affects on location & histology • Strong correlation found between anterior skull base location, intact 22q, & meningothelial • Strong correlation found between convexity location, disrupted 22q, & transitional, fibrous • Alternative histogenesis & genetic pathway likely exists for meningiomas in anterior skull base SUMMARY: There is a significant correlation between number of chromosomal imbalances & tumor grade • CM: 47% 22q loss, 33% 1P deletion • AM: 86% 1p, 71% 22q, 57% lOq, 43% 14q & 18q losses; 43% 15q & 17q gains • MM: 100% 1p loss; also losses on 9p, 10q, 14q, 15q, 18q & 22q and gains on 12q, 15q & 18p

Skull, Scalp, and Meninges

4 61

ATYPICAL AND MALIGNANT MENINGIOMA

4 62

• Combined 1p/14q deletions in 13% of CM, 43% of AM & 67% of MM • Etiology o CM: 90% inactivation of NF2 gene product "Merlin" • 1st event is 22 chromosomal loss - monosomy • "Second hit theory": Remaining single NF2 copy is mutated: Vast majority are null mutations (nonsense, frameshift, or splice donor site) • Results in truncated nonfunctional protein o AM & MM: After NF2 inactivation, additional events occur & are related to greater aggressiveness • Loss of 1p, 14q, 10q & 9p chromosomes • Reactivation of telomerase • Inactivation of CDKN2A gene (& others) o Occasionally no genetic defect found as etiology • Meningioma transcription regulation may be influenced by unproven mechanisms • Alternative mechanism is that of induced proteolysis of "Merlin" • Epidemiology o Most common primary adult intracranial neoplasm (13-20%) • AM = 7.2% of meningiomas • MM = 2.4% of meningiomas (rare) o "" 6 per 100,000 population

Gross Pathologic & Surgical Features • Firm; granular cut surface; invasive

Microscopic Features • AM features: WHO criteria o i Mitotic activity o 3 or more of • Small cells with high nucleus to cytoplasmic ratio • Prominent nucleoli • Uninterrupted patternless or sheetlike growth • Foci of spontaneous or geographic necrosis • MM features: WHO criteria o AM features + findings of frank malignancy • Malignant cytology, high mitotic index

Staging, Grading or Classification Criteria • Immunohistochemical staining with MIB-1 antibody (Ki-67) correlates with recurrence o MIB-1 = nuclear, nonhistone protein expressed during cell-cycle proliferation but not resting o Staining with MIB-1 yields labeling index (LI) for quantification of the number of dividing cells • LI < 4.4% - 82% recurrence free at 6 years • LI > 4.4% - 32% recurrence free at 6 years

0

o Africa nears 30% of adult 1 intracranial

Natural History & Prognosis • Recurrence & survival o AM 29% recurrence; 26% recurring become MM • 95% 5 year & 79% 10 year survival • Recurrence-free survival = 11.9 years • Median time to recurrence = 5 years o MM 50% recurrence • 64.3% 5 year & 34.5% 10 year survival • Recurrence-free survival = 2 years • Median time to recurrence = 2 years o CM (for comparison) = 9% recurrence

Treatment • Asymptomatic followed with serial imaging • Surgical goals o Resection of tumor & involved dura/dural "tail" (+ tumor-free margins) with duraplasty o Resection of involved or hyperostotic bone o Preoperative knowledge tumor is AM or MM may alter neurosurgery preoperative plan • More aggressive to achieve complete resection • Complication: CSF seeding • Radiotherapy: Frequently used for AM & MM o Fractionated external beam irradiation o Stereotactic radiosurgery • Recurrence treatments o Repeat surgery o External beam irradiation, stereotactic radiosurgery o Novel therapies • Angiogenesis inhibitors (e.g., lnterferon-Ol) • Growth hormone blockade (e.g., Octreotide) • Signal inhibition (e.g., Ca++ channel blocker) • Tumor cell growth inhibition (e.g., Hydroxyurea) • Growth factor blockade (e.g., Trapidil) • Gene therapy (e.g., HSV vector + Merlin gene) successful in cell tissue culture & dog models

I DIAGNOSTIC

signs/symptoms:

1.

3.

Dependent

on locale

Demographics

4.

• Age o Middle decade of life o AM occurs about 10 years earlier than CM • Gender: Male:Female ranges 1:1.5 to 1:3 • Ethnicity: More common in African-Americans • Geographic predilection

define ENTIRE tumor extent

I SELECTED REFERENCES

Presentation • Most common

CHECKLIST

Image Interpretation Pearls • Preoperatively

2.

I CLiNICALISSUES

tumors

5.

Leuraud P et al: Prognostic value of allelic losses and telomerase activity in meningiomas. J Neurosurg. 100:303-9, 2004 Grover SB et al: The CT triad of malignancy in meningioma--redefinition, with a report of three new cases. Neuroradiology. 45(11):799-803, 2003 Yang S et al: Dynamic contrast-enhanced perfusion MR imaging measurements of endothelial permeability: differentiation between atypical and typical meningiomas. AJNR Am J Neuroradiol. 24(8):1554-9, 2003 Dezamis E et al: The molecular genetics of meningiomas and genotypic/phenotypic correlations. Rev Neurol (Paris). 159(8-9):727-38,2003 Korshunov A et al: DNA topoisomerase II-alpha and cyclin A immunoexpression in meningiomas and its prognostic significance: an analysis of 263 cases. Arch Pathol Lab Med. 126(9):1079-86, 2002

Skull, Scalp, and Meninges

ATYPICAL AND MALIGNANT MENINGIOMA

(Left) Sagittal T1 C+ MR

shows enhancing tumor involving the scalp, skull, & underlying brain. Note prominent hypointense brain edema (arrow). (Right) Axial FLAIRMR demonstrates hyperintense tumor "mushrooming" inwards deforming underlying brain.

4 Variant

63 (Left) Axial FLAIRMR shows

hemorrhage evidenced by heme-fluid level in large cystic component & subarachnoid extension (hyperintense sulci; arrows). Note brain edema (open arrow) (Courtesy WS Choi, MO). (Right) Axial T1 C+ MR demonstrates markedly enhancing intraventricular tumor. Parenchymal invasion evident by ill-defined border and associated hypointense edema (arrows).

Typical (Left) Sagittal T1 C+ MR

demonstrates large fluid-intensity cystic components associated with enhancing tumor invading skull as well as superior sagittal sinus (not shown). (Right) Sagittal MRV MIP shows absence of flow within the posterior aspect of the superior sagittal sinus (arrow), invaded by meningioma. Note increased flow anteriorly (open arrow).

Skull, Scalp, and Meninges

BENIGN NONMENINGOTHELIAL TUMORS

Axial NECT demonstrates focal skull thickening with dense bone formation involving the outer table from a large skull osteoma.

4 64

o OST: Round dense lesions of outer table (much less commonly inner table) without diploic involvement

I TERMINOLOGY

Abbreviations

Sagittal NECT reformat shows calcified matrix in cartilaginous cap (arrow) atop cortical bone which is contiguous with parent cortex (open arrow). Osteochondroma (Courtesy L. Cromwell, MO).

and Synonyms

• Benign nonmeningothelial tumors (BNT), chondroma (CD), osteochondroma (OCD), osteoma (OST) • Benign mesenchymal non-meningothelial tumors of meninges

Definitions • Any nonmenigotheliomatous mesenchymal benign neoplasm or neoplastic-like processes of dura, skull, or scalp as defined by the new WHO criteria • CD, OCD, OST: Examples of BNT discussed in detail; scalp hemangiomas not discussed in text

I IMAGING FINDINGS General Features • Best diagnostic clue: Lesions of dura, skull, skull base, scalp without malignant features • Location: Dura, skull, skull base, scalp

Radiographic Findings • Radiography o CD: Expansile lesion containing matrix calcification with scalloped endosteum o OCD: Sessile or pedunculated bone-like projection

CT Findings • NECT o CD • Expansile, lobulated, soft tissue mass • Contains curvilinear matrix calcification • Scalloped endosteal bone resorption ~ "saucerization" • No stalk or peduncle as in an OCD o OCD • May see calcified matrix in cap atop cortical bone • Parent bone contiguous with cortex of OCD o OST: Round dense lesions of outer table (much less commonly inner table) without diploic involvement • CECT o CD: May have slight enhancement o OCD: May have peripheral cartilaginous cap enhancement o OST: No enhancement

MR Findings • TIWI o CD: Intermediate intensity o OCD: Mixed intensity; may see hypointense calcified matrix within cap atop cortical bone o OST: Hypointense • T2WI

DDx: lesions Appearing Similar to Benign Nonmeningothelial

Meningioma

Malig Meningioma

Osteosarcoma

Skull, Scalp, and Meninges

Tumors

Meningeal Sarcoma

BENIGN NONMENINGOTHELIAL TUMORS Key Facts • Malignant nonmeningothelial

Terminology • Any nonmenigotheliomatous mesenchymal benign neoplasm or neoplastic-like processes of dura, skull, or scalp as defined by the new WHO criteria

Imaging Findings • Best diagnostic clue: Lesions of dura, skull, skull base, scalp without malignant features • Location: Dura, skull, skull base, scalp • NECT for most • MRI + contrast for imaging non-calcified cartilage, affects on soft tissues, evaluating for malignant transformation

Top Differential

Diagnoses

• Benign meningothelial tumors • Malignant meningothelial tumors

o CD: Hyperintense o OCD: Mixed intensity; may see hypointense calcified matrix within cap atop cortical bone o OST: Variable intensity • FLAIR: Evaluates for edema adjacent to BNT • T1 C+

o CD: Enhancement of curvilinear septae (ring-and-arc pattern), scalloped margins o OCD: May have peripheral cartilaginous cap enhancement o OST: No enhancement

Nuclear Medicine

Imaging Recommendations • Best imaging tool o NECT for most o MRI + contrast for imaging non-calcified cartilage, affects on soft tissues, evaluating for malignant transformation • Protocol advice o NECT: Axial & coronal thin sections at skull base o MRI: Fat-saturation to confirm fat content or to optimize imaging scalp lesions

Benign meningothelial

tumors

• Common meningioma o Characteristic MRI/MRS appearance

Malignant meningothelial • Atypical/malignant meningioma o Infiltrative, destructive lesion o MRS characteristic

tumors

Pathology • BNT are rare to very rare • ~~~;~~~;;~rome: Multiple osteomas, skin tumors, • Maffucci syndrome: Multiple enchondromas associated with soft tissue hemangiomas • Multiple hereditary exostosis: Multiple OCD • Ollier disease = enchondromatosis

Clinical Issues • • • •

BNT are most often asymptomatic Asymptomatic lesions require no treatment Surgical indications: Relief of symptoms, cosmesis Surgical goals: Complete excision, curettage if cannot be resected completely

Malignant nonmeningothelial

tumors

• Osteosarcoma o Osteolytic + soft tissue mass & ill-defined margins o Tumoral calcification may be "sunburst" • Primary meningeal sarcoma o Extremely rare non-meningothelial tumor of meninges

[PATHOLOGY General Features

Findings

• Bone Scan o CD: Uptake if actively making bone o OCD: Varies o OST: Uptake during active growth phase; diminishing to background levels • PET: CD: Focally 1 FDG uptake

I DIFFERENTIALDIAGNOSIS

tumors

• General path comments o Skull vs skull base ossification • Skull develops by intramembranous ossification ~ origin of membranous tumors (e.g., OST) • Clivus & skull base develop by endochondral ossification ~ origin for cartilaginous tumors (e.g., CD &OCD) o CD • Benign osteocartilaginous tumor • Most commonly found in sellar/parasellar regions, rarely dura or falx • "Enchondroma" if within bone or cartilage • Multiple tumors = chondromatosis or enchondromatosis • No stalk or peduncle as in an OCD o OCD • Benign osteocartilaginous tumor • Cartilage-capped bony exostosis; sessile or pedunculated • Multiple in 12% • Usually arises from skull base, rarely dura or falx o OST: Benign membranous tumor • Etiology o CD: From clivus/skull base cartilage synchondroses • Ectopic embryologic cartilage cell rests; perivascular mesenchymal tissue metaplasia has also been proposed o OCD • Arise from a fragment of growth plate, in the skull most likely from a congenital defect

Skull, Scalp, and Meninges

4 65

BENIGN NONMENINGOTHELIAL

4

• Most common r;tdiation associated benign tumor o OST: Uncertain • Often found in auditory canals of cold water swimmers ~ may be an inflammatory reaction • Epidemiology o BNT are rare to very rare o CD: Rare, but most common benign osteocartilaginous tumor of clivus/skull base o OCD • Most common benign skeletal tumor (8-9% all primary bone tumors, 36% of those benign) • Most common cartilaginous tumor o OST are most common primary calvarial tumors ~ 0.4% of population • Associated abnormalities o Gardner syndrome: Multiple osteomas, skin tumors, colon polyps o Maffucci syndrome: Multiple enchondromas associated with soft tissue hemangiomas o Multiple hereditary exostosis: Multiple OCD o Ollier disease = enchondromatosis

Gross Pathologic & Surgical Features 66

o CD: Occur at any age, peak in 2nd to 4th decades o OCD • Mean age for multiple = 21, solitary = 30 years • Intracranial OCD has younger predilection o OST: Highest incidence in 6th decade • Gender o CD: M>F o OCD: M:F = 1.5-2.5:1 o OST = M:F = 1:3

Natural History & Prognosis • CD: Malignant transformation is rare • OCD: Malignant transformation is rare o Sessile more likely to degenerate o Risk 1 as number & size of OCD increases o Malignant transformation in osteochondromatosis 25-30% compared to ::::;1% for solitary • OST: Slow growing lesions normally asymptomatic

Treatment • Asymptomatic lesions require no treatment • Surgical indications: Relief of symptoms, cosmesis • Surgical goals: Complete excision, curettage if cannot be resected completely

• CD: Cartilage & ossified cartilage • OCD: Irregular bony mass with cartilage cap +/calcification • OST: Appears like mature lamellar bone

I DIAGNOSTIC

Microscopic

Consider

Features

• CD o Benign chondrocytes in scattered lacunae o Bone being formed by enchondral ossification o May exhibit cellular atypia • OCD: Cartilaginous cap over bony excrescence w/cortex, trabeculae, marrow, identical to normal bone • OST: Two types o Compact or "ivory": Made of mature lamellar bone; no Haversian canals or fibrous components o Trabecular: Composed of cancellous trabecular bone with marrow surrounded by cortical bone margin

Staging, Grading or Classification Criteria • Benign mesenchymal nonmeningothelial (WHO, 2000) o Lipoma, variants o Chondroma o Osteoma o Osteochondroma o Hemangioma o Benign fibrous histiocytoma

tumors

I CLiNICAL.ISSU£S Presentation • Most common signs/symptoms o BNT are most often asymptomatic o OCD & OST: May present as "bony lump" o CD & OCD: May have cranial nerve deficit(s) if at clivus/skull base; very rarely seizure

Demographics

TUMORS

CHECKLIST

• Could the patient be syndromic

I SELECTED REFERENCES Colpan E et al: Convexity dural chondroma: a case report and review of the literature. J Clin Neurosci. 10(1):106-8, 2003 Dobert N et al: Enchondroma: a benign osseous lesion with 2. high F-18 FDG uptake. Clin Nucl Med. 27(10):695-7, 2002 3. Schmidinger A et al: Natural history of chondroid skull base lesions--case report and review. Neuroradiology. 44(3):268-71, 2002 4. Robinson P et al: Periosteal chondroid tumors: radiologic evaluation with pathologic correlation. AJR Am J Roentgenol. 177(5):1183-8,2001 5. Rozylo I et al: An unusual case of intracranial osteoma in a CT image. Ann Univ Mariae Curie Sklodowska [Med]. 54:49-52, 1999 case report, 6. Haddad GF et al: Dural osteochondroma: review of the literature and proposal of a new classification. Br J Neurosurg. 12(4):380-4, 1998 7. De Coene B et al: Unusual location of an intracranial chondroma. AJNR AmJ Neuroradiol. 18(3):573-5, 1997 8. Haddad FS et al: Cranial osteomas: their classification and management. Report on a giant osteoma and review of the literature. Surg Neurol. 48(2):143-7, 1997 9. Abdelhamid K et al: Intracranial chondroma arising from the cranial vault: CT and MR appearance. J Com put Assist Tomogr. 20(4):556-8, 1996 10. Sato K et al: Osteochondroma of the skull base: MRI and histological correlation. Neuroradiology. 38(1):41-3, 1996 11. Shibata Y et al: Osteomas of the skull: comparison of magnetic resonance imaging and histological findings. Neurol Med Chir (Tokyo). 35(1):13-6, 1995 12. Bertoni F et al: Parosteal osteoma of bones other than of the skull and face. Cancer. 75(10):2466-73, 1995 1.

• Age

Skull, Scalp, and Meninges

BENIGN NONMENINGOTHELIAL TUMORS I IMAGE GALLERY (Left) Coronal NECT reformat demonstrates calcified matrix in cartilaginous cap (arrow) atop cortical bone which is contiguous with the parent cortex (open arrow). Ox = osteochondroma. (Right) Coronal Tl WI M R shows mixed intensities within the cartilaginous cap of an osteochondroma (arrow). Calcifications are hypointense (Courtesy L. Cromwell, MO).

4 67 (Left) Axial T2WI MR shows primarily hypointensity from calcifications within the cartilaginous cap of an osteochondroma (arrow). (Right) Coronal NECT demonstrates matrix calcification within a chondroma (open arrow). There was no stalk connecting it to parent bone.

(Left) Axial NECT shows a scalp hemangioma with soft tissue prominence & density greater than adjacent fat. No associated periosteal reaction is consistent with a benign lesion. (Right) Sagittal TlWI MR demonstrates a hypointense to fat scalp hemangioma with soft tissue prominence. Enhanced technique showed lesional enhancement (not shown).

Skull, Scalp, and Meninges

MALIGNANT NONMENINGOTHELIAL TUMORS

Axial CECT shows striking heterogeneous enhancement of a primary meningeal sarcoma with skull destruction, scalp infiltration, adjacent hypodense edema and mass effect.

• Size: Enlarge quickly • Morphology: Amorphous, ill-defined mass with both intra- & extra-axial components

I TERMINOLOGY Abbreviations

Axial T2WI MR demonstrates heterogeneous signal in a primary meningeal hemangiopericytoma with hypointense matrix (arrow), hyperintense cysts, & cortical buckling (open arrow).

and Synonyms

• Malignant nonmeningothelial tumors (MNT) • Intracranial sarcoma; malignant mesenchymal non-meningothelial tumors of meninges

• Radiography: Usually radiolucent lesions ~ ill-defined lytic borders, no periosteal reaction

Definitions

CT Findings

• Any nonmenigotheliomatous mesenchymal malignant neoplasm, neoplastic-like process, of dura, skull, scalp, choroid plexus stalk, as defined by WHO criteria • Tumors arising from non-meningeal cells of meninges that yield many different tumor subtypes; for example o Primary meningeal angiosarcoma (ANGlO) o Primary meningeal chondrosarcoma (CHON) o Primary meningeal fibrosarcoma (FIERO) o Primary meningeal hemangiopericytoma (HGPC) o Primary meningeal osteosarcoma (OSTEO) o Primary meningeal rhabdomyosarcoma (RHAB) o Primary meningeal sarcoma (MENSARC)

• NECT o Usually radiolucent lesions ~ ill-defined lytic borders, no periosteal reaction o ANGlO: Reactive ossification, necrosis possible o CHON: Calcifications may have stippled or "rings & arcs" appearance o MENSARC: May be dense, biconvex, mimicking acute subdural hematoma o OSTEO: Calcified "sunburst" matrix possible • CECT o Most MNT enhance o ANGlO: Marked enhancement

Radiographic Findings

MR Findings

I IMAGING FINDINGS General Features • Best diagnostic clue: Highly aggressive dural, skull, scalp, choroid plexus stalk lesions invading locally • Location: Dura, skull, scalp, choroid plexus stalk

• TlWI o Most are hypointense on Tl WI with brain infiltration o May see extremely low signal from fibrous, chondroid, osteoid tissue • T2WI

DDx: Aggressive Appearing Meningeal-based

Tumors

Malig Meningioma

Skull, Scalp, and Meninges

Metastases

MALIGNANT NONMENINGOTHELIAL TUMORS Key Facts Terminology

Pathology

• Any nonmenigotheliomatous mesenchymal malignant neoplasm, neoplastic-like process, of dura, skull, scalp, choroid plexus stalk, as defined by WHO criteria

• Most likely arise from pluripotential meningeal mesenchymal cells yielding many different tumor subtypes

• MNT, 0.5-2.7% Of 'ntr,,,anial neopl"m,

Imaging Findings

Clinical Issues

• Best diagnostic clue: Highly aggressive dural, skull, scalp, choroid plexus stalk lesions invading locally • Morphology: Amorphous, ill-defined mass with both intra- & extra-axial components • Best imaging tool: MRI + contrast

• More highly differentiated tumors appear in childhood whereas poorly differentiated in adults • Prognosis of MNT patients is generally very poor • Goal of treatment is to control disease locally • Bl'opsyisCRUCIALtoestabll'shhistl'ologl'cdiag n osis & guide treatment plan

Top Differential

Diagnoses

Diagnostic Checklist

• Benign meningothelial tumors • Malignant meningothelial tumors • Metastases

• There are no characteristic radiologic findings that· distinguish from other neoplasms

o Most are predominantly hyperintense on T2WI with heterogeneous signal & brain infiltration o May see extremely low signal from fibrous, chondroid, osteoid tissue • FLAIR: Best to evaluate edema, brain infiltration • T2* GRE: Susceptibility from fibrous, chondroid, osteoid matrix • T1 C+

o o o o

Most enhance, often intensely May have dural tail, necrotic foci ANGlO: Marked enhancement CHON: May show "honeycomb" pattern

Angiographic • DSA o Most have a o Others show • Interventional: operative time

Findings high degree of neovascularity avascular mass effect Preoperative embolization to & bleeding

Imaging Recommendations • Best imaging tool: MRI + contrast • Protocol advice: Fat suppression + contrast

IDIFFER.ENTIALOtA(jNOSIS Benign meningothelial

tumors

• Common meningioma o Characteristic MRI/MRS appearance o Not infiltrative

Malignant meningothelial

tumors

• Atypical/malignant meningioma o Infiltrative, destructive lesion o MRS characteristic o More common than MNT

Metastases • Often known extracranial malignancy • Frequently multifocal • More common than MNT

j

I PATHOLOGY General Features • Genetics o HGPC: Hyperdiploid chromosome 22 reported o MENSARC: Does NOT have chromosome abnormalities of meningiomas (e.g., 22,1,14, etc) • Etiology o Exact cause is uncertain; two theories • Sarcomatous component may arise from mesenchymal elements of perivascular sheaths (fibroblasts, endothelium, smooth muscle, pericytes) or from arachnoid • Most likely arise from pluripotential meningeal mesenchymal cells yielding many different tumor subtypes o Radiation is known cause, most commonly FIERO, with latency of 5-12 years • Epidemiology o MNT: 0.5-2.7% of intracranial neoplasms o CHON: < 0.16% of all intracranial tumors o HGPC: 2-4% of meningeal tumors; < 1% of all intracranial tumors o RHAB: < 1% of all intracranial tumors

Gross Pathologic & Surgical Features • CHON: Bluish-white glistening external surface of homogenous tan cartilaginous tissue • FIBRO: Pinkish, meaty • HGPC: Surrounding capsule, tenacious texture, grayish-white, solid or spongy, friable or granular • OSTEO: Soft tissue with foci of hemorrhage, calcification, cystic-necrosis

Microscopic Features • Given lack of clinical/radiologic findings specific for MNT, diagnosis nearly always made by histopathology • ANGlO o Irregular anastomosing vascular channels lined by anaplastic endothelial cells & pericytes o Cytokeratin,vimentin, Ulex europaeus agglutinin, anti-human endothelial cell marker CD31 positive

Skull, Scalp, and Meninges

4 69

MALIGNANT NONMENINGOTHELIAL TUMORS

4 70

• CHON o Primitive undifferentiated mesenchymal cells & well-defined islands of hyaline cartilage; vimentin & S-100 protein positive o Electron microscopy: Primitive precartilaginous mesenchyme with focal cartilaginous differentiation • FIERO o Highly cellular w/spindle-shaped cells in sheets or interlacing fascicles with herring-bone pattern o Cells contain elongated nuclei with mild hyperchromasia & high mitotic activity o Bone, osteoid, cartilage are absent • HGPC o Neoplastic cell lobules surround "staghorn" vessels o Pleomorphic, atypical, mitotically active short-spindle cells surrounding vascular spaces o Argyrophilic fibers surround individual tumor cells • MENSARC:Polymorphocellular sarcoma originating from leptomeninges • OSTEO o Single or multinucleated atypical polygonal cells in lacunae surrounded by immature osteoid o Osteoblastic, chondroblastic, & small-cell subtypes • RHAB o Malignant undifferentiated tumor w/foci of muscular differentiation o Electron microscopy: Intracytoplasmic filamentous striations of poorly formed myofibrils o Positive for actin, desmin, myoglobin, vimentin

Staging, Grading or Classification Criteria • In the WHO classification of tumors, the "other CNS neoplasms" section has 10 subsections, of which the "nonmeningothelial tumors of meninges" subsection contains o Malignant Mesenchymal (Le., MNT) • Chondrosarcoma • Hemangiopericytoma • Rhabdomyosarcoma • Meningeal sarcoma • Others o Several other categories

Iell

N I CAt ISSUES

o OSTEO: > 30 years; peak in 6th decade o RHAB:Children> > adults • Gender o Most have no sex predilection o FIERO, Ewing sarcoma = M > F o HGPC: M:F = 1.2:1

Natural History & Prognosis • Prognosis of MNT patients is generally very poor • Many have relentless tendency for local recurrence & metastases outside CNS o May recur years after diagnosis & initial treatment

Treatment • Goal of treatment is to control disease locally • Biopsy is CRUCIAL to establish histiologic diagnosis & guide treatment plan • Primary treatment: Wide radical surgical extirpation • Followed by postoperative radiation therapy o Prevent local recurrence, j risk of metastasis • Chemotherapy, brachytherapy often considered

I DIAGNOSTIC CHECKLIST Image Interpretation

I SELECTED REFERENCES 1.

2. 3. 4.

5. 6.

7.

Presentation

8.

• Most common signs/symptoms o Highly variable dependent on tumor location o Convexity: Most commonly hemiparesis, seizure o Skull base: Cranial nerve deficit(s) o Often rapidly growing mass with swelling o Headache, pain, fever, malaise • Clinical profile: No characteristic clinical findings

9.

10.

11.

Demographics • Age o More highly differentiated tumors appear in childhood whereas poorly differentiated in adults o ANGlO: Any age o CHON: 2nd & 3rd, mean age 37 years o FIERO: Usually middle-aged adults o HGPC: Average 42 years o MENSARC: Children> adults

Pearls

• There are no characteristic radiologic findings that distinguish from other neoplasms

12.

13.

Kothary N et al: Conventional and perfusion MR imaging of parafalcine chondrosarcoma. AJNR Am J Neuroradiol. 24(2):245-8, 2003 Weglewski A et al: Primary leptomeningeal sarcomatosis. Case report. Neurol Neurochir Pol. 37(1):251-8, 2003 Shi QL et al: Clinicopathological study of 1 meningeal hemangiopericytoma. Ai Zheng. 21(10):1116-9, 2002 Mitsuhashi T et al: Primary rhabdomyosarcoma associated with tumoral hemorrhage--case report. Neurol Med Chir (Tokyo). 42(2):73-7, 2002 Alen JF et al: Intracranial hemangiopericytoma: study of 12 cases. Acta Neurochir (Wien). 143(6):575-86,2001 Walker MT et al: Intradural primary chondroblastic osteosarcoma: case report. AJNR Am J Neuroradiol. 22(10):1960-2,2001 Buttner A et al: Primary meningeal sarcomas in two children. J Neurooncol. 52(2):181-8, 2001 Walker MT et al: Intradural primary chondroblastic osteosarcoma: case report. AJNR Am J Neuroradiol. 22(10):1960-2,2001 Bosma JJ et al: Primary intradural classic chondrosarcoma: case report and literature review. Neurosurgery. 48(2):420-3, 2001 Le Pessot F et al: A case of primitive meningeal rhabdomyosarcoma. Histological, immunohistochemical and ultrastructural study. Ann Pathol. 20(4):353-6, 2000 Pfluger T et al: MRI of primary meningeal sarcomas in two children: differential diagnostic considerations. Neuroradiology. 39(3):225-8, 1997 Fuse T et al: Primary intracranial epithelioid angiosarcoma--case report. Neurol Med Chir (Tokyo). 35(6):364-8, 1995 Ferracini R et al: Meningeal sarcoma with rhabdomyoblastic differentiation: case report. Neurosurgery. 30(5):782-5, 1992

Skull, Scalp, and Meninges

0

MALIGNANT NONMENINGOTHELIAL TUMORS [IMAGE GALLERY Typical (Left) Sagittal T1 C+ MR demonstrates marked enhancement of a primary meningeal sarcoma with ill-defined borders (arrow) & adjacent hypointense vasogenic edema (open arrow), both from brain infiltration. (Right) Axial T2 technique MR shows a hyperintense primary meningeal sarcoma invading brain. Note poorly defined borders & trapped CSF from this extra-axial-arising mass (arrow).

4 Typical

71 (Left) Axial CECT shows marked heterogeneous enhancement of a primary meningeal hemangiopericytoma wlskull destruction, brain infiltration, hypodense edema (arrow), scalp involvement, & mass effect. (Right) Axial T1 C+ MR demonstrates marked heterogeneous enhancement of a primary meningeal hemangiopericytoma wlskull destruction, brain infiltration, scalp involvement, & mass effect.

(Left) Super-selected DSA arteriogram in late arterial phase demonstrates extensive neovascularity of a primary meningeal hemangiopericytoma. Note irregular contours of abnormally developed tumoral vessels. (Right) Axial NECT shows extensive calcified matrix within the soft tissue mass of a large osteosarcoma.

Skull, Scalp, and Meninges

HEMANGIOMA

Coronal graphic illustrates sharply marginated expansile skull lesion with a slight honeycomb appearance pattern from intradiploic trabecular thickening.

4

Axial NECT demonstrates a sharply marginated hemangioma with a slight honeycomb appearance pattern from intradiploic trabecular thickening.

72

I TERMINOLOGY

Radiographic Findings

Abbreviations

• Osseous hemangioma, Intraosseous hemangioma, Primary intraosseous vascular anomaly

• Radiography o Sharply marginated expansile lesion o May have thin peripheral sclerotic rim o Honeycomb or sunburst appearance pattern

Definitions

CT Findings

• Benign intraosseous skull neoplasm with predominantly vascular & some avascular components

• NECT o Sharply marginated expansile lesion • Thin peripheral sclerotic rim in 1/3 o Intact inner & outer table • Outer table often more expanded than inner table • May deform overlying soft tissues o "Spoke-wheel", "reticulated", or "weblike" pattern • Intradiploic trabecular thickening o "Soap bubble" & "honeycomb" appearance possible • CECT: Enhances

and Synonyms

IIMACINCFINDINGS General Features • Best diagnostic clue: Sharply marginated expansile skull lesion • Location o Skull: 20% of intraosseous hemangiomas • Diploic space • Recent review: More often frontal & temporal • Less commonly occipital, parietal, or sphenoid o Vertebra: 28% of intra osseous hemangiomas o Flat/long bones: Rare • Size: 1-4 cm • Morphology o Usually solitary, uncommonly multiple o Well circumscribed margins

MR Findings • TlWI o Often isointense to brain • Small lesions may appear hyperintense: Fatty tissue is main cause of Tl WI hyperintensity • Larger lesions typically hypointense secondary to presence of thickened trabeculae o May be hemorrhagic • Signal dependent on hemoglobin stage • T2WI

DDx: "Holes in the Skull"

Burr Holes

x2

Metastasis

o V

Leptomeningeal

Skull, Scalp, and Meninges

Cyst

Cephalocele

HEMANGIOMA Key Facts Terminology

Pathology

• Osseous hemangioma, Intraosseous hemangioma, Primary intra osseous vascular anomaly

• General path comments: Originally classified as vascular neoplasms, now thought to be hamartomas with anomalous proliferation of endothelial-lined vascular channels • Rare: 0.2% of all osseous tumors

Imaging Findings • Best diagnostic clue: Sharply marginated expansile skull lesion • Skull: 20% of intraosseous hemangiomas • Recent review: More often frontal & temporal • Thin peripheral sclerotic rim in 1/3 • Intact inner & outer table • Intradiploic trabecular thickening • CECT: Enhances • Best imaging tool: NECT - excellent characterization of trabecular & cortical detail • Protocol advice: Bone reconstruction algorithm

o Usually mixed intensities • Often hyperintense: Slow flow or pooling of blood is main cause of T2WI hyperintensity o May be hemorrhagic • Signal dependent on hemoglobin stage • T1 C+: Enhances • MR signal characteristics dependent on o Quantity of slow-moving venous blood o Ratio of red marrow to converted fatty marrow

Angiographic

Findings

• DSA: Hypervascular, delayed persistent blush, "cluster of grapes" appearance • Supra selective embolization - devascularize to ! intraoperative bleeding & procedural morbidity

Nuclear Medicine

Findings

• Bone Scan: Variable from photopenia increased activity

to moderate

Imaging Recommendations • Best imaging tool: NECT - excellent characterization of trabecular & cortical detail • Protocol advice: Bone reconstruction algorithm

Clinical Issues • Benign slow-growing neoplasms • Rarely requires treatment

Diagnostic Checklist • Hemangiomas are just one of a large "holes in the skull" ddx that require exclusion of others • BEWARE:Routine bone biopsy & curettage may result in severe hemorrhage • A priori imaging diagnosis can prevent complications

o No peripheral sclerosis o Involves inner/outer tables • Metastases o Older patients, often history of cancer • Low grade hemangioendothelioma o Can be indistinguishable

"Holes in the skull": Solitary: Uncommon • Osteoporosis circumscripta o Hypointense on T1WI & T2WI from cortical thickening, coarse trabeculation • Epidermoid o Nonenhancing lesion with dense sclerotic borders • Cephalocele o Very young patients o NECT confirms bony defect with tissue herniation • Intradiploic arachnoid cyst o CSF isointensity on both T1WI & T2WI • Intradiploic meningioma o Homogeneously enhances o May have inner/outer table destruction • Leptomeningeal cyst o Appears as "growing fracture" on radiography/NECT

"Holes in the skull": Multiple:

I DIFFERENTIAL DIAGNOSIS "Holes in the skull": Solitary: Common • Normal anatomic variant: Fissure, foramen, canal, emissary venous channel, Pachonian (arachnoid) granulation, parietal thinning o NECT reveals normal anatomy • Surgical: Burr hole, shunt, surgical defect o Surgical history • Trauma: Fracture o Fracture confirmed on NECT • Dermoid o Well-circumscribed unilocular cyst containing fat • Eosinophilic granuloma o < 5 years o "Beveled edge", "hole-within-a-hole", "button sequestrum" on NECT

Common

• Normal anatomic variants: Fissure, foramen, canal, emissary venous channel, Pachonian (arachnoid) granulation, parietal thinning o NECT reveals normal anatomy • Surgical o Burr holes, surgical defects • Metastases o Older patients, often history of cancer • Osteoporosis o Older patients o Osteopenia, trabecular loss, cortical thinning

"Holes in the skull": Multiple:

Uncommon

• Hyperparathyroidism o "Salt and pepper" skull • Myeloma o Multiple, well-circumscribed, lytic, "punched-out", round lesions with osteopenia

Skull, Scalp, and Meninges

4 73

HEMANGIOMA o Involves both inner & outer tables • Osteomyelitis o 2-12 years; M:F = 3:1 o Mixed lytic/proliferative lesion o Characteristically moth-eaten/permeative medullary & cortical destruction with new bone formation

74

Demographics • Age o Usually adults: 4th-6th decade o All can be affected • Gender: M:F = 2: 1

Natural History & Prognosis

General Features

4

• Cavernous osseous hemangioma is most common • Capillary osseous hemangioma is rare o Freely mobile skin above lump

• General path comments: Originally classified as vascular neoplasms, now thought to be hamartomas with anomalous proliferation of endothelial-lined vascular channels • Genetics o Nearly all sporadic o In rare instances of congenital hemangiomatosis, skull, vertebra, skeletal muscle, skin & subcutaneous tissues may all be involved o Very rare "hereditary intraosseous vascular malformation of craniofacial region"; 2 families • Four affected members had multiple intraosseous hemangiomas within craniofacial bones • Homozygosity mapping excluded: Multiple cutaneous venous malformation, venous malformation w/glomus cells, hereditary hemorrhagic telangiectasia types 1 & 2, cerebral cavernous malformation types I, 2, & 3 • Etiology: Congenital or related to previous trauma • Epidemiology o Rare: 0.2% of all osseous tumors o 10% benign primary neoplasms of skull

• Benign slow-growing neoplasms

Treatment • Rarely requires treatment • Indications for surgery include: Correction of mass effect, control of hemorrhage, cosmesis o En bloc surgical excision w/rim of normal bone o Usually definitive treatment; recurrence is rare • Radiotherapy not recommended because of o Scar formation o Impairment of regional bone growth in children o Rarely malignant transformation

lotAGNOSIIC:C:HEC:KI.1Sr Consider • Hemangiomas are just one of a large "holes in the skull" ddx that require exclusion of others • BEWARE:Routine bone biopsy & curettage may result in severe hemorrhage o A priori imaging diagnosis can prevent complications

Gross Pathologic & Surgical Features

Image Interpretation

• Brownish-red

lesions under skull periosteum

Microscopic

Features

• Intact inner/outer aid in diagnosis

• Three histopathologic types o Capillary • Abundant vessels"" 10-100 microns in diameter with walls 1-3 cells thick • Vessels tend to run in parallel • Single layer of endothelial cells with no shedding and no anaplasia o Cavernous: Similar to capillary except larger lumina o Mixed capillary/cavernous • There may be reactive new bone formation which can appear similar to osteoblastoma • Radiating, weblike, or spoke-wheel trabecular thickening caused by intramembranous bone formation adjacent to angiomatous channels

I CLINICAL ISSUES

trabeculae, best

I.SElECTE[).·REFEREN.C:ES 1.

2.

3.

4.

5.

6.

Presentation • Most common signs/symptoms o Asymptomatic o Other signs/symptoms • Long-standing palpable lump, tender to pressure, spontaneous pain, deformity • Clinical profile o Osseous hemangiomas are rare; within the skull

Pearls

tables, thickened

7.

8.

Vilanova JC et al: Hemangioma from head to toe: MR imaging with pathologic correlation. RadioGraphies 24:367-85,2004 Amaral L et al: MR imaging for evaluation of lesions of the cranial vault: a pictorial essay. Arq Neuropsiquiatr. 61(3A): 521-32, 2003 Heckl S et al: Cavernomas of the skull: review of the literature 1975-2000. Neurosurg Rev. 25(1-2): 56-62; discussion 66-7, 2002 Vargel I et al: Hereditary intraosseous vascular malformation of the craniofacial region: an apparently novel disorder. Am J Med Genet. 109(1): 22-35, 2002 Suzuki Y et al: Neuroradiological features of intraosseous cavernous hemangioma--case report. Neurol Med Chir (Tokyo). 41(5): 279-82, 2001 Khanam H et al: Calvarial hemangiomas: report of two cases and review of the literature. Surg Neurol. 55(1): 63-7; discussion 67, 2001 Moore SL et al: Intraosseous hemangioma of the zygoma: CT and MR findings. AJNRAm J Neuroradiol. 22(7): 1383-5, 2001 Sweet C et al: Primary intraosseous hemangioma of the orbit: CT and MR appearance. AJNRAm J Neuroradiol. 18(2): 379-81, 1997

Skull, Scalp, and Meninges

HEMANGIOMA

Typical (Left) Lateral skull radiograph shows sharply marginated expansile hemangioma with a honeycomb appearance pattern from intradiploic trabecular thickening. Note outer table more involved than inner. (Right) Axial T2WI MR shows a heterogeneous intensity expansile hemangioma of the skull deforming overlying soft tissues.

4 75

Variant (Left) Sagittal Tl WI MR

shows isointense expansile lesion with hypointense thick trabeculae (white arrow) outer table more involved than inner; anteriorly are mixed intensities from hemorrhage (black arrow). (Right) Axial Tl C+ MR demonstrates two enhancing skull lesions (arrows) in a patient with multiple calvarial hemangiomas.

Other (Left) Craniotomy specimen

radiography shows expansile hemangioma with a "soap bubble" appearance pattern from intradiploic trabecular thickening. Note outer table is slightly more involved than inner. (Right) Surgical specimen radiography demonstrates a sharply marginated expansile hemangioma with a "soap bubble" appearance pattern.

Skull, Scalp, and Meninges

Lateral CT scout image demonstrates innumerable, tiny to small, lytic, multiple myeloma lesions of the skull.

Axial NECT shows innumerable, tiny to small, lytic, multiple myeloma lesions of the skull.

4 76

Abbreviations

o "Punched out" lytic lesion(s) o Meningeal myelomatosis: Marked hyperdensity • CECT o MM renal failure (RF) after contrast 0.6-1.25% • 0.15% in general population • Thus, not 100% risk-free, but may be performed if necessary & patient well hydrated o Meningeal myelomatosis: Uniform enhancement

and Synonyms

• Solitary = plasmacytoma myeloma (MM)

(PC)i multifocal

=

multiple

Definitions • Clonal B-Iymphocyte neoplasm of terminally differentiated plasma cells

MR Findings

General Features • Best diagnostic clue: Osteolytic skull lesion • Location o MM: Vertebra (50%) > skulli PC: Vertebra> skull o At time of diagnosis, often widely disseminated o Intracranial MM rare: Includes meningeal disease & very rarely invasion into brain • Morphology: Focal round or ovallesion(s)

• TlWI o Focal hypointensity (25%) o Absence of fatty pathologic infiltration • T2WI: Focal hyperintensity (53%) • Tl C+ o Marked lesional enhancement o Meningeal myelomatosis: Uniform enhancement

Angiographic Findings • Calvarial lesions may show tumor stain • Dural or intraparenchymal often angio negative

Nuclear Medicine

Radiographic Findings

Findings

• Bone Scan: Scintigraphy insensitive • PET o 18-Fluorodeoxyglucose (FDG) > bone scan o Conflicting reports of FDG PET vs radiography o Residual or recurrent FDG activity after therapy is poor prognostic factor

• Radiography o Osteopeniai "punched out" lytic lesion(s) o Rarely sclerotic except following therapy

CT Findings • NECT

DDx: "Holes in the Skull"

,.,

'.

"---', ...• ' ... .

Burr Holes x2

" -

Lytic Metastases

Hemangioma

Skull, Scalp, and Meninges

Brown Tumor

MYELOMA Key Facts Imaging Findings • • • •

"Punched out" lytic lesion(s) Marked lesional enhancement Best imaging tool: Radiography (skeletal survey) MRI best for rare meningeal & "intracranial" DZ

Top Differential

Diagnoses

• Surgical defect • Lytic metastasis • Many other causes of "holes in the skull"

Pathology • Underlying pathology is single plasma cell lineage expansion that replaces normal marrow & produces monoclonal immunoglobulins • 80-90% of patients have cytogenetic abnormalities • Etiology remains unknown

Other Modality

• 1% of all cancers, 2% of all cancer deaths • 2nd most prevalent blood cancer (1st = NHL) • Cell clone produces excess monoclonal (M proteins) & free light chain proteins

Clinical Issues • • • • •

Most common symptom: Bone pain (68%) Diagnosis often made with routine labs Diagnosis confirmed by marrow aspirate/biopsy Peak onset = 65-70 years 20% 5 year survivali death not from MM, but renal DZ, infection, thromboembolism • Radiography significantly influences therapy

Diagnostic Checklist • "Old fashioned" skeletal survey still highest sensitivity imaging modality

Findings

• Sensitivity of Imaging detection for diagnosis o Radiography detects 90% patients, 80% sites (30% lesions only on radiography) o Bone scan ~ 74% patients, 24-54% sites o Gallium scan ~ 55% patients, 40% sites • Up to 20% radiographs & MRI may be "normal" • MRI ~ about 10% understaging of stage III DZ

•

•

Imaging Recommendations • Best imaging tool o Best imaging tool: Radiography (skeletal survey) o CT > MRI for evaluation of specific lesion extent o MRI best for rare meningeal & "intracranial" DZ • Protocol advice: Routine unless tailored study for a specific lesion is required

I DIFFERENTIAl.. DIAGNOSIS Surgical defect • Burr hole, shunt, post-operative

•

defect

Lytic metastasis • Commonly

lung, breast, renal, thyroid

Hemangioma • Sharply marginated expansile lesion often with honeycomb or sunburst appearance pattern

Hyperparathyroidism • Local destructive lesions ("brown tumor"), 1 PTH

Many other causes of "holes in the skull"

•

o Underlying pathology is single plasma cell lineage expansion that replaces normal marrow & produces monoclonal immunoglobulins Genetics o 80-90% of patients have cytogenetic abnormalities • Chromosome 13 deletion is most common • More frequent in previously treated patients than in newly diagnosed disease Etiology o Etiology remains unknown o Possible associations and supporting evidence • Immune system decline: More common in elderly • Genetic factors: Slight 1 risk among children & siblings of MM patientsi also definite racial 1 risk • Certain occupations/chemicals: Agriculture, petroleum, leather industry, cosmetologyi herbicides, insecticides, petroleum products, heavy metals, plastics, dusts (including asbestos) • Radiation: 1 In Japanese atomic bomb survivors • Viral: Kaposi sarcoma-associated herpesvirus found in marrow cells of some MM patients Epidemiology o 1% of all cancers, 2% of all cancer deaths o 2nd most prevalent blood cancer (1st = NHL) o Incidence: 1 with age • "" 50 new cases/100,000/year at age 80 • "" 45,000 Americans have myeloma • "" 14,600 new US cases diagnosed per year o #1 primary bone malignancy 4th-8th decades • Solitary PC without MM rarei solitary skull PC very rare (0.7% of all PC) Associated abnormalities: "POEMS" syndrome: Polyneuropathy (P), organomegaly (0), endocrine abnormalities (E), myeloma (usually sclerotic lesions!) (M), skin changes (S)

!PATHOI..OGY

Gross Pathologic & Surgical Features

General Features

• Marrow replacement

• General path comments o PC = Early/initial MM stagei precedes by 1-20 years

Microscopic Features

with gelatinous red brown tissue

• Pleomorphic, enlarged plasma cells, often in sheets o Admixed with normal hematopoietic cells

Skull, Scalp, and Meninges

4 77

o Contain round/oval eccentric nuclei with clumped chromatin & perinuclear halo or pale zone o May have cytoplasmic inclusions: Mott, morula, or grape cells; Russell bodies o Cell clone produces excess monoclonal (M proteins) & free light chain proteins • M proteins may be IgA, IgD, IgG, IgE or IgM, depending on heavy chain class • Light chain proteins may be kappa or lambda

Staging, Grading or Classification Criteria

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• Durie-Salmon staging system o Stage I: All of the following • Hemoglobin value < 10 g/dL • Serum calcium value normal or ::s: 12 mg/dL • No anemia, RF, hypercalcemia, bone lesions • Low M-component: IgG value < 5 g/dL, IgA value < 3 g/dL, Bence Jones protein < 4 g/24 hrs • Low myeloma cell mass: < 0.6 cells x 1012/m2 o Stage II: Fitting neither stage I nor stage III • Intermediate cell mass: 0.6-1.2 cells x 1012/m2 o Stage III: One or more of the following • Hemoglobin value < 8.5 g/dL • Serum calcium value> 12 mg/dL • Advanced lytic bone lesions • IgG value> 7 g/dL, IgA value> 5 g/dL, Bence Jones protein> 12 g/24 hrs • High myeloma cell mass: > 1.2 cells x 1012/m2 o Subclassification (either A or B) • A = relatively normal renal function • B = abnormal renal function

I·CLlNiICAL.ISSUES Presentation • Most common signs/symptoms o Most common symptom: Bone pain (68%) o Rare signs • Hyperviscosity syndrome: Shortness of breath, confusion, & chest pain • Cryoglobulinemia: Precipitating particles cause pain/numbness in fingers/toes during cold weather • Amyloidosis: Amyloid protein deposition ~ I blood pressure & kidney, heart, or liver failure • Clinical profile o Diagnosis often made with routine labs • Normochromic normocytic anemia (62%) • Red blood cell rouleau formation • Renal insufficiency (55%) • Hypercalcemia (30-50%) • Proteinuria (88%); + Bence-Jones (50%) • Monoclonal gammopathy o Diagnosis confirmed by marrow aspirate/biopsy • MM probable if ;:::10% are plasma cells

Demographics

o African-Americans & Native Pacific Islanders have highest reported incidence; Asians lowest • 9.5 cases per 100,000 African-Americans • 4.1 cases per 100,000 Caucasian-Americans

Natural History & Prognosis • Solitary skull PC: No difference in prognosis between PC originating from bone vs dura mater • MM

o Renal insufficiency frequent o Leukopenia leads to frequent pneumonias o Secondary amyloidosis (6-15%) • 20% 5 year survival; death not from MM, but renal DZ, infection, thromboembolism o Median survival is approximately 3 years with conventional chemotherapy • Good prognosis indicators o Stage I or II disease o Normal chromosome 13 • Abnormal cytogenetics is most important factor • Chromosome 13 or llq deletions, or any translocation, predict poor prognosis • Chromosome 13 abnormalities reduces 5 year event-free survival 20% ~ 0% & overall survival 44% ~ 16%

Treatment • Radiography significantly influences therapy o 2 unequivocal rounded, punched-out lytic bone lesions indicates stage III ~ chemotherapy o Thus, important to radiographically assess osseous MM involvement at initial staging • Treatment dependent on disease status & may include o Observation with supportive care o Chemotherapy o Participation in a clinical trial o Autologous or allogenic stem cell transplant o Maintenance therapy with steroids or interferon o Repeat of primary therapy o Salvage chemotherapy

IDIAGNOS11(JCfiE(JKll$T Image Interpretation

I SELECTED 1.

2. 3.

4.

• Age o Peak onset = 65-70 years o Recent statistics indicate both increasing incidence & earlier age of onset • Gender: Male slightly> Female • Ethnicity

Pearls

• "Old fashioned" skeletal survey still highest sensitivity imaging modality

5.

REFERENCES

Angtuaco EJC et al: Multiple myeloma: Clinical review and diagnostic imaging. Radiology 231:11-23,2004 Jadvar H et al: Diagnostic utility of FDG PET in multiple myeloma. Skeletal Radiol. 31(12): 690-4, 2002 Schwartz TH et al: Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study. Neurosurgery. 49(5): 1039-44; discussion 1044-5,2001 Lecouvet FE et al: Skeletal survey in advanced multiple myeloma: radiographic versus MR imaging survey. Br J Haematol. 106(1): 35-9, 1999 Cervoni L et al: Solitary plasmacytoma of the calvarium: a review of clinical and prognostic features. Neurosurg Rev. 21(2-3): 102-5, 1998

Skull, Scalp, and Meninges

Typical (Left) Axial NECT

demonstrates paired, "punched out", expansile, lytic, skull myeloma lesions (arrows). Note multiple smaller myelomatous skull lesions. (Right) Sagittal Tl WI MR shows several calvarial myeloma lesions (arrows). There is also significant dival involvement (open arrow).

4 Typical

79 (Left) Axial T2WI MR shows

several multiple myeloma lesions as hyperintense foci relative to adjacent skull signal (arrows). (Right) Axial Tl C+ MR demonstrates marked enhancement of several multiple myeloma skull lesions (arrows).

(Left) Axial TlWI MR demonstrates a solitary

osteolytic plasmacytoma of the skull with a large tumoral component. The brain is flattened but otherwise unaffected. (Right) Axial T2WI MR shows a solitary osteolytic skull plasmacytoma with a large tumoral component. T2 best shows relatively normal dura displaced inward (black arrows). Brain is flattened but unaffected.

Skull, Scalp, and Meninges

SKULL AND MENINGEAL METASTASES

Axial graphic illustrates a destructive skull metastasis expanding the diploic space and invading the underlying dura (light blue linear structure).

4 80

Coronal T1 C+ MR demonstrates homogeneously enhancing skull metastasis; infiltrated dura is thickened, almost biconvex, flattening underlying brain. Subgaleal scalp involvement is apparent.

ITERMINQl-OQ¥

CT Findings

Abbreviations

• NECT o Any: May find hemorrhagic hyperdensity o Sub-galeal space: Relative dense lesion • CECT o SM: Enhancing mass centered in bone with osseous destruction, lacking 'benign" sclerotic border • Most are lytic; a few sclerotic (e.g., prostate) o DM & LM: Both may appear as enhancing biconvex masses displacing brain • DM characterized by calvarial involvement o Carcinomatosis: CT is insensitive, however hydrocephalus may be early sign

and Synonyms

• Skull metastases (SM), dural metastases (DM), arachnoid/subarachnoid metastases (ASAM), pial metastases (PM), leptomeningeal (pia + arachnoid) (LM) metasases

Definitions • Metastatic disease from extracranial tissues overlying the brain

primary tumor to

IIMAGINGHNDINGS

MR Findings

General Features • Best diagnostic clue: Enhancing lesion(s) with skull/meningeal destruction/infiltration • Location: Skull, dura, leptomeninges, arachnoid/subarachnoid, pia, also subgaleal • Morphology: Many manifestations: Smooth thickening, nodularity, loculation, lobulation, fungating masses

Radiographic Findings • Radiography: SM: Focal lytic or blastic lesions lacking "benign" sclerotic border

DDx: Mimics of Skull/Meningeal

Skull Myeloma

• TlWI o SM: Hypointense marrow lesion o DM & LM: Most masses hypointense to gray matter o Sub-galeal space: Relative hypointense lesion o Any: May find hemorrhagic signal • T2WI o SM: Hyperintense marrow lesion; dura usually intact o DM between skull & elevated hypointense dura o DM & LM: Most hyperintense relative to gray matter o Any: May find hemorrhagic signal • FLAIR o LM & ASAM: Diffuse hyperintense CSF

Metastases

Chronic Subdural

Neurosarcoid

Skull, Scalp, and Meninges

Meningitis

SKULL AND MENINGEAL METASTASES Facts • Accuracy of single lumbar puncture (LP) is 50-60% but 90% after 3 attempts • Bimodal ~ children (medulloblastoma & leukemia), adults (breast, lung, melanoma, prostate) • Untreated malignant meningeal metastases decreases survival time to 1-2 months • Usually radiation + chemotherapy (intrathecal and/or systemic) initiated to slow progression • Entire neuraxis must be treated as tumor cells are often widely disseminated throughout CSF • With palliative treatment, survival can be improved up to 6-10 months • Biopsy may be necessary if no evidence of 10 tumor

•

Diagnostic Checklist • Both enhanced MRI & LP should be performed, especially if initial test is negative

o ASAM infiltrating perivascular spaces (PVS): Loss of normal PVS CSF suppression ~ hyperintensity o Carcinomatosis: Hyperintense thickening; affects adjacent sulcal nulling ~ hyperintensity o Brain infiltration: Hyperintense vasogenic edema • DWI: Distinguish hyperintense ischemic cytotoxic edema from tumoral vasogenic edema in presence of vascular involvement • T1 C+

o SM: Lesion may enhance to "normal" T1 marrow signal ~ requires fat-saturation • Usually some dural thickening & enhancement o DM & LM: Both appear as enhancing biconvex masses displacing brain • DM often has calvarial involvement • LM often invades underlying brain o LM, ASAM, PM: Diffuse enhancing tissue with/without nodularity o ASAM infiltrating perivascular spaces: Tiny enhancing nodules with a miliary appearance o Carcinomatosis: Enhancing & thickened tissue, with/without nodules • May coat ependymal surfaces, cranial nerves • MRV: May be helpful in evaluation of sinus displacement, compression, thrombosis • MR CSF flow: May be helpful establishing location & degree of CSF obstruction • To differentiate intra- vs extra-axial tumor location o Look for these "trapped" structures between mass & brain to confirm extra-axial location • Dura ~ best seen after contrast • CSF clefts ~ best seen on T2WI • Displaced cortical veins ~ look for flow voids

Nuclear Medicine

Findings

• Bone Scan: SM: Usually intensely positive • PET o 18-Fluorodeoxyglucose (FDG) PET may detect small calvarial mets not seen by MRI o Caveat: Adjacent activity from normal gray matter glucose use may limit detection of SM • Indium ll1-DTPA CSF flow study o Evaluation for CSF flow obstruction

o Dynamic imaging over 1-2 hrs + 24 hour delay

Imaging Recommendations • Best imaging tool o SM: NECT, bone algorithm, for osseous evaluation • MRI + contrast if dura, scalp involved o DM, ASAM, PM, LM: MRI + Gado, although sensitivity still only"" 70% • 90% for extra cranial solid tumor mets • 55% when hematologic (lymphoma, leukemia) • Protocol advice o Fat saturation necessary to distinguish enhancement from normal hyperintense marrow & scalp fat o FLAIR> T2WI; T1 C+ > FLAIR C+

I DIFFERENTIAL DIAGNOSIS SM • Surgical defect: Burr hole, craniectomy • Myeloma: Characteristic labs

DM/LM • Epidural/subdural hematoma: Distinctive MRI • Meningioma: MR spectroscopy ~ Alanine

ASAM • Subarachnoid

hemorrhage:

Typical NECT appearance

Carcinomatosis • Sarcoidosis: CXR ~ hilar adenopathy, + Kveim-Siltzbach skin test • Infectious meningitis: CSF ~ infection/organism

I PATHOLOGY General Features • General path comments o Dura & leptomeninges provide considerable barriers to contiguous spread of mets o General mechanisms of spread • Arterial hematogenous: Arterial transfer (e.g., breast, lung, melanoma, prostate)

Skull, Scalp, and Meninges

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SKULL AND MENINGEAL METASTASES

4 82

• Venous hematogenous: Via choroid plexus or through arachnoid vessels (classic for leukemia) • Direct extension: From primary brain tumors (e.g., GBM, PNET, ependymoma) • Perineural spread: H&N cancers (classically squamous cell carcinoma (SCCA)) • Iatrogenic: Following initial resection/debulking of primary brain tumors • Etiology o SM: Hematogenous (most commonly breast, lung, prostate, kidney) or by direct extension (SCCA) o DM: Hematogenous (most commonly breast> lymphoma> prostate> neuroblastoma) o LM, ASAM, PM: Hematogenous (most commonly lung, gastric, breast, ovary, melanoma, leukemia, lymphoma) or direct extension (10 CNS tumors) • Epidemiology o 18% patients with extra- & intracranial malignancies o 6-18% of CNS mets also involve arachnoid/subarachnoid space, pia, or both o Carcinomatosis in up to 25% of cancer patients • Primary tumor never identified in 2-4% • Occurs in up to 35% breast, 25% lung small cell, 25% melanoma cancer patients • Associated abnormalities o Limbic encephalitis • Rare paraneoplastic encephalitis with affinity for limbic system; affects M > F • Altered mental status; impaired affect & memory • Most commonly from lung small cell • Pathology & imaging are nonspecific & indistinguishable from herpes encephalitis

Gross Pathologic & Surgical Features • DM: Well-defined dural masses often invading skull o Necropsy ~ nodules on inner dura (subdural) • LM, ASAM, PM: Gray-white or yellow thickening

Microscopic

Features

Demographics • Age o Bimodal ~ children (medulloblastoma & leukemia), adults (breast, lung, melanoma, prostate) o Average age"" 50 years (relatively young 2 pediatric cancer & young women with breast cancer) • Gender: Dependent on primary cancer 0

Natural History & Prognosis • Dural sinus thrombosis from invasion or compression • Obstructive hydrocephalus o Noncommunicating: Normal CSF flow obstructed, usually by cisternal metastases o Communicating: Normal CSF flow, ~ arachnoid villi absorption, obstruction 2 tumor cells, blood, debris o Important to evaluate presence prior to LP to prevent downward herniation & death o Up to 70% carcinomatosis patients have some degree of CSF obstruction • Pachymeningitis interna hemorrhagica o Rare, usually bilateral, spontaneous, subdural hematomas from meningeal mets o Commonly from breast but also prostate, melanoma • Untreated malignant meningeal metastases decreases survival time to 1-2 months 0

Treatment • Early detection of meningeal mets is crucial o MRI often provides 1st clue to disease presence o Thus imaging plays key role in patient management • Usually radiation + chemotherapy (intrathecal and/or systemic) initiated to slow progression o Entire neuraxis must be treated as tumor cells are often widely disseminated throughout CSF o With palliative treatment, survival can be improved up to 6-10 months • Biopsy may be necessary if no evidence of 1 tumor • Ventriculoperitoneal shunt may be necessary in patients with symptomatic CSF obstruction 0

• SM & DM: Metastatic cell infiltrates • LM & ASAM: Metastatic cell infiltrates, often along perivascular spaces extending into brain • All: Inflammatory cell migration

I DIAGNOSI1CiCHE€I(E1SI

I CL.INICALISSUES

• Both enhanced MRI & LP should be performed, especially if initial test is negative

Image Interpretation

Pearls

Presentation • Most common signs/symptoms o All: May be asymptomatic & unsuspected clinically o Headache is most common symptom (50%) o Less common signs/symptoms • N/V, pain, sensory deficit, weakness (33%) • Mental status change (25%) • Seizures (20%) • t ICP from CSF obstruction • Cranial nerve deficit(s) o Symptoms from brain compression ~ highly dependent on locale • Clinical profile o CSF cytology often falsely negative • Accuracy of single lumbar puncture (LP) is 50-60% but 90% after 3 attempts

I SELECTED REFERENCES 1.

2.

3.

4.

5.

Singh SK et al: MR imaging of leptomeningeal metastases: comparison of three sequences. AJNR Am J Neuroradiol. 23(5):817-21,2002 Yamamoto AJ et al: Detection of cranial metastases by F-18 FDG positron emission tomography. Clin Nucl Med. 26(5):402-4, 2001 Chamberlain MC: Neoplastic meningitis: a guide to diagnosis and treatment. Curr Opin Neurol. 13(6):641-8, 2000 Grossman SA et al: Leptomeningeal carcinomatosis. Cancer Treat Rev. 25(2):103-19, 1999 Collie DA et al: Imaging features of leptomeningeal metastases. Clin Radiol. 54(11):765-71, 1999

Skull, Scalp, and Meninges

SKULL AND MENINGEAL METASTASES I IMAGE GALLERY Typical (Left) Axial graphic illustrates diffuse leptomeningeal metastases (abnormal blue material) coating the brain and filling interdigitating sulci. (Right) Coronal Tl c+ MR shows diffuse, leptomeningeal metastases of both supra- and infratentorial compartments. Morphology is smooth rather than nodular.

4 83 (Left) Axial CECT shows diffuse, bilateral, leptomeningeal metastases. Morphology is smooth rather than nodular. (Right) Axial TI C+ MR: Carcinomatosis w/tumor along folial pia (white arrow) & also subarachnoid/CSF coating ventricle (black arrow), cranial nerves (open black arrows), brain surfaces (open white arrows).

Variant (Left) Coronal TlWI MR shows extensive renal cell metastases. Note Tl hyperintense tumoral-related hemorrhagic products (black arrows) as well as prominent flow voids of neovascularity (white arrows). (Right) Axial Tl C+ MR: Enhancing skull metastasis involves both underlying dura and overlying scalp. Superior sagittal sinus is occluded by invasion (arrow). Fat-saturation improves conspicuity.

Skull, Scalp, and Meninges

mixed pial-dural, vs. dural arteriovenous fistula, I:S8i,I:5-9 oligodendroglioma vs., 1:6-43 remote cerebellar hemorrhage vs., 1:4-20i, 1:4-21 traumatic subarachnoid hemorrhage vs., 1:2-23 vascular loop compression vs., II:3-24i, II:3-25 vein of Galen malformation vs., 1:5-13 von Hippel Lindau syndrome vs., 1:1-86i, 1:1-87 Arteriovenous shunt. See Arteriovenous fistula Arteritis intracranial atherosclerosis vs., 1:4-25 primary, of central nervous system, 1:4-46 to 1:4-48, 1:4-49i differential diagnosis, 1:4-46i, 1:4-47 Artery of Percheron infarct, 1:4-106 Arthritis, rheumatoid, II:4-31 Arthrogryposis, 1:1-67 Arylsulfatase A pseudodeficiency, 1:9-29 Aspartylacylase deficiency, 1:9-49 Asphyxia, profound perinatal, 1:9-12i, 1:9-13 Astroblastoma, 1:6-50 to 1:6-51, 1:6-Sli differential diagnosis, 1:6-S0i Astrocytoma anaplastic, 1:6-16 to 1:6-18, 1:6-19i anaplastic oligodendroglioma vs., 1:6-46i, 1:6-47 differential diagnosis, 1:6-16i, 1:6-17 glioblastoma multiforme vs., 1:6-21 gliomatosis cerebri vs., 1:6-26i, 1:6-27 low grade diffuse astrocytoma vs., 1:6-8i, 1:6-9 parenchymal metastases vs., 1:6-141 aqueductal stenosis vs., II:1-21 arachnoid cyst vs., II:3-17 arteriovenous malformation vs., 1:5-5 cerebral infarction (chronic) vs., 1:4-84i cerebral ischemia-infarction (acute) vs., 1:4-76i, 1:4-78 choroid plexus cyst vs., 1:7-31 choroid plexus papilloma vs., 1:6-6Oi craniopharyngioma vs., II:2-32i, II:2-33 cystic, enlarged perivascular spaces vs., 1:7-22i diffuse, low grade, 1:6-8 to 1:6-10, 1:6-1li differential diagnosis, 1:6-8i, 1:6-9 ganglioglioma vs., 1:6-66i, 1:6-67 mesial temporal sclerosis vs., I:IO-SOi, 1:10-51 paraneoplastic syndromes vs., 1:6-144i, 1:6-145 pleomorphic xanthoastrocytoma vs., 1:6-35 embryonal carcinoma vs., 1:6-138 encephalitis vs., 1:8-38i germinoma vs., 1:6-132i, 1:6-133 hemangioblastoma vs., 1:6-115 HIV encephalitis vs., 1:8-67 hypertrophic olivary degeneration vs., 1:10-95 hypothalamic,I:6-133 oligodendroglioma vs., 1:6-42i, 1:6-43 pilocytic, 1:6-30 to 1:6-32, 1:6-33i, 1:6-75 atypical teratoid-rhabdoid tumor vs., 1:6-100i Cowden syndrome vs., 1:1-112i, 1:1-113 differential diagnosis, 1:6-30i, 1:6-31 ependymoma vs., 1:6-S2i, 1:6-53 ganglioglioma vs., 1:6-66i, 1:6-67 hemangioblastoma vs., 1:6-114i, 1:6-115 medulloblastoma vs., 1:6-93

pleomorphic xanthoastrocytoma vs., 1:6--34i,1:6--35 schwannoma vs., 1:6-108i, 1:6-109 von Hippel Lindau syndrome vs., 1:1-87 pilomyxoid atypical teratoid-rhabdoid tumor vs., 1:6-101 pilocytic astrocytoma vs., 1:6-31 pineoblastoma vs., 1:6-84i, 1:6-85 pineocytoma vs., 1:6-89 pleomorphic xanthoastrocytoma, 1:6-34 to 1:6-36, 1:6-37i of pons, osmotic demyelination syndrome vs., 1:10-43 status epilepticus vs., 1:10-S4i, 1:10-55 subependymal giant cell, 1:6-38 to 1:6-40, 1:6-4li central neurocytoma vs., 1:6-80i, 1:6-81 choroid plexus carcinoma vs., 1:6-65 differential diagnosis, 1:6-38i, 1:6-39 subependymoma vs., 1:6-S6i, 1:6-57 teratoid-rhabdoid tumor vs., 1:6-101 teratoma vs., 1:6-137 tuber cinereum hamartoma vs., II:2-12i, II:2-13 Atherosclerosis blood blister-like aneurysm vs., 1:3-23 cerebral ischemia vs., 1:2-51 extra cranial, 1:4-28 to 1:4-30, 1:4-3li differential diagnosis, 1:4-28i, 1:4-29 extracranial dissection vs., 1:2-S8i, 1:2-59 intracranial, 1:4-24 to 1:4-26, 1:4-27i differential diagnosis, 1:4-24i, 1:4-25 primary arteritis of CNS vs., 1:4-46i, 1:4-47 vasculitis vs., 1:4-SOi, 1:4-51 intracranial dissection vs., 1:2-S6i, 1:2-57 Atherosclerotic dolichoectasia, 1:3-18 Atretic cephalocele, II:4-12 to II:4-13, II:4-13i differential diagnosis, II:4-12i, II:4-13 Atrophy cerebellar, I:IO-82i, 1:10-84 cerebello-olivary, 1:10-83 multiple system. See Multiple system atrophy (MSA) olivopontocerebellar, hereditary, 1:10-84 optic nerve, I:IO-36i, 1:10-37 small head circumference, vs. enlarged arachnoid spaces, II:1-12i, II:l-13 Atypical teratoid-rhabdoid tumor. See Teratoid-rhabdoid tumor, atypical Auditory canal, internal. See Internal auditory canal Axonal injury, diffuse (DAl), 1:2-30 to 1:2-32, 1:2-33i cerebral amyloid disease vs., 1:4-59 differential diagnosis, 1:2-30i, 1:2-31 penetrating injury vs., 1:2-4i

B Bacterial infections, brain, 1:8-17 Basal cell nevus syndrome, 1:1-100 to 1:1-102, 1:1-103i differential diagnosis, 1:1-100i, 1:1-101 Basal ganglia calcification normal, I:IO-16i, 1:10-17 pathologic,I:10-17 lesions vs. MELAS,1:9-17 punctate foci, 1:4-43

mixed pial-dural, vs. dural arteriovenous fistula, I:S8i,I:5-9 oligodendroglioma vs., 1:6-43 remote cerebellar hemorrhage vs., 1:4-20i, 1:4-21 traumatic subarachnoid hemorrhage vs., 1:2-23 vascular loop compression vs., II:3-24i, II:3-25 vein of Galen malformation vs., 1:5-13 von Hippel Lindau syndrome vs., 1:1-86i, 1:1-87 Arteriovenous shunt. See Arteriovenous fistula Arteritis intracranial atherosclerosis vs., 1:4-25 primary, of central nervous system, 1:4-46 to 1:4-48, 1:4-49i differential diagnosis, 1:4-46i, 1:4-47 Artery of Percheron infarct, 1:4-106 Arthritis, rheumatoid, II:4-31 Arthrogryposis, 1:1-67 Arylsulfatase A pseudodeficiency, 1:9-29 Aspartylacylase deficiency, 1:9-49 Asphyxia, profound perinatal, 1:9-12i, 1:9-13 Astroblastoma, 1:6-50 to 1:6-51, 1:6-Sli differential diagnosis, 1:6-S0i Astrocytoma anaplastic, 1:6-16 to 1:6-18, 1:6-19i anaplastic oligodendroglioma vs., 1:6-46i, 1:6-47 differential diagnosis, 1:6-16i, 1:6-17 glioblastoma multiforme vs., 1:6-21 gliomatosis cerebri vs., 1:6-26i, 1:6-27 low grade diffuse astrocytoma vs., 1:6-8i, 1:6-9 parenchymal metastases vs., 1:6-141 aqueductal stenosis vs., II:1-21 arachnoid cyst vs., II:3-17 arteriovenous malformation vs., 1:5-5 cerebral infarction (chronic) vs., 1:4-84i cerebral ischemia-infarction (acute) vs., 1:4-76i, 1:4-78 choroid plexus cyst vs., 1:7-31 choroid plexus papilloma vs., 1:6-6Oi craniopharyngioma vs., II:2-32i, II:2-33 cystic, enlarged perivascular spaces vs., 1:7-22i diffuse, low grade, 1:6-8 to 1:6-10, 1:6-1li differential diagnosis, 1:6-8i, 1:6-9 ganglioglioma vs., 1:6-66i, 1:6-67 mesial temporal sclerosis vs., I:IO-SOi, 1:10-51 paraneoplastic syndromes vs., 1:6-144i, 1:6-145 pleomorphic xanthoastrocytoma vs., 1:6-35 embryonal carcinoma vs., 1:6-138 encephalitis vs., 1:8-38i germinoma vs., 1:6-132i, 1:6-133 hemangioblastoma vs., 1:6-115 HIV encephalitis vs., 1:8-67 hypertrophic olivary degeneration vs., 1:10-95 hypothalamic,I:6-133 oligodendroglioma vs., 1:6-42i, 1:6-43 pilocytic, 1:6-30 to 1:6-32, 1:6-33i, 1:6-75 atypical teratoid-rhabdoid tumor vs., 1:6-100i Cowden syndrome vs., 1:1-112i, 1:1-113 differential diagnosis, 1:6-30i, 1:6-31 ependymoma vs., 1:6-S2i, 1:6-53 ganglioglioma vs., 1:6-66i, 1:6-67 hemangioblastoma vs., 1:6-114i, 1:6-115 medulloblastoma vs., 1:6-93

pleomorphic xanthoastrocytoma vs., 1:6--34i,1:6--35 schwannoma vs., 1:6-108i, 1:6-109 von Hippel Lindau syndrome vs., 1:1-87 pilomyxoid atypical teratoid-rhabdoid tumor vs., 1:6-101 pilocytic astrocytoma vs., 1:6-31 pineoblastoma vs., 1:6-84i, 1:6-85 pineocytoma vs., 1:6-89 pleomorphic xanthoastrocytoma, 1:6-34 to 1:6-36, 1:6-37i of pons, osmotic demyelination syndrome vs., 1:10-43 status epilepticus vs., 1:10-S4i, 1:10-55 subependymal giant cell, 1:6-38 to 1:6-40, 1:6-4li central neurocytoma vs., 1:6-80i, 1:6-81 choroid plexus carcinoma vs., 1:6-65 differential diagnosis, 1:6-38i, 1:6-39 subependymoma vs., 1:6-S6i, 1:6-57 teratoid-rhabdoid tumor vs., 1:6-101 teratoma vs., 1:6-137 tuber cinereum hamartoma vs., II:2-12i, II:2-13 Atherosclerosis blood blister-like aneurysm vs., 1:3-23 cerebral ischemia vs., 1:2-51 extra cranial, 1:4-28 to 1:4-30, 1:4-3li differential diagnosis, 1:4-28i, 1:4-29 extracranial dissection vs., 1:2-S8i, 1:2-59 intracranial, 1:4-24 to 1:4-26, 1:4-27i differential diagnosis, 1:4-24i, 1:4-25 primary arteritis of CNS vs., 1:4-46i, 1:4-47 vasculitis vs., 1:4-SOi, 1:4-51 intracranial dissection vs., 1:2-S6i, 1:2-57 Atherosclerotic dolichoectasia, 1:3-18 Atretic cephalocele, II:4-12 to II:4-13, II:4-13i differential diagnosis, II:4-12i, II:4-13 Atrophy cerebellar, I:IO-82i, 1:10-84 cerebello-olivary, 1:10-83 multiple system. See Multiple system atrophy (MSA) olivopontocerebellar, hereditary, 1:10-84 optic nerve, I:IO-36i, 1:10-37 small head circumference, vs. enlarged arachnoid spaces, II:1-12i, II:l-13 Atypical teratoid-rhabdoid tumor. See Teratoid-rhabdoid tumor, atypical Auditory canal, internal. See Internal auditory canal Axonal injury, diffuse (DAl), 1:2-30 to 1:2-32, 1:2-33i cerebral amyloid disease vs., 1:4-59 differential diagnosis, 1:2-30i, 1:2-31 penetrating injury vs., 1:2-4i

B Bacterial infections, brain, 1:8-17 Basal cell nevus syndrome, 1:1-100 to 1:1-102, 1:1-103i differential diagnosis, 1:1-100i, 1:1-101 Basal ganglia calcification normal, I:IO-16i, 1:10-17 pathologic,I:10-17 lesions vs. MELAS,1:9-17 punctate foci, 1:4-43

Basilar tip occlusion, 1:4-104i, 1:4-106 Beh<;:etdisease acute disseminated encephalomyelitis vs., 1:8-78i, 1:8-79 amyotrophic lateral sclerosis vs., 1:10-87 chronic hypertensive encephalopathy vs., 1:10-34 systemic lupus erythematosus vs., 1:4-55 Wallerian degeneration vs., 1:10-92 Bell palsy, II:3-20i, 11:3-21 Binswanger's disease. See Hypertensive encephalopathy, chronic Birth injuries, non-accidental trauma vs., 1:2-38i Blastomycosis, 1:8-58 Blood blister-like aneurysm, 1:3-22 to 1:3-23, 1:3-23i differential diagnosis, 1:3-22i Blood dyscrasia, 1:2-23 Blood hyperdensity, 1:4-100i, 1:4-101 Blood vessels, hyperdensity vs. dural sinus thrombosis, 1:4-97 Blue-rubber-bleb nevus syndrome, 1:1-95 Bone cyst, aneurysmal, I:I-IOOi, 1:1-101 Bone neoplasms, primary, 1:2-7 Borreliosis, Lyme. See Lyme disease Bourneville-Pringle syndrome. See Tuberous sclerosis complex Brain aging. See Aging brain, normal normal amyotrophic lateral sclerosis vs., 1:1O-86i, 1:10-87 Wallerian degeneration vs., 1:10-87 surface vessels vs. superficial siderosis, 1:3-8i, 1:3-9 Brain cysts, I:1-35 Brain death, 1:2-54 to 1:2-55, 1:2-SSi differential diagnosis, 1:2-S4i, 1:2-55 Brainstem, hypoplastic, 1:1-67 Brown tumor, II:4-76i, 11:4-77 Burr holes hemangioma vs., II:4-72i, 11:4-73 histiocytosis vs., II:4-48i, 11:4-49 myeloma vs., II:4-76i, 11:4-77 skull and meningeal metastasis vs., 11:4-81

c CADASIL(cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy), 1:4-62 to 1:4-64, 1:4-6Si arteriolosclerotic disease vs., 1:4-32i, 1:4-33 cerebral amyloid disease vs., 1:4-59 chronic hypertensive encephalopathy vs., I:IO-32i, 1:10-33 differential diagnosis, 1:4-62i, 1:4-63 Cafe-au-Iait spots, 1:1-79 Callosal dysgenesis, 1:1-18 to 1:1-20, 1:1-2li differential diagnosis, 1:1-18i, 1:1-19 heterotopic gray matter vs., 1:1-59 lissencephaly type 1 vs., 1:1-67 porencephalic cyst vs., 1:7-36i, 1:7-37 Callostotomy, 1:1-18i, 1:1-19 Calvarial thickening. See Thick skull Calvarium fracture, 11:4-14 to 11:4-16, II:4-17i

differential diagnosis, II:4-14i, 11:4-15 Canavan disease, 1:9-52 to 1:9-53, 1:9-S3i Alexander disease vs., 1:9-S4i, 1:9-55 differential diagnosis, 1:9-52, 1:9-S2i glutaric aciduria type 1vs., 1:9-49 van der Knapp leukoencephalopathy vs., 1:9-59 Candidiasis, 1:8-58 Capillary telangiectasis, 1:5-28 to 1:5-29, I:S-29i cavernous malformation vs., 1:5-25 cerebral amyloid disease vs., 1:4-59 differential diagnosis, I:S-28i, 1:5-29 hereditary hemorrhagic telangiectasia vs., 1:1-105 Carbon monoxide poisoning, 1:10-38 to 1:10-40, 1:IO-4li alcoholic encephalopathy vs., 1:10-21 deep cerebral venous thrombosis vs., 1:4-104i, 1:4105 to 1:4-106 differential diagnosis, I: 1O-38i, I:10-39 to I:10-40 Hallervorden-Spatz syndrome vs., 1:9-62i, 1:9-63 Huntington disease vs., 1:9-66i, 1:9-67 kernicterus vs., 1:10-6 MELASvs., 1:9-17 Wilson disease vs., 1:9-70i, 1:9-71 Carcinoma choriocarcinoma embryonal carcinoma vs., 1:6-138 pineoblastoma vs., 1:6-85 pineocytoma vs., 1:6-89 choroid plexus. See Choroid plexus carcinoma embryonal. See Embryonal carcinoma Carcinomatosis leptomeningeal, 11:3-36 to 11:3-39 meningeal, 11:3-36 to 11:3-39 meningitis vs., 1:8-21 neurocutaneous melanosis vs., 1:1-116i, 1:1-117 tuberculosis vs., 1:8-47 skull and meningeal metastasis vs., 11:4-81 traumatic subarachnoid hemorrhage vs., 1:2-22i, 1:2-23 Carotid-cavernous fistula, traumatic, 1:2-62 to 1:2-63, 1:2-63i differential diagnosis, 1:2-62i, 1:2-63 Cavernoma, giant, 1:6-97 Cavernous angioma. See Hemangioma, cavernous Cavernous malformation, 1:5-24 to 1:5-26, I:S-27i capillary telangiectasis vs., I:S-28i, 1:5-29 central neurocytoma vs., 1:6-81 cerebral amyloid disease vs., 1:4-S8i, 1:4-59 choroid plexus carcinoma vs., 1:6-65 differential diagnosis, I:S-24i, 1:5-25 diffuse axonal injury vs., 1:2-30i, 1:2-31 hemangioblastoma vs., 1:6-114i, 1:6-115 mesial temporal sclerosis vs., 1:10-51 multiple, hereditary hemorrhagic telangiectasia vs., 1:1-105 remote cerebellar hemorrhage vs., 1:4-20i, 1:4-21 subcortical injuries vs./ 1:2-34i, 1:2-35 subependymoma vs., 1:6-57 Cavum septi pellucidi, 11:1-8 to 11:1-9, II:1-9i cavum velum interpositum vs., II:l-lOi, 11:1-11 differential diagnosis, II:1-8i, 11:1-8 to 11:1-9 Cavum velum interpositum, 11:1-10 to 11:1-11, II:l-lli

cavum septi pellucidi vs., 1I:1-8, 1I:1-8i differential diagnosis, 1I:1-10i, 11:1-10to 11:1-11 Cavum vergae, 1I:1-11 CBD. See Cortical-basal ganglionic degeneration (CBD) Celiac disease, 1:1-95 Central incisor syndrome, 1:1-39 Central nervous system primary angiitis of CADASILvs., 1:8-63 systemic lupus erythematosus vs., 1:4-55 primary arteritis of, 1:4-46 to 1:4-49 primary lymphoma of. See Lymphoma, primary CNS Cephalocele atretic, 1I:4-12 to 1I:4-13 hemangioma vs., 1I:4-72i, 1I:4-73 sinus pericranii vs., I:S-20i, 1:5-21 Cerebellar degeneration syndromes alcoholic encephalopathy vs., 1:1O-20i, 1:10-21 cerebellar atrophy, hereditary, 1:1O-82i, 1:10-84 progressive non-familial adult onset, 1:10-83 Cerebellar dysplasia, 1:6-70i, 1:6-71 Cerebellar hemorrhage, remote, 1:4-20 to 1:4-22, 1:4-23i differential diagnosis, 1:4-20i, 1:4-21 Cerebellar infarction, 1:6-70i, 1:6-71 Cerebellar tonsil ectopia. See Chiari type 1 Cerebello-olivary atrophy, I:10-83 Cerebellopontine angle (CPA), 11:3-8 to 1I:3-49 acoustic schwannoma, 1I:3-28 to 1I:3-31 arachnoid tumor, 1I:3-16 to 1I:3-19 epidermoid cyst, 1I:3-12 to 1I:3-15 lipoma, 1I:3-8 to 1I:3-11, II:3-12i meningioma, 1I:3-32 to 1I:3-35 metastases, 1I:3-36 to 1I:3-41 Ramsay Hunt syndrome, 1I:3-20 to 1I:3-23 vascular loop compression, 1I:3-24 to 1I:3-27 Cerebral amyloid disease, 1:4-58 to 1:4-60, 1:4-61i. See also Amyloid angiopathy differential diagnosis, 1:4-S8i, 1:4-59 hypertensive intracranial hemorrhage vs., 1:416i,I:4-17 spontaneous intracranial hemorrhage vs., 1:412i,I:4A3 I Cerebral artery, posterior, 1:4-36, 1:4-36i Cerebral contusions, 1:2-26 to 1:2-28, 1:2-29i acute cerebral ischemia-infarction vs., 1:4-76i, 1:4-78 cortical venous thrombosis vs., 1:4-100i, 1:4-101 differential diagnosis, 1:2-26i, 1:2-27 to 1:2-28 penetrating injury vs., 1:2-4i Cerebral edema aneurysmal subarachnoid hemorrhage vs., 1:3-4i diffuse acute cerebral ischemia-infarction vs., 1:4-78 brain death vs., 1:2-55 traumatic, 1:2-46 to 1:2-48, 1:2-49i differential diagnosis, 1:2-46i, 1:2-47

Cerebral hemorrhage, 1:4-101 Cerebral hyperemia, acute, I:I0-28i, 1:10-29 Cerebral infarction. See also Cerebral ischemiainfarction, acute brain death vs., 1:2-55 chronic, 1:4-84 to 1:4-86, 1:4-87i differential diagnosis, 1:4-84i, 1:4-85 hypotensive, 1:4-92 to 1:4-94, 1:4-9Si differential diagnosis, 1:4-92i, 1:4-93 subacute, 1:4-80 to 1:4-82, 1:4-83i differential diagnosis, 1:4-80i, 1:4-81 to 1:4-82 traumatic subarachnoid hemorrhage vs., 1:2-23 Cerebral ischemia hypertensive encephalopathy vs., I:I0-28i, 1:10-29 traumatic, 1:2-50 to 1:2-52 differential diagnosis, 1:2-SOi, 1:2-51 Cerebral ischemia-infarction, acute, 1:4-76 to 1:478,1:4-79i differential diagnosis, 1:4-76i, 1:4-77 to 1:4-78 traumatic cerebral ischemia vs., 1:2-SOi, 1:2-51 Cerebritis acute cerebral ischemia-infarction vs., 1:4-76i, 1:4-78 anaplastic astrocytoma vs., 1:6-16i, 1:6-17 anaplastic oligodendroglioma vs., 1:6-46i, 1:6-47 cerebral contusion vs., 1:2-26i, 1:2-27 low grade diffuse astrocytoma vs., 1:6-8i, 1:6-9 oligodendroglioma vs., 1:6-42i, 1:6-43 status epilepticus vs., 1:10-55 subacute cerebral infarction vs., 1:4-80i, 1:4-82 Cerebrohepatorenal syndrome. See Zellweger syndrome Cerebrospinal fluid flow artifact vs. colloid cyst, 1:7-8i, 1:7-9 gadolinium vs. meningitis, 1:8-21 high signal on FLAIR,1:3-4, 1:8-21 infarct vs. choroid plexus cyst, 1:7-30i, 1:7-31 Cerebrospinal fluid shunts, II:1-28 to II:1-30, II:I-3li differential diagnosis, II:1-28i, 1I:1-29 Cerebrovascular accident (CVA). See Cerebral ischemia-infarction, acute Cerebrovascular disease, small vessel. See Arteriolosclerosis Chemical shift artifacts acute subdural hematoma vs., 1:2-11 chronic subdural hematoma vs., 1:2-16i, 1:2-17 colloid cyst vs., 1:7-8i, 1:7-9 subacute subdural hematoma vs., 1:2-15 Chemotherapy, 1:10-46 to 1:10-48, 1:1O-49i differential diagnosis, I:I0-46i, 1:10-47 to 1:10-48 Fahr disease vs., I:I0-16i hypomyelination vs., 1:9-9 Cherubism basal cell nevus syndrome vs., 1:1-101 fibrous dysplasia vs., II:4-34i Chiari type 1, 1:1-8 to 1:1-10, l:l-11i

acquired, II:I-28i, 11:1-29 Chiari type 2 vs., 1:1-12i, 1:1-13 differential diagnosis, 1:1-8i, 1:1-9 Chiari type 2, 1:1-12 to 1:1-14, 1:1-15i chronic shunting, rhombencephalosynapsis vs., 1:1-30i, 1:1-31 differential diagnosis, 1:1-12i, 1:1-13 heterotopic gray matter vs., 1:1-59 Chiari type 3, 1:1-16 to 1:1-17, 1:1-17i Chiari type 2 vs., 1:1-12i, 1:1-13 differential diagnosis, 1:1-16, 1:1-16i Chiari type 4, 1:1-12i, 1:1-13 Chiasm glioma, II:2-12i Chiasmatic astrocytoma craniopharyngioma vs., II:2-32i, 11:2-33 tuber cinereum hamartoma vs., II:2-12i, 11:2-13 Child abuse, 1:9-49 Cholestatic diseases, 1:10-25 Chorea-ballism, with hyperglycemia, 1:10-25 Choriocarcinoma embryonal carcinoma vs., 1:6-138 pineoblastoma vs., 1:6-85 pineocytoma vs., 1:6-89 Choristoma, 11:2-36 to 11:2-37 Choroid, physiologic enlargement, 1:6-61 Choroid artery, infarction, I:7-31 Choroid plexus carcinoma, 1:6-65i choroid plexus papilloma vs., 1:6-60i, 1:6-61 differential diagnosis, 1:6-64i, 1:6-64 to 1:6-65 supratentorial primitive neuroectodermal tumor vs., 1:6-97 Choroid plexus cyst, 1:7-30 to 1:7-32, 1:7-33i colloid cyst vs., 1:7-9 differential diagnosis, 1:7-30i, 1:7-31 ependymal cyst vs., 1:7-34, 1:7-34i Choroid plexus papilloma, 1:6-60 to 1:6-62, 1:6-63i central neurocytoma vs., 1:6-80i, 1:6-81 choroid plexus carcin0rv-a vs., 1:6-64, 1:6-64i choroid plexus cyst vs., 1:7-30i, 1:7-31 colloid cyst vs., 1:7-9 differential diagnosis, 1:6-60i, 1:6-61 to 1:6-62 ependymoma vs., 1:6-53 medulloblastoma vs., 1:6-92i, 1:6-93 obstructive hydrocephalus vs., II:I-16i, 11:1-17 subependymoma vs., 1:6-57 teratoid-rhabdoid tumor vs., 1:6-101 Choroid plexus tumors subependymal giant cell astrocytoma vs., 1:638i,I:6-39 of third ventricle, embryonal carcinoma vs., 1:6-138 Choroidal fissure cyst, I:I0-50i, 1:10-51 Chronic fatigue syndrome, 1:8-65 Chronic interstitial demyelinating polyneuropathy, 1:6-113 Circle of Willis, severely attenuated, 1:4-43 Cisterna trauma, II:4-18i Citrobacter meningitis, 1:8-16 to 1:8-19, 1:8-2Oi differential diagnosis, 1:8-16i, 1:8-17 streptococcal meningitis vs., 1:8-12i, 1:8-13

C]D. See Creutzfeldt-]akob disease (C]D) CMV. See Cytomegalovirus (CMV) infections Coagulation, disseminated intravascular, 1:4-21 Coagulopathy, spontaneous hemorrhage, 1:4-21 Coccidioimycosis, 1:8-58 Cockayne syndrome, 1:10-17 Cognitive impairment arteriolosclerotic disease vs., 1:4-33 normal brain aging vs., 1:10-59 Collagen vascular disorders, 1:2-57 Colloid cyst, 1:7-8 to 1:7-10, 1:7-10i differential diagnosis, 1:7-8i, 1:7-9 neurenteric cyst vs., 1:7-40 Coma, hepatic, 1:10-24 to 1:10-26, 1:1O-27i Compression, vascular loop, 11:3-24 to 11:3-26, II:3-27i differential diagnosis, II:3-24i, 11:3-25 Congenital diseases aqueductal stenosis, 1:6-12i, 1:6-13 cytomegalovirus encephalitis. See Cytomegalovirus (CMV) infections herpes simplex, 1:8-10 to 1:8-11, 1:8-11i, 1:8-31 HIV infections, 1:8-8 to 1:8-9, 1:8-9i Leber congenital amaurosis, 1:1-35 lymphocytic choriomeningitis, 1:8-4i, 1:8-5 muscular dystrophy, 1:1-54 to 1:1-57 vermian hypoplasia. See Vermian hypoplasia, congenital Congenital malformations, 1:1-8 to 1:1-119 basal cell nevus syndrome, 1:1-100 to 1:1-103 callosal dysgenesis, 1:1-18 to 1:1-21 Chiari types 1-3, 1:1-8 to 1:1-17 congenital vermian hypoplasia, 1:1-34 to 1:1-37 Cowden syndrome, 1:1-112 to 1:1-115 Dandy Walker spectrum, 1:1-26 to 1:1-29 encephalocraniocutaneous lipomatosis, I:1108 to 1:1-111 hemimegalencephaly, 1:1-74 to 1:1-77 hereditary hemorrhagic telangiectasia, 1:1-104 to 1:1-107 heterotopic gray matter, 1:1-58 to 1:1-61 holoprosencephaly, 1:1-38 to 1:1-45 lipoma, 1:1-23 to 1:1-25 lissencephaly type I, 1:1-66 to 1:1-69 meningioangiomatosis, 1:1-98 to 1:1-99 microcephaly, 1:1-50 to 1:1-53 neurocutaneous melanosis, 1:1-116 to 1:1-119 neurofibromatoses, 1:1-78 to 1:1-85 pachygyria, 1:1-62 to 1:1-65 polymicrogyria, 1:1-62 to 1:1-65 rhombencephalosynapsis, 1:1-30 to 1:1-33 schizencephaly, 1:1-70 to 1:1-73 septooptic dysplasia, I:1-46 to I:1-49 Sturge-Weber syndrome, 1:1-94 to 1:1-97 tuberous sclerosis complex, 1:1-90 to 1:1-93 vascular, 1:9-8i, 1:9-9 yon Hippel Lindau syndrome, 1:1-86 to 1:1-89 Connective tissue disorders, 1:4-38i, 1:4-39 Copper, liver overload, 1:10-25 Corpus callosum

agenesis. See Callosal dysgenesis destruction of, 1:1-19 dorsolateral contusions with closed head injury, 1:3-17 immature, 1:1-19 partial absence of, I:1-18i stretched, 1:1-18i, 1:1-19 Cortical-basal ganglionic degeneration (CBD) Alzheimer dementia vs., 1:10-63 Creutzfeldt-]akob disease vs., 1:10-71 frontotemporal dementia vs., 1:10-71 Parkinson disease vs., 1:10-78i, 1:10-80 Cortical dysplasia. See Polymicrogyria Cortical infarcts, 1:4-63 Cortical vein thrombosis hypertensive intracranial hemorrhage vs., 1:4-17 intracerebral hematoma vs., 1:4-9 spontaneous intracranial hemorrhage vs., 1:4-13 Cowden syndrome, 1:1-112 to 1:1-114, I:1-11Si differential diagnosis, 1:1-112i, I:1-113 CPA. See Cerebellopontine angle (CPA) Cranial injuries. See Head injuries Craniectomy, 11:4-81 Craniometaphyseal dysplasia, 11:4-35 Craniopharyngioma, 11:2-32 to 11:2-34, II:2-3Si colloid cyst vs., 1:7-9 dermoid cyst vs., I:7-12i, 1:7-13 differential diagnosis, II:2-32i, 11:2-33 epidermoid cyst vs., 1:7-16i germinoma vs., 1:6-132i, 1:6-133 pituitary apoplexy vs., II:2-28i, 11:2-29 pituitary macroadenoma vs., II:2-24i, 11:2-25 to 11:2-26, II:2-32i pituitary microadenoma vs., 11:2-21 Rathke cleft cyst vs., II:2-16i, 11:2-17 teratoma vs., 1:6-136, 1:6-136i tuber cinereum hamartoma vs., II:2-12i, 11:2-13 Craniostenoses, 11:4-8 to 11:4-10, II:4-11i differential diagnosis, II:4-8i, 11:4-9 Creatine deficiency, 1:10-6 Creutzfeldt-]akob disease (C]D), 1:10-74 to 1:1076, l:lO-77i Alzheimer dementia vs., 1:10-62i, 1:10-63 carbon monoxide poisoning vs., I:10-38i, 1:10-40 differential diagnosis, 1:1O-74i, 1:10-75 Wilson disease vs., I:9-70i, 1:9-71 Cryptococcosis, 1:8-67 CVA (cerebrovascular accident). See Cerebral ischemia-infarction, acute Cyanide poisoning Hallervorden-Spatz syndrome vs., I:9-62i, 1:9-63 MELASvs., 1:9-16i, 1:9-17 Cystic benign lymphoepitheliallesion, I:1-S4i, 1:1-55 Cysticercosis epidermoid cyst vs., I:7-16i fungal diseases vs., I:8-S8i meningioangiomatosis vs., 1:1-98, I:1-98i neuroglial cyst vs., I:7-2Oi

Cysts aqueductal,II:1-2Oi arachnoid. See Arachnoid cyst bone, aneurysmal, 1:1-100i, 1:1-101 brain, 1:1-35 choroid plexus, 1:7-30 to 1:7-33 choroidal fissure, 1:10-S0i, 1:10-51 colloid, 1:7-8 to 1:7-11, 1:7-40 dentigerous, 1:1-101 dermoid. See Dermoid cyst enlarged perivascular spaces, 1:7-22 to 1:7-24 ependymal. See Ependymal cyst epidermoid. See Epidermoid cyst hydatid, 1:7-23 incisor canal, 1:1-101 infectious, 1:7-21 inflammatory, I:7-17 leptomeningeal hemangioma vs., II:4-72i, 11:4-73 histiocytosis vs., II:4-48i, 11:4-49 neurenteric. See Neurenteric cyst neuroglial. See Neuroglial cyst nonneoplastic, 1:7-4 to 1:7-41 pituitary microadenoma vs., II:2-20i Rathke cleft cyst vs., II:2-16i pars intermedia, 11:2-21 pineal. See Pineal cyst porencephalic. See Porencephalic cyst Rathke cleft. See Rathke cleft cyst Cytomegalovirus (CMV) infections congenital, 1:8-4 to 1:8-6, I:8-7i differential diagnosis, I:8-4i, 1:8-5 metachromatic leukodystrophy vs., I:9-28i pachygyria vs., I:1-62i, 1:1-63 polymicrogyria vs., I:1-62i, 1:1-63 preterm hypoxic-ischemic encephalopathy vs., I:4-68i, 1:4-69 Zellweger syndrome vs., 1:9-36, I:9-36i congenital herpes vs., 1:8-10, I:8-1Oi congenital HIV infections vs., 1:8-8, 1:8-8i heterotopic gray matter vs., 1:1-S8i, 1:1-59 HIV encephalitis vs., 1:8-67, 1:8-71 microcephaly vs., 1:1-SOi tuberous sclerosis complex vs., 1:1-90i, 1:1-91

o DAI. See Axonal injury, diffuse (DAI) Dandy Walker spectrum, 1:1-26 to 1:1-28, I:1-29i Chiari type 3 vs., 1:1-16, I:1-16i congenital vermian hypoplasia vs., I:1-34i, 1:1-35 differential diagnosis, I:1-26i, 1:1-27 encephalocraniocutaneous lipomatosis vs., 1:1-109 muscular dystrophy vs., I:1-S4i, 1:1-55 porencephalic cyst vs., 1:7-36i, 1:7-37 De Morsier syndrome. See Septooptic dysplasia Dekaban syndrome, 1:1-35

Dementia AIDS dementia complex, 1:10-75 Alzheimer. See Alzheimer dementia frontotemporal. See Frontotemporal dementia multi-infarct. See Multi-infarct dementia vascular. See Vascular dementia Demyelination abscess vs., 1:8-24i, 1:8-25 acute hypertensive encephalopathy vs., 1:10-29 arteriolosclerosis vs., 1:4-32i, 1:4-33 developmental venous anomaly vs., 1:5-17 diffuse axonal injury vs., 1:2-31 early diffuse, glutaric aciduria type 1vs., 1:9-49 gliomatosis cerebri vs., 1:6-27 interstitial demyelinating polyneuropathy, chronic, 1:6-113 neurofibromatosis type 1 vs., 1:1-78i, 1:1-79 parenchymal metastases vs., 1:6-141 pilocytic astrocytoma vs., 1:6-31 primary CNS lymphoma vs., 1:6-123 status epilepticus vs., 1:10-55 "tumefactive," glioblastoma multiforme vs., 1:6-20i, 1:6-21 Dentigerous cyst, 1:1-101 Depression, 1:10-63 Dermal dysplasia, cerebellotrigeminal, 1:1-31 Dermoid cyst, 1:7-12 to 1:7-14, 1:7-15i atretic cephalocele vs., 11:4-13 differential diagnosis, 1:7-12i, 1:7-13 embryonal carcinoma vs., 1:6-138 ependymoma vs., 1:6-52i, 1:6-53 epidermoid cyst vs., 1:7-16i, 1:7-17 hemangioma vs., 11:4-73 histiocytosis vs., 11:4-49 lipoma vs., 1:1-22i, 1:1-23, II:3-8i, 11:3-9 neurenteric cyst vs., 1:7-40, 1:7-4Oi neurocutaneous melanosis vs., 1:1-117 ruptured, II:3-8i, 11:3-9 teratoma vs., 1:6-136, 1:6-136i Developmental venous anomaly (DVA), 1:5-16 to 1:5-18,1:5-19i capillary telangiectasis vs., 1:5-28i, 1:5-29 differential diagnosis, 1:5-16i, 1:5-17 hereditary hemorrhagic telangiectasia vs., 1:1104i,I:I-I05 Diabetes insipidus, central, 11:2-9 Diabetes mellitus gestational, I:1-5 1 osmotic demyelination syndrome vs., I:I0-42i, 1:10-43 Diffuse axonal injury. See Axonal injury, diffuse (DAI) Dilantin therapy chronic, alcoholic encephalopathy vs., I:I0-2Oi Paget disease vs., II:4-38i Dissecting aneurysm atherosclerotic fusiform aneurysm vs., 1:3-19 pseudoaneurysm vs., 1:3-16i, 1:3-17 Dissection extra cranial atherosclerosis vs., 1:4-28i, 1:4-29

intracranial atherosclerosis vs., 1:4-24i, 1:4-25 spontaneous, 1:2-58i, 1:2-59 traumatic extracranial, 1:2-58 to 1:2-60, 1:2-61i differential diagnosis, 1:2-58i, 1:2-59 traumatic intracranial, 1:2-56 to 1:2-57, 1:2-57i differential diagnosis, 1:2-56i, 1:2-57 Disseminated intravascular coagulation, 1:4-21 DNET. See Neuroepithelial tumor, dysembryoplastic (DNET) Dolichoectasia atherosclerotic, 1:3-18 vertebrobasilar non-atherosclerotic fusiform aneurysm vs., 1:3-21 vascular loop compression vs., 11:3-25 Down syndrome, 1:10-17 Drug abuse, 1:10-8 to 1:10-10, l:lO-11i amyotrophic lateral sclerosis vs., 1:10-87 differential diagnosis, I:I0-8i, 1:10-9 hypertensive intracranial hemorrhage vs., 1:4-16i intracerebral hematoma vs., 1:4-8i, 1:4-9 overdose vs. brain death, 1:2-54i, 1:2-55 primary arteritis of CNS vs., 1:4-46i, 1:4-47 spontaneous intracranial hemorrhage vs., 1:4-12i Wallerian degeneration vs., 1:10-92 Dura, thickened. See Pachymengiopathies (thickened dura) Dural arteriovenous shunt. See Arteriovenous fistula, dural Dural dysplasia, I: 1-22i, I:1-23 Dural enhancement, normal, 11:4-31 Dural sinus thrombosis. See Sinus thrombosis, dural Duret hemorrhage, 1:2-42i DVA. See Developmental venous anomaly (DVA) Dyke-Davidoff-Masson syndrome (hemispheric infarction), 1:8-42i, 1:8-43 Dysembryoplastic neuroepithelial tumor. See Neuroepithelial tumor, dysembryoplastic (DNET)

E Eclampsia, 1:2-23 Ectodermal dysplasia, 1:1-35 Ectodermal inclusion cyst. See Dermoid cyst; Epidermoid cyst Edema cerebral. See Cerebral edema lobar, hypoglycemia vs., 1:10-4, I:I0-4i pressure-related, 1:2-47 Effusions, subdural. See Subdural effusions Ehlers-Danlos syndrome fusiform aneurysm vs., 1:3-18i sickle cell disease vs., 1:4-39 18q syndrome, 1:9-8i, 1:9-9 Electron transport chain defects, 1:9-8i, 1:9-9

Embolic stroke, acute, 1:4-92i, 1:4-93 Embolism, septic, I:S-SSi, 1:8-59 Embryonal carcinoma, 1:6-138 to 1:6-139, 1:6-139i differential diagnosis, 1:6-138, 1:6-13Si pineoblastoma vs., 1:6-85 pineocytoma vs., 1:6-89 Empty sella, 1:1O-36i, 1:10-37 Empyema, 1:8-30 to 1:8-32, I:S-33i acute subdural hematoma vs., 1:2-11 differential diagnosis, I:S-30i, 1:8-31 mixed subdural hematoma vs., 1:2-21 subacute subdural hematoma vs., 1:2-15 subdural chronic subdural hematoma vs., 1:2-17 dural sinus thrombosis vs., 1:4-97 ventricular. See Ventriculitis Encephalitis, 1:8-38 to 1:8-40, I:S-4li amebic, neurocysticercosis vs., I:S-SOi brainstem, diffuse pediatric pontile glioma vs., 1:6-13 cerebral ischemia-infarction, acute, vs., 1:476i,I:4-78 chronic focal. See Rasmussen encephalitis cytomegalovirus, congenital, 1:8-4 to 1:8-6, I:S-7i differential diagnosis, I:S-3Si, 1:8-39 herpes. See Herpes encephalitis HIY. See HIV encephalitis Japanese carbon monoxide poisoning vs., 1:10-3Si, 1:10-39 Wilson disease vs., 1:9-70i, 1:9-72 limbic, herpes vs., I:S-34i, 1:8-35 Rasmussen. See Rasmussen encephalitis St. Louis, 1:10-80 subacute cerebral infarction vs., 1:4-SOi, 1:4-82 viral, gliomatosis cerebri vs., 1:6-27 Encephaloceles, occipital, 1:1-16, 1:1-16i Encephalocraniocutaneous lipomatosis, 1:1-108 to 1:1-110,1:1-11li differential diagnosis, 1:1-lOSi, 1:1-109 Encephalomalacia acute cerebral ischemia-infarction vs., 1:4-78 chronic cerebral infarction vs., 1:4-S4i cystic Citrobacter meningitis vs., I:S-16i, 1:8-17 hydranencephaly vs., 1:4-67 porencephalic cyst vs., 1:7-36i, 1:7-37 post-surgical/post-traumatic, 1:4-85 Encephalomyelitis, acute disseminated. See Acute disseminated encephalomyelitis (ADEM) Encephalomyelopathy, subacute necrotizing. See Leigh syndrome Encephalopathy alcoholic. See Alcoholic encephalopathy anoxic, 1:9-63 hepatic, 1:10-24 to 1:10-26, 1:10-27i hypertensive. See Hypertensive encephalopathy

hypoxic-ischemic. See Hypoxic-ischemic encephalopathy (HIE) metabolic, 1:2-47 mitochondrial, 1:4-73 posterior reversible. See Posterior reversible encephalopathy (PRES) subcortical arteriosclerotic. See Hypertensive encephalopathy Enterobacter spp., 1:8-13 Eosinophilic granuloma, 11:4-73 Ependymal cyst, 1:7-34 to 1:7-35, 1:7-3Si asymmetric ventricles vs., 1:7-34i, 1:7-35 cavum septi pellucidi vs., II:1-Si, 11:1-9 choroid plexus cyst vs., 1:7-30i, 1:7-31 differential diagnosis, 1:7-34i, 1:7-34 to 1:7-35 dysembryoplastic neuroepithelial tumor vs., 1:6-76i, 1:6-77 neuroglial cyst vs., 1:7-20i, 1:7-21 porencephalic cyst vs., 1:7-37 Ependymal tumor metastasis, I:S-2Si, 1:8-29 Ependymal vein malformations, I:S-2Si, 1:8-~~ Ependymitis. See Ventriculitis Ependymoma, 1:6-52 to 1:6-54 arachnoid cyst vs., 11:3-17 astroblastoma vs., 1:6-50, 1:6-S0i central neurocytoma vs., 1:6-81 Chiari type 1 vs., 1:1-Si choroid plexus carcinoma vs., 1:6-64, 1:6-64i choroid plexus papilloma vs., 1:6-60i, 1:6-61 clear cell, hemangioblastoma vs., 1:6-115 differential diagnosis, 1:6-S2i, 1:6-53 medulloblastoma vs., 1:6-92i, 1:6-93 neurofibromatosis type 2 vs., 1:1-S2i, 1:1-83 pilocytic astrocytoma vs., 1:6-30i, 1:6-31 subependymoma vs., 1:6-S6i, 1:6-57 supratentorial desmoplastic infantile ganglioglioma vs., 1:6-74i,I:6-75 primitive neuroectodermal tumor vs., 1:696i,I:6-97 teratoid-rhabdoid tumor, atypical, vs., 1:6100i, 1:6-101 Epidermal nevus syndrome, 1:1-10Si, 1:1-109 Epidermoid cyst, 1:7-16 to 1:7-18, 1:7-19i acoustic schwannoma vs., II:3-2Si, 11:3-29 arachnoid cyst vs., 1:7-4i, 1:7-5, II:3-16i, 11:3-17 atretic cephalocele vs., II:4-12i, 11:4-13 cavum velum interpositum vs., II:1-10i, 11:1-11 of cerebellopontine angle, 11:3-12 to 11:3-14, II:3-1Si differential diagnosis, II:3-12i, 11:3-13 choroid plexus cyst vs., 1:7-30i, 1:7-31 dermoid cyst vs., 1:7-12i, 1:7-13 differential diagnosis, 1:7-16i, 1:7-17 ependymal cyst vs., 1:7-34, 1:7-34i ependymoma vs., 1:6-53 hemangioma vs., 11:4-73 histiocytosis vs., 11:4-49 meningioma vs., II:3-32i, 11:3-33 neurenteric cyst vs., 1:7-40, 1:7-4Oi

I~

neurofibromatosis type 2 vs., l:l-S2i, l:l-S3 neuroglial cyst vs., 1:7-21 pineal cyst vs., 1:7-26i, 1:7-27 Rathke cleft cyst vs., 11:2-17 white, cerebellopontine angle lipoma vs., 11:3Si,II:3-9 Epidermoid tumors, 11:2-33 Epidural hematoma, 1:2-6 to 1:2-S, 1:2-9i acute acute subdural hematoma vs., 1:2-11 mixed subdural hematoma vs., 1:2-21 differential diagnosis, 1:2-6i, 1:2-7 metastatic neuroblastoma vs., 1:6-104i, 1:6-105 skull and meningeal metastasis vs., 1I:4-S1 Epilepsy. See a/so Status epilepticus myoclonic, with ragged-red fibers Fahr disease vs., 1:10-17 MELASvs., 1:9-16i, 1:9-17 Escherichia coli, I:S-12i, I:S-13 Etat crib Ie, 1:4-SSi, 1:4-S9 Evans syndrome, 1:2-56i Ewing sarcoma atypical and malignant meningioma vs., 11:460i, 11:4-61 leukemia vs., 1:6-12Si, 1:6-129 metastatic neuroblastoma vs., 1:6-105 neurofibroma vs., 1:6-113 Extramedullary hematopoiesis. See Hematopoiesis, extramedullary

F Fabry disease acute disseminated encephalomyelitis vs., I:S7Si,I:8-79 Facial nerve hyperactivity. See Vascular loop compression Fahr disease, 1:10-16 to 1:10-18, I:IO-19i differential diagnosis, I:IO-16i, 1:10-17 to 1:10-18 hepatic encephalopathy vs., 1:10-25 Fatty acid oxidation disorders, 1:9-46 Fetal alcohol syndrome, 1:1-50i, 1:1-51 Fibromuscular dysplasia extra cranial atherosclerosis vs., 1:4-2Si, 1:4-29 traumatic extracranial dissection vs., 1:2-5Si, 1:2-59 Fibrous dysplasia, 11:4-34 to 11:4-36, 1I:4-37i differential diagnosis, 1I:4-34i, 11:4-35 histiocytosis vs., 11:4-49 Paget disease vs., 1I:4-3Si, 11:4-39 Fishman syndrome. See Encephalocraniocutaneous lipomatosis FLAIR artifacts, 1:3-4i high CSF signal, non-subarachnoid hemorrhage causes of, 1:3-4 Foreign body reaction, 1:10-48 Fourth ventricle, isolated, 1:1-26i, 1:1-27

Friedreich ataxia, 1:10-83 Frontotemporal dementia, 1:10-70 to 1:10-72, I:IO-73i Alzheimer dementia vs., 1:10-63 Creutzfeldt-]akob disease vs., 1:10-75 differential diagnosis, I:IO-70i, 1:10-71 multi-infarct dementia vs., I:IO-66i, 1:10-67 normal brain aging vs., I:IO-5Si, 1:10-60 Fucosidosis, 1:9-63 Fungal diseases, 1:8-58 to 1:8-60, I:S-6li in AIDS, 1:8-72 differential diagnosis, I:S-5Si, 1:8-59 HIV encephalitis vs., 1:8-67 Fusiform aneurysm atherosclerotic, 1:3-18 to 1:3-19, 1:3-19i blood blister-like aneurysm vs., 1:3-22i differential diagnosis, 1:3-1Si, 1:3-18 to 1:3-19 non-atherosclerotic, 1:3-20 to 1:3-21, 1:3-2li differential diagnosis, 1:3-20i, 1:3-21

G Gadolinium in CSF,vs. meningitis, 1:8-21 traumatic subarachnoid hemorrhage vs., 1:2-23 Gangliocytoma, dysplastic cerebellar, 1:6-70 to 1:6-72, 1:6-73i differential diagnosis, 1:6-70i, 1:6-71 Ganglioglioma, 1:6-66 to 1:6-68, 1:6-69i Cowden syndrome vs., 1:1-112i, 1:1-113 desmoplastic infantile, 1:6-75i differential diagnosis, 1:6-74i, 1:6-74 to 1:6-75 ganglioglioma vs., 1:6-75 differential diagnosis, 1:6-66i, 1:6-67 dysembryoplastic neuroepithelial tumor vs., 1:6-76i, 1:6-77 meningioangiomatosis vs., 1:1-98, 1:1-9Si oligodendroglioma vs., 1:6-42i, 1:6-43 pilocytic astrocytoma vs., I:6-31 pleomorphic xanthoastrocytoma vs., 1:6-34i, 1:6-35 schwannoma vs., 1:6-10Si, 1:6-109 Gangliosidosis (GM2), 1:9-24 to 1:9-26, 1:9-27i differential diagnosis, 1:9-24i, 1:9-25 juvenile GMI vs., 1:9-25 Krabbe disease vs., 1:9-32i, 1:9-33 Garre sclerosing osteomyelitis, 1I:4-34i, 11:4-35 Germ cell tumors mixed malignant, 1:6-138, 1:6-13Si of pineal region, 1:6-132i, 1:6-133 pineoblastoma vs., 1:6-85 pineocytoma vs., 1:6-89 teratoma vs., 1:6-137 Germinoma, 1:6-132 to 1:6-134, 1:6-135i differential diagnosis, 1:6-132i, 1:6-133 embryonal carcinoma vs., 1:6-138, 1:6-13Si histiocytosis vs., 11:4-49 neurofibromatosis type 2 vs., 1:1-84 pineoblastoma vs., 1:6-S4i, 1:6-85

pineocytoma vs., I:6-88i, 1:6-89 subependymal giant cell astrocytoma vs., 1:6-39 tuber cinereum hamartoma vs., II:2-13 Giant serpentine aneurysm atherosclerotic fusiform aneurysm vs., 1:3-18, I:3-18i non-atherosclerotic fusiform aneurysm vs., 1:3-21 Glial cyst, pineal. See Pineal cyst Glioblastoma arteriovenous malformation vs., I:S-4i, 1:5-5 hemangioblastoma vs., 1:6-115 neurofibromatosis type 2 vs., 1:1-84 Glioblastoma multiforme, 1:6-20 to 1:6-22, I:6-23i anaplastic astrocytoma vs., 1:6-17 anaplastic oligodendroglioma vs., I:6-46i, 1:6-47 astroblastoma vs., 1:6-51 cystic, parasitic infections vs., I:8-54i differential diagnosis, 1:6-20i, 1:6-21 ependymoma vs., 1:6-53 gliosarcoma vs., 1:6-24, I:6-24i parenchymal metastases vs., I:6-140i, 1:6-141 primary CNS lymphoma vs., I:6-122i, 1:6-123 recurrent, radiation injury or chemotherapy vs., I:IO-46i, 1:10-47 supratentorial primitive neuroectodermal tumor vs., I:6-96i, 1:6-97 Glioependymal cyst. See Ependymal cyst Glioma brainstem amyotrophic lateral sclerosis vs., I:IO-86i, 1:10-87 ependymoma vs., 1:6-53 medulloblastoma vs., I:6-92i, 1:6-93 Wallerian degeneration vs., I:I0-90i, 1:10-91 deep cerebral venous thrombosis vs., I:4-104i, 1:4-105 histiocytosis vs., II:4-49 hypertrophic olivary degeneration vs., I:IO-94i low grade anaplastic astrocytoma vs., I:6-16i, 1:6-17 subacute cerebral infarction vs., I:4-8Oi malignant, parenchymal metastases vs., 1:6-141 pediatric brainstem, 1:6-12 to 1:6-14, I:6-1Si differential diagnosis, I:6-12i, 1:6-13 pilocytic, I:6-74i tectal aqueductal stenosis vs., II:1-20i pineoblastoma vs., I:6-84i pineocytoma vs., I:6-88i tuberculosis vs., I:8-46i Gliomatosis cerebri, 1:6-26 to 1:6-28, I:6-29i acute hypertensive encephalopathy vs., 1:10-29 differential diagnosis, I:6-26i, 1:6-27 herpes encephalitis vs., I:8-34i, 1:8-35 neurofibromatosis type 1 vs., I:1-78i, 1:1-79 paraneoplastic syndromes vs., I:6-144i, 1:6-145 Gliosarcoma, 1:6-24 to 1:6-25, 1:6-2Si atypical teratoid-rhabdoid tumor vs., I:6-100i, 1:6-101

differential diagnosis, I:6-24i, 1:6-24 to 1:6-25 hemangiopericytoma vs., 1:6-119 Gliosis, post-inflammatory, II:I-21 Globulomaxillary cyst, 1:1-101 Glutaric aciduria type 1 (GA-l), 1:9-48 to 1:9-50, I:9-Sli Alexander disease vs., I:9-S4i, 1:9-55 differential diagnosis, I:9-48i, 1:9-49 Leigh syndrome vs., I:9-12i, 1:9-13 non-accidental trauma vs., I:2-38i, 1:2-39 Goldenhar-Gorlin syndrome, 1:1-16 Gomez-Lopez-Hernandez syndrome, 1:1-31 Granular cell tumor. See Pituicytoma Granuloma eosinophilic, II:4-73 giant reparative, I:I-lOOi, 1:1-101 meningioma vs., II:4-57 plasma cell. See Pseudotumors, intracranial xanthogranuloma choroid plexus papilloma vs., 1:6-61 colloid cyst vs., I:7-8i, 1:7-9 Granulomatous disease dysplastic cerebellar gangliocytoma vs., 1:6-71 neurofibromatosis type 2 vs., 1:1-84 Graves' disease, I:2-62i, 1:2-63 Gray matter, heterotopic, 1:1-58 to 1:1-60, I:1-6li differential diagnosis, I:l-S8i, 1:1-59 Gunshot wounds, 1:2-4 to 1:2-5, I:2-Si differential diagnosis, 1:2-4i

H Haberland syndrome. See Encephalocraniocutaneous lipomatosis Hallervorden-Spatz syndrome, 1:9-62 to 1:9-64, I:9-6Si differential diagnosis, 1:9-62i, 1:9-63 Huntington disease vs., I:9-66i, 1:9-67 Hamartoma germinoma vs., 1:6-133 lipomatous. See Lipoma multiple. See Cowden syndrome tuber cinereum, II:2-12 to II:2-14, II:2-1Si differential diagnosis, II:2-12i, II:2-13 pituitary stalk anomalies vs., II:2-8i, II:2-9 Hashimoto thyroiditis, 1:10-83 Head circumference and atrophy, II:1-12i, II:I-13 Head injuries Alzheimer dementia vs., 1:10-63 frontotemporal dementia vs., 1:10-71 non-accidental glutaric aciduria type 1vs., 1:9-49 white matter lacerations vs. citrobacter meningitis, I:8-16i, 1:8-17 pneumocephalus vs., II:4-18i skull fracture, hemangioma vs., II:4-73 Heart valves, artificial metallic microemboli vs. cerebral amyloid disease, 1:4-59

metallic microemboli vs. hypertensive intracranial hemorrhage, 1:4-17 Hemangioblastoma, 1:6-114 to 1:6-116, 1:6-117i cavernous malformation vs., 1:5-24i desmoplastic infantile ganglioglioma vs., 1:674i, 1:6-75 differential diagnosis, 1:6-114i, 1:6-115 pilocytic astrocytoma vs., 1:6-30i, 1:6-31 schwannoma vs., 1:6-10Si, 1:6-109 subependymoma vs., 1:6-56i, 1:6-57 teratoid-rhabdoid tumor, atypical, vs., 1:6-101 yon Hippel Lindau syndrome vs., l:l-S6i, l:l-S7 Hemangioma, II:4-72 to II:4-74, 1I:4-75i atretic cephalocele vs., 1I:4-12i, II:4-13 cavernous arteriovenous malformation vs., 1:5-5 choroid plexus papilloma vs., 1:6-62 drug abuse vs., 1:10-9 differential diagnosis, 1I:4-72i, II:4-73 to II:4-74 infantile, vs. sinus pericranii, 1:5-20i, 1:5-21 myeloma vs., 1I:4-76i, II:4-77 Hemangiopericytoma, 1:6-118 to 1:6-120, 1:6-121i differential diagnosis, 1:6-11Si, 1:6-119 gliosarcoma vs., 1:6-24i, 1:6-25 Hematoma epidural. See Epidural hematoma extra-axial, leukemia vs., 1:6-129 intracerebral, 1:4-8 to 1:4-10, 1:4-11i differential diagnosis, 1:4-8i, 1:4-9 resolving, abscess vs., I:S-24i, 1:8-25 subdural. See Subdural hematoma Hematopoiesis, extramedullary, II:4-42 to II:4-43, 1I:4-43i differential diagnosis, 1I:4-42i epidural hematoma vs., 1:2-6i, 1:2-7 leukemia vs., 1:6-129 meningioma vs., 1I:4-56i, II:4-57 Hemiatrophy, 1:1-75 Hemifacial spasm. See Vascular loop compression Hemimegalencephaly, 1:1-74 to 1:1-76, 1:1-77i differential diagnosis, 1:1-74i, 1:1-75 mild, 1:1-75 pachygyria vs., 1:1-62i, 1:1-63 polymicrogyria vs., 1:1-62i, 1:1-63 of tuberous sclerosis, 1:1-75 Hemispheric infarction (Dyke-Davidoff-Masson syndrome), I:S-42i, 1:8-43 Hemophilia, 1:2-3Si, 1:2-39 Hemorrhage acute, 1:1-117 amyloid, 1:4-100i, 1:4-101 basal ganglionic, 1:4-17 Duret, 1:2"':'42i intracranial. See Intracranial hemorrhage intraventricular, I:S-2Si, 1:8-29 lobar, 1:4-17 petechial, 1:4-93 pituitary, 1I:2-2Si, II:2-29 pseudo-subarachnoid, 1:3-4 remote cerebellar, 1:4-20 to 1:4-23

subacute lipoma vs., 1:1-24 neurocutaneous melanosis vs., 1:1-117 subarachnoid. See Subarachnoid hemorrhage venous. See Venous hemorrhage Hepatic encephalopathy, 1:10-24 to 1:10-26, I:I0-27i differential diagnosis, I:I0-24i, 1:10-25 to 1:10-26 Hepatic failure, 1:9-47 Hereditary hemorrhagic telangiectasia, 1:1-104 to I:I-I06,1:1-107i differential diagnosis, I:I-I04i, 1:1-105 Herniation intracranial syndrome, 1:2-42 to 1:2-45 tonsillar, I:l-Si, 1:1-9 Herpes encephalitis, 1:8-34 to 1:8-36, I:S-37i anaplastic astrocytoma vs., 1:6-17 anaplastic oligodendroglioma vs., 1:6-47 differential diagnosis, I:S-34i, 1:8-35 HIV encephalitis vs., I:S-66i, 1:8-67 low grade diffuse astrocytoma vs., 1:6-9 miscellaneous encephalitis vs., I:S-3Si, I:S-39 oligodendroglioma vs., 1:6-43 paraneoplastic syndromes vs., 1:6-144i, 1:6-145 rickettsial diseases vs., I:S-62i, 1:8-63 status epilepticus vs., I:I0-54i, 1:10-55 Herpes simplex congenital, 1:8-10 to 1:8-11, I:S-lli, 1:8-31 differential diagnosis, I:S-lOi, 1:8-10 to 1:8-11 type 2 infections, I:S-12i, 1:8-13 urea cycle disorders vs., 1:9-47 Herpes zoster OtiCllS.See Ramsay Hunt syndrome Heterotopia, X-linked subependymal, 1:1-90i, 1:1-91 Heterotopic gray matter, 1:1-58 to 1:1-60, 1:1-61i differential diagnosis, 1:1-5Si, 1:1-59 Hexachlorophene toxicity, 1:9-43 HIE. See Hypoxic-ischemic encephalopathy (HIE) Hippocampal sulcus remnant, I:I0-50i, 1:10-51 Histiocytosis, II:4-48 to II:4-50, 1I:4-51i differential diagnosis, 1I:4-4Si, II:4-49 diffuse pediatric pontile glioma vs., 1:6-13 infundibular, neurosarcoid vs., 1I:4-52i, II:4-53 Langerhans cell. See Langerhans cell histiocytosis tuber cinereum hamartoma vs., II:2-13 Histoplasmosis, 1:8-58 HIV encephalitis, 1:8-66 to 1:8-68, I:S-69i Creutzfeldt-]akob disease vs., 1:10-75 cytomegalovirus infection vs., 1:8-71 differential diagnosis, I:S-66i, 1:8-67 diffuse encephalitis vs., 1:8-67 Fahr disease vs., 1:10-17 progressive multifocalleukoencephalopathy vs., 1:8-71 HIV infections. See also AIDS (acquired immunodeficiency syndrome) acute aseptic meningitis, 1:8-72 Alzheimer dementia vs., 1:10-63 congenital, 1:8-8 to 1:8-9

differential diagnosis, 1:8-8, I:S-Si opportunistic, 1:8-70 to 1:8-72, I:S-73i differential diagnosis, I:S-70i, 1:8-71 to 1:8-72 subacute sclerosing panencephalitis vs., I:SS2i,I:8-83 "Holes in the skull" hemangioma vs., II:4-73 myeloma vs., II:4-77 Holoprosencephaly, 1:1-38 to 1:1-40, 1:I-4li alobar classic holoprosencephaly vs., 1:1-43 hydranencephaly vs., 1:4-66i, 1:4-67 differential diagnosis, 1:1-3Si, 1:1-39 lobar classic holoprosencephaly vs., 1:1-42i, 1:1-43 septooptic dysplasia vs., 1:1-47 semilobar, 1:1-42i, 1:1-43 variants, 1:1-42 to 1:1-44, 1:1-45i differential diagnosis, I:1-42i, I:1-43 middle interhemispheric, 1:1-3Si, 1:1-39, 1:1-43 Homocystinuria, 1:4-3Si, 1:4-39 Horizontal gaze palsy with progressive scoliosis, 1:1-54i,I:I-55 Hunter syndrome glutaric aciduria type I vs., 1:9-49 hypomyelination vs., 1:9-Si, 1:9-9 Huntington disease, 1:9-66 to 1:9-68, 1:9-69i Alzheimer dementia vs., 1:10-63 differential diagnosis, 1:9-66i, 1:9-67 Hurler syndrome glutaric aciduria type I vs., 1:9-4Si, 1:9-49 hypomyelination vs., 1:9-9 Hydatid cysts, 1:7-23 Hydranencephaly, 1:4-66 to 1:4-67, 1:4-67i differential diagnosis, 1:4-66i, 1:4-66 to 1:4-67 porencephalic cyst vs., 1:7-37 schizencephaly vs., 1:1-71 Hydrocephalus acquired extraventricular obstructive enlarged subarachnoid spaces vs., II:I-13 non-accidental trauma vs., 1:2-3Si, 1:2-39 callosal dysgenesis vs., 1:1-19 glutaric aciduria type I vs., 1:9-49 intracranial herniation syndromes vs., 1:2-42i lissencephaly type 1 vs., 1:1-67 normal pressure, II:I-24 to II:I-26, 1I:1-27i differential diagnosis, II: 1-24i, II:1-25 obstructive, II:I-16 to II:I-18, 1I:1-19i differential diagnosis, II: 1-16i, II:1-17 severe chronic shunted congenital, 1:1-13 hydranencephaly vs., 1:4-66, 1:4-66i with ruptured septum pellucidum, 1:1-39 L-2-Hydroxyglutaric aciduria, 1:9-63 Hygroma acute subdural hematoma vs., 1:2-11 mixed subdural hematoma vs .. 1:2-21

arachnoid cyst vs., 1:7-5 chronic subdural hematoma vs., 1:2-17 empyema vs., I:S-30i, 1:8-31 non-accidental trauma vs., 1:2-39 Hyperalimentation hepatic encephalopathy vs., 1:10-25 kernicterus vs., 1:10-6, I:I0-6i Hyperammonemia, transient, 1:9-47 Hypercoagulability,I:4-63 Hyperdense vessel mimics, 1:4-77 Hyperemia, cerebral, I:I0-2Si, 1:10-29 Hyperostosis, diffuse, 1I:4-3Si Hyperostosis interna, 1I:4-44i, II:4-45 Hyperparathyroidism Fahr disease vs., I:I0-16i, 1:10-17 hemangioma vs., II:4-73 hepatic encephalopathy vs., 1:10-25 myeloma vs., II:4-77 Hyperperfusion syndrome, 1:10-29 Hyperphenylalaninemia, I:1-51 Hypertension CADASILvs., 1:4-62i chronic, carbon monoxide poisoning vs., I:I0-3Si drug abuse vs., I:I0-Si, 1:10-9 hemorrhage. See Intracranial hemorrhage, hypertensive idiopathic intracranial, 1:10-36 to 1:10-37, 1:10-37 differential diagnosis, 1:10-36-1:10-37, 1:1O-36i intracerebral hematoma and, 1:4-Si, 1:4-9 Hypertensive encephalopathy acute, 1:10-28 to 1:10-30, I:I0-31i. See also Posterior reversible encephalopathy (PRES) differential diagnosis, I:I0-2Si, 1:10-29 chronic, 1:10-32 to 1:10-34, I:I0-35i arteriolosclerotic disease vs., 1:4-33 differential diagnosis, I:I0-32i normal brain aging vs., I:I0-5Si, 1:10-60 normal pressure hydrocephalus vs., 11:124i, II:1-25 Creutzfeldt-]akob disease vs., 1:1O-74i osmotic demyelination syndrome vs., 1:10-43 sporadic, CADASILvs., 1:4-63 Hypertrophic pachymeningitis. See Pachymeningitis, hypertrophic Hypertrophy, pituitary. See Pituitary hyperplasia Hypodontia, 1:1-43 Hypoglossal artery, persistent, 1:4-36i, 1:4-37 Hypoglycemia, 1:10-4 to 1:10-5, 1:10-5 acute hypertensive encephalopathy vs., 1:1O-2Si coma amyotrophic lateral sclerosis vs., 1:10-87 Wallerian degeneration vs., 1:10-92 differential diagnosis, I:10-4, 1:1O-4i microcenhalv vs .. 1:1-51

Hypomyelination, 1:9-8 to 1:9-10, 1:9-11i differential diagnosis, 1:9-8i, 1:9-9 Hypoparathyroidism Fahr disease vs., 1:10-17 hepatic encephalopathy vs., 1:10-25 Hypophysitis. See Lymphocytic hypophysitis Hypoplasia, dural sinus thrombosis vs., 1:4-96i Hypotension cerebral infarction and, 1:4-92 to 1:4-94, 1:4-9Si differential diagnosis, 1:4-92i, 1:4-93 chronic subdural hematoma vs., 1:2-17 intracranial, 11:4-22 to 11:4-24, II:4-2Si acute subdural hematoma vs., 1:2-11 differential diagnosis, II:4-22i, 11:4-23 herniation syndromes vs., 1:2-43 hypertrophic pachymeningitis vs., II:4-30i, 11:4-31 hypothyroidism vs., I:I0-12i, 1:10-13 mixed subdural hematoma vs., 1:2-21 pituitary hyperplasia vs., II:2-38i, 11:2-39 spontaneous, Chiari type 1 vs., 1:1-9 subacute subdural hematoma vs., 1:2-15 Hypothalamus astrocytoma, craniopharyngioma vs., 11:2-33 tuber cinereum masses, II:2-12i, 11:2-13 Hypothyroidism, 1:10-12 to 1:10-14, I:I0-1Si Alzheimer dementia vs., 1:10-63 differential diagnosis, 1:1O-12i, 1:10-13 hepatic encephalopathy vs., 1:10-25 Hypoxia, global, 1:4-104i, 1:4-106 Hypoxic-ischemic encephalopathy (HIE) acquired craniostenosis after, 1:8-8i callosal dysgenesis vs., 1:1-19 Creutzfeldt-]akob disease vs., I:I0-74i, 1:10-75 group B streptococcal meningitis vs., 1:8-13 hepatic encephalopathy vs., 1:10-25 kernicterus vs., I:I0-6i maple syrup urine disease vs., 1:9-43 microcephaly vs., l:l-SOi, 1:1-51 mucopolysaccharidoses vs., 1:9-20i, 1:9-21 preterm, 1:4-68 to 1:4-70, 1:4-7li differential diagnosis, 1:4-68i, 1:4-69 term, 1:4-72 to 1:4-74, 1:4-7Si differential diagnosis, 1:4-72i, 1:4-73 traumatic cerebral edema vs., 1:2-46i, 1:2-47

I Immune deficiency syndromes, 1:8-59. See also AIDS (acquired immunodeficiency syndrome) Incisor canal cyst, 1:1-101 Infarction anoxic, 1:10-21 arterial, 1:4-106 artery of Percheron, 1:4-106 central pons, 1:10-43 cerebellar, 1:6-70i, 1:6-71 cerebral. See Cerebral infarction; Cerebral ischemia-infarction, acute

cerebral contusion vs., 1:2-26i, 1:2-27 choroid artery, 1:7-31 cortical, 1:4-63 embolic, drug abuse vs., I:I0-8i hemispheric, 1:8-42i, 1:8-43 hypertrophic olivary degeneration vs., 1:1094i, 1:10-95 intracranial herniation syndromes vs., 1:2-42i lacunar. See Lacunar infarction multiple. See Multi-infarct dementia peripheral, 1:2-10i, 1:2-11 subacute, 1:8-25 vein of Labbe, 1:4-12i venous, 1:4-80i, 1:4-81 Infections bacterial, 1:8-17 gas-producing, 11:4-19 hypertrophic pachymeningitis vs., 11:4-31 Infectious cysts, 1:7-21 Inflammation acute cerebral ischemia-infarction vs., 1:4-78 pilocytic astrocytoma vs., 1:6-31 Inflammatory cysts, 1:7-17 Infundibular recess, pituitary, dilated, 11:2-9 Infundibulum posterior communicating artery, blood blisterlike aneurysm vs., 1:3-23 saccular aneurysm vs., 1:3-12i, 1:3-13 Injuries. See Trauma Interhemispheric disconnection syndrome, 1:1-19 Internal auditory canal, 11:3-8 to 11:3-39 acoustic schwannoma, 11:3-28 to 11:3-31 arachnoid cyst, 11:3-16 to 11:3-19 epidermoid cyst, 11:3-12 to 11:3-15 lipoma, 11:3-8 to 11:3-11 meningioma, 11:3-32 to 11:3-35 metastases, 11:3-36 to 11:3-39 Ramsay Hunt syndrome, 11:3-20 to 11:3-23 vascular loop compression, 11:3-24 to 11:3-27 Intracranial hemorrhage hypertensive, 1:4-16 to 1:4-18, 1:4-19i differential diagnosis, 1:4-16i remote cerebellar hemorrhage vs., 1:4-21 spontaneous, neoplasm vs., 1:4-13 traumatic subarachnoid hemorrhage vs., 1:2-23 spontaneous, 1:4-12 to 1:4-14, 1:4-1Si differential diagnosis, 1:4-12i, 1:4-13 Intracranial herniation syndromes, 1:2-42 to 1:244,1:2-4Si differential diagnosis, 1:2-42i, 1:2-43 Intracranial hypotension syndrome, 1:2-43 Intracranial injuries, non-projectile, 1:2-4i Intrasellar cysts, II:2-16i Ischemia. See also Hypoxic-ischemic encephalopathy (HIE) anaplastic astrocytoma vs., 1:6-16i, 1:6-17 anaplastic oligodendroglioma vs., 1:6-47 central pons, I:I0-42i, 1:10-43

cerebral. See Cerebral ischemia; Cerebral ischemia-infarction, acute encephalitis vs., I:8-38i, 1:8-39 herpes encephalitis vs., I:8-34i, 1:8-35 low grade diffuse astrocytoma vs., I:6-8i, 1:6-9 oligodendroglioma vs., 1:6-43 status epilepticus vs., I:IO-S4i, 1:10-55 subacute, glioblastoma multiforme vs., 1:6-21 Ischemic stroke, with micro hemorrhage, 1:4-59 "Ivy sign," 1:4-43

J Jaffe-Campanacci syndrome, II:4-35 Joubert syndrome Dandy Walker spectrum vs., 1:1-27 muscular dystrophy vs., 1:1-55 rhombencephalosynapsis vs., 1:1-31

K Kallman syndrome, 1:1-47 Kaplan-Grumbach-Hoyt syndrome. See Septooptic dysplasia Karposi sarcoma, I:6-113 Kearns-Sayre syndrome Fahr disease vs., 1:10-17 Hallervorden-Spatz syndrome vs., 1:9-63 MELASvs., 1:9-17 Kernicterus, 1:10-6 to 1:10-7, I:IO-7i differential diagnosis, 1:10-6, I:IO-6i full-term hypoxic-ischemic encephalopathy vs., I:4-72i, 1:4-73 Hallervorden-Spatz syndrome vs., I:9-62i, 1:9-63 Kidney failure, chronic, II:4-35 Kippel-Trenaunay-Weber syndrome, 1:1-95 Kleebattschadel skull, I1:4-8i Krabbe disease, 1:9-32 to 1:9-34, I:9-3Si differential diagnosis, I:9-32i, 1:9-33 gangliosidosis vs., I:9-24i, 1:9-25 hypomyelination vs., 1:9-9 metachromatic leukodystrophy vs., 1:9-29

L Lacunar infarction, 1:4-88 to 1:4-90, I:4-9li CADASILvs., 1:4-63 differential diagnosis, I:4-88i, 1:4-89 enlarged perivascular spaces vs., I:7-22i, 1:7-23 Lyme disease vs., 1:8-65 subcortical injuries vs., I:2-34i, 1:2-35 Langerhans cell histiocytosis fibrous dysplasia vs., II:4-35 germinoma vs., 1:6-133 hepatic encephalopathy vs., 1:10-25 leukemia vs., I:6-128i, 1:6-129 metastatic neuroblastoma vs., I:6-104i, 1:6-105 sinus pericranii vs., 1:5-21

Lateral sclerosis, primary amyotrophic lateral sclerosis vs., 1:10-87 Wallerian degeneration vs., 1:10-91 Lateral ventricles, asymmetric, II:I-8, I1:1-8i Leber congenital amaurosis, 1:1-35 Leigh syndrome, 1:9-12 to 1:9-14, I:9-1Si alcoholic encephalopathy vs., 1:10-21 carbon monoxide poisoning vs., 1:10-40 Creutzfeldt-Jakob disease vs., I:IO-74i, 1:10-75 differential diagnosis, I:9-12i, 1:9-13 Huntington disease vs., I:9-66i, 1:9-67 MELASvs., I:9-16i, 1:9-17 osmotic demyelination syndrome vs., 1:10-43 Wilson disease vs., I:9-70i, 1:9-71 Leptomeningeal carcinomatosis, II:3-36 to II:3-38, I1:3-39i Leptomeningeal cyst hemangioma vs., I1:4-72i, II:4-73 histiocytosis vs., I1:4-48i, II:4-49 Leptomeningeal disease differential diagnosis, I:8-20i, 1:8-21 Leptomeningeal enhancement, 1:1-96 Leptomeningeal metastasis dysplastic cerebellar gangliocytoma vs., 1:6-71 Sturge-Weber syndrome vs., 1:1-96 Leukemia, 1:6-128 to 1:6-130, I:6-13li chronic subdural hematoma vs., 1:2-17 differential diagnosis, I:6-128i, 1:6-129 metastatic neuroblastoma vs., I:6-104i, 1:6-105 mixed subdural hematoma vs., I:2-20i, 1:2-21 non-accidental trauma vs., 1:2-39 Sturge-Weber syndrome vs., 1:1-96 subacute subdural hematoma vs., I:2-14i, 1:2-15 Leukodystrophy fibrinoid. See Alexander disease globoid. See Krabbe disease metachromatic, 1:9-28 to 1:9-30, I:9-3li Canavan disease vs., 1:9-52, I:9-S2i differential diagnosis, I:9-28i, 1:9-29 gliomatosis cerebri vs., I:6-26i, 1:6-27 hypomyelination vs., 1:9-9 van der Knapp leukoencephalopathy vs., I:9-S8i, 1:9-59 periventricular, I:9-38i, 1:9-39 spongiform (progressive autosomal-recessive). See Canavan disease Leukoencephalopathy Cree, 1:9-59 progressive multifocal. See Progressive multifocalleukoencephalopathy subcortical, chronic hypertensive encephalopathyvs.,I:10-34 van der Knapp. See van der Knapp leukoencephalopathies Leukomalacia periventricular, I:9-28i, 1:9-29 vacuolating megalencephalic, with subcortical cysts, 1:9-29 Lewy body disease, diffuse Alzheimer dementia vs., 1:10-63

frontotemporal dementia vs., 1:10-71 Parkinson disease vs., 1:10-80 Lhermitte-Duclose disease. See Gangliocytoma, dysplastic cerebellar Limbic encephalitis, I:S-34i, 1:8-35 Lipofuscinosis, neuronal ceroid gangliosidosis vs., 1:9-24i Hallervorden-Spatz syndrome vs., 1:9-63 Kabbe disease vs., 1:9-32i, 1:9-33 Lipoma, 1:1-22 to 1:1-24, 1:1-2Si of cerebellopontine angle, II:3-8 to II:3-lO, II:3-11i differential diagnosis, II:3-Si, II:3-9 hypothalamic, II:2-12i differential diagnosis, 1:1-22i, 1:1-23 to 1:1-24 neurocutaneous melanosis vs., 1:1-117 pituitary stalk anomalies vs., II:2-Si, II:2-9 saccular aneurysm vs., 1:3-12i, 1:3-13 tuber cinereum hamartoma vs., II:2-13 Lipomatosis, encephalocraniocutaneous, I:1-108 to 1:1-110, l:l-11li differential diagnosis, I:I-I0Si, 1:1-109 Liponeurocytoma, cerebellar, 1:1-23 Lissencephaly bilateral,I:1-67 cobblestone (type 2), 1:1-66i, 1:1-67 type I, 1:1-66 to 1:1-68, 1:1-69i differential diagnosis, 1:1-66i, 1:1-67 with cerebellar hypoplasia, 1:1-67 X-linked,I:1-67 Lithium intoxication, 1:10-83 Liver copper overload, 1:10-25 Liver failure, 1:9-47 Lowe syndrome, 1:4-69 Lumbar puncture, Chiari type 1 vs., 1:1-9 Lupus erythematosus, systemic. See Systemic lupus erythematosus (SLE) Lyme disease, 1:8-64 to 1:8-65, I:S-6Si differential diagnosis, I:S-64i, 1:8-64 to 1:8-65 encephalopathy, 1:4-55 multiple sclerosis vs., I:S-74i, I:S-75 Lymphedema, 1:1-67 Lymphocytic choriomeningitis, congenital, I:S-4i, 1:8-5 Lymphocytic hypophysitis, II:2-40 to II:2-41, II:2-41i differential diagnosis, II:2-40i, II:2-40 to II:2-41 histiocytosis vs., II:4-49 hypothyroidism vs., I:I0-12i, 1:10-13 pituicytoma vs., II:2-24i, II:2-36 pituitary hyperplasia vs., II:2-38, II:2-3Si pituitary macroadenoma vs., II:2-24i, II:2-25 Lymphocytic infundibula-neurohypophysitis, II:2-41 Lymphoepitheliallesion, cystic benign, l:l-S4i, 1:1-55 Lymphoma acoustic schwannoma vs., II:3-29 in AIDS, I:S-70i, 1:8-72 chronic subdural hematoma vs., 1:2-17

deep cerebral venous thrombosis vs., 1:4-105 gliomatosis cerebri vs., 1:6-27 hemangiopericytoma vs., 1:6-11Si, 1:6-119 histiocytosis vs., II:4-49 hypertrophic olivary degeneration vs., 1:10-95 hypertrophic pachymeningitis vs., II:4-31 intravascular (angiocentric), 1:6-126 to 1:6-127, 1:6-127i differential diagnosis, 1:6-126i, 1:6-127 malignant amyotrophic lateral sclerosis vs., 1:10-87 Wallerian degeneration vs., 1:10-91 mixed subdural hematoma vs., 1:2-21 non-Hodgkin, II:4-27 primary CNS, 1:6-122 to 1:6-124, 1:6-12Si differential diagnosis, 1:6-122i, 1:6-123 glioblastoma multiforme vs., 1:6-20i, 1:6-21 H1Vencephalitis vs., I:S-66i, 1:8-67 intravascular lymphoma vs., 1:6-126i, 1:6-127 meningitis vs., 1:8-21 primary meningeal, II:3-33 of scalp, neurofibroma vs., 1:6-112i, 1:6-113 subacute subdural hematoma vs., 1:2-15 systemic, secondary involvement, 1:6-123 toxoplasmosis vs., 1:8-71 tuberculosis vs., 1:8-71 ventriculitis vs., 1:8-28, I:S-2Si Lymphomatosis, 1:4-97 Lytic calvarial lesions, II:4-49

M Machiafavi-Bignami disease callosal dysgenesis vs., 1:1-19 hypoxic-ischemic encephalopathy, 1:9-43 Macroadenoma, pituitary. See Pituitary macroadenoma Macrocephaly benign familial, 1:9-49 glutaric aciduria type I vs., 1:9-49 with dilated perivascular spaces, 1:9-20i, 1:9-21 Malnutrition alcoholic encephalopathy vs., 1:10-21 hypomyelination vs., 1:9-9 multiple system atrophy vs., 1:10-83 Manganese, 1:4-72i, 1:4-73 Maple syrup urine disease, 1:9-42 to 1:9-44, 1:9-4Si differential diagnosis, 1:9-42i, 1:9-43 Marchiafava-Bignami syndrome, 1:2-'-31 Marfan syndrome sickle cell disease vs., 1:4-39 traumatic extra cranial dissection vs., 1:2-59 Marie ataxia, I:I0-20i, 1:10-21 Maroteaux-Lamy disease, 1:9-49 Mastoiditis, II:4-49 Measles encephalitis, 1:8-82 Meckel-Gruber syndrome Chiari type 3 vs., 1:1-16 congenital vermian hypoplasia vs., 1:1-35

Mediterranean spotted fever, 1:8-62 to 1:8-63 Medulloblastoma, 1:6-92 to 1:6-94, 1:6-9Si atypical teratoid-rhabdoid tumor vs., 1:6-100i, 1:6-101 Cowden syndrome vs., 1:1-112i, 1:1-113 differential diagnosis, 1:6-92i, 1:6-93 ependymoma vs., 1:6-S2i, 1:6-53 pilocytic astrocytoma vs., 1:6-30i, 1:6-31 Megalencephaly, 1:1-74i, 1:1-75 Megaloencephalic leukoencephalopathy with subcortical cysts. See van der Knapp leukoencephalopathies Melanosis, neurocutaneous, 1:1-116 to 1:1-118, 1:1-119i differential diagnosis, 1:1-116i, 1:1-117 superficial siderosis vs., 1:3-8i, 1:3-9 MELAS(mitochondrial encephalopathy with lactic acidosis and stroke-like episodes), 1:9-16 to 1:9-18, 1:9-19i CADASILvs., 1:8-63 differential diagnosis, 1:9-16i, 1:9-17 to 1:9-18 Fahr disease vs., 1:10-17 kernicterus vs., 1:10-6, I:I0-6i Leigh syndrome vs., 1:9-12i, 1:9-13 Rasmussen encephalitis vs., 1:8-42i, 1:8-43 status epilepticus vs., I:I0-S4i, 1:10-55 traumatic cerebral edema vs., 1:2-46i, 1:2-47 urea cycle disorders vs., 1:9-46i Meningeal carcinomatosis. See Carcinomatosis, meningeal Meningeal metastasis, 11:3-21 Meningeal sarcoma atypical and malignant meningioma vs., 11:460i, 11:4-61 benign nonmeningothelial tumors vs., 11:4Mi, 11:4-65 Meningioangiomatosis, 1:1-98 to 1:1-99, 1:1-99i differential diagnosis, I: 1-98i, I:1-98 to I:1-99 Sturge-Weber syndrome vs., 1:1-95 superficial siderosis vs., 1:3-8i, 1:3-9 Meningioma, 11:4-56 to 11:4-58, 1I:4-S9i acoustic schwannoma vs., 1I:3-28i, 11:3-29 Alzheimer dementia vs., I:I0-62i, 1:10-63 anaplastic oligodendroglioma vs., 1:6-47 arachnoid cyst vs., 11:3-17 atypical and malignant, 11:4-60 to 11:4-62, 1I:4-63i benign nonmeningothelial tumors vs., 11:464i, 11:4-65 differential diagnosis, 1I:4-60i, 11:4-61 malignant nonmeningothelial tumors vs., 1I:4-68i, 11:4-69 central neurocytoma vs., 1:6-81 of cerebropontine angle, 11:3-32 to 11:3-34, 1I:3-3Si differential diagnosis, 1I:3-32i, 11:3-33 choroid plexus carcinoma vs., 1:6-64i, 1:6-65 choroid plexus cyst vs., 1:7-31 choroid plexus papilloma vs., 1:6-60i, 1:6-61

chronic, subacute subdural hematoma vs., 1:214i,I:2-15 chronic subdural hematoma vs., 1:2-17 common benign nonmeningothelial tumors vs., 1I:4-64i malignant nonmeningothelial tumors vs., 1I:4-68i, 11:4-69 cystic, 11:3-13 differential diagnosis, 1I:4-S6i, 11:4-57 en plaque hypertrophic pachymeningitis vs., 11:4-31 intracranial pseudotumor vs., 1I:4-26i, 11:4-27 epidural hematoma vs., 1:2-6i, 1:2-7 extramedullary hematopoiesis vs., 11:4-42 fibrous dysplasia vs., 1I:4-34i, 11:4-35 germinoma vs., 1:6-133 hemangiopericytoma vs., 1:6-118i, 1:6-119 intradiploic, hemangioma vs., 11:4-73 leukemia vs., 1:6-128i, 1:6-129 lipoma vs., 1:1-23 malignant, gliosarcoma vs., 1:6-25 meningioangiomatosis vs., 1:1-98, 1:1-98i mixed subdural hematoma vs., 1:2-20i, 1:2-21 multiple, neurofibromatosis type 2 vs., 1:1-83 neurosarcoid vs., 11:4-53 pineoblastoma vs., 1:6-84i, 1:6-85 pineocytoma vs., 1:6-89 pituitary macroadenoma vs., 1I:2-24i, 11:2-25 pleomorphic xanthoastrocytoma vs., 1:6-35 skull and meningeal metastasis vs., 11:4-81 Meningitis, 1:8-20 to 1:8-22, 1:8-23i in AIDS, 1:8-72 bacterial, tuberculosis vs., 1:8-46i carcinomatous. See Carcinomatosis, meningeal cerebellopontine angle metastases vs., 1I:3-36i, 11:3-37 chronic acute subdural hematoma vs., 1:2-11 chronic subdural hematoma vs., 1:2-17 mixed subdural hematoma vs., 1:2-21 Citrobacter, 1:8-16 to 1:8-19, 1:8-20i differential diagnosis, 1:8-20i, 1:8-21 enteric, 1:8-13 gram negative, 1:8-13 granulomatous, 1:1-98 group B streptococcal, 1:8-12 to 1:8-14, 1:8-1Si high CSF signal and, 1:3-4 histiocytosis vs., 11:4-49 infectious neurocutaneous melanosis vs., 1:1-116i, 1:1-117 skull and meningeal metastasis vs., 11:480i,1I:4-81 tuberculosis vs., 1:8-47 intracranial hypotension vs., 1I:4-22i, 11:4-23 intracranial pseudotumor vs., 1I:4-26i, 11:4-27 metastasis vs., 1I:3-36i, 11:3-37 moyamoya vs., 1:4-42i, 1:4-43

• xviii

I

neurosarcoid vs., 1I:4-52i, II:4-53 nonaneurysmal perimesencephalic subarachnoid hemorrhage vs., 1:3-7 Ramsay Hunt syndrome vs., 1I:3-20i, II:3-21 Sturge-Weber syndrome vs., 1:1-96 traumatic subarachnoid hemorrhage vs., 1:222i,I:2-23 Meningoencephalitis group B streptococcal meningitis vs., 1:8-13 microcephaly vs., 1:1-51 neonatal, 1:8-12i, 1:8-13 Menkes disease, 1:2-39 Mesial temporal sclerosis, 1:10-50 to 1:10-52, 1:10-53i differential diagnosis, 1:10-50i, 1:10-51 status epilepticus vs., 1:10-55 Mesiodens, 1:1-42i, 1:1-43 Metabolic disorders acute hypertensive encephalopathy vs., 1:10-29 full-term hypoxic-ischemic encephalopathy vs.,1:4-73 Metastasis (metastatic disease) abscess vs., 1:8-24i, 1:8-25 acoustic schwannoma vs., II:3-29 astroblastoma vs., 1:6-50i, 1:6-51 atretic cephalocele vs., 1I:4-12i, II:4-13 atypical and malignant meningioma vs., 11:460i, II:4-61 capillary telangiectasis vs., 1:5-28i, 1:5-29 cavernous malformation vs., 1:5-24i central neurocytoma vs., 1:6-80i, 1:6-81 of cerebellopontine angle, II:3-36 to II:3-38, 1I:3-39i differential diagnosis, 1I:3-36i, II:3-37 choroid plexus carcinoma vs., 1:6-65 choroid plexus cyst vs., 1:7-31 choroid plexus papilloma vs., 1:6-61 chronic subdural hematoma vs., 1:2-16i, 1:2-17 dural empyema vs., 1:8-30i, 1:8-31 hemangiopericytoma vs., 1:6-118i, 1:6-119 meningioma vs., 1I:4-56i, II:4-57 ependymal tumor, vs. ventriculitis, 1:8-28i, 1:8-29 epidural hematoma vs., 1:2-6i, 1:2-7 extramedullary hematopoiesis vs., II:4-42, 1I:4-42i fungal diseases vs., 1:8-58i, 1:8-59 germinoma vs., 1:6-133 glioblastoma multiforme vs., 1:6-21 gliosarcoma vs., 1:6-24, 1:6-24i hemangioblastoma vs., 1:6-114i, 1:6-115 hemangioma vs., 1I:4-72i, II:4-73 hemorrhagic cerebral amyloid disease vs., 1:4-59 diffuse axonal injury vs., 1:2-30i, 1:2-31 histiocytosis vs., 1I:4-48i, II:4-49 hypertensive intracranial hemorrhage vs., 1:4-17 hypertrophic olivary degeneration vs., 1:10-95 intracranial hypotension vs., 1I:4-22i, II:4-23

leptomeningeal, meningioma vs., II:3-33 lipoma vs., 1:1-23 lymphocytic hypophysitis vs., 1I:2-40i, II:2-41 lytic, myeloma vs., 1I:4-76i, II:4-77 malignant nonmeningothelial tumors vs., 11:468i, II:4-69 meningeal intracranial pseudotumor vs., 1I:4-26i, II:4-27 Ramsay Hunt syndrome vs., 1I:3-20i, II:3-21 meningitis vs., 1:8-20i, 1:8-21 mixed subdural hematoma vs., 1:2-20i, 1:2-21 moyamoya vs., 1:4-42i, 1:4-43 neuroblastoma, vs. sinus pericranii, I:5-2Oi neurocysticercosis vs., I:8-5Oi neurofibroma vs., 1:6-112i, 1:6-113 neurofibromatosis type 2 vs., 1:1-84 neurosarcoid vs., 1I:4-52i, II:4-53 Paget disease vs., 1I:4-38i, II:4-39 paraneoplastic syndromes vs., 1:6-145 parasitic infections vs., 1:8-54i parenchymal, 1:6-140 to 1:6-142, 1:6-143i differential diagnosis, I:6-140i, 1:6-141 pineoblastoma vs., 1:6-85 pituicytoma vs., II:2-36, 1I:2-36i pituitary macroadenoma vs., 1I:2-24i, II:2-25 pons, osmotic demyelination syndrome vs., 1:10-43 primary eNS lymphoma vs., 1:6-123 radiation injury or chemotherapy vs., 1:10-46i, 1:10-47 remote cerebellar hemorrhage vs., 1:4-20i, 1:4-21 sarcoma, acute subdural hematoma vs., 1:2-10i schwannoma vs., 1:6-109 skull and meningeal, II:4-80 to II:4-82, 1I:4-83i differential diagnosis, 1I:4-83i, II:4-84 subacute subdural hematoma vs., 1:2-15 subependymoma vs., 1:6-57 traumatic carotid-cavernous fistula vs., 1:2-62i, 1:2-63 vascular, yon Hippel Lindau syndrome vs., 1:186i,I:I-87 Methylmalonic acidemia full-term hypoxic-ischemic encephalopathy vs., 1:4-72i, 1:4-73 Hallervorden-Spatz syndrome vs., I:9-62i, 1:9-63 kernicterus vs., 1:10-6 Microangiopathy. See Arteriolosclerosis MicrocaIcification, I:1-67 Microcephaly, 1:1-50 to 1:1-52, 1:1-53i differential diagnosis, 1:1-5Oi lissencephaly type 1 vs., 1:1-66i, 1:1-67 primary vs. secondary, 1:1-51 to 1:1-52 severe, 1:8-8i skull thickening vs., 1I:4-44i, II:4-45 Microhemorrhage hypertensive cerebral amyloid disease vs., 1:4-58i, 1:4-59 diffuse axonal injury vs., 1:2-30i, 1:2-31 intracranial hemorrhage vs., 1:4-17

ischemic stroke with, 1:4-59 Microlissencephaly pachygyria vs., 1:1-62i, 1:1-63 polymicrogyria vs., 1:1-62i, 1:1-63 Microvascular changes, II:1-24i Midbrain obstructions, extraventricular, II:1-20i, 11:1-21 Midline clefting syndromes, 1:1-55 Midline dysplasias, 1:1-39 Miller-Dieker syndrome, 1:1-67 Missile and penetrating injury, 1:2-4 to 1:2-5, 1:2-Si differential diagnosis, 1:2-4i Mitochondrial encephalopathy full-term hypoxic-ischemic encephalopathy vs., 1:4-73 hypomyelination vs., 1:9-9 Mitochondrial membrane abnormalities, 1:9-9 Mitochondrial metabolism disorders, 1:1-63 Mitochondrial SURF1 mutations, 1:9-42i, 1:9-43 Mohr syndrome, 1:1-35 Morgagni syndrome, 11:4-35 Morquio syndrome, 1:9-49 Motor neuron disease Creutzfeldt-]akob disease vs., 1:10-75 Fahr disease vs., 1:10-18 Moyamoya, 1:4-42 to 1:4-44, 1:4-4Si differential diagnosis, 1:4-42i, 1:4-43 intracranial atherosclerosis vs., 1:4-24i, 1:4-25 primary arteritis of CNS vs., 1:4-46i, 1:4-47 MS. See Multiple sclerosis (MS) Mucocele, maxillary sinus, 1:1-100i, 1:1-101 Mucopolysaccharidoses, 1:9-20 to 1:9-22, 1:9-23i Alexander disease vs., 1:9-S4i, 1:9-55 differential diagnosis, 1:9-20i, 1:9-21 glutaric aciduria type 1vS., 1:9-49 hypomyelination vs., 1:9-9 Multi-infarct dementia, 1:10-66 to 1:10-68, 1:10-69i alcoholic encephalopathy vs., 1:10-21 chronic hypertensive encephalopathy vs., 1:10-33 Creutzfeldt-]akob disease vs., 1:10-75 differential diagnosis, 1:1O-66i, 1:10-67 normal pressure hydrocephalus vs., 1:4-33, II:1-24i, 11:1-25 overlap with arteriolosclerotic disease, 1:4-33 Multiple myeloma. See also Myeloma extraosseous, 1:6-129 hemangioma vs., 11:4-73 histiocytosis vs., II:4-48i, 11:4-49 Multiple sclerosis (MS), 1:8-74 to 1:8-76, 1:8-77i acute disseminated encephalomyelitis vs., 1:878i,I:8-79 amyotrophic lateral sclerosis vs., 1:10-86i, 1:10-87 differential diagnosis, 1:8-74i, 1:8-75 to 1:8-76 hypertrophic olivary degeneration vs., 1:1094i,I:IO-95 Lyme disease vs., 1:8-64, 1:8-64i optic nerve atrophy vs. idiopathic intracranial hypertension, 1:10-36i, 1:10-37

osmotic demyelination syndrome vs., 1:10-42i parenchymal metastases vs., 1:6-14Oi primary CNS lymphoma vs., 1:6-122i radiation injury or chemotherapy vs., 1:10-46i, 1:10-47 rickettsial diseases vs., 1:8-62, 1:8-62i subacute sclerosing panencephalitis vs., 1:882i,I:8-83 systemic lupus erythematosus vs., 1:4-S4i, 1:4-55 tumefactive, supratentorial primitive neuroectodermal tumor vs., 1:6-96i, 1:6-97 Wallerian degeneration vs., 1:10-90i, 1:10-92 Multiple system atrophy (MSA), 1:10-82 to 1:1084, 1:10-8Si differential diagnosis, 1:1O-82i, 1:10-83 to 1:10-84 Parkinson disease vs., 1:10-78i, 1:10-79 MURCS (Mullerian, renal, cervical-spine), 1:1-16 Muscular dystrophy congenital, 1:1-54 to 1:1-56, 1:1-S7i differential diagnosis, 1:1-S4i, 1:1-55 lissencephaly type 1 vs., 1:1-67 Myelination, normal, 1:9-4 to 1:9-6, 1:9-7i. See also Demyelinationi Hypomyelination in infants to 12 months, 1:9-4i Myelinolysis, central pontine. See Osmotic demyelination syndrome Myeloma, 11:4-76 to 11:4-78, II:4-79i. See also Multiple myeloma differential diagnosis, II:4-76i, 11:4-77 skull and meningeal metastasis vs., II:4-80i, 11:4-81 Myoblastoma. See Pituicytoma

N Nasal blush, 1:1-104i, 1:1-105 Near-drowning, 1:2-S4i Neoplasms, 1:6-8 to 1:6-147. See also Metastasis (metastatic disease)i specific tumor types calcified, 1:5-5 cystic enlarged perivascular spaces vs., 1:7-23 epidermoid cyst vs., 1:7-17, 11:3-13 dural sinus thrombosis vs., 1:4-97 hemorrhagic drug abuse vs., 1:10-8i, 1:10-9 non-melanotic, neurocutaneous melanosis vs., 1:1-117 hypertensive bleed vs., 1:4-13 hypertrophic pachymeningitis vs., 11:4-31 infiltrating acute cerebral ischemia-infarction vs., 1:4-78 encephalitis vs., 1:8-39 intracerebral hematoma vs., 1:4-8i, 1:4-9, 1:4-13 lipoma tous differentia tion/transforma tion, 1:1-23 low-attenuating, chronic cerebral infarction vs., 1:4-85

I

low-grade, cerebral contusion vs., 1:2-26i, 1:2-27 neurocysticercosis vs., 1:8-51 parasitic infections vs., 1:8-55 porencephalic cyst vs., 1:7-37 primary, abscess vs., 1:8-24i, 1:8-25 remote cerebellar hemorrhage vs., 1:4-21 skull base, locally invasive, 1:8-59 subacute cerebral infarction vs., 1:4-81 tuberculosis vs., 1:8-47 tumor encasement vs. moyamoya, 1:4-43 Neurenteric cyst, 1:7-40 to 1:7-41, 1:7-4li arachnoid cyst vs., 1:7-5, II:3-16i, II:3-17 cerebellopontine angle epidermoid cyst vs., II:3-12i, II:3-13 lipoma vs., II:3-8i, II:3-9 differential diagnosis, 1:7-40, 1:7-4Oi ependymal cyst vs., I:7-35 Neuroblastoma, metastatic, 1:6-104to 1:6-106,1:6-107i differential diagnosis, 1:6-104i, 1:6-105 leukemia vs., 1:6-128i, 1:6-129 sinus pericranii vs., I:S-20i, 1:5-21 Neurocutaneous disorders fibrous dysplasia vs., II:4-35 melanosis. See Melanosis, neurocutaneous Sturge-Weber syndrome vs., 1:1-95 Neurocysticercosis, 1:8-50 to 1:8-52, 1:8-S3i aqueductal stenosis vs., II:1-21 choroid plexus cyst vs., 1:7-31 colloid cyst vs., 1:7-9 differential diagnosis, 1:8-SOi, 1:8-51 to 1:8-52 enlarged perivascular spaces vs., 1:7-22i, 1:7-23 epidermoid cyst vs., 1:7-16i, 1:7-17 ganglioglioma vs., 1:6-67 lacunar infarction vs., 1:4-88i, 1:4-89 parasitic infections vs., 1:8-S4i, 1:8-55 sellar, Rathke cleft cyst vs., II:2-17 Neurocytoma, central, 1:6-80 to 1:6-82, 1:6-83i choroid plexus carcinoma vs., 1:6-64i, 1:6-65 differential diagnosis, 1:6-80i, 1:6-81 subependymal giant cell astrocytoma vs., 1:638i,1:6-39 subependymoma vs., 1:6-S6i, 1:6-57 Neurodegenerative diseases, 1:10-91 Neuroectodermal tumor, primitive (PNET) astroblastoma vs., 1:6-50, 1:6-SOi desmoplastic infantile ganglioglioma vs., 1:6-74 germinoma vs., 1:6-133 histiocytosis vs., II:4-49 neurocutaneous melanosis vs., 1:1-116i neurofibromatosis type 2 vs., 1:1-84 subependymal giant cell astrocytoma vs., 1:638i,1:6-39 supratentorial, 1:6-96 to 1:6-98, 1:6-99i differential diagnosis, 1:6-96i, 1:6-97 embryonal carcinoma vs., 1:6-138, 1:6-138i teratoma vs., 1:6-137 Neuroepithelial cyst. See Ependymal cyst Neuroepithelial tumor, dysembryoplastic (DNET), 1:6-76 to 1:6-78, 1:6-79i differential diagnosis, 1:6-76i, 1:6-77

ganglioglioma vs., 1:6-66i, 1:6-67 meningioangiomatosis vs., 1:1-99 mesial temporal sclerosis vs., I: 10-5 1 oligodendroglioma vs., 1:6-42i, 1:6-43 pleomorphic xanthoastrocytoma vs., 1:6-34i, 1:6-35 Neurofibroma, 1:6-112 to 1:6-113, 1:6-113i differential diagnosis, 1:6-112i Neurofibromatosis type 1 (NFl), 1:1-78 to 1:1-80, 1:1-8li differential diagnosis, 1:1-78i, 1:1-79 diffuse pediatric pontile glioma vs., 1:6-12i, 1:6-13 hepatic encephalopathy vs., I:10-25 neurofibromatosis type 2 vs., 1:1-79 type 2 (NF2), 1:1-82 to 1:1-84, 1:1-8Si differential diagnosis, I:1-83 to I:1-84 Neuroglial cyst, 1:7-20 to 1:7-21, 1:7-2li arachnoid cyst vs., 1:7-4i, 1:7-5 differential diagnosis, 1:7-20i, 1:7-20 to 1:7-21 Neuroma, acoustic. See Acoustic schwannoma Neurons, migrating, 1:1-S8i Neuropsychiatric disorders, 1:10-18 Neurosarcoid, II:4-52 to II:4-54, II:4-SSi differential diagnosis, II:4-S2i, II:4-53 extramedullary hematopoiesis vs., II:4-42i, II:4-43 hemangiopericytoma vs., 1:6-118i, 1:6-119 leukemia vs., 1:6-129 lymphoma vs., 1:6-123, 1:6-126i, 1:6-127 meningioma vs., II:4-S6i meningitis vs., 1:8-20i, 1:8-21 skull and meningeal metastasis vs., II:4-8Oi tuberculosis vs., 1:8-46i, 1:8-47 Nigral degeneration, 1:10-80 Non-Hodgkin lymphoma, meningeal, II:4-27 Nonaneurysmal perimesencephalic subarachnoid hemorrhage. See Subarachnoid hemorrhage, nonaneurysmal perimesencephalic Nonatherosclerotic fusiform vasculopathy, 1:3-18 Nonmeningothelial tumors benign, II:4-64 to II:4-66, II:4-67i differential diagnosis, II:4-64i, II:4-65 malignant, II:4-68 to II:4-70, II:4-71i benign nonmeningothelial tumors vs., II:4-65 differential diagnosis, II:4-68i, II:4-69 Nutritional deficiencies. See Malnutrition

o Oculocerebrocutaneous syndrome, 1:1-109 Oculocerebrorenal syndrome, 1:4-69 Oligodendroglioma, I:6-42 to 1:6-45, 1:6-46i anaplastic, 1:6-46 to 1:6-48, 1:6-49i differential diagnosis, 1:6-46i, 1:6-47 low-grade oligodendroglioma vs., 1:6-43, 1:6-46i, 1:6-47 anaplastic astrocytoma vs., 1:6-17 arteriovenous malformation vs., I:S-4i, 1:5-5

astroblastoma vs., 1:6-SOi, 1:6-51 central neurocytoma vs., 1:6-81 differential diagnosis, 1:6-42i, 1:6-43 ependymoma vs., 1:6-53 ganglioglioma vs., 1:6-67 low grade diffuse astrocytoma vs., 1:6-8i, 1:6-9 meningioangiomatosis vs., 1:1-98, 1:1-98i parenchymal metastases vs., 1:6-141 pleomorphic xanthoastrocytoma vs., 1:6-34i, 1:6-35 supratentorial primitive neuroectodermal tumor vs., 1:6-96i, 1:6-97 Olivary degeneration, hypertrophic, I:10-94 to 1:10-96,1:1O-97i amyotrophic lateral sclerosis vs., 1:10-87 differential diagnosis, 1:10-94i, 1:10-95 Wallerian degeneration vs., 1:10-90i, 1:10-92 Olivopontocerebellar atrophy, hereditary, 1:10-84 Opportunistic infections AIDS-related, 1:8-70 to 1:8-72, 1:8-73i differential diagnosis, 1:8--70i,1:8-71 to 1:8-72 HIVencephalitis cytomegalovirus infection vs., 1:8-71 progressive multifocal leukoencephalopathy vs., 1:8-71 lymphoma toxoplasmosis vs., 1:8-71 tuberculosis vs., 1:8-71 Optic-infundibular dysplasia, 1:1-46i, 1:1-47 Optic nerve atrophy, 1:10-36i, 1:10-37 Optic neuritis, 1:6-31 Organ transplantation, 1:9-9 Osler-Weber-Rendu syndrome. See Hereditary hemorrhagic telangiectasia Osmotic demyelination syndrome, 1:10-42 to 1:1044, 1:10-4Si alcoholic encephalopathy vs., 1:10-21 differential diagnosis, 1:10-42i, 1:10-43 Osteitis deformans. See Paget disease Osteogenesis imperfecta, 1:2-39 Osteomyelitis, 11:4-73 Osteopetrosis, 1I:4-34i, 11:4-35 Osteoporosis, 11:4-73 Osteosarcoma atypical and malignant meningioma vs., 11:460i,II:4-61 benign nonmeningothelial tumors vs., 11:464i, 11:4-65 metastatic neuroblastoma vs., 1:6-105 Otic artery, persistent, 1:4-37 Oxygen, high inspired moyamoya vs., 1:4-42i traumatic subarachnoid hemorrhage vs., 1:2-23

p Pachygyria, 1:1-62 to 1:1-64 differential diagnosis, 1:1-62i, 1:1-63 Pachymengiopathies (thickened dura)

acute subdural hematoma vs., 1:2-10i, 1:2-11 chronic subdural hematoma vs., 1:2-17 mixed subdural hematoma vs., 1:2-21 subacute subdural hematoma vs., 1:2-14i, 1:2-15 Pachymeningitis, hypertrophic, 11:4-30 to 11:4-32, 1I:4-33i differential diagnosis, 1I:4-30i, 11:4-31 intracranial hypotension vs., 11:4-23 meningioma vs., 1I:4-S6i, 11:4-57 Paget disease, 11:4-38 to 11:4-40, 1I:4-4li differential diagnosis, 1I:4-38i, 11:4-39 fibrous dysplasia vs., 11:4-35 skull thickening vs., 1I:4-44i, 11:4-45 Papilloma, choroid plexus, 1:7-9, 1:7-30i, 1:7-31 Paraneoplastic syndromes, 1:6-144 to 1:6-146, 1:6-147i differential diagnosis, 1:6-144i, 1:6-145 multiple system atrophyvs., 1:10-83 Paraphyseal cyst. See Colloid cyst Parasitic infections fungal diseases vs., 1:8-59 miscellaneous, 1:8-54 to 1:8-56, 1:8-S7i differential diagnosis, 1:8-S4i, 1:8-55 neurocysticercosis vs., 1:8-52 Parkinson disease, 1:10-78 to 1:10-80, 1:1O-8li Alzheimer dementia vs., 1:10-63 differential diagnosis, 1:1O-78i, 1:10-79 to 1:10-80 Wilson disease vs., 1:9-72 Parkinsonism -demen tia-amyotrophic lateral sclerosis complex (PDALS),1:10-80 Paroxysmal disorder. See Zellweger syndrome Pars intermedia cyst, 11:2-21 Pelizaeus-Merzbacher disease Canavan disease vs., 1:9-52, 1:9-S2i hypomyelination vs., 1:9-9 metachromatic leukodystrophyvs., 1:9-28i, 1:9-29 preterm hypoxic-ischemic encephalopathy vs., 1:4-68i, 1:4-69 van der Knapp leukoencephalopathy vs., 1:9S8i,I:9-59 Penetrating injury, 1:2-4 to 1:2-5, 1:2-Si differential diagnosis, 1:2-4i Perinatal asphyxia, profound, 1:9-12i, 1:9-13 Peripheral nerve sheath tumor, malignant, 1:6-112 Perivascular spaces, enlarged, 1:7-22 to 1:7-24, 1:7-2Si arteriolosclerosis vs., 1:4-32i, 1:4-33 differential diagnosis, 1:7-22i, 1:7-23 lacunar infarction vs., 1:4-88i, 1:4-89 neurocysticercosis vs., 1:8-51 neuroglial cyst vs., 1:7-20, 1:7-2Oi normal, 1:9-21 Periventricular calcification, neonatal differential diagnosis, 1:8-4i, 1:8-5 heterotopic gray matter vs., 1:1-S8i, 1:1-59 Periventricular halo, normal, 1:4-68i, 1:4-69 Periventricular white matter disease, 11:4-53 Petechial hemorrhage, 1:4-93 Petrosal sinus sampling, 11:2-20, 11:2-25 PHACE syndrome, 1:1-95 Phenobarbital, prolonged use, 1:10-83

Phenytoin, prolonged use, I:1O-82i, 1:10-83 Pick disease. See Frontotemporal dementia Pineal cyst, 1:7-26 to 1:7-28, I:7-29i differential diagnosis, I:7-26i, 1:7-27 pineocytoma vs., I:6-88i, 1:6-89 Pineal tumors, 11:1-21 Pineoblastoma, 1:6-84 to 1:6-86, I:6-87i differential diagnosis, I:6-84i, 1:6-85 germinoma vs., I:6-132i, 1:6-133 pineocytoma vs., I:6-88i, 1:6-89 teratoma vs., I:6-136i, 1:6-137 Pineocytoma, 1:6-88 to 1:6-90, I:6-9li differential diagnosis, I:6-88i, 1:6-89 germinoma vs., 1:6-133 pineal cyst vs., I:7-26i, 1:7-27 pineoblastoma vs., 1:6-85 Pituicytoma, 11:2-36 to 11:2-37, II:2-37i differential diagnosis, 11:2-36, II:2-36i Pituitary abscess, 11:2-29 Pituitary adenoma. See also Pituitary macroadenoma; Pituitary microadenoma colloid cyst vs., I:7-8i, 1:7-9 cystic, Rathke cleft cyst vs., 11:2-17 lymphocytic hypophysitis vs., 11:2-40 to 11:2-41 pituicytoma vs., 11:2-36, II:2-36i Pituitary apoplexy, 11:2-28 to 11:2-30, II:2-3li differential diagnosis, II:2-28i, 11:2-29 Pituitary dwarf, II:2-40i, 11:2-41 Pituitary glands, cystic suprasellar/sellar masses, II:2-16i Pituitary hyperplasia, 11:2-38 to 11:2-39, II:2-39i differential diagnosis, II:2-38i, 11:2-38to 11:2-39 hypothyroidism vs., I:I0-12i, 1:10-13 lymphocytic hypophysitis vs., 11:2-40, II:2-40i pituicytoma vs., 11:2-36, II:2-36i pituitary macroadenoma vs., 11:2-25 pituitary microadenoma vs., II:2-20i, 11:2-21 Pituitary lobe, isolated ectopic posterior, I:I-46i, 1:1-47 Pituitary macroadenoma, 11:2-24to 11:2-26,II:2-27i craniopharyngioma vs., II:2-32i differential diagnosis, II:2-24i, 11:2-25to 11:2-26 hypothyroidism vs., 1:1O-12i, 1:10-13 lymphocytic hypophysitis vs., 11:2-40 to 11:2-41 nonhemorrhagic, pituitary apoplexy vs., 11:2-29 pituitary hyperplasia vs., 11:2-38, II:2-38i Pituitary microadenoma, 11:2-20to 11:2-22,II:2-23i differential diagnosis, II:2-20i, 11:2-21 pituitary hyperplasia vs., 11:2-38, II:2-38i Rathke cleft cyst vs., II:2-16i Pituitary necrosis. See Pituitary apoplexy Pituitary stalk anomalies, 11:2-8 to 11:2-10, 1I:2-11i differential diagnosis, II:2-8i, 11:2-9 Placenta, abruptio, 1:9-46, I:9-46i Plasma cell granuloma. See Pseudotumors, intracranial Pleomorphic xanthoastrocytoma. See Xanthoastrocytoma, pleomorphic PNET. See Neuroectodermal tumor, primitive (PNET)

Pneumocephalus, 11:4-18 to 11:4-20, II:4-2li differential diagnosis, II:4-18i, 11:4-19 Polyarteritis nodosa chronic hypertensive encephalopathyvs., 1:10-34 systemic lupus erythematosus vs., I:4-S4i, 1:4-55 vasculitis vs., I:4-SOi Polycythemia, 1:4-77 Polymicrogyria, 1:1-62 to 1:1-64, I:I-6Si differential diagnosis, I:I-62i, 1:1-63 encephalocraniocutaneous lipomatosis vs., I:1-109 mesial temporal sclerosis vs., I:10-51 Pons, central, ischemia/infarction, I:10-43 Popcorn ball lesions, I:S-24i, 1:5-25 Porencephalic cyst, 1:7-36 to 1:7-38, I:7-39i arachnoid cyst vs., I:7-4i, 1:7-5 chronic cerebral infarction vs., 1:4-84i, 1:4-85 differential diagnosis, 1:7-36i, 1:7-37 ependymal cyst vs., 1:7-35 neuroglial cyst vs., 1:7-20, I:7-20i parasitic infections vs., 1:8-55 schizencephaly vs., I:I-70i, 1:1-71 Post-ictal changes, transient, 1:2-26i, 1:2-27 Posterior reversible encephalopathy (PRES). See also Hypertensive encephalopathy, acute hypoglycemia vs., 1:10-4, I:I0-4i hypotensive cerebral infarction vs., 1:4-92i, 1:4-93 traumatic cerebral edema vs., 1:2-46i, 1:2-47 urea cycle disorders vs., 1:9-46 Postoperative complications. See Surgical defects Postural flattening, 11:4-9 Pre-eclampsia, I:1-51 Prematurity, 1:9-9 Primitive neuroectodermal tumor. See Neuroectodermal tumor, primitive (PNET) Proatlantal intersegmental artery, I:4-36i, 1:4-37 Progressive multifocalleukoencephalopathy acute hypertensive encephalopathy vs., 1:1028i,I:IO-29 gliomatosis cerebri vs., 1:6-27 HIV encephalitis vs., I:8-66i, 1:8-67, 1:8-71 primary eNS lymphoma vs., 1:6-123 radiation injury or chemotherapy vs., 1:10-47 subacute sclerosing panencephalitis vs., 1:8-82, I:8-82i Progressive supranuclear palsy, I:I0-78i, 1:10-79 Prolactinoma. See Pituitary adenoma Protein S deficiency, I:4-62i, 1:4-63 Proteus syndrome, I:I-I08i, 1:1-109 Pseudoaneurysm, 1:3-16 to 1:3-17, I:3-17i differential diagnosis, I:3-16i, 1:3-16 to 1:3-17 non-atherosclerotic fusiform aneurysm vs., 1:320i,1:3-21 saccular aneurysm vs., 1:3-13 Pseudodepression,I:IO-63 Pseudodissection, 1:2-S8i, 1:2-59 Pseudoduplication, pituitary stalk, II:2-8i, 11:2-9 Pseudohypoparathyroidism Fahr disease vs., 1:10-17 hepatic encephalopathy vs., I:10-25

Pseudolaminar necrosis, 1:4-93 "Pseudolesion," ultrasound, 1:7-30i, 1:7-31 Pseudo-pseudohypoparathyroidism, I:10-25 Pseudo-subarachnoid hemorrhage aneurysmal subarachnoid hemorrhage vs., 1:3-4 traumatic subarachnoid hemorrhage vs., 1:222i,I:2-23 Pseudo-TORCH syndrome Canavan disease vs., 1:9-52, 1:9-S2i congenital cytomegalovirus encephalitis vs., 1:8-4i, 1:8-5 metachromatic leukodystrophy vs., 1:9-28i, 1:9-29 Zellweger syndrome vs., 1:9-36, 1:9-36i Pseudotumors, intracranial, 11:4-26 to 11:4-28, II:4-29i differential diagnosis, II:4-26i, 11:4-27 inflammatory, hypertrophic pachymeningitis vs.,11:4-31 meningioma vs., 11:3-33 secondary syndromes, intracranial hypertension vs., 1:10-36 traumatic carotid-cavernous fistula vs., 1:2-62i, 1:2-63 Pseudoxanthoma elasticum, 1:10-34 Pseudo-Zellweger syndrome, 1:9-36, I:9-36i Pyocephalus. See Ventriculitis Pyogenic abscess, I:8-16i Pyruvate metabolism disorders, 1:1-63

Q Q fever, 1:8-62 to 1:8-63

R Radiation injury, 1:10-46 to 1:10-48, I:1O-49i differential diagnosis, 1:10-46i, 1:10-47 to 1:10-48 diffuse axonal injury vs., 1:2-31 Fahr disease vs., 1:1O-16i Ragged-red fibers, myoclonic epilepsy with Fahr disease vs., I:10-17 MELASvs., 1:9-16i, 1:9-17 Ramsay Hunt syndrome, 11:3-20to 11:3-22,1I:3-23i cerebellopontine angle metastases vs., II:3-36i, 11:3-37 differential diagnosis, II:3-20i, 11:3-21 Rasmussen encephalitis, 1:8-42 to 1:8-44 differential diagnosis, I:8-42i, 1:8-43 hemimegalencephaly vs., I:1-74i, 1:1-75 Rathke cleft cyst, 11:2-16 to 11:2-18, II:2-19i craniopharyngioma vs., II:2-32i, 11:2-33 differential diagnosis, II:2-16i, 11:2-17 neurenteric cyst vs., 1:7-40 pituitary apoplexy vs., II:2-28i, 11:2-29 pituitary micro adenoma vs., 11:2-21 Rathke's pouch tumor. See Craniopharyngioma Refsum disease, infantile, 1:9-36, 1:9-36i Renal failure, chronic, 11:4-35

Retinoblastoma, 1:6-133 Rhabdomyosarcoma histiocytosis vs., 11:4-49 sinus pericranii vs., 1:5-21 Rheumatoid arthritis, 11:4-31 Rhombencephalitis,I:1O-95 Rhombencephalosynapsis, 1:1-30 to 1:1-32, I:1-33i congenital vermian hypoplasia vs., I:1-34i, 1:1-35 differential diagnosis, I:1-30i, 1:1-31 dysplastic cerebellar gangliocytoma vs., 1:6-71 partial, 1:1-30i syndromic vs. nonsyndromic, 1:1-31 Rickets, non-accidental trauma vs., 1:2-39 Rickettsial diseases, 1:8-62 to 1:8-63, I:8-63i differential diagnosis, I:8-62i, 1:8-62 to 1:8-63 Rischer-Schinzel syndrome, 1:1-35 Rocky Mountain spotted fever, 1:8-62 to 1:8-63 Rubella, 1:8-11

s Saccular aneurysm, 1:3-12 to 1:3-14, I:3-1Si blood blister-like aneurysm vs., 1:3-22, I:3-22i differential diagnosis, 1:3-12i, 1:3-13 non-atherosclerotic fusiform aneurysm vs., 1:3-21 pseudoaneurysm vs., 1:3-13, 1:3-16, I:3-16i SAH. See Subarachnoid hemorrhage (SAH) Sanfillipo syndrome, 1:9-49 Sarcoid acute subdural hematoma vs., 1:2-11 chronic subdural hematoma vs., I:2-16i, 1:2-17 germinoma vs., 1:6-133 histiocytosis vs., 11:4-49 meningioangiomatosis vs., 1:1-98 meningioma vs., 11:4-57 mixed subdural hematoma vs., I:2-20i, 1:2-21 pilocytic astrocytoma vs., 1:6-31 subacute subdural hematoma vs., 1:2-15 Sarcoidosis cerebellopontine angle metastases vs., II:3-36i, 11:3-37 dysplastic cerebellar gangliocytoma vs., 1:6-71 histiocytosis vs., 11:4-49 hypertrophic olivary degeneration vs., 1:10-95 hypertrophic pachymeningitis vs., II:4-3Oi intracranial pseudotumor vs., II:4-26i, 11:4-27 Lyme disease vs., 1:8-64, I:8-64i lymphocytic hypophysitis vs., II:2-40i, 11:2-41 meningioma vs., 11:3-33 neurocutaneous melanosis vs., I:1-116i, 1:1-117 neurofibromatosis type 2 vs., 1:1-84 Ramsay Hunt syndrome vs., II:3-20i, 11:3-21 rickettsial diseases vs., 1:8-62i, 1:8-63 skull and meningeal metastasis vs., 11:4-81 Sarcoma. See also Ewing sarcoma; Gliosarcoma; Osteosarcoma Karposi, 1:6-113 meningeal

-XXiV···r

atypical and malignant meningioma vs., 1I:4-60i, II:4-61 benign nonmeningothelial tumors vs., 11:4Mi, II:4-65 metastasis vs. acute subdural hematoma, 1:2-lOi rhabdomyosarcoma histiocytosis vs., II:4-49 sinus pericranii vs., 1:5-21 of scalp, 1:6-112i, 1:6-113 Scalp anomalies, vascular, 1:5-20i, 1:5-21 Scheie syndrome, 1:9-49 Schizencephaly, 1:1-70 to 1:1-72, 1:1-73i "clastic," 1:1-70i, 1:1-71 differential diagnosis, 1:1-70i, 1:1-71 porencephalic cyst vs., 1:7-36i, 1:7-37 septooptic dysplasia vs., 1:1-47 severe bilateral, hydranencephaly vs., 1:4-66i, 1:4-67 Schwannoma, 1:6-108 to 1:6-110, 1:6-111i acoustic. See Acoustic schwannoma arachnoid cyst vs., II:3-17 differential diagnosis, 1:6-108i, 1:6-109 epidermoid cyst of cerebellopontine angle cistern vs., II:3-13 facial nerve acoustic schwannoma vs., 1I:3-28i meningioma vs., 1I:3-32i, II:3-33 multiple, neurofibromatosis type 2 vS., 1:1-83 neurenteric cyst vs., 1:7-4Oi neurofibroma vs., 1:6-112 Scoliosis, horizontal gaze palsy with, I:1-55 Seizures, transient post-ictal changes, 1:2-26i, 1:2-27 Sella turcica empty, 1:1O-36i, 1:10-37 giant thrombosed intrasellar aneurysm, II:2-29 Senescence, arteriolosclerosis vs., 1:4-32i, 1:4-33 Senior-Loken syndrome, 1:1-35 Sepsis, 1:9-47 Septooptic dysplasia, 1:1-46 to 1:1-48, 1:1-49i differential diagnosis, 1:1-46i, 1:1-47 holoprosencephaly vs., 1:1-38i, 1:1-39 Septum pellucidum, absent, 1I:1-8i, II:1-9 Shaken baby syndrome. See Trauma, nonaccidental Shear injury, 1:2-4i Shunts acute subdural hematoma vs., 1:2-11 chronic subdural hematoma vs., 1:2-17 histiocytosis vS., II:4-49 mixed subdural hematoma vs., 1:2-21 myeloma vs., II:4-77 subacute subdural hematoma vs., 1:2-15 Sickle cell disease, 1:4-38 to 1:4-40, 1:4-4li differential diagnosis, 1:4-38i, 1:4-39 traumatic intracranial dissection vs., 1:2-56i Siderosis, superficial, 1:3-8 to 1:3-10, 1:3-11i differential diagnosis, 1:3-8i, 1:3-9 Sinus occlusion, dural, II:4-31 Sinus pericranii, 1:5-20 to 1:5-22, 1:5-23i atretic cephalocele vs., 1I:4-12i, II:4-13

differential diagnosis, 1:5-20i, 1:5-21 Sinus thrombosis carotid, 1:2-63 developmental venous anomaly vs., 1:5-16i, 1:5-17 dural, 1:4-96 to 1:4-98, 1:4-99i arteriovenous fistula vs., 1:5-8i, 1:5-9 chronic, subacute subdural hematoma vs., 1:2-14i, 1:2-15 differential diagnosis, 1:4-96i, 1:4-97 drug abuse vs., I:IO-8i, 1:10-9 with venous engorgement, intracranial hypotension vs., 1I:4-22i, II:4-23 hypoglycemia vs., I:IO-4i sagittal, urea cycle disorders vs., 1:9-46, 1:9-46i Sinus tumor, endodermal pineoblastoma vs., 1:6-85 pineocytoma vs., 1:6-89 Sinuses anatomic variants vs. dural sinus thrombosis, 1:4-96i, 1:4-97 fat in, 1:4-96i, 1:4-97 trauma and pneumocephalus, 1I:4-18i Sjogren syndrome chronic hypertensive encephalopathy vs., 1:10-34 hypertrophic pachymeningitis vs., II:4-31 systemic lupus erythematosus vs., 1:4-55 Skull fracture, hemangioma vs., II:4-73 normal, 1I:4-44i, II:4-45 thickening. See Thick skull SLE.See Systemic lupus erythematosus (SLE) "Slit" ventricle syndrome, noncompliant, 1I:1-28i, II:1-29 Sly disease, 1:9-49 Small vessel disease. See Arteriolosclerosis Snedden syndrome, 1:9-29 Solitary fibrous tumor, 1:6-119 Solitary median maxillary central incisor hypodontia vs., 1:1-43 mesiodens vs., 1:1-42i, 1:1-43 Spastic paraplegia infantile-onset hereditary amyotrophic lateral sclerosis vs., 1:10-87 Wallerian degeneration vs., 1:10-91 type 2, hypomyelination vs., 1:9-9 Spinocerebellar ataxia, I:10-83 Spontaneous intracranial hemorrhage, 1:4-12 to 1:4-15 Status epilepticus, 1:10-54 to 1:10-56, I:IO-57i anaplastic astrocytoma vs., 1:6-17 brain death vs., 1:2-55 differential diagnosis, I:IO-54i, 1:10-55 encephalitis vs., 1:8-38i, 1:8-39 glioblastoma multi forme vs., 1:6-21 herpes encephalitis vs., 1:8-34i, 1:8-35 low grade diffuse astrocytoma vs., 1:6-9 MELASvs., 1:9-18 mesial temporal sclerosis vs., I:IO-50i, 1:10-51

microcephaly vs., 1:1-51 paraneoplastic syndromes vs., 1:6-144i, 1:6-145 Status marmoratus gangliosidosis vs., 1:9-24i, 1:9-25 Krabbe disease vs., 1:9-32i, 1:9-33 Steele-Richardson-Olszewski syndrome, 1:10-79 Streptococcal meningitis, group B, 1:8-12 to 1:8-14, 1:8-1Si differential diagnosis, 1:8-12i, 1:8-13 Stresses, external, 1:9-9 Striatonigral degeneration, 1:9-72 Stroke, 1:4-8 to 1:4-107 acute embolic, hypotensive cerebral infarction vs., 1:4-92i, 1:4-93 meningitis vs., 1:8-21 arteriolosclerosis, 1:4-32 to 1:4-35 atherosclerosis extra cranial, 1:4-28 to 1:4-31 intracranial, 1:4-24 to 1:4-27 CADASIL,1:4-62 to 1:4-65 cerebral amyloid disease, 1:4-58 to 1:4-61 cerebral infarction chronic, 1:4-84 to 1:4-87 hypotensive, 1:4-92 to 1:4-95 subacute, 1:4-80 to 1:4-83 cerebral ischemia-infarction, acute, 1:4-76 to 1:4-79 dural sinus thrombosis, 1:4-96 to 1:4-99 hydranencephaly, 1:4-66 to 1:4-67 hypoxic-ischemic encephalopathy preterm, 1:4-68 to 1:4-71 term, 1:4-72 to 1:4-75 intracerebral hematoma, 1:4-8 to 1:4-11 intracranial hemorrhage hypertensive, 1:4-16 to 1:4-19 spontaneous, 1:4-12 to 1:4-15 lacunar infarction, 1:4-88 to 1:4-91 metabolic, hypoglycemia vs., 1:10-4 moyamoya, 1:4-42 to 1:4-45 perinatal,I:I-70i persistent trigeminal artery, 1:4-36 to 1:4-37 primary arteritis of CNS, 1:4-46 to 1:4-49 remote cerebellar hemorrhage, 1:4-20 to 1:4-23 sickle cell disease, 1:4-38 to 1:4-41 systemic lupus erythematosus, 1:4-54 to 1:4-57 vasculitis, 1:4-50 to 1:4-53 venous thrombosis cortical, 1:4-100 to 1:4-103 deep cerebral, 1:4-104 to 1:4-107 Sturge-Weber syndrome, 1:1-94 to 1:1-96, 1:1-97i choroid plexus cyst vs., 1:7-31 developmental venous anomaly vs., 1:5-17 differential diagnosis, 1:1-94i, 1:1-95 to 1:1-96 encephalocraniocutaneous lipomatosis vs., 1:1108i,I:I-109 meningioangiomatosis vs., 1:1-99 Rasmussen encephalitis vs., 1:8-42i Subacute necrotizing encephalomyelopathy. See Leigh syndrome

Subacute sclerosing panencephalitis, 1:8-82 to 1:883,1:8-83i differential diagnosis, 1:8-82i, 1:8-82 to 1:8-83 Subarachnoid cyst. See Arachnoid cyst Subarachnoid hemorrhage (SAH) aneurysmal, 1:3-4 to 1:3-5, 1:3-Si differential diagnosis, 1:3-4, 1:3-4i nonaneurysmal vs., 1:3-4 traumatic vs., 1:2-22i, 1:2-23 meningitis vs., 1:8-20i, 1:8-21 moyamoya vs., 1:4-43 nonaneurysmal aneurysmal vs., 1:3-4 traumatic vs., 1:3-7 nonaneurysmal perimesencephalic, 1:3-6 to 1:3-7, 1:3-7i differential diagnosis, 1:3-6i, 1:3-7 skull and meningeal metastasis vs., 11:4-81 traumatic, 1:2-22 to 1:2-24, 1:2-2Si, 1:3-4i, 1:3-7 differential diagnosis, 1:2-22i, 1:2-23 Subarachnoid spaces, enlarged, 11:1-12 to 11:1-14, II:l-1Si chronic subdural hematoma vs., 1:2-16i differential diagnosis, II:I-12i, 11:1-13 Subcortical injuries, 1:2-34 to 1:2-36, 1:2-37i differential diagnosis, 1:2-34i, 1:2-35 Subdural effusions acute subdural hematoma vs., 1:2-11 chronic subdural hematoma vs., 1:2-17 empyema vs., 1:8-30i, 1:8-31 mixed subdural hematoma vs., 1:2-21 subacute subdural hematoma vs., 1:2-15 Subdural hematoma acute, 1:2-10 to 1:2-12, 1:2-13i differential diagnosis, 1:2-10i, 1:2-11 chronic, 1:2-16 to 1:2-18, 1:2-19i Alzheimer dementia vs., I:I0-62i, 1:10-63 arachnoid cyst vs., 1:7-5 differential diagnosis, 1:2-16i, 1:2-17 empyema vs., 1:8-30i, 1:8-31 hypertrophic pachymeningitis vs., II:4-30i, 11:4-31 intracranial hypotension vs., II:4-22i, 11:4-23 epidural hematoma vs., 1:2-6i, 1:2-7 extramedullary hematopoiesis vs., II:4-42i, 11:4-43 glutaric aciduria type I vs., 1:9-49 metastatic neuroblastoma vs., 1:6-104i, 1:6-105 mixed, 1:2-20 to 1:2-21, 1:2-2li differential diagnosis, 1:2-20i, 1:2-21 skull and meningeal metastasis vs., II:4-80i, 11:4-81 subacute, 1:2-14 to 1:2-15 differential diagnosis, 1:2-14i, 1:2-15 Subependymoma, 1:6-56 to 1:6-58, 1:6-S9i central neurocytoma vs., 1:6-80i, 1:6-81 choroid plexus papilloma vs., 1:6-61 colloid cyst vs., 1:7-9 differential diagnosis, 1:6-S6i, 1:6-57

subependymal giant cell astrocytoma vs., 1:6-39 Subgaleal space, fluid collections, II:4-13 Substance abuse. See Alcoholic encephalopathy; Drug abuse Sulcus trauma, II:4-18i Sulfatide lipidosis. See Leukodystrophy, metachromatic Superficial siderosis, 1:3-8 to 1:3-10, 1:3-11i differential diagnosis, 1:3-8i, 1:3-9 Suprasellar dysgenesis. See Septooptic dysplasia Suprasellar mass, cystic, II:2-16i Surgical defects acute hypertensive encephalopathy vs., 1:10-29 acute subdural hematoma vs., 1:2-11 chronic subdural hematoma vs., 1:2-17 dural thickening, intracranial hypotension vs., II:4-23 hemangioma vs., II:4-73 histiocytosis vs., II:4-49 mixed subdural hematoma vs., 1:2-21 pneumocephalus, II:4-19 skull and meningeal metastasis vs., II:4-81 subacute subdural hematoma vs., 1:2-15 Susac syndrome multiple sclerosis vs., 1:8-74i, 1:8-75 systemic lupus erythematosus vs., 1:4-S4i, 1:4-55 Suture lines, II:4-14i, 11:4-15 Syphilis Alzheimer dementia vs., 1:10-63 chronic hypertensive encephalopathy vs., 1:10-34 histiocytosis vs., II:4-49 H1V encephalitis vs., 1:8-67 non-accidental trauma vs., 1:2-39 systemic lupus erythematosus vs., 1:4-55 traumatic intracranial dissection vs., 1:2-57 Syrinx, 1:2-42i Systemic lupus erythematosus (SLE), 1:4-54 to 1:456,1:4-S7i CADAS1Lvs., 1:4-62i chronic hypertensive encephalopathy vs., I:IO-32i, 1:10-34 differential diagnosis, 1:4-S4i, 1:4-55 Fahr disease vs., 1:10-18 hypertrophic pachymeningitis vs., 11:4-31 vasculitis vs. primary arteritis of CNS, 1:4-47

T Tay-Sachs disease, 1:9-33 Taylor dysplasia dysembryoplastic neuroepithelial tumor vs., 1:6-76i, 1:6-77 tuberous sclerosis complex vs., 1:1-90i, 1:1-91 Telangiectasis capillary. See Capillary telangiectasis hereditary hemorrhagic telangiectasia, 1:1-104 to 1:1-106, I:I-I07i Temporal bone destructive processes, 11:4-49

Teratoid-rhabdoid tumor, atypical, 1:6-100 to 1:6102,1:6-103i astroblastoma vs., 1:6-50 differential diagnosis, 1:6-100i, 1:6-101 ependymoma vs., 1:6-S2i, 1:6-53 medulloblastoma vs., 1:6-92i, 1:6-93 pilocytic astrocytoma vs., 1:6-31 supratentorial primitive neuroectodermal tumor vs., 1:6-97 Teratoma, 1:6-136 to 1:6-137, 1:6-137i atypical teratoid-rhabdoid tumor vs., 1:6-101 dermoid cyst vs., 1:7-12i, 1:7-13 differential diagnosis, 1:6-136i, 1:6-136 to 1:6-137 embryonal carcinoma vs., 1:6-138, 1:6-138i lipoma vs., 1:1-22i, 1:1-23 pineoblastoma vs., 1:6-84i, 1:6-85 pineocytoma vs., 1:6-89 Thalassemia fibrous dysplasia vs., II:4-35 sickle cell disease vs., 1:4-38i, 1:4-39 Thick skull, 11:4-44 to 11:4-46, II:4-47i differential diagnosis, II:4-44i, 11:4-45 normal variation vs., 11:4-45 Paget disease vs., 11:4-39 Thromboembolic stroke, 1:6-140i, 1:6-141 Thrombophlebitis, I:S-8i, 1:5-9 Thrombosis, 1:2-59 Thrombus, non-occlusive, 1:4-25 Thunderclap headache, 1:3-Si Tic douloureux. See Vascular loop compression Tolosa-Hunt syndrome. See Pseudotumors, intracranial Tonsillar ectopia/herniation, 1:1-8i, 1:1-9 cerebellar. See Chiari type 1 TORCH infections group B streptococcal meningitis vs., 1:8-13 metachromatic leukodystrophy vs., 1:9-29 microcephaly vs., I: 1-5 1 tuberous sclerosis complex vs., 1:1-91 Toxoplasmosis in AIDS, 1:8-70i congenital cytomegalovirus encephalitis vs., 1:8-4i, 1:8-5 herpes vs., 1:8-10i, 1:8-11 H1V infections vs., 1:8-8, 1:8-8i fungal diseases vs., 1:8-59 HIV encephalitis vs., 1:8-67 lymphoma vs., 1:6-122i, 1:6-123, 1:8-71 Transplantation, organ, 1:9-9 Transverse sinus. congenital hypoplasia, 1:4-101 Trauma, 1:2-4 to 1:2-63 brain death, 1:2-54 to 1:2-55 carotid-cavernous fistula, 1:2-62 to 1:2-63 cerebral contusion, 1:2-26 to 1:2-29 cerebral edema, 1:2-46 to 1:2-49 cerebral ischemia, 1:2-50 to 1:2-53 chronic, alcoholic encephalopathy vs., 1:10-21 diffuse axonal injury, 1:2-30 to 1:2-33 epidural hematoma, 1:2-6 to 1:2-9 extracranial dissection, 1:2-58 to 1:2-61

intracranial dissection, 1:2-56 to 1:2-57 herniation syndromes, 1:2-42 to 1:2-45 penetrating injury vs., 1:2-4i missile and penetrating injury, 1:2-4 to 1:2-5 non-accidental, 1:2-38 to 1:2-40, 1:2-4li differential diagnosis, 1:2-38i, 1:2-39 enlarged subarachnoid spaces vs., II:I-12i, lI:1-13 glutaric aciduria type 1vs., 1:9-49 white matter lacerations vs. citrobacter meningitis, 1:8-16i, 1:8-17 pneumocephalus, II:4-18i, II:4-19 subarachnoid hemorrhage, 1:2-22 to 1:2-25, 1:3-4i, 1:3-7 subcortical injury, 1:2-34 to 1:2-37 subdural hematomas, 1:2-10 to 1:2-21 Trigeminal artery, persistent, 1:4-36 to 1:4-37, 1:4-37i differential diagnosis, 1:4-36i, 1:4-36 to 1:4-37 Trigeminal neuralgia. See Vascular loop compression Trigonal blush, 1:4-68i Tuber cinereum hamartoma. See Hamartoma, tuber cinereum Tuberculosis, 1:8-46 to 1:8-48, 1:8-48i differential diagnosis, 1:8-46i, 1:8-47 dysplastic cerebellar gangliocytoma vs., 1:6-71 fungal diseases vs., 1:8-58i, 1:8-59 histiocytosis vs., II:4-49 HIV encephalitis vs., 1:8-67 hypertrophic olivary degeneration vs., 1:10-95 lymphoma vs., 1:8-71 meningioangiomatosis vs., 1:1-98 meningioma vs., II:4-57 neurocysticercosis vs., 1:8-50i, 1:8-51 neurofibromatosis type 2 vs., 1:1-84 Sturge-Weber syndrome vs., 1:1-96 traumatic intracranial dissection vs., 1:2-57 Tuberous sclerosis complex, 1:1-90 to 1:1-92, 1:1-93i differential diagnosis, 1:1-90i, 1:1-91 dysplastic cerebellar gangliocytoma vs., 1:670i,l:6-71 glutaric aciduria type 1vs., 1:9-48i, 1:9-49 hemimegalencephaly vs., 1:1-75 heterotopic gray matter vs., 1:1-58i, 1:1-59 Typhus, 1:8-62 to 1:8-63

u Ultrasound "pseudolesion," 1:7-30i, 1:7-31 Urea cycle disorders, 1:9-46 to 1:9-47, 1:9-47i differential diagnosis, 1:9-46i, 1:9-46 to 1:9-47 hypoglycemia vs., 1:10-4, 1:1O-4i Uremia, 1:2-47

v van der Knapp leukoencephalopathies, 1:9-60, 1:9-6li

1:9-58 to

Alexander disease vs., 1:9-54i, 1:9-55 differential diagnosis, 1:9-58i, 1:9-59 Varadi syndrome, 1:1-35 Vascular dementia frontotemporal dementia vs., I:I0-70i, 1:10-71 intravascular lymphoma vs., 1:6-126i, 1:6-127 normal brain aging vs., I:I0-58i, 1:10-60 radiation injury or chemotherapy vs., 1:10-47 traumatic cerebral ischemia vs., 1:2-50i, 1:2-51 Vascular grooves, II:4-14i, II:4-15 Vascular loop compression, II:3-24 to II:3-26, II:3-27i differential diagnosis, II:3-24i, II:3-25 Vascular malformations, 1:5-4 to 1:5-29 aqueductal stenosis vs., II:I-20i, II:1-21 arteriovenous, 1:5-4 to 1:5-7 capillary telangiectasis, 1:5-28 to 1:5-29 cavernous, 1:5-24 to 1:5-27 congenital, hypomyelination vs., 1:9-8i, 1:9-9 developmental venous anomaly, 1:5-16 to 1:5-19 drug abuse vs., 1:10-9 dural arteriovenous fistula, 1:5-8 to 1:5-11 intracerebral hematoma vs., 1:4-8i, 1:4-9 mixed, developmental venous anomaly vs., 1:516i,l:5-17 multiple cerebral amyloid disease vs., 1:4-58i, 1:4-59 hereditary hemorrhagic telangiectasia vs., I:I-I04i,l:1-105 presenting in childhood, 1:5-12i, 1:5-13 prominent ependymal veins vs. ventriculitis, 1:8-28i, 1:8-29 remote cerebellar hemorrhage vs., 1:4-21 scalp, neurofibroma vs., 1:6-112i, 1:6-113 sinus pericranii, 1:5-20 to 1:5-23 spinal, traumatic subarachnoid hemorrhage vs., 1:2-23 spontaneous intracranial hemorrhage vs., 1:412i,l:4-13 Sturge-Weber syndrome vs., 1:1-96 vein of Galen, 1:5-12 to 1:5-15 Vascular neoplasms, 1:5-16i, 1:5-17 Vascular neurocutaneous syndrome hemangioblastoma vs., 1:6-115 von Hippel Lindau syndrome vs., 1:1-87 Vasculitis, 1:4-50 to 1:4-52, 1:4-53i autoimmune-mediated, 1:8-79 CADASILvs., 1:4-62i differential diagnosis, 1:4-50i, 1:4-51 gliomatosis cerebri vs., 1:6-26i, 1:6-27 hypotensive cerebral infarction vs., 1:4-92i, 1:4-93 intracranial atherosclerosis vs., 1:4-24i, 1:4-25 intravascular lymphoma vs., 1:6-126i, 1:6-127 Lyme disease vs., 1:8-64, 1:8-64i multiple sclerosis vs., 1:8-74i, 1:8-75 radiation injury or chemotherapy vs., 1:10-48 rickettsial diseases vs., 1:8-62, 1:8-62i sickle cell disease vs., 1:4-39 status epilepticus vs., 1:10-55

~

xxviii I

systemic lupus erythematosus, primary CNS arteritis vs., 1:4-47 traumatic intracranial dissection vs., 1:2-57 Vasculopathy intracerebral hematoma vs., 1:4-9 nonatherosclerotic fusiform, 1:3-18 Vasospasm arterial primary arteritis of CNS vs., 1:4-47 vasculitis vs., 1:4-51 blood blister-like aneurysm vs., 1:3-22, 1:3-22i extra cranial atherosclerosis vs., 1:4-29 intracranial atherosclerosis vs., 1:4-24i, 1:4-25 subarachnoid-induced, 1:2-51 traumatic extracranial dissection vs., 1:2-59 traumatic intracranial dissection vs., 1:2-S6i, 1:2-57 Vein of Galen malformation, 1:5-12 to 1:5-14, I:S-1Si differential diagnosis, I:S-12i, 1:5-13 Vein of Labbe infarction, 1:4-12i Velocardiofacial syndrome, 1:9-20i, 1:9-21 Velum interpositum, normal cistern, 11:1-10,1I:1-1Oi Venous angioma, posterior fossa, 1I:3-24i, 11:3-25 Venous congestion, II:2-39 Venous hemorrhage, perimesencephalic, 1:2-23 Venous infarction, 1:4-80i, 1:4-81 Venous lake, II:4-15 Venous occlusion hypertensive intracranial hemorrhage vs., 1:4-16i traumatic cerebral edema vs., 1:2-47 Venous thrombosis cerebral amyloid disease vs., 1:4-S8i cortical, 1:4-100 to 1:4-102, 1:4-103i differential diagnosis, 1:4-100i, 1:4-101 deep cerebral, 1:4-104 to 1:4-106, 1:4-107i differential diagnosis, 1:4-104i, 1:4-105 to 1:4-106 hypoglycemia vs., 1:10-4, l:lO-4i Venous varix, 1:5-17 Ventricular empyema. See Ventriculitis Ventricular enlargement 2° parenchymal loss, 11:116i, II:1-17 Ventriculitis, 1:8-28 to 1:8-29, 1:8-29i differential diagnosis, 1:8-28i, 1:8-28 to 1:8-29 diffuse, vs. HIV encephalitis, 1:8-67 Ventriculo-peritoneal shunt, chronic, 1:1-8i, 1:1-9 Ventriculomegaly, long-standing overt, II:1-17 Ventrobasilar insufficiency, chronic, 1:10-83 Vermian hypoplasia, congenital, 1:1-34 to 1:1-36, 1:1-37i Dandy Walker spectrum vs., 1:1-27 differential diagnosis, 1:1-34i, 1:1-35 rhombencephalosynapsis vs., 1:1-31 Vertebrobasilar dolichoectasia non-atherosclerotic fusiform aneurysm vs., 1:3-21 vascular loop compression vs., 1I:3-24i, II:3-25 Vessel loop, 1:3-12i, 1:3-13 Vessel walls, microcalcification, 1:4-77 Villous hypertrophy, 1:6-62

Virchow-Robin spaces. See Perivascular spaces, enlarged Vitamin B12 deficiency, 1:10-62i, 1:10-63 von Hippel Lindau syndrome, 1:1-86 to 1:1-88, 1:1-89i differential diagnosis, 1:1-86i, 1:1-87 hemangioblastoma vs., 1:6-114i, 1:6-115 hereditary hemorrhagic telangiectasia vs., 1:1-104i von Recklinghausen disease. See Neurofibromatosis type 1 '

w Walker-Warburg syndrome, 1:1-16 Wallerian degeneration, 1:10-90 to 1:10-92, 1:10-93i amyotrophic lateral sclerosis vs., 1:10-86i, 1:10-87 differential diagnosis, 1:10-90i, 1:10-91 to 1:10-92 hypertrophic olivary degeneration vs., 1:1094i,I:10-95 Wegener granulomatosis neurocutaneous melanosis vs., I:1-117 systemic lupus erythematosus vs., 1:4-55 Wernicke encephalopathy. See Alcoholic encephalopathy West nile virus. See Encephalitis (Miscellaneous) White matter age-related changes vs. arteriolosclerosis, 1:432i,I:4-33 periventricular disease, neurosarcoid vs., 11:4-53 vanishing, 1:9-42i, 1:9-43 White matter disease with lactate, 1:9-38i, 1:9-39 Wilson disease, 1:9-70 to 1:9-72, 1:9-73i alcoholic encephalopathy vs., 1:10-21 amyotrophic lateral sclerosis vs., 1:10-87 carbon monoxide poisoning vs., 1:10-38i, 1:10-39 Creutzfeldt-]akob disease vs., 1:10-74i, 1:10-75 differential diagnosis, 1:9-70i, 1:9-71 to 1:9-72 hepatic encephalopathy vs., 1:10-25 Huntington disease vs., 1:9-66i, 1:9-67 Leigh syndrome vs., 1:9-13 MELASvs., 1:9-16i, 1:9-17 osmotic demyelination syndrome vs., 1:10-43 Wallerian degeneration vs., 1:10-92 Wyburn-Mason syndrome hereditary hemorrhagic telangiectasia vs., 1:1-105 Sturge-Weber syndrome vs., 1:1-95

x Xanthoastrocytoma, pleomorphic, 1:6-34 to 1:6-36, 1:6-37i desmoplastic infantile ganglioglioma vs., 1:674i,I:6-75 differential diagnosis, 1:6-34i, 1:6-35 dysembryoplastic neuroepithelial tumor vs., 1:6-76i, 1:6-77

ependymoma vs., 1:6-53 ganglioglioma vs., 1:6-66i, 1:6-67 oligodendroglioma vs., 1:6-43 schwannoma vs., 1:6-108i, 1:6-109 Xanthogranuloma choroid plexus papilloma vs., 1:6-61 colloid cyst vs., I:7-8i, 1:7-9

y Yolk sac tumor embryonal carcinoma vs., 1:6-138 germinoma vs., I:6-132i teratoma vs., I:6-136i, 1:6-137

z Zellweger syndrome, 1:9-36 to 1:9-37, I:9-37i differential diagnosis, 1:9-36, I:9-36i heterotopic gray matter vs., I:1-59 pachygyria vs., I:1-62i, 1:1-63 polymicrogyria vs., I:1-62i, 1:1-63