Intracranial Arteriovenous Malformations Edited by
Philip E. Stieg
Weill Medical College of Cornell University New Yo...
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Intracranial Arteriovenous Malformations Edited by
Philip E. Stieg
Weill Medical College of Cornell University New York, New York, U.S.A.
H. Hunt Batjer
Feinberg School of Medicine Northwestern University Chicago, Illinois, U.S.A.
Duke Samson
University of Texas Southwestern Medical Center Dallas, Texas, U.S.A.
New York London
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Informa Healthcare USA, Inc. 270 Madison Avenue New York, NY 10016 © 2007 by Informa Healthcare USA, Inc. Informa Healthcare is an Informa business No claim to original U.S. Government works Printed in the United States of America on acid‑free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number‑10: 0‑8247‑0993‑4 (Hardcover) International Standard Book Number‑13: 978‑0‑8247‑0993‑8 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any informa‑ tion storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http:// www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, 978‑750‑8400. CCC is a not‑for‑profit organization that provides licenses and registration for a variety of users. For orga‑ nizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Informa Web site at www.informa.com and the Informa Healthcare Web site at www.informahealthcare.com
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Preface
The important thing in science is not so much to obtain new facts as to discover new ways of thinking about them. —Sir William Bragg (1862–1942)
During the past twenty years, great strides have been made in the management of intracranial arteriovenous malformations. This success has resulted not so much from greater understanding of the pathophysiology or anatomy of the lesions as it has from new technologies applied in their management. The greatest advances have been multifactorial. Endovascular therapy, which improves our ability to resect complex lesions, is probably the most important cause for the reduction in the incidence of postoperative hemorrhage. Intraoperative angiography, which allows confirmation of complete resection, again reduces the incidence of postoperative hemorrhage. Improvements in surgical instrumentation, such as microscopes and the bipolar cautery, have made microsurgery more effective. Improved surgical approaches have allowed the successful resection of more complex lesions. Surgical planning has been facilitated by more sophisticated preoperative imaging, including angiography, magnetic resonance imaging, magnetic resonance angiography, computed tomography angiography, and functional magnetic resonance imaging. Stereotactic radiosurgery has provided an avenue for the treatment of deep, small arteriovenous malformations. The perioperative care of our patients has been enhanced with advances in anesthesia and the creation of neurointensive care units. Each of these parameters is thoroughly reviewed in this volume, and, more importantly, all are coordinated into a cohesive management scheme. In this text we seek to document current understanding of the management of intracranial arteriovenous malformations and to define advances in the field. We begin with a review of the anatomy, classification, and pathophysiology of arteriovenous malformations. We then progress to detailed discussion of diagnosis and management. Preoperative evaluation with diagnostic and functional imaging as well as surgical planning is reviewed in detail. We conclude with consideration of future directions for treatment. A review of these chapters will enable the reader to provide the patient with better preoperative risk analyses, a thorough review of the treatment options and their risks, and a general outline of a specific treatment regimen. Selecting patients for therapy or not, and then selecting the appropriate therapy are the greatest challenges presented to the treating physician. Once treatment is recommended, integration of the complex modalities is essential. The authors of these chapters provide the reader with such insight. Each arteriovenous malformation presents clinical challenges on the basis of its size and location. These issues, which play a large part in our success in treating these lesions, are dealt with in individual chapters. The authors thoroughly discuss the surgical nuances of arteriovenous malformations in specific locations. The application of endovascular therapy as curative or, more commonly, as an adjuvant therapy is reviewed. Current understanding of the limits and complications of stereotactic radiosurgery, as well as the promise of future applications, is presented. Risks and benefits for each form of therapy are fully detailed. Finally, the application of each treatment modality is integrated into treatment algorithms based on history, location, size, and risk benefit analysis. It is the intent of the editors and authors to provide the reader with a framework for understanding and treating these complex lesions. This volume is designed for all individuals involved in the management of intracranial arteriovenous malformations. It is the only text that comprehensively reviews the subject. The authors have provided an extensive and thorough discussion of the scientific data from the literature in a prose that is easily readable and understandable for clinical application. The reader is offered an integrated system, including medical management, anesthesia, radiation therapy, neuroradiology, endovascular therapy, and microsurgery, for the management of one
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of the most challenging lesions presented to physicians involved in the care of patients with neurologic disease. We are indebted to the members of our families for the time they gave up with us so that this volume could be created. We thank Mr. Robert Gallavan and Ms. Jessica Kazmier at our institutions for their dedicated assistance. We are grateful for the skillful editorial guidance of Ms. Arlene Stolper Simon, who spent countless hours editing chapters and working with the authors. Finally, we acknowledge the support and direction provided by our Informa Healthcare USA team, Ms. Vanessa Sanchez and Mr. Alan Kaplan. Philip E. Stieg H. Hunt Batjer Duke Samson
Contents
Preface . . . . iii Contributors . . . .
xiii
SECTION I: ANATOMY AND PHYSIOLOGY 1. Surgical Anatomy 1 Helder Tedeschi, Evandro de Oliveira, Wen Hung Tzu, and Albert L. Rhoton, Jr. Introduction . . . . . . 1 Frontal Lobe AVMs . . . . . . 1 Parietal Lobe AVMs . . . . . . 2 Temporal Lobe AVMs . . . . . . 3 Occipital Lobe AVMs . . . . . . 5 Mediobasal Temporal Lobe AVMs . . . . . . 5 Interhemispheric Parafalcine and Callosal Region AVMs . . . . . . 9 Basal Ganglia Region AVMs . . . . . . 11 AVMs of the Posterior Fossa . . . . . . 18 References . . . . . . 19
2. Pathology and Genetic Factors 21 Ronald F. Moussa, John H. Wong, and Issam A. Awad Pathology . . . . . . 21 Genetic Factors . . . . . . 25 References . . . . . . 27
3. Hemodynamic Properties Michael Morgan
31
Introduction . . . . . . 31 Hemodynamic Effect within the Interstices of an AVM . . . . . . 32 Hemodynamic Effect on Cerebral Blood Vessels in the Presence of an AVM . . . . . . 33 Hemodynamic Effect on the Microcirculation of the Brain Associated with an AVM . . . . . . 37 Autoregulation and Reactivity to Changes in PaCO2 . . . . . . 38 Hemodynamic Effect on Cerebral Blood Vessels at the Time of AVM Ablation . . . . . . 40 Hemodynamic Effect on the Brain at the Time of AVM Ablation . . . . . . 40 Arterio-Capillary-Venous Hypertensive Syndromes . . . . . . 41 References . . . . . . 42
4. Use of Modeling for the Study of Cerebral Arteriovenous Malformations William L. Young, Erzhen Gao, George J. Hademenos, and Tarik F. Massoud Introduction . . . . . . 49 Importance of Modeling for AVMs . . . . . . 49 Specific Modeling Attempts–Model Construction . . . . . Model Applications . . . . . . 55 Long-Term Objectives of Computational Modeling . . . . Animal Modeling . . . . . . 59 Summary . . . . . . 61 Appendix 1. Description of a Computational AVM Model Appendix 2. Mathematical and Computational Approach Appendix 3. Vascular Stress . . . . . . 67 References . . . . . . 68
49
. 50 . . 58
. . . . . . 61 . . . . . . 63
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SECTION II: CLINICAL PRESENTATION AND DIAGNOSTIC EVALUATION 5. Natural History 73 Bernard R. Bendok, Christopher Eddleman, Joseph G. Adel, M. Jafer Ali, H. Hunt Batjer, and Stephen L. Ondra Introduction . . . . . . 73 Presenting Symptoms . . . . . . 73 Morbidity and Mortality Related to Hemorrhage . . . . . . 75 AVMs in the Gravid Woman . . . . . . 77 Anatomical Factors Influencing the Natural History of AVMs . . . . . . 77 Spontaneous Regression . . . . . . 78 References . . . . . . 79
6. Classification and Grading Systems 81 Kai U. Frerichs, Philip E. Stieg, and Robert M. Friedlander Introduction . . . . . . 81 Classification and Grading Parameters . . . . . . 81 Grading Scales . . . . . . 84 Discussion . . . . . . 91 References . . . . . . 92
7. Radiographic Diagnosis 95 R. Anthony Murray and Eric J. Russell Introduction . . . . . . 95 Epidemiology and Natural History . . . . . . 95 Therapeutic Options and Classification . . . . . . 96 Computed Tomography . . . . . . 97 Magnetic Resonance Imaging and Angiography . . . . . . 98 Conventional Angiography . . . . . . 105 Angiographically Occult AVMs . . . . . . 109 Conclusion . . . . . . 109 References . . . . . . 110
8. Functional Evaluation and Diagnosis 115 Shervin R. Dashti, Jeffrey L. Sunshine, Robert W. Tarr, and Warren R. Selman Introduction . . . . . . 115 Parenchymal Function . . . . . . 115 Relative Perfusion . . . . . . 118 Blood Pressure and Flow Analysis . . . . . . 119 Invasive Provocation . . . . . . 120 Conclusion . . . . . . 120 References . . . . . . 120
SECTION III: BASIC CONSIDERATIONS 9. Decision Analysis for Asymptomatic Lesions James McInerney and Robert E. Harbaugh
123
Introduction . . . . . . 123 Decision Analysis and Markov Modeling for the Treatment of Asymptomatic AVMs . . . . . . 124 Data Collection . . . . . . 127 Sensitivity Analysis . . . . . . 130 Conclusion . . . . . . 132 References . . . . . . 133
10. Multimodality Therapy: Treatment Algorithms 135 Philip E. Stieg, Vallabh Janardhan, and Howard A. Riina Introduction . . . . . . 135 Pathology of the AVM . . . . . . 135 Location of the AVM . . . . . . 136 Natural History . . . . . . 136
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Patient Characteristics . . . . . . 137 Diagnostic Imaging . . . . . . 137 Management Options . . . . . . 138 Decision Analysis for the Management of Unruptured AVMs . . . . . . 140 Decision Analysis for the Management of Ruptured AVMs . . . . . . 140 Conclusions . . . . . . 141 References . . . . . . 141
11. Surgical Principles 145 Christopher C. Getch, Christopher Eddleman, Melanie K. Swope, and H. Hunt Batjer Introduction . . . . . . 145 Preoperative Imaging . . . . . . 145 Embolization . . . . . . 149 Anesthesia . . . . . . 149 Neurosurgical Emergency: Intracranial Hemorrhage Related to AVM Rupture . . . . . . 151 Surgical Resection . . . . . . 152 Conclusion . . . . . . 157 References . . . . . . 157
12. Endovascular Principles 159 Charles J. Prestigiacomo and John Pile-Spellman Introduction . . . . . . 159 Historical Perspective . . . . . . 159 Role of Endovascular Therapy . . . . . . 160 Hemodynamic Considerations and Staging of Embolization . . . . . . 165 Anesthetic Considerations and Monitoring . . . . . . 166 Functional Testing . . . . . . 167 Equipment . . . . . . 168 Strategy and Technique . . . . . . 171 Outcomes . . . . . . 172 Complications and Complication Avoidance . . . . . . 172 Future Directions . . . . . . 174 References . . . . . . 174
13. Radiosurgical Principles 177 Susan C. Pannullo, Jordan Abbott, and Robert Allbright Introduction . . . . . . 177 History of Radiosurgery for AVMs . . . . . . 177 Radiobiology of AVM Radiosurgery . . . . . . 177 Pathologic Changes of AVMs After Radiosurgery . . . . . . 178 Radiosurgery Platforms . . . . . . 178 Stereotactic Radiosurgery Technique . . . . . . 178 Evaluation of Treatment Response . . . . . . 182 Complications . . . . . . 183 Combined Modality Management of AVMs . . . . . . 183 Single Fraction Versus Fractionated Therapy . . . . . . 183 Future Directions for AVM Radiosurgery . . . . . . 184 References . . . . . . 184
14. Combined Therapy: The Team Approach 189 C. Michael Cawley, III, Harry J. Cloft, Nelson M. Oyesiku, and Daniel L. Barrow Introduction . . . . . . 189 Goals of Therapy . . . . . . 189 Therapeutic Strategies . . . . . . 190 Remedies for Palliation . . . . . . 196 Conclusion . . . . . . 198 References . . . . . . 198
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SECTION IV: THERAPEUTIC MANAGEMENT 15. Anesthetic Considerations 201 Tomoki Hashimoto and William L. Young General Considerations . . . . . . 201 Cerebral Circulatory Changes in Patients with AVMs . . . . . . 202 Anesthetic Management During Surgery . . . . . . 203 Anesthetic Management During Interventional Neuroradiologic Procedures . . . . . . 206 References . . . . . . 211
16. Supratentorial Lobar Arteriovenous Malformations 215 John E. Wanebo, Jeffrey G. Ojemann, and Ralph G. Dacey, Jr. Introduction . . . . . . 215 General Considerations . . . . . . 215 Frontal Lobe AVMs . . . . . . 228 Temporal Lobe AVMs . . . . . . 231 Parietal Lobe AVMs . . . . . . 233 Occipital Lobe AVMs . . . . . . 235 References . . . . . . 237
17. Perisylvian Arteriovenous Malformations Harold J. Pikus and Roberto C. Heros
243
Introduction . . . . . . 243 Presentation . . . . . . 244 Diagnostic Studies . . . . . . 244 Management . . . . . . 246 Results . . . . . . 254 References . . . . . . 254
18. Supratentorial Periventricular Arteriovenous Malformations Charles J. Prestigiacomo and Robert A. Solomon
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Introduction . . . . . . 259 Epidemiology, Presentation, and Natural History . . . . . . 259 Anatomical Considerations . . . . . . 260 Evaluation of Patients with Periventricular AVMs . . . . . . 262 Therapeutic Options . . . . . . 263 Surgical Approaches . . . . . . 264 Conclusions . . . . . . 269 References . . . . . . 270
19. Corpus Callosum Arteriovenous Malformations 273 Vallabh Janardhan, Howard A. Riina, and Philip E. Stieg Introduction . . . . . . 273 Epidemiology . . . . . . 273 Anatomy of the Corpus Callosum . . . . . . 274 Functions of the Corpus Callosum and Callosal Syndromes . . . . . . 275 Clinical Presentation . . . . . . 275 Classification/Grading Systems for AVMs of the Corpus Callosum . . . . . . 277 Treatment . . . . . . 278 Summary . . . . . . 282 References . . . . . . 283
20. Arteriovenous Malformations of the Cerebellar Vermis and Hemispheres 285 Andrew D. Fine, Curtis L. Beauregard, and Arthur L. Day Introduction . . . . . . 285 Cerebellar Surface Anatomy and Vascular Supply . . . . . . 285 Cerebellar Functional Anatomy . . . . . . 288 Clinical Presentation . . . . . . 289 Classification and Risk Stratification . . . . . . 289
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Treatment . . . . . . 290 Summary . . . . . . 295 References . . . . . . 296
21. Infratentorial Cerebellopontine Angle Arteriovenous Malformations Giuseppe Lanzino and L. Nelson Hopkins
299
Introduction . . . . . . 299 Regional Anatomy . . . . . . 299 Clinical Presentation . . . . . . 302 Diagnosis . . . . . . 303 Therapy . . . . . . 304 Surgical Technique . . . . . . 305 Complications . . . . . . 310 Summary . . . . . . 311 References . . . . . . 312
22. Brainstem Arteriovenous Malformations Steven D. Chang and Gary K. Steinberg
315
Introduction . . . . . . 315 Natural History . . . . . . 315 Classification of Brainstem AVMs . . . . . . 315 Arterial Supply and Venous Drainage . . . . . . 316 Clinical Presentation . . . . . . 316 Indications and Contraindications for Surgery . . . . . . 316 Potential Risks . . . . . . 317 Preoperative Preparation . . . . . . 317 Anesthetic Technique . . . . . . 317 Surgical Approaches and Positioning . . . . . . 319 Closure Techniques and Postoperative Management . . . . . . 323 Special Perioperative Equipment/Techniques . . . . . . 323 Stereotactic Radiosurgery . . . . . . 324 Embolization . . . . . . 324 Clinical Outcome . . . . . . 326 Complications and Complication Avoidance . . . . . . 327 Summary . . . . . . 327 References . . . . . . 327
23. Intraoperative and Postoperative Angiography 329 Michael A. Lefkowitz, Fernando Vinuela, and Neil Martin Introduction . . . . . . 329 Intraoperative Angiography . . . . . . 329 Intraoperative Embolization . . . . . . 336 Postoperative Angiography . . . . . . 337 References . . . . . . 341
24. Associated Aneurysms 343 Bernard R. Bendok, Christopher C. Getch, and H. Hunt Batjer Introduction . . . . . . 343 Classification . . . . . . 343 Incidence . . . . . . 343 Pathophysiology . . . . . . 344 Natural History . . . . . . 344 Management . . . . . . 344 Conclusions . . . . . . 348 References . . . . . . 349
25. Arteriovenous Malformations in Pregnancy 351 Eli M. Baron, Sumon Bhattacharjee, Robert Wienecke, and Christopher M. Loftus Introduction . . . . . . 351 Epidemiology . . . . . . 351 Physiologic Changes Associated with Pregnancy . . . . . . 351 Radiologic Diagnosis of AVM in Pregnancy . . . . . . 352
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Medical Management . . . . . . 353 Surgical Management . . . . . . 354 Embolization and Radiosurgical Procedures . . . . . . 355 Ethical Considerations . . . . . . 355 Conclusions . . . . . . 355 References . . . . . . 356
26. Diagnosis and Management of Pediatric Arteriovenous Malformations Jeffrey P. Greenfield and Mark M. Souweidane Introduction . . . . . . 359 Epidemiology . . . . . . 359 Developmental Biology of AVMs in Children . . . . . . 359 Natural History . . . . . . 360 Presentation and Evaluation of AVMs in Children . . . . . . 361 Considerations for Intervention . . . . . . 363 Timing of Intervention . . . . . . 363 Preoperative Embolization . . . . . . 364 Stereotactic Radiosurgery . . . . . . 365 Surgical Technique . . . . . . 366 Complications Avoidance . . . . . . 366 Outcomes . . . . . . 367 References . . . . . . 368
27. Management of Residual Arteriovenous Malformations Daniel P. McCarthy, Stefan A. Mindea, Bernard R. Bendok, Christopher C. Getch, and H. Hunt Batjer
371
Introduction . . . . . . 371 Residual Malformations after Endovascular Embolization . . . . . . 372 Residual Malformations after Radiosurgery . . . . . . 375 Residual Malformations after Microsurgical Resection . . . . . . 378 Conclusion . . . . . . 380 References . . . . . . 380
SECTION V: SPECIAL PROBLEMS 28. Critical Care Management 383 Mark R. Harrigan and B. Gregory Thompson Introduction . . . . . . 383 Neurological Monitoring and Imaging . . . . . . 383 Perioperative Cerebral Edema . . . . . . 384 Cardiovascular Management . . . . . . 386 Pulmonary Management . . . . . . 387 Fluids and Electrolytes . . . . . . 387 Nutrition and Diabetic Management . . . . . . 388 Infectious Disease . . . . . . 389 Sedation and Analgesia . . . . . . 389 Glucocorticoids . . . . . . 390 Thrombotic Complications . . . . . . 390 Seizure Prophylaxis and Treatment . . . . . . 390 References . . . . . . 390
29. Surgical Complications 393 Sean D. Lavine and Steven L. Giannotta Introduction . . . . . . 393 Preoperative Considerations . . . . . . 393 Intraoperative Considerations . . . . . . 395 Postoperative Considerations . . . . . . 400 Summary . . . . . . 403 References . . . . . . 403
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30. Endovascular Therapy: Indications, Complications, and Outcome Adnan H. Siddiqui, P. Roc Chen, and Robert H. Rosenwasser
407
Introduction . . . . . . 407 Cerebrovascular Malformations . . . . . . 407 Natural History of AVMs . . . . . . 408 Indications for Treatment . . . . . . 408 Management Principles for Endovascular Treatment . . . . . . 417 Complications: Avoidance and Management . . . . . . 422 The Jefferson Hospital for Neuroscience Experience . . . . . . 424 Summary . . . . . . 424 References . . . . . . 424
31. Radiosurgical Complications 429 Alan C. Hartford, Paul Chapman, Philip E. Stieg, Christopher S. Ogilvy, and Jay S. Loeffler Historical Background . . . . . . 429 Risk of Hemorrhage . . . . . . 430 Transient Effects on Normal Brain Tissue . . . . . . 434 Radionecrosis and Other Long-Term Effects . . . . . . 440 Conclusions . . . . . . 446 References . . . . . . 447
SECTION VI: FUTURE CONSIDERATIONS 32. Endovascular Techniques 451 Harry J. Cloft and Jacques E. Dion Introduction . . . . . . 451 Microcatheters . . . . . . 452 Embolic Materials . . . . . . 452 Reduction of Complications . . . . . . 454 Conclusion . . . . . . 455 References . . . . . . 455
33. Radiosurgery 457 Douglas Kondziolka, L. Dade Lunsford, and John C. Flickinger Introduction . . . . . . 457 Radiobiology of Vascular Malformation Radiosurgery . . . . . . 457 Indications for AVM Radiosurgery . . . . . . 458 Clinical Experience . . . . . . 458 Stereotactic Radiosurgery Technique . . . . . . 458 AVM Obliteration . . . . . . 461 Postradiosurgery Effects . . . . . . 461 Repeat Radiosurgery . . . . . . 463 Staged Volume Radiosurgery . . . . . . 463 Future Roles for AVM Radiosurgery . . . . . . 463 Summary . . . . . . 465 References . . . . . . 465
34. Molecular Biology of Arteriovenous Malformations 469 Michael L. DiLuna, Turker Kilic, Issam A. Awad, and Murat Gunel Introduction . . . . . . 469 Angiogenesis and Vasculogenesis . . . . . . 469 Mendelian Forms of AVMs . . . . . . 471 Molecular Information on Sporadic AVMs . . . . . . 475 Future Research . . . . . . 479 References . . . . . . 479
35. Surgical Approaches 483 Daniel P. McCarthy, Bernard R. Bendok, Christopher C. Getch, and H. Hunt Batjer Introduction . . . . . . 483 Drug Delivery Systems . . . . . . 483
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Surgical Instrumentation . . . . . . 484 Anatomical, Physiological, and Operatively Integrated Imaging . . . . . . 486 Advanced Operating Suite . . . . . . 488 Conclusion . . . . . . 489 References . . . . . . 489
Index . . . .
491
Contributors
Jordan Abbott Department of Neurological Surgery, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A. Joseph G. Adel Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. M. Jafer Ali Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Robert Allbright Division of Radiation Oncology, Department of Radiology, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A. Issam A. Awad Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, and Evanston Northwestern Healthcare, Evanston, Illinois, U.S.A. Eli M. Baron Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania, U.S.A. Daniel L. Barrow Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, U.S.A. H. Hunt Batjer Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Curtis L. Beauregard Southeast Neuroscience Center, Houma, Louisiana, U.S.A. Bernard R. Bendok Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Sumon Bhattacharjee
Neuroscience Group of Northeast Wisconsin, Neenha, Wisconsin, U.S.A.
C. Michael Cawley, III Departments of Neurosurgery and Neuroradiology, Emory University School of Medicine, Atlanta, Georgia, U.S.A. Steven D. Chang Department of Neurosurgery and the Stanford Stroke Center, Stanford University School of Medicine, Stanford, California, U.S.A. Paul Chapman Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A. P. Roc Chen Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A. Harry J. Cloft Departments of Radiology and Neurosurgery, Mayo Clinic College of Medicine, Rochester, Minnesota, U.S.A. Ralph G. Dacey, Jr. Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri, U.S.A. Shervin R. Dashti Department of Neurosurgery, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio, U.S.A. Arthur L. Day Cerebrovascular Center, Department of Neurological Surgery, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, U.S.A. Evandro de Oliveira Department of Neurosurgery, State University of Campinas - UNICAMP, Sa˜o Paulo, Brazil Michael L. DiLuna Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
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Jacques E. Dion Departments of Radiology and Neurosurgery, Emory University Hospital, Atlanta, Georgia, U.S.A. Christopher Eddleman Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Andrew D. Fine Neurosurgery and Spine Specialists, Sarasota, Florida, U.S.A. John C. Flickinger Departments of Neurological Surgery and Radiation Oncology, The Center for Image Guided Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A. Kai U. Frerichs Cerebrovascular Center, Department of Neurosurgery, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, U.S.A. Robert M. Friedlander Cerebrovascular Center, Department of Neurosurgery, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, U.S.A. Erzhen Gao Supertron Technologies Inc., Newark, New Jersey, U.S.A. Christopher C. Getch Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Steven L. Giannotta Department of Neurosurgery, University of Southern California, Los Angeles, California, U.S.A. Jeffrey P. Greenfield Department of Neurological Surgery, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A. Murat Gunel Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A. George J. Hademenos Science Department, Richardson High School, Richardson, Texas, U.S.A. Robert E. Harbaugh Department of Neurosurgery, The Pennsylvania State University, Hershey, Pennsylvania, U.S.A. Mark R. Harrigan Alabama, U.S.A.
Department of Neurosurgery, University of Alabama, Birmingham,
Alan C. Hartford Section of Radiation Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire, U.S.A. Tomoki Hashimoto Department of Anesthesia and Perioperative Care, UCSF Center for Cerebrovascular Research, University of California, San Francisco, California, U.S.A. Roberto C. Heros Florida, U.S.A.
Department of Neurological Surgery, University of Miami, Miami,
L. Nelson Hopkins Departments of Neurosurgery and Radiology, Toshiba Stroke Research Center, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, U.S.A. Vallabh Janardhan Division of Interventional Neuroradiology, Department of Radiology, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A. Turker Kilic Vascular and Oncological Neurosurgery, Gamma-Knife Radiosurgery, Marmara School of Medicine, Istanbul, Turkey Douglas Kondziolka Departments of Neurological Surgery and Radiation Oncology, The Center for Image Guided Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A. Giuseppe Lanzino Departments of Neurosurgery and Radiology, Illinois Neurological Institute, University of Illinois College of Medicine at Peoria, Peoria, Illinois, U.S.A. Sean D. Lavine Departments of Neurological Surgery and Radiology, Columbia University, College of Physicians and Surgeons, New York Neurological Institute, New York, New York, U.S.A.
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Michael A. Lefkowitz New York, U.S.A.
Long Island Neurological Associates, New Hyde Park,
Jay S. Loeffler Department of Radiation Oncology, Northeast Proton Therapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A. Christopher M. Loftus Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania, U.S.A. L. Dade Lunsford Departments of Neurological Surgery and Radiation Oncology, The Center for Image Guided Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A. Neil Martin Division of Neurosurgery, UCLA School of Medicine, University of California–Los Angeles, Los Angeles, California, U.S.A. Tarik F. Massoud University Department of Radiology, University of Cambridge School of Clinical Medicine, Cambridge, U.K. Daniel P. McCarthy Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. James McInerney Department of Neurosurgery, The Pennsylvania State University, Hershey, Pennsylvania, U.S.A. Stefan A. Mindea Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Michael Morgan Department of Neurosurgery, School of Advanced Medicine, Macquarie University, Sydney, Australia Ronald F. Moussa Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A. R. Anthony Murray Illinois, U.S.A.
Department of Radiology, Northwestern Memorial Hospital, Chicago,
Christopher S. Ogilvy Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A. Jeffrey G. Ojemann Department of Neurosurgery, University of Washington/Children’s Hospital and Regional Medical Center, Seattle, Washington, U.S.A. Stephen L. Ondra Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Nelson M. Oyesiku Georgia, U.S.A.
Department of Neurosurgery, Emory University School of Medicine, Atlanta,
Susan C. Pannullo Department of Neurological Surgery, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A. Harold J. Pikus
Department of Neurological Surgery, University of Miami, Miami, Florida, U.S.A.
John Pile-Spellman Departments of Radiology, Neurosurgery, and Neurology, New York Neurological Institute, Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, New York, U.S.A. Charles J. Prestigiacomo Departments of Neurological Surgery and Radiology, Neurological Institute of New Jersey, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, U.S.A. Albert L. Rhoton, Jr. Department of Neurological Surgery, University of Florida College of Medicine, Gainesville, Florida, U.S.A. Howard A. Riina Departments of Neurological Surgery, Neurology, and Radiology, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
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Robert H. Rosenwasser Department of Neurosurgery, Division of Cerebrovascular Surgery and Interventional Neuroradiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A. Eric J. Russell Department of Radiology, Northwestern Memorial Hospital, and the Northwestern University Feinberg School of Medicine, Chicago, Illinois, U.S.A. Warren R. Selman Department of Neurosurgery, Case Western Reserve University School of Medicine, and Department of Neurological Surgery, University Hospitals of Cleveland, Cleveland, Ohio, U.S.A. Adnan H. Siddiqui Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A. Robert A. Solomon Department of Neurological Surgery, New York Neurological Institute, Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, New York, U.S.A. Mark M. Souweidane Department of Neurological Surgery, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A. Gary K. Steinberg Department of Neurosurgery and the Stanford Stroke Center, Stanford University School of Medicine, Stanford, California, U.S.A. Philip E. Stieg Department of Neurological Surgery, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A. Jeffrey L. Sunshine Department of Radiology, Case Western Reserve University School of Medicine, and Division of Magnetic Resonance Imaging, University Hospitals of Cleveland, Cleveland, Ohio, U.S.A. Melanie K. Swope Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A. Robert W. Tarr Division of Neuroradiology, Department of Radiology, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio, U.S.A. Helder Tedeschi Department of Neurosurgery, State University of Campinas - UNICAMP, Sa˜o Paulo, Brazil, and University of Florida, Gainesville, Florida, U.S.A. B. Gregory Thompson Michigan, U.S.A.
Department of Neurosurgery, University of Michigan, Ann Arbor,
Wen Hung Tzu Department of Neurosurgery, University of Sa˜o Paulo School of Medicine, Sa˜o Paulo, Brazil, and University of Florida, Gainesville, Florida, U.S.A. Fernando Vinuela Department of Radiological Sciences, Endovascular Therapy Service, UCLA School of Medicine, University of California–Los Angeles, Los Angeles, California, U.S.A. John E. Wanebo Department of Neurosurgery, National Naval Medical Center, Bethesda, Maryland, U.S.A. Robert Wienecke
Neuroscience Specialists, Oklahoma City, Oklahoma, U.S.A.
John H. Wong Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A. William L. Young Departments of Anesthesia and Perioperative Care, Neurological Surgery, and Neurology, UCSF Center for Cerebrovascular Research, University of California, San Francisco, California, U.S.A.
Section I
ANATOMY AND PHYSIOLOGY
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Surgical Anatomy Helder Tedeschi Department of Neurosurgery, State University of Campinas - UNICAMP, Sa˜o Paulo, Brazil, and University of Florida, Gainesville, Florida, U.S.A.
Evandro de Oliveira Department of Neurosurgery, State University of Campinas - UNICAMP, Sa˜o Paulo, Brazil
Wen Hung Tzu Department of Neurosurgery, University of Sa˜o Paulo School of Medicine, Sa˜o Paulo, Brazil, and University of Florida, Gainesville, Florida, U.S.A.
Albert L. Rhoton, Jr. Department of Neurological Surgery, University of Florida College of Medicine, Gainesville, Florida, U.S.A.
INTRODUCTION The advances in microneurosurgical equipment and techniques, combined with the evolution of endovascular and radiosurgical treatments, have greatly facilitated the management of arteriovenous malformations (AVMs) of the brain. The continuous development in the field of neuroimaging has contributed enormously to the understanding of the anatomical characteristics of AVMs. Nevertheless, the intricate anatomy related to AVMs still presents a problem to the average neurosurgeon (1). Although the vessels involved with the arterial supply and with the venous drainage of AVMs appear disorganized, they usually follow the same pattern of the normal vasculature. Detailed three-dimensional anatomical knowledge of the normal brain structures enables the surgeon to understand and access an AVM with less difficulty and to perform surgical resection in a rational way. In this chapter, we describe the basic anatomical features to be considered in planning surgical strategy for AVMs of different areas of the brain. These areas include the frontal, parietal, temporal, and occipital convexities, the mesial temporal region, the interhemispheric parafalcine region (includes the frontal, parietal, occipital, and callosal regions), the region of the basal ganglia (includes ventricular and insular AVMs), and the region of the posterior fossa (includes cerebellar and brain stem lesions). FRONTAL LOBE AVMs Neural Relationships The lateral surface of the frontal lobe is bounded posteriorly by the central sulcus, which separates the frontal from the parietal lobes, and above by the superior border of the hemisphere, which parallels the superior sagittal sinus. The lower border of the lateral surface has an anterior part, the superciliary border, which rests on the orbital roof, and a posterior part, the sylvian border, which faces the temporal lobe across the sylvian fissure. The lateral surface is traversed by three sulci that divide it into one vertical gyrus, which parallels the central sulcus, and three horizontal gyri, which are oriented in the same direction as the sylvian fissure. The precentral gyrus, which parallels the central sulcus, is bounded behind by the central sulcus and in front by the precentral sulcus. The surface in front of the precentral sulcus is divided by two sulci, the superior and inferior frontal sulci, into three roughly horizontal convolutions, the superior, middle, and inferior frontal gyri.
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The inferior frontal convolution, which is situated between the sylvian fissure and the inferior frontal gyrus, is divided from anterior to posterior into a pars orbitalis, a pars triangularis, and a pars opercularis by the anterior horizontal and anterior ascending rami of the sylvian fissure. The inferior surface of the frontal lobe is concave from side to side and rests on the cribriform plate, orbital roof, and the lesser wing of the sphenoid bone. The olfactory sulcus, which overlies the olfactory bulb and tract, divides the orbital surface into a medial strip of cortex, the gyrus rectus, and a larger lateral part, the orbital gyri. The lateral gyri are divided by the orbital sulci into the anterior, medial, posterior, and lateral orbital gyri. Arterial Relationships AVMs situated in the lateral and basal surfaces of the frontal lobe usually derive their arterial supply from the M1 and M2 branches of the middle cerebral artery. In larger lesions, or in those situated close to the margins of the hemispheres, the arterial supply may involve branches from segments of both the anterior and middle cerebral arteries. Venous Relationships The veins draining AVMs in the lateral surface of the frontal lobe are divided into an ascending group, which empties into the superior sagittal sinus, and a descending group, which courses toward the sylvian fissure to join the superficial sylvian veins. Basal surface frontal AVMs are drained through an anterior group of veins, which course toward the frontal pole and empty into the superior sagittal sinus, and a posterior group, which drain backward to join the veins at the medial part of the sylvian fissure, where they converge on the anterior perforated substance to form the basal vein (2,3). Most AVMs located in the lateral and basal surfaces of the frontal lobe can be managed through a fronto-temporo-sphenoidal craniotomy. Those AVMs that reach, or that are located in, the upper convexity require that the craniotomy be extended to the midline to secure the branches of the anterior cerebral artery during surgery (Fig. 1A, B, and C). PARIETAL LOBE AVMs Neural Relationships The lateral surface of the parietal lobe is demarcated anteriorly by the central sulcus, posteriorly by a line joining the preoccipital notch to the point where the parietooccipital sulcus reaches the superior edge of the hemisphere, and inferiorly by a line directed along the posterior ramus of the sylvian fissure. The lateral surface is subdivided into three areas by the postcentral and intraparietal sulci. The postcentral sulcus divides the parietal lobe into an anterior convolution, the postcentral gyrus, situated behind and parallel to the central sulcus, and a large posterior part, which is subdivided by the intraparietal sulcus, into the superior and inferior parietal lobules. The inferior parietal lobule is divided into an anterior part formed by the supramarginal gyrus, which arches over the upturned end of the posterior ramus of the sylvian fissure, and a middle part formed by the angular gyrus, which arches over the upturned end of the inferior temporal sulcus and extends onto the anterior part of the occipital lobe. The superior parietal lobule extends from the intraparietal sulcus to the superior margin of the hemisphere. Arterial Relationships AVMs located in the lateral surface of the parietal lobe usually derive their arterial supply from branches of the anterior and middle cerebral arteries. At times, these malformations may receive perforators from a ventricular branch of the posterior cerebral artery, the lateral posterior choroidal artery (Fig. 2A and B). Venous Relationships The veins that drain AVMs located in the lateral surface of the parietal lobe are divided into an ascending group, which empties into the superior sagittal sinus, and a descending group, which drains into the veins along the sylvian fissure.
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Figure 1 (A) Anatomical venous dissection of the right cerebral hemisphere: 1. Vein of Trolard; 2. superficial sylvian vein; 3. vein of Labbe´. (See color insert.) (B) Right digital carotid angiogram of a frontal opercular arteriovenous malformation (AVM) showing the usual venous drainage pattern of such lesions. (C) Intraoperative view of the same patient showing the enlarged superficial veins that drain the AVM. (See color insert.) (D) Right digital carotid angiogram of a sylvian AVM showing the usual venous drainage pattern of such lesions.
Large parietal lobe AVMs are usually associated with a high risk of surgical morbidity. The feeding vessels from the middle cerebral artery are usually pathologically tortuous and elongated with fragile walls that are at times extremely difficult to coagulate. TEMPORAL LOBE AVMs Neural Relationships The lateral surface of the temporal lobe is situated below the sylvian fissure and anterior to an imaginary line extending upward from the preoccipital notch to the parietooccipital sulcus. The lateral surface of the temporal lobe is divided by two sulci, the superior and inferior temporal sulci, into three gyri, the superior, middle, and inferior temporal gyri, which are oriented parallel to the sylvian fissure. The superior temporal gyrus lies between the sylvian fissure and the superior temporal sulcus. It is continuous around the lip of the fissure with the transverse temporal gyri, which extend obliquely forward and laterally from the border of the insula to form the lower wall of the deep portion of the sylvian fissure. The middle temporal gyrus lies between the superior and inferior temporal sulci. The inferior temporal gyrus lies below the inferior temporal sulcus and continues around the inferior border of the hemisphere to form the lateral part of the inferior surface of the lobe. The inferior surface of the temporal lobe is formed, from medial to lateral, by the parahippocampal and occipitotemporal gyri and by the lower surface of the inferior temporal gyrus. The parahippocampal gyrus forms the medial part of the inferior surface and is separated laterally from the occipitotemporal gyrus by the collateral and rhinal sulci. The parahippocampal gyrus extends backward from the temporal pole to the posterior margin of the corpus callosum, where it is continuous around the splenium with the cingulate gyrus. The anterior end of the parahippocampal gyrus projects medially to form a hook-like prominence called the uncus.
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Figure 2 (A) Anatomical dissection of the brain with the frontal lobes removed to the level of the anterior perforated substance to expose the anterior portion of the poligone of Willis: 1. Corpus callosum; 2. lateral ventricle; 3. basal ganglia; 4. M2 branches of the middle cerebral artery; 5. anterior communicating artery; 6. recurrent artery of Heubner; 7. lenticulostriate arteries; 8. M4 segment of the middle cerebral artery; 9. M1 segment of the middle cerebral artery; 10. A1 segment of the anterior cerebral artery; 11. internal carotid artery. (See color insert.) (B) Left digital carotid angiogram of an arteriovenous malformation (AVM) located in the convexity of the parietal lobe. (C) Right digital carotid angiogram of an AVM located in the uncus of the temporal lobe.
The occipitotemporal gyrus is separated laterally by the occipitotemporal sulcus from the lower surface of the inferior temporal gyrus. Arterial Relationships According to their location, AVMs arising at the lateral and basal surfaces of the temporal lobe may derive their arterial supply from branches of the internal carotid artery and from the middle and posterior cerebral arteries. AVMs located in the temporal pole are usually supplied by branches of the M1 segment of the middle cerebral artery and at times by branches of the anterior choroidal artery and of the P2 segment of the posterior cerebral artery (Fig. 2C). Those AVMs located in the superior temporal gyrus are usually supplied by branches of the middle cerebral artery, although they may also receive deep tributaries from intraventricular arteries. AVMs located in the middle and inferior temporal gyri are often supplied by both the middle and posterior cerebral artery territories. Inferior temporal surface AVMs are invariably supplied by branches of the posterior cerebral artery. Venous Relationships The veins that drain AVMs arising in the lateral surface of the temporal lobe are divided into an ascending group, the temporosylvian veins, which course toward the sylvian fissure, and a descending group, which empty into the venous sinuses below the temporal lobe. AVMs arising in the basal surface of the temporal lobe are drained by two groups of veins. The lateral group drains into the sinuses in the anterolateral part of the tentorium. The medial group, formed by the uncal, anterior hippocampal, and medial temporal veins, empties into the basal vein as it courses along the medial edge of the temporal lobe. The part of the basal surface circa the temporal pole is commonly drained by the temporosylvian veins.
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OCCIPITAL LOBE AVMs Neural Relationships The lateral surface of the occipital lobe is poorly delimited from the parietal lobe. It lies behind a line joining the preoccipital notch to the point where the parietooccipital sulcus, which is prominent on the medial surface of the hemisphere, intersects the superior margin of the hemisphere. The lateral surface is composed of a number of irregular convolutions that are divided by a short horizontal sulcus, the lateral occipital sulcus, into the superior and inferior occipital gyri. The inferior surface of the occipital lobe lies behind a line that extends laterally from the anterior end of the calcarine sulcus to the preoccipital notch. The inferior surface is formed by the lower part of the lingula and the posterior part of the occipitotemporal and inferior temporal gyri. Arterial Relationships AVMs located in the lateral and inferior surfaces of the occipital lobe are usually supplied by terminal branches of the middle and posterior cerebral arteries. Venous Relationships The lateral surface of the occipital lobe is drained by the occipital vein, which arises from tributaries that drain the lateral surface of the occipital pole. This vein usually empties into the lower margin of the superior sagittal sinus 4 to 5 cm from the torcular (2). The inferior surface of the occipital lobe is drained by the inferior occipital vein that empties into the lateral tentorial sinus. MEDIOBASAL TEMPORAL LOBE AVMs The mediobasal temporal region can be divided into three parts: anterior, middle, and posterior. The anterior part is limited posteriorly by a transverse line passing at the posterior end of the uncus, and the middle and posterior parts are separated by an extension of the anterior splenial line. Neural Relationships The anterior part has three surfaces: anterosuperior, inferior, and medial. The anterosuperior surface, consisting of the semilunar and ambient gyri, faces the medial end of the sylvian fissure and the carotid cistern. The inferior surface is the parahippocampal gyrus, which is separated anterolaterally from the occipitotemporal gyrus by the rhinal sulcus. This sulcus continues posteriorly as the collateral sulcus in the middle part of the mediobasal temporal region. More laterally over the inferior surface the occipitotemporal sulcus, another anteroposteriorly oriented sulcus, separates the occipitotemporal gyrus from the inferior temporal gyrus. The medial surface of the anterior part contains the anterior end of the parahippocampal gyrus and the uncus. These structures face the anterior two-thirds of the cerebral peduncle, with the crural cistern interposed between the peduncle and the uncus. The middle part of the mediobasal temporal region has two surfaces: inferior and medial. On the inferior surface the collateral sulcus separates the most medially situated parahippocampal gyrus from the occipitotemporal gyrus. Lateral to the occipitotemporal gyrus, and separated from it by the occipitotemporal sulcus, is the inferior temporal gyrus. The parahippocampal gyrus ends at the level of the anterior splenial line. From this point, the lingual gyrus continues posteriorly, and the isthmus of the cingulate gyrus continues posteriorly and superiorly. The occipitotemporal gyrus is a long gyrus extending from the anterior temporal base to the occipital pole. The collateral sulcus extends from the anterior to the posterior parts of the mediobasal temporal region. The occipitotemporal sulcus usually has its course close to the inferolateral margin of the temporal lobe, over the temporal base. From inferior to superior, the medial surface of the middle part consists of the subiculum of the parahippocampal gyrus, the dentate gyrus, and the fimbria of the fornix. It faces the posterior one-third of the cerebral peduncle and the tegmentum of the mesencephalon and is separated from them by the ambient cistern. The posterior part of the mediobasal temporal region includes part of the occipital and parasplenial area to which some AVMs may extend. This part has three surfaces: inferior,
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medial, and anterior. On the inferior surface, continuous with the posterior part of the parahippocampal gyrus, is the lingual gyrus, which is separated laterally from the occipitotemporal gyrus by the collateral sulcus. The parasplenial region forms the medial surface of the posterior part. It contains the isthmus of the cingulate gyrus anteriorly, surrounding the splenium of the corpus callosum, and the inferior extension of the precuneus, posterior to the isthmus from which it is separated by the subparietal sulcus. Inferolaterally to these two gyri is the lingual gyrus, separated from them by the anterior part of the calcarine sulcus. The anterior surface is composed of the anterior end of the isthmus of cingulate gyrus, the posterior end of the dentate gyrus and the fasciolar gyrus, which is continuous anteriorly with the dentate gyrus. This surface faces the tectum of the mesencephalon and the pulvinar of the thalamus, from which it is separated by the posterior end of the ambient cistern and by the quadrigeminal cistern. From a practical point of view, the posterior part of the mediobasal temporal region can be divided into a superior and inferior area, the former superoanterior to the anterior part of the calcarine sulcus and the latter inferoposterior to this sulcus. Arterial Relationships The arterial supply of the anterior surface of the anterior part comes mainly from the early branches of the M1 segment of the middle cerebral artery. The most medial area of this surface may receive a branch from the carotid artery and also receives a branch from the anterior choroidal artery, called the uncal artery. The inferior surface receives branches from the first cortical branch of the posterior cerebral artery, the hippocampal arteries (Fig. 3A). The medial surface is supplied by branches of the anterior choroidal artery and by the hippocampal artery. The inferior surface of the middle part of the mediobasal temporal region receives branches from the posterior cerebral artery: the anterior, middle, and posterior temporal arteries. These arteries originate from the lateral surface of the posterior cerebral artery, pass through the ambient cistern laterally, and cross the tentorial edge to reach the temporal base. Passing under the parahippocampal gyrus, they enter the collateral sulcus. After exiting this sulcus, these arteries run over the occipitotemporal gyrus and enter the occipitotemporal sulcus. They end finally over the surface of the inferior temporal gyrus. The medial surface of the middle part has the choroidal fissure at its highest point. The anterior choroidal artery enters through this fissure at its anteroinferior end, the inferior choroidal point. Several posterior choroidal arteries enter the choroidal fissure posteriorly to the anterior choroidal artery. In the posterior part of the mediobasal temporal region, the two major terminal branches of the posterior cerebral artery, the parietooccipital and calcarine arteries, cross posterolaterally over the anteroinferior end of the isthmus of the cingulate gyrus. The parietooccipital artery sends branches to the posterior half of the precuneus and also to the anterior half of the cuneus. The calcarine artery sends branches to the posterior half of the cuneus and to the lingual gyrus. Venous Relationships The venous system related to the mediobasal temporal region is mainly the basal vein system. The vein of Galen may receive veins that drain the temporooccipital junction area and the parasplenial area. The anterosuperior surface of the anterior part of the mediobasal temporal region is drained by the uncal vein. This vein drains into the deep middle cerebral vein or directly into the first segment of the basal vein of Rosenthal. The medial surface is also drained by the uncal vein and by the anterior hippocampal vein, which runs posteriorly and drains into the main trunk of the inferior ventricular vein or directly into the second segment of the basal vein. The inferior surface of the middle part of the mediobasal temporal region is drained by the medial temporal vein, which drains directly into the basal vein. The anterior longitudinal hippocampal vein runs over the medial surface of the middle part and drains into the inferior ventricular vein, the anterior hippocampal vein, or the basal vein at the inferior choroidal point. The inferior surface of the posterior part of the mediobasal temporal region is drained by the occipitotemporal vein, which drains into the third segment of the basal vein. The medial
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Figure 3 (A) Anatomical dissection of the posterior cerebral artery and its branches (viewed from the basal surface of the brain): 1. Internal carotid artery; 2. posterior communicating artery; 3. anterior choroidal artery; 4. posterior cerebral artery; 5. posterior thalamoperforating artery; 6. medial posterior choroidal artery; 7. anterior temporal artery; 8. medial temporal artery; 9. posterior temporal artery; 10. parietooccipital artery; 11. calcarine artery. (See color insert.) (B) Digital vertebral angiogram of a right-sided anterior mediobasal temporal lobe arteriovenous malformation (AVM). (C) Digital vertebral angiogram of a right-sided middle mediobasal temporal lobe AVM. (D) Digital vertebral angiogram of a right-sided posterior mediobasal temporal lobe AVM. (See color insert.)
surface of this posterior part is drained by the internal occipital vein, which frequently joins the posterior pericallosal vein near the splenium before terminating into the internal cerebral vein or into the vein of Galen. The anterior surface of this posterior part is drained by the posterior longitudinal hippocampal vein, which may drain into the third segment of the basal vein, the internal cerebral vein, the lateral atrial vein, or the medial atrial vein. Temporal Horn of the Lateral Ventricle In addition to the superficial anatomy, a thorough knowledge of the anatomy of the temporal horn of the lateral ventricle is of major importance in the surgical approach to vascular malformations of the mediobasal temporal region. The temporal horn extends forward from the atrium below the pulvinar into the medial part of the temporal lobe and ends blindly immediately behind the amygdaloid nucleus. The floor of the temporal horn is formed medially by the hippocampus and laterally by the collateral eminence. The roof is formed medially by the inferior surface of the thalamus and the tail of the caudate nucleus, which are separated by the striothalamic sulcus, and laterally by the tapetum of the corpus callosum, which sweeps inferiorly to form the lateral wall of the temporal horn. The medial wall is little more than a narrow cleft, the choroidal fissure, situated between the inferolateral part of the thalamus and the fimbria of the fornix.
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The choroid plexus in the lateral ventricle has a C-shaped configuration that parallels the fornix. It is attached to the tela choroidea along the choroidal fissure, the narrow C-shaped cleft situated between the fornix and the thalamus in the medial part of the body, atrium, and temporal horn. The inferior termination of the choroidal fissure, called the inferior choroidal point, is located just behind the uncus and amygdaloid nucleus and just lateral to the lateral geniculate body (4,5). The choroid plexus of the lateral ventricles is supplied by the anterior and posterior choroidal arteries, each giving branches to the neural structures along their course. The choroid plexus of the temporal horn is supplied by the anterior choroidal artery and by the lateral posterior choroidal arteries. The roof and lateral wall of the temporal horn are drained predominantly by the inferior ventricular vein, and the floor is drained by the transverse hippocampal veins. The veins from the temporal horn join the basal vein or its tributaries. The posterior part of the roof and floor of the temporal horn may be drained by the veins coursing in the walls of the atrium, the medial and lateral atrial veins. According to their location, mediobasal temporal lobe AVMs are divided into three groups: anterior, middle, and posterior. The anterior mediobasal temporal lobe AVMs are located in the uncus, anterior area of the parahippocampal gyrus, and amygdala (Fig. 3B). They are supplied by the proximal branches of the M1 segment of the middle cerebral artery, by branches of the anterior choroidal artery, by perforating branches of the internal carotid artery, and by temporal branches of the posterior cerebral artery, especially the hippocampal artery. The venous drainage is in general by the basal vein of Rosenthal through numerous tributaries draining the cortex of the uncus and parahippocampal gyrus. When there is stenosis or absence of the basal vein of Rosenthal, the drainage occurs initially through the superficial sylvian vein, and then retrogradely to the sphenoparietal sinus, longitudinal sinus, or lateral sinus. Many surgeons approach anterior mediobasal temporal lobe AVMs by a transsylvian route through a fronto-temporo-sphenoidal (pterional) craniotomy (6–9). We use a combination of the pterional and subtemporal approaches, called a pretemporal approach with complete exposure of the temporal pole (10–12). Through a wide opening of the sylvian cistern we initially expose the afferent branches from the proximal portion of M1 segment of the middle cerebral artery, from the internal carotid artery, and from the anterior choroidal artery. By retracting the temporal pole posteriorly, we can expose and coagulate the afferent branches from the posterior cerebral artery and then start the last phase of the surgery, the resection of the vascular lesion. Whenever possible, we initiate the resection of the AVM only after the complete occlusion of the afferent vessels. Sometimes the AVM can be approached through the inferior sulcus of the insula at the level of the limen insula, as described by Yasargil et al. (13). The middle mediobasal temporal lobe AVMs involve the parahippocampal gyrus posterior to the uncus and are limited posteriorly by the anterior splenial line (Fig. 3C). Medially they are related to the cerebral peduncle and superomedially to the thalamus, optic pathways, and lateral geniculate body. Eventually these AVMs may extend laterally, compromising the fusiform gyrus, the hippocampus, and the choroid plexus of the temporal horn. These AVMs are mainly supplied by cortical temporal branches of the posterior cerebral artery. When the vascular lesion extends laterally, it can be supplied by branches of the intraventricular segment of the anterior choroidal artery. Venous drainage is usually from the posteromedial aspect of the malformation to the basal vein of Rosenthal. Rarely, these lesions drain superficially to the transverse sinus through cortical veins on the inferior surface of the temporal lobe. The middle mediobasal temporal lobe AVMs can be accessed by a subtemporal approach (7,14,15) through a cortical incision on the superior or middle temporal gyrus (16), through a cortical incision on the inferior temporal gyrus or on the fusiform gyrus (6,15), through a cortical incision on the parahippocampal gyrus (17), through the resection of a small portion of the inferior temporal gyrus (4,15), or through the collateral sulcus (8). We approach middle mediobasal temporal lobe AVMs through the occipitotemporal sulcus, crossing the temporal horn of the lateral ventricle and using the choroidal fissure to get to the ambient cistern. We rarely use the collateral sulcus because in addition to being too medial over the inferior surface of the temporal lobe, it has a medial to lateral orientation toward the ventricle that requires great cerebral retraction to adequately expose the lesion. When these middle AVMs are slightly more anterior, they can also be approached through the inferior
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sulcus of the insula. After the identification of the anterior choroidal artery inside the ventricle and of the posterior cerebral artery in the ambient cistern, these arteries are followed posteriorly up to the AVM, occluding the branches to the malformation, and preserving the medial branches to the brain stem and basal ganglia. The excision of the AVM localized in the parahippocampal gyrus follows an anterior to posterior direction, because its venous drainage is generally from the posteromedial aspect of the lesion to the basal vein of Rosenthal. The posterior mediobasal temporal lobe AVMs are localized in the posterior part of the parahippocampal gyrus, posteriorly to the anterior splenial line (Fig. 3D). They may extend also to the isthmus of the cingulate gyrus, the anterior area of the precuneus, and the lingual gyrus. These AVMs are related to the medial portion of the ventricular trigone, to the mesencephalic tegment, and to the pulvinar of the thalamus. Sometimes they extend inferiorly to involve the fusiform gyrus and/or superiorly to involve the cingulate gyrus around the splenium of the corpus callosum. Usually their posterior limit is the occipitoparietal sulcus. The arterial supply to these malformations comes from branches of the posterior cerebral artery, including the posterolateral choroidal branches. When the AVM extends superiorly, it can receive afferents from the distal segment of the pericallosal artery. The venous drainage is to the distal segment of the basal vein of Rosenthal, directly to the vein of Galen, or, rarely, to the straight sinus or to the transverse sinus through a dural sinus localized in the tentorium. The posterior mediobasal temporal lobe AVMs are also difficult to approach and excise. When the lesion extends to the posterior region of the ventricular trigone, it can be accessed through the choroidal fissure, using the occipitotemporal sulcus. The complexity of the group of veins that form the vein of Labbe´ is frequently a great obstacle for the utilization of this approach. The approach is complicated as well by the deep location of the AVM and by the curvature of the tentorium. When the lesion extends superiorly to the cingulate gyrus, we prefer an interhemispheric parafalcine posterior approach through the calcarine and occipitoparietal sulci with minimum retraction of the brain. The inconveniences of this approach are the great distance to the arterial afferents and the premature access to the venous drainage of the lesion. INTERHEMISPHERIC PARAFALCINE AND CALLOSAL REGION AVMs AVMs that arise along the interhemispheric fissure can compromise the medial cortical surface of the cerebral hemispheres, the corpus callosum, and the midline structures related to the walls of the cerebral ventricles. These AVMs can present different anatomical and surgical features according to their location along the interhemispheric fissure. AVMs that compromise the medial cortical surface of the cerebral hemispheres in the anterior third of the interhemispheric fissure are usually supplied by branches of the proximal A2 segment of the anterior cerebral artery and drain into the anterior third of the superior sagittal sinus (Fig. 4). Those interhemispheric malformations
Figure 4 (A) Anatomical dissection of the medial aspect of the left cerebral hemisphere. 1. Cingulate gyrus; 2. body of corpus callosum; 3. splenium of corpus callosum; 4. genu of corpus callosum; 5. rostrum of corpus callosum; 6. body of lateral ventricle; 7. fornix; 8. internal cerebral vein; 9. vein of Galen; 10. third ventricle; 11. anterior cerebral arteries. (See color insert.) (B) Left carotid digital subtraction arterial angiogram of an arteriovenous malformation located in the anterior part of the cingulate gyrus and body of the corpus callosum. Note the arterial supply through the anterior cerebral artery and the venous drainage through the septal vein into the internal cerebral vein.
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that are located in proximity to the gyrus rectus, i.e., to the basal surface of the frontal lobe, can also be supplied by branches of the A1 segment of the anterior cerebral artery. According to their size, these malformations can extend laterally and recruit vessels from branches of the middle cerebral artery. AVMs that involve the corpus callosum alone are not common (Fig. 5). These lesions usually involve portions of the cingulate gyrus, and sometimes may extend inferiorly to include the midline structures of the lateral and third ventricles. Those AVMs that involve the anterior third of the corpus callosum are supplied by branches of the anterior cerebral artery. They may have superficial drainage into the superior sagittal sinus or drain into the septal and thalamostriate veins in the ventricles. AVMs arising in the middle third of the interhemispheric fissure are usually very difficult to approach. The exposure is usually hampered by the veins that drain either the malformation or the normal brain, and by the proximity of the sensory-motor cortex that prohibits any excessive retraction. These malformations are usually supplied by branches of the pericallosal or callosomarginal arteries, and when the malformation extends to the ventricles, by branches of the posterior choroidal arteries. The venous drainage to the superficial system occurs through bridging veins to the superior or inferior sagittal sinuses, and at times, to the deep venous system through ependymal veins and the internal cerebral veins. AVMs that arise in the posterior third of the interhemispheric fissure comprise those located in the posterior parietal and mesial occipital regions, which are related to the posterior third of the falx cerebri.
Figure 5 (A) Anatomical dissection of the right cerebral hemisphere. 1. Cingulate gyrus; 2. body of corpus callosum; 3. genu of corpus callosum; 4. rostrum of corpus callosum; 5. fornix; 6. splenium of corpus callosum; 7. right anterior cerebral artery; 8. third ventricle; 9. internal cerebral vein; 10. vein of Galen; 11. straight sinus. (See color insert.) (B) Magnetic resonance image (sagittal view) of an arteriovenous malformation (AVM) located in the entire corpus callosum supplied by the anterior cerebral arteries and drained through the internal cerebral veins into the vein of Galen. (C) Anatomical dissection of the brain where both hemispheres were separated in the midline to show the interhemispheric course of the anterior cerebral arteries. The optic chiasm was displaced inferiorly to show the anterior communicatinganterior cerebral artery complex. 1. Orbital surface of the frontal lobe; 2. olfactory nerve; 3. gyrus rectus; 4. corpus callosum; 5. right anterior cerebral artery; 6. anterior communicating artery; 7. right middle cerebral artery; 8. internal carotid artery; 9. optic chiasm; 10. posterior cerebral artery. (See color insert.) (D) Right carotid digital subtraction arterial angiogram of the same case showing the interhemispheric AVM supplied by the anterior cerebral arteries.
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Figure 6 (A) Anatomical dissection of the neural and arterial structures of the interhemispheric aspect of the right cerebral hemisphere: 1. Superior frontal gyrus; 2. cingulate gyrus; 3. precuneus; 4. corpus callosum; 5. fornix; 6. splenium of the corpus callosum; 7. parietooccipital sulcus; 8. cuneus; 9. anterior cerebral artery; 10. lamina terminalis; 11. third ventricle; 12. posterior medial choroidal artery; 13. parietooccipital artery; 14. calcarine artery; 15. calcarine fissure; 16. optic chiasm; 17. cerebral peduncle; 18. internal carotid artery; 19. posterior cerebral artery. (See color insert.) (B) Left vertebral angiogram of an arteriovenous malformation located in the depths of the parietooccipital sulcus (anteroposterior view) supplied by branches of the posterior cerebral artery and drained along the basal surface of the temporal lobe to the vein of Labbe´. (C) Same in lateral view.
The medial surface of the occipital lobe is separated from the parietal lobe by the parietooccipital sulcus. The calcarine fissure, which extends forward from the occipital pole toward the splenium, divides this surface into an upper part, known as the cuneus, located between the parietooccipital and the calcarine sulci, and a lower part, the lingula. Posterior-third parafalcine AVMs can be located in the cuneus, in the cortex of the precuneus adjacent to the parietooccipital sulcus, and may involve the isthmus of the cingulate gyrus and the lingula. These AVMs are usually supplied by branches of the posterior cerebral artery, the parietooccipital and calcarine arteries, and occasionally by branches of the middle cerebral artery and posterior branches of the anterior cerebral artery. Depending on the extension of the AVM, these lesions can reach the ventricular trigone and be supplied by branches of the lateral posterior choroidal arteries (Fig. 6). The venous drainage is through cortical veins into the superior sagittal sinus or through the group of veins that drain into the vein of Galen. AVMs that involve the splenium of the corpus callosum are supplied by branches of the posterior pericallosal artery, lateral posterior and medial posterior choroidal arteries, and from the posterior cerebral artery. In cases in which the AVM extends to the ventricles, it may drain through subependymal veins into the basal vein of Rosenthal and then into the vein of Galen. The surgical approach to posterior-third parafalcine AVMs is somewhat difficult because, similar to those AVMs in the mesial temporal lobe, these lesions tend to be buried in the depths of the sulci. BASAL GANGLIA REGION AVMs The region of the basal ganglia has as its anterior limit an imaginary line that passes just anterior to, and between the frontal horn of the lateral ventricle and the anterior portion of the circular sulcus of the insula. It is limited anteroinferiorly by the anterior extent of the
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anterior perforated substance; laterally by the insular cortex; medially by the inferior portion of the lateral wall and floor of the lateral ventricle and by the wall of the third ventricle; and posteriorly where the lateral and medial limits meet at the level of the pulvinar of the thalamus. The superior and inferior limits are somewhat imprecise. The deep cerebral white matter located above the ventricles is the superior limit, and the inferior limit corresponds to the inferior aspect of the thalamus. Anteroinferior Limit The superior aspect of the anterior limit is related to the frontal horn of the lateral ventricle and to the anterior limit of the circular sulcus of the insula. The structures that form the anteroinferior aspect of the anterior limit are of extreme importance and are reviewed in detail. Neural Relationships The anterior perforated substance is limited anteriorly by the lateral and medial olfactory striae; posteriorly by the optic tract and uncus of the temporal lobe; laterally by the limen insulae; and medially it extends above the optic chiasm to the interhemispheric fissure. The deep cerebral structures located directly above the anterior perforated substance are the frontal horn of the lateral ventricle and the anterior part of the caudate nucleus, putamen, and internal capsule. Arterial Relationships The arteries passing below and sending branches to the anterior perforated substance are the internal carotid, the anterior choroidal, the middle and anterior cerebral, and the recurrent arteries. The anterior perforating arteries pass through the parts of the caudate nucleus, putamen, and internal capsule directly above the anterior perforating substance, and spread posteriorly to supply larger parts of these structures and the adjacent areas of the globus pallidus and thalamus. The internal carotid branches penetrating the anterior perforating substance irrigate the genu of the internal capsule, the adjacent part of the globus pallidus, the posterior limb of the internal capsule, and the thalamus. The anterior choroidal artery supplies the medial two segments of the globus pallidus, the inferior part of the posterior limb of the internal capsule, and the anterior and ventrolateral nuclei of the thalamus. The middle cerebral artery branches, the lenticulostriate arteries, supply the upper part of the internal capsule, the body and head of the caudate, and the lateral part of the globus pallidus. The A1 branches of the anterior cerebral artery supply the area around the optic chiasm, the anterior commissure, the anterior hypothalamus, the genu of the internal capsule, and the anterior part of the globus pallidus. The recurrent artery supplies the most anterior and inferior parts of the head of the caudate nucleus and putamen, and the adjacent part of the anterior limb of the internal capsule (18). Venous Relationships The area of the anterior perforated substance is drained by the anterior segment of the basal vein of Rosenthal. This segment begins below the anterior perforated substance, at the union of the deep middle cerebral and anterior cerebral veins. It receives tributaries from the deep middle cerebral, anterior cerebral, insular, frontoorbital, olfactory, uncal, peduncular, and inferior striate veins (11). Anteroinferior Type AVMs Basal ganglia region AVMs of the anteroinferior type are located in the region of the anterior perforated substance. They may be medial to the internal carotid bifurcation and receive arterial supply from perforating branches of the A1 (lenticulostriate arteries) and A2 segments of the anterior cerebral artery, recurrent artery of Heubner, and anterior communicating artery, or they may be lateral to the internal carotid bifurcation and receive arterial supply from the recurrent artery of Heubner and the lenticulostriate arteries of the M1 segment of the middle cerebral artery. Venous drainage occurs through the small veins to the basal vein of Rosenthal (Fig. 7A and B). These lesions are considered for surgical treatment only in very selected cases, such as in cases of repeated bleeding or in the presence of a hematoma. In those cases the approach is
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Figure 7 (A) Anatomical dissection of the brain where the right frontal lobe was removed at the level of the anterior perforated substance in order to expose the basal ganglia. In the left cerebral hemisphere the frontal and the parietal lobes have been removed, and the insula and basal ganglia were sectioned along the choroidal fissure to expose the course of the posterior cerebral artery and of the vein of Labbe´ in the ambient cistern: 1. Calcarine artery; 2. choroid plexus; 3. M2 branches of the middle cerebral artery; 4. fimbria of the fornix; 5. temporal horn; 6. posterior cerebral artery; 7. basal vein of Rosenthal; 8. middle cerebral artery; 9. internal carotid artery; 10. anterior cerebral artery; 11. lenticulostriate arteries; 12. lenticular nucleus; 13. internal capsule; 14. caudate nucleus; 15. vein of Galen. (See color insert.) (B) Anteroinferior basal ganglia arteriovenous malformation (AVM). Right side (anteroposterior) digital carotid angiogram showing a laterally located anteroinferior basal ganglia AVM. (C) Medial anterior basal ganglia AVM. Right side (anteroposterior) digital carotid angiogram showing a basal ganglia AVM located in the head of the right caudate nucleus. (See color insert.)
carried out through the transsylvian route. Depending on location, some of these AVMs can be approached through the superior portion of the circular sulcus of the insula. Lateral Limit The lateral limit of the region of the basal ganglia is related to the cortex of the insula and to the structures immediately adjacent to it. It is divided into anterior, middle, and posterior portions that are related to the insula and to the frontoparietal and temporal operculae. Neural Relationships The insula has a pyramidal shape and is situated deep to the frontoparietal and temporal operculae in the depths of the sylvian fissure. Its apex, or anterior pole, is directed inferomedially toward the limen insula, which delineates the insula from the anterior perforated substance. The central sulcus of the insula, which runs in a posterosuperior direction from the anterior pole and limen, divides the insula into two groups of short and long gyri. The outer periphery of the insula is surrounded incompletely by a sulcus, referred to as the circular sulcus. The circular sulcus forms a cleft between the insula and the opercula, termed the insular cleft
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(19). The anterior part of the lateral limit is located in the anterior-most portion of the sylvian cistern, lateral to the limen insulae and between the frontal and temporal operculae. The middle part of the lateral limit is located over the cortex of the insula, in the middle portion of the sylvian cistern. At the posterior-most extension of the sylvian cistern the surface of the insula lies very deep, as the insular cleft and the space between the temporal and parietal lobes are almost virtual. At this point the surface of the insula lies in close proximity to the lateral ventricle. The deep cerebral structures located directly adjacent to the insular cortex are the extreme capsule, the claustrum, the external capsule, and the putamen. Arterial Relationships The arterial supply to the lateral limit of the region of the basal ganglia is predominantly from branches of the middle cerebral artery. The M1 segment of the middle cerebral artery arises from the internal carotid artery at the medial end of the sylvian fissure and passes laterally below the anterior perforated substance to become the M2 segment at the level of the limen of the insula. The M2 segment courses over the insula, lateral to the body of the lateral ventricle. The middle cerebral artery sends a series of perforating branches, called lenticulostriate arteries, which supply structures in the area lateral to the frontal horn and body of the lateral ventricle. The anterior portion of the lateral limit receives mainly branches from the lateral group of lenticulostriate arteries and branches from the M2 segment of the middle cerebral artery. The middle and posterior portions of the lateral limit of the region of the basal ganglia are supplied mainly by branches of the M2 segment. Venous Relationships The veins of the cortex of the insula predominantly drain through connections between the deep sylvian vein and the superficial cortical veins bordering the sylvian fissure, i.e., sylvian vein, vein of Labbe´, and vein of Trolard. They may also drain into the basal vein of Rosenthal. Lateral Type AVMs Basal ganglia region AVMs of the lateral type are located on the insular cortex. They can be subdivided into anterior, middle, and posterior types. These AVMs are usually approached through the transsylvian route (Fig. 1D). Anterior lateral AVMs are located in the most anterior portion of the insula, between the frontal and temporal operculae, lateral to the limen insulae. They may project to the frontal or the temporal operculae or to the anterior perforated substance. They usually are supplied by perforating branches originating from the M1 or M2 segments of the middle cerebral artery and at times by perforating branches from the A1 segment of the anterior cerebral artery. Venous drainage is through the deep sylvian vein into the basal vein of Rosenthal or through a superficial sylvian vein into the sphenoparietal sinus (Fig. 1A). These AVMs are located in a usually wide cisternal space and can be surgically approached in cases were there is no extension into the anterior perforated substance. Middle lateral AVMs are located over the cortex of the insula, medial to the M2 branches of the middle cerebral artery and lateral to the internal capsule, in the middle portion of the sylvian cistern. They are supplied by branches of the M2 segment of the middle cerebral artery and, depending on their extension and size, can receive perforators from the M1 segment of the middle cerebral artery and at times also from the A1 segment of the anterior cerebral artery. The venous drainage is usually superficial through the superficial sylvian vein, the vein of Labbe´, or the vein of Trolard. Surgical indications for these malformations depend on the depth of the lesion, and surgery is always difficult because of the necessity to work between the branches of the middle cerebral artery. Posterior lateral AVMs are situated in the most posterior extension of the cortex of the insula. At this point the space between the temporal and parietal lobes is almost virtual, and the sylvian cistern is very deep and in close proximity to the lateral ventricle. The vascular supply to these AVMs is through the M2 and M3 branches of the middle cerebral artery and at times from ventricular branches of the lateral posterior choroidal artery. The venous drainage is through the superficial system. In larger cases, where branches of the lateral posterior choroidal artery contribute to the vascular supply, the venous drainage may be through the deep system. Due to their location and vascular supply, posterior lateral AVMs, especially those on the left side, are sometimes technically very difficult to approach.
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Medial Limit The medial limit of the region of the basal ganglia is closely related to the lateral wall and floor of the lateral ventricle and to the lateral wall of the third ventricle. It is divided into an anterior part, related to the head of the caudate nucleus; a middle part divided by the internal cerebral veins into a superior portion, related to the floor of the body of the lateral ventricle; and an inferior portion, related to the wall of the third ventricle; and a posterior part, related to the pulvinar of the thalamus. Neural Relationships The lateral wall of the frontal horn, the part of the lateral ventricle located anterior to the foramen of Monro, constitutes the anterior portion of the medial limit of the region of the basal ganglia. The frontal horn has a medial wall formed by the septum pellucidum, an anterior wall formed by the genu of the corpus callosum, a narrow floor formed by the rostrum of the corpus callosum, and a lateral wall formed by the head of the caudate nucleus. The columns of the fornix, as they pass anterior to the foramen of Monro, are in the posteroinferior part of the medial wall. The middle portion of the medial limit of the region of the basal ganglia is divided into a superior and an inferior part by the body of the fornix. The middle superior portion corresponds to the floor and lateral wall of the body of the lateral ventricle, and the middle inferior portion corresponds to the lateral wall of the third ventricle. The body of the lateral ventricle extends from the posterior edge of the foramen of Monro to the point where the septum pellucidum disappears and the corpus callosum and fornix meet. The roof is formed by the body of the corpus callosum, the medial wall by the septum pellucidum above and the body of the fornix below, the lateral wall by the body of the caudate, and the floor by the superomedial aspect of the thalamus (5). The caudate nucleus and the thalamus are separated by the striothalamic sulcus, the groove in which the stria terminalis and the thalamostriate vein course. The third ventricle is located between the cerebral hemispheres, the two halves of the thalamus, and the two halves of the hypothalamus. It communicates at its anterosuperior margin with each lateral ventricle through the foramen of Monro. The third ventricle has a roof formed by the body of the fornix, and by two thin membranous layers of tela choroidea that contain the internal cerebral veins and their tributaries, and the medial posterior choroidal arteries and their branches. Parallel strands of choroid plexus project downward on each side of the midline from the inferior layer of tela choroidea into the superior part of the third ventricle. The lateral margin of the roof is formed by the cleft between the lateral edge of the fornix and the superomedial surface of the thalamus known as the choroidal fissure. The lateral wall is formed by the thalamus superiorly and the hypothalamus inferiorly. The anterior half of the floor of the third ventricle is formed by diencephalic structures, and the posterior half is formed by mesencephalic structures. The anterior wall viewed from within the third ventricle is formed, from superior to inferior, by the columns of the fornix, foramen of Monro, anterior commissure, lamina terminalis, optic recess, and optic chiasm. The posterior wall viewed from within the third ventricle is formed, from superior to inferior, by the suprapineal recess, the habenular commissure, the pineal body and its recess, the posterior commissure, and the aqueduct of Sylvius (20). The posterior portion of the medial limit of the region of the basal ganglia is related to the pulvinar of the thalamus. The pulvinar constitutes the anterolateral wall of the atrium of the lateral ventricle. The roof of the atrium is formed by the body, splenium, and tapetum of the corpus callosum. The medial wall is formed by the bulbus of the corpus callosum, and by the calcar avis. The lateral wall has an anterior part, formed by the caudate nucleus as it wraps around the lateral margin of the pulvinar, and a posterior part formed by the fibers of the tapetum of the corpus callosum. The anterior wall has a medial part composed of the crus of the fornix as it wraps around the posterior part of the pulvinar, and a lateral part, formed by the pulvinar of the thalamus. Arterial Relationships The arterial supply to the anterior portion of the medial limit of the region of the basal ganglia is provided predominantly by the medial group of lenticulostriate arteries originating from the M1 segment of the middle cerebral artery but may also occur through perforating branches from the A1 segment of the anterior cerebral artery (Figs. 2A and 4A). The middle and posterior
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portions receive arterial supply from the internal carotid and from the anterior, middle, and posterior cerebral arteries. The branches from the posterior communicating artery penetrate the floor of the third ventricle and hypothalamus to reach the thalamus in the area below the body of the lateral ventricle. The choroidal segment of the internal carotid artery sends branches through the anterior perforated substance to supply structures in or near the walls of the lateral ventricles. The recurrent artery and the segment of the anterior cerebral artery proximal to the anterior communicating artery also send branches into the area of the lateral wall of the frontal horn and body. The intermediate and lateral groups of lenticulostriate arteries pass through the putamen and adjacent part of the globus pallidus and arch medially and posteriorly to supply the upper anteroposterior parts of the internal capsule and body and head of the caudate nucleus. The medial lenticulostriate arteries irrigate the lateral part of the globus pallidus, the superior part of the anterior limb of the internal capsule, and the anterior superior part of the head of the caudate nucleus. The anterior choroidal artery sends branches along its course that, among other structures, will supply the globus pallidus, genu and posterior limb of the internal capsule, tail of the caudate, and the thalamus. The lateral posterior choroidal artery arises from the posterior cerebral artery or its cortical branches and enters the ventricle, passing laterally around the pulvinar and through the choroidal fissure at the level of the fimbria or the crura of the fornix to reach the choroid plexus in the temporal horn, atrium, and body. Along its course it sends branches to the thalamus, geniculate bodies, cerebral peduncle, pineal body, posterior commissure, caudate nucleus, and splenium. The medial posterior choroidal artery arises from the proximal posterior cerebral artery and encircles the midbrain to enter the roof of the third ventricle at the sides of the pineal gland to course in the velum interpositum, between the thalami, adjacent to the internal cerebral vein. It supplies the choroid plexus in the roof of the third ventricle and may send branches to the cerebral peduncles, geniculate bodies, tegmentum, colliculi, pulvinar, pineal body, posterior commissure, habenula, stria medullaris thalami, occipital cortex, and thalamus. The anterior and posterior thalamoperforating arteries branch from the posterior communicating artery and the P1 segment of the posterior cerebral artery, respectively, and enter the brain through the posterior perforated substance to supply the anterior two-thirds of the thalamus in the area below the floor of the body of the lateral ventricle, the cerebral peduncles, hypothalamus, and internal capsule. The thalamogeniculate arteries enter the brain in the area of the geniculate bodies and send branches into the posterolateral part of the thalamus and the adjacent part of the internal capsule (5). Venous Relationships The lateral aspect of the frontal horn of the lateral ventricle is drained by the anterior caudate veins that course on the ventricular surface of the head of the caudate nucleus and terminate near the foramen of Monro in the thalamostriate vein or join the posterior caudate veins in the body of the lateral ventricle. In the middle part, the thalamostriate vein arises from tributaries that drain the lateral wall of the body and pass forward in the striothalamic sulcus, between the caudate nucleus and the thalamus, to penetrate the foramen of Monro and enter the velum interpositum to join the internal cerebral veins. The veins from the superior and medial portions of the thalamus empty into the internal cerebral or great vein or their tributaries, and those from the inferior and lateral portions of the thalamus drain into the basal vein or its tributaries. The lateral atrial veins course forward on the lateral wall of the atrium across the tail of the caudate nucleus where they turn medially on the posterior surface of the pulvinar and pass through the choroidal fissure to reach the quadrigeminal cistern and join the internal cerebral, basal, or great vein. The venous relationships in the quadrigeminal cistern medial to the atrium are extremely complex because the internal cerebral, basal, great vein and their tributaries converge to that area. The veins from the frontal horn, body, and part of the atrium drain into the internal cerebral veins that course through the velum interpositum and terminate in the great vein. The basal vein terminates within the quadrigeminal cistern by joining the internal cerebral or great vein. The great vein passes below the splenium to enter the straight sinus at the tentorial apex. Medial Type AVMs Basal ganglia region AVMs of the medial type are also subdivided into three types: anterior, middle, and posterior.
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Anterior medial AVMs are located in the region of the head of the caudate nucleus. They are supplied by perforators from the M1 segment of the middle cerebral artery and by perforators from the A1 segment of the anterior cerebral artery. The venous drainage is through caudate veins to the internal cerebral veins. We prefer to approach these lesions directly through a transsulcal route through the posterior portion of the superior frontal sulcus, as we find there is need for excessive brain retraction when the transcallosal route is used (Fig. 7A and C). The middle medial AVMs are located superiorly to the internal cerebral veins and thus are related to the floor and lateral wall of the lateral ventricle or are located inferior to the vein and related to the wall of the third ventricle. Those related to the floor of the lateral ventricle are usually in close relationship to the body of the caudate and to the superior aspect of the thalamus. They are supplied by branches of the lateral posterior choroidal artery and at times by posterior thalamoperforating arteries. Venous drainage occurs through the internal cerebral veins. We approach such lesions through a transcallosal transventricular route. Lesions located on the walls of the third ventricle are supplied by branches from the medial posterior choroidal artery and by anterior and posterior thalamoperforating arteries from the internal carotid artery and the P1 segment of the posterior cerebral artery, respectively. Venous drainage occurs through the internal cerebral veins. Surgery for these lesions is controversial. The risk of major neurological deficits is high because of the technical difficulties posed by their very deep location and by the difficulties encountered in controlling the arterial perforators (Fig. 8).
Figure 8 (A) Anatomical dissection showing the venous drainage pattern of the right cerebral hemisphere: 1. Body of corpus callosum; 2. body of lateral ventricle; 3. splenium of corpus callosum; 4. internal cerebral vein; 5. vein of Galen; 6. straight sinus; 7. basal vein of Rosenthal (cut); 8. third ventricle; 9. posterior cerebral artery. (See color insert.) (B) Right vertebral digital subtraction arterial angiogram of a similar arteriovenous malformation (AVM) located in the third ventricle in the anterior thalamus supplied by the posterior thalamoperforating arteries and drained into the internal cerebral vein. Note that the internal cerebral vein is a reliable landmark for the exact location of the AVM. (C) Right vertebral digital subtraction arterial angiogram of an AVM located in the third ventricle in the anterior thalamus and velum interpositum cistern supplied by the posterior thalamoperforating arteries and drained into the internal cerebral vein.
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Medial posterior AVMs are located in the posterior limit of the region of the basal ganglia in the medial portion of the pulvinar of the thalamus. These AVMs can be supplied by the medial and lateral posterior choroidal arteries and by the thalamogeniculate artery. They usually drain into the vein of Galen through the basal vein of Rosenthal or through the internal cerebral vein. These lesions are amenable to surgical treatment although it may be technically very difficult as the deep draining veins tend to be in the way of the approach to the malformation. We prefer an interhemispheric parietal approach where a small portion of the splenium of the corpus callosum has to be resected, or a interhemispheric occipital supratentorial approach, where the tentorium cerebelli is opened and the AVM is approached through the isthmus of the cingulate gyrus. These cases are sometimes referred for preoperative embolization. Superior Type AVMs Basal ganglia region AVMs of the superior type are related to the deep cerebral white matter that surrounds the ventricles. They are usually related to the ventricular walls and may invade the nuclei in the basal ganglia. The arterial supply is through branches of the M2 and M3 segments of the middle cerebral artery and the lenticulostriate arteries. Venous drainage usually is through the deep venous system. AVMs OF THE POSTERIOR FOSSA For surgical purposes, AVMs presenting in the posterior fossa can be classified into three major groups: those entirely located in the cerebellum (either in the hemispheres or in the vermis), those that exclusively involve the brain stem, and those that have mixed cerebellar and brain stem components. According to their location, these malformations then can be subdivided into superficial and deep lesions. Anatomically the superficial AVMs that involve the cerebellum are classified according to the cortical surface that they involve. Lesions that involve the tentorial surface of the cerebellum are supplied primarily by branches of the superior cerebellar artery. These lesions usually drain anteriorly into the vein of Galen and into the straight sinus through an anterior branch of the superior vermian vein, or they may drain directly into the torcular through a posterior branch of the superior vermian vein. AVMs located in the tentorial surface of the cerebellum are preferably approached through a supracerebellar infratentorial route. In cases where the AVM extends inferiorly, the craniotomy also should include exposure of the suboccipital surface of the cerebellum. Some AVMs that are located anteriorly in the cerebellar hemispheres, i.e., those in the quadrangular lobule of the cerebellum, can be approached through a pretemporal (10) exposure with section of the tentorium. Lesions that involve the petrosal surface of the cerebellum are supplied primarily by branches of the anterior inferior cerebellar artery (AICA) and drained through the superior petrosal vein—formed by the union of the transverse pontine vein, vein of the middle cerebellar peduncle, vein of the cerebellomedullary fissure, and the pontotrigeminal vein—into the superior petrosal sinus. AVMs located in the petrosal surface are best approached through a suboccipital retromastoid approach that reaches the level of the foramen magnum with exposure of the transverse and sigmoid sinuses. Those AVMs that are located in the suboccipital surface of the cerebellum are usually supplied by branches of the posterior inferior cerebellar artery (PICA) and drain through the inferior vermian vein and cortical hemispheric veins into the transverse sinus. These lesions are usually approached through a large midline suboccipital craniotomy or craniectomy that often includes the resection of the posterior arch of the atlas. Large lesions can receive blood supply from all three arterial systems in the posterior fossa and at times can recruit meningeal branches from the extracranial vertebral artery. Such lesions should be approached following the same principles of wide exposure of the cisterns, blood supply, and venous drainage involved with the lesion. Lesions that involve the cerebellar vermis are usually supplied by vermian branches of the superior cerebellar or posterior inferior cerebellar arteries. Vermian AVMs located in the tentorial surface are drained primarily through the superior vermian veins, which are divided
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into an anterior and a posterior group. Lesions in the anterior portion of the superior vermis are drained through the anterior vermian vein, whereas those in the posterior portion are drained through the posterior vermian vein. Vermian AVMs located in the suboccipital surface are usually drained through the inferior vermian vein. Deep cerebellar AVMs that involve the cerebellar peduncles can be surgically excised when the lesion does not involve the structures located in front of the level of the flocculus. Lesions extending beyond that point are intimately related to important structures of the brain stem. Lesions involving the brain stem are surgically approached only in cases where a pial surface can be identified. The arterial supply to such lesions usually comes from perforating branches from the superior cerebellar artery, AICA, and PICA. In our opinion lesions that are located deeply in the brain stem are beyond the scope of any of today’s available treatments. AVMs located in the dorsal aspect of the midbrain, i.e., posterior to the lateral mesencephalic sulcus, can be approached through the supracerebellar infratentorial route, whereas those located in the lateral aspect of the midbrain are best approached through a pretemporal transtentorial approach. Lesions located in the lateral surface of the pons or of the medulla are approached through the suboccipital retrosigmoid route. REFERENCES 1. de Oliveira E, Tedeschi H, Siqueira MG, Ono M, Rhoton AL Jr., Peace D. Anatomic principles of cerebrovascular surgery for arteriovenous malformations. Clin Neurosurg 1993; 41:364–380. 2. Ono M, Kubik S, Abernathey CD. Atlas of the Cerebral Sulci. Stuttgart: Georg Thieme Verlag, 1990: 35–135. 3. Ono M, Rhoton AL Jr., Peace D, et al. Microsurgical anatomy of the deep venous system of the brain. Neurosurgery 1984; 15:621–657. 4. Ono M, Ono M, Rhoton AL Jr., Barry M. Microsurgical anatomy of the region of the tentorial incisura. J Neurosurg 1984; 60:365–399. 5. Timurkaynak E, Rhoton AL Jr., Barry M. Microsurgical anatomy and operative approaches to the lateral ventricles. Neurosurgery 1986; 19:685–723. 6. Ojemann RG, Heros RC, Crowell RM. Surgical Management of Cerebrovascular Disease. 2d ed. Baltimore: Williams & Wilkins, 1988:347–413. 7. Stein BM. Arteriovenous malformations of the medial cerebral hemisphere and the limbic system. J Neurosurg 1984; 60:23–31. 8. Yasargil MG. Microneurosurgery. AVM of the Brain. Vol. IIIB. Stuttgart: Georg Thieme Verlag, 1988:204–367. 9. de Oliveira E, Siqueira MG, Tedeschi H, Peace DA. Technical aspects of the fronto-temporosphenoidal craniotomy. In: Surgical Anatomy for Microneurosurgery VI. Japan, 1994:3–8. 10. de Oliveira E, Tedeschi H, Siqueira MG, Peace D. The pretemporal approach to the interpeduncular and petroclival regions—technical note. Acta Neurochir 1995; 136(3–4):204–211. 11. Sano K. Temporo-polar approach to aneurysm of the basilar artery at and around the distal bifurcation: technical note. Neurol Res 1980; 2:361–367. 12. de Oliveira E, Tedeschi H, Siqueira M G, Peace D. Surgical approaches for aneurysms of the basilar artery bifurcation. In: Surgical Anatomy for Microneurosurgery VI. Japan, 1994:34–44. 13. Yasargil MG, Teddy PJ, Roth P. Selective amygdalo-hippocampectomy, operative anatomy and surgical technique. In: Symon L et al., eds. Advances and Technical Standards in Neurosurgery. Vol. 12. Wien: Springer-Verlag, 1985:93–119. 14. Drake CG. Cerebral arteriovenous malformations: considerations for and experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–208. 15. Heros RC. Arteriovenous malformations of the medial temporal lobe. Surgical approach and neuroradiological characterization. J Neurosurg 1982; 56:44–52. 16. Wilson CB, Martin NA. Deep supratentorial arteriovenous malformations. In: Wilson CB, Stein BM, eds. Intracranial Arteriovenous Malformations. Baltimore: Williams & Wilkins, 1984:184–208. 17. Solomon RA, Stein BM. Surgical management of arteriovenous malformations that follow the tentorial ring. Neurosurgery 1986; 18:708–715. 18. Rosner SS, Rhoton AL Jr., Ono M, Barry M. Microsurgical anatomy of the anterior perforating arteries. J Neurosurg 1984; 61:468–485. 19. Gibo H, Carver CC, Rhoton AL Jr, Lenkey C, Mitchell RJ. Microsurgical anatomy of the middle cerebral artery. J Neurosurg 1981; 54:151–169. 20. Yamamoto I, Rhoton AL Jr., Peace DA. Microsurgery of the third ventricle: part 1. microsurgical anatomy. Neurosurgery 1981; 8:334–356.
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Pathology and Genetic Factors Ronald F. Moussa and John H. Wong Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
Issam A. Awad Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, and Evanston Northwestern Healthcare, Evanston, Illinois, U.S.A.
PATHOLOGY In the middle of the 18th century, Hunter (1757) (1) and Petit (1774) (2) developed the first systematic description of human vascular anomalies. During the next century, the works of Hooper (1841) (3), Bell (1815) (4), and Virchow (1863) (5) led to further terminology to describe vascular lesions. A more rational analysis was later developed by Reinhoff (6) and Malan (7), who based developmental pathogenesis on errors in embryogenesis that occur at specific time points and their consequences on vasculogenesis. Their efforts led to a classification system of vascular anomalies with four categories on the basis of developmental considerations: capillary, venous, arteriovenous, and troncular arteriovenous anomalies. Most recently, the pathoanatomic works of McCormick et al. (8–12), and Russel and Rubinstein (13) led to the foundation for the current widely accepted classification system for cerebral vascular anomalies. This classification system consists of four categories: arteriovenous malformations (AVMs), cavernous malformations, venous malformations, and capillary telangiectasias. Several mixed lesion types have been described with transitional or mixed features in the same lesion (14,15). Location and Angioarchitecture Cerebral AVMs are encountered throughout the central nervous system. They seem to predominate in areas supplied by the middle cerebral artery (8). Ninety-three percent are located supratentorially in the frontotemporal lobes. Intracranial dura may be affected, leading to the formation of dural vascular malformations. Angiography remains the gold standard method for diagnosing and evaluating AVMs and provides invaluable information about their angioarchitecture. Analysis of vascular patterns is useful in understanding the pathology of this disease. Arterial Supply Cerebral AVMs typically receive their blood supply from intracranial branches of the internal carotid artery and vertebrobasilar systems. Arterial feeders are often multiple, but may sometimes be unique in arteriovenous fistulas. Valavanis in 1996 proposed a classification of arterial feeders based on embryological studies (16). The first type of arterial feeder is termed a terminal or dedicated type that ends in the nidus itself and corresponds to primitive penetrating vessels. The second type is the pseudoterminal ‘‘functional’’ type or vessels ‘‘de passage,’’ which supply the brain beyond the nidus. These vessels are hypothesized to have initiated growth at a later stage or have developed from an established arterial source. The last type is the indirect type and represents ‘‘satellite’’ branches from an artery in close proximity to the nidus. They correspond to vessel ingrowth after final structural development of the brain has been completed. Other sources of blood supply to AVMs may exist, such as those emerging from the choroid plexus (17) or meningeal branches of the external carotid artery. The frequency of meningeal arterial contribution is significantly higher in superficial AVMs, especially in the temporal, parietal, and occipital regions. Larger AVMs and lesions with higher degrees of angiographic arteriovenous shunting with steal phenomena are also factors that favor meningeal arterial development. Meningeal feeders were previously thought to be congenital, but recent evidence suggests that they may develop during growth of the AVM (18).
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Stenoses of the feeding arteries to cerebral AVMs have been reported in approximately 20% of cases. It is possible that if these stenoses progress, thrombosis of the AVM may occur (19). Nidus Architecture The nidus is best conceived as a functional unit rather than a pathoanatomic entity. Yasargil described two types of arteriovenous connections within the lesion nidus: a direct fistulous connection between arteries and veins, and a plexiform pattern with ramifications existing between afferent and efferent vessels (20). Houdart et al. (21) in 1993 proposed three types of niduses based upon hemodynamic and radiological features: the arteriovenous fistula, where direct communications exist between arteries and veins; the arteriolovenous fistula that exists between several arterial branches and a vein; and the arteriolovenulous fistula, which is the most classical type and is marked by ramifications between arteries and venules. Venous Drainage Venous blood from the AVM can drain through a single or multiple channels toward the superficial or deep venous systems. In high flow fistulas, an aneurysmal dilatation of the great vein of Galen can be observed (22). Multiplicity and Associated Lesions Multiple intracranial AVMs are exceptional (23,24). The occurrence of multiple AVMs in one patient should raise the diagnosis of hereditary hemorrhagic telangiectasia (HHT). The association of intracranial and intraspinal AVMs is also rare (25). Other unusual associations include AVM and multiple congenital cardiac defects or tumors (26). Oligodendrogliomas and metastases have been reported to occur in proximity to AVMs, raising the question of whether there is a pathophysiological relationship between the two entities (27,28). Associated aneurysms are reported to occur with AVMs in 3% to 28% of patients in most case series (29–31). Three types of aneurysms have been described in relation to the location of the nidus: those related to vessels feeding the AVM, those remote from the AVM, and those that are intranidal. Perata et al. classified aneurysms associated with AVMs into four categories (32). Type 1 aneurysms are dysplastic lesions located on the circle of Willis independent from the nidus. Type 2 aneurysms are located on the circle of Willis on the same artery supplying the AVM. Type 3 lesions are related to a vessel feeding the AVM. Type 4 aneurysms are intranidal. Gross Pathology Autopsy analysis provides valuable information about the macroscopic features of AVMs. The postmortem appearance of an AVM is often less impressive than its intraoperative appearance because of the collapse of previously distended vessels (13). The living appearance of an AVM can in some measure be restored by the postmortem intravascular injection of a suitable medium. The most typical gross appearance is that of a ‘‘bag of worms’’ (Fig. 1). The mass is often wedge shaped, extending from the leptomeningeal surface deep into the parenchyma,
Figure 1 Gross appearance of a cerebral arteriovenous malformation in the occipital lobe. Source: Courtesy of J.H. Kim. (See color insert.)
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Figure 2 Histologic appearance of cerebral arteriovenous malformation nidus. Hematoxylin and eosin stain, 40x. Thrombosed red blood cells (red); arterialized vessel walls (purple); gliotic brain (blue). Source: Courtesy of J.H. Kim. (See color insert.)
frequently reaching or entering the ventricular system. This configuration accounts for the occurrence of bleeding within the intracranial compartment with the potential of extension toward the ventricles or the subarachnoid space. The vessels vary in size and may exceed one centimeter in diameter. Conversely, very small AVMs can be totally missed on pathologic examination even with thin slices. These malformations are typically cryptic or angiographically occult (33). They may be responsible for intraparenchymal hemorrhage where no etiology is found on angiographic or even intraoperative examinations. The vessel walls are variably thickened, and atheroma or calcification may be encountered macroscopically (8). Associated aneurysms may be observed on feeding or intranidal vessels. The arachnoid covering is usually discolored and thickened, while adjacent convolutions show variable degrees of atrophy as a result of chronic ischemia (13). Pigmentation from previous hemorrhage may be present in the adjacent brain, with loss of normal distinction between gray and white matter. Histopathology The histologic appearance of AVMs may range from relatively well-differentiated arteries and veins to malformed, thickened, or thin-walled hyalinized vessels (Fig. 2) (8,34). Arteries and arterialized veins may be difficult to distinguish from one another. A normal capillary bed interposed between arteries and veins is lacking (22). Ultrastructural analysis reveals that the endothelium of these vessels is different from other cerebrovascular endothelium (20). Segmental dilatation of vessels is often present with deposition of amyloid-like material in the vessel wall. Ossification is rare (8). A close analysis of the arterial component of the AVM reveals that the usual lamination of elastic and muscle fibers in the vessel wall is altered in that the internal elastic lamina may be reduplicated or interrupted (Fig. 3). The muscular media varies in thickness even within the
Figure 3 Histologic demonstration of elastic fibers in the arterialized vessels of a cerebral arteriovenous malformation. Elastic von Gieson stain, 40x. Source: Courtesy of J.H. Kim. (See color insert.)
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same blood vessel. In areas of maximal thinning, aneurysms may develop, whereas thickened areas can evoke leiomyoma nodules (35). The use of monoclonal antibody against vascular musculature has permitted the identification of actin abnormalities of the muscular layer. Described abnormalities included partially developed media, two layers of the media separated by a well-formed internal elastic membrane, total or partial disarray of the muscle coat, and partial absence of the media. Vessels previously thought to be large capillaries have been determined to be postcapillary venules by virtue of the presence of a distinct muscular layer (34). Determining the presence of actin can be a useful adjunct to conventional histologic stains for the accurate and selective detection of smooth muscle cells (36). Atheroma, fibrosis, and patchy calcification can also be observed in the vessel wall. On the venous side, thickening of the vein due to collagenous tissue is usually noted. Thrombosis may be found. The brain parenchyma within the nidus is typically discolored and gliotic. The parenchyma around and within the malformation is consistently degenerated with multiple foci of lymphocytic infiltration (8). Neuronal loss in the brain secondary to a vascular steal phenomenon by the AVM (37) and increase in fibrillary glia are usually reported. Hemosiderin pigment is commonly found, especially within hemosiderin granules in macrophages (8,13). Immunohistochemistry Immunostaining studies can be used to analyze protein expression associated with AVMs (Fig. 4). Rothbart et al. demonstrated the expression of vascular endothelial growth factor (VEGF) in a study of surgically excised vascular malformations (38). VEGF expression was predominantly identified in the subendothelial layer and media of vessels of all sizes in AVMs. Basic fibroblast growth factor was faintly expressed around individual monocytes and fibrocytes. Structural and matrix proteins have also been examined with immunohistochemical and immunofluorescent techniques. The expression of laminin, factor VIII antigen, and fibronectin was variable. These proteins may play important roles in homeostasis of the vessel wall and in its permeability and response to injury. The vascular cellular adhesion molecule and intercellular adhesion molecule-1 were also expressed in some AVMs, consistent with developing vessels in early phases of embryogenesis. AVMs also expressed collagen type IV and alpha smooth muscle actin. The pattern of expression of these different factors suggests diffuse activation of angiogenesis without specific relation to individual vessel types or recent hemorrhage. Defining the role of angiogenesis in vascular malformations can provide insight into their pathogenesis and suggest novel strategies for modification of their behavior. Effect of Embolization and Radiation Therapy The increasing use of embolization and radiosurgery as surgical adjuncts for the treatment of AVMs has allowed study of their pathological responses to such interventions. Embolization induces a chain of events that results from interaction between the embolizing agent and the vessel wall (39) and depends on the type of embolizing agent used such as bucrylate
Figure 4 Immunohistochemical analysis of arteriovenous malformation (AVM) vessels. (A) Laminin (a component of the basement membrane that regulates vessel wall stability) immunoexpression in an AVM vessel, 20x. (B) VEGF immunoexpression in an arterialized draining vein of an AVM specimen, 40x. (C) Flk-1 (an endothelial-specific receptor tyrosine kinase) immunoexpression in the endothelium of an AVM vessel, 40x. (See color insert.)
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(isobutyl-2-cyanoacrylate), silk, or polyvinyl alcohol. Histologic reactions vary from patchy mural angionecrosis, thinning of the vessel wall with rupture, mononuclear infiltration, necrotizing vasculitis, and an intense granulomatous response (39,40). Radiosurgery can induce pathologic changes in and around the AVM. Nataf et al. proposed a classification scheme of postradiosurgical effects identified on magnetic resonance imaging, ranging from no parenchymal change (grade 1) to contrast enhancement with central and peripheral hypointensity suggesting necrosis (grade 4) (41). The latter finding was significantly related to clinical deterioration. Postradiation changes have also been studied in surgical and autopsy AVM specimens. Schneider et al. used routine histopathological stains and immunohistochemical techniques to detect smooth-muscle actin, factor VIII, and type IV collagen in nine AVM specimens obtained 10 months to more than 5 years after gamma knife radiosurgery (42). Blood vessels in the AVMs showed progressive changes leading to narrowing or obliteration of the lumen. The earliest change was damage to endothelial cells. The next change was progressive thickening of the intimal layer caused by proliferation of smooth muscle cells that elaborate an extracellular matrix, which includes type IV collagen. Finally, cellular degeneration and hyaline transformation were noted. The degree of histopathological change and the relative number of vessels showing such changes were significantly correlated with time after radiosurgery and with reduction in AVM size demonstrated on follow-up imaging. The authors concluded that radiosurgery of AVMs causes endothelial damage, which induces the proliferation of smooth muscle cells and the elaboration of extracellular collagen by these cells, leading to progressive stenosis and obliteration of the AVM nidus. Normal surrounding blood vessels may also be affected by high-dose, single-fraction irradiation, although the abnormal AVM vessels have been reported to be more susceptible (43). However, segmental hyalinization of AVM vessels with a patent nidus has been reported and may explain the occurrence of hemorrhage after radiosurgery (44). Recurrence and Spontaneous Obliteration Sonstein et al. described several children who developed recurrent AVMs despite normal postoperative angiography after surgical resection (45). On the basis of the increased levels of VEGF found on immunocytochemistry staining, they hypothesized that VEGF produced by perilesional astrocytes may lead to the formation or recurrence of cerebral AVMs, especially in children, due to an immature cerebral vasculature or dysregulation of blood vessel formation during early development. This study suggests that ongoing angiogenesis plays a role in the growth or recurrence of AVMs. The recurrence of AVMs after partial embolization and recruitment of feeding vessels from distant vascular beds also suggest that angiogenic paracrine signaling pathways participate in the development of AVMs. AVMs of the cerebral circulation rarely regress spontaneously. Abdulrauf et al. identified a total of 30 cases of AVMs, including those in the medical literature, that obliterated spontaneously without definitive treatment (46). The majority of such lesions presented with hemorrhage, had a small vascular nidus, and had a single draining vein possibly predisposing to lesion thrombosis. Using immunohistochemical studies, the authors also found that AVM nidal vessels demonstrated possible ongoing angiogenesis after documented angiographic obliteration. GENETIC FACTORS Careful assessment of the genetic background of patients harboring AVMs is important not only during clinical assessment and screening, but also in understanding potential underlying hereditary disease and molecular factors. AVMs may be related to possible genetic mechanisms in several ways. A genetic basis underlying an AVM may be clearly identified such as in patients suffering from HHT. However, cases of familial AVMs have been described where several relatives harbor cerebrovascular pathology without clear demonstration of any known genetic defect (47). AVMs may also be present in association with neurocutaneous disorders that arise from embryonic maldevelopment such as Sturge–Weber disease and Wyburn–Mason syndrome. In 1928, Pfeifer hypothesized that AVMs arise from the persistence of one of multiple arteriovenous fistulas that normally form and disappear during development. This theory was rejected by Campbell (48), Scharrer (49), and Vidyasagar (50), all of whom favored the
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hypothesis that AVMs develop from a fistula created by fetal transverse veins crossing at right angles to developing longitudinal arteries before the fetus reaches 80 mm in length. This hypothesis was supported by the observation that adult AVMs frequently demonstrate evidence of an early failure in venous maturation. Deshpande et al. (51) identified arterialized venous channels in AVMs that microscopically resembled persistent embryonic veins. These authors proposed that the intimal lining of the persistent embryonic veins reflects the approximate fetal age during which the arteriovenous fistula is likely to have occurred. Mullan et al. suggested that a combination of congenital predisposition and extrinsic factors might result in the AVM development (47), thus offering an explanation for why these presumably congenital lesions become symptomatic in later life. The report of growth of an AVM in a newborn confirms the evolution of these lesions (52). The role of abnormal gene regulation in the pathogenesis of cerebral AVMs has also been investigated. Repression of the preproendothelin-1 gene in intracranial AVMs has been studied by Rhoten et al. (53). They demonstrated the absence of endothelin-1 peptide and preproendothelin-1 messenger ribonucleic acid in the intranidal AVM vasculature, whereas these factors were predominantly expressed in control subjects with normal cerebral vasculature. This study provides supplementary evidence for the role of genetic defects in the genesis and development of AVMs. Hereditary Conditions Hereditary Hemorrhagic Telangiectasia Known as Osler-Weber-Rendu disease, HHT belongs to a group of familial inherited disorders with transmission of an autosomal dominant trait and high penetrance (54,55). HHT typically involves multiple dermal, mucosal, and visceral telangiectasias and AVMs, leading to recurrent bleeding episodes. The prevalence of neurological symptoms ranges from 8% to 27% (56), including headache, seizures, brain abscess, hepatic encephalopathy, infarct, and intracerebral and subarachnoid hemorrhage (57). Structural cerebral lesions are characterized by vascular malformations that represent abnormal arteriovenous connections that fail to differentiate into arteriolar, capillary, and venular channels (58). Neurologic complications such as cerebral ischemic events can occur secondary to pulmonary AVMs. In a recent study, Fulbright et al. showed that the prevalence of cerebral vascular malformations on magnetic resonance imaging was 23% in a series of patients afflicted with HHT (56). Among these lesions, most (76%) were indeterminate lesions with variable signal intensity, 8% were venous malformations, and 16% were AVMs. Other lesions encountered include pial arteriovenous fistulas, telangiectasias, and aneurysms (57). Multiple AVMs in the same patient were present in one-third of all HHT patients with cerebral AVMs. This entity has never been reported sporadically in a single patient (59,60). Genetic studies have shown that HHT disease expression is linked to chromosome 9q33-q34 in certain families and to chromosome 12q in others (55,61). On chromosome 9, the defect has been localized to a gene (ENG) that codes for endoglin, a protein abundant in endothelial cells. This protein normally binds to the transforming growth factor-b and initiates responses to growth factors (54). The locus on chromosome 12q, named ORW2, has been identified as active in receptor-like kinase gene (ACVRLK1) expression (62). Other Genetic Syndromes Associated with Cerebral AVMs Bannayan syndrome is an inherited autosomal dominant disease involving hamartomas (usually hemangiomas and lipomas) and macrocephaly with other inconstant features. Complex intracranial AVMs occurring in one family have been reported (63). Autosomal dominant polycystic kidney disease, a relatively common genetic disorder, has been associated with intracranial AVMs as well as with intracranial aneurysms (64). Sporadic Conditions Sturge–Weber Syndrome Sturge–Weber disease is a neurocutaneous syndrome characterized by facial ‘‘port wine’’ nevi in the cutaneous region served by the ophthalmic division of the trigeminal nerve, angiomatous lesions of the leptomeninges, retinal angiomas, hemiatrophy, and cortical calcifications. Also known as encephalotrigeminal angiomatosis (65), the neurological picture is characterized by seizures along with moderate to severe mental retardation.
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Radiological studies demonstrate the characteristic ‘‘tram track’’ type of calcification seen on plain film radiography and extensive cortical enhancement on computed tomographic and magnetic resonance imaging (66). The use of technetium-99m-hexamethylpropyleneamine oxime brain single-photon emission computed tomography to detect regions of hypoperfusion not otherwise evident on imaging has been advocated (67). Pathological examination typically reveals a plexus of telangiectatic capillaries or venules lying between the pia and arachnoid with adjacent cerebral cortical atrophy (68). The genetic cause of this disease is unknown. A number of families with lesions affecting several members in successive generations due to incomplete manifestation of a familial form of this disease have been reported (69). Wyburn–Mason Syndrome Also known in the literature as the ‘‘bonnet-blanc-dechaume’’ syndrome or mesencephalooculo-facial angiomatosis, Wyburn–Mason syndrome is a developmental nonhereditary condition characterized by a unilateral retinocephalic vascular malformation. Bilateral intracranial vascular anomalies and large deeply located AVMs have been reported (70). Other Syndromes Associated with Cerebral AVMs The association of cerebral and cutaneous vascular hamartomas distinct from the Sturge– Weber syndrome has been reported and constitutes a distinct, hereditary entity with autosomal dominant inheritance and variable penetrance. The clinical manifestations of this syndrome are visible, painful vascular nevi, epilepsy, cerebral hemorrhage, and focal neurological deficits. The preponderance of male patients with the full expression of this ill-defined syndrome suggests a possible hormonal influence on disease expression (71). Whether this entity is a separate genetic disorder or an incomplete form of Sturge–Weber disease has yet to be established. Familial Cases of AVMs Familial AVMs have been reported to occur in several members of a family unrelated to any known genetic disorders such as HHT (72). A possible autosomal dominant inheritance pattern has been reported in a family where AVMs were present in three successive generations (73). In cases of suspected familial AVM, screening and treatment of asymptomatic persons with a family history of cerebral vascular malformation is an important consideration (74–79). REFERENCES 1. Hunter W. The history of an aneurysm of the aorta with some remarks on aneurysms in general. Med Observ Inquir 1757; 1:323. 2. Petit JL. Traie des maladies chirurgicales et operation. Paris: Didot, 1774. 3. Hooper R. Lexicon Medicum. New York: Harper and Brothers, 1841. 4. Bell J. The Principles of Surgery. London: Longman, Hurst, Ree, 1815:456–489. 5. Virchow R. Angiome. Die Krankhaften Geschwulste. Berlin: August Hirschwald, 1863:306–425. 6. Reinhoff WF. Congenital arteriovenous fistula, an embryological study, with report of a case. Bull Johns Hopkins Hosp 1924; 35:271. 7. Malan E. Vascular malformations (angiodysplasias). Milan: Carlo Erba Foundation, 1974:15–26. 8. McCormick WF. The pathology of vascular (‘‘arteriovenous’’) malformations. J Neurosurg 1966; 24:807–816. 9. McCormick WF, Nofzinger JD. Cryptic vascular malformations of the central nervous system. J Neurosurg 1966; 24:865–875. 10. McCormick WF, Hardman JM, Boulter TR. Vascular malformations (angiomas) of the brain, with special reference to those occurring in the posterior fossa. J Neurosurg 1968; 28:241–251. 11. McCormick WF. Pathology of vascular malformations of the brain. In: Wilson CB, Stein BM, eds. Intracranial Arteriovenous Malformations. Baltimore: Williams & Wilkins, 1984:44–63. 12. McCormick WF. The pathology of angiomas. In: Fein J, Flamm ES, eds. Cerebrovascular Surgery. New York: Springer-Verlag, 1985:1073–1095. 13. Russel DS, Rubinstein LJ. Pathology of Tumors of the Nervous System. Vol. 3rd. Baltimore: William & Wilkins, 1971:93–102. 14. Houkin K, Sato M, Echizenya K, Nakagawa T. Mixed pial–dural arteriovenous malformation. Case report. No Shinkei Geka 1984; 12:347–352.
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44. Elisevich K, Redekop G, Munoz D, Fisher B, Wiese K, Drake C. Neuropathology of intracranial arteriovenous malformations following conventional radiation therapy. Stereotact Funct Neurosurg 1994; 63:250–254. 45. Sonstein WJ, Kader A, Michelsen WJ, Llena JF, Hirano A, Casper D. Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study. J Neurosurg 1996; 85:838–845. 46. Abdulrauf SI, Malik GM, Awad IA. Spontaneous angiographic obliteration of cerebral arteriovenous malformations. Neurosurgery 1999; 44:280–287. 47. Mullan S, Mojtahedi S, Johnson DL, Macdonald RL. Embryological basis of some aspects of cerebral vascular fistulas and malformations. J Neurosurg 1996; 85:1–8. 48. Campbell ACP. The vascular architecture of the cat’s brain: a study by vital injection. Res Nerv Ment Dis 1938; 18:69–93. 49. Scharrer E. Arteries and veins in the mammalian brain. Anat Rec 1940; 78:173–196. 50. Vidyasagar C. Persistent embryonic veins in arteriovenous malformations of the brain. Acta Neurochir (Wien) 1978; 40:103–116. 51. Deshpande DH, Vidyasagar C. Histology of the persistent embryonic veins in arteriovenous malformations of brain. Acta Neurochir (Wien) 1980; 53:227–236. 52. Haase J, Hobolth N, Ringsted J. Growing intracranial arteriovenous malformation in a newborn. Childs Nerv Syst 1986; 2:270–272. 53. Rhoten RL, Comair YG, Shedid D, Chyatte D, Simonson MS. Specific repression of the preproendothelin-1 gene in intracranial arteriovenous malformations. J Neurosurg 1997; 86:101–108. 54. McAllister KA, Grogg KM, Johnson DW, et al. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 1994; 8:345–351. 55. Shovlin CL, Hughes JM, Tuddenham EG, et al. A gene for hereditary haemorrhagic telangiectasia maps to chromosome 9q3. Nat Genet 1994; 6:205–209. 56. Fulbright RK, Chaloupka JC, Putman CM, et al. MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations. Am J Neuroradiol 1998; 19:477–484. 57. Roma´n G, Fisher M, Perl DP, Poser CM. Neurological manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): report of 2 cases and review of the literature. Ann Neurol 1978; 4:130–144. 58. Bird RM, Jacques WE. Vascular lesions of hereditary hemorrhagic telangiectasia. N Engl J Med 1959; 260:597–599. 59. Putman CM, Chaloupka JC, Fulbright RK, Awad IA, White RIJ, Fayad PB. Exceptional multiplicity of cerebral arteriovenous malformations associated with hereditary hemorrhagic telangiectasia (OslerWeber-Rendu syndrome). Am J Neuroradiol 1996; 17:1733–1742. 60. King CR, Lovrien EW, Reiss J. Central nervous system arteriovenous malformations in multiple generations of a family with hereditary hemorrhagic telangiectasia. Clin Genet 1977; 12:372–381. 61. Vincent P, Plauchu H, Hazan J, Faure´ S, Weissenbach J, Godet J. A third locus for hereditary haemorrhagic telangiectasia maps to chromosome 12q [published erratum appears in Hum Mol Genet 1995; 4(7):1243]. Hum Mol Genet 1995; 4:945–949. 62. Johnson DW, Berg JN, Baldwin MA, et al. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet 1996; 13:189–195. 63. Palencia R, Ardura J. Bannayan syndrome with intracranial arteriovenous malformations. Anales Espanoles de Pediatria 1986; 25:462–466. 64. Proesmans W, Van Damme B, Casaer P, Marchal G. Autosomal dominant polycystic kidney disease in the neonatal period: association with a cerebral arteriovenous malformation. Pediatrics 1982; 70: 971–975. 65. Smirniotopoulos JG, Murphy FM. The phakomatoses. Am J Neuroradiol 1992; 13:725–746. 66. Osborn AG. Disorders of histogenesis. Neurocutaneous syndromes. In: Diagnostic Neuroradiology. St. Louis Mosby-Year Book, 1994:72–113. 67. Bar-Sever Z, Connolly LP, Barnes PD, Treves ST. Technetium-99m-HMPAO SPECT in Sturge-Weber syndrome. J Nucl Med 1996; 37:81–83. 68. Barkovich AJ. The phacomatoses. In: Pediatric Neuroimaging. New York: Raven Press, 1995:277–319. 69. Louis-Bar D. Sur l’heredite de la maladie de Sturge-Weber-Krabbe. Confina Neurologica 1947; 7: 238–244. 70. Patel U, Gupta SC. Wyburn-Mason syndrome. A case report and review of the literature. Neuroradiology 1990; 31:544–546. 71. Leblanc R, Melanson D, Wilkinson RD. Hereditary neurocutaneous angiomatosis. Report of four cases. J Neurosurg 1996; 85:1135–1142. 72. Boyd MC, Steinbok P, Paty DW. Familial arteriovenous malformations. Report of four cases in one family. J Neurosurg 1985; 62:597–599. 73. Larsen PD, Hellbusch LC, Lefkowitz DM, Schaefer GB. Cerebral arteriovenous malformation in three successive generations. Pediatr Neurol 1997; 17:74–76. 74. Aberfeld DC, Rao KR. Familial arteriovenous malformation of the brain. Neurology 1981; 31:184–186. 75. Roussey M, Le Marec B, Le Francois C, Senecal J. Familial occurrence of arteriovenous malformation of the brain. J Neurosurg 1991; 74:585–589.
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76. Yokoyama K, Asano Y, Murakawa T, et al. Familial occurrence of arteriovenous malformation of the brain. J Neurosurg 1991; 74:585–589. 77. Zellem RT, Buchheit WA. Multiple intracranial arteriovenous malformations: case report. Neurosurgery 1985; 17:88–93. 78. Allard JC, Hochberg FH, Franklin PD, Carter AP. Magnetic resonance imaging in a family with hereditary cerebral arteriovenous malformations. Arch Neurol 1989; 46:184–187. 79. Barre RG, Suter CG, Rosenblum WI. Familial vascular malformation or chance occurrence? Case report of two affected family members. Neurology 1978; 28:98–100.
3
Hemodynamic Properties Michael Morgan Department of Neurosurgery, School of Advanced Medicine, Macquarie University, Sydney, Australia
INTRODUCTION The hemodynamic properties of arteriovenous malformations (AVMs) have been the subject of observation and speculation for many years. The first hemodynamic observations about arteriovenous fistuale were made by William Hunter, who reported in 1764 on a ‘‘particular species of aneurysm... where there is an anastomosis... between the artery and vein... so that blood passes immediately from the trunk of the artery into the trunk of the vein’’ arising as a complication of phlebotomy at the elbow (1). He observed ‘‘the artery... will become larger in the arm, and smaller at the wrist, than it was in the natural state’’ and the vein ‘‘will be dilated or become varicose.’’ He defined the anatomical changes as due to hemodynamic factors, as he explained ‘‘the stream from the (proximal) artery (becomes) larger.’’ This observation clearly demonstrates many of the key features present in AVMs of the brain. The progress in understanding the hemodynamics of AVMs of the brain expanded after the advent of angiography. However, the initial emphasis was on the hemodynamic effects on the brain rather than on the hemodynamics of the lesion itself. Elvidge reported the poor angiographic visualization of arteries in the immediate vicinity of AVMs in 1938 (2). Olivecrona and Riives in 1948 reported the first large series of patients with cerebral AVMs that had been studied angiographically and proposed that progressive deficits, cognitive dysfunction, and cerebral atrophy were due to ‘‘anoxemia of the brain due to shunting of the blood’’ (3). Shortly thereafter, Norlen reported improvement in angiographic visualization of vessels surrounding the AVM upon its resection (4). This preferential diversion of blood from brain to shunt became known by the emotive term ‘‘steal’’ (5). Despite the increasing evidence for circulatory perturbations arising as a consequence of arteriovenous shunting in the brain, the lack of quantification of this disturbance has created significant controversy. As late as 1987 Yasargil published that ‘‘the controversy regarding cerebrovascular steal has not been so much a question as to whether it occurs . . . but whether it is of clinical significance’’ (6). Indeed, as recently as 1982 Malis argued that steal should only occur if there is a restriction of collateral flow to the AVM because of a compensatory increase in carotid flow (7). This argument is based on an understanding of the cerebral circulation that dates back more than 300 years. Willis suggested that carotid flow could increase markedly to supply ‘‘changing needs’’: ‘‘in an humane head, where the generous affections, and the great forces and ardours of the souls are stirred up, the approach of the blood to the confines of the brain, ought to be free and expeditious; and it is behoveful for its river not to run narrow and manifoldly divided rivulets, which would scarce drive a mill, but always with a broad and open channel, such as might bear a ship under sail’’(8). This comment provides some insight into Willis himself, who originally commenced training as a minister of religion, and early speculation into the ability of the flow within the carotids to increase in velocity. A second controversy of AVM hemodynamics is the consequence of their removal. A year before the first successful removal of a cerebral AVM in 1889 by Pean [cited by Yasargil (6)], Gowers described a condition called ‘‘congestive apoplexy’’ as the most severe complication of cerebral congestion (9). He defined ‘‘partial active congestion’’ as that occurring ‘‘when an artery is obstructed, and the adjacent branches of the main vessel receive too much blood.’’ This hyperemia appears to be the central argument today applied to the controversy of hemorrhage and edema complicating surgery for large AVMs. The underlying pathophysiological disturbance has been attributed to loss of autoregulation and has been termed the ‘‘normal perfusion pressure breakthrough’’ theory (10). Challenges to this theory and alternate pathophysiological mechanisms are exemplified by ‘‘occlusive hyperemia’’(11).
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Our understanding of the hemodynamic properties of AVMs is far from complete. Nonetheless it is timely to bring the current clinical controversies into focus against what is known about the hemodynamics that underscore the clinical scenarios thought to be due to perturbations of this physiology. HEMODYNAMIC EFFECT WITHIN THE INTERSTICES OF AN AVM The hemodynamic consequences of AVMs depend in large part on the cross-sectional area of the narrowest point in the communication between the arterial-type vessel and the venoustype vessel. The smallest communications identified in shunting have been suggested to range from less than 0.05 mm (12) to greater than 3.0 mm (as evident by reports of spheres not arrested during embolization procedures) (13–16). That a significant proportion of AVMs have as their narrowest points cross-sectional diameters of greater than 100 mm and at least occasionally greater than 300 mm (12–17) is of significance because in the normal circulation the greatest part of the pressure reduction (therefore, the site of maximal resistance) occurs in vessels of diameter less than 300 mm (18) with the maximum resistance occurring in vessels less than 100 mm (19). Thus, the hemodynamic response results from the low resistance to flow. The consequence of this low resistance has a huge impact on the cerebral circulation, including its effect within the AVM interstices itself. One clinical manifestation of this effect is the development of a bruit. The audible bruit known to be characteristic of AVMs well before the introduction of angiography (20,21) arises as a consequence of vessel wall vibration (22). This vibration occurs as a consequence of the random fluctuation of velocity and pressure within the vessel, i.e., turbulence (23). Turbulence has a significant impact on both the vessel wall within the AVM and the blood itself. The site of turbulent flow within the nidus is influenced by the velocity of flow, diameter of the vessels, change in vessel diameter, and branch morphology. The velocity of flow and the vessel diameter are related in the Reynolds number (Re ¼ qVD/m, where q ¼ density of the fluid (gm/mL), V ¼ velocity (cm/s), D ¼ diameter of the tube, and m ¼ fluid viscosity (poise)). The Re for steady flow through straight tubes predicts the transition from laminar to turbulent flow; the higher the Re, the more likely the flow will be turbulent. Although blood flow in the AVM nidus is not in straight tubes, the general relationship is likely to be applicable. The superimposition of focal stenosis and dilatations present in AVMs lowers the threshold for turbulent flow predicted by the Re. A further potential site for the generation of turbulence is at branch points. If the branch-to-trunk area ratio is one or greater, turbulence is likely to ensue (24). Turbulence has a significant effect on the vessel wall. Three main physiological events account for this effect (25). These are conversion of kinetic energy of blood moving with high velocity into potential energy with consequent lateral pressure; random fluctuation of pressure creating impact shocks leading to distension; and high frequency pressure fluctuation causing structural fatigue. These factors lead to focal dilatations characteristic of the venous varix found in proximity to the AVM nidus. Downstream from the venous varix (in a region of laminar flow), the higher than normal measured velocity and the high measured venous pressure (as high as 21 to 23 mmHg) (26,27) must result in a high shear stress. Inasmuch as the propensity for structural fatigue is less marked with the transition of flow from turbulent to laminar, it can be surmised that shear stress and wall structural fatigue are even greater in the region of turbulence (i.e., the variceal segments). These forces leading to dilatation are also those predisposing to the site of rupture within the nidus of an AVM. Thus, one site of likely rupture is where turbulence occurs on the venous side of the nidus. Turbulent flow may incite more than a mechanical response leading to fatigue in the vessel wall. An increase in endothelial DNA synthesis is reported to occur (28), and endothelial turnover may well be influenced by these shear stresses. A modulation of endothelial transport, an increase in endothelial microfilament bundles, and ultrastructural changes in the subendothelial layer all have been reported to result from high shear stress (29–31). Therefore, the observed pathological changes in normal vessel wall histology may well be, at least in part, an acquired response to the hemodynamic perturbations rather than related to genetically determined structural abnormalities. The high-frequency fluctuations of velocity and pressure associated with turbulence-producing high shear stresses can be detrimental to blood elements. Although no major study of the direct measurements of the Reynolds shear stress in the region of the venous varix has been
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published, evidence that such shear stresses may be of significance is suggested in the experimental arteriovenous fistula, where the introduction of turbulence produced platelet aggregation (32). High shear stress can lead to platelet activation, platelet aggregation, and hemolysis of red cells. HEMODYNAMIC EFFECT ON CEREBRAL BLOOD VESSELS IN THE PRESENCE OF AN AVM Arteries Modeling the pressure flow relationship in the vessels of the brain has often involved invoking the equation of Poiseuille published in 1846 (33). This equation is a special solution of the Navier-Stokes equations of the motion of viscous liquids and was considered as such by Hagenbach (34), who solved the constant in Poiseuille’s equation by producing the equation presented in the familiar form in Table 1. Despite considerable deviation from the ideal, Green and Rapela demonstrated that Poiseuille’s equation can be reasonably applied to vessels of diameter above 100 mm (35), i.e., the size of vessels involved in AVMs. Thus, it is applicable to the arteries that feed AVMs. The lower than normal resistance arising as a consequence of the absence of the smallest arteries and arterioles results in an increase in volume flow per unit time. This circumstance produces a dilatation of the feeding arterial and draining venous systems in response to the high shear stress on the wall and the low transmural pressure. That vessels enlarge with time in response to arteriovenous shunting (the hemodynamic forces) was first described by Hunter in 1764 and conceptively applied to AVMs of the brain in 1958 by Hook and Johanson (36). Physiological parameters measured in AVMs of the brain include blood flow, which has been known for more than 50 years to be as high as three times that of the normal cerebral circulation (37). More invasive measures include the pressure of the dilated feeding vessels, first measured by Nornes and Grip to be between 40 and 70 mmHg with vessel flow velocities as high as 550 cc min1 (at a systemic arterial pressure of between 95 and 105 mmHg at the time of the study) (26). Hassler and Steinmetz (38) found this measurement at the time of craniotomy to range from 45% to 62% of that of the radial artery. These pressures were considered to be significantly below that expected of arteries at this site not supplying AVMs (Fig. 1). Independent investigators have confirmed these observations with pressures calculated in the intact skull with angiographic microcatheters. Although this catheter technique suffers from comparing the cerebral catheter in a downstream direction (thus being lower than the true lateral pressure by the kinetic energy of flow in that vessel) with a catheter directed upstream (thus being higher than the true lateral pressure by the kinetic energy of flow in that vessel), similar results are obtained, with the average feeding artery being 67% to 71% that of the pressure in the femoral catheter (39,40). In comparison, the distal cortical arterial pressure (pial arteries) in individuals without AVMs has been measured at 90% of systemic arterial pressure (41–43). One study of pial artery pressures found that on the side of the AVM they were 6l% of the peripheral systemic pressure and were significantly less than 78% on the matched contralateral side (44) (Table 1). Again, the difference in kinetic energy of flow between the two sides needs to be considered and may reduce this difference. The point of measurement of pressure is crucial as the pressure will be influenced by the distance along the arterial feeder system (Fig. 1). Fogarty-Mack et al. showed this to be the case for a group of AVMs predominantly 2.5–4 cm in diameter. For these cases the pressure in the artery proximal to the AVM when compared with peripheral systemic Table 1 Poiseuille Equation Q ¼ pR4(P1 P2)/8mL Q ¼ volume flow per unit time; R ¼ internal radius; P1 P2 ¼ pressure drop along L; L ¼ the length of the tube; m ¼ viscosity. The conditions under which Poiseuille’s equation apply include the following: The fluid is homogeneous, and its viscosity is the same at all rates of shear. The liquid does not slip at the wall. The flow is laminar (i.e., the liquid at all points is moving parallel to the walls of the tube). The rate of flow is steady. The tube is long. The tube is rigid.
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Figure 1 Profile of the pressure along the length of the vascular pathway in the brain. The maximal deviation from the normal is where resistance in the AVM is no greater than that of the arterial system (straight fistula). The vasculature within the sphere of influence of the AVM will deviate from normal and toward this curve. On occlusion of the fistula, the curve will move towards the maximal response anticipated, which will be above the normal curve, because the arteries have a larger diameter than is normal (see text). In addition, the pulsatility will increase above normal because of the increased reflectance. Abbreviations: AVM, arteriovenous malformation; lCA, intemal carotid artery; A1, M1, P1, pressure in these arteries; AVM or capillary, pressure at the level of the AVM or capillary. (See color insert.)
arterial pressure was 97% in the supraclinoid internal carotid artery (ICA) (or basilar artery); 75% in the A1, M1, or P1; 61% in the artery halfway from the above to the nidus; and 50% in the terminal feeder immediately prior to the nidus (44) (Table 1). These differences were significant. In a study of larger AVMs, the range of feeding artery pressures varied considerably, and half the cases had pressures less than 50% of the femoral pressure (45). There was a tendency for the larger AVM and the terminal feeder to have the lowest pressures (39,40). Studies of the responsiveness of the feeding artery to various stimuli show a response ranging from normal to reduced. In those where there is a reduced response to CO2 inhalation or hyperventilation in vivo (46,47) or where in vitro testing demonstrated no spontaneous activity and a reduced response to vasoactive substances (such as serotonin) (48), there is an increased likelihood of hemodynamic perturbations both before and after resection. The responsiveness detected is likely a result of the degree of arteriovenous shunting rather than an intrinsically distinct population of feeding arteries. The response of the feeding arteries of the AVM to systemic elevations or falls in blood pressure would be predicted to be dampened given the paucity of small resistance arteries and arterioles. Without the intrinsic control of autoregulation in the feeding arterial system (indeed, there is no microcirculation to protect within the arteriovenous interstices), elevations in proximal blood pressure would be expected to lead to a lesser increase in feeder pressure (Fig. 1). This blunted response has been demonstrated to occur by using microcatheters and systemic blood pressure elevation with phenylephrine (49). Aneurysm Formation The development of aneurysms is likely to be related to sites of maximal shear stress [shear stress being the product of m ¼ fluid viscosity and the shear rate (du/dx) (u ¼ axial stream velocity, x ¼ distance from wall)] and the consequent structural fatigue. Shear stress is further compounded by the repetitive cyclic change of stress seen with pulsatile flow (50), and is maximal at the distal carina of branch points or changes in direction.
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Hemodynamic stress induced by arteriovenous shunting as a cause of aneurysm formation was first reported more than 40 years ago (51). In more than 600 cases of AVMs, aneurysms have been reported to be present on arteries that feed the AVM in 11.2% of cases, but are present on arteries not feeding the AVM in only 0.8% of cases (52). This relatively high prevalence of aneurysms on feeding vessels has been reported in other large series (7–10%) of more than 400 cases (6,53–55). These findings compare with a prevalence of 1% in a similarly aged population undergoing angiography for reasons other than cerebrovascular disease (56). The high incidence of aneurysms on the feeding artery of AVMs is almost certainly related to the hemodynamic stress, given that angiographically and historically these aneurysms are identical to other saccular aneurysms (the etiology of which is thought to be on the basis of hemodynamic stress) (57–63) and that removal of the stress can lead to spontaneous disappearance of the aneurysm (52,54,55). That the aneurysm is within the hemodynamic sphere of influence of the fistula is underscored by the cases of aneurysmal rupture on shunt ablation—an event that must be associated with elevated pressure in the feeding artery (55,64). Further evidence in support of the hemodynamic etiology of aneurysm formation in AVMs is the tendency for aneurysms to be located more proximally in the arterial feeding network of large AVMs and closer to the nidus with smaller lesions (59). This observation is in keeping with the lower transmural pressures anticipated in the distal feeding artery of larger shunting AVMs. Associated aneurysms are a predictor of hemorrhage in patients with AVMs (59,65). The risk of hemorrhage in patients with an unruptured AVM with an associated arterial aneurysm is 7% per year compared with 1.7% if no aneurysm is present (59). The annual risk of hemorrhage has been estimated to be 5.3% for those aneurysms on the proximal arteries feeding an AVM and 9.8% when the aneurysm is within the AVM nidus (52). The increased risk of hemorrhage in patients with both aneurysm and AVM can only be partially explained by the sum of the individual risks of rupture from AVM and aneurysm, because in patients presenting with hemorrhage with both aneurysm and AVM, at least 50% of the time the origin of hemorrhage is the AVM (52). Therefore, the dramatically increased risk of hemorrhage from 1.7% to 7% with the presence of a feeding artery aneurysm would not be seen if the risks of the two lesions were merely additive. The presence of aneurysms should more correctly be considered a marker of advanced wear and tear on the integrity of the vasculature. Relationship of Feeding Artery Pressure and Prediction of Hemorrhage Hemorrhage from a blood vessel can be expected at some point with elevation in transmural blood pressure. In the case of AVMs, feeding artery blood pressure and wall fragility must interplay to predict the likelihood of hemorrhage. Indeed, a positive correlation between feeding artery pressure and the likelihood of AVM presentation with hemorrhage has been clinically verified (66–68). However, a distinction needs to be made between presentation of hemorrhage and risk of hemorrhage because of the increased likelihood that large AVMs with their lower feeding artery pressures will herald their presence by other means (e.g., seizure). The two explanations for high feeding artery pressure are first, that the fistula shunting is so minimal that the physiological perturbations are minimal, and second, that there has been high shear stress damage to the vasculature in the past but feeding artery pressure has recently risen (e.g., a recently acquired venous outflow obstruction). In the former case, one would expect that the shear stress would be approaching that of the normal circulation and thus would not be a significant risk for hemorrhage. In the second case, a rise in feeding artery pressure may precipitate hemorrhage where the damage from high shear stress is more recently accompanied by venous occlusive disease. Veins Predicted by the lack of intervening resistance vessels between feeding arteries and draining veins is an elevation in draining vein pressure that drops on AVM resection (Fig. 1). This prediction has been confirmed to be the case for human AVMs (49). The draining vein pressure correlates with the feeding artery pressure with the difference between the two inversely proportional to the AVM nidus size. The nature of flow within the draining vein of the AVM has been found to be pulsatile with high velocity (in contradistinction to the normal venous circulation) (69). Coupling the higher than normal pressure, pulsatility with high peak pressures, and higher than normal velocity of flow results in a higher than normal shear stress on the vein wall.
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Nornes and Grip demonstrated that the venous flow close to the AVM nidus was turbulent and became non-turbulent at a distance from the AVM (26). As with the discussion above on the consequences of high shear stress within the AVM nidus, endothelial turnover may well be altered and ultrastructural changes in the subendothelial layer may occur (29–31). These
Figure 2 (Caption on facing page)
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possibilities may explain the development of variceal dilatation and the acquisition of venous webs in the venous outflow of AVMs. Yasargil reported that 30% of all AVMs have associated venous abnormalities and that the incidence of venous abnormalities was positively correlated with AVM size (6). These observations have been confirmed by others (70). An increase in venous resistance, as caused by venous drainage occlusion, can lead to an increase in the risk of hemorrhage (70–73). If the venous occlusive or stenotic lesion is acquired in response to the AVM shunt flow (and this is likely to be the case), then the pressure in the AVM nidus and feeding artery will increase with time. This increase is likely to be the predominant hemodynamic factor in AVM hemorrhage associated with venous abnormalities (see above). HEMODYNAMIC EFFECT ON THE MICROCIRCULATION OF THE BRAIN ASSOCIATED WITH AN AVM Critical to the function of brain is the transmural pressure at the beginning and end of the capillary. Either a reduction in arterial pressure or an elevation of venous pressure can threaten brain function. Both events occur in brain surrounding an AVM to a varying extent (Fig. 2). Three questions are raised by this phenomenon: Is the arterial hypotension and/or venous hypertension sufficient to compromise cerebral blood flow (CBF)? If there is a reduction in CBF, is it sufficient to become clinically manifest? If there is a reduction in CBF, how does the microcirculation respond to further alterations in cerebrovascular physiology? Effect of Brain AVMs on Cerebral Blood Flow A baseline reduction in CBF may occur in the presence of an AVM. Direct measurements of CBF by intraoperative cortical CBF techniques (using intravenous 133xenon clearance, laser doppler blood flow, and thermal diffusion probes), single photon emission tomography (SPECT), and positron emission tomography (PET) have demonstrated that some patients have regional reductions in CBF adjacent to the AVM nidus (12,27,74–84). However, not all studies have confirmed evidence for reduced CBF in association with AVMs. Of note is the largest published study of a group of patients undergoing intraoperative CBF measurements (85). However, very few of the patients in that study had measurements of CBF adjacent to the AVM; most had local measurements of CBF more than 4 cm from the AVM margin, a distance beyond that expected to have the maximal impact on CBF (27). It is reasonable to conclude from the clinical evidence that in some patients the reduction in feeding artery pressure and the elevation in venous draining pressure are sufficient to compromise CBF in the resting state adjacent to the AVM. However, CBF is rarely, if ever, reduced at a distance from the AVM. The effects on CBF caused by the arteriovenous shunt flow in the absence of the physical nidus (eliminating the error inherent in having the AVM nidus in close proximity to the CBF region of interest) has been investigated in a rat model of AVM, and the findings confirmed the reduction in flow suggested by many human studies (86–89). Thus, the reduction in CBF in humans adjacent to the AVM is likely to be a response due to the arteriovenous shunting. As the magnitude of the shunting is variable, so too will be the magnitude of CBF response.
Figure 2 (Facing page) Model of possible arterio-capillary-venous units coming under the influence of an AVM. (A)The pressure within the artery and vein of the AVM drop over a short distance at the point of turbulence within the AVM and at the point of venous stenosis (if this exists). (B) The quantification of this pressure drop is variable. As shown in (A) parenchymal arteries and veins can arise at a distance (1 ¼ artery branch; 4 ¼ venous tributary) or in close proximity (2 ¼ artery branch; 3 ¼ venous tributary) to the fistula, producing the four classes of arterio-capillary-venous units: A, B, C and D. Pressure profiles will be determined by the specific parenchymal vascular pathway, and many such profiles will be present around an AVM. Examples of such profiles are illustrated by the pressure profiles between points 1 and 3, points 1 and 4, points 2 and 3, and points 2 and 4, representing the various arterio-capillary-venous units, shown in (B). With occlusion of the fistula the pressure profile within the arteriocapillary-venous units will rise towards the line indicating ‘‘profile from maximal effect from fistula ablation,’’ which is higher on the arterial side and lower on the proximal venous side than normal because of the dilatation of the vasculature (see text). Thus, at any one point in the arterio-capillary-venous unit, the pressure after ligation can be traced with a vertical line from the arterio-capillary-venous unit to the post-ligation pressure. It should also be remembered that these lines represent mean pressures and peak pressures, and the increase in pulsatility will be even greater. Abbreviations: AVM, arteriovenous malformation; ICA, internal carotid artery; A1, proximal anterior cerebral artery; M1, proximal middle cerebral artery; P1, proximal posterior cerebral artery. (See color insert.)
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Clinical Response to Blood Flow Disturbance ‘‘Steal’’ is the term for the preferential diversion of blood from functional brain to fistula flow (5). It has been considered the basis for neurologic deficits and seizures for more than five decades (3,4,14,64,90–96). However, Drake has raised the possibility that occult hemorrhage may be responsible for symptoms ascribed to steal (64). Moreover, seizure foci can be associated with hemosiderin (arising as a consequence of hemorrhage), and this too may be responsible for deficits thought to be ‘‘steal’’ (97,98). A second explanation for symptoms ascribed to ‘‘steal’’ is pulsatile compression by the AVM mass. In support of this explanation is the bone erosion that can arise in response to the AVM (64,99) and the vascular compressive syndromes that lead to neuronal dysfunction in other states (100–102). A third explanation for ‘‘steal’’ symptomatology is venous hypertension (in the absence of concurrent arterial hypotension). Both generalized venous hypertension leading to a malabsorption of cerebrospinal fluid (CSF) and localized venous hypertension arising from parenchymal drainage have been posed as explanations for the clinical presentation of ‘‘steal’’ (27,95,103–108). In support of this possibility is the role of venous hypertension in the clinical presentation of spinal dural AVMs (109–113). ‘‘Steal’’ has been considered by some to be a term applied to clinical disorders confined to reduced feeding artery pressure as opposed to reduced perfusion pressure. In this narrow definition confined to arterial hypotension, physiological evidence in support of ‘‘steal’’ is contradictory (114). Indirect evidence in support of ‘‘steal’’ comes from the knowledge that non-hemorrhagic presentations (due either to serendipity or to a circulatory disorder) have as a group a lower feeding artery pressure compared with those presenting with hemorrhage (66,68). However, the feeding artery pressure is only part of the equation determining microvascular flow and ‘‘steal.’’ There is a correlation between feeding artery pressure and draining vein pressure (49). Thus, an assessment of the difference in these two pressures may be a more accurate measure of the validity of the concept of clinical ‘‘steal,’’ as a low feeding artery pressure was generally matched with a low draining vein pressure. Cerebral blood flow evidence that ‘‘steal’’ may be clinically relevant comes from studies showing hypoperfusion correlating with sites of epileptic focus and cognitive impairment (76). The concept that the presence of an arteriovenous fistula resulting in non-infarctional cerebral hypoperfusion may lead to altered brain function is supported by neurophysiological evidence of impaired neuronal function and behavior in rats (115–117). These studies confirm a clinical response to altered neuronal function secondary to chronic non-infarctional ischemia induced by an arteriovenous fistula. As the fistula is remote from the brain, there can be no hemorrhage, compression, infarction, or other mechanisms to explain the results. In summary, the hypoperfusion resulting from the variable combinations of reduced arterial pressure and increased venous pressure is likely to be clinically manifest in some patients with AVMs. However, the emotive term ‘‘steal’’ should be replaced with terminology that more appropriately reflects the physiological perturbations such as arterial hypotension and venous hypertension.
AUTOREGULATION AND REACTIVITY TO CHANGES IN PaCO2 Autoregulation Some evidence suggests that autoregulation is preserved in the brain surrounding AVMs even when the microcirculation of this brain is compromised because of low perfusion pressure (39). Such evidence stems from the measurement of regional CBF while measuring feeding artery pressure during an acute rise in systemic arterial pressure. However, because autoregulation of CBF can be defined both in terms of CBF constancy over a wide range of perfusion pressures (118) and an inverse relationship between arterial radius change and perfusion pressure change (119), a change in feeding artery pressure may not reflect the magnitude of change in perfusion pressure. Therefore, a true assessment of autoregulation also requires an understanding of the venous pressure. Under normal circumstances the venous side of this equation contributes minimally to perfusion pressure, but not in the case of AVMs. In the presence of an AVM a rise in arterial pressure is accompanied by a rise in draining venous pressure (49). The rise in venous draining pressure will, in part, be experienced by the perinidal brain tissue.
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This event has a negative impact on the potential for any planned perfusion pressure change arising as a consequence of systemic arterial pressure change during autoregulation challenge. Therefore, caution needs to be exercised in interpreting studies of altered systemic arterial pressure in terms of whether or not autoregulation is intact. In the experimental model of AVMs where baseline CBF is reduced by 25% to 50% (but insufficient to cause infarction) (86), attempts at assessing autoregulation by systemic blood pressure changes yield results that are analogous to that found in humans, i.e., blood flow is lower than normal but unaltered with elevations or reductions in blood pressure (88,120). However, when perfusion pressure is reduced by elevations in intracranial pressure with continuous ventricular infusion of artificial CSF, CBF is reduced in fistula animals at a lower intracranial pressure than it is in control animals (121). This finding is consistent with either no autoregulation or being below the lower limit of autoregulation. Thus, a ‘‘pseudo-autoregulation’’ may be seen when autoregulation is tested by measuring changes in systemic arterial pressures rather than the true perfusion pressure at the level of the microcirculation of interest. In summary, the constancy of blood flow in the face of alterations in systemic blood pressure in the brain surrounding the AVM may reflect true autoregulation where the impact on the microcirculation is insufficient to affect CBF, or it may reflect ‘‘pseudo-autoregulation’’ if the impact on the microcirculation in the resting state is significant. ‘‘Pseudo-autoregulation’’ is the preferred term because no arterial radius change is responsible for maintaining this constant but low CBF. Whether or not the arterioles can constrict (and at what pressure) with restoration of normal perfusion pressure cannot be determined by the usual methods of studying autoregulation. Reactivity to Changes in PaCO2 The effect of AVMs on cerebrovascular reactivity to carbon dioxide is of great interest. Although some patients with reduced CBF exhibit a predicted increase in the volume of ischemic tissue with acetazolamide challenge (78), other patients with low CBF experience a paradoxical increase in CBF in response to acetazolamide (78,80,84). The paradox is that if these regions are capable of increasing their blood flow, why do they remain ischemic at rest? The answer must in part be explained by the mechanism of blood flow increase. In normal brain, this increase must reflect the response of the arteries, all of which (except for choroidal vessels) are supplying similarly functioning microcirculations. However, for the brain adjacent to an AVM nidus, the influence of the arteriovenous fistula must be taken into consideration. In a passive microcirculation, both in parallel with an arteriovenous fistula and in parallel with a microcirculation capable of normal physiological responses, it can be anticipated that with a generalized stimulus for arterial dilatation (e.g., in response to an increase in PaCO2 or acetazolamide) the branch arteries from the feeding artery to the AVM will have a drop in their pressure due to the generalized reduction in total cerebrovascular resistance. This will lead to a reduction in arteriolar pressure and a reduction in microcirculation flow in a system that is unable to further vasodilate. As a result, some patients with reduced CBF exhibit an increase in the volume of ischemic tissue with acetazolamide challenge. However, in addition to this response, the fistula flow itself will be reduced with the reduction in the feeding artery pressure, and this will result in a reduction in the draining vein pressure. Microcirculations feeding into this system will then experience a fall in their resistance and a tendency to increase their blood flow even without a capacity to further vasodilate. Hence, some patients with low CBF may experience a paradoxical increase in blood flow in response to acetazolamide. The balance between the reduction in arterial pressure into a microcirculation and the reduction in venous pressure will determine the overall effect. When this balance favors a paradoxical increase in blood flow with acetazolamide, the risk for the development of edema and hemorrhage with AVM excision is likely to increase (84). Reactivity to changes of PaCO2 occurs in animal models of arteriovenous fistula despite hypoperfusion (87). It has not been determined whether this is due to a disconnection between the autoregulation response and CO2 reactivity, which can occur (87), or to a disproportionately greater effect of a reduction in venous pressure over a reduction in arterial pressure with the reduced fistula flow. Retention of CO2 reactivity may be possible despite being on the pressure-cerebral blood flow curve below the lower limit of autoregulation in the chronic hypoperfusion state.
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HEMODYNAMIC EFFECT ON CEREBRAL BLOOD VESSELS AT THE TIME OF AVM ABLATION The ablation of an arteriovenous fistula removes from the brain the low resistance circulation that was in parallel with the normal circulation. The feeding artery pressure increases towards the systemic arterial pressure, and the pulsatility also increases (27,40) (Figs. 1 and 2). Because the radii of arteries feeding the AVM do not immediately return to normal after AVM ablation, the resistance to flow within these arteries will be lower than normal (as predicted by the Poiseuille equation, Table 1). The arterial pressure drop-off normally seen along the vessels before the arteriolar level will be reduced, and thus the pressure that occurs in these arteries after ablation of the fistula will be higher. This pressure can be expected to be greater than normal and may nearly approximate that of the extracranial carotid artery (Fig. 1). The Poiseuille equation predicts that if the radius is increased, as it is in the feeding artery, the pressure gradient must be reduced in order to supply the brain with the same blood flow as before AVM ablation (Fig. 1). In addition, the larger than normal diameter redundant feeding artery system, with its normal downstream microcirculation, will generate a larger reflected wave than a normal diameter vessel, resulting in a greater than normal pulsatility and hence even higher peak pressures within the cardiac cycle (122). This increase in pressure and pulsatility (above normal for the equivalent vessel in this location in a normal brain) may challenge the integrity of the arterial wall, particularly at sites of aneurysmal weakness, or of distal branches of the feeding artery that may have been extremely thin walled due to the chronic local hypotension. These vessels are modeled to the previous requirement for high flow to and from the AVM and, depending on the radius and the relevant requirement for run off, will have the propensity to develop stagnation and thrombosis (38). Thrombosis may develop either in arteries or in veins prone to stagnation, and veins in particular may be prone to delayed propagated thrombosis with their high incidence of stenotic lesions (see above). Propagated venous thrombosis of the major draining system is responsible for clinical deterioration in 1% to 3% of operated cases (11,123). After resection of an AVM, there is a high incidence of vasospasm despite a low volume of subarachnoid hemorrhage associated with those AVMs requiring extensive basal dissection (123,124). This occurrence suggests an increase in the vasoreactivity of these vessels. The mechanism may be that the increase in the pressure within the arteries (from low to normal) leads to an increase in contractile tone which, coupled with the normal predisposing factors of subarachnoid hemorrhage, produces an increased likelihood for the development of vasospasm. HEMODYNAMIC EFFECT ON THE BRAIN AT THE TIME OF AVM ABLATION Few topics in neurosurgery are as controversial as the hemodynamic consequences of AVM ablation. The three major questions are: Does the microcirculation of brain surrounding the AVM react to the restoration of normal arterial and venous pressures similarly to that of remote brain? If there are major physiological abnormalities, are they sufficient to produce a clinical problem? Are there additional pathophysiological insults to the microcirculation? After AVM resection, CBF may increase in the brain adjacent to the AVM (27,74,77,85, 120,125,126). Significant error may be present in the numerical value for the post-surgical increase in CBF depending on the methodology used (e.g., stagnant arteries and veins may allow diffusion of isotope into these ‘‘reservoirs’’ without this being correlated with blood flow). Thus, caution must be exercised in considering post-resection blood flow that may be returning from ischemic values as representing hyperemia. However, evidence in support of the likelihood of hyperemia in some cases arises from other clinical states of reversal of cerebral ischemia that produce hyperemia, such as after carotid endarterectomy (127–129) and large caliber vein bypass grafting (130). The common underlying mechanism is the sudden reversal of non-infarctional cerebral hypoperfusion. This mechanism is supported experimentally in cerebral hyperperfusion caused by arteriovenous fistula ablation where CBF was reduced by 25% to 50% of normal prior to ligation of the fistula (86,87,89). The mechanism for hyperemia after AVM resection has been ascribed to a loss of autoregulation (10), a resetting of the upper limit of autoregulation downward (131), and a neuropeptide-mediated disturbance (132). The resetting of the upper limit of autoregulation
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to a lower blood pressure is an attractive hypothesis as there is a precedent for this possibility in other physiological states with chronic alteration in cerebral perfusion pressure (133–135). It is argued that in these states, vasodilation of the larger caliber cerebral resistance vessels will induce a shift to the left of the upper and lower limits of autoregulation (136). Such chronic dilatation is certainly a feature of AVM feeding vessels. To assess pressure autoregulation after AVM resection, Young et al. performed intraoperative studies. They found that blood flow was the same after elevation of blood pressure to 20 mmHg (137). However, regional CBF was measured more than 5 cm from the nidus, and the PaCO2 was at 24 mmHg. The presence of hypocapnia confounds the effect of blood pressure on autoregulation (138). The fact that autoregulation is intact and shifted to the left is supported in animal models of arteriovenous fistula (89,120). Hyperemia alone may be insufficient to account for hemorrhage or edema. Many patients having an AVM excision with CBF monitoring have hyperemia without development of hemorrhage and edema (27,125,126). Furthermore, much higher CBF levels and more dramatic changes in CBF occur during seizures, a condition not characterized by brain swelling and hemorrhage (139–141). In summary, the evidence suggests that at least some cases of AVM excision are associated with hyperemia. This hyperemia is due to a restoration of normal pressure (in fact, this pressure may be greater than normal and may approach the more proximal systemic arterial pressure) within the feeding arterial system now perfusing brain where the autoregulation curve has been shifted to the left and its upper limit has been exceeded. However, hyperemia alone cannot account for the pathological processes variously termed ‘‘normal perfusion pressure breakthrough’’(10), ‘‘congestive apoplexy’’(9), ‘‘overload’’(64), or ‘‘vasogenic turgescence of the brain’’(142). Hyperemia may be an epiphenomenon of the malignant vascular process rather than the basis for the observed complications. ARTERIO-CAPILLARY-VENOUS HYPERTENSIVE SYNDROMES Many reported cases of postoperative hemorrhage or edema are thought to represent examples of ‘‘normal perfusion pressure breakthrough’’ (NPPB) (10,26,64,77,84,85,95,105,123,124,142–154). A similar phenomenon has been reported to complicate a sudden restoration of perfusion pressure to the brain after treatment of carotid and vertebral fistulae (155), carotid endarterectomy for high grade stenosis (127), and revascularization of the brain with large caliber bypass (130). The underlying mechanism remains in question. Spetzler et al. described three patients who developed brain swelling (two cases) or hemiplegia (one case) after surgery (one surgery being feeder ligation) as well as an experimental study of five cats with a carotid jugular fistula that developed a loss of both autoregulation and PaCO2 response after fistula ligation (10). The authors concluded that ‘‘the autoregulatory control, wherever it is located, possibly at the arteriolar level, having been chronically dilated, cannot sufficiently increase the resistance to the new perfusion pressure to protect the capillary, which leads to breakthrough with resultant edema or hemorrhage’’ (10). Central to this ‘‘NPPB’’ hypothesis is the loss of autoregulation and vascular damage at the level of the capillary. With evidence that autoregulation may be intact (although with curve shift to the left) (see above) and the concern that the hyperemia may be an epiphenomenon rather than a central process in the vascular destruction, some have questioned the existence of this syndrome as it stands (11,77,84,85). Indeed, several neurosurgeons with large operative series have argued strongly against the existence of NPPB (7,156,157). In addition, ‘‘normal’’ pressure is a misnomer, as both the mean pressure and the pulse pressure are greater than what they would have been had the AVM never existed (see above), even while the feeding system remains abnormally dilated. Alternate explanations that may appear to be clinically similar to those cases ascribed to have NPPB include proximal feeder vessel rupture and propagated venous occlusive syndromes. Both have as their underlying common pathophysiological perturbation a local intravascular pressure rise (Fig. 2) (11,123). This is the same underlying process that is alleged to occur in NPPB (i.e., intravascular—in this case capillary–hypertension), and a unifying pathophysiological label for each of these processes is ‘‘arterio-capillary-venous hypertensive syndrome’’ (123). The central role of hypertension in one region or another of the vasculature is the critical determinant for the genesis of these complications of AVM resection. Furthermore,
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the original site leading to intravascular hypertension can often be difficult to distinguish and may in fact be multifactorial. An example of arterio-capillary-hypertensive syndrome is when edema complicates resection of an AVM with large variceal draining veins. It is expected that a varix may thrombose after surgery, but in the presence of edema it is tempting to attribute the edema to the thrombosis rather than to it being a coincidental association. However, there can be no debate on the presence of intravascular hypertension, or on whether or not the venous thrombosis caused the edema. In addition to the intravascular hypertension contributing to a failure of the integrity of vascular wall and capillary function, a lowering of the threshold for such injury may not only be present in the thin-walled precapillary vessels but also in the capillary wall itself. In experimental models of arteriovenous fistula where chronic non-infarctional ischemia is produced, many capillaries can be identified to have no astrocytic foot processes (158). If this is the case in humans with AVM, it may suggest that either the blood-brain-barrier function or the wall integrity may be more easily breached than is the case in normal brain. The time course for resolution of the propensity to develop the ‘‘arterio-capillary-venous hypertensive syndrome’’ must depend on the time course in the normalization of vessel caliber and integrity. Therefore, AVM size, shunt flow, the degree of feeder and venous dilatation, and local intravascular pressure contribute to the time course. In a series of delayed deficits, no patient developed complications related to ‘‘arterio-capillary-venous hypertensive syndrome’’ more than eight days after surgery (123). It is likely that resolution of the risk for this complication has occurred in the majority of AVM patients during the first week to ten days after surgery.
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The association of arteriovenous angioma and saccular aneurysm of the arteries of the brain. J Pathol Bacteriol 1959; 77:101–110. 58. Batjer H, Suss RA, Samson D. Intracranial arteriovenous malformations associated with aneurysms. Neurosurgery 1986; 18:29–35. 59. Brown RD Jr., Wiebers DO, Forbes SG. Unruptured intracranial aneurysms and arteriovenous malformations: frequency of intracranial hemorrhage and relationship of lesions. J Neurosurg 1990; 73:859–863. 60. Okamoto S, Handa H, Hashimoto N. Location of intracranial aneurysms associated with cerebral AVM: statistical analysis. Surg Neurol 1984; 22:335–340. 61. Ferguson GG. Physical factors in the initiation, growth and rupture of human intracranial saccular aneurysms. J Neurosurg 1972; 37:666–677. 62. Ferguson GG. Turbulence in human intracranial saccular aneurysms. J Neurosurg 1970; 33:435–497. 63. Stehbens WE. Etiology of intracranial berry aneurysms. J Neurosurg 1981; 70:823–831. 64. Drake CG. Considerations for and experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–206. 65. Turjman F, Massoud TF, Vinuela F, Sayre JW, Guglielmi G, Duckwiler G. Correlation of the angioarchitectural features of cerebral arteriovenous malformations with clinical presentation of hemorrhage. Neurosurgery 1995; 37:856–862. 66. Spetzler RF, Hargraves RW, McCormick PW, Zabramski JM, Flom RA, Zimmerman RS. Relationship of perfusion pressure and size to risk of hemorrhage from arteriovenous malformations. J Neurosurg 1992; 76:918–923. 67. Kader A, Young WL, Pile-Spellman J, et al. The influence of hemodynamic and anatomic factors on hemorrhage from cerebral arteriovenous malformations. Neurosurgery 1994; 34:801–808. 68. Duong DH, Young WL, Vang MC, et al. Feeding artery pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral arteriovenous malformations. Stroke 1998; 29: 1167–1176. 69. Murayama Y, Usami S, Hata Y, et al. Transvenous hemodynamic assessment of arteriovenous malformations and fistulas. Preliminary clinical experience in Doppler guidewire monitoring embolotherapy. Stroke 1996; 27:1358–1364. 70. Vinuela F, Nombela L, Roach MR, Fox AJ. Pelz DM: Stenotic and occlusive disease of the venous drainage system of deep brain AVMs. J Neurosurg 1985; 63:180–184. 71. Dobbelaere P, Jomin M, Clarrisse J, Laine E. Interet pronostique de letude du drainage verneux de aneurysms arterio-veneux cerebraux. Neurochirugie 1979; 25:178–184. 72. Marks MP, Lane B, Steinberg GK, et al. Hemorrhage in intracerebral arteriovenous malformations: angiographic determinants. Radiology 1990; 176:807–813. 73. Miyasaka Y, Yada K, Ohwada T, Kitahara T, Kurata A, Irikura K. An analysis of the venous drainage system as a factor in hemorrhage from arteriovenous malformations. J Neurosurg 1992; 76:239–243. 74. Okabe T, Meyer JS, Okayasu H, et al. Xenon-enhanced CT CBF measurement in cerebral AVMs before and after excision. J Neurosurg 1983; 59:21–31. 75. Tyler JL, Leblanc R, Meyer E, et al. Hemodynamic and metabolic effects of cerebral arteriovenous malformations studied by positron emission tomography. Stroke 1989; 20:890–898. 76. Homan RW, Devous MD Sr, Stokely EM, Bonte FJ. Quantification of intracerebral steal in patients with arteriovenous malformation. Arch Neurol 1986; 43:779–785. 77. Batjer HH, Devous MD Sr, Meyer, YJ, Purdy PD, Samson DS. Cerebrovascular hemodynamics in arteriovenous malformation complicated by normal perfusion pressure breakthrough. Neurosurgery 1988; 22:503–509. 78. Hacein-Bey L, Nour R, Pile-Spellman J, Van Heertum R, Esser PD, Young WL. Adaptive changes of autoregulation in chronic cerebral hypotension with arteriovenous malformations: an acetazolamideenhanced single-photon emission CT study. AJNR 1995; 16:1865–1874. 79. Spetzler RF, Martin NA, Carter LP, Flom RA, Raudzens PA, Wilkinson E. Surgical management of large AVMs by staged embolization and operative excision. 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81. Marks MP, O’Donahue J, Fabricant JI, et al. Cerebral blood flow evaluation of arteriovenous malformations with stable xenon CT. AJNR 1988; 9:1169–1175. 82. Jinkins JR. Encephalopathic cerebrovascular steal: dynamic CT of arteriovenous malformations. Neuroradiology 1988; 30:201–210. 83. Takeuchi S, Kikuchi H, Karasawa J, et al. Cerebral hemodynamics in arteriovenous malformations: evaluation by single-photon emission CT. AJNR 1987; 8:193–197. 84. Batjer HH, Devous MD. The use of acetazolamide-enhanced regional blood flow measurement to predict risk to arteriovenous malformation patients. Neurosurgery 1992; 31:213–217. 85. Young WL, Kader A, Ornstein E, et al. Cerebral hyperemia after arteriovenous malformation resection is related to ‘‘breakthrough’’ complications but not to feeding artery pressure. Neurosurgery 1996; 38:1085–1095. 86. Morgan MK, Anderson RB, Sundt TM Jr. A model of the pathophysiology of cerebral arteriovenous malformations by a carotid-jugular fistula in the rat. Brain Research 1989; 496:241–250. 87. Morgan MK, Anderson RE, Sundt TM Jr. The effects of hyperventilation on cerebral blood flow in the rat with an open and closed carotid-jugular fistula. Neurosurgery 1989; 25:606–612. 88. Morgan MK, Sundt TM Jr., Anderson RE, Weber N. The hemodynamic consequences of a carotidjugular fistula in the rat during hypocapnia. J Clin Neurosci 1994; 1:193–196. 89. Irikura K, Morii S, Miyasaka Y, Yamada M, Tokiwa K, Yada K. Impaired autoregulation in an experimental model of chronic cerebral hypoperfusion in rats. Stroke 1996; 27:1399–1404. 90. Kusske JA, Kelly WA. Embolization and reduction of the ‘‘steal’’ syndrome in cerebral arteriovenous malformations. J Neurosurg 1974; 40:313–321. 91. Albert P. Personal experience in the treatment of 178 cases of arteriovenous malformations of the brain. Acta Neurochirurgia 1982; 61:207–226. 92. Girvin JP, Fox AJ, Vinuela F, Drake CG. Intraoperative embolization of cerebral arteriovenous malformations in the awake patient. Clin Neurosurg 1984; 31:188–247. 93. Davis CH, Symon L. The management of cerebral arteriovenous malformations. Acta Neurochirurgia 1985; 74:4–11. 94. Fox AJ, Girvin JP, Vinueia F, Drake CG. Rolandic arteriovenous malformations: Improvement in limb function by IBC embolization. AJNR 1985; 6:572–582. 95. Morgan MK, Johnston I. Intracranial arteriovenous malformations: an 11 year experience. Med J Aust 1988; 148:65–68. 96. Batjer HH, Devous MD Sr., Seibert GB, et al. Intracranial arteriovenous malformation: relationships between clinical and radiographic factors and ipsilateral steal severity. Neurosurgery 1988; 23: 322–328. 97. Hughes JT, Oppenheimer DR. Superficial siderosis of the central nervous system. A report on nine cases with autopsy. Acta Neuropath (Berlin) 1969; 13:56–74. 98. Leblanc R, Feindel W, Ethier R. Epilepsy from cerebral arteriovenous malformations. Can J Neurol Sci 1983; 10:91–95. 99. Azar-Kia, Palacios E, Danley R. Bone erosion associated with intracranial arteriovenous malformations. Illinois Med J 1977; 152:116–119. 100. Dandy WE. Concerning the cause of trigeminal neuralgia. Am J Surg 1934; 24:447–455. 101. Gardner WJ. The mechanism of tic doleureux. Trans Am Neurol Assoc 1953; 78:168–173. 102. Jannetta PJ. Observation on the etiology of trigeminal neuralgia. Definitive microsurgical treatment and results in 117 patients. Neurochir 1977; 20:145–154. 103. Weisberg LA, Pierce JF, Jabbari B. Intracranial hypertension resulting from cerebrovascular malformation. South Med J 1977; 70:624–626. 104. Vassilouthis J. Cerebral arteriovenous malformation with intracranial hypertension. Surg Neurol 1979; 11:402–404. 105. Barrow DL. Unruptured cerebral arteriovenous malformations presenting with intracranial hypertension. Neurosurgery 1980; 23:484–490. 106. Obrader S, Sato M, Silvela J. Clinical syndromes of arteriovenous malformations of the transversesigmoid sinus. J Neurol Neurosurg Psychiatry 1975; 38:436–451. 107. Houser OW, Campbell JK, Campbell RJ, Sundt TM Jr. Arteriovenous malformation affecting the transverse venous sinus—an acquired lesion. Mayo Clin Proc 1979; 54:651–661. 108. Lasjaunias P, Chiu M, TerBrugge K, Tolia A, Hurth M, Bernstein M. Neurologic manifestations of intracranial dural arteriovenous malformations. J Neurosurg 1986; 64:724–730. 109. Aminoff MJ, Barnard RO, Logue V. The pathophysiology of spinal vascular malformations. J Neurol Sci 1974; 23:255–263. 110. Logue V. Angiomas of the spinal cord: review of the pathogenesis, clinical features, and results of surgery. J Neurol Neurosurg Psychiat 1974; 42:1–11. 111. Symon L, Kuyama H, Kendall B. Dural arteriovenous malformation of the spine. J Neurosurg 1984; 60:238–247. 112. Yasargil MG, Syrnon L, Teddy PJ. Arteriovenous malformation of the spinal cord. In: Symon L, ed. Advances and Technical Standards in Neurosurgery (Wien). Vol II. Springer, 1984:61–198. 113. Oldfield EH, Di Chiro G, Quidlen EA, et al. Successful treatment of a group of spinal cord arteriovenous malformations by interruption of dural fistula. J Neurosurg 1983; 59:1019–1030.
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114. Mast H, Mohr JP, Osipov A, et al. ‘‘Steal’’ is an unestablished mechanism for the clinical presentation of cerebral arteriovenous malformations. Stroke 1995; 26:1215–1220. 115. Sekhon LHS, Morgan MK, Spence I, Weber NC. Chronic cerebral hypoperfusion in the rat. Temporal delineation of effects and the in vitro ischemic threshold. Brain Research 1995; 704:107–111. 116. Sekhon LHS, Morgan MK, Spence I, Weber NC. Chronic cerebral hypoperfusion: Pathological and behavioral consequences. Neurosurgery 1997; 40:548–556. 117. Sekhon LHS, Morgan MK, Spence I. Weber NC. Chronic cerebral hypoperfusion inhibits calciuminduced long-term potentiation in rats. Stroke 1997; 28:1043–1048. 118. Lassen NA. Autoregulation of cerebral blood flow. Circ Res 1964; 14–15(suppl 1):1201–1204. 119. Heistad DD, Kontos HA. Cerebral circulation. In: Shepherd JT, Abboud FM, eds. Handbook of Physiology. Section 2: The Cardiovascular System. Volume III. Peripheral Circulation and Organ Blood Flow, Part 1. Bethesda, Maryland: American Physiological Society, 1983:137–182. 120. Rosen DM. Cerebral arteriovenous malformations: Cerebrovascular hemodynamics, collateral circulation, nitric oxide and hyperperfusion syndrome. Thesis submitted for PhD, The University of Sydney, 1997. 121. Jacobson E. Mechanics of CSF circulation. Thesis submitted for PhD, The University of Sydney, 1998. 122. Nichols WW, O’Rourke MF. McDonald’s Blood Flow in Arteries. Theoretic, Experimental and Clinical Principles, 3rd ed, London, Edward Arnold, 1990:254. 123. Morgan MK, Sekhon LHS, Finfer S, Grinnell V. Delayed neurological deterioration following resection of arteriovenous malformations of the brain. J Neurosurg 1999; 90:695–701. 124. Morgan MK, Day MJ, Little N, Grinnell V, Sorby W: The use of intra-arterial papaverine in the management of vasospasm complicating the resection of arteriovenous malformations of the brain: a report of two cases. J Neurosurg 1995; 82:296–299. 125. Young WL, Prohovnik I, Omstein E, et al. Monitoring of intraoperative cerebral hemodynamics before and after arteriovenous malformation resection. Anesth Analg 1988; 67:1011–1014. 126. Rosenblum BR, Bonner RF, Oldfield EH. Intraoperative measurement of cortical blood flow adjacent to cerebral AVM using laser Doppler velocimetry. J Neurosurg 1987; 66:396–399. 127. Piepgras DG, Morgan MK, Sundt TM Jr., Yanagihara T, Mussman LM. Intracerebral hemorrhage after carotid endarterectomy. J Neurosurg 1988; 68:532–536. 128. Schroeder T, Sillesen H, Sorensen O, Engell HC. Cerebral hyperperfusion following carotid endarterectomy. J Neurosurg 1987; 66:824–829. 129. Powers AD, Smith RR. Hyperperfusion syndrome after carotid endarterectomy: A transcranial Doppler evaluation. Neurosurgery 1990; 26:56–60. 130. Sundt TM Jr., Piepgras DG, Marsh WR, Fode NC. Bypass vein grafts for giant aneurysms and severe intracranial occlusive disease in the anterior and posterior circulation. In: Sundt TM Jr, ed. Occlusive Cerebrovascular Disease. Diagnosis and Surgical Management. Philadelphia: WB Saunders, 1987: 439–464. 131. Spetzler RF, Hamilton MG. Pressure autoregulation is intact after arteriovenous malformation resection. Neurosurgery 1993; 33:772–773. 132. Macfarlane R, Moskowitz MA, Sakas DE, Tasdemiroglu E, Wei EP, Kontos HA. The role of neuroeffector mechanisms in cerebral hyperperfusion syndromes. J Neurosurg 1991; 75:845–855. 133. Folkow B, Halba¨ck M, Lundgren Y, Silverston Y, Weiss L. Importance of adaptive changes in vascular design for establishment of primary hypertension, studied in man and in spontaneously hypertensive rats. Circ Res 1973; 32/33(suppl 11):l12–116. 134. Bill A, Linder J. Sympathetic control of cerebral blood flow in acute arterial hypertension. Acta Physiol Scan 1976; 96:114–121. 135. Barry Dl, Jarden JO, Paulson OB, Gaharn DL, Strandgaard S. Cerebrovascular effects of converting enzyme inhibition. Effects of intravenous captopril in spontaneously hypertensive and normotensive rats. J Hypertension 1984; 2:589–597. 136. Postiglione A, Bobkiewicz T, Vinholdt-Pedersen E, Lassen NA, Paulson OB, Barry DL. Cerebrovascular effects of angiotensin converting enzyme inhibition involving large artery dilatation in rats. Stroke 1991; 22:1363–1368. 137. Young WL, Kader, A, Prohovnik I, et al. Pressure autoregulation is intact after arteriovenous malformation resection. Neurosurgery 1993; 32:491–497. 138. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 1990; 2:167–192. 139. Nilsson B, Rehncrona S, Siesjo¨ BK. Coupling of cerebral metabolism and blood flow in epileptic seizures, hypoxia and hypoglycaemia. Ciba Found Symp 1978; 56:199–218. 140. Tenny RT, Sharbrough FW, Anderson RE, Sundt TM Jr. Correlation of intracellular redox states and pH. Ann Neurol 1980; 8:564–573. 141. Nitsch C, Suzuki R, Fujiwara K, Klatzo I. Incongruence of regional cerebral blood flow increase and blood-brain barrier opening in rabbits at the onset of seizures induced by bicuculline, methoxypyridoxine, and kainic acid. J Neurol Sci 1985; 67:67–79. 142. Pertuiset B, Sichez JP, Philippon J, Fohanno D, Horn YE. Mortality and morbidity following the surgical excision of 162 intracraniai arteriovenous malformations (1958–1978). Rev Neurol 1979; 35:319–327.
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143. Mullan S, Brown FD, Patronas MJ. Hyperemic and ischemic problems of surgical treatment of arteriovenous maiformations. J Neurosurg 1979; 51:757–764. 144. Day AL, Friedman WA, Sypert GW, Mickle P. Successful treatment of the normal perfusion pressure breakthrough syndrome. Neurosurgery 1982; 11:625–630. 145. Luessenhop AJ, Ferraz FM, Rosa L. Estimate of the incidence and importance of circulatory breakthrough in the surgery of cerebral arteriovenous malformations. Neural Res 1982; 4:177–190. 146. Solomon RA, Michelsen WJ. Defective cerebrovascular autoregulation in regions proximal to arteriovenous malformation of the brain. A case report and topic review. Neurosurgery 1984; 14:78–82. 147. Bonnal J, Born JD, Hans P. One-stage excision of high-flow arteriovenous malformations. J Neurosurg 1985; 62:128–131. 148. Aoki N, Mizutani H. Arteriovenous malformation in the territory of the occluded middle cerebral artery with massive intraoperative brain swelling. Case report. Neurosurgery 1985; 16:660–662. 149. Yamada K, Hayakawa T, Yashimine T, Nakao K, Ushio Y, Mogami H. Surgery of high-flow arteriovenous malformation with special reference to normal perfusion pressure breakthrough phenomenon. No Shinkei Geka 1986; 14:741–748. 150. U HS. Microsurgical excision of paraventricular arteriovenous malformations. Neurosurgery 1985; 16:293–303. 151. Morgan MK, Johnston IH, Sundt TM Jr. Normal perfusion pressure breakthrough complicating surgery for the vein of Galen malformation. Report of three cases. Neurosurgery 1989; 24:406–410. 152. Morgan MK, Sundt TM Jr., Houser OW. Arterio-inferior sagittal sinus fistula. Case report. Neurosurgery 1989; 25:971–975. 153. Morgan MK, Sundt TM Jr. The case against staged operative resection of cerebral arteriovenous malformations. Neurosurgery 1989; 25:429–432. 154. Morgan MK, Johnston IH, Hallinan JM, Weber N. Complications of surgery for arteriovenous malformations of the brain. J Neurosurg 1993; 78:176–182. 155. Halbach VV, Higashida RT, Hieshima GB, Norman D. Normal perfusion pressure breakthrough occurring during treatment of carotid and vertebral fistulas. AJNR 1987; 8:751–756. 156. Parkinson D. Staged treatment of arteriovenous malformations. J Neurosurg 1988; 68:658–659. 157. Yasargil MG, Curcic M, Kis M, Teddy PJ, Valavanis A. Microneurosurgery. Volume III B. New York, Thieme Medical Publishers, 1988. 158. Sekhon LHS, Morgan MK, Spence I, Weber NC. Normal perfusion pressure breakthrough: The role of capillaries. J Neurosurgery 1997; 86:519–524.
4
Use of Modeling for the Study of Cerebral Arteriovenous Malformations William L. Young Departments of Anesthesia and Perioperative Care, Neurological Surgery, and Neurology, UCSF Center for Cerebrovascular Research, University of California, San Francisco, California, U.S.A.
Erzhen Gao Supertron Technologies Inc., Newark, New Jersey, U.S.A.
George J. Hademenos Science Department, Richardson High School, Richardson, Texas, U.S.A.
Tarik F. Massoud University Department of Radiology, University of Cambridge School of Clinical Medicine, Cambridge, U.K.
INTRODUCTION A model may be defined as a computational or physical construct that has some functional equivalence to a real system. Hypothetical essential properties of the real original system are represented, while the potentially confounding irrelevancies are ignored (1). Models may be useful in the understanding of relationships between cause and effect in a complex physiological or pathological process. Their great strength is a flexibility that is not possible with an intact system. Their great weakness is that they are critically dependent on the assumptions made in their construction. The critical importance of these two considerations must always be kept in clear perspective when attempting to construct a model of a biologic process (2). The general principles and philosophical premises of modeling in biomedical research have been reviewed in detail (2). Models can generally be used as a framework within which clinical phenomena may be better understood (2,3). Modeling results are generally not intended to be extrapolated immediately to single-patient management. Rather, they are to be used to better define issues and frame hypotheses for further experimental work. Models can narrow the field between a large number of potential avenues for designing experimental investigations, but successful modeling requires critical evaluation of results by comparison with experimental data (4). For the circulatory system, computational models might be termed an instrumentalist approach to describing vascular and circulatory behavior. Such an instrumental approach can be viewed merely as a mathematical tool for deducing one set of variables from another (5). Pioneered by physiologists such as Guyton (6), modeling has been used as a research technique at all levels of the cardiovascular system, from total system to capillary dynamics (7–17). In the neurosciences, efforts have been aimed at the level of neural systems (1) and in the study of the cerebrovasculature. For example, control mechanisms of cerebral blood flow (18–22) and the mechanical properties of cerebral aneurysms (23–26) have been studied. The primary focus of this chapter is computational models. However, mechanical and animal models have been described in the study of arteriovenous malformations (AVMs), and brief discussions or appropriate references are included. IMPORTANCE OF MODELING FOR AVMs Cerebral AVMs have long been regarded as a demanding clinical and experimental challenge. They are considered to be complex entities due to their anatomical and morphological heterogeneity, their hemodynamic and pathophysiological effects, and their unpredictable clinical
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natural history. This complexity is further compounded by their unknown etiology and pathogenesis. Of the three main compartments of an AVM (feeders, nidus, draining veins), the central core or nidus is the least accessible to study because at present (a) it is usually impossible to catheterize its plexiform microvessels (to gain intranidal hemodynamic information) due to their small size (average 250 mm) (27) and fragile nature, and (b) their small caliber precludes adequate spatial resolution (for intranidal morphological characterization) using current tomographic imaging modalities (magnetic resonance imaging, MRI). Therefore, the nidus of an AVM represents both an inaccessible ‘‘black box’’ and a system of considerable complexity with respect to its morphology and hemodynamics. The interaction of intranidal and surrounding extranidal environment yields a vascular bed that is highly susceptible to spontaneous rupture and hemorrhage. Under these circumstances, experimental model construction of cerebral AVMs provides a useful set of analytical tools for indirect investigatation (28) and can increase knowledge of vascular pathology that is otherwise not amenable to study by direct means (29–35). SPECIFIC MODELING ATTEMPTS–MODEL CONSTRUCTION Initial attempts at biomathematical models have simulated hemodynamics in AVMs using elementary feeding and draining pedicle anatomy and a nidus composed typically of a single or multiple array of parallel, compartmentalized vessels. A general review of published AVM models is shown in Table 1 (28–37). For example, the AVM model introduced by Lo et al. consisted of three linked compartments representing arterial feeders, shunting arterioles, and the core vessels of the AVM with flow draining into the central venous drainage (34,35,38). These investigators simulated hemodynamics within small and large AVMs and obtained results comparable to those clinically observed, but they neglected the appearance of draining veins. Hecht et al. expanded upon this concept with simulations in an AVM nidus composed of 1,000 nidus vessel compartments (37). Ornstein et al. introduced a more complex AVM model by considering the influence of inductance, conductance, and autoregulation (29). Extranidal Model As described in detail in the following sections, our group has expanded on these initial models (Fig. 1). To simulate the arteriolar resistance beds and brain tissue, Gao et al. (31) introduced ‘‘microvessel groups’’ (MVGs) as special compartments. The model contains 20 MVGs, each of them consisting of 5,000 parallel small vessels 0.1 mm in diameter. As shown in Figure 1, six of the 20 MVGs are perfused by the anterior cerebral artery (ACA), ten are perfused by the middle cerebral artery (MCA), and four are perfused by the posterior cerebral artery (PCA). They are symmetrically distributed in left and right hemispheres. Assuming a brain weight of 1500 g, each MVG represents a brain tissue weight of 75 g. The MVG also incorporates autoregulatory function into the normal (non-AVM) vasculature. Our model improves on all previous models in the following respects. In previous models, the AVMs were fed by a single arterial feeder with either a single or no draining vein. Our model consists of the major conductance arteries supplying the intracranial circulation, most major intracranial arteries and veins, and their major branches. This model is much more useful to simulate clinical observation and treatment of an AVM. For example, with our model, the effects of changing extranidal circulation (systemic hypertension or hypotension, or occlusion of normal vessels) on the AVM, the complex feeder and drainage configuration, and the effects of the AVM on different parts of the cerebral circulation can be simulated. Furthermore, the model uses an AVM with an intranidal structure, including plexiform and fistulous vessels, to study the effects of changing extranidal circulation patterns on different parts or compartments of an AVM. Results can be compared to previously reported experimental observations for normal circulatory parameters as well as pressure changes induced by high flow through an AVM shunt (39) (Fig. 2). There was good agreement between experimental observations (40) and modeled predictions. UCLA Intranidal Model A detailed analysis of intranidal hemodynamics has been offered by Hademenos, Massoud and colleagues to model the risk of AVM rupture (30,41,42).
No No
No No Yes No No No No No No
Elastic modulus
Pulsatile flow
Autoregulation
Pressure distribution
Velocity distribution
Shear stress
Vessel dilation
Consideration of vessel branching exponents Cerebral blood volume No
No
No
Yes
No
No
No
No
Yes
16 for normal structure
44
30
34,35 150 (105)
36
Yes Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
ACA þ MCA þ PCA þ circle Same as left þ of Willis þ microvessels AVM nidus þ veins (bilateral) Yes Yes
No
No
No
No
No
No
No
No
Simple
121 (105)
31
Reference Numbers of Study
3 (62)
Abbreviations: ACA, anterior cerebral artery; MCA, middle cerebral artery; PCA, posterior cerebral artery.
No
No
No
No
Yes
Yes
Yes
Simple
Simple
Model structure
4
4
29
Number of compartments (vessels)
32,33
Table 1 Comparison of Published Models of Cerebral Arteriovenous Malformations
No
No
No
No
No
No
No
No
Intracranial þ extracranial þ AVM nidus No
139
28
No
No
No
No
No
No
No
No
No
Simple
3 (1002)
37
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Figure 1 Schematic diagram of the model of intracranial blood vessel network. A thick line represents a compartment that contains a number of identical vessels in parallel with each other. The numbers indicate the nodes. Between the arteries and the veins are 20 microvessel groups (MVGs), each of which consists of 5,000 microvessels. A thin line between an MVG and a vein does not represent a compartment but indicates a connection between these two compartments. A middle cerebral artery (MCA) arteriovenous malformation (AVM) used in several of the simulations is also shown. It connects nodes 90 and 91. Source: From Ref. 31.
By using electrical analogies, the circulatory network can be represented by an electrical circuit of connected wires with variable resistance through which current or flow, powered by an electrical voltage source or pressure gradient, traverses. The equivalent relationship between the parameters of electrical circuit and the hemodynamics are (a) current vs. flow and (b) voltage vs. pressure. Each wire or vessel represents a connection between nodes or location where flow converges or diverges. With respect to intranidal modeling of a cerebral AVM and its surrounding circulation, a node resembles the start or end of a vascular branch, e.g., a bifurcation or trifurcation.
Figure 2 Pressure ratios in zones E, I, T, H, F, and Hc compared with clinical observations. The predicted values of our model for the medium AVM are close to the mean values of the experimental observations of Fogarty-Mack et al. (78). E ¼ Extracranial: systemic pressure at level of coaxial catheter in extracranial vertebral artery or internal carotid artery; in this model, node 7. I ¼ Intracranial: supraclinoid internal carotid artery or basilar artery; in this model, node 11. T ¼ Transcranial Doppler insonation site: Al, Ml, or PI; in this model, node 23. H ¼ Halfway: arbitrarily ‘‘halfway’’ between T and the feeding artery; in this model, node 25. F ¼ Feeder; in this model, node 90. Hc ¼ Contralateral distal arterial pressure; in this model, node 26. The node numbers are as used in Fig. 1. E, I, T, H, F and Hc vascular zones taken from Fogarty-Mack et al. (40). Source: From Refs. 31, 40, 78.
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Figure 3 Schematic diagram of the electrical network describing the biomathematical AVM hemodynamic model. Source: From Ref. 42.
Electrical network analysis was used to construct a theoretical AVM intranidal model aimed at providing an accurate rendering of transnidal/intranidal hemodynamics (30). The AVM model was developed with four arterial feeders (AFs), two draining veins (DVs), and a nidus consisting of 28 interconnected plexiform and fistulous vessels, as shown in Figure 3. Parameters for construction of this intranidal model were derived from anatomic and physiological data obtained from published clinical, histopathological, and angiographic observations. There were two kinds of intranidal vessels: plexiform and fistulous. In this intranidal model, the vessel radius of plexiform was half of that of fistulous. The flow through the AVM nidus proceeds from the AF side to the DV side of the intranidal model and was calculated in accordance with two rules: (a) the algebraic sum of the currents at any node must be zero, i.e., flow into a node is equal to flow out of the node, and (b) the algebraic sum of the changes in potential (pressure gradient) encountered in a complete traversal of the circuit (loop) must be zero (30). These rules result in the derivation of nodal and loop equations for the circuit comprising the AVM intranidal model and yield a system of linear equations that can be solved with elementary matrix analysis. The solution yields the flow rate for each vessel in the vascular network. From the flow rate, other hemodynamic parameters, including the flow velocity and intravascular pressure gradient, were calculated. To determine the appropriateness of the hemodynamic and biophysical parameters used in the AVM intranidal model, a separate parameter sensitivity analysis and a qualitative validation study were performed with combinations and permutations of values for parameters used to construct the intranidal model (41). These parameters included systemic mean arterial pressure (SMAP), feeding mean arterial pressure (FMAP), draining vein pressure (DVP), cerebral venous pressure (CVP), and radii and length of plexiform and fistulous vessels. The risk of AVM rapture was based on the functional distribution of the critical radius of a cylindrical nidus vessel normalized to a possible range of clinically observed pressure gradients across the nidus. By using only the minimum and maximum values of each parameter to construct the model, it was found that there were approximately 200 combinations of values that could be used with this AVM intranidal model, each set of parameters providing a realistic representation of a different cerebral AVM. By inputting any set of parameter values from within the minimum to maximum range, it is theoretically possible to construct an infinite variety of AVM intranidal models. The corollary is that it is possible to fit the hemodynamic and structural characteristics of this AVM intranidal model to reflect/replicate those measured from cerebral AVMs in individual patients. For example, volumetric blood flow through one typical
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AVM intranidal model was 814 mL/min. Hemodynamic analysis of this AVM showed the flow rate to vary from 5.5 to 57.0 mL/min through the plexiform vessels and from 595.1 to 640.1 mL/min through the fistulous vessels. The risk of rupture for individual nidus vessels for this particular intranidal model ranged from 4.4% to 91.2%. Combined Intranidal and Extranidal Model The use of both an intranidal and an extranidal/whole brain approach may permit the formation of a more integrative view of AVM hemodynamics. Gao et al. explored the feasibility of using a computational model to simulate the risk of spontaneous AVM hemorrhage (64) combining aspects from previously published work on intranidal and extranidal components (36). Data from 12 patients were collected from a prospective databank that documented the angioarchitecture and morphologic characteristics of the AVM and the FMAP measured during initial superselective angiography before any treatment. By using previously developed intranidal and extranidal models, a new hybrid model was constructed to maximize the advantages of both models. The hybrid model with an AVM is shown in Figure 4A. The intranidal structure is detailed in Figure 4B.
Figure 4 Schematic diagram of the model combining the blood vessel network and the intranidal model. (A) A thick line represents a compartment that contains a number of identical vessels in parallel with each other. The numbers indicate the nodes. Between the arteries and the veins are 20 microvessel groups (MVGs), each of which consists of 5,000 microvessels. A thin line between an MVG and a vein does not represent a compartment but indicates a connection between these two compartments. Source: From Ref. 36. (B) The cerebral arteriovenous malformation intranidal network used in this model.
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Table 2 Geometric and Structural Parameters of the Vessels in Representative Model Compartments Compartment Number [N1 ! N2]
Diameter (mm)
Length (mm)
20 3.5 0.8 2.1 2.9 2.1 4 3.5 20 0.2 0.1
40 100 5 40 40 40 40 60 50 5 5
0 [1 ! 2] 7 [7 ! 9] 13 [13 ! 14] 23 [13 ! 21] 25 [11 ! 23] 31 [19 ! 86] 55 [49 ! 50] 60 [55 ! 49] 112 [0 ! 1] 141 [105 ! 108] 142 [106 ! 108]
Name Aortic arch Internal carotid artery (ICA) Anterior communicating artery (ACoA) Anterior cerebral artery (ACA) Middle cerebral artery (MCA) Posterior cerebral artery (PCA) Superior sagittal sinus Frontal ascending vein Heart Fistulous intranidal vessel Plexiforrn intranidal vessel
Abbreviations: N1, N2, Nodes representing the two ends of the compartment; Name, name of the vessel (or symbol used). Source: From Ref. 36.
The element used to construct the model was a compartment. The geometric parameters of the vessel (or compartment) network of this model, the position of its two ends within the model, are demonstrated by representative compartments in Table 2. The model construction is given in detail in Appendix 1. Intranidal structures were either (a) pure plexiform, (b) mixed plexiform and fistulous, or (c) pure fistulous. MODEL APPLICATIONS Cerebral Hyperemia Gao et al. evaluated the effects of step-wise shunt occlusion at normal cortical sites both near to and distant from the nidus (39). Cerebral blood flow (CBF) values were calculated for normal brain regions after AVM shunt flow obliteration in the absence of autoregulation, which is analogous to ‘‘vasomotor paralysis’’ of the arteriolar bed. There were two main findings. First, there was a very limited regional increase in CBF that was restricted to hypotensive circulatory beds adjacent to the AVM nidus (Fig. 5). Second, the degree of CBF increase was comparable to the hyperemia that is encountered clinically during, for example, CO2 inhalation (Fig. 6) (43). What remains to be explored further is the influence of shifts in the lower and upper limits of autoregulation in the presence of an AVM, thereby extending experimental observations (44,45) and a previously reported simulation (32,33). Increases in Feeding Artery Pressure with Embolization Therapy (Extranidal) Gao et al. used their model to study the magnitude of expected pressure changes along the vascular tree with shunt ablation to assess the hemodynamic risk of AVM treatment (39). They estimated the changes in intravascular pressure, velocity, biomechanical stress, and shear stress that might be expected from either endovascular or surgical ablation of an AVM. Two AVM sizes and two feeding artery constellations were simulated. The effect of different shunt flows on vascular pressure was modeled, and AVMs were occluded in a stepwise fashion. The effects of systemic hypertension and hypotension in the various vascular zones also were simulated. Because of the non-linearity of the arterial pressure increase that occurs with gradual occlusion of the shunt at the feeding artery level, the authors introduced the concept of ‘‘%occlusion at half-maximal pressure.’’ This corresponds to the percent of the AVM flow that must be cut off to increase feeding artery pressure from its baseline pretreatment level to a level midway to the final vascular pressure expected with complete occlusion of shunt flow (Fig. 7) (39). In the Gao et al. simulations, a large (1,000 mL/min) AVM was occluded, and feeding arterial pressure increased from 18 mmHg to 68 mmHg; the %-occlusion at half-maximal pressure increase was 92%. For a medium (500 mL/min) AVM, feeding arterial pressure increased from 37 mmHg to 66 mmHg; the %-occlusion at half-maximal pressure increase was 71%. Shunt obliteration increased pressure in the nidus and feeding arteries, but there was little effect on proximal vascular structures nearer the circle of Willis. During manipulation of the
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Figure 5 Regional cerebral blood flow (CBF) in the presence of a large middle cerebral artery (MCA) arteriovenous malformation (AVM) (located at the right hemisphere) compared with that after complete occlusion of the AVM. In the presence of the AVM, the CBF of ipsilateral fields MCA1, MCA2, and MCA3 decreased from normal values of 50 mL/ 100 g/min to 32, 21, and 26 mL/100 g/min, respectively. In other ipsilateral regions and the contralateral hemisphere, the CBF values were normal. After occlusion, the CBF of ipsilateral MCA1, MCA2, and MCA3 increased to approximately 70 mL/100 g/min due to the absence of autoregulation in these three regions, suggesting a limited potential for severe increases in CBF after shunt occlusion purely on a hemodynamic basis. Source: From Ref. 31.
systemic pressure, there was a "buffering" effect of the AVM fistula such that higher flow fistulas were exposed to smaller variations in intravascular pressure in feeding artery and nidal pressures during manipulation of systemic arterial pressure. Although the model was extensively compared to previously reported experimental observations (31), the paper addressing pressure changes and aneurysms (39) contained only a single case report as a means of verifying the predictions of the model simulations. However, the primary importance of the Gao et al. study was to generate a framework for interpretation
Figure 6 Illustration of the mean increase in cerebral blood flow after arteriovenous malformation obliteration in the various simulations of near-field regions with and without autoregulation. Source: From Ref. 31.
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Figure 7 Mean arterial feeding pressure (PF) changes during occlusion of two arteriovenous malformations (AVMs) fed by the anterior cerebral artery (ACA) and middle cerebral artery (MCA). (A) Mean systemic pressure was 80 mmHg. The simulations were carried out by a stepwise occlusion of the AVM from the initial blood flows of 1000 mL/min and 500 mL/min, respectively. The concept of ‘‘%-occlusion at half-maximal pressure increase’’ is also illustrated. As the 1000 mL/min AVM was occluded, PF increased from 18 mmHg to 68 mmHg, and increased by half of the maximal pressure increase at 92% occlusion (indicated by dashed lines). As the 500 mL/min AVM was occluded, PF increased from 37 mmHg to 66 mmHg, and increased by half of the maximal pressure increase at 71% occlusion (indicated by dotted lines). The observed changes in feeding artery pressure in the case report were similar to those that would be predicted for a shunt flow midway between the medium and large AVM model and are indicated in (A). (B) The two predicted curves are also shown for the arterial zone T (PT); there were no data from the case report available for this level of the circulation. Source: From Ref. 39.
of clinical phenomena and to generate further hypotheses. A model is most useful when it can predict values that are either difficult or impossible to measure clinically. Estimation of Hemorrhagic Risk (Intranidal) Intranidal modeling is somewhat hampered by the lack of precise details of intranidal threedimensional architecture. There have been two approaches, which are discussed below. Hademenos and Massoud investigated the theoretical hemodynamic consequences of venous drainage impairment on the risk of AVM rupture (42). Progressively greater stages of obstruction were simulated in the DVs. It was found that the risk reached 100% (i.e., rupture occurred) with a > 86% obstruction of DV1 (i.e., the DV fed by the intranidal fistula) and a patent DV2. Rupture was primarily due to the dramatic shift in the hemodynamic burden from the fistulous nidus vessels toward the weaker plexiform vessels. It was concluded that, on theoretical grounds, venous drainage impairment was predictive of AVM nidus rupture and was strongly dependent on AVM morphology (presence of intranidal fistulae and their spatial relationship to DVs) and transnidal hemodynamics. Estimation of AVM Rupture Risk (Combined) Two model risk (Riskmodel) calculations (hemodynamic- and structural-weighted estimates) were performed by using the patient-specific models (36). By using the University of California Los Angeles (UCLA) approach, a variable called Riskmodel was calculated with the simulated intranidal pressures related to its maximal and minimal values. Another variable, termed a structural-weighted estimate, was developed and described. This parameter included the vessel mechanical properties and probability calculation, which were considered in more detail than in the hemodynamic-weighted estimate. Riskmodel was then compared to
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experimentally determined risk, termed Riskexp, which was calculated with a statistical method for determining the relative risk of having initially presented with AVM hemorrhage (46). The Riskmodel calculated by both hemodynamic- and structural-weighted estimates correlated with experimental risks with v2 ¼ 6.0 and 0.64, respectively. The risks of the structural-weighted estimate were more highly correlated with experimental risks. Using two different approaches to the calculation of AVM hemorrhage risk, we found a general agreement with independent statistical estimates of hemorrhagic risk based on patient data. Computational approaches are feasible; future work can focus on specific pathomechanistic questions. Detailed patient-specific computational models can also be developed as an adjunct to individual patient risk-assessment for risk-stratification purposes (see below). A description of the mathematical treatment of the problem is presented in Appendix 2. LONG-TERM OBJECTIVES OF COMPUTATIONAL MODELING Patient-Specific Physiological Simulator A long-term goal is to be able to compile a real-time physiologic bedside model of an individual patient’s hemodynamic properties, analogous to current anatomic computer modeling, to aid in treatment planning. This compilation could be aided by adding detailed 3-D reconstructions of individual patient MR angiography data into the computational model. For example, all imaging and physiologic data could be loaded into a computational model for a given patient, and various manipulations could then be assessed for their hemodynamic consequences, such as vessel occlusion or degree of nidus obliteration. Technology Development It may be possible to use computational models to aid in the development of novel materials for endovascular therapy of cerebrovascular disease, e.g., new embolic materials and glues, or their delivery (47). Theoretical properties of known agents can be tested for optimal design of safety and efficacy studies. Likewise, the development of novel agents or techniques could be facilitated by having functional computational models to identify desired physical or physiological attributes. This applies to both agents and techniques, such as induced hypotension, or their delivery. Parameter Sensitivity Analysis Parameter sensitivity analysis is the investigation of the influence of external variables on the output of a closed system. Given a closed system (the AVM model with parameters that are fixed but can vary), we are interested in using the system to obtain a result (output). In this case, the output is hemodynamic data (flow/pressure), which depend on the fixed parameters of the AVM model. We have proceeded as well to the next step of relating the hemodynamic data to the probability of AVM rupture. Therefore, changing the fixed parameters of the AVM model influences the output or hemodynamic data, which in turn dictates the probability of AVM rupture. Parameter sensitivity analysis looks at all possible variations of parameters of the AVM model to ensure that the output is insensitive to the fixed parameters and hence rupture probability can be more accurately assessed. Real-time Physiologic Response and Mechanisms of CBF Regulation To achieve the long-term objective of compiling a real-time physiologic bedside model, the realtime physiologic response should be included in the model. The real-time responses are usually described by feedback loops that respond to changes in the circulation and influence the continued activity of the system. In our AVM model, three loops are involved for determining the blood flow in a vessel: (a) hemodynamic, (b) arterial pressure CBF autoregulation, and (c) shear stress-induced vasodilation, as shown in the light boxes in Figure 8. The hemodynamic feedback loop, described by physics and hemodynamics laws such as Poiseuille’s formula, is used for all vessels. The arterial pressure CBF autoregulation feedback loop is a descriptive response that determines the CBF in MVGs as a function of the arterial pressure in terms of the observed autoregulation curve or the observed response of cerebral arteries and arterioles to acute hypotension and hypertension. This loop is used for arteries and arterioles (MVG) only.
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Figure 8 Feedback loops (light boxes) in the Gao et al. arteriovenous malformation model. Source: From Ref. 31.
The shear stress-induced vasodilation feedback loop is used to calculate the radius change of normal large vessels due to the additional blood flow to the AVM. This loop is a relatively long-term feedback compared with a real-time physiologic response (31,36). The physiologic responses of the cerebral circulation system describe the mechanisms of CBF regulation. A representative investigation of CBF regulation has been demonstrated by Ursino (48). Unlike our cerebral blood circulation model for AVM study, which has large coverage of cerebral arterial and venous vessels, Ursino’s mathematical model is focused on the mechanisms of CBF regulation, in which the arterial tree is treated as a circulatory system with one blood flow loop. In Ursino’s model, the functional structure of the cerebrovascular bed has been analyzed in detail and the major feedback regulatory mechanisms, which are now assumed to work on the cerebral circulation have been separately examined, as shown in Figure 9. The introduction of the physiologic regulatory mechanisms described in Ursino’s model into our model will enable our model to predict the response of a patient’s cerebral blood circulatory system to designed treatments. Applications of AVM Models to Design of Clinical Trials Risk stratification is a necessary part of the design of clinical trials. Computational modeling can aid in the assessment of risk factors used to stratify treatment or interventional trials. It may be better able to predict which factors are more likely to be associated with an increased risk of hemorrhage, either in the natural course or perhaps even in the course of treatment. It is possible that high-risk patients could be better identified to evaluate treatment options. ANIMAL MODELING For many years, experimental research on cerebral AVMs was hampered by the lack of a suitable laboratory animal model possessing biological behavior and offering ‘‘biovariability’’ traits that are unavailable in mathematical or plastic models. The unavailability of an adequate in vivo AVM model has stemmed partly from the extreme rarity of naturally occurring animal AVMs. To construct an AVM model experimentally, two fundamental AVM characteristics
Figure 9 Block diagram describing the main subsystems involved in cerebral blood flow regulation and their mutual relationships in Ursino’s model. Source: From Ref. 48.
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Table 3 Characteristics of University of California Los Angeles Swine Rete AVM Model Advantages Model is simple to create. Surgery can be mastered relatively quickly. Large neck vessels can be surgically manipulated with ease during formation of a carotid-jugular fistula. Blood coagulation system of swine is similar to that of the human, a significant feature when attempting to model human vascular pathology. Use of swine is appropriate from an economical and ethical point of view. Nidus is composed of a plexus of microarteries of similar caliber to human AVM nidus vessels. Overall size is similar to small human AVMs. Nidus is easily accessible with angiographic catheters via the main arterial feeder and the main draining vein. All components of the AVM (feeders, nidus, drainers) are clearly demonstrable at angiography. Hemodynamic features are similar to simple human AVMs. The degree of blood shunting across the nidus is variable, thus simulating a spectrum of lower-flow and higher-flow AVMs. Model can be maintained chronically (for many months) for temporal hemodynamic, angiographic, and histologic studies, and for following up the effects of experimental treatment. All components of the model are easily accessible and removable en bloc at animal autopsy for gross examination and histological studies. Chronic histological features in the nidus vessels are those of a high-flow angiopathy; many changes are similar to those encountered in human AVMs. Model can be used as a laboratory simulator of simple human AVMs for the purpose of developing cognitive and technical skills in endovascular embolotherapy and for testing new embolization strategies and embolic materials and histopathological verification following embolotherapy. Disadvantages Model is a simplistic representation of most AVMs encountered in clinical practice. AVM is not surrounded by brain. It is situated at the skull base. Bilateral internal carotid arteries exit the nidus to supply the circle of Willis and the brain, whereas only veins drain human AVMs. Nidus vessels are composed of thick microarteries that do not rupture. Also, the draining vein is histologically an artery that carries retrograde flow and therefore drains (hemodynarnically speaking) the nidus. Abbreviation: AVM, arteriovenous malformation.
have to be replicated adequately: (a) a morphological component (a nidus composed of microvessels), and (b) a hemodynamic component (rapid blood shunting through the nidus). Previously reported so-called ‘‘AVM’’ models in rats (49,50), cats (51), and monkeys (52) were created mainly to investigate pathophysiological derangements accompanying AVMs, such as ‘‘cerebral steal’’ and ‘‘perfusion pressure breakthrough.’’ These models created carotid-jugular fistulae to mimic the high flow in conductance vessels that occurs with an AVM, but they do not possess an AVM nidus. Table 4 Comparison of Human, Animal, and Computational Models Purpose (Ref.) Simulator for training in endovascular embolotherapy (69) Testing new embolic agents (70) Development of new embolization techniques (47) Study of temporal histopathologic changes in chronic AVM models (71) Study of changes in hemodynamics (46,72–75)
Linking hemodynamics to patient outcome (46,76,77)
Human Studies Best for well-developed methods after safety and efficacy documented Best for well-developed methods after safety and efficacy documented Best for well-developed methods after safety and efficacy documented Definitive information
Best information, but limited access
Direct comparison possible
Abbreviation: AVM, arteriovenous malformation.
Animal Models Ideal for initial studies
Ideal for initial studies
Ideal for initial studies
Provides some useful information but indirect/ uncertain relationship of model to human disease Good information, better access, but incomplete applicability to human disease due to relatively simplistic models Indirect at best
Computational Models Possibly good for making predictions and design of study Theoretical advantages and drawbacks can be described Theoretical advantages and drawbacks can be described Never attempted
Ideal for generating hypothesis to test in human studies that are limited by sample size or measurement abilities Never attempted
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The normal swine carotid rete mirabile was proposed as a morphological replica of an AVM nidus (53–55). The carotid rete mirabile of swine is a fine network of vessels ranging in size from 70 mm to 275 mm (mean of 154 mm) (53) with connections across the midline, situated at the termination of both ascending pharyngeal arteries as they perforate the skull base. The complex plexus of microarteries that make up each rete extensively anastomose to give the appearance of a single structure on gross examination. Bilateral retia and their midline connections measure about 2.5 cm x 2.5 cm x 1.5 cm in size. To combine high flow shunting with a reasonable model of AVM nidal structures, an experimental porcine model of an AVM was attempted previously by iatrogenic traumatic shunting from the rete into the surrounding cavernous sinus (56). Drawbacks of this model are that (a) it requires the relatively invasive insertion of a long spinal needle through the animal’s orbit, with consequent post-procedural orbital hemorrhages and proptosis; (b) it involves iatrogenic puncture/transection of the rete vessels, i.e., trauma to the ‘‘nidus’’ of the ‘‘AVM’’; and (c) ensuing spontaneous thrombosis readily occurs because arteriovenous shunting is at the level of the normal rete microvessels, thus essentially limiting this model to an acute-phase one. To address some of these shortcomings, Massoud et al. developed an animal model of an AVM with closer resemblance to human lesions (57). The model still makes use of the carotid rete mirabile of swine, but with the added experimentally induced feature of faster blood flow and unidirectional shunting through bilateral retia. Briefly, following surgical right-sided common carotid to external jugular fistula formation and selective occlusion of various neck arteries ipsilateral to the fistula (which has been omitted in more recent uses of our model), left carotid and ascending pharyngeal arteriography demonstrates an angiographic simulation of an AVM, with rapid circulatory diversion from the left ascending pharyngeal artery (simulated ‘‘main or terminal feeder’’) across both retia mirabilia (simulated ‘‘nidus’’), and fast retrograde flow into the right ascending pharyngeal and common carotid artery (simulated ‘‘draining vein’’) toward the fistula. Recruitment of surrounding arteries (branches from the left external carotid system: ramus anastomoticus and arteria anastomotica) results in these smaller arteries simulating ‘‘en passage’’ feeders. The advantages and disadvantages of this swine AVM model are outlined in Table 3. SUMMARY Table 4 summarizes key concepts discussed in our review. The computer-modeling approach may be useful to better characterize both the pathophysiology and the clinical course of cerebral AVMs. Estimating risk of hemorrhage might be an enormous aid in the construction of rational clinical trials. Overall, interdisciplinary modeling studies of the cerebral circulation can be an important adjunct to experimental studies for increasing the knowledge of cerebral pathophysiology and devising treatment strategies, either by screening proposed theories or by testing existing ones. APPENDIX 1. DESCRIPTION OF A COMPUTATIONAL AVM MODEL In this appendix, we describe one system for constructing a model of AVM hemodynamics and risk of rupture. For further details and results of the application of this model, the reader is referred to the published report of this work (36). Model Construction On the basis of the intranidal model previously developed by the UCLA group (30,41,42) and the whole-brain (extranidal) model described by the Columbia group (31,39), a new hybrid model was constructed to maximize the advantages of both (36). This new hybrid model of an AVM embedded in a normal brain is shown in Figure 4A and 4B. The basic element used to construct the model is a compartment. A compartment has one or more vessels arranged in parallel. The geometric parameters of the vessel (or compartment) network of this model, the position of its two ends within the model, are demonstrated by representative compartments in Table 2. A complete list of vascular parameters has been previously published (31).
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Embedded in the extranidal model, the vessels of a previously developed intranidal model (41,42) were substituted by corresponding compartments. The number of the vessels in one intranidal compartment is the same as in others, which is assumed to be proportional (the proportionality was chosen to be one) to the calculated AVM volume. The effects of AVM size for a specific patient can be considered easily by changing the number of the vessels in the compartments without changing the network structure. The nodes in the intranidal structures are shown in Figure 4B. There were two kinds of intranidal compartments: plexiform and fistulous. The distribution of plexiform vessel numbers vs radius (frequency) follow the distribution suggested by histopathologic examinations and neuroradiologists’ observation to determine the number of fistulous connections. The fistulas were the compartments collecting nodes 90 and 108 vs nodes 93, 99, and 105. The radii of plexiform and fistula were 0.05 and 0.01 mm, respectively. To simulate the arteriolar resistance beds and brain tissue, we constructed ‘‘microvessel groups’’ (MVGs) as special compartments. The model contains 20 MVGs, each of them consisting of 5,000 parallel small vessels, which are 0.1 mm in diameter. As shown in Figure 4A, six of the 20 MVGs are perfused by the anterior cerebral artery (ACA), ten are perfused by the middle cerebral artery (MCA), and four are perfused by the posterior cerebral artery (PCA). They are symmetrically distributed in left and right hemispheres. Assuming a brain weight of 1500 g, each MVG represents a brain tissue weight of 75 g. The MVG also incorporates autoregulatory function into the normal (non-AVM) vasculature. Model of Physiological Simulations Poiseuille’s formula was used for single vessel hemodynamics (30): Q¼
pR4 DP 8Lg
ðA1:1Þ
where Q is the flow rate through the vessel, DP is the pressure drop across the vessel, R is the inner radius, L is length, and g is the blood viscosity (g ¼ 3.5 centipoise). If the transmural pressure of the vessel is P, the relationship between R and P can be approximated as R ¼ R0 ðI þ mPÞ
ðA1:2Þ
where R0 is the vessel radius at P ¼ 0 and m is the elastic coefficient of the vessel (29). m can be calculated from elastic modulus, E(e), and wall thickness, h0 (31), as m ¼ R0 =EðeÞh0
ðA1:3Þ
where e is the strain defined as e ¼(RR0)/R0. For the inclusion of autoregulation, the precapillary arterioles (embedded in the MVGs) are assumed to regulate flow constant between pressures of 50 and 150 mmHg; flow becomes pressure-passive above and below these boundaries (31). The number of the vessels in plexiform and fistulous compartments is inversely proportional to the AVM resistance: AVM Resistance ¼
DP 8Lg ¼ 4 Q pR
/ ðAVM dimensionÞ3 / 1=AVM volume
ðA1:4Þ
where L and R are assumed to be approximately proportional to AVM dimension. Therefore, the number of the vessels in each compartment is approximately proportional to the AVM volume. Clinically, conductance blood vessels dilate if there is a chronic increase in blood flow. Although the mechanisms of vessel dilation remain unclear, shear stress on the vessel wall is one possible effector of dilation (58,59). In this model, whenever the mean shear stress is greater than 10 times normal, the vessel dilates to adjust so that shear stress is equal to 10 times the normal value. We have found that this adjustment is necessary to make modeled predictions agree with experimental ones (31). By using Poiseuille’s Law to calculate the flow, turbulence of the blood flow was ignored in our model.
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APPENDIX 2. MATHEMATICAL AND COMPUTATIONAL APPROACH The pressures at all N nodes are used as N-independent variables. The continuity condition, the flow to a node equals the flow from the node, is used to build N-independent equations. Numeral iterations are used to solve these equations. A detailed description can be found in Gao et al. (31). Determination of Riskmodel Gao et al. used this model to estimate AVM rupture risk with clinical data from 12 patients (36). Clinical data included the largest AVM size in any dimension, venous drainage pattern, number of draining veins reaching a sinus, and measurements of feeding artery and systemic arterial mean pressures. For the purpose of this feasibility study, the number of feeders was fixed at 3 for all patient-specific models. AVM feeding supply was set at anterior/middle/posterior cerebral artery (ACA/MCA/PCA). Feeder radii were set: 0.5 mm for ACA feeders, 1 mm for MCA feeders, and 0.5 mm for PCA feeders. The radius of the draining vein (DV) was fixed at 1 mm for large DVs and 0.5–0.7 mm for small DVs. After each patient-specific model was built, it was simulated. The intranidal pressure and radius were calculated for Riskmodel of both hemodynamic- and structural-weighted estimates. Model Risk (Riskmodel) Calculated for Hemodynamic-weighted Estimate The method to calculate Riskmodel for hemodynamic-weighted estimates is based on our previous risk calculation (42). The critical radius (Rc) represents the theoretical radius of the cylindrical blood vessel just prior to rupture and a. depends on the elastic modulus, wall thickness (h), and transmural pressure (P); b. describes the theoretical radius prior to rupture of a single, isolated blood vessel. The objective is to apply the expression for the Rc to nidus vessels within an AVM. In addressing the first point, because the Rc is dependent on three variables, there can be an almost infinite number of possible combinations of these three variables that would yield the same Rc. It thus becomes reasonable to assert that the elastic modulus and h for all nidus vessels within a given AVM are uniform, based on the fact that biomechanical data pertaining to the elastic modulus and h of nidus vessels are virtually non-existent. This simplifies the expression of the Rc to only one variable (P), with elastic modulus and h now constant. Because the AVM nidus consists of a large and random distribution of interconnected vessels, the expression for the Rc cannot be directly applied to a single nidus vessel. Since we are dealing with a number of interconnected nidus vessels in an AVM, the individual pressure value of a nidus vessel becomes dependent not only on surrounding nidus vessels, but also on the number and individual pressure measurements of arterial feeders. To accommodate the wide range of possible pressure values through the entire nidus, we must look at the theoretical distribution of pressures experienced by the nidus. However, because in vivo hemodynamic measurements cannot be accessed to any degree inside nidus vessels, we can only hypothesize about the possible limits of pressure experienced by a nidus vessel. We hypothesized that the lower limit of pressure (Pmin) experienced by the nidus microvessels is equivalent to a cerebral venous pressure (CVP) of approximately 5 mmHg. The upper limit of pressure experienced by the nidus microvessels before rupture is likely to occur during considerable systemic hypertension (i.e., blood pressure that is then transmitted to the arterial feeders and the nidus). We have assumed that the normally low pressure arterial feeders may reach a maximum value of 74 mmHg during mean systemic (SMAP) hypertensive levels of 118 mmHg (derived by assuming a linear relationship between these two parameters). Therefore, 74 mmHg was chosen (somewhat conservatively) as the upper limit of blood pressure (Pmax) possibly encountered by nidus vessels before rupture. Risk of rupture is lowest at values closest to those of CVP and increases in an exponential fashion to a maximum value at pressures equal to or greater than the Pmax. The theoretical distribution of the Rc for the nidus vessel over the range from Pmin and Pmax serves as a baseline value for the RC of all vessels within the nidus. This in turn serves as
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a normalization factor for the assessment of RC of any nidus vessel. The same calculation of an experimental factor is performed for a particular nidus vessel using the same lower limit of pressure (CVP) as that for the normalization factor. The upper limit of pressure is the pressure for each nidus vessel, determined at simulation. The risk of rupture can be determined by the ratio of the experimental factor to the normalization factor multiplied by 100% and is represented mathematically (42): Riskmodel ¼ lnðPi =Pmin Þ=lnðPmax =Pmin Þ
ðA2:1Þ
where Pi is the transmural pressure of vessel i. If the experimental factor (numerator) is greater than the normalization factor (denominator) (which occurs when the experimental pressure (Pi) approaches Pmax), then the risk of rupture approaches 100%, implying that rupture has occurred. It is shown in Eq. (A2.1) that the contribution of the vessel to AVM rupture risk depends on pressures Pi, Pmax, and Pmin. Because Pmax and Pmin are the same for all vessels, intranidal transmural pressure, Pi, determines the risk. The risk is hemodynamically dominated (so-called hemodynamic-weighted risk). Since the intranidal pressure changes minimally from vessel to vessel, every vessel has almost the same risk as other vessels. The risk is distributed within the AVM uniformly. As the denominator is constant, the hemodynamic-weighted estimate of Riskmodel is proportional to the natural logarithm function of intranidal transmural pressure. Model Risk (Riskmodel) Calculated for Structural-Weighted Estimate To describe the uncertainty of vessel rupture, a random distribution function can be used. There are several frequently used functions, such as Gaussian, Rayleigh, Beta, Gamma, and v2. We used the Rayleigh (60) distribution function. Although the Gaussian distribution is the most frequently used distribution function due to its simplicity, it is not suitable for our model because it has a finite value in the negative range. A Rayleigh distribution function has a form similar to the Gaussian function, but it approaches zero when the parameter (radius) goes to zero. Critical Radius The Rc of a vessel can be calculated by vessel critical strain and unloaded vessel radius. However, there is no theory to precisely predict the rupture of a vessel, because of the many unknowns and the uncertainty of parameters. As described previously (42), the critical radius of a vessel can be written as Rc ¼ Eh0 =Pc
ðA2:2Þ
where E and h0 are elastic modulus and thickness of the vessel wall, respectively, and Pc is the critical pressure (the maximal pressure the vessel can support). Equation (A2.2) indicates that for the same material properties of the vessel wall, E and h0 being constant, Rc is inversely proportional to Pc: a vessel ruptured at high pressure has small critical radius. In a vessel ruptured at the same pressure, Pc being constant, Rc is positively proportional to either E or h0. The relationship between vessel radius and pressure depends on the material properties of the vessel wall and geometry of the vessel. The description of the elastic properties of arterial vessel wall is available (61,62). The experimental data represented in this literature indicate that the dependence of the radius on the pressure is nonlinear, which usually makes the calculation very complicated. Using Eq. (A2.2) and linear elastic approximation R ¼ R0 (I þ mP), one can eliminate the pressure and obtain an equation for critical radius of the vessel (36): Rc ¼ R0 ð1 þ mEh0 =Rc Þ
ðA2:3Þ
where m ¼ R0/E(e)h0 is the elastic coefficient of the vessel. Reforming Eq. (A2.3), we have R2c Rc R0 mEh0 R0 ¼ 0
ðA2:4Þ
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Substituting Eq. (A2.3) into (A2.4), we have: R2c Rc R0 RR0 2 ¼ 0
ðA2:5Þ
Solving Eq. (A2.5) and dropping the negative root, we have Rc ¼ 1:62R0
ðA2:6Þ
Eq. (A2.6) states that the vessel will rupture when its radius increases by a factor of about 1.62. Strain is defined as the relative change of radius: e ¼ ðRc R0 Þ=R0 ¼ 0:62
ðA2:7Þ
Eq. (A2.7) shows that the same rupture strain is predicted for any vessel under the linear approximation. This result is not very precise because the material is assumed to be linear and the thickness of the vessel wall is constant. Actually, the vessel wall is non-linear and the thickness decreases if the radius increases. The elastic increases with the pressure, or the elastic coefficient decreases with the pressure and also depends on E and h0. However, Eq. (A2.7) still gives a first-order approximation of critical radius. Based in part on previous experimental data (63), we feel it is reasonable to assume that the degree of elongation just before the vessel rupture is about 30%, that is Rc ¼ 1:3R0
ðA2:8Þ
The detailed analysis of the force exerted by blood on the vessel wall is provided in Appendix 3. AVM Rupture Risk Even though the parameters of vessels are the same, unknown factors or fluctuations may cause some to rupture, while others do not. Thus it cannot be predicted with absolute certainty whether a vessel will rupture. Instead, the probability or statistical risk of rupture may be determined. The derivation of the formulas of risk is given as follows: The rupture risk of a single vessel is described by a probability distribution function as Z R qi ðRÞdR ðA2:9Þ Ui ðRÞ ¼ 0
where Ui ðRÞ is the probability that a vessel ruptures at any value of radius smaller than R, and qi(R) is the probability distribution function, which equals the rupture probability of the vessel if it ruptures when the radius is in a unit interval around R. Rayleigh Distribution Function If the Rayleigh distribution function is used, the risk of rupture of a single vessel is R2 Ui ðRi Þ ¼ 1 exp i2 2Ric The AVM rupture risk is the probability sum over all intranidal vessels, such that ! 1 X Ri0 Pi 2 1þ Riskmodel ¼ 1 exp 3:38 i EðeÞhi0
ðA2:10Þ
ðA2:11Þ
Equation (A2.11) shows that the contribution of the vessel to AVM rupture risk depends on P and R0 to h0 ratio exponentially. The vessel with lowest h0/R0 has the most risk of rupture, or is the most dangerous to the AVM. Since the intranidal vessel thickness-to-radius ratio varies significantly, and intranidal transmural pressure changes minimally from vessel to vessel in the
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AVM, Riskmodel mainly depends on the vessel structures of the few weakest vessels. Hence, Riskmodel is vessel-structure dominated. Because the intranidal structure of the AVM was not described for each patient before preliminary calculations, the vessel thickness-to-radius ratio was assumed to be 0.60%. In Table A2-1, the key assumptions for the model risk calculations and their limitations as compared to their usefulness are presented. Morphologic, Hemodynamic, and Clinical Criteria Predicting Spontaneous Hemorrhagic Presentation (Riskexp) We used an experimentally derived estimate of relative hemorrhagic risk in AVM patients (Riskexp) (64). Briefly, we examined data from a large cohort of patients studied prospectively. Because of the strong evidence of our group and of others that future hemorrhage in the natural course of the disease is related to the initial mode of presentation (65–67), risk factors that are associated with initial hemorrhagic presentation can be used as a surrogate estimate of the propensity for hemorrhage in the natural course (Note that not all authors agree that initial hemorrhage is related to subsequent hemorrhage) (68). A stepwise variable selection procedure considered all significant univariate predictors that were selected from a large dataset that included factors such as anatomic (eloquent location, AVM side, AVM border), vascular (aneurysms, pial-to-pial collateral to nidus, venous drainage patterns) and clinical (cerebral arterial and systemic pressures, sex, age). The variables that were independently associated with increased hemorrhagic risk were identified using a standard multivariate logistic model. The stepwise variable selection procedure considered all significant univariate predictors. We found that two factors were the most powerful associative risk factors for initial hemorrhagic presentation of an AVM: (a) higher feeding mean arterial pressure (FMAP) at the point where embolic agents are injected, and (b) the presence of deep-only venous drainage (DVD-only, i.e., venous outflow into the internal cerebral vein or Galenic system, not into the major superficial sinuses). For a dataset of 129 cases, the risk (hazard ratio) per 10 mmHg increment in FMAP was 1.40 (95% confidence interval (CI) 1.08, 1.80; P < 0.01). For DVD only, the hazard ratio was 3.69 (95% CI 1.39, 9.75; P < 0.01), which is a dichotomous variable. We used a multivariate logistic regression procedure in which the probability, Riskexp, of an event is the same as the relative experimental risk and is expressed as: Riskexp ¼
1 1 þ eW
ðA2:12Þ
Table A2-1 Assumptions and Limitations of the Circulatory Model Assumption
Description
Improvement/Advantage
Curvature of vessels
Normal vessels, and especially AVM-related vessels, have significant curvatures
Network intranidal structure
Intranidal structure is Simplifies complicated assumed to be a network vascular structure and of plexiform and/or combination of plexiform fistulous compartments and fistulous nidus Linear elasticity is assumed Simple but good for vessel wall approximation Shunt flow is assumed to be Simple to calculate and consistent with our steady and non-turbulent flow in the intranidal estimates vessels
Linear vessel wall distensibility Steady and non-turbulent flow
Simplified as straight vessels
Abbreviations: AVM, arteriovenous malformation; MRA, magnetic resonance angiography. Source: From Ref. 36.
Limitation/Disadvantage Less accurate prediction; unknown effect; large conductance vessel image perhaps available from MRA in the future Increases the amount of computer calculations; exact structure not known Vessel wall may have nonlinear elasticity The details of flow in large intranidal vessels and at nodes have not been well described: therefore, the validation of this assumption is not available
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where W ¼ a0 þ a1 x1 þ a2 x2 , x1 ¼ deep-drainage only, and x2 ¼ FMAP. The coefficients are a0 ¼ 1.9157, a1 ¼ 1.3043, and a2 ¼ 0.0335. This calculation was used on a case-by-case basis to derive the values for mean Riskexp. Statistical Procedures A chi-square statistic was used to assess goodness of fit as follows: 2 N X Riskexp Riskmodel 2 v ¼ Riskexp i¼1
ðA2:13Þ
The significance of differences in model estimates of risk was assessed using McNemar’s test comparing the deviations of each of the two model risks for hemodynamic- and structuralweighted estimates from Riskexp. The relationship between measured pressure in the feeding artery and model-predicted pressure was tested by linear regression. APPENDIX 3. VASCULAR STRESS The force exerted by blood on a unit area of vessel wall can be separated into two components: the component perpendicular to (transmural pressure, P) and the component tangential to (shear stress, s) the inner surface of the vessel wall (both of which can be expressed in units of dyne/cm2). A vessel wall is an elastic material. The transmural pressure on the vessel wall tends to expand the vessel. Expansion is counteracted by the elastic forces within the vessel wall. These opposing forces applied to the vessel wall per unit area are defined as biomechanical stress (S, dyne/cm2). During normal stable conditions in the vessel wall, the transmural pressure is always balanced by biomechanical stress. The biomechanical stress inside the vessel wall can be separated into two components: circumferential stress (SC): SC ¼ Pr=h
ðA3:1Þ
Figure A3.1. Schematic representation of a thin-walled cylindrical vessel with blood flow. The stresses and pressures (forces per unit area) exerted on the vascular wall are indicated: transmural pressure (P); shear stress (s); biomechanical stress consisting of circumferential (Sc) and longitudinal (SL) stresses. See Appendix 3 for explanation. Source: From Ref. 39.
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and longitudinal stress (SL): SL ¼ Pr=2h
ðA3:2Þ
where r is the radius of the vessel and h is the thickness of the vessel wall. These stresses are shown diagrammatically in Fig. A3.1. Readers who are interested in the balance conditions or derivation of these formulae are referred to Chandran (61). According to the above formulae, the circumferential stress is greater than longitudinal stress (SC > SL). Therefore, circumferential stress will result in rupture before longitudinal stress will, and for the purpose of the model only circumferential stress was simulated and discussed (note that this assumes that the structural integrity of the vessel wall is similar in all directions). From S ¼ Pr/h, it can be seen that biomechanical stress is high with high pressure, large radius, and thin vessel wall. Shear stress is produced by blood flow and is always in the direction of flow, as shown in Fig. A3.1. Shear stress can be estimated as s ¼ 4gQ=Pr
ðA3:3Þ
where g and Q are the viscosity and flow of blood, respectively (30). The importance of shear stress for a modeling study was reported in one of our previous papers where it exerted an influence on the endothelial surface and was a control factor of flow-induced vasodilation (31). The direction of shear stress is parallel to longitudinal biomechanical stress. However, the relative contribution of shear stress to biomechanical stress is probably negligible.
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The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment [comments in J Neurosurg 1991 (Aug); 75(2):338–339]. J Neurosurg 1990; 73:387–391. 69. Massoud TF, Ji C, Vinueia F, et al. Laboratory simulations and training in endovascular embolotherapy with a swine arteriovenous malformation model. AJNR 1996; 17:271–279. 70. Massoud TF, Ji C, Guglielmi G, Vinuela F. Endovascular treatment of arteriovenous malformations with selective intranidal occlusion by detachable platinum electrodes: technical feasibility in a swine model. Am J Neuroradiol 1996; 17:1459–1466. 71. Massoud TF, Vinters HH, Chao K, Vinuela F, Jahan R. Histopathology of a chronic arteriovenous malformation in a swine model: Preliminary study. AJNR 2000; 21:1268–1276. 72. Murayama Y, Massoud TF, Vinuela F. Transvenous hemodynamic assessment of experimental arteriovenous malformations. Doppler guidewire monitoring of embolotherapy in a swine model. 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75. 76. 77. 78.
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[see comments by Lo, Eng H: J Neurosurg 1993 (Jan); 78(l): 156–158; Chaloupka, John C, et al. J Neurosurg 1993 (May); 78(5):850–853]. J Neurosurg 1992; 76:918–923. Kader A, Young WL, Pile-Spellman J, et al. The Columbia University AVM Study Project. The influence of hemodynamic and anatomic factors on hemorrhage from cerebral arteriovenous malformations. Neurosurgery 1994; 34:801–807 [discussion 807–808]. Hartmann A, Mast H, Mohr JP, et al. Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformation. Stroke 1998; 29:931–934. DeMeritt JS, Pile-Spellman J, Mast H, et al. Outcome analysis of preoperative embolization with N-butyl cyanoacrylate in cerebral arteriovenous malformations. Am J Neuroradiol 1995; 16:1801–1807. Fogarty-Mack P, Pile-Spellman J, Hacein-Bey L, et al. Superselective intraarterial papaverine administration: effect on regional cerebral blood flow in patients with arteriovenous malformations. J Neurosurg 1996; 85:395–402.
Section II
CLINICAL PRESENTATION AND DIAGNOSTIC EVALUATION
5
Natural History Bernard R. Bendok, Christopher Eddleman, Joseph G. Adel, M. Jafer Ali, H. Hunt Batjer, and Stephen L. Ondra Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A.
INTRODUCTION Arteriovenous malformations (AVMs) are lesions composed of arteries and veins without intervening capillary beds. A high flow profile leads to vascular recruitment and arterialization of venous structures (1). It is believed that these lesions are most often congenital, arising at approximately the third week of gestation. At that point, an arrest in development results in the formation of direct arteriolar to venous communications without an intervening capillary bed (2). AVMs comprise 1.5% to 4% of intracranial masses and are thought to occur approximately one-tenth as often as intracranial aneurysms (3). Although only 2000 new cases are reported per year in the United States (2), it is estimated that over 300,000 Americans harbor these lesions at any given time (4). Stapf et al. reported on an ongoing, prospective, population-based incidence and case-control study designed to determine AVM detection rates and the incidence and prevalence of AVM-associated morbidity, mortality, and case fatality rates. Those authors in their New York Islands’ population found an average annual AVM detection rate of 1.34 per 100,000 person-years (5). Approximately 65% of all intracranial AVMs are hemispheric. An additional 15% occur in the deep midline structures, and 20% are found in the posterior fossa (6). Multifocal AVMs of the brain have been reported (6). Intracranial AVMs occur in men slightly more often than in women (3). A review of 545 cases of intracranial AVMs by Perret and Nishioka revealed a 1.1:1 male to female ratio (3). The most common presentations of intracranial AVMs include hemorrhage, convulsions, headaches, progressive neurologic deficits, and mental deterioration (3). Most patients with AVMs develop symptoms between the ages of 20 and 40; peak incidence appears to be in the late second or early third decade of life with no age differences between women and men (5). A number of studies have tried to elucidate the natural history of these vascular lesions. However, most reports have been limited by small sample size, short inconsistent follow-up, and selection bias of the available study population. When different databases are compared, significant differences are noted between the many features of this kind of lesion. In this chapter, we review this literature and attempt to provide some conclusions about the fate of the untreated intracranial AVM. PRESENTING SYMPTOMS Hemorrhage Most intracranial AVMs present with symptoms related to hemorrhage (7,8). A multicenter prospective analysis has estimated this figure at approximately 53% (9). In their study of 284 patients with AVMs, Stapf et al. found a crude incidence rate of first-ever AVM hemorrhage (n ¼ 108) of 0.51 per 100,000 person-years and an estimated prevalence of AVM hemorrhage among detected cases (n ¼ 144) of 0.68 per 100,000 (5). This study, however, is limited by short follow-up (27 months) as of this report. Numerous studies have speculated on the incidence of hemorrhage in patients suffering from these lesions. Graf et al. estimated the risk of rebleeding after hemorrhage from such lesions to be 6% during the first year and 2%
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per year for up to 20 years after the initial hemorrhage. In this study, mean follow-up in patients with ruptured AVMs was two years (maximum of 37) (10). In a study of 168 patients with unruptured AVMs at the Mayo Clinic, 18% experienced hemorrhage during a mean follow-up period of 8.2 years, with an average risk of hemorrhage from previously unruptured AVM estimated at 2.2% per year. Among the survivors, a significant risk of hemorrhage persisted for at least 20 years (11). In their retrospective survey of 217 patients who did not undergo any form of surgery or irradiation, Crawford et al. reported that the yearly risk of hemorrhage was 2.6% for unruptured AVMs and 1.7% for ruptured lesions. This study had a mean follow-up period of 10.4 years (7). In 1985, Wilkins prepared a review of 1500 patients compiled from earlier clinical studies. He reported that unruptured AVMs carry an annual risk of hemorrhage of 2% to 3%. The rate of hemorrhage after an initial bleed was 6% in the first year and the same as for unruptured lesions thereafter (12). The literature on this topic often focuses on attempts to somehow stratify risk according to presentation. Graf et al., using life survival statistics, reported a rebleed rate of 42% by 20 years in patients presenting with hemorrhage but only a 37% risk for patients presenting with epilepsy. In this series, patients who presented without hemorrhage or epilepsy had a risk of hemorrhage of 45% (10). Fults and Kelly reported a 67% incidence of repeat hemorrhage over 15 years in those presenting with hemorrhage and a 27% incidence of hemorrhage in patients presenting with seizure (13). Some authors have also attempted to stratify the risk of hemorrhage according to the age of the patient. While some of these reports suggest a higher risk of hemorrhage in older patients (7,10), others suggest a relatively higher rate of bleeding in children with AVMs (13). The fact that most studies relating to the natural history of AVMs of the brain have been limited by small sample size, short inconsistent follow-up studies, and selection bias of the available study population presumably accounts for the great variability in statistics reported in the literature. In 1990, Ondra and colleagues updated a Finnish series of 166 prospectively followed, unoperated, symptomatic patients with AVMs of the brain (8). Follow-up data were obtained for 96% of the original study population with a mean follow-up period of 23.7 years. The relative geographic and linguistic isolation of the Finnish population combined with the centralization of medical care and meticulous record keeping allowed for a unique level of reliability for the study. Patients were divided into three groups: those who presented with hemorrhage, those who presented with seizure without history or evidence of seizure, and those who had headaches, asymptomatic bruits, or other vague neurological complaints but no evidence of hemorrhage. The annual bleeding rate in these patients was found to be 4%, and there was, in contrast to other reports, no significant difference in the rate of hemorrhage between these groups. The incidence of bleeding remained constant over 20 years of follow-up. The overall relatively higher rates of bleeding than those reported in earlier studies were attributed to the length and overall completeness of follow-up review in a well-defined, centrally cared-for population. In addition, the average interval between bleeding events was reported at 7.7 years, which was as long as or longer than the average follow-up intervals reported in previous studies. The authors suggested that this might also have contributed to the apparent underestimation of the rebleeding incidence in prior studies (8). Although the findings of studies addressing the issue of bleeding with intracranial AVMs are variable, some conclusions can be drawn from a review of the literature on this topic. It appears that unruptured AVMs are probably more harmful than earlier investigators had thought and that they appear to bleed with similar frequency to AVMs that initially present with hemorrhage. The incidence of hemorrhage appears to be between 2% to 4% per year. Finally, according to the most rigorous study available, the incidence of bleeding in these patients remains constant over the life of the patient. Although it is important for neurosurgeons to understand the risk of bleeding in patients with intracranial AVMs, it is equally important that these statistics be interpreted correctly and presented to patients so that they may put them in the proper perspective when they make decisions on treatment. Kondziolka et al. (14) demonstrated that, within the neurosurgical community, knowledge varied about the use of such statistics to predict long-term risks of hemorrhage. At two different national meetings in 1988 and 1994, the authors asked 119 neurosurgeons (36 residents, 80 attending neurosurgeons, and 3 nonspecified) to assess the risk of bleeding from an untreated AVM in a young adult over a 20- to 30-year period given
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a 3% to 4% annual risk of hemorrhage. Answers ranged from 1% to 100%, and were arrived at by many different means of calculation. To simplify the use of these statistics in clinical practice, the authors suggested the following formula based on the multiplicative law of probability to estimate the lifetime risk of hemorrhage in a patient not treated for an AVM: Risk of hemorrhage ¼ 1 ðAnnual risk of no hemorrhageÞexpected years of remaining life Clearly, a number of assumptions are made when the formula is applied to individual patients. First, it is assumed that there exists some degree of population homogeneity. This assumption is reasonable on the basis of results reported by investigators in the United States (11), Japan (15), Sweden (16), France (17), Great Britain (7), and Finland (8). Second, the formula assumes some degree of uniformity in the natural history of AVMs. Given that the study with the longest follow-up showed a constant bleeding rate over 20 years regardless of presentation (8), this assumption seems reasonable as well. Although a number of other variables exist that may apply to a particular patient, this formula provides a quick means of estimating lifetime risk of hemorrhage in patients that can easily be used in a clinical setting.
MORBIDITY AND MORTALITY RELATED TO HEMORRHAGE Estimations of morbidity and mortality rates in patients with intracranial AVMs have been reported. Graf et al. reported a morbidity rate of 81% of 191 patients after hemorrhage between 1946 and 1980 (10). Perret and Nishioka observed a 58% neurologic morbidity rate associated with AVM hemorrhage (18). Crawford et al., in their retrospective chart review, reported that of the patients who suffered AVM hemorrhage, 62% showed no neurologic handicap, 25% had minor disability, and 6% had major deficits. Crawford et al. (7) estimated the risk of a neurological deficit from AVM hemorrhage to be 27% over 20 years. This study also reported a mortality rate from all causes in patients harboring AVMs of 29% during this projected time period. Sixty-five percent of the deaths were thought to be a direct result of the AVM, most often due to hemorrhage (7). Svien and McRae reported ‘‘good survival quality’’ in 85% of the patients with AVMs who suffered incident hemorrhages, and 86% in those with subsequent hemorrhages (19). Brown et al. (11) reported that 29% of the patients who bled from AVMs died from the hemorrhage and that 23% had long-term morbidity. Overall, however, the authors described functional independence in at least 86% of the patients with AVMassociated hemorrhages. Wilkins et al. reported the annual mortality rate from ruptured AVMs as approximately 1% (12). In the study by Ondra et al. of 166 unoperated patients with AVMs, 40% suffered at least one major hemorrhage during the follow-up period (mean ¼ 23.7 years) (8). Of those patients who had hemorrhages after enrollment in the study, 85% suffered a major morbidity or died. An overall annual mortality rate in patients with AVMs was reported at 1%, was not affected by mode of presentation, and stayed constant throughout the length of the study. This conclusion that the rate of death in symptomatic patients with AVMs remains constant for their entire lives contradicts the conclusions of other AVM studies with fewer subjects and shorter follow-up (7,13). In total, 23% of the patients who enrolled in this study died as a direct result of hemorrhage. A conservative estimate of the combined annual major morbidity and mortality rates in patients harboring AVMs was reported at 2.7% per year and was constant throughout the follow-up period. Of note, the morbidity rate was higher in patients who initially presented with hemorrhage than in those who presented otherwise. The authors attributed this phenomenon to ‘‘additive injury’’ that was superimposed on neurological impairment from the earlier bleeding episodes and the resultant depletion of reserves to accommodate subsequent hemorrhages (8). A study conducted by Hartman et al. with data from the Columbia-Presbyterian AVM Study Project focused on neurological impairments secondary to bleeding from cerebral AVMs (20). These authors argued that most of the studies of morbidity secondary to AVM hemorrhages were based on retrospective analyses of hospital charts, often before the availability of modern brain imaging, and frequently did not specify the degree of impairment or the time interval between hemorrhages and follow-up assessment. Their study, in which hemorrhages were defined by computed tomography (CT) and magnetic resonance imaging
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(MRI), showed a lower morbidity rate for AVM-related hemorrhages than the literature suggests. Eighty-four percent of their patients had no neurological deficit or were independent (Rankin 0 or 1) after the first hemorrhage. In addition, functional outcomes in patients with both incident and subsequent hemorrhages were similar to outcomes of patients with single hemorrhages. The authors argued that this finding contradicted the importance of a cumulative effect of recurrent hemorrhages. While this study raises interesting questions, the mean follow-up time was only 16.2 months. To add perspective, the mean interval between hemorrhages reported by Ondra et al. was 7.7 years (8). Although modern imaging techniques would help to better elucidate the nature of the AVM and its bleeding type, the application of these techniques to the issue of the natural history of AVMs is difficult. The advent of such technology has been accompanied by increasingly sophisticated surgical and endovascular techniques that result in few AVMs being left untreated. The imaging used by Hartmann et al., however, does give insight into the pattern of bleeding associated with AVMs. Of the 115 incident hemorrhages they reported, 30% were subarachnoid, 23% were parenchymal, 16% were intraventricular, and 31% were located in combined areas (20). Some generalizations can be made after a review of the literature on the morbidity and mortality rates of AVM-associated hemorrhages. First, the risk of death for a patient suffering an AVM rupture is likely between 10% and 15%. Overall, the combined risk of morbidity and mortality is approximately 15% for each bleeding episode. For both previously ruptured and unruptured AVMs, the likelihood of a subsequent bleed appears to be approximately 2% to 4% per year with an average interval between bleeding events of about seven to eight years. Finally, the annual mortality risk in patients harboring intracranial AVMs is approximately 1%, and the neurologic morbidity risk is likely 2% to 3% per year. Epilepsy/Seizures After hemorrhage, epilepsy is the second most common symptom in patients harboring intracranial AVMs (21). In the study by Ondra et al., 24% of the patients with AVMs presented with seizure (8). In the study by Graf et al., 43 (32.1%) of 134 patients with AVMs who bled suffered convulsions (10). The timing of these convulsions varied. In just under one-half of the patients, the first seizure was believed to have occurred at the time of hemorrhage. However, approximately 19% of the patients suffered seizures some time after a bleeding episode (mean 4.8 years), and an additional one-third of those suffering convulsions did so before their first documented hemorrhage (mean 11.1 years). In another study, the risk of de novo epilepsy was projected as 18% 20 years after diagnosis (7). It is clear that epilepsy can manifest itself in patients with AVM before, during, or after hemorrhage, although it is difficult to estimate the incidence in each of these categories. In a prospective analysis by Hofmeister et al. of 1289 patients with brain AVMs from three independent databases, patients with AVMs presented with focal seizures about 10% of the time and with generalized seizures an additional 30% of the time (9). This analysis, however, did not distinguish between ruptured and unruptured AVMs. A review of the literature suggests that the annual incidence of de novo epilepsy is likely between 1% and 4% (7,10). Signs and Symptoms of AVMs Without Hemorrhage In most cases, AVMs of the brain present with either hemorrhage or seizure. However, other modes of presentation are documented. In a study of 48 patients with AVMs of the cerebral hemispheres, Pool et al. observed that initial symptoms were hemorrhage (42%), epilepsy (33%), hemiparesis (23%), headache (14%), aphasia (8%), or bruit (2%) (22). Brown et al. also found a variety of signs and symptoms on presentation of 146 patients with symptomatic intracranial AVMs. When categorized by ‘‘main indication for work-up,’’ 25 patients presented with headache attributable to an AVM. Of note, only three of these patients had ruptured lesions. Twelve patients presented with focal ischemia spells due to their AVMs, while only one of these patients presented with hemorrhage. Neurological deficits secondary to mass effect resulted in the work-up of five patients, none of whom had ruptured AVMs. An additional three patients presented with cranial or orbital bruits as their main indication for work-up. Of these, only one patient had a ruptured intracranial AVM (11). Thus, AVMs can
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result in a variety of signs and symptoms, and these modes of presentation are often not indicative of the integrity of the lesion itself. Apart from hemorrhage, several mechanisms have been proposed to explain the symptoms in patients with intracranial AVMs, including arterial steal phenomenon, interference with venous drainage, mass effect, hydrocephalus, venous ischemia, and neurological dysfunction secondary to passive congestion of venous outflow (23,24). At present, however, the complexity of the angioarchitecture of AVMs makes it difficult to definitively identify a single nonhemorrhagic mechanism responsible for any given symptom (23). AVMs IN THE GRAVID WOMAN Crawford et al. noted that one in four females between the ages of 20 and 29 who presented with AVM hemorrhage was pregnant (7). Although this report is compelling, the literature regarding the natural history of intracranial AVMs in the gravid woman is limited. Further studies will be required before generalizations can be confidently derived from these data. However, the available literature is sufficiently intriguing to underscore the need to explore this issue further. Reports have suggested that spontaneous subarachnoid hemorrhage secondary to ruptured aneurysms or AVMs may account for approximately 4.4% of all deaths in pregnant women. It has been reported that up to 50% of pregnant women presenting with intracranial hemorrhage have ruptured AVMs and that the course of AVM rupture may actually be more aggressive in these patients when compared to nongravid women. There is also evidence that rupture of AVMs in pregnant women may occur more frequently between week 20 of gestation and six weeks postpartum, and may be attributable to hemodynamic, hormonal, and coagulation changes that occur during this time (25,26). For a more thorough review of this issue, the reader should refer to Chapter 25 entitled ‘‘Arteriovenous Malformations in Pregnancy.’’ ANATOMICAL FACTORS INFLUENCING THE NATURAL HISTORY OF AVMs Several studies have speculated that anatomic variables related to intracranial AVMs may influence their natural history. Graf et al. reported that whereas the risk of rupture for small AVMs was 52% five years after initial diagnosis, the risk of hemorrhage for larger AVMs was only 10% (10). In a larger study, Crawford et al. found a smaller difference at a five-year follow-up, with rupture occurring 21% of the time in smaller AVMs and 18% in larger lesions (7). Guidetti and Delitala found that initial bleeding in smaller AVMs was more common than in larger AVMs, but smaller lesions had a lower frequency of second bleeds (27). Spetzler et al. also reported an increased frequency of bleeding with smaller AVMs and attributed this finding to increased feeding artery pressures in small lesions (28). They suggested that larger AVMs have higher flow and lower feeding artery pressures that may offer some level of protection from hemorrhage. The authors speculated, however, that these same anatomic features of larger AVMs might also predispose them to other phenomena such as cerebral steal and seizures. The notion that patients with larger AVMs are more likely to present with seizures, whereas those with small AVMs more often present with hemorrhage has been speculated on by other authors as well (29,30). In addition to large size, some authors have speculated that certain locations of intracranial AVMs make them more likely to present with seizure. AVMs located in the temporal and parietal lobes have been associated with higher risk of epilepsy when compared to AVMs occurring in the other lobes of the brain (7,31). In addition, seizures associated with parietal AVMs are predominantly focal, whereas those occurring with frontal lesions are more frequently generalized (12). Special anatomical features of AVMs that are thought to be related to major bleeding episodes include associated aneurysms and certain characteristics of AVM angioarchitecture such as venous stenosis and deep venous drainage. Associated aneurysms have been reported in approximately 10% of the patients with cerebral AVMs and can be located on the primary feeding vessels or other vessels (32). The role of aneurysms associated with AVMs is an issue of ongoing controversy. Mansemann et al. distinguished between aneurysms within the AVM nidus and those occurring on the feeding vessels (33). In their study, 191 (54%) of 357 patients
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without associated aneurysms exhibited hemorrhage. Similarly, 67 (54%) of 124 patients with exclusively proximal associated aneurysms suffered hemorrhage. Furthermore, 48 (57%) of 84 patients with exclusively intranidal aneurysms exhibited hemorrhage. Of the 97 patients who had both proximal and intranidal-associated aneurysms, 42 (43%) suffered an intracranial bleed (33). Whereas Mansemann et al. did not find an association between the presence of intranidal aneurysms or feeding artery aneurysms and hemorrhage, others have reported to the contrary. Brown et al. found the risk of hemorrhage when aneurysms and intracranial AVMs coexist to be 7% per year compared with a reported 1.7% per year for patients with intracranial AVMs alone (11). Turjman et al. also found that the presence of AVM-associated aneurysms, including both intranidal and feeding artery aneurysms, correlated significantly with the clinical presentation of hemorrhage (p ¼ 0.001) (34). Thus, symptomatic aneurysms associated with intracranial AVMs should probably be obliterated. The morbidity and mortality rates associated with ruptured aneurysms are significantly higher than those associated with intracranial AVMs (34). The appropriate management of associated asymptomatic aneurysms is less clear. However, until the natural history of these lesions becomes clearer, it seems prudent to proceed with treatment of these aneurysms as well. For a thorough discussion of AVM-associated aneurysms, the reader is directed to Chapter 24. It is has been hypothesized that any variable of AVM angioarchitecture that contributes to venous hypertension increases the risk of hemorrhage (33). The transmission of high arterial pressures may subject venous structures to pressures that they are not suited to tolerate. Nataf et al. (35) showed correlation between incidence of hemorrhage secondary to intracranial AVM and four variables: exclusively deep venous drainage, venous stenosis, venous reflux, and a higher ratio of feeding to draining systems (afferent/efferent ratio). Venous recruitment was reported to be a favorable prognostic indicator. In another study, arterial stenosis, arterial angioectasia, and arteriovenous fistulae were negatively correlated with hemorrhage, while venous stenosis, in most instances, showed a positive correlation. These authors also noted that the location of the AVMs seemed to modify their venous drainage characteristics. Venous stenosis was not positively associated with hemorrhage for cortical AVMs (33). Turjman et al. found that AVMs in certain locations such as the basal ganglia or a midline location are significantly correlated with hemorrhage (34). Possible mechanisms cited for this anatomical propensity for hemorrhage include vein of Galen stenosis, short arteries with high pressure in AVMs that are deeply situated and possess deep venous drainage, and an association of central venous drainage and AVMs in periventricular locations (34). This relationship between deep venous drainage and AVM hemorrhage has been described in other reports as well (36,37). SPONTANEOUS REGRESSION Spontaneous regression of intracranial AVMs is rare. In a review of the literature, Abdulrauf et al. reported 24 cases of spontaneous angiographic obliteration of AVMs (38). The majority of cases occurred in adults at intervals ranging from 6 months to 21 years after diagnosis, and in most cases, regression was acute. Gradual regressions have also been observed (39). Several mechanisms have been postulated to explain spontaneous regression, including arteriosclerosis of feeding vessels (39), embolism from an associated thrombosed aneurysm (40), and the compressive forces of a hematoma or local edema secondary to hemorrhage (41). Lakke hypothesized that frequent microbleedings of an intracranial AVM with consequent organization and gliosis of the clot caused kinking of the feeding vessels, thereby facilitating its thrombosis (42). There is no clear generalizable mechanism involved in spontaneous regression of these lesions. However, the most common feature appears to be compression of the vascular nidus from AVM hemorrhage, although total spontaneous regression has been reported without hemorrhage or thrombotic phenomena (39). Three of the cases reviewed by Abdulrauf et al. involved patients whose AVMs had been partially resected. The interval to angiographic obliteration in these three patients ranged from five months to eight years. All three residual AVMs were classified as small and were associated with one draining vein. Two of the three appeared to have had limited arterial supply (38). This kind of phenomenon raises questions about the management of residual AVMs, especially in cases involving eloquent cortex. In general, we still advocate prompt resection of residual AVMs with persistent shunting. However, the management of small residual AVMs
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in eloquent cortex that are associated with a single draining vein is less clear. Patients with possible residual AVMs should be followed for several years to confirm absence of further natural history risk. Adjuvant therapies such as endovascular treatment or stereotactic radiosurgery need to be considered. REFERENCES 1. Rothbart D, Awad IA, Lee J, Kim J, Harbaugh R, Criscuolo GR. Expression of angiogenic factors and structural proteins in central nervous system vascular malformations. Neurosurgery 1996; 38:915–924. 2. Stein BM, Wolpert SM. Arteriovenous malformations of the brain. I. Current concepts and treatment. Arch Neurol 1980; 37:1–5. 3. Perret G, Nishioka H. Arteriovenous malformations. In: Sahs AL, Perret GE, Locksley HB, Nishioka H, eds. Intracranial Aneurysms and Subarachnoid Hemorrhage: A Cooperative Study. Philadelphia: Springer Publishing, 1969:200–222. 4. Challa VR, Moody DM, Brown WR. Vascular malformations of the central nervous system. J Neuropathol Exp Neurol 1995; 54:609–621. 5. Stapf C, Mast H, Sciacca RR, et al; New York Islands AVM Study Collaborators. The New York Islands AVM Study: design, study progress, and initial results. Stroke 2003; 34:e29–e33. 6. Schlachter LB, Fleischer AS, Faria MA, Tindall GT. Multifocal intracranial arteriovenous malformations. Neurosurgery 1980; 7:440–444. 7. Crawford PM, West CR, Chadwick DW, Shaw MDM. Arteriovenous malformations of the brain: natural history in unoperated patients. J Neurol Neurosurg Psychiatry 1986; 49:1–10. 8. Ondra SO, Troupp H, George ED, Schwab K. The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg 1990; 73:387–391. 9. Hofmeister C, Stapf C, Hartmann A, et al. Demographic, morphological, and clinical characteristics of 1289 patients with brain arteriovenous malformation. Stroke 2000; 31:1307–1310. 10. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983; 58:331–337. 11. Brown RD, Wiebers DO, Forbes G, et al. The natural history of unruptured intracranial arteriovenous malformations. J Neurosurg 1988; 68:352–357. 12. Wilkins RH. Natural history of intracranial vascular malformations: a review. Neurosurgery 1985; 16:421–430. 13. Fults D, Kelly DL. Natural history of arteriovenous malformations of the brain: a clinical study. Neurosurgery 1984; 15:658–662. 14. Kondziolka D, McLaughlin MR, Kestle JRW. Simple risk predictions for arteriovenous malformation hemorrhage. Neurosurgery 1995; 37:851–855. 15. Itoyama Y, Uemura S, Ushio Y, et al. Natural course of unoperated intracranial arteriovenous malformation: study of 50 cases. J Neurosurg 1989; 71:805–809. 16. Forster DMC, Steiner L, Hakanson S. Arteriovenous malformations of the brain. J Neurosurg 1972; 37:562–570. 17. Jomin M, Lesoin F, Lozes G. Prognosis for arteriovenous malformations of the brain in adults based on 150 cases. Surg Neurol 1985; 23:362–366. 18. Perret G, Nishioka H. Report on the cooperative study of intracranial aneurysms and subarachnoidal hemorrhage. Section VI. Arteriovenous malformations. J Neurosurg 1966; 25:467–490. 19. Svien HJ, McRae JA. Arteriovenous anomalies of the brain: fate of patients not having definitive surgery. J Neurosurg 1965; 23:23–28. 20. Hartman A, Mast H, Mohr JP, et al. Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformation. Stroke 1998; 29:931–934. 21. Yeh H-S, Kashiwagi S, Tew JM, Berger TS. Surgical management of epilepsy associated with cerebral arteriovenous malformations. J Neurosurg 1990; 72:216–223. 22. Pool JL. Treatment of arteriovenous malformations of the cerebral hemispheres. J Neurosurg 1962; 19:136–141. 23. Hurst RW, Hackney DB, Goldberg HI, Davis RA. Reversible arteriovenous malformation-induced venous hypertension as a cause of neurological deficits. Neurosurgery 1992; 30:422–425. 24. Lasjaunias P, Chiu M, Brugge KT, Tolia A, Hurth M, Bernstein M. Neurological manifestations of intracranial dural arteriovenous malformations. J Neurosurg 1986; 64:724–730. 25. Sadasivan B, Malik GM, Lee C, Ausman JI. Vascular malformations and pregnancy. Surg Neurol 1990; 33:305–313. 26. Lanzino G, Jensen ME, Cappelletto B, Kassell NF. Arteriovenous malformations that rupture during pregnancy: a management dilemma. Acta Neurochir (Wein) 1994; 126:102–106. 27. Guidetti B, Delitala A. Intracranial arteriovenous malformations: conservative and surgical treatment. J Neurosurg 1980; 53:149–152. 28. Spetzler RF, Hargraves RW, McCormick PW, Zabramski JM, Flom RA, Zimmerman RS. Relationship of perfusion pressure and size to risk of hemorrhage from arteriovenous malformations. J Neurosurg 1992; 76:918–923.
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29. Norris JS, Valiante TA, Wallace MC, et al. A simple relationship between radiological arteriovenous malformation hemodynamics and clinical presentation: a prospective, blinded analysis of 31 cases. J Neurosurg 1999; 90:673–679. 30. Kader A, Young WL, Pile-Spellman J, et al. The influence of hemodynamic and anatomic factors on hemorrhage from cerebral arteriovenous malformations. Neurosurgery 1994; 34:801–808. 31. Parkinson D, Bachers G. Arteriovenous malformations: summary of 100 consecutive supratentorial cases. J Neurosurg 1980; 53:285–299. 32. Malik GM. Special considerations in treating arteriovenous malformations. In: Welch KMA, Caplan LR, Reis DJ, Siesjo BK, Weir B, eds. Cerebrovascular Diseases. San Diego: Academic Press, 1997: 525–528. 33. Mansmann U, Meisel J, Brock M, Rodesch G, Alvarez H, Lasjaunias P. Factors associated with intracranial hemorrhage in cases of cerebral arteriovenous malformation. Neurosurgery 2000; 46:272–281. 34. Turjman F, Massoud TF, Vinuela F, Sayre JW, Guglielmi G, Duckwiler G. Correlation of the angioarchitectural features of cerebral arteriovenous malformations with clinical presentation of hemorrhage. Neurosurgery 1995; 37:856–862. 35. Nataf F, Meder JF, Roux FX, et al. Angioarchitecture associated with haemorrhage in cerebral arteriovenous malformations: a prognostic statistical model. Neuroradiology 1997; 39:52–58. 36. Marks MP, Lane B, Steinberg GK, Chang PJ. Hemorrhage in intracerebral arteriovenous malformations: angiographic determinants. Radiology 1990; 176:807–813. 37. Miyasaka Y, Yada K, Ohwada T, Kitahara T, Kurata A, Irikura K. An analysis of the venous drainage system as a factor in hemorrhage from arteriovenous malformations. J Neurosurg 1992; 76:239–243. 38. Abdulrauf SI, Malik GM, Awad IA. Spontaneous angiographic obliteration of cerebral arteriovenous malformations. Neurosurgery 1999; 44:280–288. 39. Marconi F, Parenti G, Puglioli M. Spontaneous regression of intracranial arteriovenous malformation. Surg Neurol 1993; 39:385–391. 40. Omojola MF, Fox AJ, Vinuela FV, Drake CG. Spontaneous regression of intracranial arteriovenous malformations. J Neurosurg 1982; 57:818–822. 41. Eisenman JL, Alekoumbides A, Pribam H. Spontaneous thrombosis of vascular malformations of the brain. Acta Radiol (Diagn) 1972; 13:77–85. 42. Lakke JPWF. Regression of an arteriovenous malformation of the brain. J Neurol Sci 1970; 11:489–496.
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Classification and Grading Systems Kai U. Frerichs Cerebrovascular Center, Department of Neurosurgery, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, U.S.A.
Philip E. Stieg Department of Neurological Surgery, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
Robert M. Friedlander Cerebrovascular Center, Department of Neurosurgery, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, U.S.A.
INTRODUCTION Arteriovenous malformations (AVMs) of the brain consist of abnormal primitive connections between the arterial and venous systems, single or multiple. They can occur throughout the brain with a predilection for the cerebral hemispheres supplied by branches of the middle cerebral artery (MCA) (1–4). AVMs are congenital lesions that develop most likely between the fourth and the eighth weeks of embryonic life (5,6). The lesion is characterized by a persistent direct connection of the arterial inflow and venous outflow without an intervening capillary bed. The primordial vascular plexus first differentiates into afferent, efferent, and capillary components. The more superficial plexus forms large vascular channels destined to be arteries and veins, while the deeper part develops into the capillary component associated with the brain surface. Perfusion of the embryonic brain starts at week four. AVMs arise from failure to develop an intervening capillary system. There is no genetic predisposition. Most AVMs are diagnosed initially in individuals between ages 20 and 40 who typically present with seizures, hemorrhages, and progressive deficits. In children, hemorrhage is the presenting symptom in approximately 80% of cases, and is about seven times more likely than seizure (7,8). This proportion is significantly higher than that found in adults. The reasons for the propensity of pediatric AVMs to hemorrhage are not understood. The mortality rate for AVM hemorrhage in children (25%) (9) is higher than that in adults, which approaches 6% to 10% (7). This may be due to the fact that AVMs in children are more prevalent in the posterior fossa (approximately 24%), where the effects of hemorrhage are more catastrophic, as compared with the predominantly supratentorial location in adults (7,9,10). Treatment modalities include surgical resection, stereotactic radiosurgery, embolization, and combinations of all of them. Surgical grading systems have been developed over the decades. Their primary purpose has been to prognosticate surgical outcomes, and their secondary purpose has been to select the appropriate treatment modalities for a specific AVM. This chapter will review the various grading systems and their potential usefulness in optimizing the treatment of AVMs. CLASSIFICATION AND GRADING PARAMETERS The following parameters will introduce the ‘‘raw material’’ from which grading scales and AVM classifications have been derived and used in various combinations. The most important factors are the anatomical features of the AVM. Hemodynamic parameters and general clinical factors also will be discussed. Anatomy Anatomic parameters include AVM size, location, drainage pattern, arterial supply, and associated aneurysms. These parameters form the critical basis for most grading scales as surgical prognosticators.
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Size Size can be determined as a simple diameter or as volume, the latter being more important for the planning of radiosurgery. For most grading scales, the largest diameter of the lesion is the size grading parameter, and this parameter is correlated with surgical outcome (4,10–17). Size estimation would appear to be a straightforward process, but some limitations and sources of error exist. Computed tomography (CT) uses linear projection techniques that do not distort the geometry of the object on its image. Magnetic resonance imaging (MRI) has several sources of potential errors such as the presence of signal voids and field inhomogeneity generated by various flow patterns that can cause errors in size estimation of up to 5 mm (18–20). With digital subtraction angiography, the gold standard technique for the diagnosis and grading of AVMs, magnification errors occur because of the divergent geometry of the incident x-ray beam (21,22). Errors in linear measurements may be up to 13% at a distance of 7 cm from the calibration plane. Accordingly, errors in area and volume measurements increase even more, up to 25% for area estimates and up to 40% for volume determinations. Linear errors increase further if nonspherical objects are inclined in the viewing direction. Such errors may be avoided if stereotactic markers and algorithms are used. This problem may also be overcome by the use of stereotactic digital dynamic angiographic imaging and an interactive volume rendering algorithm. These solutions do not address the added complexity of AVMs with multiple compartments or separating vessels that are part of the lesion and vessels that are en-passage, which may increase interobserver variability. Neither MRI nor angiography can solve these problems alone. It is critical, however, to optimize accuracy as much as possible because it is likely that AVM volume, rather than maximal linear diameter, will be the ideal size parameter for future studies that compare outcomes from surgical resection and from stereotactic radiosurgery. MRI, angiography, and CT angiography in conjunction will continue to be useful methods for estimating size and volume of AVMs, and consensus about a standard measurement technique would be highly desirable to optimize grading. Location The location of the AVM plays a critical role in the treatment plan. A small AVM located in the pons would be considered inoperable but may be amenable to other types of treatment. The same small AVM located in the right frontal pole would be easily amenable to surgical resection. Although AVMs can occur in any location in the brain, approximately 70% to 93% of AVMs are supratentorial, with a predilection for the cerebral hemispheres (9,15,23–25). In general, the location could be subdivided into regions of accessibility and type of neurological function that is subserved by the region in question (26,27), thereby creating the issue of ‘‘eloquent’’ versus ‘‘noneloquent’’ tissue (1). Eloquent areas are viewed as those whose destruction would result in an obvious and (for most) disabling deficit, such as the loss of speech or the use of an extremity. More subtle deficits may arise from damage to so-called noneloquent areas such as parts of the frontal and temporal lobe, which for some might be just as disabling (28). These considerations illustrate a general point: grading scales for AVMs or similar neurosurgical problems are useful only if each individual patient and the clinical circumstances are carefully assessed as well. Most neurosurgeons would agree, however, to divide the brain into regions of eloquence and ‘‘vital’’ importance as follows: &
Cortical (noneloquent) including the cerebellar hemispheres; the frontal, parietal, and temporal lobes with exception of the speech areas; sensory motor cortex, and the occipital lobes, depending on whether or not a visual field cut is viewed as a significant neurological deficit. & Cortical (eloquent) including sensory motor cortex, speech areas, and visual cortex. & Deep (nonvital) including insula, basal ganglia, anterior limb of the internal capsule, corpus callosum, deep medial temporal lobe, intra- and periventricular and deep cerebellar nuclei. & Deep (vital) including the genu and posterior limb of the internal capsule, thalamus, hypothalamus, brain stem, and any lesion extending into these structures. Drainage Pattern The venous drainage pattern is an important determinant of AVM complexity, can best be determined on angiograms, and may be divided into superficial and deep (12,16,17). The AVM drainage is considered deep if any or all of the venous outflow involves deep veins, such
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as the internal cerebral veins, basal veins, or precentral cerebellar vein. Transcerebral veins allow drainage from superficially located AVMs to the deep venous system. Deep venous drainage can pose a significant surgical challenge, as accessibility is poor and veins may retract deep into the parenchyma, thereby precluding bipolar cauterization (16,29). Although this impression is shared by many neurosurgeons, others do not place as much importance on the direction of the venous drainage (30–33). As indicated above, AVM drainage may involve not just a single venous channel but multiple draining veins. Associated venous anomalies such as varicosities that can reach aneurysmal proportions (34), as well as stenoses and occlusions (4) of such draining veins, may also add to the surgical complexity. Agenesis of the straight sinus associated with a venous steal and other venous abnormalities may be related to a worse prognosis (10,35,36). Arterial Supply The arterial supply of AVMs can arise from a single or multiple vascular territories and involve single or multiple feeders. AVMs located at border zones may be supplied by vessels from two or more territories. Feeding arteries have formed abnormal connections with the venous system in an area that would normally be supplied and drained by these vessels. In some cases, the external carotid circulation may participate and even be the sole source of AVM supply (37,38). These circumstances may not add significantly to the level of surgical difficulty (31). Feeding arteries enlarge secondary to the increased flow through the arteriovenous shunt (39,40). This enlargement in itself may increase the surgical risk (11). High venous pressures and high volume flow lead to increased tortuosity and enlargement of the draining veins. The hemispheric circulation can be further subcategorized into epicerebral, transcerebral, and subependymal circulation. Epicerebral arteries are short penetrating branches that are derived from small pial arteries and enter the cortex at a right angle to supply the cortical gray matter. Transcerebral vessels are longer, enter the deep cortical white matter, and terminate in the periventricular plexus. AVMs that involve mainly the transcerebral vessels may not be visible on the cortical surface. High flow shunting may lead to a steal phenomenon in adjacent brain regions, thereby leading to neurological symptoms. A simple terminal feeder may be ligated without consequence. It may be difficult to ligate multiple feeders completely without compromising adequate blood supply to important structures. This consideration is particularly important for the deep arterial system such as the lenticulostriate, choroidal, and deep perforating arteries at skull base (26,32). Therefore, the number and location of arterial feeders may correlate with surgical risk and prognosis. Furthermore, the specific anatomic origin of the feeding artery may invoke specific difficulties and correlate with a higher risk for complications (33). Associated Aneurysms Aneurysms are frequently associated with AVMs (41–47). The incidence of AVM-associated aneurysms is between 10% and 20%, but an incidence of up to 58% has been reported (47). Most of these reported aneurysms were intranidal and were diagnosed on angiograms that may be prone to interobserver variability. Such aneurysms have been suspected to be related to a higher risk of hemorrhage as the presenting symptom. Furthermore, they may influence the natural history and clinical course of the disease. It is estimated that the annual risk of hemorrhage from an AVM with coexisting aneurysms is 7% versus 1.7% for patients with AVMs only (44). AVM-related aneurysms may be categorized as intranidal, flow-related proximal, flowrelated distal, and unrelated (45). So-called venous aneurysms, however, are probably better described as venous pouches or varicosities that arise secondary to increased AVM shunt flow. Such venous pouches may, however, be associated with an increased risk for hemorrhage and represent an ominous feature (34). Proximal flow-related aneurysms occur on major vessels of the circle of Willis, the proximal middle cerebral (M1) and internal carotid (ICA) arteries, or the vertebrobasilar trunk, which eventually supply the AVM. Distal flow-related aneurysms are located more directly on feeding arteries. Intranidal aneurysms fill early during angiography and are located within the AVM nidus. Unrelated aneurysms do not have an apparent relationship with the AVM and may be coincidental. In their series of 632 AVM patients, Redekop et al. (45) found that 15.3% had at least one aneurysm. Of those, 36% had intranidal aneurysms, 73% had flow-related aneurysms, and 5% had unrelated aneurysms. Of all flow-related aneurysms, 68% were proximal and 32% were distal. The great majority of all flow-related aneurysms were small (less than 12 mm) in size (proximal 95% and distal 97%). No convincing correlation
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has been found between features of the AVM and the associated aneurysms, and therefore the aneurysms could be the result of complex interactions of host-specific and hemodynamic factors. More aneurysms appear to occur, however, in association with larger AVMs (43). The concept that AVM-related aneurysms are flow-related is supported by several observations including statistical analysis of the excessive number of aneurysms on high flow feeding vessels related to AVMs (48) and the disappearance of aneurysms after resection of the AVM (49,50). Aneurysms close to the nidus (distal flow-related) have a much higher rate of spontaneous regression after AVM resection than proximal ones. This finding correlates with more profound flow changes close to the nidus after AVM treatment compared with relatively minor changes proximally (45). Most of the evidence indicates that intranidal aneurysms are also true aneurysms rather than pseudoaneurysms that result from a hemorrhagic episode. The bleeding risk from proximal aneurysms may not be increased (42), whereas intranidal aneurysms or aneurysms close to the nidus may have a significantly increased risk of hemorrhage, especially if they are multiple (42,45,47). The management of these aneurysms is somewhat controversial. It may be beneficial to recommend treatment of the associated aneurysm first regardless of the definitive AVM treatment protocol. This paradigm is followed out of concern for the increased risk of hemorrhage in these patients (42,47). It is unclear if the presence of such aneurysms and their intraoperative surgical treatment increases the overall surgical risk. Hemodynamics AVMs have been categorized on the basis of hemodynamic factors (51,52). This scheme is based on the velocity within the AVM (high- and low-flow lesions), the steal phenomenon, and the velocity in vessels outside the AVM on proximal feeders including extracranial vessels. Spetzler and Martin (16) do not consider flow by itself but view it mainly in its relationship to the size of the AVM. Hemodynamic parameters can be determined during angiography or intraoperatively by directly measuring pressures and flow velocities or by transcranial Doppler for measurement of flow velocities. The steal phenomenon, which deprives other brain regions of adequate perfusion, may be related to the volume and level of shunting, which in turn is related to the AVM size. The presence of steal may increase the risk of hyperemic complications after AVM resection (11). Attempts have been made to assess the degree of steal, which was felt to correlate with the surgical risk, through the use of tagged red cell nuclear blood flow scans (51,52). Steal was classified as no steal, steal peripheral to the AVM, steal beyond AVM borders, and massive steal without connection to the AVM. Other factors such as AVM flow velocity and velocity in the cervical vessels were also felt to have an impact on the risks of surgical morbidity. Pasqualin et al. (32) created two prognostic groups on the basis of AVM flow velocities of greater or less than 120 cm/sec. Duong et al. (46) found a strong correlation between both feeding artery pressure and restricted venous outflow and the propensity of AVMs to hemorrhage. Decreased pulsatility (pulsatility index) within arterial feeders as determined by transcranial Doppler ultrasonography correlates with postoperative neurological outcome, and has been used as a predictor (53). The pathophysiologic correlates of such measurements remain to be determined. Clinical Features Clinical features can influence surgical outcomes for all neurosurgical procedures, and AVM surgery is no exception. The presence of neurological deficits and altered consciousness affect prognosis adversely. Likewise, significant comorbidity may be a contraindication for surgery. Age may also be a poor prognostic factor, although the age at which prognosis significantly worsens is disputed (11,15,17,26,52) and some do not consider age an important prognosticator at all (33). Conversely, young age carries the burden of the significant cumulative risk of subsequent hemorrhages and a greater propensity to develop a seizure disorder. Females may have a more favorable prognosis than males (4,15,33). GRADING SCALES Luessenhop and Gennarelli (1977): Number of Arterial Feeders The first AVM grading system, published by Luessenhop and Gennarelli in 1977 (31) was based on anatomic features that were analyzed on 300 angiograms. Excluded were lesions that
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were infratentorial, extended into the brain stem, or involved the vein of Galen. Three components of AVM-related vascular alterations were identified: & & &
Anatomic location of the AVM (specifically, where the shunt occurs); Enlargement of feeding arteries; and Enlargement of draining veins.
The grading scale is based on the number of tertiary named arteries that feed the AVM, with grades I to IV corresponding to the number of feeding arteries from one vascular territory [MCA, anterior cerebral artery (ACA), and posterior cerebral artery (PCA)]. If the number of arteries exceeds four, no additional grade is assigned, and the lesion is deemed inoperable. In cases of multiple territories, the grade is determined by the highest number of arteries from one territory. The scale provides for the following exceptions: &
The number of lenticulostriate arteries supplying an AVM are counted as if they were named arteries. & AVMs of the choroid plexus are considered grade III as they typically involve supply from one anterior and two posterior choroidal arteries. & AVMs of the corpus callosum supplied by branches from the pericallosal arteries are grade II, unless additional supply comes from the PCA (grade III). In addition to these parameters, the clinical status and the functional anatomical location of the lesion are loosely tied to the grading scheme. The clinical grading is supposed to correspond to the grading of patients with subarachnoid hemorrhage (SAH). The importance and impact of these auxiliary parameters increases with the angiographic grade. Grade I AVMs are considered operable with very low risk and hardly any restriction. Decisions about grades II to III AVMs become more complex. A good correlation of surgical morbidity and mortality rates with this grading system was found when it was applied to 49 cases. Grade IV AVMs were not seen in this series. The major weakness of this scale, however, involves the lack of clear guidelines for integrating the clinical and functional anatomical factors. Drake (1979): Preoperative Clinical Condition Drake (1) graded AVMs by size because he felt that large AVMs are more likely to involve eloquent brain, hemorrhage, and be followed by hyperemic complications after resection. In his series of 166 cases that were surgically treated, AVMs were classified in terms of size as (i) small, less than 2.5 cm; (ii) moderate, 2.5 to 5 cm; and (iii) large, greater than 5 cm. In his report, Drake made no formal attempt, however, to correlate this sizing scale to outcome. In fact, size itself was not seen as the critical obstacle to successful surgical resection. Instead, Drake felt that the preoperative clinical and neurological status of the patient was the single most important correlate of postsurgical outcome. Patients were classified preoperatively as either good or poor risk based on a 5-grade clinical scale: good risk, clinical grades 1 to 2; poor risk, clinical grades 3 to 5. An excellent correlation was found between postsurgical outcome and this preoperative risk assessment. In 140 surgically treated patients, 106 were good risk. In this group, 50% had excellent, 39% good, and 5% poor outcomes, and 6% died. In the poor risk group, outcomes were 3% excellent, 33% good, 32% poor, and 12% died. The short-coming of such a grading system is over-simplification, rendering it unhelpful as a grading scale but useful as a general guideline during decision making for preoperative planning. Pelletieri et al. (1980): Risk Profile Including Several Anatomic and Clinical Parameters This scale is based on various parameters that form a risk profile primarily for the purpose of deciding between surgical versus conservative treatment for 166 consecutive patients with AVMs (15). The scale was evaluated retrospectively by assessing the parameters and features of the AVM that had led to the decision regarding operability. The relative impact of each feature was statistically analyzed. Outcomes were divided into good (no or mild neurological deficit)
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and poor. The following variables in descending order of their impact on the decision-making process were included: & & & & & & &
AVM size: small (less than or equal to 3 cm) versus large (greater than 3 cm) Deep versus superficial location Age: less than or equal to 40 years or greater than 40 years Female versus male SAH versus no SAH Presence versus absence of neurological deficit at presentation ‘‘Silent’’ versus ‘‘nonsilent’’ area (nonsilent constituted the motor cortex and the sylvian fissure)
Factors favoring surgery were a small, superficial AVM in a silent region in a younger female presenting with SAH without neurological deficit. The prognostic risk profiles were found to be identical for patients who underwent surgery and those who were conservatively treated. The individual variables were ranked differently, however, in terms of their relative impact. The risk factor constellation that favors good outcomes in both the surgically and conservatively treated groups are listed in descending order of importance in Table 1. The risk constellation that favors surgical treatment is shown as well. Variables with negative impact were summed up with negative polarity, meaning that a patient with only negative variables was 7 on this scale. A patient without risk factors was 0. The statistical analysis was then extended to assign arbitrary numbers to variables based on the overall prognostic impact in both surgically and conservatively treated groups, with the scale extending from 16 to þ16. Overall, patients with (numerically) similar risk profiles fared better with surgery than with conservative treatment. The grading system, however, fails to provide a useful and simple guide on which decisions about operability and surgical risk can be based. In an attempt to equalize the risk factor constellation in both groups of patients, the study may have shown that surgically treated patients did better, but it did not provide reasons. For example, why would SAH be a favorable variable? Overall, the scale proved too complex for bedside use and did not gain broad application. Luessenhop and Rosa (1984): Size In 1984, Luessenhop and Rosa (30) simplified the 1977 grading system (see above) by grading only the size of the lesion on angiograms. In fact, it was suspected that the number of arterial feeders, to some degree, correlated with AVM size. Deep lesions form a notable exception. This new grading system could now also include cerebellar AVMs but continued to exclude brain stem lesions and vein of Galen malformations. AVM size was graded as follows: & & & &
Grade Grade Grade Grade
1: 2: 3: 4:
<2 cm 2–4 cm 4–6 cm >6 cm
Table 1 Risk Factor Constellations (Ranked) that Favor a Decision for Surgery and Good Outcomes in Both the Surgically Treated and Conservatively Managed Groups Favorable Outcomes Factor Rank
Decision for Surgery
Surgically Treated
Conservatively Managed
1 2 3 4 5 6 7
Small size Superficial Age < 40 years Female SAH No neurological deficit Silent area
No neurological deficit Age < 40 years Female Small size SAH Superficial Silent
Age < 40 years No neurological deficit Superficial Silent area Small size Female SAH
Abbreviation: SAH, subarachnoid hemorrhage. Source: From Ref. 15.
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Table 2 Correlation Between the Luessenhop and Rosa Grade and the Morbidity and Mortality Rates for 90 Surgically Treated Patients AVM Grade I II III
Number of Cases
Morbidity
Mortality
29 45 16
0 3 (6.7%) 7 (44%)
0 0 2 (12.5%)
Abbreviation: AVM, arteriovenous malformation.
This new system was applied to 90 patients, and the operative results are shown in Table 2. The authors found a good correlation between grade and outcome. Unfortunately, the definition of morbidity in this series lacks precision. For example, a ‘‘minor’’ sensorimotor deficit in a previously intact patient was not considered morbidity and additional qualifiers were included. Nevertheless, it appeared that small (grades 1 and 2) AVMs had a very low surgical morbidity rate, and the authors concluded that these malformations should be excised. They suggested that concessions to factors such as a critical location, age, or complicating disease were not necessary because the benefits of surgery appeared to outweigh the risks associated with the natural history of the disease. The commonly quoted rates for AVM hemorrhage are 2% to 3% for a first hemorrhage, 6% for recurrent hemorrhage during the first year, and 2% per year for a recurrent hemorrhage thereafter (54). For higher-grade lesions, a careful comparison of surgical risk versus natural history becomes much more important, and additional features such as a critical AVM location, age, and comorbidity weigh more heavily into the decision-making process. In addition, presentation with seizures alone skewed the authors toward conservative management for higher-grade lesions. In general, the authors concluded that surgical risk probably exceeds natural risk for lesions classified as grade III and higher in most patients beyond the fourth to fifth decades of life. This scale places significant emphasis on individual patient parameters except for all but low-grade lesions. In cases of small, deep-seated lesions in elderly patients with comorbidity, such a simplification may not be applicable. Spetzler and Martin (1986): Size, Pattern of Venous Drainage, Eloquence The grading system developed by Spetzler and Martin (16) is the most widely used scale today. The authors considered the most important factors for determining the difficulty of AVM resection to be size, number of arterial feeders, amount of flow through the AVM, amount of steal from neighboring areas, eloquence of the tissue, and pattern of venous drainage. Spetzler and Martin felt, however, that size, number of arterial feeders, amount of steal, and amount of flow through the AVM correlated well enough to be combined into one single variable, size. The AVM size was graded by the largest diameter of the nidus. Deep venous drainage was considered to be closely associated with surgical difficulty, as the deep veins are friable and have the propensity to retract and bleed. Drainage was considered deep if some or all of the drainage was through the deep veins (e.g., internal cerebral veins, basal veins, and precentral cerebellar vein). Resection of an AVM close to or within an area of eloquence also carried a higher risk for postoperative neurological deficit in this scheme. The following regions were classified as eloquent: sensorimotor cortex, cortical language areas (Broca, Wernicke), visual cortex, hypothalamus, thalamus, brain stem, and cerebellar peduncles. To assign an AVM grade, size, venous drainage pattern, and eloquence were determined on angiogram, CT, and MRI. Care was taken to correct for any angiographic magnification error (see above). The final grade consisted of the summation of points assigned to these parameters, as shown in Table 3. The scale consists of 5 grades with 12 possible combinations. A separate category was considered for very large lesions involving eloquent areas such as the thalamus or brainstem in which surgical resection would invariably lead to death or major deficit (‘‘grade 6’’ or inoperable). The grading scale was tested on 100 consecutive AVMs that were surgically resected. Outcome was graded as no deficit, including deficits lasting less than three days; minor deficits, including temporary worsening of neurological function beyond three days, mild residual ataxia, or ‘‘very mild’’ increase in brainstem deficit; or major deficit, including hemiparesis, aphasia, and hemianopia. No deaths occurred in this group. Outcomes correlated well with this grading scheme, as seen in Table 4.
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Table 3 Spetzler–Martin Scale for Grading Arteriovenous Malformations Variable
Points
Size <3 cm 3–6 cm >6 cm Venous drainage Superficial Deep Brain region Noneloquent Eloquent
1 2 3 0 1 0 1
This grading scale was very reliable owing to the simplicity of the variables and the low interobserver variability. The scale was applied retrospectively to other series of patients and was found to correlate well with surgical outcome (55–57). As with all grading scales, compromises were made between simplicity and practicality of a scale and the true complexity of each patient harboring an AVM. Criticism can be leveled at each point of this scale, and controversies surround all of them. Luessenhop and Rosa, for example, do not believe that deep venous drainage increases the surgical risk (30). Furthermore, controversy exists about the definition of eloquence and the relative impact of such regions on the surgical morbidity risks in each individual case (28,30,58). Malik et al. (58) point out that a large (greater than 6 cm) frontal lobe AVM and a small thalamic AVM with deep drainage would both be classified as grade III lesions, although the frontal lobe AVM should be much easier to resect. This scale does not formally include individual patient parameters. Shi and Chen (1986): Size, Location, Arterial Supply, Drainage Shi and Chen (26) proposed their scale in the same issue of the Journal of Neurosurgery as Spetzler and Martin (16). AVMs were graded according to the following parameters: 1. Size—largest diameter of the nidus on angiogram excluding distal parts of the draining veins. Sizes less than 2.5 cm, 2.5 to 5 cm, 5 to 7.5 cm, and greater than 7.5 cm correspond to grades 1 to 4, respectively. 2. Location and depth—superficial versus deep, ‘‘functional’’ versus ‘‘non-functional,’’ corpus callosum, brain stem, diencephalon. Grades 1 to 4 are assigned on the basis of increasing anatomic complexity and ‘‘functionality.’’ 3. Arterial supply—single superficial feeders (MCA/ACA) (grade 1), multiple superficial feeders (MCA/ACA) (grade 2), branches of PCA or deep MCA/ACA branches or vertebral artery (grade 3), main branches of all three territories or vertebrobasilar system (grade 4). 4. Venous drainage—single superficial (grade 1), multiple superficial (grade 2), deep (vein of Galen, straight sinus, etc.) (grade 3), deep with aneurysmal venous dilatation (grade 4).
Table 4 Correlation Between the Spetzler–Martin Grading Scale and the Morbidity and Mortality of 100 Surgically Treated Patients Degree of Deficit None
Minor
Major
Grade
No. of Patients
No.
(%)
No.
(%)
No.
(%)
Death (%)
I II III IV V Total
23 21 25 15 16 100
23 20 21 11 11 86
100 95 84 73 69 86
0 1 3 3 3 10
9 5 12 20 19 10
0 0 1 1 2 4
0 0 4 7 12 4
0 0 0 0 0 0
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Table 5 Correlation Between the Shi and Chen Grading Scale and the Morbidity and Mortality of 100 Surgically Treated Patients Operative Morbidity
Operative Mortality
Grade
No. of Cases
No.
(%)
No.
(%)
I I–II II II–III III III–IV Total
6 13 28 18 30 5 100
0 0 0 3 6 4 13
0 0 0 17 20 80 13
0 0 0 0 0 1 1
0 0 0 0 0 20 1
The final grade is determined by a simple algorithm and matched with the highest grade(s) if at least two criteria are in that grade. If only one criterion falls in the highest grade, the grade falls between two grades, such as grade III to IV. Operative results in 100 consecutive patients were classified by the presence or absence of operative morbidity and mortality. Operative morbidity was somewhat ill-defined as minor (able to live independently), and major (in need of major assistance or institutionalization). No grade IV patient was subjected to surgery. Surgical morbidity and mortality correlated well with the AVM grade, as shown in Table 5. This scale shares common features with the Spetzler–Martin scale, although it is somewhat more complex. The scale does not take any other individual patient factors into consideration. Tamaki et al. (1991): Size, Depth, Arterial Supply The outcomes of 151 patients treated either surgically or conservatively were assessed with a new grading scale (17). Patients in the surgical group had undergone complete resection, partial resection (intended or not intended), or palliative surgery (ventricular catheter, evacuation of hematoma, feeder clipping, and partial embolization). Twenty-nine patients were treated conservatively. AVMs were graded as follows: 1. Size—maximal diameter on angiogram: less than 4 cm (0 points), greater than or equal to 4 cm (2 points). 2. Location—superficial (0 points) versus deep (1 point), including periventricular, basal ganglia, and corpus callosum. Lesions in the thalamus and brain stem were excluded. 3. Feeding arteries—fewer than three arterial systems (0 points) and three or more systems (1 point). Each of the following was considered one system: ACA, MCA, PCA, anterior and posterior choroidals, lenticulostriates, thalamoperforators, AICA, or PICA. By adding points, grades 0 to 4 are possible. Outcome was assessed in five gradations from dead to no deficit and by the Karnofsky scale. Each variable was found to correlate independently with outcome and resectability on the basis of regression analysis. Because size was found to have the strongest correlation, two points were assigned to large AVMs. In Table 6,
Table 6 Correlation Between the Grading Scale of Tamaki et al. and Outcome Including the Karnofsky Scale Grade 0 1 2 3 4 Significance
No. of Surgically Treated Casesa 48 17 17 11 3
Total Excisions No. 45 14 13 7 2 p < 0.005
a Total excision or only a small part of the lesion remaining. Source: From Ref. 17.
(%) 94 82 76 64 67
Satisfactory Outcome No. 43 14 12 7 1 p < 0.001
(%)
Karnofsky Scale
90 82 71 64 33
86.7 14.0 83.5 16.6 76.5 12.7 68.2 19.4 66.7 20.8 p < 0.05
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outcomes are presented for those patients who underwent total resection or in whom only a small part of the lesion remained; outcomes are listed as satisfactory if the patient was at least able to return to work, although with some possible restrictions. This study evaluated the effects of age, venous drainage pattern, and eloquence on outcome. Patients ages 19 and younger were found to have better outcomes than patients ages 50 and older. No correlation was found between venous drainage pattern or eloquence and surgical morbidity. A formula to predict the postoperative Karnofsky scale was also used, in which size was weighed more heavily: Karnofsky scale ¼ 87.1 – 11.5 size 5.4 location 5.1 feeders. It is difficult to compare this scale, however, with the Spetzler–Martin scale because thalamic and brain stem lesions were not excluded and all AVMs were completely resected in the latter study. Furthermore, it was unclear how patients were assigned to the surgical versus conservative groups in Tamaki’s series. Pertuiset et al. (1991): Anatomical, Hemodynamic, Clinical One of the most complex grading systems was developed by Pertuiset et al. (52) on the basis of their experience with 57 cases. A score system was developed for a variety of factors in one of the three categories: anatomy, hemodynamics, and clinical. The final score would allow prediction of surgical outcome and operability. This system, in fact, was the first to incorporate hemodynamic factors by using Doppler flow studies and tagged red cell scans to evaluate the amount of steal. Briefly, anatomical parameters included the following: 1. 2. 3. 4. 5. 6.
Main feeding artery system (carotid, basilar, and combinations); Caliber of feeding arteries; Presence of deep feeders; Straightening of the main feeder; Localization (brainstem, thalamus, insula, hypothalamus get highest score); and Number of vascular territories (sectors). Hemodynamic factors included:
1. Volume (99Tc-tagged red cells scan) and vascular autoregulation; 2. Steal (semiquantitative); and 3. Flow velocity in neck vessels for each carotid and vertebral artery. Clinical factors included: 1. Previous rupture; and 2. Associated diseases, age over 50 years, vital organ malformations. A total score was calculated and was used to determine operability. A special (veto) score was given to a single parameter if, by itself, it should preclude surgery regardless of the other scores (e.g., a lesion in the brain stem). This scoring system correlated well with operative outcome. The mortality in this series was high and reached 14%. This type of scoring system is too complicated to gain wide acceptance and parameters within the scoring system are not always well defined. The prognostic significance of the hemodynamic factors may also be questionable. Ho¨llerhage et al. (1992): Clinical Grade, Origin of Feeders, Shunting Ho¨llerhage et al. (33) used multiple regression analysis in 107 patients to retrospectively determine and weigh the variables best suited for predicting the risk of surgical morbidity. Clinical status at presentation was determined by a 5-grade scale similar to the Hunt and Hess scale for SAH. Outcome was determined by the Glasgow Outcome Scale. The factors listed in Table 7 were identified as having a significant impact on outcome. Similar to the analysis by Shi and Chen (26), deep versus superficial venous drainage had no impact on outcome. Surprisingly, size also did not reach significance as a prognosticator. The authors proposed a grading system based on the marked factors in Table 7, assigning the number 1 or 0 to each, except the clinical grade on admission, which was dichotomized and assigned a 1 or 2 (to avoid a grade of 0) with a maximum overall score of 7. In a deviation from their
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Table 7 Statistical Analysis of the Impact of Various Factors on Outcome Adverse Factors Male sex Eloquent area A1 feedersa M1 feedersa Rolandic feedersa Fronto-orbital feeders Shunt through anterior communicating arterya Poor clinical gradea
Significance (p <)
Favorable Factors
Significance (p < )
0.05 0.025 0.001 0.001 0.05 0.025 0.01
Female sex PCA feeders Drainage to straight sinus
0.05 0.05 0.05
0.02
a
Indicates that this variable was retained as a major prognostic factor, confirmed by multivariate analysis. Abbreviation: PCA, posterior cerebral artery.
original intention to base this scale on statistical analysis only, the presence of P1 segment or posterior communicating artery feeders also earn a point, although they were not presented as part of the regression analysis. A reasonably good correlation with outcome was found when this scale was applied. In fact, the rank correlation coefficient rho, a statistical measure used to determine the predictive value of the ranking scale, was 0.55 (0 indicating complete independence, and 1 complete correlation). This value compares favorably with other scales (Shi 0.12, Luessenop 0.14, and Spetzler–Martin 0.22). This study stresses the importance of multivariate analysis compared with simple bivariate comparisons. The fact that eloquence dropped out as a prognosticator in multivariate analysis may have simply indicated that it became superfluous and was overridden by the greater importance of certain feeders supplying eloquent regions. The importance of shunting through the anterior communicating artery may be related to the high flow of shunting and associated complications. Overall, this grading scheme was carefully created but is somewhat counterintuitive because size and eloquence were excluded as parameters. Malik et al. (1994): AVM Volume, Location, Nature of Arterial Feeders After analyzing other grading scales, Malik et al. (27) proposed a new system based for the first time on AVM volume, location, and nature of arterial feeders as follows: Volume is approximated by using the formula: length width height/2. Volumes are divided into six grades. & Location is divided into four categories following the scheme of Shi and Chen: &
Cortical simple: noneloquent cortex including visual cortex; Cortical functional: sensorimotor/speech; Deep nonvital: insula, basal ganglia, anterior limb of internal capsule, corpus callosum, medial temporal lobe, intra- and periventricular, and cerebellar nuclei; Deep vital: genu and posterior limb of internal capsule, thalamus and hypothalamus, and brain stem. &
Arterial feeders are divided into superficial or deep, including lenticulostriates, thalamoperforators, choroidals, and brain stem perforators.
The final grade is determined by characterizing the type of location followed by size. An ‘‘A’’ was attached if any of the arterial feeders were deep. This grading scale has not yet been clinically tested but introduces a valuable addition by using volume rather than the more imprecise measure of maximum diameter. DISCUSSION AVM grading scales have been developed to predict surgical outcome. Most of the described scales are in some way complementary. The Spetzler–Martin scale is currently the most widely
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used system, and its overall usefulness, despite the limitations inherent in all grading scales, has been proven repeatedly (55–57). Deruty et al. (55) applied the scale to 52 patients with AVMs and found satisfactory correlation with outcome. They also found that grades I, II, and III were similar in outcomes. As a measure of further simplification and for all practical purposes, they combined grades I to III and grades IV and V into low- and high-grade lesions, respectively. In our opinion, no further simplification is necessary for the Spetzler–Martin scale. As pointed out earlier, problems with actual grading in the Spetzler–Martin scale arise mainly from the determination of eloquence, and the addition of MRI analysis will help in this matter. Using the initial Luessenhop and Gennarelli scale (31), it may sometimes be difficult to ascertain all the arterial feeders, especially in the sylvian fissure. In their comparison of several grading scales, Steinmeier et al. (57) found that the Spetzler–Martin scale was superior in predicting surgical outcome compared with the scales of Shi and Chen (26), Luessenhop et al. (both scales) (30,31), and Pelletieri et al. (15). Luessenhop and Gennarelli’s initial scale (31) tends to correlate better with psychosocial outcome, which may be more related to the total size of the AVM and secondarily related to the number of arterial feeders. In the future, the Spetzler–Martin scale could be modified to use volume rather than maximal nidal diameter in view of the importance of this parameter for radiosurgery. Furthermore, it seems logical to reconsider the inclusion of some clinical parameters, such as advanced age and/or significant comorbidity into a new scale, perhaps by adding a grade for the presence of these complicating factors. REFERENCES 1. Drake CG. Cerebral arteriovenous malformations: considerations for and experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–208. 2. Drake CG, Friedman AH, Peerless SJ. Posterior fossa arteriovenous malformations. J Neurosurg 1986; 64:1–10. 3. Yasargil MG, Symon L, Teddy PJ. Arteriovenous malformations of the spinal cord. Adv Tech Stand Neurosurg 1984; 11:61–102. 4. Yasargil MG. Microneurosurgery. Vol. IIIA. AVMs of the Brain, History, Embryology, Pathological Considerations, Hemodynamics, Diagnostic Studies, Microsurgical Anatomy. Stuttgart: Thieme, 1987. 5. Sabin FR. Preliminary note on the differentiation of angioblasts and the method by which they produce blood vessels, blood plasma, and red blood cells as seen in the living chick. Anat Rec 1917; 13:199–204. 6. Streeter GL. The developmental alterations in the vascular system of the brain. Contrib Embryol 1918; 8:5–38. 7. Kondziolka D, Humphreys RP, Hoffman HJ, Hendrick EB, Drake JM. Arteriovenous malformations of the brain in children: a forty-year experience. Can J Neurol Sci 1992; 19:40–45. 8. Gerosa MA, Cappellotto P, Licata C. Cerebral arteriovenous malformations in children (56 cases). Childs Brain 1981; 8:356–371. 9. Perret G, Nishioka H. Arteriovenous malformations: an analysis of 545 cases of cranio-cerebral arteriovenous malformations and fistulae reported to the cooperative study. J Neurosurg 1966; 25:467–490. 10. Jomin M, Lesion F, Lozes G. Prognosis for AVMs of the brain in adults based on 150 cases. Surg Neurol 1985; 23:362–366. 11. Batjer HH, Devous MD, Seibert GB, Purdy PD, Bonte FJ. Intracranial AVMs: relationship between clinical factors and surgical complications. J Neurosurg 1989; 24:75–79. 12. Hernesniemi J, Keranen T. Microsurgical treatment of AVMs of the brain in a defined population. Surg Neurol 1990; 33:384–390. 13. Mingrino S. Supratentorial AVMs of the brain. In: Krayenbu¨hl H, ed. Advances and Technical Standards in Neurosurgery. Wien: Springer, 1978:93–126. 14. Parkinson D, Bachers G. Arteriovenous malformations. Summary of 100 consecutive supratentorial cases. J Neurosurg 1980; 53:285–299. 15. Pelletieri L, Carlsson CA, Grevstens S, Norlen G, Uhlemann C. Surgical versus conservative treatment of intracranial arteriovenous malformations. A study in surgical decision making. Acta Neurochir 1980; 29:1–86. 16. Spetzler RF, Martin NA. A proposed grading system for AVMs. J Neurosurg 1986; 65:476–483. 17. Tamaki N, Ehara K, Lin TK, et al. Cerebral arteriovenous malformations: factors influencing the surgical difficulty and outcome. Neurosurgery 1991; 29:856–863. 18. Bradford R, Thomas DG, Bydder GM. MR imaging-directed stereotactic biopsy of cerebral lesions. Acta Neurochir Suppl (Wien) 1987; 39:25–27. 19. Heilbrun MP, Sunderland PM, McDonald PR, Wells TH, Cosman E, Ganz E. Brown-Roberts-Wells stereotactic frame modifications to accomplish magnetic resonance imaging guidance in three planes. Appl Neurophysiol 1987; 50:143–152.
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20. Villemure JG, Marchand E, Peters TM, Leroux G, Olivier A. Magnetic resonance imaging stereotaxy: recognition and utilization of the commissures. Appl Neurophysiol 1987; 50:57–62. 21. Elisevich K, Cunningham IA, Assis L. Size estimation and magnification error in radiographic imaging: implications for classification of arteriovenous malformations. AJNR Am J Neuroradiol 1995; 16:531–538. 22. Elisevich K, Cunningham I, Assis L, Peters T. A table-mounted stereotactic system for digital angiography: a means of standardizing arteriovenous malformation measurement. Stereotact Funct Neurosurg 1994; 63:168–171. 23. Okazaki H. Fundamentals of Neuropathology. Tokyo: Igaku-Shoin, 1989. 24. Michelson WJ. Natural history and pathophysiology of arteriovenous malformations. Clin Neurosurg 1979; 26:307–313. 25. Pool JL, Potts DG. Aneurysms and arteriovenous anomalies of the brain: diagnosis and treatment. New York: Harper & Row, 1965:326–373. 26. Shi YQ, Chen XC. A proposed scheme for grading intracranial arteriovenous malformations. J Neurosurg 1986; 65:484–489. 27. Malik GM, Pasqualin A, Ausman JI. A new grading system for cerebral arteriovenous malformations. In: Pasqualin A, Pian RD, eds. New Trends in Management of Cerebro-Vascular Malformations. Wien: Springer, 1994:328–332. 28. Duff T. AVM grading in assessment of surgical risk (letter). J Neurosurg 1987; 66:787–788. 29. Spetzler RF, Zabramski JM. Grading and staged resection of cerebral arteriovenous malformations. Clin Neurosurg 1990; 36:318–337. 30. Luessenhop AJ, Rosa L. Cerebral arteriovenous malformations. Indications for and results of surgery, and the role of intravascular techniques. J Neurosurg 1984; 60:14–22. 31. Luessenhop AJ, Gennarelli TA. Anatomical grading of supratentorial arteriovenous malformations for determining operability. Neurosurgery 1977; 1:30–35. 32. Pasqualin A, Barone G, Cioffi F, Rosta L, Scienza R, Da Pian R. The relevance of anatomic and hemodynamic factors to a classification of cerebral arteriovenous malformations. Neurosurgery 1991; 28: 370–379. 33. Ho¨llerhage HG, Dewenter KM, Dietz H. Grading of supratentorial arteriovenous malformations on the basis of multivariate analysis of prognostic factors. Acta Neurochir 1992; 117:129–134. 34. Pritz MB. Ruptured supratentorial arteriovenous malformations associated with venous aneurysms. Acta Neurochir 1994; 128:150–162. 35. Dobbelaere P, Jomin M, Clarisse E. Interet pronostique de l’etude du drainage veineux des aneurysmes arterioveineux cerebreaux. Neurochirurgie 1979; 25:178–184. 36. Laine E, Jomin M, Clarisse J, Combelles G. Les malformations arterioveineuses profondes. Classification topographiques possibilites et resultats therapeutiques. A propos de 46 observations. Neurochirurgie 1981; 27:147–160. 37. Dahl RE, Kline DG. Intraparenchymal arteriovenous malformations with predominant external carotid artery contribution. J Neurosurg 1974; 41:681–687. 38. Russell EJ, Berenstein A. Meningeal collaterization to normal cerebral vessels associated with intracerebral arteriovenous malformations: functional angiographic considerations. Radiology 1981; 139: 617–622. 39. Garretson HD. Postoperative pressure and flow changes in the feeding arteries of cerebral arteriovenous malformations. Neurosurgery 1979; 4:544–545. 40. Delitala A, Delfini R, Vagnozzi R, Esposito S. Increase in size in cerebral angiomas: a case report. J Neurosurg 1982; 57:556–558. 41. Cunha Sa MJ, Stein BM, Solomon RA, McCormick PC. The treatment of associated intracranial aneurysms and arteriovenous malformations. J Neurosurg 1992; 77:853–859. 42. Marks MP, Lane B, Steinberg GK, Chang PJ. Hemorrhage in intracerebral aneurysms and arteriovenous malformations: frequency of intracranial hemorrhage and relationship of lesions. J Neurosurg 1990; 73:859–863. 43. Thompson RC, Steinberg GK, Levy RP, Marks MP. The management of patients with arteriovenous malformations and associated intracranial aneurysms. Neurosurgery 1998; 43:202–211 [discussion 211–212]. 44. Brown RD, Wiebers DO, Forbes GS. Unruptured intracranial aneurysms and arteriovenous malformations: frequency of intracranial hemorrhage and relationship of lesions. J Neurosurg 1990; 73:859–863. 45. Redekop G, TerBrugge K, Montanera W, Willinsky R. Arterial aneurysms associated with cerebral arteriovenous malformations: classification, incidence, and risk of hemorrhage. J Neurosurg 1998; 89: 539–546. 46. Duong GH, Young WL, Vang MC, et al. Feeding artery pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral arteriovenous malformations. Stroke 1998; 29: 1167–1176. 47. Turjman F, Massoud TF, Vinuela F, Sayre JW, Guglielmi G, Duckwiler G. Correlation of the angioarchitectural features of cerebral arteriovenous malformations with clinical presentation of hemorrhage. Neurosurgery 1995; 37:856–860. 48. Okamoto S, Handa H, Hashimoto N. Location of intracranial aneurysms associated with cerebral AVM: statistical analysis. Surg Neurol 1984; 22:335–340.
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49. Lasjaunias P, Piske R, Terbrugge K. Cerebral arteriovenous malformations (C. AVM) and associated arterial aneurysms (AA). Analysis of 101 C. AVM cases with 37 AA in 23 patients. Acta Neurochir (Wien) 1988; 91:29–36. 50. Suzuki J, Onuma T. Intracranial aneurysms associated with arteriovenous malformations. J Neurosurg 1979; 50:742–746. 51. Pertuiset B, Ancri D, Clergue F. Preoperative evaluation of hemodynamic factors in cerebral arteriovenous malformations for selection of a radical surgery tactic with special reference to vascular autoregulation disorder. Neurol Res 1982; 4:209–233. 52. Pertuiset B, Ancri D, Kinuta Y, et al. Classification of supratentorial arteriovenous malformations. A score system for evaluation of operability and surgical strategy based on an analysis of 66 cases. Acta Neurochir 1991; 110:6–16. 53. Kilic T, Pamir N, Budd S, Ozek MM, Erzen C. Grading and hemodynamic follow-up study of arteriovenous malformations with transcranial Doppler ultrasonography. J Ultrasound Med 1998; 17: 729–738. 54. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983; 58:331–337. 55. Deruty R, Pelissou-Guyotat I, Mottolese C, Amat D, Bascoulergue Y. Prognostic value of the Spetzler’s grading system in a series of cerebral AVMs treated by a combined management. Acta Neurochir 1994; 131:169–175. 56. Heros RC, Korosue K, Diebold PM. Surgical excision of cerebral arteriovenous malformations: late results. Neurosurgery 1990; 26:570–578. 57. Steinmeier R, Schramm J, Mu¨ller HG, Fahlbusch R. Evaluation of prognostic factors in cerebral arteriovenous malformations. Neurosurgery 1989; 24:193–200. 58. Malik GM, Ausman JI, Mann R. Grading system for AVMs [letter]. J Neurosurg 1987; 67:473–474.
7
Radiographic Diagnosis R. Anthony Murray Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois, U.S.A.
Eric J. Russell Department of Radiology, Northwestern Memorial Hospital, and the Northwestern University Feinberg School of Medicine, Chicago, Illinois, U.S.A.
INTRODUCTION The radiographic diagnosis and characterization of cerebral arteriovenous malformations (AVMs) has undergone revolutionary changes with the developments of computed tomography (CT) and magnetic resonance imaging (MRI). Exquisite characterization of cerebral AVMs continues to evolve as these modalities are improved and expanded [e.g., CT angiography (CTA), magnetic resonance angiography (MRA), and functional MRI]. Together with conventional catheter angiography, the available imaging armamentarium permits highly accurate characterization of AVMs, enabling definitive therapeutic planning. Cerebral AVMs have been classified by McCormick as one of the four types of intracranial vascular malformations (1). As elucidated in Chapter 2, cerebral AVMs are congenital, hamartomatous vascular lesions that consist of direct arteriovenous communications in the absence of an intervening capillary bed (2,3). They are typically classified on the basis of their arterial supply (pial vs. dural) and the morphological characteristics of the arteriovenous shunts (fistulous vs plexiform) (4). Pial malformations form the basis of this chapter. Their importance stems from their deleterious effects on neighboring normal cerebral tissue and their inherent tendency to hemorrhage. Only rarely is the radiographic diagnosis of a pial AVM made incidentally. Most often, AVMs present with headaches, the onset of an acute neurological event, or progressive neurological decline. The simple imaging documentation of its presence, while vital, constitutes only a very small portion of the information required for proper prognostication and therapeutic planning. Proper characterization of cerebral AVMs and, therefore, correct interpretation of imaging studies, requires a thorough understanding of the anatomy, pathophysiology, epidemiology, natural history, and therapeutic options available. EPIDEMIOLOGY AND NATURAL HISTORY The overall incidence of cerebral AVMs is estimated to be approximately 0.1% of the population with no apparent sex predilection (5). Most patients become symptomatic by the age of 40 years (6). Approximately 50% of patients present with intracranial hemorrhage, 25% with seizures, and the rest with variable presentations that include headache, acute or progressive neurological deficit, subjective or objective bruit, visual disturbance, sensory disturbance, weakness, nausea and vomiting, ataxia, syncope, hemiparesis, cranial nerve palsy, and/or cognitive impairment (7–11). Although subarachnoid and intraventricular hemorrhage may occur, intracranial hemorrhage is most often parenchymal. Predominant subarachnoid hemorrhage in the setting of a known AVM should be assumed to be secondary to an associated aneurysm until proven otherwise (4). Most articles on the subject estimate the annual risk of hemorrhage at 2% to 4% per year (7–11). By applying the multiplicative law of probability, one can estimate the lifetime likelihood of an intracranial hemorrhagic complication (12). If 3% annual risk is assumed, the chance of bleeding over X number of years is 1–.97X, while the probability of not bleeding is .97X. For a 20-year old with an AVM uncomplicated by hemorrhage and with a conservative life expectancy of 60 more years, the lifetime risk of hemorrhage would approach 1–.9760 or 84%. Multiple morphological and hemodynamic characteristics are believed to be associated with an increased risk of hemorrhage (13–20), including associated aneurysms, deep or
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peri/intraventricular location, central or deep venous drainage, venous outflow obstruction, higher feeding arterial pressures, small size (<3 cm), and small number of draining veins. Many of these characteristics are interrelated. Most deeply located or intraventricular AVMs have deep venous drainage and shorter arterial feeders with higher perfusion pressures. Small AVMs may simply be less epileptigenic than larger malformations and, therefore, not as likely to present clinically until hemorrhage occurs. Supply from the vertebrobasilar system has also been implicated as a risk factor for intracranial hemorrhage (21). Whereas supratentorial AVMs may have supply from the posterior circulation, infratentorial pial AVMs always have supply from the vertebrobasilar system. A greater percentage of posterior fossa AVMs present with intracranial hemorrhage, not because of their vascular supply, but because they do not produce other early signs (i.e., seizures). Not unexpectedly, hemorrhage associated with an infratentorial nidus is more likely to be fatal, due to the proximity of the brainstem (7). ‘‘Angiomatous change’’ and superficial venous drainage (in the absence or presence of a deep venous component) have been described as characteristics of an AVM associated with a lower incidence of intracranial hemorrhage (19). Angiomatous change is an angiographic finding defined by Marks et al. as ‘‘multiple dilated cortical vessels that feed the AVM with collateral supply from arteries that do not directly supply the AVM nidus’’ (19). Feeding artery pressures may be lower in AVMs that demonstrate angiomatous change, thereby explaining the apparent protective effect. This in turn may be related to their typically more superficial location and, therefore, longer arterial pedicles with lower mean feeding artery pressures (18). Seizures are the second most common mode of presentation. Location is the key predictor of a seizure presentation; the lesions must be supratentorial. Temporal lobe location and/or a peripheral position within or adjacent to cerebral cortex or the hippocampal formations is predictive of a seizure presentation (22). Presentation with acute or progressive neurological deficit or intellectual impairment in the absence of intracranial hemorrhage has been attributed to the ‘‘steal phenomenon’’ (23). These patients typically present with acute or gradual motor weakness and/or memory/ cognitive impairment. Decreased vascular resistance within the AVM nidus results in diversion of cerebral blood flow from normal neighboring cerebral tissue, with its normal high resistance capillary bed, toward the lower resistance AVM nidus. Large AVMs and those demonstrating angiomatous change correlate highly with symptoms of clinical steal (23). A large nidus usually has greater arteriovenous shunting with lower perfusion pressures, leading to greater recruitment of collaterals. These collaterals are, in most cases, leptomeningeal in origin and become dilated but do not demonstrate early venous drainage. They do not directly feed the AVM nidus but rather supply it indirectly. The cerebral territory they would normally supply is thus underperfused. MRI and CT may demonstrate infarction or gliosis involving these underperfused regions. Neurological decline in the absence of intracranial hemorrhage or angiographic steal may also be secondary to venous hypertension, mass effect from venous varices, or decreased perfusion distal to an arterial stenosis (4). THERAPEUTIC OPTIONS AND CLASSIFICATION The goal of any treatment strategy is complete obliteration of the AVM nidus to eliminate the risk of intracranial hemorrhage without unacceptable consequences. Endovascular embolization, radiosurgery, surgical resection, and combined therapies are useful treatment options (see Chapters 9 and 10). Several classification and grading systems have been proposed to predict the success and complication risk associated with treatment (24–29). The Spetzler and Martin surgical grading system, which estimates the difficulty of surgical resection, remains the most widely used (see Chapter 6) (24). Multiple anatomic factors help to predict the difficulty of surgical resection (e.g., size, number of feeding arteries, location). Only three variables are considered in the Spetzler and Martin schema: (i) AVM nidus size, (ii) pattern of venous drainage, and (iii) location with regard to eloquent or noneloquent tissue. Eloquence, as defined by Spetzler and Martin, are those regions of the brain ‘‘that speak to readily identifiable neurological function and if impaired result in disabling neurological deficit.’’ These areas include primary sensorimotor, language, and visual cortices, the hypothalamus and thalamus, the internal capsules, the brain stem, the cerebellar peduncles, and the deep cerebellar nuclei. Our current understanding of ‘‘eloquent’’ tissue continues to evolve with advances in functional MRI, which
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has demonstrated evidence for the translocation of cortical function (30). Noneloquent areas control ‘‘more subtle neurological function and do not result in disabling deficit if injured.’’ These areas include the anterior frontal and temporal lobes as well as the cerebellar cortex. The size of the nidus is determined from conventional cerebral angiography (corrected for magnification). A point system is used with one point assigned to nidus size less than 3 cm, two points for size 3–6 cm, and three points for size greater than 6 cm. No points are added for AVMs with exclusive superficial cortical venous drainage, while one point is assigned for the presence of any deep venous drainage. No points are added if noneloquent brain is involved, while one point is assigned for the involvement of eloquent regions. AVMs are assigned point totals from one to five and subsequently assigned a Grade I to V. Grade I lesions pose relatively minor surgical difficulties, while Grade V AVMs carry the highest acceptable surgical risk. An additional Grade VI, or inoperable grade, is assigned to those AVMs that are so large and/or involve such vital eloquent structures that surgical resection would lead to death or total disability. Clinical and anatomic factors have been identified that are predictive of a successful response to radiosurgery (27–29). These factors include small AVM size (usually < 2 to 3 cm), small number of draining veins, slow flow plexiform nidus, and young age. Because the small, superficially located nidus is usually easily resected surgically, radiosurgery is now generally reserved for small, deep-seated AVMs. Radiosurgery, however, entails a latency period ranging from four months to greater than three years (29,31–35). During this period, as long as residual AVM nidus exists, the annual risk of hemorrhage remains 2% to 4% (36). As of yet, no endovascular classifications have been proposed. Endovascular embolization, primarily with acrylic glue, may alone obliterate the AVM nidus. More often, however, endovascular techniques are used as a method to reduce the size and flow through the nidus to improve the ease of surgical resection or improve the success rate of radiosurgery. Important considerations for endovascular management include the angioarchitecture of the nidus, the presence of associated aneurysms, and the time between embolization and surgery (26,37,38). Imaging and treatment strategies vary for each patient and are based on the initial clinical presentation, as well as on a thorough understanding of the size, location, and angioarchitecture of the AVM. While conventional cerebral angiography remains the definitive modality for exquisite characterization of cerebral AVMs, CT and MRI have irreplaceable roles in defining certain aspects of these lesions. COMPUTED TOMOGRAPHY Although limited in its ability to characterize AVMs, CT in many respects plays the most important role in radiographic diagnosis. Easy accessibility and high sensitivity to acute intracranial hemorrhage often makes CT the initial imaging study obtained in patients with acute neurological deficits, severe headaches, or new onset seizure. Noncontrast CT remains, for now, the most sensitive means of diagnosing hyperacute intracranial hemorrhage, which typically appears as abnormal hyperattenuation, whether parenchymal or extra-axial (Fig. 1) (39,40). The diagnosis of an underlying AVM may be difficult with CT alone, especially in the presence of an acute parenchymal hematoma, which may obscure the underlying lesion. In the absence of intracranial hemorrhage, the CT may appear normal, especially if intravenous contrast is not used to enhance abnormal vasculature. Whether or not an acute hematoma is present, subtle clues may alert the reader to the presence of an AVM. The presence of a fluid–fluid level within a hematoma is, in the absence of a bleeding diathesis, a suspicious sign of an underlying causative lesion and may be seen in association with some AVMs (41). Mixed attenuation regions in the absence of significant mass effect suggest the diagnosis of AVM (Fig. 2) (42–48). Areas of decreased density (hypoattenuation) may be related to gliotic tissue, areas of infarction, resolving hematoma and/or surrounding vasogenic edema. Regions of increased density (hyperattenuation), in addition to suggesting the presence of blood in dilated vessels, may occur with associated hematoma or may be due to thrombosed vessels and/or calcifications (Fig. 3) (39,43,46). Acutely thrombosed veins can be misinterpreted as parenchymal hematomas. Serpiginous hyperattenuating vascular structures, which may be only slightly increased relative to normal brain, may represent feeding arteries or draining veins (deep, cortical, medullary, ependymal). The presence of this finding should prompt the use of intravenous contrast (39). Patent vascular portions of the AVM will show dramatic contrast
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Figure 1 Left parietal arteriovenous malformation (AVM). (A) Noncontrast axial computed tomography demonstrates a large, acute, hyperattenuating hematoma. (B) After the administration of intravenous contrast, small enhancing vessels are noted at the periphery of the hematoma (arrows). Their presence suggests the presence of an underlying AVM. (C) Sagittal reconstruction from three-dimensional time-of-flight magnetic resonance angiography demonstrates the left parietal AVM with supply from superior and inferior parietal branches of the anterior cerebral artery. Superficial cortical venous drainage to the superior sagittal sinus is evident.
enhancement (Figs. 1 and 4). In the presence of a hematoma, adjacent homogeneous or serpiginous enhancement may permit the diagnosis of AVM (41). CT may also demonstrate obstructive or nonobstructive hydrocephalus, or perilesional atrophy (47). CT is the imaging modality of choice for visualizing the distribution of embolic material (Fig. 5) (43,49). Although CTA can be used as a noninvasive imaging tool, it has not found widespread application other than for treatment planning in stereotactic radiosurgery and localization of small AVMs requiring intraoperative image guidance. In the absence of CT findings that define an underlying AVM, further imaging is often warranted. For example, in the case of new onset seizures, MRI is more sensitive than CT for vascular and nonvascular etiologies. If intracranial hemorrhage is identified on the initial CT, conventional cerebral angiography will often be the next step. Zhu et al. concluded that conventional catheter angiography should be performed for all spontaneous intracranial hemorrhages, especially isolated intraventricular hemorrhage, except for those isolated to the putamen, thalamus, or posterior fossa in patients older than 45 years with preexisting hypertension (50). MAGNETIC RESONANCE IMAGING AND ANGIOGRAPHY The proper interpretation of MR images necessitates a basic understanding of MR physics, which is beyond the scope of this chapter. Whereas CT may have an advantage for detecting
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Figure 2 Right frontal arteriovenous malformation. Noncontrast axial computed tomography demonstrates a large mixed attenuation lesion. Low attenuation regions represent encephalomalacic parenchyma, while subtle hyperattenuating regions represent patent, enlarged vessels. Dystrophic calcifications are recognized. Intraventricular hemorrhage is present.
hyperacute intracranial hemorrhage, intracranial calcification, and embolic material, MRI is the noninvasive imaging modality of choice for the delineation of AVMs, and is quite effective at showing acute hemorrhage (5,39,43,49,51). MRI is superior to CT and, at times, conventional angiography, for defining the size of the AVM nidus. MRI is clearly the procedure of choice to define the precise anatomic location in relation to eloquent tissue (45,47,49,51,52). It is likewise the best exam for detecting subacute and chronic hemorrhage, perilesional parenchymal changes, and any associated mass effect (49,53). The typical spin-echo MRI appearance of an AVM is a tangle of serpiginous low signal areas (flow voids) (Fig. 6) (5,39,47,49). For parenchymal AVMs, a conical shape is classic, with the base at the cortex and the apex extending through white matter to approach the subependymal region of the ventricle. Morphologic and anatomic clues can sometimes differentiate between feeding arteries (direct course to nidus) and draining veins (tortuous course and irregular caliber). Parent artery feeder origin can often be inferred from the nidus location (e.g., middle cerebral artery territory), while the location of tortuous draining veins indicates
Figure 3 Left parietal arteriovenous malformation (AVM). Noncontrast axial computed tomography demonstrates a large, patent, hyperattenuating venous varix draining a parietal AVM nidus (not shown). Focal dystrophic calcifications are identified in its walls. There is mass effect on the underlying left parietal lobe with an element of vasogenic edema suggested. Source: Courtesy of Tim Malisch, Northwestern Memorial Hospital.
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Figure 4 Left frontal arteriovenous malformation (AVM). Contrast-enhanced axial computed tomography, displayed at wide (blood) windows, demonstrates dramatic contrast enhancement of patent AVM vessels (arrow) at the periphery of a large acute parenchymal hemorrhage.
superficial versus deep drainage (Fig. 7). Venous varices are readily identified if present, with or without associated mass effect (Fig. 8). While gadolinium is not essential in the evaluation of AVMs, slow flow in portions of the nidus, collateral arteries, or venous outflow may show contrast enhancement. A very small AVM nidus with slow flow may be difficult to visualize without contrast. In this circumstance, the only clue to its presence may be identification of enhancing arteries or veins in parenchyma, a cerebral sulcus, or basilar cistern (5,47). The presence of very low signal from calcification, air, cortical bone, deoxyhemoglobin (e.g., thrombosed vessel on T2-weighted images), or remote hemorrhage (ferritin) may mimic a flowvoid seen in AVM vessels. The use of gradient-recalled echo (GRE) imaging may prove helpful for differentiation. Flowing blood on GRE images demonstrates increased signal rather than flowvoids (absent signal), while the other structures remain dark (54,55). Despite their exquisite sensitivity to the presence of hemorrhage, GRE techniques may be degraded by susceptibility artifacts at air-soft tissue interfaces or around metallic hardware and may therefore be limited. The artifacts generated around the paranasal sinuses, petrous apices, vascular clips, dental braces, and ventriculoperitoneal shunts significantly degrade these images (55). Therefore, a conventional or fast spin-echo T2-weighted pulse sequence is commonly employed as part of the exam.
Figure 5 Left medial parietal arteriovenous malformation (AVM). Hyperdensity within the parasagittal left cerebral hemisphere represents endovascularly placed N-butyl cyanoacrylate (acrylic glue, NBCA) within an AVM nidus. Source: Courtesy of Tim Malisch, Northwestern Memorial Hospital.
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Figure 6 Left parietal arteriovenous malformation (AVM). (A) Noncontrast T1-weighted sagittal image demonstrates an AVM nidus, consisting of a tangle of flow voids. (B) Frontal projection from three-dimensional time-of-flight magnetic resonance angiography demonstrates supply from parietal left middle cerebral artery branches.
Perilesional gliosis and infarction, in some cases related to the steal phenomenon, are readily demonstrated with MRI as parenchymal regions of increased signal on T2-weighted and fluid attenuated inversion recovery (FLAIR) images (Fig. 9). FLAIR pulse sequences utilize an inversion recovery pulse to null the signal from cerebrospinal fluid (CSF), yielding heavily T2-weighted images with dark CSF. The combination allows easier detection of parenchymal lesions that border CSF spaces such as the ventricles. Acute perilesional infarcts adjacent to AVMs are best defined by diffusion-weighted imaging (DWI), the most sensitive imaging tool for detection of acute cerebral infarction (56,57). Diffusion-weighted images, which can be obtained within 15 seconds if performed with strong gradient coils that permit echo-planar (ultrafast) imaging, are sensitive to regions of restricted water diffusion such as are seen in cytotoxic edema due to acute infarction. Acute infarcts are readily identified as increased signal on DWI, and these scans remain positive for a week to 14 days after the event. Atrophy or frank encephalomalacia may be the consequence of prior hemorrhage or steal phenomenon (47). Although CT remains the imaging modality of choice for acute intracranial hemorrhage, subacute and chronic hemorrhages are best evaluated with MRI. A complete discussion
Figure 7 Right thalamic arteriovenous malformation. (A) Noncontrast T1-weighted sagittal image demonstrates multiple thalamoperforator arteries, seen as right thalamic/basal cistern flow voids, and a prominent vein of Galen and straight sinus, indicating deep venous drainage. (B) Proton density-weighted axial image clearly documents the thalamic flow voids and mild mass effect, and confirms deep venous drainage through the basal vein of Rosenthal and vein of Galen.
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Figure 8 Left frontal arteriovenous malformation. T2-weighted axial image demonstrates a patent venous varix as a serpiginous flow void. Multiple nidal flow voids and other draining veins surround the varix.
of the MRI appearance of intracranial hemorrhage is beyond the scope of this chapter. Table 1 lists the typical T1- and T2-weighted spin-echo appearances of the different stages of parenchymal hematomas (58). The appearance varies not only with the age of the hematoma, but also with the magnetic field strength (e.g., .5 vs. 1.5 Tesla) and specific sequence parameters (53,59). Recognition of blood byproducts on MRI facilitates the identification of thrombosed portions of the AVM, whether spontaneous or after treatment (49). Chronic parenchymal hemorrhage, in the form of hemosiderin and ferritin, is demonstrated as T2 shortening, that is, very dark signal on T2-weighted images. T2 shortening may persist at the site of hemorrhage for years. GRE MR images are most sensitive to susceptibility-induced signal loss and, therefore, most sensitively demonstrate parenchymal hemorrhages. The extent of the hemorrhage may be exaggerated on GRE images, due to magnetic susceptibility artifact (blooming) at the margins. Superficial or ependymal siderosis, seen as extremely dark signal coating the pial surface or ventricular lining, suggests multiple prior subarachnoid or intraventricular hemorrhages (Fig. 10).
Figure 9 Left frontal arteriovenous malformation (AVM). (A) T2-weighted and (B) fluid attenuated inversion recovery (FLAIR) axial images demonstrate the AVM nidus. Neighboring parenchyma demonstrates abnormal increased signal consistent with gliosis. The parenchymal changes are more conspicuous on the FLAIR images (B), secondary to the suppression of cerebrospinal fluid signal.
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Table 1 T1- and T2-Weighted Spin-Echo Appearances of the Different Stages of Parenchymal Hematomas Stage Hyperacute Acute Early subacute Late subacute Chronic
Time
Blooda
T1-Imageb
T2-Imageb
0–12 hr 12 hr–3 days 3 days–1 wk 1 wk–months Months–years
Oxyhemoglobin DeoxyHb MetHb (intra)c MetHb (extra)c Ferritin
Isointense to low signal Isointense to low signal High signal High signal Low signal
High signal Low signal Low signal High signal Low signal
a
Metabolic phase of hematoma. Signal relative to normal brain parenchyma. c Intracellular and extracellular methemoglobin. Source: From Ref. 58. b
As mentioned previously, aneurysms found in association with an intracranial AVM increase the risk of hemorrhage. Perata et al. have classified four types of aneurysms associated with AVMs (60). Dysplastic or remote aneurysms arise from parent arteries unrelated to the AVM’s supply and have the same incidence as in the general population. Proximal aneurysms arise from parent arteries supplying the AVM nidus and are most commonly found at the circle of Willis. Pedicular aneurysms arise from the midcourse of a feeding artery. Finally, intranidal aneurysms have been reported in up to 58% of AVMs when superselective angiography is performed (21). Intranidal aneurysms may demonstrate histologically definable, but thin vascular walls, or may represent pseudoaneurysms (61,62). Detection of these aneurysms by MRI alone is problematic because other vascular structures may obscure them. In fact, superselective conventional angiography may demonstrate the presence of these aneurysms when more proximal carotid or vertebral injections may not. On spin-echo MR images, aneurysms on parent arteries, or large intranidal aneurysms, appear as rounded flow voids with or without inhomogeneous higher signal related to turbulent flow or intraluminal thrombus. MRA may aid in the search for associated aneurysms by suppressing background signal and producing high signal in the aneurysm. However, the detection of aneurysms less than 5 mm in size is less reliable, and there is still poor detection of intranidal aneurysms (63–66). MRA may provide information unattainable with conventional MR images and may be particularly useful for stereotactic treatment planning (67,68). Advances in computer software, which allow surface rendering of cortical anatomy and the superimposition of MRA images, are increasingly utilized for the presurgical workup of AVMs, especially for those located at the convexity (69,70). Studies suggest that in combination with MR imaging,
Figure 10 Left thalamic arteriovenous malformation (AVM). (A) Gradient-recalled echo coronal image demonstrates superficial siderosis, the result of multiple previous intracranial hemorrhages, as abnormal low signal along the cortical surface of the right frontal lobe (arrow). (B) Axial source image from a three-dimensional time-of-flight magnetic resonance angiography (a gradient echo technique) demonstrates flow-related enhancement within patent vessels of the AVM (arrow).
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these advanced MRA techniques may also play an important role in the follow-up of AVMs following radiosurgical ablation, resulting in a reduction in the number of required posttherapeutic catheter angiograms (71–74). Time-of-flight (TOF) and phase contrast (PC) MRA techniques maybe used for AVM evaluation. TOF MRA is a GRE technique, based on the principle of flow-related enhancement (FRE), in which fully magnetized spins (water protons in blood) continuously flow into an imaging volume of stationary tissues that have been saturated with repeated radiofrequency pulses (43,70,75–78). The saturated stationary tissue signal is suppressed, while the inflow of ‘‘fresh’’ spins from flowing blood produces increased signal (FRE) (Fig. 10). Most applications today use three-dimensional (volumetric) rather than two-dimensional techniques because of higher resolution. Advances that have dramatically improved the quality of 3D TOF MRA include the utilization of flow compensation, magnetization transfer suppression of background, shorter echo times, multiple overlapping thin slab acquisition technique, and tilted optimized nonsaturating excitation pulses (43,76,77,79–82). From flat base sectional images, maximum intensity projection (MIP) reconstructions are generated, creating an ‘‘angiogram’’ that can be freely rotated for multiple projection review (Figs. 1, 6, and 11). The axial base (source) images should always be reviewed along with the MIP reconstructions to minimize errors in interpretation. Phase shift differences between stationary tissues and flowing blood result from the application of bipolar gradients during MR imaging and form the basis of PC MRA (43,64,77,78). This technique offers several advantages over TOF MRA (43,64,77,81,83,84). The phase shift accumulated by moving spins is proportional to their velocity. The technique can, therefore, be velocity encoded, and the study customized to highlight flow of differing velocities. Thus, images of arterial inflow may be generated separate from the venous drainage. Because images are created with subtraction techniques, PC MRA offers superior background suppression, allowing better visualization of smaller vessels with slower flow. Structures with short T1 relaxation times (e.g., fat, methemoglobin, neurohypophysis) that appear as high signal intensity resembling blood flow and can, therefore, be mistaken for AVM vessels or aneurysms on TOF images, are also subtracted out. PC MRA is also insensitive to certain artifacts that are inherent to TOF techniques (e.g., saturation effects). Both techniques allow for depiction of flow direction. This information is inherent in PC MRA techniques but also can be obtained with TOF MRA through the use of selectively placed presaturation pulses (more labor intensive) (64,84). Quantitative flow analysis is possible only from PC techniques (85). PC MRA is, however, limited by aliasing artifacts and relatively long imaging times (43,64,81,83). The higher resolution possible with TOF MRA and the long imaging times associated with PC MRA have made TOF techniques the most widely used for both extra- and intracranial evaluations.
Figure 11 Right paracentral lobule arteriovenous malformation. (A) Magnified sagittal projection from threedimensional time-of-flight magnetic resonance angiography demonstrates supply from enlarged anterior cerebral artery branches. (B) The size and location of the compact nidus are exquisitely demonstrated on this T1-weighted axial image.
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Complete evaluation of a cerebral AVM requires the accurate depiction of all arterial feeders, the central nidus, all draining veins, associated aneurysms, and changes of vascular angiopathy, and the detection of venous outflow obstruction. All presently available MRA techniques fall short of achieving this goal. Studies of the usefulness of TOF MRA for imaging cerebral AVMs have revealed many limitations (43,51,64,76,77,79,80,82,84,86,87). The nidus of a small AVM is not consistently well demonstrated. All feeding arteries and draining veins may not be identified. The lack of easily obtained temporal information makes the detection of the steal phenomenon difficult and the differentiation between angiomatous change from AVM nidus unreliable. As mentioned previously, associated aneurysms less than 5 mm in size may go unrecognized as well. CONVENTIONAL ANGIOGRAPHY Whereas CT and MRI play important roles in the radiographic diagnosis of cerebral AVMs, definitive characterization for treatment planning requires conventional catheter angiography (4,88). Technical advances with the development of hydrophilic microcatheters (whether flowdirected or wire-directed) have made superselective angiography an additional diagnostic requirement (89). Angiography allows for direct temporal visualization of arteriovenous shunting, including determination of nidal transit time, with ready identification of early draining veins. Catheter techniques allow for the definitive evaluation of the angioarchitecture of all feeding arteries, the central nidus, and all draining veins. In the acute setting after intracranial hemorrhage, the angiographic depiction of an underlying AVM may be compromised by nidal compression from associated mass effect or thrombosis. In this setting the AVM may go undetected. In the proper clinical setting, angiography should be repeated after resolution or evacuation of the hematoma. The investigation begins with selective catheterization and arteriograms performed of both internal carotid arteries (ICA) and vertebral arteries (4). Biplane filming is standard with oblique views acquired as needed. Depending on the AVM location (e.g., peripheral cortical location, posterior fossa), both external carotid arteries may need to be explored (Fig. 12). Standard catheter angiography displays the arterial supply and venous drainage and allows a gross assessment of the central nidus (Fig. 13). Pretherapeutic characterization of the AVM components and associated vascular findings often requires superselective angiography with microcatheters. The angioarchitecture of feeding arteries is assessed for several factors. The total number of feeders has implications for surgical and/or endovascular therapy. The type of arterial feeders, their relationship to the nidus, and whether or not they also supply normal brain are characterized. Any associated aneurysms or changes secondary to high-flow angiopathy
Figure 12 Right parietal arteriovenous malformation. (A) Lateral digital subtraction angiogram, vertebral artery injection, demonstrates predominant supply from parieto-occipital and calcarine branches. (B) Meningeal supply is evident on this frontal right external carotid artery injection.
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Figure 13 Right parietal and ganglionic arteriovenous malformations. (A) Lateral digital subtraction angiogram image from right internal carotid injection clearly demonstrates supply from the anterior cerebral artery and the middle cerebral artery branches and superficial cortical venous drainage to the superior sagittal sinus. (B) Lateral projection in a different patient demonstrates a deep-seeded nidus with deep venous drainage through the basal vein of Rosenthal, vein of Galen, and straight sinus. Source: Courtesy of Tim Malisch, Northwestern Memorial Hospital.
(see below) are assessed. Cerebral AVMs may show dominant supply from pial, penetrating or choroidal arteries, and also may have contributions from meningeal arteries (Fig. 13). Meningeal arteries may also supply normal brain made ischemic by steal toward the AVM by retrograde pial flow (90). Feeding arteries have been classified as terminal, pseudoterminal or indirect (4). Terminal feeders may supply normal brain proximally, but they eventually end directly within the nidus. Pseudoterminal feeders supply normal brain distal to their supply to the AVM nidus. They may be indistinguishable from terminal feeders at angiography, but their location suggests supply to normal brain. Indirect feeders terminate in the AVM nidus, but they arise, typically at right angles, from larger arteries that feed normal brain parenchyma. Indirect feeders have been termed ‘‘en passage’’ feeders, and may be too small to catheterize for endovascular therapy (Fig. 14). The lack of an intervening capillary bed reduces the overall resistance of the underlying vascular malformation and results in high flow states. The resultant abnormal hemodynamics may lead to morphological changes in the feeding arteries (i.e., high-flow angiopathy). These changes include ectasia, tortuosity, stenosis, thrombosis and/or aneurysm formation (Fig. 15) (91). Hemodynamically induced proximal, pedicular and remote aneurysms can be reliably defined at angiography. Their detection has important management implications (92). Angiomatous change can be reliably recognized as ectatic and tortuous pial collaterals (Fig. 16). Although the appearance can superficially resemble additional AVM nidus, there is no early venous drainage.
Figure 14 Left frontal arteriovenous malformation. Magnified oblique digital subtraction angiogram image from left internal carotid artery injection demonstrates innumerable, small ‘‘en passage’’ feeders arising from both anterior cerebral artery and middle cerebral artery branches.
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Figure 15 Large right hemispheric arteriovenous malformation (AVM). (A) Frontal right internal carotid arteriogram demonstrates subtle vessel irregularities consisting of stenoses, dilatations, and focal outpouchings (arrowhead). An intranidal aneurysm is identified (arrow). (B) Magnified lateral view demonstrates several aneurysms proximal to the AVM nidus (arrows). Source: Courtesy of Tim Malisch, Northwestern Memorial Hospital.
Surgical resection or endovascular embolization of these collaterals is usually contraindicated, because occlusion would result in parenchymal infarction. The central nidus remains the target of all therapeutic interventions and is only accurately depicted with superselective angiography (Fig. 17). Houdart et al. have suggested a morphological classification that may have implications for endovascular therapy (26). An arteriovenous fistula consists of one to three arterial feeders reaching a single draining vein. A plexiform arterial network reaching a single draining vein is termed an arteriolovenous shunt. Lastly, arteriolovenulous shunting refers to a plexiform arterial supply with multiple venous drainers. True intranidal aneurysms are recognized on the arterial side of the nidus prior to venous filling and are therefore differentiated from venous varices (Fig. 15) (61). Intranidal pseudoaneurysms may also be present and may be difficult to identify as such. They can reside on the arterial or the venous side of the nidus (62). Definitive distinction between the two can be made if the aneurysm is a new finding when the angiogram is compared to a previous one. The differentiation is of academic interest only and has no therapeutic implications. Venous drainage is recognized as cortical, deep, or mixed (Fig. 13). Just as arterial feeders may demonstrate high-flow angiopathic changes, varices and venous stenoses may be present (Fig. 18). Findings suggestive of venous hypertension (e.g., ectasia proximal to a
Figure 16 Large right hemispheric AVM. (A) Early and (B) late frontal left internal carotid arteriograms demonstrate cross-filling to dilated and tortuous right ACA branches, which have undergone angiomatous change. The vessels then supply a portion of the AVM nidus in a retrograde fashion. Dominant supply arose from the right MCA. Note the lack of early venous drainage from the area of angiomatous change, thus allowing differentiation from the actual nidus, which demonstrates deep venous drainage.
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Figure 17 Left parietal arteriovenous malformation. Magnified lateral digital subtraction angiogram image from superselective catheterization demonstrates the terminal arterial feeder (small arrow), the central nidus (open arrow), and the solitary draining vein (curved arrow). Note the position of the microcatheter tip (long arrow). Source: Courtesy of Tim Malisch, Northwestern Memorial Hospital.
Figure 18 Large hemispheric arteriovenous malformations. (A) Late phase lateral digital subtraction angiogram (DSA) image demonstrates tortuous deep and superficial venous outflow. A focal venous stenosis is noted at the venosinal junction (arrow). (B) Magnified late phase lateral DSA image demonstrates multiple large venous varices in a different patient.
Figure 19 Right cerebellar arteriovenous malformation (AVM). (A) Frontal right vertebral arteriogram demonstrates the large AVM. (B) Late phase from same run demonstrates findings of marked venous hypertension. Bilateral cerebellar, supratentorial, and even spinal (arrow) venous outflow is present. Source: Courtesy of Tim Malisch, Northwestern Memorial Hospital.
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Figure 20 Left parietal cavernous malformation. (A) Proton density-weighted axial image demonstrates the classic mixed signal (popcorn) appearance of a cavernous malformation due to internal blood byproducts of differing ages. Notice the uninterrupted peripheral low signal ring of hemosiderin/ferritin. The appearance of this lesion on magnetic resonance imaging is indistinguishable from that of an angiographically occult arteriovenous malformation. (B) Gradient-recalled echo axial image demonstrates a marked susceptibility artifact as a result of the presence of hemorrhagic byproducts. Notice how the artifact ‘‘blooms’’ and thus overestimates the true size of the lesion.
venous stenosis, reflux from dural sinus into cortical veins) or frank venous thrombosis should be noted (Fig. 19). Their presence indicates an increased risk of hemorrhage.
ANGIOGRAPHICALLY OCCULT AVMs Angiographically occult AVMs demonstrate abnormal arteriovenous connections histologically but are not revealed by catheter angiography (93–99). Their cryptic nature is thought to result from their small size, relatively slow flow, mass effect from associated hematoma, and/or complete thrombosis. Although the presence of a histologically definable arterial component separates true occult AVMs from other occult vascular malformations, their appearance on imaging may be indistinguishable. CT and MRI play the major role in radiographic diagnosis. If occult AVMs are large enough and not obscured by adjacent hematoma, they may appear on CT as iso- or slightly hyperdense lesions, often containing foci of calcification (93,96,98). On MRI, a ‘‘popcorn’’ appearance of mixed high and low signal intensities on both T1- and T2-weighted images is classic (Fig. 20A) (93,95–99). The signal characteristics are the result of internal hemorrhagic by-products of differing ages. On T2-weighted images the lesions demonstrate a concentric and uninterrupted peripheral low signal rim secondary to hemosiderin and ferritin. In the presence of these hemorrhagic components, GRE images demonstrate marked susceptibility artifacts, which may overestimate the size of the lesion (Fig. 20B). It should be noted that this popcorn appearance on MRI is also pathognomonic for cavernous malformations (100). Not unlike typical AVMs, the occult AVM usually does not demonstrate mass effect or surrounding vasogenic edema. The lesions may show contrast enhancement on CT and MRI, but it is usually diffuse and mild. Large feeding arteries and draining veins are conspicuously absent.
CONCLUSION CT, MRI, and conventional angiography play complementary roles in the radiographic diagnosis of cerebral AVMs. CT is often the initial imaging modality utilized in the acute presentation. Subsequent complete evaluation of any individual AVM is best accomplished with MRI and conventional angiography. Future technical advances will continue to aid the multidisciplinary team in prompt diagnosis as well as guide therapeutic strategies.
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Petereit D, Mehta M, Turski P, et al. Treatment of arteriovenous malformations with stereotactic radiosurgery employing both magnetic resonance angiography and standard angiography as a database. Int J Radiation Oncology Biol Phys 1993; 25:309–313. 69. Kesava P, Baker E, Turski P. Staging of arteriovenous malformations using three-dimensional timeof-flight MR angiography and volume-rendered displays of surface anatomy. Am J Roentgenol 1996; 167:605–609. 70. Pant B, Sumida M, Kuriso K, et al. Usefulness of two-dimensional time-of-flight MR angiography combined with surface anatomy scanning for convexity lesions. Neurosurg Rev 1997; 20:108–113. 71. Quixling RG, Peters KR, Friedman WA, Tart RP. Persistent nidus flow in cerebral arteriovenous malformation after stereotactic radiosurgery: MR imaging assessment. Radiology 1991; 180:785–791. 72. Kauczor HU, Engenhart R, Layer G, et al. 3D TOF MR angiography of cerebral arteriovenous malformations after radiosurgery. J Comput Assist Tomogr 1993; 17:184–190. 73. Guo WY, Lindquist C, Karlsson B, Kihlstrom L, Steiner L. Gamma knife surgery of cerebral arteriovenous malformations: serial MR imaging studies after radiosurgery. Int J Radiation Oncology Biol Phys 1993; 25:315–323. 74. Pollock B, Kondziolka D, Flickinger J. Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery. J Neurosurg 1996; 85:1044–1049. 75. Bosmans H, Marchal G, Lukito G, et al. Time-of-flight MR angiography of the brain: comparison of acquisition techniques in healthy volunteers. Am J Roentgenol 1995; 164:161–167. 76. Marchal G, Bosmans H, Van fraeyenhoven L, et al. Intracranial vascular lesions: optimization and clinical evaluation of three-dimensional time-of-flight MR angiography. Radiology 1990; 175:443–448. 77. Edelman RR. MR angiography: present and future. Am J Roentgenol 1993; 161:1–11. 78. Kesava PP, Turski PA. Magnetic resonance angiography of vascular malformations. Neuroimag Clin North Am 1998; 8:349–370. 79. Davis WL, Blatter DD, Harnsberger HR, Parker DL. Intracranial MR angiography: Comparison of single-volume three-dimensional time-of-flight and multiple overlapping thin slab acquisition techniques. Am J Roentgenol 1994; 163:915–920. 80. Jung HW, Chang KH, Choi DS, Han MH, Han MC. Contrast-enhanced MR angiography for the diagnosis of intracranial vascular disease: optimal dose of gadopentetate dimeglumine. Am J Roentgenol 1995; 165:1251–1255. 81. Atlas SW. MR angiography in neurological disease. Radiology 1994; 193:1–16. 82. Lin W, Tkach JA, Haacke EM, Masaryk TJ. Intracranial MR angiography: application of magnetization transfer contrast and fat saturation to short gradient-echo, velocity-compensated sequences. Radiology 1993; 186:753–761. 83. Pant B, Sumida M, Arita K, Tominaga A, Ikawa F, Kurisu K. Usefulness of three-dimensional phase contrast MR angiography on arteriovenous malformations. Neurosurg Rev 1997; 20:171–176. 84. Edelman RR, Wentz KU, Mattle HP, et al. Intracerebral arteriovenous malformations: evaluation with selective MR angiography and venography. Radiology 1989; 173:831–837. 85. Enzmann D, Ross M, Marks M, Pelc NJ. Blood flow in major cerebral arteries measured by phasecontrast cine MR. Am J Neuroradiol 1994; 15:123–129. 86. Tanaka H, Numaguchi Y, Konno S, Shrier DA, Shibata DK, Patel U. Initial experience with helical CT and 3D reconstruction in therapeutic planning of cerebral AVMs: comparison with 3D time-of-flight MRA and digital subtraction angiography. J Comput Assist Tomogr 1997; 21:811–817. 87. Baumgartner RW, Mattle HP, Aaslid R. Transcranial color-coded duplex sonography, magnetic resonance angiography, and computed tomography angiography: methods, applications, advantages, and limitations. J Clin Ultrasound 1995; 23:89–111. 88. Wolpert SM, Caplan LR. Current role of cerebral angiography in the diagnosis of cerebrovascular diseases. AJR Am J Roentgenol 1992; 159:191–197. 89. Aletich VA, Debrun GM, Koenigsberg R, Ausman JI, Charbel F, Dujovny M. Arteriovenous malformation nidus catheterization with hydrophilic wire and flow-directed catheter. Am J Neuroradiol 1997; 18:929–935.
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90. Russell EJ, Berenstein A. Meningeal collateralization to normal cerebral vessels associated with intracerebral arteriovenous malformations: functional angiographic considerations. Radiology 1981; 139:617–622. 91. Pile-Spellman JMD, Baker KF, Liszczak TM, et al. High-flow angiopathy: cerebral blood vessel changes in experimental chronic arteriovenous fistula. Am J Neuroradiol 1986; 7:811–815. 92. Thompson RC, Steinberg GK, Levy RP, Marks MP. The management of patients with arteriovenous malformations and associated intracranial aneurysms. Neurosurgery 1998; 43:202–211. 93. Hallam DK, Russell EJ. Imaging of angiographically occult cerebral vascular malformations. Neuroimag Clin North Am 1998; 8:323–347. 94. Lobato RD, Perez C, Rivas JJ, Cordobes F. Clinical, radiological, and pathological spectrum of angiographically occult intracranial vascular malformations. J Neurosurg 1988; 68:518–531. 95. Wilson CB. Cryptic vascular malformations. Clin Neurosurg 1986; 38:49–84. 96. New PF, Ojemann RG, Davis KR, et al. MR and CT of occult vascular malformations of the brain. Am J Neuroradiol 1986; 7:771–779. 97. Ogilvy CS, Heros RC, Ojemann RG, New PF. Angiographically occult arteriovenous malformations. J Neurosurg 1988; 69:350–355. 98. Ebeling JD, Tranmer BI, Davis KA, Kindt GW, DeMasters BK. Thrombosed arteriovenous malformations: a type of occult vascular malformation. Neurosurgery 1988; 23:605–610. 99. Atlas SW. Intracranial vascular malformations and aneurysms. Radiol Clin North Am 1988; 26:821–837. 100. Perl J, Ross JS. Diagnostic imaging of cavernous malformations. In: Awad IA, Barrow DL, eds. Cavernous Malformations. Park Ridge, IL: American Association of Neurological Surgeons, 1993:37–48.
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Functional Evaluation and Diagnosis Shervin R. Dashti Department of Neurosurgery, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio, U.S.A.
Jeffrey L. Sunshine Department of Radiology, Case Western Reserve University School of Medicine, and Division of Magnetic Resonance Imaging, University Hospitals of Cleveland, Cleveland, Ohio, U.S.A.
Robert W. Tarr Division of Neuroradiology, Department of Radiology, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio, U.S.A.
Warren R. Selman Department of Neurosurgery, Case Western Reserve University School of Medicine, and Department of Neurological Surgery, University Hospitals of Cleveland, Cleveland, Ohio, U.S.A.
INTRODUCTION Arteriovenous malformations (AVMs) are developmental abnormalities of blood vessels in which the preservation of one or more direct primitive connections between arterial and venous channels results in rapid arterial-venous shunting. The proper management of individual AVMs is often complex. Consideration must be given to the natural history of an AVM and its physiological consequences on surrounding brain parenchyma. A detailed knowledge of the angioarchitecture of the AVM is essential. Also, risk assessment of specific therapeutic regimens with regard to the functional integrity of the surrounding brain is imperative. The most devastating consequences of AVMs occur as the result of intracranial hemorrhage. Before 1990, studies on the natural history of AVMs suffered from an absence of standardized criteria, an insufficient number of patients, and a lack of long-term follow-up. In 1990, Ondra et al. (1) updated the population-based study first reported by Troup et al. (2,3) and significantly refined our understanding of the natural history of these lesions. They found the risk of hemorrhage from an AVM to be 4% per year. The mean interval between hemorrhagic events was 7.7 years and did not vary among patients who initially presented with bleeding, seizures, or headaches. The AVM-related risks of significant morbidity and mortality were 1.7% and 1% per year, respectively. The natural history of AVMs underscores the need for therapeutic intervention in selected patients, despite a recent report (4) suggesting that the natural history of AVMs is not as aggressive as was previously thought. Deferring treatment until an AVM becomes symptomatic carries significant risk because the morbidity and mortality rates from an initial hemorrhage are approximately 40% and 17%, respectively (5). Risk analysis for treatment of individual AVMs must consider the function of the surrounding brain parenchyma. Information about physiologic significance can be gathered from various diagnostic tests that have been developed to evaluate local cerebral function and blood flow. This chapter describes the diagnostic tests that can be used to enhance the safety of therapy for AVMs. PARENCHYMAL FUNCTION Positron Emission Tomography Positron emission tomography (PET) scanning has the ability to quantitate both local cerebral function and blood flow. As PET radioisotopes decay, positrons are released. These positrons travel about 1 cm on average before colliding with a random neighboring electron. The interaction of the positron with the electron produces an annihilation event that yields two 511 kcV
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photons that travel apart at 180 . Coincident detector arrays and back projection software are used to assess the location and concentration of radioisotope accumulation in the brain. 18 F (fluorine) radiolabeled as fluorodioxyglucose (FDG) is an excellent agent for studying cerebral glucose metabolism and, thus, functional activity (6). After extraction by metabolically active tissues in the brain, FDG is phosphorylated to FDG-6 phosphate, but it does not undergo glycolysis and remains trapped in the cell. Therefore, energy released from the decay of 18F is an indicator of cellular glucose uptake and relates to local metabolic demand. Arterial sampling can be utilized to calculate regional cerebral metabolic rates of glucose (rCMRglc) metabolism. However, given variations in PET scanners, data acquisition, and mathematical assumptions, standardization within an individual PET center is critical to insure the validity of rCMRglc measurements. 15 O (oxygen) labeled water is the most widely used PET tracer for measuring regional cerebral blood flow (rCBF). Again using arterial sampling, quantitative CBF values can be obtained. rCBF is coupled with regional glucose consumption in the brain and is a robust marker for changes in cortical neuronal activity. Either glucose uptake or local CBF can be used for functional local cortical mapping in patients with AVMs. When functional tasks are performed, a local increase in blood flow accompanies the local increase in glucose uptake. In patients with AVMs, task specific functional PET scanning has been used to demonstrate the relationship of the AVM to adjacent eloquent parenchyma (7). Functional localization with PET has been shown to be accurate when compared to direct intraoperative cortical mapping (8). Additionally, the combined use of FDG and H2O15 PET scanning can assess the local metabolic and CBF disturbances that occur in relationship with AVMs (9). In the normal brain, there is a tight coupling of rCBF and metabolic rates such as rCMRglc or regional cerebral metabolic rate of oxygen. The detection of regions of increased oxygen extraction fraction, decreased rCBF, and relatively preserved rCMRglc adjacent to an AVM is an indicator of at risk ischemic disease. Functional Magnetic Resonance Imaging Since 1992, functional magnetic resonance imaging (fMRI) has been used to evaluate local changes in CBF related to underlying altered metabolism (10). Comparisons are performed at the same anatomic level but between alternating states of rest and task activation in the patient (e.g., rest vs. visual observation, or rest vs. hand motor action). In the case of normal cerebral vascular response, brain with increased activity and metabolic demand will demonstrate an increased delivery of blood to the local area. The increased flow outweighs the effect of increased oxygen consumption, thereby resulting in a relative increase in oxygenated blood in the area. The oxygenated blood in turn is seen as increased signal change on MR sequences with appropriate sensitivity to susceptibility effects of the free electrons on oxyhemoglobin. Such a sequence is run repetitively during the various on and off states of the task, and motion correction algorithms are applied to minimize artifact. Each pixel is then analyzed for a correlative change in signal with change in task (11). Those that correlate at a specified statistical level of significance are considered metabolically active areas and are deemed ‘‘activated.’’ The interpretation of such activation maps requires careful attention to motion correction (12) and the presence of large cortical veins (13). The acceptance of fMRI required validation of the technique by comparison with established techniques for mapping cortical activity. Studies have demonstrated acceptable match fidelity between fMRI and intraoperative direct cortical stimulation and sensory evoked potential recording for determination of the location of primary motor and sensory cortex (14). In another study, fMRI results obtained for patients performing complex tasks (finger, lip, and tongue movement, as well as counting or speaking) were compared with intraoperative mapping allowing assessment of the precision of localization. The corroboration appeared to be on the order of 1 cm (15). Additionally, the use of fMRI to locate language direction (receptive and silent generative) was compared with the results of intraoperative mapping and showed similar correlation with an approximately 1-cm error (16). In patients with congenital AVMs, the locations of cerebral functions may be altered through developmental plasticity. fMRI can be used to identify functionally active cortex, even in unexpected locations, to help choose an appropriate therapeutic modality and to guide therapy. For example, fMRI has demonstrated the transposition of language dominance
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to the right hemisphere in some individuals with a left temporal AVM (17). Of potentially greater importance for pretreatment planning, fMRI has shown sensorimotor function within the volume of AVM nidus (Fig. 1). Blind resections of such AVMs may produce contralateral hemiparesis (17). Delineation of active tissue from malformation allows safer placement of boundaries for radiosurgery or selection of resection planes (18), although intraoperative speech and motor mapping remain the gold standard. The superimposition of the activation data onto modern treatment plans for radiosurgery should allow minimization of dose delivery to nearby functionally vital tissue (19).
Figure 1 Functional MRI and PET scan. (A) Two T1-weighted axial MR images, of which the second image shows the nidus as a faint area of increased signal intensity to the right of midline in the frontal lobe. The colored pixels represent areas of activation from left foot motion. (B) Four axial images from an FDG-PET study with increased metabolic activity medially adjacent to the arteriovenous malformation generated by left foot motion. Together these studies confirm the close approximation of the nidus to eloquent cortex. Abbreviations: PET, positron emission tomography; MRI, magnetic resonance imaging; FDG, fluorodioxyglucose. (See color insert.)
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Magnetoencephalography Magnetoencephalography (MEG) is another functional imaging modality. It can be used to localize the motor and sensory cortices in unaffected individuals and in patients with AVMs whose pathology distorts normal anatomic relations. The technique is noninvasive and is based on the detection of fluxes in surface magnetic fields generated by the transient electric current in activated neuronal regions. As with fMRI, these fluxes must be temporally correlated with sensory stimuli or motor activation. This technique offers the potential for extremely fine temporal resolution, limited only by the analog-to-digital conversion rate (20). Currently, the technique is limited by the requirements for a shielded room, given the very low signal-to-noise ratio, and by a limited field of view. Nevertheless, MEG has been successfully applied to presurgical evaluation of distances from cortical lesions to functionally important tissue (Fig. 2). The precision of this technique has assisted in developing a functional risk categorization based on spatial separation (21). When compared to fMRI, MEG demonstrates an increased sensitivity for lesion detection. There are fewer false negative tests, and the technique has the ability to localize function deep into the brain surface (16).
RELATIVE PERFUSION The evaluation of cerebral perfusion around an AVM typically reveals a defect secondary to the high flow of the malformation. The perfusion can be measured with several modalities. Cold xenon computed tomography (CT) has shown strong sensitivity and accurate quantification, although it lacks spatial resolution and requires patient tolerance to the side effects of the xenon. Nuclear SPECT, using the lipophilic tracer hexamethylpropyleneamine oxime, can produce semiquantitative perfusion measures with improved spatial resolution. Advances in CT perfusion imaging, coupled with its relatively fast speed and low cost, make it an attractive option for measuring cerebral perfusion. CT perfusion has been used for the quantitative assessment of cerebral ischemia in acute stroke and in the setting of vasospasm secondary to subarachnoid hemorrhage (22–24). The CT perfusion technique involves the administration of a single bolus of iodinated contrast material, followed by cine CT image acquisition during the passage of contrast through the cerebral vasculature. For each voxel in a CT image slice, a transient change in brain parenchymal enhancement is measured and plotted as a time density curve. The maximum slope of the time density curve can be used to calculate CBF, cerebral blood volume (CBV), and time-to-peak (TTP). TTP is the delay between the
Figure 2 Magnetoencephalography. The image depicts magnetic mapping points superimposed on the patient’s T1-weighted magnetic resonance image. The indicated activity was derived from somatosensory stimulation of the left second toe and is marked as a solid square. The surrounding circle represents a statistical confidence volume (closer to the square being greater confidence). Thus, the nidus straddles not only the anatomic central sulcus, but also the functionally defined one shown here, centered over the leg region. Source: Courtesy of Howard A. Rowley, UCSF Medical Center. (See color insert.)
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Figure 3 Xenon CT blood flow. Images represent flow maps from cold xenon CT with areas in white set to reflect flows of at least 30 mL/100 g/min. The first image was obtained as a baseline. The second was generated after IV challenge with acetazolamide. Note the relative decrease in flow to the right frontal region (arrows) signifying a lack of residual autoregulatory reserve ipsilateral to the known arteriovenous malformation. On the contralateral side there is no decrease but there is also a lack of increase in the frontal region with challenge compared to the parietal area (arrowheads). Abbreviation: CT, computed tomography.
appearance of contrast in the major arteries included in the CT image slice and the local bolus peak in the brain parenchyma. TTP is delayed in ischemic brain, reflecting a delay in perfusion because of collateral flow (24). Color coded TTP maps, as well as CBF and CBV measurements, can thus be used to identify ischemic areas surrounding an AVM. Overall, the best resolution (approximately 1 cm) is achieved with H2O15 PET scanning. The short half-life of H2O15 combined with the short scan acquisition time allows for multiple scans to be acquired on the same patient. Thus, parameters such as systemic blood pressure or PCO2 can be altered or acetazolamide may be administered to assess the vascular reserve of tissue adjacent to an AVM. In a PET study of seventeen patients with AVMs, a significant increase in CBV along with an increased relative mean transit time of blood through the ipsilateral hemispheres was seen, but CBF was unaltered overall (9). Although these perturbations in flow have been documented, their predictive value for outcome or usefulness in guiding therapy choice has not been validated. Cold xenon CT has been used in combination with acetazolamide challenge to test vascular reserve about an AVM. Results have revealed varying levels of dysfunction in vascular autoregulation (Fig. 3). The majority of patients tested encountered a decreased ability to augment CBF, most often in vascular distributions near the site of the malformation (25). This lost autoregulation may represent a compromise in hemodynamic reserve or the presence of a ‘‘vascular steal’’ phenomenon.
BLOOD PRESSURE AND FLOW ANALYSIS Analysis of blood pressure and flow in arteries feeding AVMs may reflect the risk of hemorrhage. In a study of several hundred patients with AVMs, the mean arterial pressure was measured in the feeding arteries. Also recorded were the AVM size and location, the presence of aneurysms, and the patterns of arterial supply and venous drainage. A high pressure in a feeding artery and exclusively deep venous drainage were the most significant indicators of increased risk of future hemorrhage (26). This information may aid natural history risk analysis for individual AVMs. In a study of a cohort of nearly one hundred patients with AVMs, intra-arterial pressures were decreased in vessels closer to the nidus. This finding may, as suggested by these authors, produce a regional area of chronic hypoperfusion (27). Further understanding of the regions described above may permit more precise estimation of tissue at risk for hemorrhagic complications during treatments.
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Similarly, flow analyses within feeding vessels may add to full pretreatment evaluation. The application of transcranial Doppler techniques allows a noninvasive estimate of flow velocities, even in vessels that may have a normal caliber lumen on angiogram. Manchola et al. used transcranial Doppler to study 40 patients with AVMs who were admitted for proton beam therapy (28). The authors correlated mean flow velocity, pulsatility index, vessel diameter, and flow volume in feeding vessels with the patients’ symptom history including hemorrhage, headache, seizure, and progressive neurological deficit. They found that the flow volumes of feeding vessels in patients with a history of hemorrhage were significantly lower than those in patients with other symptoms, and that the flow volumes of feeding vessels in patients with progressive neurological deficits were significantly higher than those in patients without this symptom. The authors speculated that surgical ligature of high flow vessels might incrementally increase the risk of the development of an adverse edematous response in surrounding normal cerebral parenchyma. It may be important to analyze regional disturbances of blood flow in relation to partial AVM treatment such as staged embolization. Wasserman et al. used noninvasive MR angiography techniques to assess blood flow in patients with AVMs (29). They demonstrated progressive decrease in main pedicle flow velocity after sequential embolization stages. Similarly, Jungreis and coworkers documented a progressive increase in pedicle pressure during embolization of the pedicle. They hypothesized that a large change in pedicle pressure during AVM embolization may predispose to periprocedural hemorrhage (30). In fact, Fogarty-Mack et al. showed that AVMs with higher feeding pedicle pressure have a significantly higher natural history risk of hemorrhage (27). Stable Xenon-CT has been used to study the local hemodynamic effects of AVM embolization. Tarr et al. found new areas of decreased vascular reserve after AVM embolization (31). These areas normalized to baseline several weeks after an embolization procedure. These results suggest that appropriate time intervals should be inserted between embolization stages. A complete functional evaluation of any AVM might therefore include review of pressure and flow dynamics into and out of the malformation. Such information could improve the design of partial or staged treatments, and perhaps decrease perioperative flow-related hemorrhagic or edematous complications. INVASIVE PROVOCATION Wada and Rasmussen initially developed the concept of infusion of sodium amytal (a short acting barbiturate) into an internal carotid artery to localize language function (32). This approach was subsequently modified to the superselective arterial injection of amytal (33) and, more recently, of the ultra short acting sodium methohexital or brevital (34). This modification allows for direct provocative testing of any feeding vessel distribution in order to minimize coincident loss of brain function with treatment. The application of such a technique can elicit areas of displaced parenchymal function secondary to the underlying disease process. As an example, Lazar et al. demonstrated the unexpected anterior location of language function in patients with left hemispheric AVMs before treatment (35). CONCLUSION Modern practitioners have a wide armament of tests at their disposal for the demonstration of important cerebral function. One may argue that pretreatment evaluation of many AVMs should include at least one measure of surrounding parenchymal activity and at least one measure of the surrounding flow dynamics. The knowledge gained about each particular malformation may guide risk analysis and increase the margin of safety during treatment. REFERENCES 1. Ondra SL, Troup H, George EP, Schwab K. The natural history of symptomatic arteriovenous malformations of the brain: 24-year follow-up assessment. J Neurosurg 1990; 73:387–391. 2. Troup H. Arteriovenous malformations of the brain: what are the indications for operation? In: Morley TP, ed. Current Controversies in Neurosurgery. Philadelphia: W.B. Saunders, 1976:210–216.
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3. Troup H, Martilla I, Halonen V. Arteriovenous malformations of the brain prognosis without operation. Acta Neurochir (Wein) 1970; 22:125–128. 4. Stapf C, Mast H, Sciacca RR, et al.; New York Islands AVM Study Collaborators. The New York Islands AVM Study: design, study progress, and initial results. Stroke 2003; 34:e29–e38. 5. Barrow DL. Intracranial aneurysms and vascular malformations. Clin Neurosurg 1992; 40:3–9. 6. Hamacher K, Coeen HH, Stocklin G. Efficient stereoscopic synthesis of no-carrier-added 2–18Fflouro-2-dioxy-D-glucose using aminopoly ether-supported nucleophillic substitution. J Nucl Med 1986; 27:235–284. 7. Leblanc E, Meyer E, Zatorre R, Tampieri D, Evans A. Functional PET scanning in the preoperative assessment of cerebral arteriovenous malformations. Stereotact Funct Neurosurg 1995; 65:60–64. 8. Vinas FC, Zamorano L, Mueller RA, et al. (15)-water PET and intraoperative brain mapping: a comparison in the localization of eloquent cortex. Neurol Res 1997; 19:601–608. 9. Tyler JL, Leblanc R, Meyer E, et al. Hemodynamic and metabolic effects of cerebral arteriovenous malformations studied by positron emission tomography. Stroke 1989; 20:890–898. 10. Kwong KK, Belliveau JW, Chesler DA, et al. Dynamic magnetic resonance imaging of human activity during primary sensory stimulation. Proc Natl Acad Sci USA 1992; 89:5675–5679. 11. Cox RW, Jesmanowicz A, Hyde JS. Real-time functional magnetic resonance imaging. Magn Reson Med 1995; 33:230–236. 12. Wu DH, Lewin JW, Duerk JL. Inadequacy of motion correction algorithms in functional MRI: role of susceptibility-induced artifacts. J Magn Reson Imaging 1997; 7:365–370. 13. Boxerman JL, Bandettini PA, Kwong KK, et al. The intravascular contribution to fMRI signal change: Monte Carlo modeling and diffusion-weighted studies in vivo. Magn Reson Med 1995; 34:4–10. 14. Jack CR, Thompson RM, Butts RK, et al. Sensory motor cortex: correlation of presurgical mapping with functional MR imaging and invasive cortical mapping. Radiology 1994; 190:85–92. 15. Yetkin FZ, Mueller WM, Morris GL, et al. Functional MR activation correlated with intraoperative cortical mapping. Am J Neuroradiol 1997; 18:1311–1315. 16. FitzGerald DB, Cosgrove GR, Ronner S, et al. Location of language in the cortex: a comparison between functional MR imaging and electrocortical stimulation. Am J Neuroradiol 1997; 18: 1529–1539. 17. Maldjian J, Atlas SW, Howard RS, et al. Functional magnetic resonance imaging of regional brain activity in patients with intracerebral arteriovenous malformations before surgical or endovascular therapy. J Neurosurg 1996; 84:477–483. 18. Latchaw RE, Hu X, Ugurbil K, Hall W, Madison MT, Heros RC. Functional magnetic resonance imaging as a management tool for cerebral arteriovenous malformations. Neurosurgery 1995; 37: 619–625. 19. Hamilton RJ, Sweeney PJ, Palizzari CA, et al. Functional imaging in treatment planning of brain lesions. Int J Radiat Oncol Biol Phys 1997; 37:181–188. 20. Roberts TP, Rowley HA. Mapping of the sensorimotor cortex: functional MR and magnetic source imaging. Am J Neuroradiol 1997; 18:871–880. 21. Hund M, Rezai AR, Kronberg E, et al. Magnetoencephalographic mapping: basics of a new functional risk profile in the selection of patients with cortical brain lesions. Neurosurgery 1997; 40:936–942. 22. Klotz E, Konig M. Perfusion measurements of the brain: using dynamic CT for the quantitative assessment of cerebral ischemia in acute stroke. Eur J Radiol 1999; 30:170–184. 23. Koenig M, Kraus M, Theek C, et al. Quantitative assessment of the ischemic brain by means of perfusion related parameters derived from perfusion CT. Stroke 2001; 32:431–437. 24. Harrigan MR, Magnano CR, Guterman LR, Hopkins LN. Computed tomographic perfusion in the management of aneurysmal subarachnoid hemorrhage: new application of an existent technique. Neurosurgery 2005; 36:304–316. 25. Tarr RW, Johnson DW, Rutigliano M, et al. Use of acetazolamide-challenge xenon CT in the assessment of cerebral blood flow dynamics in patients with arteriovenous malformations. Am J Neuroradiol 1990; 11:441–448. 26. Duong DH, Young WL, Vang MC, et al. Feeding artery pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral arteriovenous malformations. Stroke 1998; 29: 1167–1176. 27. Fogarty-Mack P, Pile-Spellman J, Hacein-Bey L, et al. The effect of arteriovenous malformations on the distribution of intracerebral arterial pressures. Am J Neuroradiol 1996; 17:1443–1449. 28. Manchola IF, DeSalles AA, Foo TK, Ackerman RH, Candia GT, Kjellberg RN. Arteriovenous malformation hemodynamics: a transcranial Doppler study. Neurosurgery 1993; 33:556–562. 29. Wasserman BA, Lin W, Tarr RW, Haacke EM, Muller E. 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Section III
BASIC CONSIDERATIONS
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Decision Analysis for Asymptomatic Lesions James McInerney and Robert E. Harbaugh Department of Neurosurgery, The Pennsylvania State University, Hershey, Pennsylvania, U.S.A.
INTRODUCTION Any clinical decision in medicine is made to maximize the benefit to a patient’s health. A decision to make some type of intervention brings an additional dimension of risk to the decision-making process. The decision then becomes a matter of weighing the risk of an intervention against the benefit it should confer. In many cases, these risks are so small that they are not even considered. For example, if a person is having chest pain at home, should they be taken to the emergency room? A small risk is involved with that transfer—there could be a motor vehicle accident along the way, for example. However, this risk is so small in comparison to the benefit of receiving acute medical care in such a situation that it is essentially ignored. Surgery always carries with it many additional risks. Some of these risks are out of the control of the surgeon, such as the age of the patient or the risk of anesthesia. Other risks are more in the surgeon’s control, such as the complexity of the operation or the sterile technique used. The decision to proceed with surgery also must take into account the possibility that no or minimal benefit may be conferred by the procedure. Perhaps the proposed procedure is not the best course of action for a particular patient or the particular lesion. Overall, the most fundamental decision is well within the surgeon’s control, and that is whom to bring to the operating room. Again, there is a spectrum for the difficulty of this decision. The patient whose condition is rapidly deteriorating because of an expanding intracranial hematoma needs an operation urgently; for this patient, the risks of not operating are far outweighed by the likely results of surgery. The decision to proceed with operative intervention becomes more clouded when the patient is healthy and asymptomatic despite the presence of the lesion. The risks in this situation are more formidable, the benefits are perhaps less obvious, and the entire decision needs careful consideration. Much of vascular neurosurgery involves just this type of statistical decision, whether it be for a critical carotid stenosis, an unruptured intracranial aneurysm, or an arteriovenous malformation (AVM). In each case, the decision to intervene surgically is made because the likelihood of long-term benefit is outweighed by the short-term risks of the procedure. Experience with carotid stenosis, for example, has shown that for a symptomatic lesion that causes a greater than 70% occlusion, the likelihood of having a stroke in the near future is greater than the likelihood of having one with surgery (1). The decision is then made to go ahead with an operative intervention despite the fact that a certain small percentage of the treated patients will have a stroke. Our ability to come up with this decision-making paradigm has been aided by the fact that carotid occlusive disease is a relatively common disorder, and the results of various courses of action have been exhaustively studied. In the case of intracranial AVMs, the decision is much more difficult. AVMs are a more heterogeneous set of lesions, with various sizes and locations as well as different patterns of arterial supply and venous drainage. They are congenital lesions and therefore present an entire lifetime of risk to a patient, which is believed to be relatively constant. The risk, specifically, is of hemorrhage, which can lead to death, major neurological deficits, minor neurological deficits, or no problem at all. Again, these possible outcomes appear to happen with predictable percentages of patients who have hemorrhages. Finally, since these lesions are somewhat uncommon, clinical experience with them is limited. As a result, long-term,
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well-controlled studies comparing therapeutic interventions for intracranial AVMs are difficult to design or carry out, and they simply do not exist at present. In this type of difficult decision-making situation, the tool of decision analysis has frequently been used to aid in making appropriate decisions (2). The larger decision is broken down into its possible outcomes, and a mathematical probability is assigned to each. The probabilities can be assigned on the basis of the known experience as reported in the literature. With this information a model can be constructed that will total the relative risk values of each individual pathway to an overall outcome. Finally, the most favorable pathway can be chosen for a given situation, and the accuracy of this choice can be challenged through sensitivity analysis where each input is varied through its range of possible values (3–11). Decision analysis was used for AVMs in the past for exactly these reasons (12–16). Historically, the decision analyses that were completed were flawed by their lack of consideration for the complexity of the decision or by their lack of information about the risks and benefits of various treatment options. Ultimately, they became outdated as new information became available about the risks and benefits of each treatment approach. One of the earliest decision analyses for the treatment of AVMs suggested that observation was favored over surgical excision (15). In this study the risk of surgical mortality was estimated at 10% and the risk of morbidity at 27%. The accuracy of these numbers could not be challenged with data from the literature at the time. Moreover, an accurate range could not be established for the purposes of sensitivity testing. A subsequent decision analysis demonstrated that with lower estimates of the risk of surgical morbidity (8.99%) and mortality (5.54%), surgery was the favored strategy (13). These authors did not have the benefit of the more detailed information about natural history and the stratification of the surgical treatment risk that was accomplished through the Spetzler-Martin grading system after the publication of their studies. More recent studies confirm that surgery is the favored strategy, often with the option of radiosurgery embedded in the analyisis (12,17,18). In this chapter, we will review and update the process of decision analysis for asymptomatic AVMs. Consideration is given to the most recent publications available about the natural history of these lesions and the risks and benefits of the different modalities used to treat them. DECISION ANALYSIS AND MARKOV MODELING FOR THE TREATMENT OF ASYMPTOMATIC AVMs For a decision analysis to be applicable, it must mirror reality by accurately portraying the implications of each aspect of the decision. There are many levels of complexity in the decision to treat an asymptomatic intracranial AVM. To analyze the decision appropriately, a comprehensive model that deals with all possible outcomes and the implications of each possible treatment decision over the course of a hypothetical cohort of patients’ lives must be constructed (4–8,10). We used a computer-supported Markov model to examine the clinical outcomes of patients with AVMs that were managed by 1 of 3 treatment strategies (TreeAge Software Inc., Williamstown, MA). Such a clinical treatment option analysis can be presented in the form of a simple decision tree. Each decision node allows the clinician to compare the accepted prognosis for the patient if given treatment 1 versus treatments 2 or 3. The predicted outcome or resulting health status of the patient translates into ‘‘the utility’’ of each option. Clinical decisions with long-term implications for a patient’s health status and survival require models that allow the values of utility and probability to vary throughout the life span of the patient. Conventional decision trees must become very large, repetitive, and essentially unreadable to achieve such a dynamic quality. A Markov analysis, presented in the form of a decision tree, gracefully incorporates a clinical decision process in which the variables change with time (3). Since it is dynamic, the Markov model allows the clinician or decision-maker to examine the events within each treatment strategy that may occur over the patient’s entire life span. A patient will or will not move between a set of mutually exclusive health states during each year of life. Each health state, one of which is death, is associated with an ‘‘incremental utility’’ that enumerates the relative value of being in that state versus another. A transition from one state to another is associated with the ‘‘transition probabilities’’ of clinical events each year and is dependent on the choice of treatment, health state of the patient in the previous year, and the
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patient’s age. The utility of each treatment option is calculated using probabilities of finite outcomes such as death and probabilities of less finite outcomes such as multiple levels of health status. The tree can thus reflect how short-term outcomes directly play a role in the utility of future events that may occur for the same patient. If the short-term event is death, the patient will obviously remain dead in the future. However, if the short-term event is motor function loss, the future is different from that of a patient who suffered no functional loss. This portion of the model is referred to as discounting. In short, this term suggests that the value of a year in the future is not as great as the next year. This can be because of the risk of a change in quality that may occur at some time, or simply because the next year must be lived before any year in the future can be. The total incremental utility generated by the cohort for a given year is found by multiplying the utility value for each state by the fraction of the cohort within that state and then summing across all of the states. For our purposes, this value is in units of quality-adjusted life years (QALYs). If a monetary value is used in addition, it makes the model a cost-benefit analysis as well. This application becomes particularly important when the decision path that provides the greatest number of QALYs is also more costly. The cumulative utility is defined as the running sum of the total incremental utility generated during each year. As the years from the decision increase, more of the patients will transition to death, due to both the adverse effects of treatment and the accepted natural life expectancy of the cohort. Therefore, fewer individuals will contribute to the cumulative utility. Ultimately, the model will terminate when all patients transition to death. The advantage of decision analysis is its ability to provide information for decision making about relatively rare lesions, such as AVMs, where recorded experience is minimal. Where the data to answer a given question are relatively sparse, a decision analysis model substitutes for actual clinical experience. Relevant data can then be collected and plugged into the model that has been constructed to encompass all possible outcomes. Hypothetical cohorts of patients can be run through the model, and the group that acquires the most QALYs represents the best strategy. These conclusions can then be scrutinized through sensitivity testing. This aspect of decision analysis allows the examination of a broad range of scenarios. By trying out a range of values for each variable entered, sensitivity testing identifies the factors most influential on the model as well as the cross-over points where different strategies become more favorable. The underlying disadvantage of decision analysis is that its use is limited to strategies with published results and observed percentages reported in the literature. It does not allow for the testing of novel hypotheses since there would be no data available to build the model. In addition, the accuracy of the results depends on the accuracy of published reports of comparable situations and the accuracy of assumptions made within the model. In summary, for the dynamic clinical decisions involved in the treatment of AVMs, the decision analysis model provides a practical way to analyze how a hypothetical cohort would fare with a given treatment strategy. The Markov aspect of the model adds the method by which the cohort progresses through a decision analysis tree as well as an intrinsic predefined natural life expectancy. The computer-supported model is able to incorporate both the immediate tradeoffs among multiple therapeutic options as well as the resulting likelihood of events and tradeoffs that might occur in the future. The preferred treatment strategy is identified as the group that acquires the most QALYs. Assumptions and Definitions in Modeling The first step in decision analysis is to define outcomes and make underlying assumptions. Asymptomatic must be defined. For the purposes of this analysis, the definition is simply that the patient does not have symptoms resulting from the lesion at the time of evaluation. It is the unusual patient who presents for evaluation because of a completely incidental finding. Often patients have an inconsequential hemorrhage, seizures, headaches, or progressive neurological deficits that lead to a study diagnosing the lesion. The reasons for presentation are not taken into consideration here, and thus a patient who may have had symptoms in the past leading to their presentation can still be considered in the analysis if they are not affected by the symptoms at the time of analysis. In this way, all patients enter into the model with an equal quality of life. Cure is defined as an angiographically negative lesion, whether accomplished by surgery or stereotactic radiosurgery (SRS), and is considered to provide
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complete protection against future hemorrhage. Any hemorrhage is considered to cause at least a minor neurological deficit. Because all patients are equally exposed to the risk of an angiogram to diagnose their lesions, this risk is not factored into the model. Natural life expectancy does need to be factored into the model, so that all patients will eventually move to the dead state even if they have no untoward events from their lesions. The patients within the analysis then must also start from a specific age so that they have equivalent life expectancies. For the purposes of this model the starting age was 35 because that was the average age of patients in all the natural history studies used. The probabilities of each individual outcome or health state for each intervention must be established from the literature. This information is used to assign the appropriate probabilities and quality values of each decision path. It follows then that the possible therapeutic modalities must be established at the beginning of the analysis. Although this is the strength of the methodology, it also presents a limitation. Only strategies that have previously been studied and reported in the literature can be applied in the model. Thus, an innovative technique or strategy that has been minimally reported or unreported cannot be addressed by decision analysis. For the purposes of this study, the therapeutic options considered were the treatment modalities with adequate data available for comparison. Specifically, these were surgery, SRS, and observation, which is equivalent to the natural history of the disease. Embolization was not reported in the literature as an effective treatment on its own and therefore was not used as a separate arm in the model. It was, however, used as an adjunct to large AVMs in the model. The possible health states are considered to be death, major neurological deficit, minor neurological deficit, and well. These states must also be defined before the model is developed so that they can be used to screen the various studies that serve as inputs to the model. The numerical value of their quality must also be assigned. The definition of death is self-evident and its value of 0 intuitive. A major neurological deficit is defined as any deficit that permanently decreases the ability of patients to lead their previous lives. This state encompasses a broad spectrum of possibilities including patients so debilitated that they require nursing care in a long-term facility as well as those who might have a hemiplegia and yet remain employable. Nonetheless, this definition represents an easily identifiable difference in health states, and the value that studies have placed on it is 0.39 (19). A minor neurological deficit is any transient deficit or a permanent deficit that does not interfere with a patient leading a normal life. Well is defined as no neurological deficit or event. The value of 0.95 is assigned for both well and minor neurological deficit. This value was chosen to represent that living with a lesion is a less than perfect quality of life. There is no difference in value for minor neurological deficit and well because in either case the patient is leading a normal life. Minor neurological deficits are treated in the model with a disutility of three months instead of a reduction in quality. A disutility is a subtraction of the time that is lost because of a given event. For example, if a patient were to have a hemorrhage from an AVM and suffer transient deficit, the time that it takes to have the event diagnosed, to be treated, and to recover from it would be subtracted from the overall total of QALYs. Although these values may seem arbitrary, they have a methodological basis (19). The next step is to define the possible results of a given treatment. Here again, the literature provides an accurate source for the possible outcomes, which vary for each treatment strategy given the specific risks and benefits. For observation, the benefit is no risk of an intervention. The risk of intervention could include a perioperative morbidity or mortality risk as well as a neurological injury from radiation delivered as part of SRS. There is no protection from the risk of the lesion bleeding, however, which is the downside to this strategy. For surgery, a risk is associated with doing the procedure. A small percentage of patients are expected to suffer from a perioperative neurological deficit, either major or minor, and some will die from the procedure. The cure attainable with a complete surgical resection justifies the perioperative risk and is the benefit of this treatment option. SRS is a more complicated option to address. For all patients, there is thought to be a lower perioperative risk since SRS is a one-time outpatient procedure. The benefit of SRS is that it provides complete protection from risk of hemorrhage, but only in a percentage of patients. The mechanism behind its effectiveness involves the gradual proliferation of the endothelium in the abnormal vessels receiving the radiation dose. Until the proliferation results in complete obliteration of the lesion, however, the risk remains at the natural history
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level with the possibility of having a hemorrhage or not, and for those who do hemorrhage, the possibilities of having a neurological deficit (major or minor) or dying from the event. These possibilities raise the issue of the time required for complete obliteration of the lesion as well as the overall percentage of patients cured at the end of this period of time, both of which need to be established and incorporated into the model. Values for this list of outcome variables in the decision to treat an asymptomatic AVM can be obtained from the literature. Nevertheless, error exists in any measurement, and it is even greater in a meta-analysis of this type because one paper never completely recapitulates another. At this point another important strength of the decision analysis technique comes into play, specifically sensitivity testing. The model will provide an answer to the question put to it once it has been completed, i.e., the decision tree constructed, the percentages and quality values entered, and the overall number of QALYs for each outcome calculated. Next, each individual variable can be varied within an acceptable range to determine the effect of that variable on the overall results of the model. This test verifies the accuracy of the model, identifies the variables that have a larger or smaller effect on the overall results, and finally identifies the crossover points at which the favorable strategy changes from one to another. This tool also provides a technique to circumvent the dependence of the methodology on the accuracy of the previous studies, the underlying assumptions, and the model itself. DATA COLLECTION Natural History The available literature was reviewed extensively to identify studies of the natural history of AVMs that would fit into the breakdown of the four outcomes that we had established at the outset. The majority of natural history studies report outcomes in much this way, and thus the collection shown in Table 1 represents a good cross-section of the available studies. Slight adjustments to the numerical data were made to enable comparison between studies and to make all denominators equivalent. Occasionally, a study added more levels of neurological deficits and therefore needed interpretation to break the outcomes down into the established categories for the model. Another area where an adjustment was needed came under the minor neurological deficit category. According to the rules of the model, any hemorrhage resulted in at least a minor neurological deficit. In some studies, a hemorrhage that resulted in no deficit was not counted among the minor deficits. These numbers were adjusted upward accordingly, with the higher numbers listed parenthetically in the table. Finally, the total number of minor neurological morbidities was re-adjusted down, so that the entire number of morbidities and mortalities was equal to the total number of hemorrhages. This final change was made to make the model run more smoothly, and sensitivity analysis confirmed that it made no difference in the final output of the model. Surgical Treatment A review of the literature readily showed that an appropriate method for dividing the lesions was according to Spetzler–Martin Grade. Although this grading system was developed as a prognostic tool for surgical outcome only, most of the surgical studies divided the treated lesions this way, as did many of the radiosurgical studies. Since the results were vastly Table 1 Natural History Data Collection Study (Ref. No.) Forster et al. (1972) (20) Graf et al. (1983) (21) Fults & Kelly (1984) (22) Crawford et al. (1986) (23) Brown et al. (1988) (24) Itoyama et al. (1989) (25) Ondra et al. (1990) (26) Totals Percent per year
Patients
Patient Years
Hemorrhage
Death
Major Morbidity
Minor Morbidity
35 191 131 217 168 50 160 1089
420 542 722 2257 1378 670 3792 9781
10 63 60 77 31 14 147 402 4.11
6 17 20 31 9 5 37 125 1.28
4 31 8 6 18 4 62 133 1.36
3 84 24 (32) 17 (40) 40 5 (48) (252) 2.58 (1.47)
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Table 2 Surgical Morbidity and Mortality, Spetzler–Martin Grades I–III Study (Ref. No.) Spetzler & Martin (1986) (27) Heros et al. (1990) (28) Sisti et al. (1993) (29) Spetzler & Hamilton (1994) (30) Pikus & Harbaugh (1998) (31) Totals Percent
Patients
Death
Major Morbidity
Minor Morbidity
69 91 67 76 54 357
0 1 0 1 0 2 0.56
1 0 8 1 0 10 2.80
4 10 24 8 1 47 13.2
different for Grades I–III compared to Grades IV and V, different models with different baseline rates were constructed for these two situations. Once again, the studies used had to easily conform to the overall model in terms of outcomes. Some slight interpretation was required for some studies to make their outcomes analogous and comparable. However, it is clear from Tables 2 and 3 that there was relatively little variation among the studies examined. The numbers obtained represented a one-time risk of surgery and differed from the lifetime risk of hemorrhage and its resultant outcomes used for the natural history arm of the model. Embolization, shown in Table 4, was considered to be an additional one-time risk that patients with Grade IV or V lesions were exposed to as a presumed adjunct to their treatment. Stereotactic Radiosurgery SRS is newer than surgery, and, as a result, much of the available literature concerns understanding the treatment parameters as well as giving overall outcomes. This makes defining the clinical course more difficult. The available data may not adequately mirror the reality of the treatment. This concern is the weakness of this type of model. Fortunately, sensitivity-testing ultimately proved that it did not make a difference in the decision analysis. The data for radiosurgery were taken from studies primarily of small AVMs. Consequently, comparison between SRS and surgery was carried out only for Spetzler–Martin Grade I to III lesions. Table 5 shows the morbidity and mortality during the period between the initial treatment and the ultimate angiographic obliteration, referred to here as the latent period. These numbers are better than the risk seen with natural history, which probably represents a percentage of the lesions proceeding to obliteration, and therefore a zero risk, during this latent period of observation. Since this information was documented for a large number of patients and patient-years, these risk figures were used in the model. Tables 6 and 7 focus on two troubling, unanswered questions about SRS treatment: how long is the latent period, and what percent of lesions are angiographically obliterated at the end of this period? It would certainly seem that these numbers would be important to the decision-making process, although sensitivity analysis could also answer the questions. It was clear from the data that very few lesions were obliterated at one year. Most studies, indeed, reported two-year obliteration rates. Since this time period was most commonly reported, it was used in the model. Many who treat these lesions think that three-year obliteration rates are even better, but no data are available to test this hypothesis in the model. More difficult to ascertain is just how many lesions are obliterated at the two-year interval. The data in the studies are usually presented as the number of patients with negative angiograms out of the total number of patients with follow-up angiograms. The problem is that many of the patients treated do not have follow-up angiograms. The stated reason is usually Table 3 Surgical Morbidity and Mortality, Spetzler–Martin Grades IV and V Study (Ref. No.) Spetzler & Martin (1986) (27) Heros et al. (1990) (28) Spetzler & Hamilton (1994) (30) Pikus & Harbaugh (1998) (31) Totals Percent
Patients
Death
Major Morbidity
Minor Morbidity
31 62 44 18 155
0 2 0 0 2 1.29
3 3 3 2 9 5.81
6 16 13 3 40 25.81
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Table 4 Embolization Morbidity and Mortality Study (Ref. No.) Pasqualin et al. (1991) (32) Vinuela et al. (1991) (33) Totals Percent per year
Patients
Mean Years of Follow-Up
49 101 150
5.2 1.94 7.1
Hemorrhage
Death
Major Morbidity
Minor Morbidity
0 1 1 14.1
0 2 2 28.1
5 11 16 225
that they have another study, such as magnetic resonance imaging, which suggests obliteration, or because they live too far from the referral center where they were treated. The true proportion of patients with negative angiograms probably lies some where between 77.4% and 5.2%. Nevertheless, 77.4% was used for the model in order to favor SRS because of its non-invasive nature. The problem was also addressed with sensitivity analysis. The Decision Analysis Tree After this extensive review of the literature, the model that had been roughly approximated could be constructed with the confidence of specific percentages that could be applied to encompass all possible outcomes. A simplified version of the model is shown in Figure 1. It became apparent from the literature that outcomes worsened when the lesions reached a higher Spetzler–Martin grade. Moreover, the treatment stategies would be different at higher grades. Since adequate data had been collected in a useful format, the different grades could be stratified into two groups and decision trees could be constructed for each. For patients with Spetzler–Martin Grades I to III AVMs, the possible treatments were observation, surgery, and SRS. Patients undergoing observation were exposed to the risk of life expectancy as well as the risk of hemorrhage from their lesion at the rates reported in the literature for each cycle (year) of the model. Those who had hemorrhages were further broken down into death, major neurological deficit, and minor neurological deficit at the reported rates. The appropriate decreases in quality of life were applied, QALYs were totaled for the cycle, and the discount rate was applied. At the end of each yearly cycle, patients would be re-exposed to these risks for the next cycle. The model continued in this fashion, accumulating QALYs until there were no patients left in the cohort. For patients undergoing surgery, the possible outcomes were death, major neurological deficit, minor neurological deficit, or well. The risk that patients would be exposed to was a one-time event (surgery), after which the model assumed no further risk from the lesion. If the patients were well or suffered only a minor neurological deficit, they were exposed only to life expectancy risks in the remainder of the model and continued to acquire QALYs through each yearly cycle. If a major neurological deficit resulted, the life expectancy was lower and the quality was adjusted down. The patients who died could contribute no QALYs to the total. For the group treated with SRS, a lag period of two years was imposed. During this time they would be exposed to life expectancy risks as well as a risk of hemorrhage from their lesion that was slightly lower than the risk from natural history. This risk corresponded to the lower risk of hemorrhage reported in the literature for this period of time and almost certainly mirrors the fact that some AVMs disappear more Table 5 Radiosurgical Morbidity and Mortality Study (Ref. No.) Betti et al. (1989) (34) Colombo et al. (1989) (35) Lunsford (1991) (36) Friedman & Bova (1992) (37) Steiner et al. (1992) (38) Pollock et al. (1994) (39) Karlsson et al. (1996) (40) Total Percent per year
Patients
Patient Years
66 97 227 80 228 65 1604 2367
80 138 265 125 590 190 2340 3728
Hemorrhage
Death
Major Morbidity
Minor Morbidity
5 4 10 2 9 5 49 84 2.25
4 0 2 0 6 2 14 28 0.75
2 1 10 2 12 1 10 38 1.02
0 2 (3) 7 6 16 3 25 60 1.61
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Table 6 Radiosurgical Arteriovenous Malformation (AVM) Obliteration at One Year (by Angiography)
Study (Ref. No.) Betti et al. (1989) (34) Colombo et al. (1989) (35) Lunsford (1991) (36) Friedman & Bova (1992) (37) Steiner et al. (1992) (38) Pollock et al. (1994) (39) Karlsson et al. (1996) (40) Total
Patients Total 66 97 227 80 228 65 1604 2367
No. of Patients with Angiogram at 1 Year
No. with 100% Obliteration at 1 Year
50 17 41
26 13 16
227 335
84 139
% with 100% Obliteration at 1 Year 52 76 10
37 41.5
% of Total Patients 27 6 10
5 5.9
quickly than others. At the end of two years, 77.4% of the group were considered to be cured and were exposed only to life expectancy risk for the remainder of the model. The other 22.6% were exposed to the natural history risk in addition to life expectancy for the remainder of the model. QALYs were similarly totaled. Lesions of Spetzler–Martin Grades IV and V required a slightly different model. The treatment options were observation and surgery. SRS is not usually performed on large AVMs because of the large radiation dose required to treat these lesions and because the technique is simply less effective. Very few results of treatment have been reported for AVMs of this size. Since Spetzler–Martin Grades IV and V are large lesions by definition, SRS was not considered to be part of the treatment alternatives in the model. The other difference in the model relates to the strategy of treatment. Lesions of this size would likely be embolized before surgery, and therefore the risk of embolization would have to be included with the risk of surgery. Otherwise, the model proceeded in the same manner as did the Spetzler–Martin Grade I–III model. Preferred Strategies For the Spetzler–Martin Grade I to III lesions, the surgical treatment group acquired 21.53 QALYs over the course of the model. This result was striking in comparison to the 16.97 and 16.40 QALYs acquired by the SRS and observation groups, respectively. In the Spetzler– Martin Grade IV and V lesions, the surgical group acquired 20.18 QALYs, while the observation group acquired 16.20 QALYs. Again, this result suggests a strong preference for surgical treatment. SENSITIVITY ANALYSIS To test the accuracy of these results, the model was subjected to sensitivity analysis. The concept behind this process is to vary the individual inputs to the model within an appropriately acceptable range. As the input is varied, there are two possible outcomes: the preferred strategy may change, or it may stay the same. If the preferred strategy does not change while an input is varied, then that input is relatively unimportant to the overall decision making process. Conversely, if the preferred strategy does change, then the value of the input at which the Table 7 Radiosurgical Arteriovenous Malformation (AVM) Obliteration at 2 Years (by Angiography)
Study (Ref. No.) Betti et al. (1989) (34) Colombo et al. (1989) (35) Lunsford et al. (1991) (36) Friedman & Bova (1992) (37) Steiner et al. (1992) (38) Pollock et al. (1994) (39) Karlsson et al. (1996) (40) Total
Patients Total 66 97 227 80 228 65 1604 2367
No. of Patients with Angiogram at 2 Years
No. with 100% Obliteration at 2 Years
40 20 46 21
27 15 37 17
32
27
159
123
% with 100% Obliteration at 2 Years 67 75 80 81 81 84 77.4
% of Total 41 15 16 21 42 5.2
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Decision Analysis for Asymptomatic Lesions Well Minor Deficit Surgery Major Deficit Death Well Minor Deficit Asymptomatic AVM
Radiosurgery
Natural history x2 years Major Deficit Death Well Minor Deficit
Observation Hemorrhage
Major Deficit Death
Figure 1 Simplified decision tree for Spetzler–Martin Grade I to III AVMs. Abbreviation: AVM, arteriovenous malformation.
strategy becomes less favorable can be identified. Such a cross-over point can represent the goal that an unpreferred treatment needs to attain to become a favorable outcome or the morbidity at which a preferred treatment is no longer acceptable. For the small AVM decision analysis, a preliminary sensitivity analysis was done by varying each input between the highest and lowest points reported in the literature. The only input factors found able to change the overall outcome were morbidity and mortality in the perioperative period and during the latent period of SRS treatment. The reasons are apparent. Only perioperative morbidity and mortality yield a significant decrease in the number of QALYs accumulated by the surgical cohort. Minor neurological deficits represent a small decrease in quality of life and do not affect the rate at which QALYs are acquired by this cohort. In the case of morbidity and mortality during the SRS lag period, Figure 2 gives the best demonstration of the effect seen. This figure represents the status of the patients in the various hypothetical cohorts after the first year of the model. At this point patients in the surgical arm have already been exposed to all the risk that they will encounter from their lesions. All the SRS group, meanwhile, are completely within the latent period and considered to be untreated and exposed to risk. At this point the SRS group is already behind the surgical Well + Minor - 98.88%
Surgery
Major Neurologic Deficit - 0.56%
Death - 0.56% AVM Well + Minor - 98.23%
Radiosurgery
Major Neurologic Deficit - 1.02%
Death - 0.75%
Figure 2 Simplified decision tree for Spetzler–Martin Grade I to III AVMs after one cycle (year). Abbreviation: AVM, arteriovenous malformation.
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8 7 6
Lower Limit
5
Study Rate
4
Upper Limit
3
Crossover Rate
2 1 0 Radiosurgery (during latent period)
Microsurgery (perioperatively)
Figure 3 Sensitivity analysis for mortality and major neurological morbidity.
group in overall number of QALYs acquired. From this point on, both groups continue to be exposed to the risks of life expectancy. However, patients in the surgical group are exposed to no further risk from their lesions, while those in the SRS group are exposed. Under these circumstances it is clear that the SRS group will never be able to acquire the same number of QALYs as the surgical group. If the rate of hemorrhage could be lowered in this group to 0.7% per year, the strategy would cross over to being favorable. However, Figure 3 demonstrates that this possibility represents a greater than 50% reduction in the lowest hemorrhage rate reported in the literature. For SRS treatment to attain this rate of hemorrhage, unacceptably high radiation doses would need to be used—likely, in fact, to induce neurological deficits alone. A corollary is that the overall cure rate for SRS has no effect on the final decision since the surgical group is ahead before this even comes into play. The sensitivity analysis also demonstrates the bias of the study. The study rates between the high and low rates reported in the literature are shown in Figure 3. The study rate used for microsurgery is the highest morbidity and mortality rate reported in the literature, while the study rate for SRS morbidity and mortality is close to the lowest rate reported. These choices effectively bias the study toward SRS. Other factors that could be treated with sensitivity analysis include the natural history stroke rate, the age of the patients entering the study, the values assigned to various outcome states, and the discount rate. The first two might change the analysis in terms of the decision between surgery and observation, but would be unlikely to affect the surgery versus SRS decision. Quality values and discount rates largely function to decrease the difference between two strategies over a long period of time and as such would be unlikely to change the result, which in the case of small AVMs is actually determined after a single cycle (year) of the model. Other considerations that are not dealt with here are the medical co-morbidities and the possible role of SRS for lesions in eloquent locations. These situations represent times when a radiosurgical approach might still be favored. These conditions are not reported on extensively in the literature and are, therefore, difficult to treat with decision analysis. CONCLUSION We have reviewed decision analysis as a technique and presented portions of a new decision analysis. We have attempted to illustrate the usefulness of this approach in considering the treatment options for a given patient with an asymptomatic AVM. In considering the situation, we use the most current natural history data and employ the Spetzler–Martin grading system for the first time in an attempt to more accurately depict the clinical scenario. The future direction for this tool will be to make the entire process more accessible to the individual surgeon. Ideally, surgeons—both microsurgical and radiosurgical—should be able to input the morbidity and mortality rates of the procedures in their own hands, rather than relying on a standard set by the leaders in the field, whose complication rates might be
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expected to be lower given their experience. Furthermore, a grading system designed to predict the morbidity associated with the individual lesion rather than the morbidity associated with a specific treatment of that lesion would be more useful in terms of making appropriate clinical decisions in individualized circumstances. Finally, the ultimate application of this tool would be to enter an individual patient’s data. With this type of automation, a decision analysis addressing the appropriate risks could be tailored for the actual clinical situation at hand. Although not a substitute for the surgeon’s overall clinical judgment or the patient’s wishes, such an unbiased, mathematically rigorous, and informative approach would certainly aid in counseling patients with dangerous lesions such as AVMs. REFERENCES 1. Cronenwett JL, Birkmeyer JD, Nackman GB, et al. Cost–effectiveness of carotid endarterectomy in asymptomatic patients. J Vasc Surg 1997; 25:298–311. 2. Birkmeyer JD, Birkmeyer NO. Decision analysis in surgery. Surgery 1996; 120:7–15. 3. Beck JR, Pauker SG. The Markov process in medical prognosis. Med Decis Making 1983; 3:419–458. 4. Detsky AS, Naglie G, Krahn MD, Naimark D, Redelmeier DA. Primer on medical decision analysis: Part 1-Getting started. Med Decis Making 1997; 17:123–125. 5. Detsky AS, Naglie G, Krahn MD, Redelmeier DA, Naimark D. Primer on medical decision analysis: Part 2-Building a tree. Med Decis Making 1997; 17:126–135. 6. Krahn MD, Naglie G, Naimark D, Redelmeier DA, Detsky AS. Primer on medical decision analysis: Part 4-Analyzing the model and interpreting the results. Med Decis Making 1997; 17:142–151. 7. Naglie G, Krahn MD, Naimark D, Redelmeier DA, Detsky AS. Primer on medical decision analysis: Part 3-Estimating probabilities and utilities. Med Decis Making 1997; 17:136–141. 8. Naimark D, Krahn MD, Naglie G, Redelmeier DA, Detsky AS. Primer on medical decision analysis: Part 5-Working with Markov processes. Med Decis Making 1997; 17:152–159. 9. Pauker SG, Kassirer JP. Decision analysis. N Engl J Med 1987; 316:250–258. 10. Sonnenberg FA, Beck JR. Markov models in medical decision making: a practical guide. Med Decis Making 1993; 13:322–338. 11. Koprowski CD, Longstreth WT Jr., Cebul RD. Clinical neuroepidemiology. III. Decisions. Arch Neurol 1989; 46:223–229. 12. Fisher WS III. Therapy of AVMs: a decision analysis. Clin Neurosurg 1995; 42:294–312. 13. Fisher WS III. Decision analysis: a tool of the future: an application to unruptured arteriovenous malformations. Neurosurgery 1989; 24:129–134. 14. Elstein AS, Balla JI, Iansek R. Application of decision analysis to unruptured arteriovenous malformations. Neurosurgery 1990; 26:545–546. 15. Iansek R, Elstein AS, Balla JI. Application of decision analysis to management of cerebral arteriovenous malformations. Lancet 1983; 1:1132–1135. 16. Hudgins WR. Decision analysis of the treatment of AVMs with radiosurgery. Stereotact Funct Neurosurg 1993; 61(suppl):11–19. 17. Nussbaum ES, Heros RC, Camarata PJ. Surgical treatment of intracranial arteriovenous malformations with an analysis of cost-effectiveness. Clinical Neurosurgery 1994; 42:348–369. 18. Porter PJ, Shin AY, Detsky AS, Lefaive L, Wallace MC. Surgery versus stereotactic radiosurgery for small, operable cerebral arteriovenous malformations: a clinical and cost comparison. Neurosurgery 1997; 41:757–766. 19. Russell LB, Gold MR, Siegel JE, Daniels N, Weinstein MC. The role of cost-effectiveness analysis in health and medicine. Panel on cost-effectiveness in health and medicine. JAMA 1996; 276:1172–1177. 20. Forster DM, Steiner L, Hakanson S. Arteriovenous malformations of the brain. A long-term clinical study. J Neurosurg 1983; 58:331–327. 21. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983; 58:321–327. 22. Fults D, Kelly DL Jr. Natural history of arteriovenous malformations of the brain: a clinical study. Neurosurgery 1984; 15:658–662. 23. Crawford PM, West CR, Chadwick DW, Shaw MD. Arteriovenous malformations of the brain: natural history in unoperated patients. J Neurol Neurosurg Psychiatry 1986; 49:1–10. 24. Brown RD Jr., Wiebers DO, Forbes G, et al. The natural history of unruptured intracranial arteriovenous malformations. J Neurosurg 1988; 68:352–357. 25. Itoyama Y, Uemura S, Ushio Y, et al. Natural course of unoperated intracranial arteriovenous malformations: study of 50 cases. J Neurosurg 1989; 71:805–809. 26. Ondra SL, Troupp H, George ED, Schwab K. The natural history of symptomatic arteriovenous malformations of the brain: a 24–year follow-up assessment. J Neurosurg 1990; 73:387–391. 27. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483.
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28. Heros RC, Korosue K, Diebold PM. Surgical excision of cerebral arteriovenous malformations: late results. Neurosurgery 1990; 26:570–578. 29. Sisti MB, Kader A, Stein BM. Microsurgery for 67 intracranial arteriovenous malformations less than 3 cm in diameter. J Neurosurg 1993; 79:653–660. 30. Hamilton MG, Spetzler RF. The prospective application of a grading system for arteriovenous malformations. Neurosurgery 1994; 34:2–7. 31. Pikus HJ, Beach ML, Harbaugh RE. Microsurgical treatment of arteriovenous malformations: analysis and comparison with stereotactic radiosurgery. J Neurosurg 1998; 88:641–646. 32. Pasqualin A, Scienza R, Cioffi F, et al. Treatment of cerebral arteriovenous malformations with a combination of preoperative embolization and surgery. Neurosurgery 1991; 29:358–368. 33. Vinuela F, Dion JE, Duckwiler G, et al. Combined endovascular embolization and surgery in the management of cerebral arteriovenous malformations: experience with 101 cases. J Neurosurg 1991; 75:856–864. 34. Betti OO, Munari C, Rosler R. Stereotactic radiosurgery with the linear accelerator: treatment of arteriovenous malformations. Neurosurgery 1989; 24:311–321. 35. Colombo F, Benedetti A, Pozza F, Marchetti C, Chierego G. Linear accelerator radiosurgery of cerebral arteriovenous malformations. Neurosurgery 1989; 24:833–840. 36. Lunsford LD, Kondziolka D, Flickinger JC, et al. Stereotactic radiosurgery for arteriovenous malformations of the brain. J Neurosurg 1991; 75:512–524. 37. Friedman WA, Bova FJ. Linear accelerator radiosurgery for arteriovenous malformations. J Neurosurg 1992; 77:832–841. 38. Steiner L, Lindquist C, Adler JR, Torner JC, Alves W, Steiner M. Clinical outcome of radiosurgery for cerebral arteriovenous malformations. J Neurosurg 1992; 77:1–8. 39. Pollock BE, Lunsford LD, Kondziolka D, Maitz A, Flickinger JC. Patient outcomes after stereotactic radiosurgery for ‘‘operable’’ arteriovenous malformations. Neurosurgery 1994; 35:1–8. 40. Karlsson B, Lindquist C, Steiner L. Effect of gamma knife surgery on the risk of rupture prior to AVM obliteration. Minim Invas Neurosurg 1996; 39:21–27.
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Multimodality Therapy: Treatment Algorithms Philip E. Stieg Department of Neurological Surgery, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
Vallabh Janardhan Division of Interventional Neuroradiology, Department of Radiology, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
Howard A. Riina Departments of Neurological Surgery, Neurology, and Radiology, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
INTRODUCTION The first decision to be made in the management of brain arteriovenous malformations (AVMs) is whether or not to treat the lesion. If the cumulative lifetime risk estimate of rupture of an AVM far exceeds the immediate risks of intervention for a particular patient, treatment is indicated. For each individual patient, a specific treatment plan needs to be tailored (Fig. 1). In this chapter we discuss factors that affect decision analysis and treatment design as well as currently available treatment options. We then indicate how decision analysis proceeds for the treatment of ruptured and unruptured AVMs. Factors that play a major role in the decision analysis and in designing the treatment plan include the pathology and location of the lesion; the natural history; patient characteristics such as age, co-morbidities, and compliance; and the experience and outcomes associated with the treating physician and the institution. Each of these factors shapes the selection of the individual or multiple modalities available for the treatment of AVMs. The four treatment modalities currently available include observation, stereotactic radiosurgery, endovascular surgery, and microsurgery. Each has relative risks and benefits, which may overlap. The integration of this information affects the decision to treat and the selection of the appropriate modality or combination of modalities that leads to the best patient outcome. PATHOLOGY OF THE AVM The anatomical and pathological characteristics of brain AVMs are thoroughly described in Chapters 1 and 2. Broadly, vascular anomalies of the brain can be divided into benign proliferating and non-proliferating malformations. Although brain AVMs are characterized as non-proliferating malformations, there is a body of literature documenting their histopathological changes over time within the same patient (1–9). The role that these anatomical variations play over time in the natural history of AVMs and presentation of patients with these lesions remains unclear. Typically, brain AVMs are classified anatomically as fistulous or plexiform (Fig. 2). This gross anatomical description is not helpful in predicting symptoms related to the lesion; however, angioarchitectural features such as high mean arterial pressure in the feeding artery, intranidal aneurysms, single draining veins, central deep nidus location, deep venous drainage, small nidus size, venous reflux, and venous outflow stenosis may be associated with an increased risk for hemorrhage (10–18). In one study, angioarchitectural features that were significantly associated with an initial hemorrhage presentation were identified as the presence of venous ectasias, deep location, and the presence of a small number of draining veins (19). Thus, evaluation of a patient’s risk for a poor outcome secondary to an untreated AVM must include anatomical assessment for these specific characteristics (Table 1).
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Figure 1 Schematic representation of the treatment modalities available for the management of arteriovenous malformations (AVMs). The goal of treatment is to treat the AVM completely with the fewest complications.
LOCATION OF THE AVM The location of an AVM as it relates to functional cortex is one of the most important factors in selecting the appropriate treatment plan. The larger the size of an AVM, the more likely it is to be near or include eloquent cortex or projections to and from eloquent regions. Deep-seated AVMs in the basal ganglia, thalamus, and brainstem, as well as AVMs in eloquent cortex, are difficult to access surgically. Thus, other treatment paradigms should be considered. NATURAL HISTORY Presenting symptoms in patients with brain AVMs include headache, seizure, and focal neurologic deficits from vascular steal phenomena or hemorrhage (14,15,20,21). The most dreaded outcome is hemorrhage and its related sequelae. The annual bleeding risk in symptomatic patients is 4% with an annual mortality rate of 1% (20). Studies also indicate that 25% to 50% of patients present with seizures. The severity, frequency, and response to medical management also play a role in decision analysis. The data regarding increased hemorrhage risk after the initial bleed are inconclusive (10,14,20,22,23). The risk of spontaneous hemorrhage is also not thoroughly understood (24,25). The management of asymptomatic and symptomatic brain AVMs is somewhat obscured by a lack of understanding regarding prevalence. Most data suggest a prevalence between 0.06% and 0.11% (26,27). Long-term data collection regarding the risks for hemorrhage indicates that the majority of AVMs will bleed (4,10,14,15,20,28). However, recent data suggest
Figure 2 Anatomic classification of arteriovenous malformations. (A) Anteroposterior angiogram of fistulous form. (B) Lateral angiogram of plexiform type.
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Table 1 Angioarchitectural Characteristics of Arteriovenous Malformations Related to Risk of Hemorrhage Consistent risk factors Deep venous drainage Single draining vein Venous stenosis High mean arterial pressure in the feeding artery Inconsistent risk factors Intranidal aneurysms Small nidus Deep location Venous stasis Potential risk factors Systemic hypertension Vertebrobasilar supply Perforator supply Increasing age Smoking Pregnancy Potential protective factors Arterial stenosis Venous recruitment
that the hemorrhage risk may be lower for asymptomatic AVMs (24). In contrast to symptomatic AVMs, the hemorrhage risk for asymptomatic lesions remains less clear. Thus, the decision to treat asymptomatic AVMs is based less on epidemiology and natural history data and more on anatomical and clinical criteria. PATIENT CHARACTERISTICS The cumulative lifetime risk of hemorrhage for the patient depends on the age at the time of discovery of a brain AVM. If the annual hemorrhage risk among people with unruptured AVMs is approximately 2% to 4%, then the cumulative lifetime risk of intracranial hemorrhage in a person with an unruptured brain AVM can be predicted by the following formula (29,30): Lifetime risk ð%Þ ¼ 105 patient age in years Younger patients have a longer life expectancy and therefore a higher cumulative lifetime risk of rupture. Although older patients (age greater than 60 years) have a shorter life expectancy, they have an increased risk for hemorrhagic presentation (31). As AVMs in older patients are significantly associated with several high-risk angioarchitectural features of rupture, such as the presence of concurrent arterial aneurysms and small AVM nidus size, it is important to stratify older patients on the basis of the presence of these high-risk factors as part of the decision analysis (31). Patients with co-morbidities have a higher perioperative risk as compared to individuals without co-morbidities. Risks from general anesthesia are also increased in patients with significant co-morbidities. Therefore, it is also important to stratify patients based on their perioperative and anesthetic risks. High-risk patients might be better managed with nonsurgical treatment modalities (32). Patients undergoing radiosurgery require close follow-up, as the lesion is obliterated over time with a known latency period (33). Patients who may be poorly compliant with clinical follow-up are better candidates for definitive therapies, such as microsurgery. DIAGNOSTIC IMAGING Diagnostic modalities, such as computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and angiography, are the mainstays. However, improved image quality and new technology allow greater pre-interventional analysis. Improved image quality with CTA and MRA allows minimally invasive evaluation for angioarchitectural risk factors. Functional MRI and superselective angiography with Wada
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testing allow more precise functional analysis as the AVM approaches eloquent cortex. Noninvasive imaging using CT, CTA, MRI, and MRA combined with better computer software treatment planning programs allow for better definition and treatment of the AVM nidus with stereotactic radiosurgery. Thus, improved diagnostic imaging has helped refine treatment paradigms for patients with brain AVMs.
MANAGEMENT OPTIONS The goal for managing patients with intracranial AVMs is to achieve a quality of life free from symptoms related to the AVM. Treatment options include observation, stereotactic radiosurgery, embolization, and surgery. In the absence of prospective trials or multicenter outcomes data, physicians are often forced to create subjective treatment plans based on local experience with some guidance from the literature (32). We review the risks and benefits associated with the various management options and then present an algorithm for treatment. The algorithm takes all the variables discussed into consideration and includes a multimodality approach. Observation The decision not to treat an AVM implies that the risks associated with intervention outweigh those associated with the natural history of the lesion. Patients with a low natural history risk, such as elderly patients with asymptomatic AVMs, might elect this treatment paradigm. Conversely, elderly patients with medical co-morbidities also may be best treated with observation. Large AVMs that include eloquent cortex and are not accessible to multimodality therapy also carry a high treatment risk. Some patients may refuse therapy. Patients with headaches and seizures can have these symptoms treated medically. Endovascular Therapy The diverse patient population as well as the continuous development of more advanced catheter technologies and embolic agents provides the treating physician with varied results regarding the ‘‘cure rate’’ described after embolization (33). The range of success for achieving permanent and complete obliteration with intranidal embolization is 5% to 40% (34,35). Predictors for complete obliteration include fistulous anatomy or a single pial arterial feeding vessel (36). Obliteration is achieved most commonly in small (<3 cm) AVMs. Typically, embolization is used as an adjunct to radiosurgery or microsurgery. As an aid to radiosurgery, embolization is most effective when used to eliminate a compartment of the AVM and thereby reduce the overall volume of the lesion targeted for radiation. A permanent embolic agent such as N-butyl-cyanoacrylate must be used to treat the AVM nidus. The long-term impact of partial embolization on the hemorrhage rate from brain AVMs remains unclear (37). The described risk reduction ranges from 0% to 74%. Partial embolization as a single therapy is considered when the risk of multimodality therapy outweighs the natural history risk. In these situations, specific regions of the AVM are targeted for embolization. Targets include fistulas, intranidal aneurysms, and regions that are causing a ‘‘steal phenomenon’’ associated with a focal neurologic deficit. The use of embolization in the treatment of Spetzler–Martin Grade I–II AVMs is debatable (Chapter 6). Typically, these lesions are removed microsurgically. Factors that lead to pre-microsurgical embolization in this group of patients include the possibility of cure, a low risk of morbidity, and proximity of the AVM to eloquent cortex. Our personal experience has been very favorable with this approach. Stereotactic Radiosurgery The application and future directions of stereotactic radiosurgery in the treatment of AVMs are thoroughly reviewed in Chapters 13, 31, and 33. Radiosurgery-based grading systems have been proposed; factors associated with successful obliteration have been described; predictive factors for obliteration have been outlined; differing views on hemorrhage risk during
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Figure 3 Integration of the Spetzler–Martin (S–M) scale and radiosurgical volume. Closed boxes meet stereotactic radiosurgical criteria on the basis of volume. Hatched boxes may meet stereotactic radiosurgical criteria if the volume is appropriate. No box means the patient does not meet stereotactic radiosurgical volume criteria.
the latency period and after radiosurgery have been presented; and postradiosurgery injury expression scores have been described (33,38–41). In summary, the ideal candidate for stereotactic radiosurgery is a younger patient with a small volume (10 cm3), hemispheric AVM with a small number of draining veins. This same population carries a low surgical risk as well. The Spetzler–Martin grading scale is not a predictor for successful radiosurgery but must be compared and integrated with the radiosurgical data when creating a treatment paradigm for a specific patient. The assumption in this type of integration is that AVM location is the key factor in surgical series and AVM volume is the key factor in radiosurgical series (Fig. 3). Given the low surgical morbidity and mortality rates associated with Spetzler–Martin Grade I–III AVMs and the 10% to 20% possibility that stereotactic radiosurgery will not lead to AVM obliteration, microsurgical removal is usually recommended for these patients. The location and volume issue needs to be evaluated closely. Many patients whose AVMs are deemed inappropriate for surgery because of location (basal ganglia, thalamus, and brainstem) undergo stereotactic radiosurgery. The volume and radiation dosing constraints in these regions are not insignificant (42,43). These constraints result in low obliteration rates and morbidity. In these complex cases multimodality therapy must be employed (44–48).
Microsurgery In general, small (10 cm3), lobar AVMs located in non-eloquent regions can be microsurgically removed with excellent results. The management of large, critically located AVMs remains poorly defined. Staged resections and combinations of therapy have provided limited success (49–52). The principles that guide surgical management of AVMs are discussed in Chapters 11 and 29. Operative experience plays a crucial role during the decision analysis in choosing the appropriate treatment modality or combination of modalities. Surgeons must be aware of their personal and institutional outcomes for the treatment of AVMs, as these statistics may vary from reported outcomes in large tertiary care hospitals. In addition, the data from large centers are obfuscated by inclusion biases, retrospective analysis, and lack of independent neurologic evaluation (53–57). Deep AVMs are not included in large numbers in these studies, and in general it is recommended that they be treated by other means (58–60).
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Unrupted brain AVM SM Grade 1-3 Location (Other) Age ≥ 60
Age < 60
Embo + XRT
Low peri-op risk Low anesthetic risk
Embo + Surg
Conservative
Embo + XRT
High peri-op risk High anesthetic risk
Angioarchitecture Low risk for rupture Conservative
Location (Deep/Eloquent)
SM Grade 4-5
Angioarchitecture High risk for rupture
Embo + XRT
Figure 4 Schematic representation of the decision analysis involved in the management of unruptured AVMs. Abbrevations: AVMs, arteriovenous malformations; Embo, embolization; XRT, stereotactic radiosurgery; Surg, surgery; SM, Spetzler–Martin.
DECISION ANALYSIS FOR THE MANAGEMENT OF UNRUPTURED AVMs The decision analysis algorithm used at our institution for the management of unruptured AVMs is summarized in Figure 4. Patients are initially stratified on the basis of their Spetzler– Martin grades. In patients with Spetzler–Martin Grades I–III AVMs, the location of the lesion is the next factor to address. Deep-seated AVMs located in the basal ganglia, thalamus, and brainstem, as well as AVMs located in the eloquent cortex are difficult lesions to approach surgically. If unruptured AVMs are in these locations, then presurgical embolization followed by radiosurgery is the preferred treatment. For patients with AVMs in other locations, age becomes the next consideration. Younger patients have a higher cumulative lifetime risk, and therefore presurgical embolization followed by surgery is the preferred treatment. Older patients have a lower cumulative lifetime risk of rupture. In older patients for whom the operative and anesthetic risks are low, presurgical embolization followed by surgery is recommended. In older patients with high operative and anesthetic risks, the angioarchitecture of the AVM comes into play. If this group of patients has any high-risk angioarchitectural features for rupture, then we recommend presurgical embolization followed by radiosurgery. If these patients do not have any high-risk angioarchitectural features of rupture, then it is reasonable to manage them conservatively. Patients with Spetzler–Martin Grades IV and V AVMs have poor surgical outcomes, and thus conservative management is recommended.
DECISION ANALYSIS FOR THE MANAGEMENT OF RUPTURED AVMs The decision analysis algorithm used at our institution for the management of ruptured AVMs is summarized in Figure 5. Patients are initially stratified on the basis of their Spetzler–Martin grades. In patients with Spetzler–Martin Grades I–III AVMs, the location of the lesion is the next factor to address. Deep-seated AVMs located in the basal ganglia, thalamus, and brainstem, as well as AVMs located in the eloquent cortex, are difficult lesions to approach surgically. If ruptured AVMs are in these locations, then presurgical embolization followed by radiosurgery is the preferred treatment. For patients with AVMs in other locations, presurgical embolization followed by surgery is the preferred treatment. For patients with Spetzler–Martin Grades IV and V AVMs, palliative embolization of the AVM is the preferred initial treatment to decrease the immediate risk of rupture by treatment of the high-risk angioarchitectural features. If the AVMs are located in the basal ganglia, thalamus, and brainstem, or in the eloquent cortex, then further presurgical embolization followed by radiosurgery is recommended. If the AVMs are in other locations, then it is important to stratify the patients based on their operative and anesthetic risks. In patients with low operative and anesthetic risk, presurgical embolization followed by surgery is recommended. In patients with high operative or anesthetic risk, presurgical embolization followed by radiosurgery is recommended.
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Figure 5 Schematic representation of the decision analysis involved in the management of ruptured brain arteriovenous malformations. Abbrevations: Embo, embolization; XRT, stereotactic radiosurgery; Surg, surgery; SM, Spetzler–Martin.
CONCLUSIONS The management of brain AVMs is complex and is often based on data from small series or from tertiary referral centers, which may not be applicable to a particular patient or physician’s experience. The surgeon must take the ‘‘long view’’ when designing a treatment plan. The duration between hemorrhages reported in studies of natural history permits the use of multiple modalities, possibly multiple times. After thorough review of the literature and considerable personal experience, we offer the following recommendations: 1. Small (10 cm3), lobar, cortically located AVMs are best treated by microsurgical excision. Embolization may be used if there is the opportunity for cure (fistulous, single feeding artery) or low risk for morbidity. 2. Small (10 cm3), deep or eloquently located AVMs should be treated with stereotactic radiosurgery. Embolization may be attempted if cure is a possibility. 3. Large (>10 cm3) AVMs in noneloquent regions are treated with multimodality therapy including embolization followed by surgery. 4. Large (>10 cm3) AVMs in eloquent regions are observed if they are asymptomatic or are treated with multimodality therapy including embolization followed by stereotactic radiosurgery. 5. Giant AVMs (>20 cm3) are usually followed or treated with palliative embolization. Protocols for fractionated stereotactic radiotherapy or radiosurgery are also being applied.
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Brain arteriovenous malformations: analysis of the angioarchitecture in relation to hemorrhage. J Neuroradiol 1988; 15:225–237. 19. Stefani MA, Porter PJ, TerBrugge KG, et al. Angioarchitectural factors present in brain arteriovenous malformations associated with hemorrhagic presentation. Stroke 2002; 33:920–924. 20. Ondra S, Troupp H, George E, et al. The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow up assessment. J Neurosurg 1990; 73:387–391. 21. Brown R, Wiebers D, Torner J, et al. Frequency of intracranial hemorrhage as a presenting symptom and subtype analysis: a population–based study of intracranial vascular malformations in Olmstead County, Minnesota. J Neurosurg 1996; 85:29–32. 22. Hartmann A, Mast H, Mohr J, et al. Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformation. Stroke 1998; 29:931–934. 23. Forster D, Steiner L, Hakansson S. Arteriovenous malformations of the brain. A long–term clinical study. J Neurosurg 1972; 37:562–570. 24. Stapf C, Mast H, Sciacca RR, et al.; New York Islands AVM Study Collaborators. The New York Islands AVM study: design, study progress, and initial results. Stroke 2003; 34:e29–e33. 25. Mast H, Young W, Koennecke H–C, et al. Risk of spontaneous hemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet 1997; 350:1065–1068. 26. Al–Shahi R, Warlow C. A systematic review of the frequency and prognosis of arteriovenous malformations of the brain in adults. Brain 2001; 124:1900–1926. 27. Soderman M, Andersson T, Karlsson B, et al. Management of patients with brain arteriovenous malformations. European J Radiol 2003; 46:195–205. 28. Apsimon HT, Reef H, Phadke RV, et al. A population–based study of brain arteriovenous malformations. Long–term treatment outcomes. Stroke 2002; 33:2794–2800. 29. Kondziolka D, McLaughlin MR, Kestle JR. Simple risk predictions for arteriovenous malformation hemorrhage. Neurosurgery 1995; 37:851–855. 30. Brown RD. Simple risk predictions for arteriovenous malformation hemorrhage [comment]. Neurosurgery 2000; 46:1024. 31. Stapf C, Khaw AV, Sciacca RR, et al. Effect of age on clinical and morphological characteristics in patients with brain arteriovenous malformation. Stroke 2003; 34:2664–2669. 32. Ogilvy CS, Stieg PE, Awad I, et al. Recommendations for the management of intracranial arteriovenous malformations: a statement for healthcare professionals from a special writing group of the stroke council, American Stroke Association. Stroke 2001; 32:1458–1471. 33. Maruyama K, Kawahara N, Shin M, et al. The risk of hemorrhage after radiosurgery for cerebral arteriovenous malformations. N Engl J Med 2005; 352:146–153. 34. Valavanis A, Yasargil MG. The endovascular treatment of brain arteriovenous malformation. Adv Tech Stand Neurosurg 1998; 24:131–214. 35. Wikholm G, Lundqvist C, Svendsen P. The Giteborg cohort of embolized cerebral arteriovenous malformations: a 6-year follow-up. Neurosurgery 2001; 49:799–805 [discussion pp. 805–896]. 36. Willinsky R, Goyal M, TerBrugge K, et al. Embolization of small (<3 cm) brain arteriovenous malformations. Intervent Neuroradiol 2001; 7:19–27. 37. Meisel HJ, Mansmann U, Alvarez H, et al. Effect of partial targeted N–butyl–cyano–acrylate embolization in brain AVM. Acta Neurochir (Wien) 2002; 144:879–888. 38. Pollock BE, Flickinger JC. A proposed radiosurgery–based grading system for arteriovenous malformations. J Neurosurg 2002; 96:79–85.
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39. Pollock BE, Flickinger JC, Lunsford LD, et al. Factors associated with successful arteriovenous malformation surgery. Neurosurgery 1998; 42:1239–1244. 40. Karlsson B, Lax I, Soderman M. Can the probability for obliteration of arteriovenous malformations following radiosurgery be accurately predicted? Internat J Radiat Oncol Biol Phys 1999; 43:313–319. 41. Flickinger JC, Kondziolka D, Lunsford LD, et al. A multi-institutional analysis of complication outcomes after arteriovenous malformation radiosurgery. J Radiat Oncol Biol Phys 1998; 44:67–74. 42. Pollock BE, Gorman D, Brown PD. Radiosurgery for arteriovenous malformation of the basal ganglia, thalamus, and brainstem. J Neurosurg 2004; 100:210–214. 43. Maruyama K, Kondziolka D, Niranjan A, et al. Stereotactic radiosurgery for brainstem arteriovenous malformations: factors affecting outcome. J Neurosurg 2004; 100:407–413. 44. Foote K, Friedman W, Ellis T, et al. Salvage retreatment after failure of radiosurgery in patients with arteriovenous malformations. J Neurosurg 2003; 98:337–341. 45. Masaaki U, Satoh K, Matsubara S, et al. Does multimodality therapy of arteriovenous malformations improve patient outcome? Neurol Res 2004; 26:50–54. 46. Hoh B, Chapman P, Loeffler J, et al. Results of multimodality treatment for 141 patients with brain arteriovenous malformations and seizures: factors associated with seizure incidence and seizure outcomes. Neurosurgery 2002; 51:303–311. 47. Chang S, Marcellus M, Marks M, et al. Multimodality treatment of giant intracranial arteriovenous malformations. Neurosurgery 2003; 53:1–13. 48. Hoh B, Ogilvy C, Butler W, et al. Multimodality treatment of nongalenic arteriovenous malformation in pediatric patients. Neurosurgery 2000; 47:346–358. 49. Morgan M, Sundt T. The case against staged operative resection of cerebral arteriovenous malformations. Neurosurgery 1989; 25:429–436. 50. Spetzler RF, Martin NA, Carter LP, et al. Surgical management of large AVMs by staged embolization and operative excision. J Neurosurg 1987; 67:17–28. 51. Nakstad PH, Nornes H. Superselective angiography, embolisation and surgery in treatment of arteriovenous malformations of the brain. Neuroradiology 1994; 36:410–413. 52. Soderman M, Rodesch G, Karlsson B, et al. Gamma knife outcome models in the embolisation of cerebral arteriovenous malformations. Acta Neurochir 2001; 143:801–810. 53. Hamilton M, Spetzler R. The prospective application of a grading system for arteriovenous malformations. Neurosurgery 1994; 34:2–7. 54. Heros R, Korosue K, Diebold P. Surgical excision of cerebral arteriovenous malformations: late results. Neurosurgery 1990; 26:570–578. 55. Sisti M, Kader A, Stein B. Microsurgery for 67 intracranial arteriovenous malformations less than 3 cm in diameter. J Neurosurg 1994; 79:653–660. 56. Pikus HJ, Beach ML, Harbaugh RE. Microsurgical treatment of arteriovenous malformations: analysis and comparison with stereotactic radiosurgery [see comments]. J Neurosurg 1998; 88:641–646. 57. Pik HJ, Morgan MK. Microsurgery for small arteriovenous malformations of the brain: results in 110 consecutive patients. Neurosurgery 2000; 47:571–575 [discussion pp. 575–577]. 58. Pasqualin A, Barone G, Cioffi F, et al. The relevance of anatomic and hemodynamic factors to a classification of cerebral arteriovenous malformations. Neurosurgery 1991; 28:370–379. 59. Heros RC, Morcos J, Korosue K. Arteriovenous malformations of the brain. Surgical management. Clin Neurosurg 1993; 40:139–173. 60. Schaller C, Schramm J, Haun D. Significance of factors contributing to surgical complications and to late outcome after elective surgery of cerebral arteriovenous malformations. J Neurol Neurosurg Psychiatry 1998; 65:547–554.
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Surgical Principles Christopher C. Getch, Christopher Eddleman, Melanie K. Swope, and H. Hunt Batjer Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A.
INTRODUCTION The decision to surgically treat an intracranial arteriovenous malformation (AVM) is arrived at after a careful evaluation of the patient’s clinical presentation, a comparison of the treatment risk against the natural history risk of an untreated AVM, and a consideration of the risks associated with alternative treatments, such as radiosurgery and embolization. Before a surgical course of treatment is initiated, the total risk of treatment should be assessed, not only from the surgical procedure itself but also from any adjuvant treatment such as staged embolization. When an intracranial AVM is evaluated with the goal of complete surgical resection, there are a number of clinical, anatomic, and radiographic factors that can add risk and influence surgical difficulty. Size of nidus, close relationship to physiologically eloquent areas, and deep venous drainage have been correlated with surgical outcome (1). Heros et al., in a report of their series of surgically excised AVMs, found a good correlation between the Spetzler–Martin grade of the AVM and early outcomes (2). However, there are a number of additional factors that can directly influence surgical difficulty and thus potentially the outcome. Clinically, the presence of a previous hemorrhage cavity can facilitate the dissection of a difficult AVM as it provides a direct pathway from the cortical surface to the AVM nidus. Tew et al. noted that the presence of previous hemorrhage helped to define the surgical planes for resection of deep-seated caudothalamic AVMs (3). By contrast, the presence of previous hemorrhage can make the removal of an AVM technically more difficult as the nidus can become fragmented, thus increasing the chance of leaving a small residual piece not visualized during removal of the larger portion of the nidus. Anatomically, a number of factors can contribute to the difficulty of surgical resection, including a compact or diffuse nidus (angiomatous change), the presence of lenticulostriate or deep posterior cerebral artery (PCA) feeders, the presence of en passage vessels (Fig. 1), and nidal juxtaposition with eloquent cortex and vital white matter tracts. The presence of deep versus cortical venous drainage has not, in the authors’ experience, made the resection of an AVM more difficult as it is encountered late in dissection and is easier to work around. In fact, superficial drainage can complicate resection as it narrows surgical corridors and when retracted can increase AVM turgor. Complex AVMs, which have multiple arterial feeding pedicles with significant arterial supply from the contralateral hemisphere, recruitment of perforators, a paucity of filling of normal cortical branches (steal), and external carotid supply, are associated with an increased chance of the development of a hyperemic state during and after resection; this problem can lead to intraoperative edema and postoperative bleeding (4). A careful consideration of each of these factors before surgery can lead to a more accurate assessment of risk, a strategically designed treatment plan, a better prepared surgeon, and, it is hoped, a more successful outcome for the patient. PREOPERATIVE IMAGING Multiple currently available imaging options can help in the diagnosis, surgical planning, and intraoperative resection of an intracranial AVM. The issue is not so much which imaging modality to use but what information is essential for the safe and complete removal of the AVM. Digital subtraction angiography remains, in the authors’ opinion, the one critical study for both the diagnosis and intraoperative management of an AVM. A six-vessel angiogram
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Figure 1 (A) Intraoperative view of right insular cortical arteriovenous malformation demonstrating multiple middle cerebral artery branches. (See color insert.) (B) Right internal carotid angiogram demonstrating en passage middle cerebral artery vessels (arrow).
should be performed initially to give the most complete picture anatomically. Critical information derived from the arterial phase includes a detailed anatomy of the feeding pedicles, whether they are single or multiple, and in which territory they lie. The presence of flow-related proximal aneurysms is important to establish, as strong consideration should be given to securing these aneurysms before or at the time of surgery (Fig. 2A). The presence of deep feeding vessels such as branches of the PCAs, lenticulostriates, and specific vessels such as the anterior choroidal artery or anterior inferior cerebellar artery (AICA) must be carefully analyzed as they can be associated with technical difficulty and increased risk during resection of a specific AVM (Fig. 3A, B). Essential information derived from the angiogram about the nidus includes whether it is compact or diffuse, as is often encountered in younger patients, and whether fragmentation has occurred secondary to hemorrhage. Determining AVM nidal compartmentalization based on feeding pedicles is also helpful in designing a surgical strategy for devascularization. Essential information derived from the venous phase is, first and foremost, identification of the dominant venous drainage. In terms of hemorrhage risk assessment, venous outflow obstruction with varices is important to identify, and from a surgical standpoint, it is critical to identify whether there is deep or superficial drainage or single or multiple draining veins. In cases where the AVM does not have cortical surface representation, using a major draining vein as a road map to lead to the AVM nidus can be helpful (Fig. 4B). Magnetic resonance images (MRI) in the axial, coronal, and sagittal planes also provide essential information for the successful surgical resection of an AVM. MRI demonstrates the anatomical relationship of the nidus to the normal surrounding brain tissue. Furthermore, MRI provides essential information on the AVM’s cortical or pial representation, its relationship to eloquent cortex,
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Figure 2 (A) Vertebral injection demonstrating multiple flow-related proximal aneurysms. Endovascular treatment of the large proximal aneurysm (arrow) should be considered before arteriovenous malformation (AVM) resection. (B) Intraoperative view demonstrating a Guglielmi detachable coil mass in an anterior cerebral feeding artery placed in anticipation of surgical resection of the AVM. Intraoperative identification of embolized arteries can be useful for intraoperative orientation. (See color insert.)
whether there are existing dissection planes from previous hemorrhage, and whether there is AVM representation along the ventricular surface. In the authors’ experience, T2-weighted sequences obtained in all three planes are the most useful for facilitating surgical planning for corridors of access and AVM removal. Functional MRI (fMRI) imaging can provide useful information about the proximity of the AVM to a primary function and whether the AVM has displaced a normal function, either ipsilaterally around the AVM or to the contralateral hemisphere (Fig. 5). Large AVMs with significant flow, in our experience, can reduce the reliability of fMRI. Critical assessment of language or motor function is most reliably done with awake mapping in this circumstance. Plain computed tomography (CT) in the acute setting can give vital information as to the presence of subarachnoid, subdural, or parenchymal
Figure 3 (A) Vertebral angiogram demonstrating significant posterior cerebral artery contribution to a posterior occipital arteriovenous malformation (AVM). The deep medial location of these feeders makes them surgically difficult to access during resection, and strong consideration should be given to embolizing them before surgical treatment. (B) Vertebral injection demonstrating enlarged posterior cerebral artery perforators feeding a deep basilar ganglial AVM. Multiple hemorrhages of this AVM provided a corridor of access for surgical resection. Before resection, the deep perforator feeding vessel was embolized.
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Figure 4 (A) Intraoperative view demonstrating thickened arachnoid overlying a cortical arteriovenous malformation (AVM). The arachnoidal phase of dissection begins by defining the feeding arterial supply and pial margins if the AVM has cortical representation. (B) Intraoperative view of an AVM with no direct cortical representation demonstrating the value of utilizing the major draining vein as a guide to reach the AVM nidus. (See color insert.)
hemorrhage related to AVM rupture. It can be used rapidly to diagnose whether there is intraventricular blood and associated hydrocephalus. More recently, CT in combination with CT angiography (CTA) can be used to rapidly diagnose the presence of an AVM in the setting of an acute intracranial hemorrhage, and in a more elective setting it can provide a 3D reconstitution of the nidus, which can be helpful when dissecting the nidus (Fig. 6). CT or MR images can be integrated with frameless stereotactic guidance systems and used in planning
Figure 5 Functional magnetic resonance imaging study in a patient with a left hemispheric AVM (small arrow) with displacement of primary motor hand function to the collateral hemisphere (large arrow). Abbreviation: AVM, arteriovenous malformation. (See color insert.)
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Figure 6 Arteriovenous malformation visualized on computed tomographic angiography 3D reconstructions of right internal carotid artery (A) and left internal carotid artery (B) feeding arteries.
the incision and bone flap, placement of burr holes around the dural venous sinuses, identification of feeding arterial pedicles, and localization during the parenchymal phase of dissection (Fig. 7A). Surgical planning and the efficient surgical excision of an AVM requires not only high-quality presurgical imaging but also a clear, 3D understanding of that imaging before entering the operating room. EMBOLIZATION Embolization is an important adjunct therapy for patients where complete surgical resection of the AVM is the goal. The decision to embolize an AVM before surgery, however, must be made carefully as each stage of embolization adds risk to the overall treatment of the AVM. The role of embolization in the treatment of an AVM must be individualized and goal-directed. Careful consideration must be given to embolizing, for example, middle cerebral artery (MCA) branches of a cortical AVM as they may be readily accessible surgically. In the authors’ experience, embolization of lenticulostriates or deep posterior cerebral feeders that are often encountered late in the resection of an AVM is most useful (Fig. 2A, B). Selective embolization can be used to facilitate dissection of an AVM when it is located near eloquent cortex, allowing a tighter dissection plane along the nidus by creating a more hemostatic dissection. In the setting of large AVMs, staged reduction of flow over several weeks can be helpful in preventing intraoperative cerebral swelling and potential intra- or postoperative hemorrhage. Typically, when we use staged embolization, we separate the stages by approximately seven to ten days with the final embolization being performed within 24 hours of the planned surgical procedure. When external supply is present, it should be embolized before the craniotomy to minimize blood loss (Fig. 8). Embolization of flow-related aneurysms should be considered strongly when they are remote from the nidus and not easily accessible surgically because they can rupture after the AVM is removed (Fig. 2A). ANESTHESIA Properly administered neuroanesthesia is as critical to patient outcome as is good surgical technique. Gentle induction with careful attention to blood pressure control at the time of pin placement is important to prevent premature rupture of the AVM. Large bore central line access is important should rapid volume resuscitation be required during resection of the AVM. Typically the central line is placed in either the internal jugular or the subclavian vein contralateral to the major outflow of the AVM to prevent any venous outflow restriction. The patient is typically typed and cross-matched for two to four units of blood or more in very large AVM cases. Mannitol, dexamethasone, and antibiotics are routinely administered.
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Figure 7 (A) Intraoperative frameless stereotactic guidance can be utilized for optimal bone flap design and selection of the optimal trajectory for surgical resection of an AVM. (See color insert.) (B) Schematic diagram of large bone flap centered over the AVM for a parasagittal parietal AVM. (C) Schematic diagram of bone flap centered over right frontal AVM. Abbreviation: AVM, arteriovenous malformation.
Electrophysiological monitoring is not routinely used but can be helpful, particularly in infratentorial AVMs where temporary occlusion of an AICA or posterior inferior cerebellar artery (PICA) may be anticipated. Intraoperatively, the systolic blood pressure is maintained slightly hypotensive with IV agents such as nicardipine, and hyperventilation is used to decrease cerebral perfusion and provide brain relaxation. The IV blood pressure infusion is maintained throughout the period of patient emergence from anesthesia and during the postoperative period for strict blood pressure control to lessen the chance of postoperative hemorrhage.
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Figure 8 Selective left external carotid angiogram demonstrating significant transcranial external carotid supply to an intracranial parenchymal arteriovenous malformation.
NEUROSURGICAL EMERGENCY: INTRACRANIAL HEMORRHAGE RELATED TO AVM RUPTURE Emergent surgical removal of an intracerebral hematoma related to an AVM rupture is occasionally required (5) (Fig. 9). Determining the etiology of the hemorrhage is important, whether it is from flow-related aneurysms, nidal aneurysms, rupture of the AVM nidus itself, or post-embolization, as the source of hemorrhage may impact the treatment strategy. Hemorrhage related to a flow-related aneurysm, particularly in the proximal circle of Willis, should be treated in the same manner as all ruptured aneurysms, as they have the same aggressive natural history. In the authors’ opinion, the aneurysm should be treated independent of the AVM and secured either surgically or endovascularly at the earliest opportunity. Whether the aneurysm is secured surgically or endovascularly depends on the standard consideration of shape, size, location, and accessibility. Securing the aneurysm surgically can be particularly more difficult in the setting of engorged AVM arteries and veins, which may limit or narrow a
Figure 9 (A) Noncontrast head computed tomography (CT) in a 47-year-old patient with acute intracranial hemorrhage from a ruptured right posterior parietal arteriovenous malformation (AVM). The patient was taken emergently to surgery for evacuation of the hematoma. The AVM was not resected at the time of hematoma evacuation, as hemostasis was easily achieved and complete imaging was not available before surgery. (B) Noncontrast head CT in a 27-year-old patient with a previously unknown AVM who presented with a rapid decline in mental status and was emergently taken to the operating room for evacuation of the intracranial hemorrhage. At the time of surgery, the AVM was resected because of difficulty in obtaining intraoperative hemostasis.
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Figure 10 (A) Left internal carotid artery angiogram demonstrating a left parietal arteriovenous malformation. (B) Noncontrast head computed tomography immediately after embolization, demonstrating glue casting of the major draining vein (large arrow) with associated acute nidal parenchymal hemorrhage (small arrow).
corridor of access. The decision about treatment of the aneurysm is also linked to the plan for the AVM. If treatment of the AVM is indeed planned, endovascular treatment of the aneurysm is even more attractive as flow reduction after AVM resection should decrease recurrence risk for the coiled aneurysm. One of the most important issues when confronted with an intracranial hemorrhage related to an AVM is whether the AVM nidus can and should be removed at the time of the intracranial hemorrhage evacuation. This decision depends on the clinical status of the patient, the completeness of the radiological workup, the anticipated difficulty of AVM resection based on its assumed size and location, the presence of severe cortical edema at the time of surgery, and the ability to achieve intraoperative hemostasis once the hematoma has been removed (Fig. 9). If adequate decompression has been achieved after evacuation of the hemorrhage and the surgical bed is dry, resection of the nidus can be delayed for up to four to six weeks, as the natural history suggests a low rate of re-rupture in the immediate post-decompression period. Delaying the removal of the AVM nidus allows for assessment of the patient’s neurologic status post-rupture and before removal of the AVM, completion of radiographic studies, and resection in the setting of decreased brain swelling. In the setting of an intracranial hemorrhage after embolization, particularly with compromised venous outflow (Fig. 10), simultaneous resection of the AVM nidus should be strongly considered. SURGICAL RESECTION The safe and effective resection of an intracranial AVM results from the combination of careful presurgical planning and meticulous intraoperative surgical technique. The patient should be thoughtfully positioned to provide an optimal working angle to the AVM nidus while providing the surgeon with the most comfortable position in which to work. Extreme flexion, extension, or rotation of the patient’s neck should be avoided to minimize venous outflow obstruction, and an attempt should be made to place the head slightly above the heart to promote venous drainage. The scalp flap and craniotomy bone flap should be large enough to allow visualization of the normal cortical surface around the AVM and allow multiple working angles. For lesions abutting the falx, particular attention should be given to optimizing the gravitational displacement of the brain, thus expanding the surgical corridor. Image-guided intraoperative neuronavigation may be helpful in centering the flap over the AVM and identifying large dural sinuses for optimal burr hole placement, as in medial hemispheric AVMs, which require an interhemispheric approach (Fig. 7B, C). The surgeon must resist the tendency, when using intraoperative image-guided navigation, to make a smaller craniotomy bone flap. Similarly, a generous dural opening should be performed so as not to limit the visualization of the surgical field. Opening of the dura should initially be undertaken
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away from the draining veins over normal cortex and subsequently mobilized toward and over the AVM nidus. Often there are arachnoidal adhesions from dura to vascular structures of the AVM, which should be carefully divided sharply. Should a critical draining vein be injured during opening of the dura, it should be gently tamponaded with cotton, as gel-foam does not work as effectively with arterialized veins. Once the dura is opened, a careful analysis of both the arterial and venous anatomy must be undertaken before the dissection is begun and the anatomy correlated with the imaging. In the authors’ experience with cortical AVMs, the venous anatomy is often easier to understand, as the veins tend to be located directly on the surface of the brain. Understanding the relationship derived from the preoperative angiogram of the feeding arteries to these veins can help in their intraoperative localization. Further intraoperative anatomical understanding of the AVM can be derived from analyzing and roadmapping the feeding arteries that were embolized. For this reason, in addition to the relevant angiographic images obtained before embolization, it is important to have access in the operating room at the time of resection to the post-embolization angiogram images. A non-contrast axial CT can also be helpful in demonstrating which part of the AVM nidus was embolized, as the glue is quite dense. The authors have found that embolized arteries are often very useful, for example, when resecting AVMs located in the insular cortex, as en passage vessels can be rapidly distinguished from embolized AVM feeders. For those AVMs that do not have obvious cortical surface access, a plan to reach the AVM must be devised. Occasionally, a transvenous route by skeletonizing the major draining vein of the AVM can provide a route of access to the nidus. Care must be exercised in choosing which side of the draining vein to work over, as excessive or repetitive retraction of the major draining vein can lead to injury or occlusion. Subarachnoid Dissection Once the AVM anatomy has been correlated with what is seen on the cortical surface with a clear understanding of the outflow anatomy, it is advisable to approach the AVM with a systematic plan for arterial devascularization. The superficial arteries should be identified and sacrificed systematically during this arachnoidal phase of dissection as close to the nidus as possible to avoid an inadvertent normal branch sacrifice (Fig. 4). This is especially important with insular AVMs, which may have MCA feeders in the setting of vessels en passage. Sacrificing the arterial feeders at this stage helps to reduce hemorrhage risk and the turgor of the nidus, facilitating dissection. Some small draining veins can be sacrificed at this point to further aid in dissection. If there is any doubt on the contribution of a particular draining vein, a temporary clip can be placed on the vein and the nidus observed for several minutes for distension. Before the parenchymal phase of dissection is started, the arachnoidal dissection should be completed circumferentially, defining the dissection planes on the pial surface (Fig. 11). Additionally, Clatterbuck et al. have advocated early, sharp arachnoidal dissection around the AVM’s major draining vein. By mobilizing the vein, it is subjected to less stress and potential injury during manipulation of the AVM nidus (6).
Figure 11 Intraoperative view of left frontal arteriovenous malformation (AVM) with cortical representation demonstrating circumferential pial coagulation defining the resection margins of the AVM prior to beginning the parenchymal dissection phase. (See color insert.)
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Parenchymal Dissection In general, the parenchymal dissection of an AVM is carried out with a circumferential spiral dissection that gradually deepens (Fig. 12). The bipolars, in concert with the suction, should be used to mobilize the abnormal AVM vessels out of the brain, toward the nidus, shrinking the AVM nidus in the process. Often, a gliotic plane surrounding the AVM can facilitate this phase of dissection. Caution must be used not to work in a limited area, creating a deep hole, as bleeding encountered in this setting can be difficult to visualize and control. Dissection should be accomplished by gently sweeping the suction in the plane around the AVM and simultaneously coagulating, shrinking, and withdrawing the AVM away from the brain. A dissection plane, once completed, can be marked with tapered Telfa pledgets (Fig. 13), which make identification and return to the previous dissection planes easier. Small feeding vessels that are bridging between the brain parenchyma and the nidus are often encountered during this phase of dissection. They frequently do not coagulate well because of their high flow and the dissipation of the bipolar heat and are best secured with mini-clips. In AVMs with ventricular representation, dissection should be carried out through the ependymal lining of the ventricle. Care should be taken to limit the amount of blood entering the ventricle during this phase of dissection, as it can lead to postoperative hydrocephalus. Cotton pledgets or large pieces of gel-foam placed in the ventricle can be helpful. When the ventricle is entered, a plaque of AVM tissue is often removed, leaving an ependymal window (Fig. 14). Specifically, in the setting of posterior fossa AVMs, Batjer and Samson advocate additional intraventricular exploration to ensure complete surgical removal of the AVM (7). The ultimate goal of dissection is to free the AVM nidus completely, leaving it on a single pedicle consisting of the major draining vein. Persistent filling of the nidus at this point may be from some small arteries that accompany and are often located beneath the major draining vein. Once the AVM nidus has been removed from the surgical field, the bed should be inspected for residual AVM and the cortical veins surrounding the resection cavity for any persistent AV shunting. A provocative maneuver by raising the blood pressure at this point should be performed to assess for the durability of the hemostasis.
Figure 12 (A) Schematic diagram illustrating systemic parenchymal dissection phase of the arteriovenous malformation (AVM) nidus based on arterial pedicles. (B) Intraoperative view of a cortical AVM with a parenchymal dissection plane (multiple small arrows) developed circumferentially around the AVM nidus, which is still connected via a vascular pedicle consisting of the major draining vein (large arrow). (See color insert.)
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Figure 13 Intraoperative views (A and B) demonstrating use of tapered Telfa pledgets to mark dissection planes. (See color insert.)
Recognizing and Getting Out of Trouble A successful surgical outcome is achieved not only through careful planning and meticulous intraoperative technique but also through recognizing and dealing with problems that arise during AVM resection. The problem most likely encountered is hemorrhage from the nidus during the parenchymal phase of dissection. Brisk bleeding encountered during the parenchymal resection of the nidus usually results from carrying the dissection plane into the nidus. Several strategies can be employed to deal with this problem. If the bleeding site can be reasonably visualized but is difficult to coagulate, it can be tamponaded with a small piece of cotton. The cotton should be placed with pressure directed laterally against the bleeding site and not with pressure directed downward, as the bleeding can continue unrecognized into the brain parenchyma beneath the cotton. If the bleeding site is difficult to visualize, further dissection in the nidus to identify and coagulate it may only make the situation worse. At this point, do not go to the site of bleeding but re-establish the correct dissection plane by entering the brain parenchyma more superficially and dissect past the site of bleeding, widening the margin. The widened dissection plane should be directed toward the likely source of inflow. The additional tissue should be mobilized against the bleeding site as the dissection site is deepened, tamponading it. In situations where there is significant bleeding in early stages of dissection, temporary arterial occlusion of the proximal feeding vessels with burst suppression can reduce bleeding enough to allow better visualization and systematic control of the bleeding sites. In our experience, having two surgeons in this situation, where one has only to keep the field clear, significantly facilitates re-establishing hemostasis. Bleeding that is encountered near the ventricular surface can be difficult to control. Caution must be exercised when tamponading bleeding in this location as this action may
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Figure 14 (A) Intraoperative view of deep insular AVM with representation to the lateral ventricular surface (arrow). (B) Surgical view after removal of insular AVM, demonstrating the ependymal window into the lateral ventricle (arrow). (C) Schematic diagram of AVM with ventricular representation and periventricular vascular supply. Periventricular vessels can be controlled by circumferentially coagulating the tissue in the ventricular wall. Abbreviation: AVM, arteriovenous malformation. (See color insert.)
force the blood into the ventricle, resulting in rapid brain swelling in an already narrow field. If this situation is suspected, rapid entry into the ventricle with evacuation of blood is essential to restore working room. A rapidly swelling brain encountered during AVM resection can have several different etiologies and must be dealt with quickly. A common cause is occult bleeding into the parenchyma from the nidus at a previous site of dissection or into the ventricle as noted above. In this situation, abandoning microdissection and pulling out the microscope to see the whole field can facilitate a rapid re-exploration of the dissection planes around the nidus and identification of the source of bleeding. If intraventricular bleeding is suspected, rapid entry into the ventricle with evacuation of blood is essential to restore working room. When an occult hemorrhage is not the source, the anesthesiologist should be directed to check the airway for possible obstruction. In the late stages of dissection, particularly with the removal of a large, complex AVM, the normal brain can become acutely swollen secondary to hyperemia. This usually results from a redirection of flow into the normal brain with an autoregulatory dysfunction. In this case, the dissection field should be rapidly inspected to rule out an occult hematoma, either in the parenchyma or in the ventricle. If no hematoma is identified, inspection of the margins of the brain around the dissection cavity may reveal AV shunting with hemorrhagic conversion and diffuse bleeding. Depending on the stage of dissection and the severity of the situation, microdissection should be abandoned and the remaining AVM nidus removed as rapidly as possible. Simultaneously, the anesthesiologist should be made aware of the situation and should take immediate measures to reduce cerebral blood flow with barbiturates and keep up with expected blood loss. Additional removal of the hemorrhagic tissue around the AVM resection cavity after abandoning microdissection should be undertaken rapidly until hemostasis is achieved. Multiple mini-clips are extremely useful
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in this setting, as the bleeding is often from a multitude of small, dilated parenchymal vessels. In advance of the resection of large AVMs, we often have the cell saver available in case this situation arises. The combination of two experienced surgeons working simultaneously coupled with a systematic plan for achieving hemostasis and simple persistence is usually eventually rewarded with a dry AVM cavity, but in the authors’ experience, it may take several hours. Postoperation Once surgical closure has been achieved, careful attention must be paid to the blood pressure to allow the brain to re-establish autoregulation. Typically, the patient’s blood pressure is maintained in the 100–120 mmHg systolic range with continuous infusion IV of an antihypertensive agent for 24 to 48 hours, depending on the size of the AVM. The pressure is then allowed to gradually rise back to the patient’s baseline. In the setting of intraoperative hyperemia and diffuse bleeding as mentioned above, the patient may be placed in a barbiturate coma for several days until autoregulation has been restored. The timing of the postoperative angiogram varies and depends on the complexity of the AVM resected and the surgeon’s suspicion for residual AVM. Intraoperative angiograms can be used to demonstrate complete resection, but in our experience, the resolution may not be adequate to detect subtle AV shunting. For a routine AVM with a low suspicion for residual, we typically perform the angiogram the following day. If unexplained bleeding is encountered, or there is any doubt as to the completeness of resection, an immediate postoperative angiogram while the patient is still under general anesthesia is warranted. Rarely, immediate postoperative AV shunting can be seen on angiogram that subsequently resolves; however, this must be careful correlated with the preoperative angiogram to determine if it truly represents residual AVM nidus versus a hyperemic brain state or leptomeningeal collateral. When residual AVM nidus is clearly present on postoperative angiogram, an early return to surgery is warranted because of the potential risk of hemorrhage from the altered hemodynamics in the residual piece of AVM. CONCLUSION Careful patient selection, multimodality imaging, and a well reasoned and meticulously executed surgical plan are all paramount to assure a successful resection of an intracranial AVM with good outcome. The collaborative efforts of an anesthesiologist, a neuroendovascular surgeon, a neurosurgeon, and neurocritical care staff must be coordinated to deliver the optimal care plan. Essential safe surgical principles necessary for AVM resection include preoperative localization of all relevant vascular structures, adequate surgical exposure, appropriate systematic devascularization of the AVM nidus, preservation of normal brain and vascular structures including en passage vessels, complete resection of the AVM nidus with angiographic confirmation, and meticulous postoperative monitoring. REFERENCES 1. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 2. Heros RC, Korosue K, Diebold PM. Surgical excision of cerebral arteriovenous malformations: Late results. Neurosurgery 1990; 26:570–577; [discussion 577–578]. 3. Tew JM Jr., Lewis AI, Reichert KW. Management strategies and surgical techniques for deep-seated supratentorial arteriovenous malformations. Neurosurgery 1995; 36:1065–1072. 4. Batjer HH, Devous MD Sr., Seibert GB, Purdy PD, Bonte FJ. Intracranial arteriovenous malformation: Relationship between clinical factors and surgical complications. Neurosurgery 1989; 24:75–79. 5. Yasargil M. Microneurosurgery: AVM of the Brain, Clinical Considerations, General and Special Operative Techniques, Surgical Results, Nonoperated Cases, Cavernous and Venous Angiomas, Neuroanesthesia. New York: Thieme Medical Publishers, Inc., 1988. 6. Clatterbuck RE, Hsu FP, Spetzler RF. Supratentorial arteriovenous malformations. Neurosurgery 2005; 57:164–167; [discussion 164–167]. 7. Batjer H, Samson D. Arteriovenous malformations of the posterior fossa. Clinical presentation, diagnostic evaluation, and surgical treatment. J Neurosurg 1986; 64:849–856.
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Endovascular Principles Charles J. Prestigiacomo Departments of Neurological Surgery and Radiology, Neurological Institute of New Jersey, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, U.S.A.
John Pile-Spellman Departments of Radiology, Neurosurgery, and Neurology, New York Neurological Institute, Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
INTRODUCTION The treatment of complex intravascular disorders presents a great challenge to clinicians. Because they are relatively rare and because of their very nature, the successful obliteration of intracranial arteriovenous malformations (AVMs) can create a significant amount of risk for the patient. An integrated approach to the management of patients with AVMs by neurologists, neuroanesthesiologists, neuroradiologists, neurovascular surgeons, and neurological critical care physicians has substantially reduced, but by no means nullified, the risk of poor outcomes. As technology in all these fields continues to improve, increasing numbers of patients with highly complex AVMs are now considered treatable, whereas they were not several decades ago. One important advance in the treatment of AVMs came with the advent of interventional neuroradiology, known also as neuroendovascular surgery or surgical endovascular neuroradiology. The rapid progress in catheter technology and the development of newer embolic agents have made the embolization of AVMs safer, more effective, and an integral part of the treatment plan for almost any AVM. Endovascular therapy of AVMs has also provided clinicians and researchers with a venue to better understand the complex flow dynamics present in an AVM. In this chapter, we describe the rationale and principles for the use of endovascular techniques in the treatment of AVMs. We will touch on the history of the field, the role for embolization as one of the treatment modalities for AVMs and as an adjunct for surgery or radiosurgery, and the decision analysis regarding the various endovascular treatment options. We will then describe the equipment and techniques involved in AVM embolization. Finally, we will examine and discuss the complications and complication avoidance with AVMs and point out some possible future directions for the endovascular management of AVMs. HISTORICAL PERSPECTIVE Although clinicians of the time had sound theories about how best to treat AVMs endovascularly, the rate-limiting step in advancing the field was the available technology. Historically, endovascular therapy developed in two major phases. The first phase focused on the development of catheter technology and delivery systems for embolic materials. The second phase saw the development of numerous particulate and liquid embolic agents that could be mated to the existing technologies. Embolization of lesions was first documented in 1904 when Dawbarn successfully embolized a malignant tumor via an external carotid artery injection of a paraffin–petrolatum mixture (1). In 1930, Brooks described the use of small pieces of muscle to obliterate a traumatically induced carotid cavernous fistula (2). Luessenhop and Spence performed the first flow-directed embolization of an AVM by surgically exposing the external carotid artery, introducing a catheter into the internal carotid artery, and injecting Silastic spheres into an AVM (3). This technique had significant drawbacks. It was non-selective and carried a significant risk of embolizing normal feeding vessels, especially in the late stages of the procedure. It achieved proximal occlusion of the feeding vessels, without much penetration into the nidus, thus allowing for collateralization of flow
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through the nidus. Finally, it was not applicable to small- or medium-sized AVMs because there was no significant preferential flow, or to AVMs with primarily deep feeding arteries. Flow-assisted particulate embolization continued to be developed (4,5), and despite the limitations, it did provide some benefits to the treatment of AVMs. In 1974, Serbinenko (6) introduced percutaneous selective endovascular therapy with the use of detachable balloons for several neurovascular disorders, including the treatment of AVMs. However, the lack of adequate microcatheter technology prohibited the navigation to higher order cerebral vessels and thus rendered the endovascular treatment of AVMs inadequate. Nonetheless, the microballoons were then used as a delivery system for embolic materials by puncturing the tip of the balloon to allow a slow leak of embolic material into the AVM. This ‘‘calibrated leak balloon’’ technique became the standard in the endovascular treatment of AVMs. Kerber (7) and later Pevsner (8) modified this technique by introducing smaller Silastic catheters and liquid embolic agents. Kerber then was able to navigate into higher order vessels and with balloon inflation, create the temporary, but necessary flow arrest required for the successful embolization of the AVM feeding vessels. This technique was not without risk. Vessel rupture secondary to balloon inflation and retained catheters did occur. The mid-1980s saw a dramatic change in catheter technology. Polymer science produced variable stiffness catheters that could be navigated either via a thin torqueable microguidewire or by the flow of blood. With these microcatheters, higher order vessels could be safely approached and embolic materials precisely delivered to an AVM. The concept of embolizing the pedicle feeder or the nidus itself was now feasible. With the advent of the variable stiffness, steerable microcatheter, the use of large particulate embolizing agents diminished. Although silk threads and small-sized polyvinyl alcohol particles can be delivered with wire-guided microcatheters, flow-directed microcatheters are compatible only with liquid agents. Isobutyl-2-cyanoacrylate was the agent of choice in the 1980s (9,10). Reports of local toxicity effects and carcinogenicity in animal studies (11–15) resulted in the removal of this compound from the market and the introduction of N-butyl-2cyanoacrylate (NBCA) (Fig. 1) (16). Its properties have rendered it safer to use than its preceding isoform, but great care still is required during injection. Catheter retention during long glue depositions can still occur. First developed in 1990, ethylene vinyl alcohol copolymer in dimethyl sulfoxide (DMSO) solution (Onyx; Micro Therapeutics, Irvine, California, U.S.A.) has now been approved for preoperative use in AVMs (Fig. 2) (17). A cohesive, rather than adhesive polymer, Onyx is injected slowly and essentially precipitates out of solution as the DMSO diffuses into the blood. The subsequent cast can then slowly be extended into the deeper portions of the nidus. The advantage of this agent is that each deposition can last for several minutes to more than an hour (in rare cases) instead of several seconds, with the ability to perform control angiography during the deposition. Case series suggest a higher rate of cure as a consequence of the long injection times and deeper penetration of the embolic agent (18). Evaluations are ongoing. In step with the advances in catheters, coils, and embolic materials are the vast improvements in imaging, such as three-dimensional rotational angiography and the nascent three-dimensional roadmapping techniques. Such advances have rendered the navigation and visualization of higher order cerebral vessels safer and more efficacious, making endovascular treatment of AVMs an important adjunct in curing these lesions.
ROLE OF ENDOVASCULAR THERAPY Embolization of AVMs involves highly selective endovascular access to feeding vessels of a malformation and the introduction of an agent that will occlude the AVM nidus totally or in part. The successful accomplishment of this process requires an understanding of the angiographic anatomy of the lesion and its surrounding structures as well as an understanding of the characteristics of the arterial and venous walls, local hemodynamic effects, and the effects of the clotting cascade. Each of these parameters may interact differently with any given embolic agent, thereby altering the outcome of the procedure. Thus, the most important aspect of endovascular therapy is to determine the goal of the procedure and then to make use of these complex interactions to tailor the treatment for achieving the goal while minimizing risk to the patient.
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Figure 1 N-butyl-2-cyanoacrylate, Trufill (Cordis Neurovascular Corp., Miami, Florida, U.S.A.). The packaged kit includes lipiodol, which serves as a hydrophobic contrast agent that also delays polymerization time on the basis of the relative concentration of lipiodol to Trufill. A 2:1 lipiodol:Trufill concentration (v:v, or 33%) is a relatively standard concentration, although polymerization time can be made faster or slower by decreasing or increasing the amount of lipiodol added. (See color insert.)
Decision analysis for the treatment of AVMs, both symptomatic and asymptomatic, is discussed elsewhere (Chapters 9 and 10). In general, young patients who present with AVMs that can be cured by any modality with high efficacy and low accepted morbidity risk should be treated. Treatment of an AVM should result in the obliteration of the fistulous connections within the abnormal collection of thin-walled vessels termed ‘‘the nidus.’’ Thus the goal for embolization
Figure 2 Ethylene vinyl alcohol copolymer, Onyx (Micro Therapeutics, Irvine, California, U.S.A.). Currently, two viscosities are approved for the treatment of ateriovenous malformations, Onyx 18 and Onyx 34. Both are prepackaged and require vigorous agitation for 20 minutes to resuspend the tantalum, which serves as the opacifying agent. (See color insert.)
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Table 1 Classification of Arteriovenous Malformations Type I II III IV V
Name
Description
Multiple unit Single unit Straight line Combined Venous wall
Multiple arteries and veins Single fistula (small) Direct arteriovenous shunt Combined (cerebral and extracranial supply) Extracranial supply to venous complex (modern day dural arteriovenous fistula)
Source: From Ref. 26.
of AVMs can be definitive, adjuvant, or palliative and can be better determined when superselective angiography and provocative testing are performed. Embolization of AVMs has been curative in only approximately 5% to 10% of certain case series (19–25). Characteristics that may make an AVM amenable to definitive endovascular therapy include those of Parkinson and Bachers types 2, 3, and 5 (Table 1) (26) or Spetzler–Martin Grades 1 or 2 (Table 2) (27). When embolization is used as an adjunct, it is important to know from the outset the modality that will be used to obliterate the AVM, since this technique will determine what the primary strategy of embolization should be. These strategies include the following: (i) the obliteration of deep feeding vessels; (ii) the embolization of AVMs located in eloquent areas, where provocative testing will help to reduce the risk of embolizing vessels that supply normal parenchyma; (iii) the embolization of AVMs with deep perforators or choroidal contribution; (iv) the embolization of high flow or very large AVMs; and (v) the embolization of AVMs with symptomatic venous hypertension. As an adjuvant therapy, embolization has significantly improved the overall outcome of patients undergoing surgical resection of AVMs (28,29). By targeting and successfully occluding those pedicles and the associated nidus that are potentially problematic to the surgeon during resection, embolization makes the surgery safer for the patient (Fig. 3). However, the vessels that can be problematic during surgery [e.g., anterior choroidal or lenticulostriate vessels, which can carry more than a 20% risk of complication in some studies (28,29)] also carry significant risk when being treated endovascularly. In addition to vessel selection, the choice of an embolic agent is critical to the success of the procedure. The timing of the surgery in relation to the embolization, the ability to access the target vessel, and the eloquence of surrounding brain parenchyma all affect the choice of the embolic agent. When used in conjunction with radiosurgery, the goal of embolization is the permanent reduction in the volume of the AVM nidus so as to decrease the target volume (30–35). The primary objective should be the occlusion of feeding vessels with an embolic agent that will permanently obliterate that portion of the AVM. If this objective is to be achieved safely, vessels near eloquent cortex can be targeted to help reduce the radiation dose in that area and thus decrease possible radiation-induced complications. However, studies have demonstrated that there is a significant rate of recanalization of an embolized portion of an AVM (36), ultimately resulting in the need for further radiosurgery at that site. Endovascular techniques may be helpful in instances where previously ruptured AVMs have an identifiable site of hemorrhage (e.g., the presence of a pseudoaneurysm or a true aneurysm of a proximal feeding artery) (Fig. 4). In these instances, embolization of these vessels with liquid polymers or coils Table 2 Grading System for Arteriovenous Malformations Feature Size
Eloquence Venous drainage
Description
Points
Small (<3 cm) Medium (3–6 cm) Large (>6 cm) Non-eloquent Eloquent Superficial Deep
1 2 3 0 1 0 1
Note: Grades are determined by adding the total number of points for each feature, with grade 1 having the most favorable outcome and grade 5 the least favorable outcome. Source: From Ref. 27.
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Figure 3 A Spetzler–Martin Grade 3, 4.5-cm, left frontal arteriovenous malformation (AVM) in a 32-year-old man who presented with new onset seizures. (A, B) Initial angiographic evaluation [anteroposterior (AP) and lateral views, respectively] revealed contribution from the anterior cerebral artery and A1 perforators with drainage via the sagittal sinus and cavernous sinus. (C, D) Post-embolization stage II angiogram revealed substantial reduction in the overall filling of the malformation (AP and lateral views, respectively). (E, F) Postoperative angiography demonstrating no residual AVM post-resection (AP and lateral views, respectively).
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Figure 4 Arteriovenous malformation (AVM) in a 53-year-old woman who presented with acute intraventricular hemorrhage. (A) Computed tomography angiography confirmed the presence of a Spetzler–Martin Grade 2 AVM in the left motor region with an aneurysmal dilatation in the periventricular region. (B) Angiography confirmed lenticulostriate contribution to the deep portion of this malformation with a distal aneurysm. (C) Microcatheter injection of the feeding pedicle confirmed mild flow control of contrast in this vessel, suggesting that successful embolization with N-butyl-2-cyanoacrylate could be achieved. (D) Glue cast incorporating the aneurysm and proximal feeding pedicle is noted. (E) Successful occlusion is confirmed on control angiography.
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in the case of arterial aneurysms, where clipping is not indicated, may confer protection against rehemorrhage during the 1- to 3-year latency period between treatment and the obliteration of the AVM. In addition, superselective stereotactic angiography may be helpful in better delineating the AVM nidus for radiosurgical planning. Despite all the technological advances in the various fields of clinical neuroscience, numerous AVMs still are deemed ‘‘untreatable’’ because of size or location. In most instances, such lesions have a demonstrable effect on the individual, including progressive neurological deficits secondary to cerebral steal, medically intractable seizures, dangerous pseudoaneurysms with their associated hemorrhages, and cardiac failure. No definitive treatment algorithm can be given in such instances. Some cases have been reported in which staged embolization at least temporarily reduced the cerebral steal phenomenon and subsequently improved cognitive function (37,38). When the palliative treatment of an AVM is attempted, attention should be primarily directed to the high-risk portion of the malformation. Further investigation is required to help determine the risk–benefit ratio for these patients. HEMODYNAMIC CONSIDERATIONS AND STAGING OF EMBOLIZATION The nidus of an AVM, angiographically and pathologically, is generally composed of a series of compartments. Each compartment can have one or two discrete pedicles, but they can communicate with other compartments. Draining veins can receive input not just from individual nidal compartments but also from normal surrounding parenchyma. In addition to the direct arterial feeders that are visualized on angiography, a number of collateral pathways (pial as well as dural) exist that may contribute to the AVM and are not visible on angiography. These collateral vessels at the time of the angiogram may be smaller than the resolution of the imaging equipment, or, because of the tremendous flow through the feeding pedicles, their contribution of flow to the AVM nidus may be minimal. When the decision to embolize an AVM is made, a better understanding of the various compartments, the actual and potential collateral channels that can be recruited when the AVM is partially embolized, and the respective drainage patterns are essential to safely obliterate the AVM without sacrificing normal parenchyma. Superselective angiography before the occlusion of a vessel is vital. Once the angiographic anatomy of a particular pedicle is determined, the decision to embolize the entire nidus or its proximal feeding pedicle must be made. In all cases, if technically feasible and safe, every attempt should be made to embolize the nidus and the pedicle at the entry point of the nidus. This technique helps to reduce the incidence of recruitment of collateral vessels and minimizes intraoperative bleeding. With the potential for the recruitment of collateral feeding vessels, an important issue in the endovascular treatment of AVMs is the need for staging the procedure. Although the goal would seem to be to reduce the flow through the AVM nidus by as much as possible during one stage so as to minimize the time a patient is exposed to the procedure, this is often not the case. Staging the embolization allows the potentially large hemodynamic shifts that occur with embolization to take place slowly so that normal parenchyma surrounding the AVM can compensate. One of these concerns about reducing the flow to the AVM too rapidly is that described by Spetzler et al. as normal cerebral perfusion pressure breakthrough (39). This condition has not been seen in our institutions. Some studies have shown that vasoreactivity of parenchymal vessels surrounding the AVM normalizes approximately 2 weeks after embolization (40). In addition, a rapid decrease in the flow through the capacious venous outflow channels can result in stagnant flow and predispose to thrombosis, potentially resulting in venous infarction. Finally, since embolic agents used for AVM occlusion do result in a variable local inflammatory response, there is the concern that numerous embolizations needlessly increase local tissue edema, which may prove harmful. As a result, although no controlled studies have been performed (41–43), most interventionalists using liquid embolic agents will embolize two or three vessels and wait several weeks between successive stages. This process allows the normal vessels to adapt to the new flow dynamics while the probability of developing new collaterals is reduced (44). The ideal time interval between the final stage of embolization and surgery is unclear. In our institutions, we usually perform the final stage of embolization several days to several weeks before surgical resection. Intraoperative evaluation of the nidus and the surrounding parenchyma at the time of surgery has not shown any significant amount of edema.
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ANESTHETIC CONSIDERATIONS AND MONITORING The need for neuroanesthesiology for all endovascular procedures cannot be overemphasized. Successful embolization of AVMs relies on a number of parameters that must be monitored and at times controlled in the patient, such as blood pressure, anticoagulation status, and level of consciousness. At one of our institutions, most adults are treated with conscious sedation so that neurological examinations can be conducted during provocative testing and after embolization of each feeding pedicle. General anesthesia with endotracheal intubation is used at other institutions where provocative testing is not employed. A primary goal of anesthetic care during embolization of AVMs is immediate intervention in the event of a catastrophic complication (such as intraprocedural hemorrhage or thrombosis), when specific interventions (e.g., reversal of anticoagulation or moderate systemic hypotension) may be required. At times, monitored anesthetic care may be inadequate to allow for proper visualization of the microvasculature in preparation for deposition of the embolic agent. Conscious Sedation The primary goals for conscious sedation are to maximize the patient’s level of comfort, to relieve anxiety, to keep the patient immobile at critical portions of the procedure, and to titrate the level of consciousness so as to perform reliable neurological examinations when required. Patients report discomfort during femoral puncture, manipulation of guiding catheters in the carotid and vertebral arteries, contrast injection, and with the abrupt withdrawal of microcatheters after injection of cyanoacrylates. Despite every attempt to put patients in a comfortable position, the long hours of lying still add to the overall discomfort of the procedure. A combination of neuroleptic anesthetics during the initial femoral artery puncture renders the patient immobile and unaware of what is occurring, yet arousable and spontaneously breathing. The remaining portions of the procedure are performed primarily with careful titration of propofol to allow rapid return to consciousness for neurological testing. Anticoagulation Although careful management of coagulation is required to prevent thromboembolic complications during and after the procedure, the actual algorithms for anticoagulation remain controversial (45,46). Whether heparinization should be used for every case of intracranial catheterization is not clear. The authors feel strongly that heparinized saline be used at high flow rates and supplemented with heparin boluses as necessary, especially in the setting of difficult superselective catheterization. In addition to thrombus formation from foreign bodies in the circulation, a considerable amount of thrombogenic endothelial damage may be done by the passage of the superselective catheter. Anticoagulation is especially necessary during embolization procedures to help reduce the likelihood of thrombus formation and propagation in the parent vessel of occluded feeding pedicles or in veins draining the AVM. At one of our institutions, a 5000-unit/70-kg bolus of heparin is given intravenously after the femoral sheath has been secured and a baseline activated clotting time (ACT) is obtained. ACT levels two times above baseline are desirable, and hourly checks are performed. After the conclusion of the procedure, a continuous heparin infusion is initiated and may be continued through the first night in the setting of poor drainage in the capacious veins of the AVM, maintaining partial thromboplastin time (PTT) between 1.5 and 2 times baseline. When used overnight, heparin is discontinued the next day as a period of 24 hours is felt to be sufficient for a ‘‘pseudoendothelial’’ layer to form and prevent either retrograde or antegrade thrombus formation that may propagate along the arterial tree (and the venous system in AVMs) with potentially disastrous results. The femoral introducer sheath is removed after the procedure with the aid of several devices to close the arteriotomy site. Monitoring A baseline arterial blood gas at the time of femoral artery access is useful to correlate baseline O2 and pCO2 levels with O2 saturation and end-tidal CO2 as measured through a nasal cannula. Patients receive large quantities of fluid and contrast and may diurese considerably; thus baseline hematocrit determination is helpful. Based on available evidence, extremes of both
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hemodilution and hemoconcentration should be avoided and euvolemia should be maintained. Intravenous solutions containing dextrose are not used during interventional procedures, because dextrose has been shown to be deleterious in the setting of cerebral ischemia, should it occur periprocedurally (47). Induced Hypotension The primary indication for elective deliberate hypotension is to slow flow in an AVM feeding artery during injection of embolic agent or to better assess the angiographic anatomy of highflow AVMs during certain stages of superselective angiography. With the patient properly sedated, mean arterial pressures of approximately 50 mmHg can be safely reached and easily reversed. Such values are more easily achieved in the setting of general anesthesia. Selective angiography of the feeding pedicles demonstrates a significant increase in the contrast agent’s transit time, and thus allows the interventionalist greater control over the injection of glue into the nidus. In instances where this degree of hypotension fails to sufficiently slow flow through the arteriovenous shunt, adenosine-induced cardiac pause has allowed us to achieve sustained mean arterial pressures of less than 40 mmHg for periods of up to 20 seconds. This time is usually sufficient to allow for the safe and precise deposition of glue into the AVM nidus and feeding pedicle without transiting into the venous system. In patients under monitored anesthetic care, short-acting beta-blockers are the agents of choice. Patients who do not respond to these medications may require other agents such as sodium nitroprusside (SNP) (29). The greatest disadvantage of SNP is that it can be difficult to titrate, and as a result, a patient may become momentarily severely hypotensive. Under the conditions of conscious sedation, the onset of hypotension-induced nausea and vomiting can be disastrous as it can result in catheter migration and possible vessel dissection with the retching that may ensue. Furthermore, the nausea may be confused with acute intracranial hypertension from vascular perforation. In patients treated under general anesthesia, blood pressure may be more easily titrated by mildly deepening the level of anesthesia with short-acting inhalation agents. FUNCTIONAL TESTING Functional or provocative testing may reduce the complications of arterial embolization (48–50). It is performed before therapeutic embolization to determine if embolization at that site will jeopardize normal brain tissue. Such testing is a variation and extension of the Wada and Rasmussen test (51), in which amobarbital is injected into the internal carotid artery to determine hemispheric dominance and language function. The ideal mode of testing, which most closely mimics the injection of some embolic agents, is the temporary occlusion of the target vessel with a balloon. This procedure would allow any collateral blood flow distal to the site of occlusion to supply the parenchyma. The disadvantage to temporary balloon occlusion is that it does not mimic the total occlusion that can occur with deeply penetrating agents such as the cyanoacrylates. The injection of a drug such as amobarbital into the proposed site of occlusion affects any tissue that is supplied downstream to the site of injection and thus simulates destruction, yielding a false-positive result. This technique, however, is safer and technically easier than the introduction of balloons. It also mimics the deep penetration that is obtained by the liquid embolic agents such as the cyanoacrylates or ethanol. Other modes of temporary vessel occlusion for provocative testing are not appropriate. Before testing, the level of sedation should be decreased by stopping the propofol infusion. After a baseline neurological examination is performed, sodium amobarbital (30 mg) is given first and then lidocaine (30 mg) mixed with contrast is given via the microcatheter. An angiogram is obtained to document the distribution of the drug/contrast mixture. Sodium amobarbital is used for investigating gray matter areas. Lidocaine may be used for evaluating the integrity of the white matter tracts (52,53). The use of lidocaine in intracerebral testing is controversial (49). After drug injection, the neurologic examination is repeated in the exact order in which the baseline was obtained. Attention is directed to areas at risk including higher cortical functions such as language, spatial relationships, and memory. A negative provocative test predicts the safe occlusion of the target vessel even with deeply penetrating agents, if the glue
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remains distal to the tip of the microcatheter. Therefore, most interventionalists perform provocative testing slightly proximal to the intended site of glue injection so as to have a safety margin within which reflux of agent will be safe. A positive provocative test result requires a careful reevaluation of the superselective angiogram in an attempt to determine the cause. If a normal branch is noted distal to the catheter tip, the catheter can be advanced beyond it and the pedicle reassessed. A negative provocative test result indicates that it is safe to proceed to permanent occlusion. If a positive provocative test result persists, consideration should be given as to whether the deficit is an acceptable permanent deficit compared with the option of not treating the pedicle. In some instances, one may choose to proceed with occlusion of the pedicle with mechanical agents such as coils. In so doing, collateral circulation may be spared and thus not result in a deficit. Some institutions forego the use of provocative testing in most instances of cerebral AVM embolization, suggesting that navigation of the microcatheter to within millimeters of the nidus precludes sacrificing any important normal branches; this approach is primarily used at one of our institutions. In general, provocative testing under conscious sedation is employed in the setting where embolization into the nidus may not have a significant amount of proximal ‘‘safety.’’ For example, at one of our institutions, patients with AVMs containing numerous en-passage feeding arteries in dominant, eloquent territories undergo provocative testing prior to glue deposition, whereas general anesthesia is used in all other patients. EQUIPMENT Vascular Access Most procedures are performed via a percutaneous transfemoral artery route using the Seldinger technique (54). All punctures should be performed below the inguinal ligament to avoid retroperitoneal or intraperitoneal hemorrhage. In certain circumstances, other routes may be required such as brachial artery or even direct carotid artery puncture. A triaxial system is used for all superselective angiograms and embolization procedures. This system consists of a 6-French (3 French ¼ 1 mm) femoral sheath; a 6-French guiding catheter which rests in the parent vessel (such as the internal carotid artery or vertebral artery); and the microcatheter, from which all superselective injections are performed. All catheters and sheaths are perfused with heparinized saline (2000 units/500 mL normal saline). Air bubbles are bled from the entire system, and all three components of the triaxial system are transduced to pressure monitors. The femoral sheath line provides accurate systemic arterial blood pressure, which is critical for the success of the procedure. The guiding catheter pressures are used to determine if there are differences in pressure gradient between what is considered systemic pressure and the pressures recorded in the internal carotid or vertebral arteries. The microcatheter pressures have provided us with a wealth of information regarding pedicle and intranidal flow dynamics (55–58). Catheters and Microcatheters Guiding catheters of 5 to 6 French are used for the embolization of AVMs (Fig. 5). Although various catheters are available, most possess the desired characteristics of being thin-walled, non-thrombogenic, trackable, shapeable, and flexible. Most importantly, they must possess an atraumatic tip. These guiding catheters serve as firm, stable platforms from which the flimsy, almost spaghetti-like microcatheters are delivered. Guiding catheters remain in the internal carotid or vertebral arteries throughout the procedure. Extreme care is given to checking and rechecking guiding catheter location, since inadvertent migration of the catheter distally may result in intimal dissection and subsequent parent vessel thrombosis. Catheters whose distal tips are 1 to 3 French in size (0.33–1.0 mm) are termed microcatheters and are used to reach almost any distal field in the body (Fig. 6). These catheters are manufactured with variable-stiffness properties, so that the distal portion of the microcatheter is very flexible. This property reduces the torquability of the catheter, making shaping of the microcatheter very important for the successful navigation of the higher order vessels. Most materials involved in the making of microcatheters are thermoplastic at body temperatures, that is, they can develop memory for specific vessel contours. There are two major types of microcatheters: wire-guided and flow-directed.
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Figure 5 Guiding catheters. Unlike diagnostic catheters, guiding catheters designed for neurovascular use are specifically made with soft, pliable tips and a braided internal design to provide the necessary pushability and trackability to the catheter, while minimizing the risk of vessel dissection or spasm. (A) Artist rendition of the Envoy guiding catheter exhibiting variable areas of stiffness (Cordis Neurovascular Corp., Miami, Florida, U.S.A.). (See color insert.) (B) Variable flexibility is also seen in these guiding catheters produced by Boston Scientific Corp. (Freemont, California, U.S.A.).
Wire-guided or geometry-guided catheters are stiff enough to be advanced along a straight vessel without the aid of a guide wire. The navigation of curves, however, requires the lead of a soft guide wire over which the catheter is advanced. Attempts to ‘‘force’’ the catheter around a vessel curve can result in vessel dissection and thrombosis. Because of their relative stiffness, it is difficult to negotiate these catheters passed second- or third-order branches of the intracranial vessels. Flow-directed microcatheters have distal segments between 1.2 and 1.8 French in size that are very floppy and depend on the flow of blood in a vessel to carry them to target sites. Some have a hydrophilic coating, which makes navigation faster and easier. Although these
Figure 6 Microcatheters. Polymer science has resulted in the development of microcatheters that can be safely navigated by over-the-wire techniques or by the flow of blood to distal targets along the cerebral arterial circulation, changing the art and science of AVM embolization. (A) Artist rendition of a Marathon microcatheter, compatible with Onyx use (Micro Therapeutics). (B) Magic microcatheters are the only truly flow-guided microcatheters that can achieve distal positioning in tortuous vasculature (Balt, Montmorency, France). Several varieties of microcatheters exist and are compatible with N-butyl-2-cyanoacrylate. (See color insert.)
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catheters are very gentle on the vessels, navigation can be quite challenging. Flow-directed microcatheters are used primarily for the injection of liquid embolic agents. Both catheters can be used with the aid of microguidewires as small as 0.008 inches in diameter, although in the case of flow-directed catheters, the guide wire is rarely advanced beyond the catheter tip. The introduction of the guide wire does provide some additional stiffness to the catheter that can make navigation easier in certain situations. Embolic Agents In general, any agent that can be delivered via a catheter to a desired location and obstruct flow can be considered an embolic agent. Consequently, many agents have been used for the obliteration of AVMs. Some are no longer in use and are only of historical interest, whereas others are used in varying degrees and are chosen in specific instances because of their distinct properties. All embolic agents can be subdivided into three types, each of which has advantages and disadvantages. Particulate Particulate agents, although initially the only agents available for embolization, are not considered to be permanent. They are now used primarily in cases where surgical excision of the AVM will be performed within days of the embolization. Generally considered safer than other agents, they still require meticulous technique and precise placement of the microcatheters. Polyvinyl alcohol. These particles come in a variety of sizes ranging from 50 to 1000 mm. Although the particles are considered permanent (i.e., they do not dissolve over time), the effective vessel occlusion is not, and recanalization of the target vessel occurs within months. Gelfoam. Gelatin sponges have been used primarily for the occlusion of small- and medium-sized vessels of the external circulation that may be contributing to an intracranial AVM. They are also used to occlude a parent vessel just distal to an AVM pedicle feeder so as to protect normal parenchyma before the introduction of a liquid or other particulate embolic agent. In so doing, the capillary bed of normal functional tissue is spared and supplied by collateral vessels. Again, careful evaluation of the superselective angiograms and functional testing are required before using this technique. Silk sutures. When 6–0 silk suture is cut into lengths of approximately 5 to 10 mm, it can be used in combination with other particulate agents (such as polyvinyl alcohol), and it can be a rather effective embolic agent for small- to medium-sized vessels. The indication for use in intracranial AVMs is limited, but it is useful in some instances where other particulates are not indicated. Mechanical Mechanical agents include numerous types of microcoils made from a variety of metal alloys ranging from platinum to stainless steel. Those most applicable to the treatment of intracranial AVMs are the platinum microcoils and the liquid coils. Despite their thrombogenic capacity, the permanence of occlusion with these agents is unclear. Platinum microcoils. Manufactured by a number of different companies (Cook, Inc., Bloomington, Indiana, U.S.A.; Boston Scientific Corp., Fremont, California, U.S.A.; and Cordis Neurovascular Corp., Miami, Florida, U.S.A.), these coils come in a variety of shapes and sizes and can be used to obliterate proximal dedicated feeding pedicles. With the use of certain thrombogenic agents such as Dacron, these coils have been useful in certain instances for vessel protection as well. Liquid coils. Boston Scientific Corporation has released ultra-fine platinum coils, which are primarily flow-directed and intended for use in the treatment of AVMs in conjunction with the use of cyanoacrylates. They reduce flow through the nidus in preparation for glue injection, thus reducing the risk of glue migration to the venous outflow tracts. Liquid Liquid embolic agents appear to provide the most permanent results. Although numerous experimental agents hold promise (e.g., various hydrogels and plastics), they are still investigational and not available in the United States. The most commonly used agents are the cyanoacrylates
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[predominantly NBCA—Histacryl, B. Braun Melsungen A.G, Leinfelden, Germany, and Trufill, Cordis Neurovascular Corp.], ethylene polyvinyl alcohol, and dehydrated ethanol. N-butyl-2 cyanoacrylate. NBCA is easily delivered through microcatheters and can be used to infiltrate the AVM nidus. Polymerization occurs when the liquid comes in contact with any ionic substance (e.g., blood or vessel wall). The polymerization time can be controlled and the cyanoacrylate rendered radiopaque by diluting the compound with a mixture of lipiodol and/or tantalum powder. The addition of more than 50% lipiodol may lead to absorption of the adhesive and thus may contribute to the reports of recanalization that occur 2 or 3 years after the occlusion (29,59). The polymerization rate can also be controlled with the addition of very small amounts of glacial acetic acid (60). In so doing, almost 100% NBCA can be delivered, resulting in a very rapid polymerization time. However, the inability to visualize the deposition of the glue and the high risk of bonding the catheter in place make the use of glacial acetic acid dangerous. Ethylene vinyl alcohol copolymer (Onyx). Approved in 2005 for use in the presurgical embolization of cerebral AVMs, this cohesive polymer solubilized in DMSO allows for prolonged injection and penetration into the nidus of the malformation. Premixed in two different viscosities (Onyx 18 and Onyx 34), the endovascular therapist simply chooses one of the two on the basis of the angiographic characteristics of the vessel to be treated. In general, the higher viscosity solution, Onyx 34, is used for the treatment of high-flow fistulae. Ethanol. Ethanol has been used for sclerotherapy of vascular malformations of the skin. Its use in the treatment of lesions of the central nervous system, AVMs in particular, is limited (61). When in contact with blood, ethanol denudes the vessel walls of their endothelium and precipitates the endothelial protoplasm. Because of its low viscosity, the migration of ethanol distally or its infiltration into surrounding capillary beds can result in necrosis of normal parenchyma. Therefore, its use is limited only to instances where selective angiography has demonstrated that the infusion will involve only the abnormal vasculature. STRATEGY AND TECHNIQUE The endovascular treatment plan depends largely on the size of the AVM and whether there is involvement of the deep gray matter (particularly the thalamus) or the primary efferent or afferent white matter tracts. The endovascular tactics used for each patient depend on the strategy, the goals, and the embolic agent(s) to be used. The vascular anatomy, including the size of the vessels, number of loops, collateral flow, watershed anastomosis, anomalies, venous outflow, and functional anatomy, all need to be considered. Attention should first be directed to areas of the AVM that pose a particular risk for bleeding, such as pedicles containing aneurysms or pseudoaneurysms. It is then best to approach the largest macrofistula component of the AVM first to reduce the overall flow of the AVM. This stratagem permits greater understanding of the remaining AVM and decreases some of the venous hypertension. However, it is usually the deep periventricular feeders that are the most challenging surgically and that are the sources of bleeding. As mentioned, hypotension is often useful to allow more control during embolization and to keep the embolic agent from passing into the cranial or systemic venous system. Total flow arrest can also be helpful and can be achieved by introducing a second catheter with a balloon into the system. This technique is rarely used, as we now use adenosine-induced cardiac pause to achieve near-flow arrest (57). More commonly, we can achieve flow arrest or flow control in the feeding pedicle by essentially achieving a wedge position with the microcatheter within the feeding pedicle. Surgical exposure of the AVM feeders in those rare cases in which it is needed can be helpful but is not often used. The technique for children is similar, although it requires miniaturization of the materials and additional attention to details (62). The nuances to the use of each of these agents are beyond the scope of this chapter. The technical methods can be broken down stepwise to include preoperative, operative, and postoperative considerations. As with all skills, the nuances of interventional methods are best learned through one-on-one instruction. Superselective angiography and superselective Wada testing are extremely useful in limiting postembolization neurologic deficit with even small AVMs. They are particularly useful in patients who have had a stroke or in patients with AVMs in eloquent areas. The authors’ preference for embolic agents is either NBCA or ethylene vinyl alcohol copolymer as opposed to ethanol or the particulate agents. These agents
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represent the most permanent of the embolic agents available. They are controllable, allow for deep penetration into the nidus, and can flow easily through the microcatheter. Importantly, the techniques for the use of one agent do not necessarily apply for the use of others. Whereas pedicle embolization with NBCA is performed over the course of seconds, ethylene vinyl alcohol copolymer is injected over the course of several minutes. OUTCOMES What is a ‘‘good’’ outcome in the endovascular management of AVMs, and do the potential benefits of endovascular treatment justify the risks? It is difficult to define a clear end-point in the neuroendovascular treatment of AVMs. At this time, the endovascular treatment of cerebral AVMs is primarily as an adjunct to surgery. Therefore, the definition of a ‘‘good’’ outcome means the successful obliteration of feeding arteries to the AVM nidus without clinical sequelae. The resection of the AVM then is simplified, and the risk for complications during the surgery is significantly reduced (63). Objective measurement of this benefit of embolization is difficult. Numerous series describe how embolization has significantly reduced the total operative time for AVM resection without significantly increasing the morbidity of the procedure. Several studies have tried to compare cohorts of patients who underwent surgery alone with those who underwent preoperative embolization and surgical resection (44,56,64–67). Although the patients undergoing embolization and surgery had more complex AVMs, as noted by the Spetzler–Martin grade, the outcomes were comparable to those patients with smaller, less complicated AVMs who did not undergo preoperative embolization. The conclusions that can be drawn from such studies are limited but extremely important. It is clear that preoperative endovascular management of AVMs provides a significant clinical benefit to the treatment of these lesions. Indeed, this therapy has made certain inoperable lesions now operable. Yet, it is difficult to clearly quantify this benefit. Studies evaluating the benefits of embolization for small lesions with a relatively low surgical complication rate (Spetzler–Martin Grade 1) are needed. Another assessment of outcome would be the rate of cure achieved with a given procedure. The use of embolization to cure AVMs has been limited (22–25). Although the literature quotes a 5% to 12% cure rate with embolization, long-term follow-up is lacking. Further experience with ethylene vinyl alcohol copolymer may demonstrate a relative increase in the cure rate from endovascular treatment of these lesions for high-grade AVMs (Spetzler– Martin Grade 3 or higher). COMPLICATIONS AND COMPLICATION AVOIDANCE Wolpert and Stein (68) first quantified the complications resulting from endovascular techniques. They noted that there was a higher incidence of neurological deficits secondary to embolic events than to intracerebral hemorrhage. Major complications associated with the embolization of AVMs before surgery are reported to range between 5% and 20% (24,69– 75). However, a review of 32 case series with 1246 patients reports the permanent and temporary morbidity rates at 8% and 10%, respectively, and a mortality rate of 1% (76). Minor and transient complications are highly variable. Minor, transient ischemic attacks occur in approximately 1% to 5% of cases (28). Other minor complications such as groin hematomas or small pseudoaneurysms that resolve without surgical intervention are not clearly reported (28). We will briefly review some of the more common complications encountered in the embolization of AVMs. Retrograde thrombosis of the parent vessel can occur when a large arterial feeding vessel to the AVM is occluded and the parent vessel (previously enlarged by the flow demand of the AVM) now supplies one or two small branches to normal parenchyma. Because of the sudden decrease in flow through this parent vessel or because of endothelial damage from passage of the microcatheter, thrombosis with subsequent infarction of the area supplied by these branches can occur. The incidence of this complication is not well documented. Keeping the patient euvolemic throughout the procedure (post-procedure as well), adequate heparinization during and after the procedure, and maintaining the patient in a normotensive state can avoid retrograde thrombosis. If retrograde thrombosis occurs, emergent computed
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tomography (CT) to rule out hemorrhagic infarction, a heparin bolus, and emergent angiography with possible thrombolysis may be required. Non-target occlusion (28) can occur secondary to catheter-induced thrombotic emboli or reflux of embolic agents into normal arterial branches. With the use of a constant heparinized saline flush through the femoral sheath, guiding catheter, and microcatheter, and with meticulous hand flushing of the catheters after every manipulation, the risk of catheter-induced thrombotic emboli is significantly reduced. The avoidance of reflux or migration of embolic agents to non-target vessels depends on careful analysis of digitally subtracted angiograms along with careful provocative testing. If indicated, parent vessels can be protected with the use of small liquid coils (Boston Scientific Corp., Fremont, California, U.S.A.) as previously described to reduce the likelihood of aberrant reflux of embolic agents into normal parenchyma. Venous thrombosis may result when embolization of a feeding pedicle significantly reduces flow in a draining vein. Because of the sluggish flow in such a capacious vessel, thrombosis may occur and can involve tributary veins from normal parenchyma. The best way to minimize the risk of this complication involves the adequate hydration and heparinization of the patient before, during, and sometimes after the procedure. Additionally, when a significant reduction in venous outflow is noted, no further embolization is performed at that stage. The patient is brought back for an additional stage of embolization within several weeks’ time. Venous thrombosis may also occur when embolic agents migrate to the venous outflow tract and result in venous obstruction without complete obliteration of the AVM compartments that are drained by that vein. As is possible during surgical resection of these lesions, the AVM can rupture, with potentially catastrophic results. If there is evidence of migration of an embolic agent to a draining vein with concomitant obliteration of outflow, it is imperative that systemic hypotension be continued and that the feeding pedicle and nidus be thoroughly obliterated before the conclusion of the procedure. Periembolic inflammation has occurred in instances where ethanol has been used for embolization (28) and can become symptomatic. The aggressive use of steroids in this situation is warranted. Perforation or dissection of arterial feeders has been reported with various consequences (77). Most perforations have been reported to be secondary to guide wires. As the average diameter of these wires is small (<28 gauge), the perforation may not be clinically relevant. If a perforation is significant, heparinization must be reversed, an emergent CT should be performed, and preparations should be made for possible emergent surgical intervention. The use of flowdirected catheters in higher order vessels and the judicious use of the microguidewires may reduce the incidence of this complication. Sometimes, tortuous vessels can be successfully navigated by advancing the guide wire to, but not beyond the tip of the microcatheter. By providing some rigidity to the system, the catheter sometimes is able to negotiate difficult turns and engage the appropriate vessel. Because of their adhesive properties and rapid polymerization time, microcatheter retention is associated exclusively with cyanoacrylate agents and has been reported to occur in approximately less than 3% of all embolization procedures (78). Several steps can be taken to reduce the risk of this event. First, care should be taken to try to achieve wedging of the microcatheter whenever technically possible. By essentially ‘‘wedging’’ the catheter tip against the walls of the feeding artery, one can avoid the reflux of glue proximally along the microcatheter. Other techniques that help to reduce the incidence of microcatheter retention include the use of a slower-setting mixture, removal of all redundant loops of microcatheter, and aspiration of the injecting syringe while abruptly pulling the microcatheter and guiding catheter at the conclusion of the injection. Not only does this technique minimize the likelihood of microcatheter retention, but also in the case of such an event, the catheter will usually fracture distally, approximately 15 to 25 cm from the tip. In most cases, the retained catheter will not recoil and will eventually endothelialize in situ. Patients with this complication should undergo oral anticoagulation for 3 to 6 months. However, if the microcatheter recoils, the risk that the retained catheter will result in parent vessel thrombosis is substantial, and the retained portion of the microcatheter should be surgically removed. In certain instances, the fractured microcatheter might be ‘‘tacked’’ into position with the use of self-expanding stents. Such a technique would require the use of clopidogrel bisulfate (Plavix) or another antiplatelet agent for several months.
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FUTURE DIRECTIONS Neuroendovascular techniques are in their infancy. In the last 30 years, tremendous advances in polymer science, catheter technology, adhesives, and imaging have made the techniques safer and more effective. Innovations in techniques and materials will continue. Transvenous approaches are being explored not just for dural arteriovenous fistulae, but also for the treatment of parenchymal AVMs. Microcatheters are used to obtain valuable information on the hemodynamics of AVMs both before and after embolization. New polymers are being evaluated that will be safer, easier to use, and permanent. Computer-aided navigation of microcatheters is being studied. New delivery systems for gene therapy are being developed. Although no one can predict how AVMs will be treated 30 years from now, one can be certain that interventional techniques will be an integral component of the cure, if not the cure itself.
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54. Seldinger S. Catheter replacement of the needle in percutaneous arteriography: a new technique. Acta Radiol 1953; 139:368–376. 55. Young WL, Pile-Spellman J, Prohovnik I, Kader A, Stein BM. Evidence for adaptive autoregulatory displacement in hypotensive cortical territories adjacent to arteriovenous malformations. Columbia University AVM Study Project. Neurosurgery 1994; 34:601–610. 56. DeMeritt JS, Pile-Spellman J, Mast H, et al. Outcome analysis of preoperative embolization with N-butyl cyanoacrylate in cerebral arteriovenous malformations. Am J Neuroradiol 1995; 16: 1801–1807. 57. Pile-Spellman J, Young WL, Joshi S, et al. Adenosine-induced cardiac pause for endovascular embolization of cerebral arteriovenous malformations: technical case report. Neurosurgery 1999; 44: 881–886. 58. Duong DH, Young WL, Vang MC, et al. Feeding artery pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral arteriovenous malformations. Stroke 1998; 29:1167–1176. 59. Cromwell LD, Kerber CW. Modification of cyanoacrylate for therapeutic embolization: preliminary experience. Am J Radiol 1979; 132:799–801. 60. Spiegel SM, Vinuela F, Goldwasser MJ, et al. Adjusting polymerization time of isobutyl-2cyanoacrylate. Am J Neuroradiol 1986; 7:109–112. 61. Yakes WF, Krauth L, Ecklund J, et al. Ethanol endovascular management of brain arteriovenous malformations: initial results. Neurosurgery 1997; 40:1145–1152. 62. Rodesch G, Lasjaunias P, TerBrugge K, Burrows P. Intracranial arteriovenous vascular lesions in children. Role of endovascular techniques apropos of 44 cases. Neurochirurgie 1988; 34:293–303. 63. Wikholm G, Lundqvist C, Svendsen P. Embolization of cerebral arteriovenous malformations: Part 1— Technique, morphology, and complications. Neurosurgery 1996; 39:448–457. 64. Wikholm G, Lundqvist C, Svendsen P. Transarterial embolization of cerebral arteriovenous malformations: improvement of results with experience. Am J Neuroradiol 1995; 16:1811–1817. 65. Wallace RC, Flom RA, Khayata MH, et al. The safety and effectiveness of brain arteriovenous malformation embolization using acrylic and particles: the experiences of a single institution. Neurosurgery 1995; 37:606–615. 66. Friedman DM, Verma R, Madrid M, Wisoff JH, Berenstein A. Recent improvement in outcome using transcatheter embolization techniques for neonatal aneurysmal malformations of the vein of Galen. Pediatrics 1993; 91:583–586. 67. Jafar JJ, Davis AJ, Berenstein A, Choi IS, Kupersmith MJ. The effect of embolization with N-butyl cyanoacrylatc prior to surgical resection of cerebral arteriovenous malformations. J Neurosurg 1993; 78:60–69. 68. Wolpert SM, Stein BM. Catheter embolization of intracranial arteriovenous malformations as an aid to surgical excision. Neuroradiology 1975; 10:73–85. 69. Debrun G, Vinuela F, Fox A, Drake CG. Embolization of cerebral arteriovenous malformations with bucrylate. J Neurosurg 1982; 56:615–627. 70. Deruty R, Lapras C, Pierluca P, et al. Perioperative embolization of cerebral arteriovenous malformations with butylcyanoacrylate (18 cases). Neurochirurgie 1985; 31:21–29. 71. Lasjaunias P, Manelfe C, TerBrugge K, Lopez Ibor L. Endovascular treatment of cerebral arteriovenous malformations. Neurosurg Rev 1986; 9:265–275. 72. Merland JJ, Rufenacht D, Laurent A, Guimaraens L. Endovascular treatment with isobutyl cyanoacrylate in patients with arteriovenous malformation of the brain. Indications, results and complications. Acta Radiol Suppl 1986; 369:621–622. 73. Berthelsen B, Lofgren J, Svendsen P. Embolization of cerebral arteriovenous malformations with bucrylate. Experience in a first series of 29 patients. Acta Radiol 1990; 31:13–21. 74. Bonati A. Interventional neuroradiology for the treatment of inaccessible arteriovenous malformations. Acta Neurochir 1992; 118:76–79. 75. Schumacher M, Horton JA. Treatment of cerebral arteriovenous malformations with PVA. Results and analysis of complications. Neuroradiology 1991; 33:101–105. 76. Frizzel RT, Fisher WS. Cure, morbidity and mortality associated with embolization of brain arteriovenous malformations: a review of 1246 patients in 32 series over a 35-year period. J Neurosurg 1995; 37:1031–1040. 77. Halbach VV, Higashida RF, Dowd CF, et al. Management of vascular perforations that occur during neurointerventional procedures. Am J Neuroradiol 1991; 12:319–327. 78. Aletich VA, Debrun GM. Intracranial arteriovenous malformations: the approach and technique of cyanoacrylate embolization. In: Connors JJ, Wojak JC. Interventional Neuroradiology: Strategies and Practical Techniques. Philadelphia: W.B. Saunders, 1999: 240–258.
13
Radiosurgical Principles Susan C. Pannullo and Jordan Abbott Department of Neurological Surgery, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
Robert Allbright Division of Radiation Oncology, Department of Radiology, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
INTRODUCTION Stereotactic radiosurgery is an appropriate treatment technique for selected patients with arteriovenous malformations (AVMs). Thousands of patients worldwide have been treated with stereotactic radiosurgery for intracranial AVMs (1). Radiosurgery may be performed either alone or in combination with AVM resection or embolization (2). In this chapter, we review the basic principles of radiosurgery as they apply to the management of patients with AVMs. Stereotactic radiosurgery is defined, in its purest form as a technique for delivery of highly focused radiation to a target in a single session with extreme precision, to create a desired radiobiologic response with minimal effect on normal surrounding structures (3,4). In contrast, external beam radiation is a multisession treatment technique in which uniform doses of radiation are delivered to larger volumes of tissue. This strategy is useful in certain situations and formed the original basis for the treatment of AVMs. Radiosurgical techniques allow delivery of high doses of energy to chosen target foci within the brain while minimizing exposure of normal structures. Multiple beams of highenergy electromagnetic radiation converge on one or several isocenters. Each beam travels through a separate path to reach the isocenter, limiting the dose of radiation delivered to nontargeted structures. In theory, an appropriate radiation dose is thus delivered to the AVM to produce the desired therapeutic effect (obliteration of the AVM nidus) while minimizing undesired side effects from exposure of normal brain tissues to radiation energy (5). HISTORY OF RADIOSURGERY FOR AVMs The concept of radiosurgery was developed at the Karolinska Institute by Lars Leksell in 1951 (6). Gamma knife radiosurgery for AVMs was first reported in 1972 (7). Its use spread internationally in the 1970s and reached North America in 1987 (8). An appreciation of the sensitivity of normal brain tissue surrounding the AVM was gained through the development of AVM proton beam radiosurgery by Kjellberg et al. (9), and this work became the basis for dose selection in radiosurgery. Linear accelerators (LINACs) were adapted for AVM radiosurgery in the early 1980s (10–13). Early radiosurgery was limited by the few imaging options available. Kjellberg’s single fraction proton beam radiosurgery was performed utilizing cerebral angiograms and a stereotactic device (14). For years, cerebral angiography was the imaging technique used for AVM diagnosis, radiosurgery treatment planning, and outcome evaluation (15). Computed tomography (CT) and magnetic resonance imaging (MRI) now make possible a more accurate delineation of the target volume and structure in three dimensions (16–18). RADIOBIOLOGY OF AVM RADIOSURGERY Conventionally fractionated radiotherapy is generally unsuccessful in the treatment of AVMs. Studies from the early 1990s with conventional fractionated radiation techniques and doses showed poor obliteration rates (19,20). A radiation dose delivered in a single fraction has a much greater biological effect than the same total dose given in a conventional fractionated scheme. This
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phenomenon can be understood from a radiation measure known as the a/b ratio, which indicates the sensitivity of a particular tissue type to fractionation (21). The a/b ratio is high for malignant brain tumors and low for normal brain tissue as well as for AVMs (22). Tissues with low a/b ratios are more resistant to fractionation and, conversely, are more responsive to a single large fraction. For AVMs, achieving the same effect with fractionated therapy as with single-fraction treatment would require doses that exceed normal tissue tolerance. PATHOLOGIC CHANGES OF AVMs AFTER RADIOSURGERY The precise mechanism through which radiation damage of the AVM vasculature induces obliteration of the nidus is unknown. It is assumed that radiation causes changes in cellular components of the vessels (23). Histologic examination of postmortem radiosurgery-treated AVM tissue reveals progressive closure of the lumen through a sequence of events analogous to wound healing (24). The primary event involves radiation damage to endothelium in targeted vessels. Studies have identified myofibroblasts in the intima of occluded vessels after endothelial damage. These cells are implicated in the secretion of collagen and the contraction of the vessel lumen (25). Contraction of the myofibroblasts leads to closing of the irradiated vessel. In vitro studies suggest that radiosurgically treated AVM endothelial cells initiate the transformation of intimal fibrocytes into myofibroblasts (26,27). Other characteristics of irradiated AVMs include intimal thickening, fragmentation of the elastic laminae, and mineralization in the vessel wall (27). The end response of the AVM vessel to this damage, similar to responses seen in other irradiated vessels, is progressive loss of cellularity and development of hyalinization. Several sources have postulated variation in the radiosensitivity of AVM vessels. Mavroidis et al. suggested that centrally located and large AVM vessels are less responsive to radiation (28). Another study described patients whose AVMs show no therapeutic response to unflawed radiosurgical treatment plans (29). A third study correlated the radiosensitivity of AVMs with that of skin fibroblast radiosensitivity (30). At present, there is no clinically applicable marker for the radiosensitivity of AVMs. It has also been difficult to characterize the radiosensitivity of AVM tissue in dose-response studies (31). RADIOSURGERY PLATFORMS The three major platforms for delivery of stereotactic radiosurgery are the gamma knife, modified or dedicated LINACs, and particle beam units. In gamma knife radiosurgery, 201 beams of cobalt-60 pass through various sized holes (collimators) in a helmet, converging on a fixed location on the target or isocenter (in this case, the AVM) placed in the center of the beams. The dose delivered is determined for each segment of the therapy by the size of the collimator and the exposure time of the target to the cobalt sources (32). LINACs create high-energy photons to deliver radiation to a target. In LINAC radiosurgery, the photon beams are very highly focused, generally in a single fraction, on the AVM (13,33,34). LINACs used for AVM radiosurgery may be modified multiuse LINACs fitted with hardware to allow mounting of the stereotactic headframe and software to permit radiosurgical treatment planning. Dedicated LINACs designed for stereotactic radiosurgery have been developed. These systems include the CyberKnife, a miniaturized LINAC on a robotic arm. The CyberKnife utilizes an image-guidance system to determine the precise target position without the need for a rigid headframe (35). The CyberKnife has been used for the treatment of extracranial sites and spinal AVMs (36,37). In particle beam radiosurgery, charged particles rather than photons are delivered during treatment. Because charged particles are produced in a prohibitively expensive cyclotron or synchrotron, there are few active units in the United States. The major benefit of particle beam radiosurgery is the ability to minimize entry and exit doses via the Bragg peak effect, in which the particles drop off their energy at one point (38). Both protons and helium nuclei have been used in the treatment of AVMs (39,40). STEREOTACTIC RADIOSURGERY TECHNIQUE The oldest and currently the most widely used technique for AVM radiosurgery is gamma knife radiosurgery. Major considerations in performing gamma knife radiosurgery are outlined
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below. Similar considerations apply to other types of radiosurgery except for frame-related issues, which are irrelevant in platforms such as the CyberKnife that do not utilize a headframe. Patient Selection Success of AVM radiosurgery is dependent on delivering a compact, sufficient radiation dose to the AVM nidus while excluding bordering structures from radiation damage. Both size and location of the AVM are major determinants of success (41–44). Additional factors include complexity of the AVM shape, radiation dose, accurate characterization of the AVM, and the natural history of the lesion. The radiosurgical option is currently pursued in the hopes of reducing the risk of morbidity associated with surgery, particularly in patients whose AVMs are deemed inoperable. Small, centrally located AVMs are frequently treated by radiosurgery, but recent reports describe staging strategies for effectively treating large AVMs as well (45,46). Several characteristics of the AVM itself—prior hemorrhage, small size, deep draining veins, and evidence of high flow rate—correlate with a higher risk of hemorrhage. These factors are also considered in decisions to perform radiosurgery because of concerns about hemorrhage during the latency period between treatment and obliteration (47). Aneurysms associated with AVMs may occur in up to 10% of the cases and may warrant management with open surgery or endovascular techniques before radiosurgery (48–52). Patient considerations include motivation and ability to cooperate with a procedure generally performed under local anesthesia. When necessary, especially in children, radiosurgery may be performed under general anesthesia. Body habitus is relevant in that extremely obese patients may be difficult to position in the gamma knife, especially if they have broad shoulders and short necks. These patients may be more easily treated in LINACs, especially with frameless systems such as the CyberKnife. Patients for whom open surgery is contraindicated, such as those with major comorbidities, are excellent candidates for radiosurgery. In addition, because of the minimal to noninvasive nature of radiosurgery, the need for continued anticoagulation is not a contraindication for radiosurgery. The Spetzler–Martin grading system, although not devised for assessing the response to radiosurgery, is generally used to determine the appropriateness of radiosurgery for treatment of a given AVM as compared to open surgery (53). The response of an AVM to radiosurgery correlates with its size and location (41–44), both of which are factors in the Spetzler–Martin scale. Grades I and II AVMs, which are both small and accessible, are most appropriately treated with surgery (54). Pikus et al. reported 100% angiographic obliteration after surgery with no new neurologic defects in patients with AVMs smaller than 3 cm in maximum diameter (55). AVMs that are grade IV and above are generally considered inappropriate candidates for surgery, because their location presents increased risk for serious neurologic sequelae (56). These AVMs, when appropriate, are treated by radiosurgery. For other high grade AVMs such as large, centrally located AVMs, the risk of treatment is equivalent to the risk of the natural course of disease, and these lesions are not treated. Controversy exists over the optimal treatment strategy for grade III AVMs. The results of a recent study suggest that among this class, larger and more eloquently located grade III AVMs carry surgical risks similar to those of higher grade AVMs and are more amenable to radiosurgery (57). Soderman et al. asserted that centrally located AVMs with a nidus volume of lesser than 10 mL should be treated with radiosurgery, and any AVM with a nidus volume of more than 10 mL should be treated with partial embolization and radiosurgery (58). The responses to radiosurgery and microsurgery are influenced by different factors; however, currently used grading systems are designed to predict surgical success. Multiple attempts have been made at devising grading systems to accurately predict the response to radiosurgery (28,42,59,60), but none is universally used. To date, comparisons between radiosurgery and microsurgery have favored the approach of microsurgery, but the studies are flawed by unmatched patient populations (61). No direct comparisons of the results of radiosurgery and microsurgery for similar grade AVMs have been performed. Because low Spetzler–Martin grade AVMs are consistently associated with radiosurgical nidus obliteration (42,62–64), a subset of AVMs of Spetzler–Martin Grades I and II may be good candidates for either microsurgery or radiosurgery. In these cases, patient preference should be considered, as well as the level of experience of the surgeon and radiation oncologist (65). Multiple morphological factors of AVMs, including compact compared with diffuse nidus,
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neovascularity, ease of nidus identification, number of draining veins, venous stenoses/ectasias, and intranidal aneurysms have been examined to inform this decision, but only AVMs with diffuse morphology and associated neovascularity were found to be at higher risk for radiological failure after radiosurgery (44). Higher radiation dose is the one factor that correlates consistently and strongly with radiosurgical success (42,62,63). Frame Application The stereotactic headframe provides immobility of the head and therefore, of the radiosurgical target, and it serves as a fixation point for devices such as the stereotactic fiducial box used in radiosurgery imaging. Correct placement of the stereotactic headframe is critical to the success of frame-based radiosurgery (Fig. 1). In gamma knife radiosurgery, the target is placed in a three-dimensional space as close to the center of the headframe as possible to facilitate patient positioning within the collimator helmet. Failure to optimally place the headframe may lead to the inability to ‘‘reach’’ the intended target due to collisions between the patient’s head or components of the frame and the collimator helmet (66). The headframe is placed under sterile conditions and local anesthesia. Frame placement procedures vary by center. At our institution, the patient is generally given mild oral sedation with 1 mg lorazepam after final patient consent is obtained. Topical anesthetic cream is applied to the four areas of anticipated pin placement, followed by injections of a lidocaine/ bupivacaine combination. A comfortable and comforting environment is provided at all times to maximize patient tolerance of the procedure. Treatment Planning Imaging Targeting techniques for AVM radiosurgery vary by center but generally involve performance of stereotactic MRI and MR angiography (MRA) (or CT scan if the patient cannot undergo MRI) and cerebral angiography after placement of the stereotactic headframe. MRI and MRA images are fused at the planning workstation with digitized anteroposterior and lateral angiogram images that best demonstrate the nidus as selected by the radiosurgeon and the interventional neurosurgeon or neuroradiologist. Treatment planning may also be done utilizing CT angiography rather than conventional angiography. In fact, CT angiography has become the imaging modality of choice at our institution for LINAC radiosurgery. Imaging techniques such as functional MRI may further enhance treatment planning for AVM radiosurgery (Fig. 2). Creation of a Treatment Plan Treatment planning is carried out by a team composed of the radiation oncologist, neurosurgeon, and physicist in concert with the computer. Target identification is confirmed, and dosing to the AVM target and other structures is calculated. Collision avoidance is an important part of treatment planning as well, but is not definitively established until the patient is actually positioned in the collimator helmet. Collimator helmet size is determined during
Figure 1 Gamma knife headframe placement. (See color insert.)
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Figure 2 Arteriovenous malformation radiosurgery treatment plan. (See color insert.)
treatment planning as well; collimators available in the Leksell gamma knife include 4, 8, 14, and 18 mm sizes (Fig. 2). Dosing The dosing objective in treatment planning for AVM radiosurgery is delivery of the highest effective dose to the target while limiting radiation exposure of the surrounding normal tissue. Three-dimensional stereotactic MR and stereotactic angiography delineate the usually irregular shape of an AVM nidus (67), decreasing the likelihood of inadequate radiation dosing to the AVM margins. Dose-response studies demonstrate a correlation between the minimum dose supplied to the margins and the obliteration rate (42,62,63). While the marginal dose significantly influences AVM obliteration, increases in dose and/or increases in volume irradiated produce increases in complications. The volume of irradiated tissue that receives 12 Gy has been shown to correlate with radiation-induced complications (63,68,69). It is generally believed that the lower efficacy of radiosurgery for large AVMs results from decreased doses as a precautionary measure, in an attempt to minimize this ‘‘12 Gy volume.’’ Dose-response studies indicate a meaningful response increment up to 25 Gy. Above this point, there is minimal increase in obliteration rates but a significant increase in complications (Fig. 2) (27). Treatment Delivery Once a treatment plan has been produced, the team members ‘‘sign off’’ on it, and the treatment delivery phase proceeds. Using stereotactic coordinates, the patient’s head is placed in the collimator helmet. More than one collimator helmet size may be used in treatment; helmets are changed during the procedure by the treatment team. The patient is positioned on the treatment couch, which is moved into the gamma knife machine. The unit has doors that open for the duration of the treatment, exposing the cobalt-60 sources. The cobalt-60 is collimated by the holes in the collimator helmet, delivering the prescribed radiation dose (Fig. 3).
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Figure 3 Gamma knife radiosurgery treatment delivery. (See color insert.)
Radiosurgery is generally an outpatient procedure. After treatment, the headframe is removed, antibiotic ointment and a small headwrap may be applied, and the patient is discharged from the unit.
EVALUATION OF TREATMENT RESPONSE Cerebral angiography is required to confirm nidus obliteration (70). To minimize the risks associated with angiography, other imaging modalities such as MRI and MRA are used to track AVM response until approximately three years after radiosurgery, when AVM obliteration is probably completed (71). Historically, angiography was performed at one-year intervals after radiosurgery; however, some centers now perform MRI/MRA every 6 to 12 months and perform confirmatory angiograms only if these studies suggest that obliteration has occurred. MRI scans alone are not adequate to determine whether an AVM has completely disappeared after radiosurgery, but the technique is useful for documenting treatment effects such as edema and radiation necrosis (71,72). It has been generally believed that an inherent latency period exists from the time of radiosurgery to the time of angiographic obliteration of the AVM, and that during this period the risk of hemorrhage is not significantly reduced from the risk before radiosurgery (48,73). The latency period has been found to be three to five years; risk of hemorrhage remains 3% to 4% per year (74). Some authors have asserted that this latency period is a major disadvantage of AVM radiosurgery when compared to open surgery, where the reduction of the risk of hemorrhage is immediate and definitive (55,75). The results of a recent study suggest that the risk of hemorrhage during the latency period is reduced from that of the pretreatment level (76). Once angiographic obliteration has occurred, the risk of hemorrhage diminishes dramatically, although it does not become zero (77). The failure of the AVM to occlude three years after radiosurgery is considered an indication for retreatment. Reasons for failed occlusion may be inadequate imaging, inadequate appreciation of the target volume, targeting error, and, possibly, radioresistance of the AVM (62). A relationship between the size of the AVM and the success rate for obliteration has been demonstrated (41–44,78). Success rates for AVM radiosurgery range from 65% to 80%, with small AVMs (less than 3 cm) having the highest chance for obliteration (9,29,42,74,79–83). AVM-related symptoms such as seizures, headaches, or neurological deficits may persist
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despite angiographically confirmed obliteration (84). These symptoms are believed to result from radiation-induced tissue changes that develop in tissue around the AVM. COMPLICATIONS Early Complications Seizures, nausea, vomiting, and headache have been reported to occur immediately after radiosurgery (85). In general, however, early complications are transient and mild (85). Headache is treated with mild analgesics (86). Ice packs are applied as necessary to pin sites. In patients who have a known seizure history, it is particularly important to confirm compliance with medications and acceptable preoperative seizure control; and anticonvulsant levels should be documented where appropriate. In patients with cortical AVMs, some neurosurgeons advocate use of perioperative prophylactic anticonvulsants, although this practice has not been well supported by data. Late Complications Late complications of radiosurgery for AVMs are discussed extensively in Chapter 31. These complications include seizure, hemorrhage, symptomatic edema, radiation necrosis, and cyst formation (84,87–89). The overall risk for complications is associated with treatment dose and volume, brainstem or thalamic location of the lesion, and patient age (90). The risk of hemorrhage is associated with prior hemorrhage, single draining vein, diffuse AVM morphology, and associated proximal aneurysm (48,91). Asymptomatic MRI changes and increased seizure frequency are often transient (72). MRI abnormalities are considered a treatment effect and are generally not considered true complications. Seizure frequency may increase, although radiosurgery reduces seizure frequency in the majority of patients (92,93). Glucocorticoids may be effective on a temporary basis for management of symptomatic radiation-induced edema. Occasionally, surgery may be necessary for management of large necrotic masses or postradiosurgery cysts (94). COMBINED MODALITY MANAGEMENT OF AVMs Surgery Plus Radiosurgery Although in the majority of cases in which it is used, surgical resection is definitive management of an AVM, occasionally residual nidus or recurrent nidus appears on a follow-up angiogram and may warrant adjuvant radiosurgical treatment (95). In these cases, the nidus is generally small, and as with primarily treated small AVMs, successful obliteration rates are high. The presence of associated aneurysms, as discussed above, may also prompt a combination of open surgical and radiosurgical approaches. Embolization Plus Radiosurgery Preradiosurgery embolization may be useful in ‘‘downsizing’’ a large AVM to make it a better radiosurgical target (96–105). In some cases, however, embolization does not improve the target, and occasionally it makes targeting more difficult (106). Embolization has been used after radiosurgery to treat AVMs that did not respond to radiosurgery (107). Some have expressed concern that recanalization of a previously embolized AVM may be responsible for some cases of radiosurgery failure, as transiently obscured parts of the AVM were not targeted during radiosurgery (108). Objectives for embolization are generally reviewed before consideration of combined modality treatment. SINGLE FRACTION VERSUS FRACTIONATED THERAPY Although AVM radiosurgery has traditionally been carried out in a single session, alternate radiation strategies, including planned fractionation and sequential partial AVM treatment, are sometimes used to treat larger lesions (109–111). The terms ‘‘fractionated stereotactic radiosurgery’’ and ‘‘fractionated stereotactic radiotherapy’’ have been used to describe multifraction techniques. The indications, radiation doses, and outcomes for fractionated strategies are less well defined than those for single fraction treatment.
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FUTURE DIRECTIONS FOR AVM RADIOSURGERY Technology developments in neuroimaging and delivery platforms may improve targeting of AVMs and simplify treatment. In addition, improved understanding of the radiobiology of the AVM response to radiosurgery may lead to better approaches for increasing obliteration rates and shortening the latency period to obliteration. Radiosensitizers may increase the sensitivity of AVM vasculature to radiation; this concept has been more deeply explored for tumor radiosurgery to date (112). Targeted therapies such as gene therapy have been studied as potential radiation sensitizing techniques; these concepts may be applied as well to the treatment of AVMs (112). Normal brain tissue may be protected from radiation through various strategies including the use of cerebral protective agents, and radiation-damaged brain tissue may be repaired with the use of neural stem and progenitor cells (113). Selective protection from radiation of normal tissue surrounding an AVM would permit the delivery of higher doses to the nidus without an increase in complications. REFERENCES 1. Yamamoto M. Stereotactic radiosurgery for arteriovenous malformations. In: Pollock BE, ed. Contemporary Stereotactic Radiosurgery: Technique and Evaluation. New York: Futura Publishing Company, 2002:75–106. 2. Ogilvy CS, Stieg PE, Awad I, et al. AHA Scientific Statement: recommendations for the management of intracranial arteriovenous malformations: a statement for healthcare professionals from a special writing group of the Stroke Council, American Stroke Association. Stroke 2001; 32(6):1458–1471. 3. Heros RC, Korosue K. Radiation treatment of cerebral arteriovenous malformations. N Engl J Med 1990; 323(2):127–129. 4. Pollock BE, Lunsford LD. A call to define stereotactic radiosurgery. Neurosurgery 2004; 55(6): 1371–1373. 5. Pellettieri L, Blomquist E. Differences in radiosensitivity between brain, small and large arteriovenous malformations. A tentative explanation of the incongruent results of radiotherapy. Med Hypotheses 1999; 52(6):551–556. 6. Leksell L. The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 1951; 102(4): 316–319. 7. Steiner L, Leksell L, Greitz T, et al. Stereotaxic radiosurgery for cerebral arteriovenous malformations. Report of a case. Acta Chir Scand 1972; 138(5):459–464. 8. Lunsford LD, Flickinger J, Lindner G, Maitz A. Stereotactic radiosurgery of the brain using the first United States 201 cobalt-60 source gamma knife. Neurosurgery 1989; 24(2):151–159. 9. Kjellberg RN, Hanamura T, Davis KR, et al. Bragg-peak proton-beam therapy for arteriovenous malformations of the brain. N Engl J Med 1983; 309(5):269–274. 10. Loeffler JS, Alexander E III, Siddon RL, et al. Stereotactic radiosurgery for intracranial arteriovenous malformations using a standard linear accelerator. Int J Radiat Oncol Biol Phys 1989; 17(3):673–677. 11. Podgorsak EB, Pike GB, Pla M, et al. Radiosurgery with photon beams: physical aspects and adequacy of linear accelerators. Radiother Oncol 1990; 17(4):349–358. 12. Colombo F, Benedetti A, Pozza F, et al. Stereotactic radiosurgery utilizing a linear accelerator. Appl Neurophysiol 1985; 48(1–6):133–145. 13. Greitz T, Lax I, Bergstrom M, et al. Stereotactic radiation therapy of intracranial lesions. Methodologic aspects. Acta Radiol Oncol 1986; 25(2):81–89. 14. Kjellberg RN, Davis KR, Lyons S, et al. Bragg peak proton beam therapy for arteriovenous malformation of the brain. Clin Neurosurg 1983; 31:248–290. 15. Sadler LR, Jungreis CA, Lunsford LD, Trapanotto MM. Angiographic technique to precede gamma knife radiosurgery for intracranial arteriovenous malformations. Am J Neuroradiol 1990; 11(6): 1157–1161. 16. Pelizzari CA. Image processing in stereotactic planning: volume visualization and image registration. Med Dosim 1998; 23(3):137–145. 17. Bova FJ, Friedman WA. Stereotactic angiography: an inadequate database for radiosurgery? Int J Radiat Oncol Biol Phys 1991; 20(4):891–895. 18. Phillips MH, Kessler M, Chuang FY, et al. Image correlation of MRI and CT in treatment planning for radiosurgery of intracranial vascular malformations. Int J Radiat Oncol Biol Phys 1991; 20(4): 881–889. 19. Laing RW, Childs J, Brada M. Failure of conventionally fractionated radiotherapy to decrease the risk of hemorrhage in inoperable arteriovenous malformations. Neurosurgery 1992; 30(6):872–875; discussion 875–876. 20. Redekop GJ, Elisevich KV, Gaspar LE, et al. Conventional radiation therapy of intracranial arteriovenous malformations: long-term results. J Neurosurg 1993; 78(3):413–422.
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21. Larson DA, Flickinger JC, Loeffler JS. The radiobiology of radiosurgery. Int J Radiat Oncol Biol Phys 1993; 25(3):557–561. 22. Hall EJ, Brenner DJ. The radiobiology of radiosurgery: rationale for different treatment regimes for AVMs and malignancies. Int J Radiat Oncol Biol Phys 1993; 25(2):381–385. 23. Szeifert GT, Major O, Fazekas I, Nagy Z. Effects of radiation on cerebral vasculature: a review. Neurosurgery 2001; 48(2):452–453. 24. Schneider BF, Eberhard DA, Steiner LE. Histopathology of arteriovenous malformations after gamma knife radiosurgery. J Neurosurg 1997; 87(3):352–357. 25. Szeifert GT, Kemeny AA, Timperley WR, Forster DM. The potential role of myofibroblasts in the obliteration of arteriovenous malformations after radiosurgery. Neurosurgery 1997; 40(1):61–65; discussion 65–66. 26. Major O, Szeifert GT, Fazekas I, et al. Effect of a single high-dose gamma irradiation on cultured cells in human cerebral arteriovenous malformation. J Neurosurg 2002; 97(suppl 5):459–463. 27. Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD. An analysis of the dose-response for arteriovenous malformation radiosurgery and other factors affecting obliteration. Radiother Oncol 2002; 63(3):347–354. 28. Mavroidis P, Theodorou K, Lefkopoulos D, et al. Prediction of AVM obliteration after stereotactic radiotherapy using radiobiological modelling. Phys Med Biol 2002; 47(14):2471–2494. 29. Pollock BE, Gorman DA, Coffey RJ. Patient outcomes after arteriovenous malformation radiosurgical management: results based on a 5- to 14-year follow-up study. Neurosurgery 2003; 52(6): 1291–1296; discussion 1296–1297. 30. Raaphorst GP, Malone S, Alsbeih G, et al. Skin fibroblasts in vitro radiosensitivity can predict for late complications following AVM radiosurgery. Radiother Oncol 2002; 64(2):153–156. 31. Flickinger JC, Pollock BE, Kondziolka D, Lunsford LD. A dose-response analysis of arteriovenous malformation obliteration after radiosurgery. Int J Radiat Oncol Biol Phys 1996; 36(4):873–879. 32. Yamamoto M. Gamma Knife radiosurgery: technology, applications, and future directions. Neurosurg Clin N Am 1999; 10(2):181–202. 33. Betti OO, Galmarini D, Derechinsky V. Radiosurgery with a linear accelerator. Methodological aspects. Stereotact Funct Neurosurg 1991; 57(1–2):87–98. 34. Betti OO. Treatment of arteriovenous malformations with the linear accelerator. Appl Neurophysiol 1987; 50(1–6):262. 35. Adler JR Jr., Chang SD, Murphy MJ, et al. The Cyberknife: a frameless robotic system for radiosurgery. Stereotact Funct Neurosurg 1997; 69(1–4 Pt 2):124–128. 36. Ryu SI, Chang SD, Kim DH, et al. Image-guided hypo-fractionated stereotactic radiosurgery to spinal lesions. Neurosurgery 2001; 49(4):838–846. 37. Takacs I, Hamilton AJ. Extracranial stereotactic radiosurgery: applications for the spine and beyond. Neurosurg Clin N Am 1999; 10(2):257–270. 38. Lyman JT, Phillips MH, Frankel KA, et al. Radiation physics for particle beam radiosurgery. Neurosurg Clin N Am 1992; 3(1):1–8. 39. Steinberg GK, Fabrikant JI, Marks MP, et al. Stereotactic helium ion Bragg peak radiosurgery for intracranial arteriovenous malformations. Detailed clinical and neuroradiologic outcome. Stereotact Funct Neurosurg 1991; 57(1–2):36–49. 40. Kjellberg RN. Stereotactic Bragg peak proton beam radiosurgery for cerebral arteriovenous malformations. Ann Clin Res 1986; 18(suppl 47):17–19. 41. Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD. Analysis of neurological sequelae from radiosurgery of arteriovenous malformations: how location affects outcome. Int J Radiat Oncol Biol Phys 1998; 40(2):273–278. 42. Karlsson B, Lindquist C, Steiner L. Prediction of obliteration after gamma knife surgery for cerebral arteriovenous malformations. Neurosurgery 1997; 40(3):425–430; discussion 430–431. 43. Yamamoto Y, Coffey RJ, Nichols DA, Shaw EG. Interim report on the radiosurgical treatment of cerebral arteriovenous malformations. The influence of size, dose, time, and technical factors on obliteration rate. J Neurosurg 1995; 83(5):832–837. 44. Zipfel GJ, Bradshaw P, Bova FJ, Friedman WA. Do the morphological characteristics of arteriovenous malformations affect the results of radiosurgery? J Neurosurg 2004; 101(3):393–401. 45. Ganapathy K, Shankarnarayanan V, Saji, et al. Obliteration of giant corpus callosum AVM with linac based stereotactic radiosurgery. J Clin Neurosci 2003; 10(2):272–276. 46. Firlik AD, Levy EI, Kondziolka D, Yonas H. Staged volume radiosurgery followed by microsurgical resection: a novel treatment for giant cerebral arteriovenous malformations: technical case report. Neurosurgery 1998; 43(5):1223–1228. 47. Stereotactic Radiosurgery for Patients with Intracranial Arteriovenous Malformations (AVM). Radiosurgery Practice Guideline Report: International RadioSurgery Association, 2003, v. 2–03. 48. Pollock BE, Flickinger JC, Lunsford LD, et al. Hemorrhage risk after stereotactic radiosurgery of cerebral arteriovenous malformations. Neurosurgery 1996; 38(4):652–659; discussion 659–661. 49. Thompson RC, Steinberg GK, Levy RP, Marks MP. The management of patients with arteriovenous malformations and associated intracranial aneurysms. Neurosurgery 1998; 43(2):202–211; discussion 211–212.
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50. Deruty R, Mottolese C, Soustiel JF, Pelissou-Guyotat I. Association of cerebral arteriovenous malformation and cerebral aneurysm. Diagnosis and management. Acta Neurochir (Wien) 1990; 107(3–4): 133–139. 51. Redekop G, TerBrugge K, Montanera W, Willinsky R. Arterial aneurysms associated with cerebral arteriovenous malformations: classification, incidence, and risk of hemorrhage. J Neurosurg 1998; 89(4):539–546. 52. Piotin M, Ross IB, Weill A, et al. Intracranial arterial aneurysms associated with arteriovenous malformations: endovascular treatment. Radiology 2001; 220(2):506–513. 53. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65(4):476–483. 54. Heros RC, Korosue K, Diebold PM. Surgical excision of cerebral arteriovenous malformations: late results. Neurosurgery 1990; 26(4):570–577; discussion 577–578. 55. Pikus HJ, Beach ML, Harbaugh RE. Microsurgical treatment of arteriovenous malformations: analysis and comparison with stereotactic radiosurgery. J Neurosurg 1998; 88(4):641–646. 56. Hamilton MG, Spetzler RF. The prospective application of a grading system for arteriovenous malformations. Neurosurgery 1994; 34(1):2–6; discussion 6–7. 57. Lawton MT. Spetzler–Martin Grade III arteriovenous malformations: surgical results and a modification of the grading scale. Neurosurgery 2003; 52(4):740–748; discussion 748–749. 58. Soderman M, Andersson T, Karlsson B, et al. Management of patients with brain arteriovenous malformations. Eur J Radiol 2003; 46(3):195–205. 59. Pollock BE, Flickinger JC. A proposed radiosurgery-based grading system for arteriovenous malformations. J Neurosurg 2002; 96(1):79–85. 60. Karlsson B, Lax I, Soderman M. Can the probability for obliteration after radiosurgery for arteriovenous malformations be accurately predicted? Int J Radiat Oncol Biol Phys 1999; 43(2):313–319. 61. Pollock BE. Radiosurgery and microsurgery for AVMs. J Neurosurg 1998; 89(4):691–693. 62. Ellis TL, Friedman WA, Bova FJ, et al. Analysis of treatment failure after radiosurgery for arteriovenous malformations. J Neurosurg 1998; 89(1):104–110. 63. Friedman WA, Bova FJ, Bollampally S, Bradshaw P. Analysis of factors predictive of success or complications in arteriovenous malformation radiosurgery. Neurosurgery 2003; 52(2):296–307; discussion 307–308. 64. Pollock BE, Flickinger JC, Lunsford LD, et al. Factors associated with successful arteriovenous malformation radiosurgery. Neurosurgery 1998; 42(6):1239–1244; discussion 1244–1247. 65. Pollock BE, Lunsford LD, Kondziolka D, et al. Patient outcomes after stereotactic radiosurgery for ‘‘operable’’ arteriovenous malformations. Neurosurgery 1994; 35(1):1–7; discussion 7–8. 66. Treuer H, Hunsche S, Hoevels M, et al. The influence of head frame distortions on stereotactic localization and targeting. Phys Med Biol 2004; 49(17):3877–3887. 67. Herman MG, McCullough EC. Physical Aspects of Cranial Stereotactic Radiosurgery. New York: Futura Publishing Company, 2002:17–34. 68. Flickinger JC, Kondziolka D, Pollock BE, et al. Complications from arteriovenous malformation radiosurgery: multivariate analysis and risk modeling. Int J Radiat Oncol Biol Phys 1997; 38(3): 485–490. 69. Korytko T, Radivoyevitch T, Colussi V, et al. 12 Gy gamma knife radiosurgical volume is a predictor for radiation necrosis in non-AVM intracranial tumors. Int J Radiat Oncol Biol Phys 2006; 64(2): 419–424. 70. Nussel F, Wegmuller H, Huber P. Comparison of magnetic resonance angiography, magnetic resonance imaging and conventional angiography in cerebral arteriovenous malformation. Neuroradiology 1991; 33(1):56–61. 71. Pollock BE, Kondziolka D, Flickinger JC, et al. Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery. J Neurosurg 1996; 85(6): 1044–1049. 72. Flickinger JC, Lunsford LD, Kondziolka D, et al. Radiosurgery and brain tolerance: an analysis of neurodiagnostic imaging changes after gamma knife radiosurgery for arteriovenous malformations. Int J Radiat Oncol Biol Phys 1992; 23(1):19–26. 73. Friedman WA, Blatt DL, Bova FJ, et al. The risk of hemorrhage after radiosurgery for arteriovenous malformations. J Neurosurg 1996; 84(6):912–919. 74. Steiner L, Lindquist C, Adler JR, et al. Clinical outcome of radiosurgery for cerebral arteriovenous malformations. J Neurosurg 1992; 77(1):1–8. 75. Schaller C, Schramm J. Microsurgical results for small arteriovenous malformations accessible for radiosurgical or embolization treatment. Neurosurgery 1997; 40(4):664–672; discussion 672–674. 76. Maruyama K, Kawahara N, Shin M, et al. The risk of hemorrhage after radiosurgery for cerebral arteriovenous malformations. N Engl J Med 2005; 352(2):146–153. 77. Shin M, Kawahara N, Maruyama K, et al. Risk of hemorrhage from an arteriovenous malformation confirmed to have been obliterated on angiography after stereotactic radiosurgery. J Neurosurg 2005; 102(5):842–846. 78. Friedman WA, Bova FJ, Mendenhall WM. Linear accelerator radiosurgery for arteriovenous malformations: the relationship of size to outcome. J Neurosurg 1995; 82(2):180–189.
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Int J Radiat Oncol Biol Phys 1999; 44(1): 67–74. 85. Werner-Wasik M, Rudoler S, Preston PE, et al. Immediate side effects of stereotactic radiotherapy and radiosurgery. Int J Radiat Oncol Biol Phys 1999; 43(2):299–304. 86. Plowman PN. Glucocorticoids and prostate cancer in castrate men. J Clin Oncol 1999; 17(12): 3856–3860. 87. Izawa M, Hayashi M, Chernov M, et al. Long-term complications after gamma knife surgery for arteriovenous malformations. J Neurosurg 2005; 102(suppl):34–37. 88. Edmister WB, Lane JI, Gilbertson JR, et al. Tumefactive cysts: a delayed complication following radiosurgery for cerebral arteriovenous malformations. Am J Neuroradiol 2005; 26(5):1152–1157. 89. Husain AM, Mendez M, Friedman AH. Intractable epilepsy following radiosurgery for arteriovenous malformation. J Neurosurg 2001; 95(5):888–892. 90. Barker FG II, Butler WE, Lyons S, et al. Dose-volume prediction of radiation-related complications after proton beam radiosurgery for cerebral arteriovenous malformations. J Neurosurg 2003; 99(2): 254–263. 91. Pollock BE, Flickinger JC, Lunsford LD, et al. Factors that predict the bleeding risk of cerebral arteriovenous malformations. Stroke 1996; 27(1):1–6. 92. Schauble B, Cascino GD, Pollock BE, et al. Seizure outcomes after stereotactic radiosurgery for cerebral arteriovenous malformations. Neurology 2004; 63(4):683–687. 93. Hoh BL, Chapman PH, Loeffler JS, et al. Results of multimodality treatment for 141 patients with brain arteriovenous malformations and seizures: factors associated with seizure incidence and seizure outcomes. Neurosurgery 2002; 51(2):303–309; discussion 309–311. 94. Pollock BE, Brown RD Jr. Management of cysts arising after radiosurgery to treat intracranial arteriovenous malformations. Neurosurgery 2001; 49(2):259–264; discussion 264–265. 95. Chang SD, Marcellus ML, Marks MP, et al. Multimodality treatment of giant intracranial arteriovenous malformations. Neurosurgery 2003; 53(1):1–11; discussion 11–13. 96. Gobin YP, Laurent A, Merienne L, et al. Treatment of brain arteriovenous malformations by embolization and radiosurgery. J Neurosurg 1996; 85(1):19–28. 97. Duffner F, Freudenstein D, Becker G, et al. Combined treatment effects after embolization and radiosurgery in high-grade arteriovenous malformations. Case report and review of the literature. Stereotact Funct Neurosurg 2000; 75(1):27–34. 98. Pollock BE, Lunsford LD, Kondziolka D, Flickinger JC. Embolization and radiosurgery for AVMs. J Neurosurg 1997; 86(2):319–320; author reply 320–321. 99. Apostolides PJ, Lawton MT, Smith KA, Spetzler RF. Embolization and radiosurgery for AVMs. J Neurosurg 1997; 86(2):318–319; author reply 320–321. 100. Mathis JA, Barr JD, Horton JA, et al. 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Combined Therapy: The Team Approach C. Michael Cawley, III Departments of Neurosurgery and Neuroradiology, Emory University School of Medicine, Atlanta, Georgia, U.S.A.
Harry J. Cloft Departments of Radiology and Neurosurgery, Mayo Clinic College of Medicine, Rochester, Minnesota, U.S.A.
Nelson M. Oyesiku and Daniel L. Barrow Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, U.S.A.
INTRODUCTION As the knowledge of the natural history of intracranial arteriovenous malformations (AVMs) has evolved, it has become clear that these lesions, no matter their presentation, pose a significant risk to the health and welfare of those individuals harboring them. The morbidity and mortality risks associated with AVMs have been discussed in Chapter 5. Therefore, it is sufficient to say that for most patients whose life expectancy is at least 15 years, some form of treatment should be contemplated for all but the most dangerous lesions. In our opinion, the primary form of treatment for Spetzler–Martin Grades I–III lesions remains microsurgical removal. Grade VI AVMs, in general, cannot be cured without an unacceptable rate of morbidity (up to 50%) (1,2); thus the appropriate therapeutic plan for patients with these lesions is usually observation. It is in the treatment of Grade IV and V (and some Grade III) lesions that multimodality therapy is most beneficial. We will focus on these AVMs in this chapter. AVMs are relatively uncommon, and their cumulative morbidity and mortality risks are significant (3–5). We believe that optimal management is provided by a multidisciplinary team composed of a vascular neurosurgeon, a neurosurgical radiosurgeon, an interventional neuroradiologist, a vascular neurologist, a radiation oncologist, and a radiation physicist. Each team member brings different talents that, when combined, allow the team to recommend and carry out the treatment of an individual lesion in an individual patient with the lowest risk and the highest chance of success (6–13). The team should be headed by a vascular neurosurgeon, who is uniquely able to evaluate the surgical risks for each lesion. With refinement of microsurgical techniques and experience, risks of microsurgical resection of AVMs have declined to the point where most AVMs may be managed surgically with low morbidity and complete, immediate cure (1,2,5). Should a particular lesion be judged unsuitable for microsurgical resection alone, the assets of a multidisciplinary panel are brought to bear. The interventional neuroradiologist is best equipped to judge the potential benefits and risks of adjunctive or curative embolization, while the radiosurgeon is familiar with the potential and limitations of focused radiation. Through honest discussion, a consensus may be reached with the patients’ best interests in mind.
GOALS OF THERAPY The goals of treatment must be clearly identified by the team for each specific case. The relief of intractable headaches, repression/reversal of progressive neurologic deficit, and management of intracranial hypertension often do not require complete obliteration of an AVM. The reduction or obliteration of flow through dural feeders may ameliorate headaches, and the reversal of vascular steal created by the sump effects of arteriovenous shunts may halt progressive neurologic deficits that result from chronic ischemia. Such palliative treatment
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regimens are most often carried out with superselective embolization. The elimination of hemorrhage risk, by contrast, requires complete obliteration. If even the smallest residual tuft of AVM remains, no protection against hemorrhage is provided. In fact, some studies indicate that smaller lesions may rupture with more frequency, presumably due to increased feeding artery pressure (14–20). For reasons discussed elsewhere in this text (Chapters 10 and 12), embolization alone is rarely able to achieve complete and lasting obliteration of an AVM. Although radiosurgery alone provides cure in up to 85% of relatively small lesions (<2.5 cm diameter), there is a well-documented delay in therapeutic benefit of 18 months to three years. During this time the patient remains unprotected from the risk of hemorrhage. Larger lesions have been found to be unsuitable for radiosurgery alone due to a low total obliteration rate and an increased risk of radiation damage to surrounding brain. These limitations are discussed in more detail in Chapters 13 and 33. Multimodal therapy may offer the best chance for cure of the recalcitrant AVM. ‘‘Recalcitrant’’ lesions usually fall into the Spetzler–Martin Grade III–V category and may be defined as those AVMs which, because of size, location, or configuration, are not amenable to standard surgical or radiosurgical measures. A particular lesion may be identified as recalcitrant at presentation or evolve into one as more standard therapies fail. In such cases at least two and perhaps all three therapeutic modalities may be used to reach the treatment goal. Although the treatment of Spetzler–Martin Grade IV and V AVMs must be individualized, several generalizations may be made. First, the multidisciplinary team, led by the neurovascular surgeon, must set attainable goals. Second, a coherent strategy, including a timetable must be established. Third, as the treatment proceeds, the team must not let expectations and the failure to meet certain expectations interfere with the reality of what can be accomplished with a revision of treatment goals. Above all, then, flexibility is key to devising and implementing a treatment plan to achieve the most desirable result.
THERAPEUTIC STRATEGIES Embolization and Surgery (Figs. 1–4) Leussenhop et al. were the first to describe the embolization of an intracranial AVM (21–23). Subsequently, catheter technology advanced remarkably to allow the superselective catheterization of all but the smallest vessels (24). Catheters as small as 1.5 F (0.50 mm) are available in both steerable and flow-guided varieties. Advancements in embolic agents led to the development of a variety of liquid adhesives, particulates, and coils. These agents are each suited for specific situations. N-butyl cyanoacrylate (NBCA) is the most commonly used liquid adhesive but may not be ideal as a surgical adjunct due to its relative non-compressibility. The,
Figure 1 Axial (A) and coronal (B) magnetic resonance imaging scans demonstrating an arteriovenous malformation in the left sylvian fissure and operculum.
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Figure 2 Anteroposterior (A) and lateral (B) left carotid angiogram after embolization showing endovascular ‘‘glue’’ in the nidus of the arteriovenous malformation (AVM). (C) Anteroposterior intraoperative angiogram documents complete obliteration of the AVM after surgical resection.
‘‘dilution’’ of the adhesive liquids with lipiodol has become more widespread, diminishing many problems associated with hard glue casts encountered during surgery. However, particulates, such as polyvinyl alcohol (PVA), are still the most commonly used agents as adjuncts to surgery (25). The particles, which vary in size from 50–1000 mm, are mixed in a slurry with
Figure 3 Axial (A) and coronal (B) magnetic resonance imaging scans demonstrating an arteriovenous malformation in the left frontal region.
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Figure 4 Anteroposterior (A) and lateral (B) left carotid angiogram showing arteriovenous malformation (AVM) fed by branches of the internal carotid artery and middle cerebral arteries. (C) Lateral left carotid angiogram obtained during embolization of AVM with endovascular ‘‘glue.’’ (D) Anteroposterior and (E) lateral intraoperative angiogram documenting complete obliteration of the AVM.
normal saline. The solution is released in a flow-directed manner, and the particles occlude feeding arteries and fistulae smaller than their diameter. PVA is safer than glue because it is easily directed by the flow characteristics of the AVM, and there is little chance of inadvertent venous drainage occlusion as the non-occlusive particles are washed through and filtered by
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the lungs. However, PVA shortly becomes repermeable, allowing fistula or pedicle recanalization (26,27). For this reason, PVA is not generally used in combination with radiosurgery. PVA is, however, ideal as a preoperative adjunct (provided resection is carried out within about one week) due to its compressibility at surgery (28). The decision to use embolization as an operative adjunct must be made in a multidisciplinary framework. The benefits of preoperative embolization may include decreased operating time, decreased blood loss, obliteration of difficult-to-reach feeders, and a staged throttling of a high-flow AVM (15). This allows a more gradual redistribution of blood flow to dysautoregulated surrounding brain, thus decreasing the risk of normal perfusion pressure breakthrough (29–33). The risks of preoperative embolization also must be kept in mind. The morbidity and mortality rates are additive to those of surgery, and these rates are in the range of 6% and 3%, respectively (6,30,34–36). We do not routinely recommend preoperative adjunctive embolization for Spetzler– Martin Grades I and II lesions, as the risks of surgery alone are low (1,2). For Grades III and IV lesions for which definitive surgery is planned, preoperative obliteration of deep feeding vessels is the primary goal. These vessels are difficult to isolate surgically and are often enlarged branches of the lenticulostriates, the anterior and posterior choroidals, the thalamoperforators, or deep posterior cerebral vessels. Embolization of superficial feeders from the middle and anterior cerebral artery circulation is usually unnecessary as these vessels are near the exposed surface of the brain and are easily occluded at surgery. Embolization of the AVM through these feeders, however, may be warranted for high-flow lesions to more gradually redirect blood flow to the normal brain. The surgeon and the neuroradiologist must agree on a therapeutic strategy to ensure that the preoperative embolization is directed to that component of the AVM that will provide optimal benefit to the surgeon. As mentioned above, particulate embolization with PVA is most effective for nidal embolization with proximal release and provides a soft, compliant, and mobile mass at surgery. Should it be desirable to endovascularly occlude a large high-flow pedicle preoperatively, liquid adhesives such as NBCA are preferred. Regardless of the agents, the goal of preoperative embolization is feeder and nidus penetration and thrombosis, not venous outflow occlusion. The latter scenario may lead to post-embolization hemorrhage (36). We routinely perform embolization under general anesthesia to allow safe catheterization of small, distal arterial branches and to optimize controlled injection of embolic agents. Moderate doses of glucocorticoids or calcium-channel blockers may be administered periprocedurally. We use systemic anticoagulation with low-dose heparin to minimize the risk of a catheter-related embolic event. In our experience, microguidewire/microcatheter vessel perforation has occurred only occasionally. Usually, any small hemorrhage is asymptomatic, and the systemic anticoagulation can be reversed immediately with protamine if necessary. Embolization is much more rarely used as an intraoperative adjunct to surgery. Experienced groups have advocated such combined therapy in high-grade lesions, where morbidity and mortality rates approach 50% (37,38). These groups have developed a protocol whereby preoperative embolization with NBCA or PVA is carried out to diminish flow through a particular Grade IV–V AVM by as much as two-thirds. Surgery is then performed to isolate residual feeders, which are cannulated with 2.5-4 F catheters through which more embolic agent may be introduced (39). The final stage in such a protocol often involves radiosurgery. Advances in microcatheter technology, however, now have made it possible for interventional neuroradiologists to access the majority of feeding arteries to AVMs, making intraoperative embolization rarely necessary. Radiosurgery and Surgery Surgery is most often undertaken after radiosurgery when the latter treatment has failed. In such cases, microsurgical resection of residual AVM is often prompted by the presence of an intracerebral clot producing mass effect. Reports have analyzed only small numbers of patients (10). Staged Surgery Two surgical procedures are performed most commonly in the treatment of an AVM when postoperative angiography uncovers residual malformation. At our center, we feel that this
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eventuality can be virtually eliminated with the routine use of intraoperative angiography. Improvements in the quality of the digitally subtracted images obtained in the operating suite allow highly detailed examination of the intracranial vasculature comparable to that obtained in a conventional angiography suite. In our most recent series, we found residual AVM identified on intraoperative angiography in approximately 10% of cases. Having such information in a timely fashion allows us to locate such a residuum and resect it during one procedure. In no cases have postoperative angiograms differed from intraoperative studies; in fact, we no longer routinely perform postoperative studies. Less commonly, staged surgery is anticipated. Some authors have described its use in the treatment of high-flow AVMs with or without adjunctive embolization (1,2). Theoretically, staged procedures may allow for more gradual redistribution of previously shunted blood and thus lessen the chance of perfusion pressure breakthrough. Excessive intraoperative bleeding, brain swelling, and anesthetic complications may also dictate a staged approach to the removal of a particular lesion. In such cases, meticulous hemostasis must be achieved, and strict systemic blood pressure control and seizure prophylaxis must be maintained between procedures. Embolization and Radiosurgery Focused radiation has repeatedly been shown by postoperative angiography to be effective in obliterating 80% to 90% of selected AVMs with a diameter of up to 3 cm (40–43). The advantage of such treatment is that it is much less invasive than surgery and can be focused on malformations too deep to be safely accessed surgically. Disadvantages include a latent period of 18 to 36 months from treatment to AVM obliteration, during which no protection from hemorrhage is afforded (17,43,44). Other concerns include a 3% to 5% radiation necrosis rate and a 10% to 15% rate of treatment failure after three years (6,41–43). Failure rates are significantly higher for larger AVMs. Because of these drawbacks, we agree with other experts who continue to recommend surgery as the first line of treatment. Radiosurgery is indicated in cases where there exist medical contraindications to surgery, where surgery has failed, or where the anticipated surgical morbidity and mortality risks are high (45). In those cases where radiosurgery in indicated, it is an excellent option for small lesions (nidus 2–3 cm). However, although dosimetry hardware and software have improved greatly, allowing a more precise ‘‘shaping’’ of a radiation beam, some AVMs are simply too large to treat without an unacceptable risk of collateral radiation injury (41,42,46). In such cases, pre-radiation embolization is a reasonable option. The goal of this adjunct is to diminish the nidus size to below 3 cm in diameter. The embolizate must be permanent, and therefore a glue is usually used. Peripheral vessels are targeted, leaving the more tightly packed nidus and deep feeding vessels to be treated with radiosurgery. Cure rates with such a multidisciplinary approach in very high-grade malformations may reach 50% to 60% (8,11). Caution must be exercised in advocating pre-radiosurgical embolization in lesser grade AVMs. While the numbers of radiated AVMs that have been embolized is increasing, the leader of a multidisciplinary team must consider the risks associated with embolization (43,47). In one study, of 46 patients who underwent embolization as an adjunct to radiosurgery, nine developed neurologic complications from the embolization (48). In 16 of the 46 patients, AVM collaterals re-established themselves between embolization and radiation-induced obliteration. Such reports reinforce our opinion that embolization should be used only when the benefits clearly outweigh the risks and that only durable embolic agents should be used. ‘‘Triple Therapy’’ (Figs. 5–8) The multidisciplinary approach to the treatment of complex AVMs must, above all, be flexible. Various combinations of embolization, radiosurgery, and surgery must be employed with the interests of the patient being paramount. Only in rare cases are all three modalities required. Such a situation usually results after preoperative embolization and surgical resection have left a small residual lesion. Depending upon the location of such a residuum, and the surgeon and patient’s preference, the option of minimally invasive radiosurgery may be considered. Although it is preferable to re-explore the resection bed to accomplish cure immediately, radiosurgery has obvious benefits to a patient who has just undergone a stressful and extensive surgical procedure (cure, of course, would then be accomplished only after the aforementioned
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Figure 5 (A) Axial computed tomography scan showing left thalamic and intraventricular hemorrhage. (B) Coronal magnetic resonance imaging scan demonstrating an arteriovenous malformation in the left thalamus.
Figure 6 (A) Lateral superselective angiogram of left posterior cerebral artery during embolization of thalamic arteriovenous malformation (AVM) fed by posterior choroidal and thalamoperforating arteries. (B) Lateral and (C) anteroposterior vertebral angiogram showing thalamic AVM after embolization and during stereotactic radiosurgery.
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Figure 7 (A) Coronal magnetic resonance imaging scan and (B) anteroposterior vertebral angiogram performed two years after radiosurgery documenting reduction in the size of the arteriovenous malformation but significant residual nidus.
radiosurgical latency period). Less common is the situation in which pre-radiosurgical embolization has failed, resulting in late recanalization of an embolized but non-radiated AVM. In such a situation, repeat radiosurgery or surgical removal are options for completing treatment. In these cases, the lesion is usually much smaller and more manageable than the original lesion, rendering surgery less risky. REMEDIES FOR PALLIATION Certain high-grade AVMs cannot be cured without unacceptable risk. The leader of a multidisciplinary team must recognize such cases in which the natural history of a lesion poses less risk than its complete obliteration. In such situations, palliative therapies may be offered to try to modify the risks of living with an untreated high-grade AVM. Hemorrhage (Fig. 9) One of the most devastating risks associated with AVMs is hemorrahge, either intracerebral or subarachnoid. Certain characteristics such as flow-related aneurysms are present in 7% of AVMs, three-quarters of which are located on a major feeding vessel (4,49); such aneurysms are believed to possess the same risks as other intracranial aneurysms. Thus, either surgical or endovascular therapies are often aimed at obliterating flow-related aneurysms and thereby
Figure 8 (A) Anteroposterior and (B) lateral postoperative vertebral angiogram documenting complete obliteration of the arteriovenous malformation.
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Figure 9 (A) Axial magnetic resonance imaging (MRI) scan demonstrating left basal ganglia arteriovenous malformation (AVM) and associated hemorrhage with evidence of deep venous drainage shortly following presentation with intracerebral and intraventricular hemorrhage. (B) Follow-up MRI three years after stereotactic radiosurgery demonstrating dramatic reduction in the size of the AVM. (C) Anteroposterior left carotid angiogram three years after second radiosurgical procedure documenting complete obliteration of the AVM. A residual aneurysm arising at the origin of the feeding lenticular striate vessel was successfully clipped.
negating their significant morbidity and mortality implications—even if the malformation itself is left untreated (49). Although our bias continues to be toward surgical treatment of intracranial aneurysms as a first choice, flow-related aneurysms in close proximity to a large, high-grade AVM may more appropriately be treated endovascularly (assuming aneurysm characteristics are favorable for coiling). Progressive Neurologic Deficit The phenomenon of progressive neurologic deficits is believed to result from ‘‘vascular steal.’’ The high-flow, low-resistance AVM acts as a sump, preferably shunting blood away from surrounding normal brain. Such steal may result in progressive, insidious loss of function in the areas of brain surrounding a large AVM, leading to neurologic sequelae specific
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to the anatomic location of the lesion. Selective occlusion of large shunts within a high-grade malformation may decrease this sump effect and restore blood flow to normal brain. This occlusion is best accomplished by endovascular means. Such therapy is usually aimed at the occlusion of major shunts at the site of the shunt itself, and always with permanent embolic agents (50). The procedure must often be staged over weeks in order to slowly alter the hemodynamics of the AVM and yet avoid venous outflow obstruction with its risk of catastrophic consequences. It must be remembered that the malformation may continue to recruit vessels and re-route around embolized vessels. Thus, such treatment is often temporary, and close follow-up is required. Headache Palliative treatment may also be offered to those patients harboring incurable AVMs who are plagued with severe headaches. Some large pial malformations recruit dural vessels over time. These expanded, pulsatile vessels may stretch the pain-sensitive dura, resulting in intractable headaches. Therapies for the amelioration of such symptoms are aimed at the embolization of enlarged dural feeding vessels and often achieve significant success (51). Such therapies may have only transient benefits, and repeat procedures may be required. CONCLUSION Modern treatment of high-grade AVMs must make use of the talents of a number of different sub-specialists. Even the treatment of lower grade malformations is appropriately discussed in a multidisciplinary setting. The participants in such a working group must understand the risks and benefits of each separate treatment modality, as well as their combined effects on the desired outcome. A team led by a neurovascular surgeon, with the equal participation of interventional neuroradiologists, radiosurgical specialists, and vascular neurologists is best able to evaluate and implement new technologies and therapeutic strategies. REFERENCES 1. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 2. Hamilton MG, Spetzler RF. The prospective application of a grading system for arteriovenous malformations. Neurosurgery 1994; 34:2–7. 3. Ondra SL, Troupp H, George ED, et al. The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg 1990; 73:387–391. 4. Crawford PM, West CR, Chadwick DW, et al. AVM of the brain: natural history in unoperated patients. J Neurol Neurosurg Psychiatry 1986; 49:1–10. 5. Kondziolka D, McLaughlin MR, Kestle JRW. Simple risk predictions for arteriovenous malformation hemorrhage. Neurosurgery 1995; 37:851–855. 6. Dawson RC, Owens D, Barrow DL. A multidisciplinary approach to recalcitrant arteriovenous malformations of the brain. In: Maciunas R, ed. Endovascular Neurological Intervention. Park Ridge: American Association of Neurological Surgeons, 1995:201–216. 7. Cromwell LD, Harris AB. Treatment of cerebral arteriovenous malformations: combined neurosurgical and neuroradiological approach. Am J Neuroradiol 1983; 4:366–368. 8. Dawson RC III, Tarr RW, Hecht ST, et al. Treatment of arteriovenous malformations of the brain with combined embolization and stereotactic radiosurgery: results after 1 and 2 years. Am J Neuroradiol 1990; 11:857–864. 9. Deruty R, Pelissou-Guyotat I, Mottolese C, et al. The combined management of cerebral arteriovenous malformations experience with 100 cases and review of the literature. Acta Neurochir 1993; 123:101–112. 10. Lasjaunias P, Manelfe C, TerBrugge K, et al. Endovascular treatment of cerebral arteriovenous malformations. Neurosurg Rev 1986; 9:265–275. 11. Marks MB, Lane B, Steinberg GK, et al. Endovascular treatment of cerebral arteriovenous malformations following radiosurgery. Am J Neuroradiol 1993; 14:297–303. 12. Morgan MK, Sundt TM Jr. The case against staged operative resection of cerebral arteriovenous malformations. Neurosurgery 1989; 25:429–436. 13. Vinuela F, Dion JE, Duckwiler G, et al. Combined endovascular embolization and surgery in the management of cerebral arteriovenous malformations: experience in 101 cases. J Neurosurg 1991; 75:856–864. 14. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983; 58:331–337.
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15. Jafar JJ, Davis AJ, Berenstein A, et al. The effect of embolization with N-butyl-cyanoacrylate prior to surgical resection of cerebral arteriovenous malformations. J Neurosurg 1993; 78:60–69. 16. Mathis JM, Barr JD, Horton JA, et al. The efficacy of particulate embolization combined with stereotactic radiosurgery for treatment of large arteriovenous malformations of the brain. Am J Neuroradiol 1995; 16:299–306. 17. Ogilvy CS. Radiation therapy for arteriovenous malformations: a review. Neurosurgery 1990; 26:725–735. 18. Purdy PD, Batjer HH, Samson D. Management of hemorrhagic complications from preoperative embolization of arteriovenous malformations. J Neurosurg 1991; 74:205–211. 19. Vinuela F, Dion JE, Fox A, et al. Interventional neuroradiology for intracranial arteriovenous malformations. In: Barrow DL, ed. Intracranial Vascular Malformations. Park Ridge, IL: American Association of Neurological Surgeons, 1990:169–178. 20. Spetzler RF, Hargraves RW, McCormick PW, et al. Relationship of perfusion pressure and size to risk of hemorrahge from arteriovenous malformations. J Neurosurg 1992; 76:918–923. 21. Khayata MH, Wakhloo AK, Medkhour AM, et al. Intravascular occlusion of cerebral arteriovenous malformations. In: Carter LP, Spetzler RF, eds. Neurovascular Surgery. New York: McGraw-Hill, Inc., 1995; 957–978. 22. Luessenhop AJ, Spence WT. Artificial embolization of cerebral arteries: report of use in a case of arteriovenous malformation. J Am Med Assoc 1960; 172:1153–1155. 23. Luessenhop AJ, Rosa L. Cerebral arteriovenous malformations. Indications for and results of surgery, and the role of intravascular techniques. J Neurosurg 1984; 60:14–22. 24. Benati A, Beltramello A, Maschio A, et al. Endovascular treatment of intracranial AVMs. Combined embolization with a multi-purpose mobile-wing microcatheter system. J Neuroradiol 1987; 14:99–113. 25. Germano IM, Davis RL, Wilson CB, Hieshima GB. Histopathological follow-up study of 66 cerebral arteriovenous malformations after therapeutic embolization with polyvinyl alcohol. J Neurosurg 1992; 76:607–614. 26. Hall WA, Oldfield EH, Doppman JL. Recanalization of spinal arteriovenous malformations following embolization. J Neurosurg 1989; 70:714–720. 27. Taki W, Yonekawa Y, Iwata H, et al. A new liquid material for embolization of arteriovenous malformations. Am J Neuroradiol 1990; 11:163–168. 28. Purdy PD, Samson D, Batjer HH, Risser RC. Preoperative embolization of cerebral arteriovenous malformations with polyvinyl alcohol particles: experience in 51 cases. Am J Neuroradiol 1990; 1:501–510. 29. Spetzler RF, Wilson CB, Weinstein P, et al. Normal perfusion pressure breakthrough theory. Clin Neurosurg 1978; 25:651–672. 30. Willis D, Harbit MD. Transcatheter arterial embolization of cerebral arteriovenous malformations. J Neurosci Nurs 1990; 22:280–284. 31. Batjer HH, Devous MD Sr., Meyer YJ, et al. Cerebrovascular hemodynamics in arteriovenous malformations complicated by normal perfusion pressure breakthrough. Neurosurgery 1988; 22:503–509. 32. Spetzler RF, Martin NA, Carter LP, et al. Surgical management of AVMs by staged embolization and operative excision. J Neurosurg 1987; 67:17–28. 33. Fournier D, TerBrugge KG, Willinsky R, et al. Endovascular treatment of intracerebral arteriovenous malformations: experience in 49 cases. J Neurosurg 1991; 75:228–233. 34. Korosue K, Heros R. Complications of complete surgical resection of AVMs of the brain. In: Barrow DL, ed. Intracranial Vascular Malformation. Park Ridge, IL: American Association of Neurological Surgeons, 1990:157–168. 35. Pelz DM, Fox AJ, Vinuela F, et al. Preoperative embolization of brain AVMs with isobutyl-2cyanoacrylate. Am J Neuroradiol 1988; 9:757–764. 36. Vinuela FV, Debrun GM, Fox AJ, et al. Dominant hemisphere arteriovenous malformations: therapeutic embolization with isobutyl-2-cyanoacrylate. Am J Neuroradiol 1983; 4:959–966. 37. Girvin JP, Fox AJ, Vinuela F, Drake CG. Intraoperative embolization of cerebral arteriovenous malformations in the awake patient. Clin Neurosurg 1983; 31:188–247. 38. Marks MP, Lane B, Steinberg GK, Chang PJ. Hemorrhage in intracerebral arteriovenous malformations: angiographic determinants. Radiology 1990; 176:807–813. 39. Samson D, Ditmore QM, Beyer CW Jr. Intravascular use of isobutyl-2-cyanoacrylate. Part 1. Treatment of intracranial arteriovenous malformations. Neurosurgery 1981; 8:43–51. 40. Hamilton AJ, Stea B, Lulu BA. Stereotactic radiosurgery for vascular malformations of the brain. In: Carte LP, Spetzler RF, eds. Neurovascular Surgery. New York: McGraw-Hill, Inc., 1995:1073–1087. 41. Colombo F, Benedetti A, Pozza F, et al. Linear accelerator radiosurgery of cerebral arteriovenous malformations. Neurosurgery 1989; 24:833–840. 42. Friedman WA, Bova FJ. Linear accelerator radiosurgery for arteriovenous malformations. J Neurosurg 1992; 77:832–841. 43. Lunsford LD, Kondziolka D, Bissonette DJ, et al. Stereotactic radiosurgery of brain vascular malformations. Neurosurg Clin North Am 1992; 3:79–98. 44. Fabrikant JI, Levy RP, Steinberg GK, et al. Charged-particle radiosurgery for intracranial vascular malformations. Neurosurg Clin North Am 1992; 3:99–139. 45. Heros RC, Korosue K. Radiation treatment of cerebral arteriovenous malformations. N Engl J Med 1990; 323:127–129.
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46. Steinberg GK, Fabrikant JI, Marks MP, et al. Stereotactic heavy charged-particle Bragg peak radiation for intracranial arteriovenous malformations. N Engl J Med 1990; 323:96–101. 47. Friedman WA. Radiosurgery for arteriovenous malformations. In: Batjer HH, ed. Cerebrovascular Disease. Philadelphia: Lippincott-Raven, 1997:749–763. 48. Guo WY, Wikholm G, Karlsson B, et al. Combined embolization and gamma knife radiosurgery for cerebral arteriovenous malformations. Acta Radiol 1993; 34:600–606. 49. Cunha MJ, Stein BM, Solomon RA, et al. The treatment of associated intracranial aneurysms and arteriovenous malformations. J Neurosurg 1992; 77:853–859. 50. Fox AJ, Girvin JP, Vinuela F, et al. Rolandic arteriovenous malformations: improvement in limb function by IBC embolization. Am J Neuroradiol 1985; 6:575–582. 51. Sugita M, Takahashi A, Ogawa A, et al. Improvement of cerebral blood flow and clinical symptoms associated with embolization of a large arteriovenous malformation: case report. Neurosurgery 1993; 33:748–751.
Section IV
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Anesthetic Considerations Tomoki Hashimoto Department of Anesthesia and Perioperative Care, UCSF Center for Cerebrovascular Research, University of California, San Francisco, California, U.S.A.
William L. Young Departments of Anesthesia and Perioperative Care, Neurological Surgery, and Neurology, UCSF Center for Cerebrovascular Research, University of California, San Francisco, California, U.S.A.
GENERAL CONSIDERATIONS For optimal anesthetic management of patients with arteriovenous malformations (AVMs), the anesthesiologist should be familiar with the general pathophysiology of AVMs as well as with the various types and strategies of treatment. AVMs may exert a deleterious effect on brain function by several mechanisms, including mass effects (e.g., hematoma, edema, or gradually expanding abnormal vascular structures such as venous aneurysms), metabolic depression (diaschisis), and seizure activity. However, the primary goal of treatment is to decrease the risk of spontaneous bleeding. The risk of spontaneous hemorrhage from an AVM is in the range of 2% to 10%/year (1,2), and patients initially presenting with hemorrhage have a higher rate, perhaps as high as 17% (3). A conservative estimate of patients who are moderately to severely disabled after AVM hemorrhage is in the range of 6% (4). High feeding artery pressure and venous outflow restriction are strongly associated with hemorrhagic presentation and appear to be more strongly related to initial bleeding than the AVM size or location, or the presence of arterial aneurysms (5,6). In addition to prophylaxis against future spontaneous hemorrhage, there are certain other indications for treatment. In patients with progressive neurologic deficits or intractable seizures, the obliteration of high-flow feeders may be of benefit, probably by treating the expanding mass effect of abnormal vascular structures. There are three modes for treatment of AVMs: endovascular embolization, radiosurgery, and surgical excision. Treatment strategies, especially for complex lesions, frequently involve more than one modality. In general, endovascular therapy is performed as a preparatory adjunct to surgery. Using various glues or other embolic materials, the blood supply to the fistula can be reduced, most commonly in several stages. As a preoperative adjunct, embolization is thought to facilitate operative removal with less bleeding (7) and seems to be associated with better surgical outcome (8). Embolization also can eliminate deep vascular pedicles that might be difficult to control surgically. The application of radiosurgery at present is probably ideally reserved for smaller lesions that are surgically inaccessible (9). There are several important differences between aneurysms and AVMs of which the anesthesiologist should be aware. Approximately 10% of patients with AVMs also harbor intracranial aneurysms. The converse, however, is not true; the prevalence of AVMs in patients with aneurysms is probably similar to the prevalence of AVMs in the general population. Intracerebral hemorrhage from aneurysms is usually associated with subarachnoid hemorrhage, whereas AVMs more commonly bleed into the ventricle or into parenchyma. This difference explains why vasospasm is uncommon in patients with AVMs. Spontaneous hemorrhage during the perioperative period as a result of variations in systemic blood pressure is probably less frequent in patients with AVMs due to a ‘‘buffering’’ capacity of the fistula on changes in systemic pressure (10,11).
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CEREBRAL CIRCULATORY CHANGES IN PATIENTS WITH AVMs There are two primary characteristics of the cerebral circulatory changes brought about by an AVM. Rapid shunt flow results in an increased total amount of bulk through the AVM. This increased flow results in cerebral arterial hypotension along the path of the shunt. Patients with AVMs have a progressive decrease in arterial pressure that proceeds from the circle of Willis to the AVM nidus (12). The corollary of this observation is that circulatory beds in parallel with the shunt system will be perfused at lower-than-normal pressures, even if flow remains relatively normal. In large, high flow AVMs, cerebral arterial hypotension may be below the range of normal autoregulation. Despite significant cerebral arterial hypotension, most patients with AVMs have no ischemic symptoms. Hypotensive but functionally normal brain regions can be demonstrated to have normal rates of tissue perfusion, implying some adaptive change in total cerebrovascular resistance. This phenomenon may be explained by ‘‘adaptive autoregulatory displacement’’ (13). In vascular territories adjacent to AVMs, the lower limit of the autoregulation curve appears to be shifted to the left, which is opposite to the effect of chronic systemic (essential) arterial hypertension on the cerebral autoregulation curve (14). This adaptive shift to the left places the lower limit at a level considerably lower than the lower limit postulated for normal brain (50 or 60 mmHg) (15,16). Therefore, the presence of chronic hypotension does not necessarily result in vasoparalysis in the arteriolar resistance bed. Although CO2 reactivity may be impaired in brain regions surrounding AVMs, the responsiveness to CO2 before and after surgical resection is generally preserved; this finding lends further support to the notion of intact autoregulatory capacity (14). Historically, it was believed that not the AVM itself, but rather decreased perfusion pressure in adjacent, functional tissue, was responsible for both pretreatment ischemic and posttreatment hyperemic symptoms, namely cerebral steal and normal perfusion pressure breakthrough (NPPB), respectively. These widely discussed concepts have limited anecdotal evidence to support their existence. Cerebral steal is felt by many authors to explain focal neurologic deficits in patients with AVMs; it is attributed to local hypotension. It has been postulated that arteriolar vascular resistance in territories adjacent to AVMs is at or near a state of maximal vasodilation, and therefore steal ensues if perfusion pressure decreases. Although cerebral arterial hypotension in normal brain areas is common in patients with AVMs, clinical presentations with focal neurologic deficits are rare (10%). Moreover, there is no relation between local hypotension and focal neurologic deficits (17). It is likely that local mass effects from the abnormal vessels of the AVM are more important than local hemodynamic failure to account for symptomatic focal neurologic deficit unrelated to intracerebral hemorrhage or seizure activity. The intraoperative appearance of diffuse bleeding from the operative site or brain swelling and the postoperative occurrence of hemorrhage or swelling have been attributed to NPPB or hyperemic complications. The concept of NPPB is as follows. After shunt obliteration, reversal of arterial hypotension is not matched by a corresponding increase in cerebrovascular resistance and results in hyperemia and, in its worst case, swelling or intracranial hemorrhage. Although the incidence of postoperative hyperemic complications has been estimated to be as high as 25% to 50%, it is probably lower than 5% (18). A difficulty in studying the problem arises due to the heterogeneous set of criteria used by different authors in defining exactly what a hyperemic complication is. One study shows that increase in global cerebral blood flow (CBF) after AVM resection is itself associated with an NPPB-type complication but that there is no relationship between preoperative regional arterial hypotension and CBF changes after AVM resection (18). Therefore, repressurization of hypotensive vascular beds is not a sufficient condition for hyperemic complications. There may not be a single mechanism for NPPB-type complications. The states of steal and NPPB probably do exist in some rare minority of cases, but they are the exception rather than the rule. In perioperative management, the diagnosis of NPPB should be a diagnosis of exclusion made after all other correctable causes for malignant brain swelling or bleeding have been excluded. In addition to other supportive and resuscitative measures, preventing severe postoperative hypertension may be useful in preventing and treating this syndrome.
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It is probably not a simple hemodynamic mechanism that accounts for most cases of NPPB. For example, Batjer et al. advanced the argument that posttreatment hyperemia may be due to a deranged vascular bed that actively participates in swelling, and not simply to the passive behavior of a paralyzed vascular bed (19–21). Batjer et al. made the surprising observation that patients who developed hyperemic complications (these were liberally defined as various signs of edema, swelling, or hemorrhage) responded to acetazolamide challenge with increased, abnormally high, vasoreactivity, as determined by 133-Xe SPECT imaging. A hemodynamic model of perfusion failure would require that CO2 or acetazolamide reactivity was decreased. Other than indirectly (22), the ‘‘active-participation’’ paradigm has not been studied further. There is some evidence that mechanisms related to the autonomic and sensory innervation of the cerebrovascular bed can significantly influence CBF in various pathophysiologic states, e.g., via trigeminal axonal projections in the intracerebral bed (23,24). An ‘‘axon-like’’ reflex might be mediated by peptides such as calcitonin gene-related peptide, substance P, and neurokinin A. Release of these peptides may induce vasodilation and an increase in blood-brain barrier permeability. This hypothesis remains untested in patients undergoing AVM treatment.
ANESTHETIC MANAGEMENT DURING SURGERY Preoperative Because AVM resection is almost never emergent, careful review of the patient’s perioperative status and assessment of potential intraoperative difficulties is possible. Preexisting medical conditions should be optimized; neurologic dysfunction as a result of presenting hemorrhage, presumed effect of the AVM, or preoperative embolization (infarction or edema), should be factored into the intraoperative management plan regarding choice of monitoring, vascular access, anesthetic agents, vasoactive drugs, muscle relaxants, and postoperative airway control. A critical consideration throughout the operative period is the potential for massive and rapid blood loss. The choice of intraoperative monitoring is tempered by this eventuality, and an adequate supply of blood, along with access for its administration, should be at hand. Intraoperative Monitoring In addition to routine monitors—such as electrocardiogram (ECG), pulse oximeter, end-tidal CO2, temperature probe, and direct arterial pressure transduction—central access should be considered for resection of larger lesions. Monitoring cerebral hemodynamics during AVM resection is desirable for several reasons. The ideal goals for cerebral hemodynamic monitoring are shown in Table 1. Unfortunately, our ability to monitor the central nervous system lags far behind our ability to monitor other systems, and the development of suitable technologies is still in its infancy. There is no consensus about optimum monitoring techniques. Choice of Agents The control of intracranial pressure is rarely a problem with AVM patients undergoing elective resection. Nonetheless, these patients may have decreased intracranial compliance, so the usual caveats about avoiding cerebral vasodilators are reasonable. Except for cerebral vasodilators, the specific choice of anesthesia may be guided primarily by other cardio- and cerebrovascular considerations. An isoflurane/N2O technique offers good systemic blood pressure control. Total intravenous (IV) anesthetic techniques, or combinations Table 1 Ideal Goals for Cerebral Hemodynamic Monitoring Titrate drug effects for cerebral protection (barbiturate) or brain relaxation (hypocapnia) Monitor for the occurrence of regional cerebral ischemia during vascular manipulation Monitor for the occurrence of global cerebral ischemia during induced hypotension Monitor for the occurrence of cerebral hyperperfusion Assist the surgeon in differentiating arterial and venous structures Identify patients at high risk for postoperative complications
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of inhalational and IV methods, may optimize rapid emergence (25). Some centers use additional barbiturate loading during the resection to afford increased protection against cerebral ischemia, resulting in perhaps a greater degree of brain relaxation and protection against acute hyperemia (26). Barbiturates can be titrated to an electroencephalogram (EEG)-endpoint of burst-suppression. The main price to be paid for barbiturate use is delayed emergence and forgoing an early postoperative neurologic examination. There is no compelling evidence that outcome is affected. If metabolic suppression is desired [and we by no means endorse this as a unique, effective method of intraoperative protection (27)], propofol or etomidate may be considered. Metabolic suppression may be useful in the event of an intraoperative catastrophe, as described below under ‘‘induced hypotension.’’ Nonpharmacologic Cerebral Protection The goals of a modern neuroanesthetic should not revolve around provision of pharmacologic brain protective therapy, per se. A number of basic considerations will maximize nonpharmacologic cerebral protection and provide protection from injury (summarized in Table 2). Protective efforts are guided toward two general types of damage: neurosurgical (anatomic) and anesthetic (physiologic) trespass. Possible mechanisms of neurosurgical injury include brain retraction, direct vascular injury (ischemia, thrombosis, and venous occlusion), and mechanical disruption of neuronal tissue or white matter tracts. Anesthetic injury may result from systemic hypo- or hypertension, decreased O2 content, hypo-osmolarity, or hyperglycemia. The mechanisms of damage are interactive. For example, a modest amount of brain retraction coupled with a modest reduction of systemic blood pressure may have synergistic effects on emergence or neurologic outcome. Management goals should include provision of a relaxed brain, controlled systemic and cerebral hemodynamics, maintenance of isotonicity and euglycemia, mild hypothermia, and a controlled emergence. Brain Relaxation Adequate brain relaxation begins with good head position to promote intracranial venous drainage. The least amount of flexion and rotation necessary for the operative approach should be planned with the surgeon. Careful positioning of the head may also prevent postoperative tongue swelling, a rare but morbid occurrence. A rule of thumb might be given as ‘‘two finger breadths per 70 kg’’ between the mandible and clavicle (not the sternum) after the head is positioned in rigid pin fixation. The head of the table should be positioned to prevent venous engorgement. Cerebrospinal fluid removal is an effective means of brain relaxation, obtained by direct lumbar puncture or ventricular drainage. Diuretic therapy with mannitol and/or furosemide
Table 2 Nonpharmacologic Brain Protection Relaxed brain Good head position CSF drainage Diuretics/osmotherapy Avoidance of excessive cerebral vasodilators Controlled systemic and cerebral hemodynamics Euvolemia Optimal cerebral perfusion pressure Fluid and electrolyte management Isotonicity Euglycemia Temperature management Toleration of modest hypothermia intraoperatively Prevention of hyperthermia postoperatively Controlled emergence Tailored awakening Autonomic control Abbreviation: CSF, cerebrospinal fluid.
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is widely applied. The most important consideration for anesthetic choice intraoperatively is the avoidance of cerebral vasodilators. Euvolemia and Blood Pressure Control Fluid restriction was a time-honored means of guarding against brain swelling in the neurosurgical patient. Adequate volume status to maintain stable systemic hemodynamics, especially with the application of induced hypotension, may require liberal fluid administration. Recent evidence reconciles these two apparently divergent goals (the influence of serum tonicity on fluid movement into the brain is discussed below). Control of cerebral hemodynamics begins with control of systemic arterial pressure, which in turn is predicated on adequate cardiac preload (euvolemia). Iatrogenic dehydration, as practiced in years past, has no place in modern neurosurgical practice. Indeed, in the setting of aneurysmal subarachnoid hemorrhage, it is clearly deleterious. During manipulation of the intracranial contents or their vascular supply, the anesthesiologist should strive to maintain the optimal cerebral perfusion pressure (CPP), i.e., the highest clinically acceptable blood pressure for the particular clinical circumstance. Brain relaxation is probably also served by maintenance of a normal arterial pressure. Cerebral blood volume is kept to a minimum by appropriate autoregulatory vasoconstriction (28). Fluid and Electrolyte Management The tonicity of replacement therapy strongly influences water movement into both normal and damaged brain (29). Even mildly hypotonic fluids such as lactated Ringers solution, if given in sufficient quantity, may aggravate brain swelling more than do isotonic crystalloids or colloids. Isotonic fluid replacement with blood, saline, or hetastarch after forebrain ischemia in the rat appears to yield similar results in terms of cerebral edema formation (30). The most important point is that fluid should never be withheld at the expense of a stable cardiovascular status. Serum osmolarity can be easily monitored if large volumes of crystalloid are needed. The choice of colloids is not a clear one. Although hetastarch has been implicated as a cause of coagulation disorders, this concern is probably not important for volumes under 1 L used intraoperatively. Cost is the primary concern when choosing between hetastarch and human serum albumin. The use of hetastarch postoperatively is more controversial (31). Glucose aggravates cerebral injury not only in animals but also in humans (32,33). Routine administration of perioperative glucocorticoids may cause some degree of hyperglycemia. In the absence of clear guidelines, the most rational approach is to avoid glucose-containing fluids, unless there is a specific indication. One such indication would be a diabetic patient receiving insulin therapy. In this case, ‘‘tight’’ rather than ‘‘loose’’ control of serum glucose seems reasonable; it is probably not worth risking hypoglycemia in an anesthetized patient for any presumptive protective effect of lowering a mildly elevated glucose level. How does one define optimal levels? Observational evidence suggests that glucose elevations are associated with worsened outcome after various types of brain injury. For example, in patients with severe head injury (Glasgow Coma Score less than or equal to 8), a serum glucose level greater than 200 mg/dL postoperatively is associated with a worsened outcome (33). Mild Hypothermia The induction of general anesthesia results in an obligatory core temperature decrease as peripheral vasodilation redistributes heat to the periphery. Mild hypothermia (with core temperature decreases as little as 1.5–3 C) has been shown to provide dramatic cerebral protection against ischemic insult in animal models (34). This protective effect is greater than what would be expected from metabolic suppression alone and may be related to a decrease in excitatory neurotransmitter release from ischemic cells (35). Two randomized controlled clinical trials showed the beneficial effect of mild hypothermia in patients with severe traumatic brain injury (36,37). However, a large multicenter, prospective, randomized trial (IHAST2: Intraoperative Hypothermia for Aneurysm Surgery Trial 2) did not show favorable effects of intraoperative mild hypothermia on prevention of postoperative neurologic deficits in patients who underwent aneurysm clipping surgery (38). A majority of the patients enrolled in this study were at low risk for developing postoperative neurologic deficits. Selective use of mild hypothermia for high-risk patients may have beneficial effects.
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Anesthetized patients can be easily cooled to the mild hypothermic range (33–34 C), although complete intraoperative rewarming may be difficult to achieve (39). Even mild degrees of hypothermia carry potential risk. Passive rewarming is associated with peripheral vasoconstriction, shivering, and subsequent increases in oxygen consumption and myocardial work. Drug metabolism is decreased, prolonging the effect of even short-acting anesthetic drugs. Postoperative hypothermia (<35 C) is complicated by increased rates of myocardial ischemia, angina, and arterial hypoxemia in populations at risk for coronary artery disease (40). Moderate hypothermia (<33 C) has other well-documented potential effects, including increased susceptibility to infection, cardiac arrhythmias, hyper-coagulability, thrombocytopenia, impaired platelet aggregation, and activation of fibrinolysis, all of which are reversed with rewarming (39,40). Most of these adverse effects have been observed in patients who leave the operating room while still hypothermic. It is unclear whether the potential benefits of cerebral protection gained from mild hypothermia and partial rewarming are offset by the systemic physiologic stress induced, particularly if shivering occurs on emergence. Temperature monitoring should continue throughout the perioperative period; hyperthermia must be avoided as it potentiates ischemic damage (41). Emergence and Initial Recovery: Blood Pressure Control A particularly challenging aspect of perioperative care is emergence and initial recovery. It is our impression that the AVM patient tends to be systemically (and in the worst case, cerebrally) hyperdynamic (42). We typically use a moderate phenylephrine-induced blood pressure augmentation (20–30% above normal MAP) during drying of the operative bed to inspect for hemostasis. After hemostasis is achieved and the volatile agent is discontinued, we routinely use large doses of labetolol and, after a 0.5 to 1 mg/kg loading dose, a variable esmolol infusion to maintain the patient’s blood pressure within 10% below the usual ward values. Without firm outcome data indicating the superiority of one drug regimen or another, the choice of agent to manipulate blood pressure must be placed in the context of the clinical situation (e.g., avoiding use of beta adrenergic blockers in patients with bronchospastic airway disease or the use of nitroglycerin in patients with coronary artery disease) and the experience of the practitioner. The most sensitive monitor of cerebral function remains the neurologic examination. Prompt emergence ensures that drug residua do not become confused with or obscure focal neurologic damage. The control of systemic hemodynamics is of critical importance during the emergence phase as the patient makes the transition from the anesthetized to the conscious state. Postoperative The points related to intraoperative blood pressure management apply here; we find esmolol to be an effective agent to smoothly cap the blood pressure swings common in the initial Intensive Care Unit (ICU) period. There are seemingly refractory cases of postoperative hypertension, however, and the clinician must be prepared to draw upon all the agents in the available armamentarium. The sword of aggressive blood pressure control can cut both ways. There are cases of ischemic deficits due to intraoperative sacrifice of, for example, an en passage feeding vessel (a vessel feeding the AVM and also sending distal branches to normal brain) that may result in a deficit ascribed to brain retraction or the resection itself. Marginally perfused areas may be critically dependent on collateral perfusion pressure. The maintenance of low or even normal blood pressure may be inadequate and result in infarction if unrecognized. Postoperative hyperthermia may be detrimental (41) and even exacerbated by intraoperative mild induced hypothermia (39). Therefore, careful attention should be paid to the control of patient temperature in the ICU. ANESTHETIC MANAGEMENT DURING INTERVENTIONAL NEURORADIOLOGIC PROCEDURES The three primary functions of the anesthesiologist in the interventional suite are (i) provision of a physiologically stable and immobile patient, (ii) manipulation of the systemic blood pressure as dictated by the needs of the procedure, and (iii) disaster management. In adults, these
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may be accomplished by traditional methods of general anesthesia with endotracheal intubation or IV sedation to render patients unaware of their surroundings yet allow for rapid return to consciousness for intermittent assessment of neurologic function during manipulation of the vasculature. Deep IV sedation implies that the patient breathes spontaneously with an unprotected airway. Because there is no good nomenclature for such an anesthetic state, we will simply refer to it as IV sedation in the following discussion. The term ‘‘conscious sedation’’ can be misleading because it does not adequately communicate the concerns of the anesthesiologist to the rest of the operative team about airway management. Small children and uncooperative adult patients will require general anesthesia with endotracheal intubation. Choice of Anesthetic Technique: Intravenous Sedation Versus General Anesthesia The choice of anesthetic technique for endovascular cases is controversial. There are two schools of thought on how to manage the patient undergoing embolization of an AVM. One is to rely on the knowledge of neuroanatomy and vascular architecture to ascertain the likelihood of neurologic damage after deposition of glue. The ‘‘anatomy’’ school, therefore, prefers to embolize under general anesthesia. Arguments for this approach include improved visualization of structures with the absence of patient movement, especially under temporary apnea. Furthermore, it is argued that if the glue is placed intranidally, then by definition no normal brain is threatened. The other school, the ‘‘physiologic’’ school, trades off the potential for patient movement for the increased knowledge of the true functional anatomy of a given patient. Localization of cerebral function may not always follow textbook descriptions. Furthermore, the AVM nidus or a previous hemorrhage may result in a shift or relocalization of function. The physiologic approach requires deep IV sedation so that the patient may be awakened for selective Wada testing before injection of embolic material (discussed below). Preprocedure Considerations In addition to the usual preanesthetic evaluation of the neurosurgical patient, previous experience with angiography and contrast reactions (including general atopy and iodine/shellfish allergies) should be noted. Neck, back, or joint problems may influence the ability to secure the airway or impede the tolerance of the patient to lie supine for several hours. Because of significant radiation exposure, the possibility of pregnancy in female patients should be explored. An anxiolytic agent may be given if appropriate to the patient’s sensorium. Prophylaxis for cerebral ischemia is in a state of development. Procedural Considerations Patient Positioning Because the procedure may take hours, having the patient as comfortable as possible before beginning sedation is essential. No amount of IV sedation can substitute for careful patient positioning. A comfortable air or foam mattress, and some type of device for good head and neck positioning are needed. After the femoral introducer sheath has been placed, a pillow is placed under the knees to obtain a modest amount of flexion; this position may improve patient tolerance for a prolonged period of lying supine. Patients may return for multiple treatments, and therefore continued patient acceptance is important. Because the head position must remain constant, a headrest that discourages movement or paper tape across the patient’s forehead is used as a ‘‘reminder.’’ The use of rigid fixation should be avoided as it might increase the likelihood of aspiration if emesis occurs. Vascular Access and Arterial Pressure Monitoring Secure IV access should be available with adequate extension tubing to allow drug and fluid administration at maximal distance from the image intensifier during fluoroscopy. When the patient is draped with arms restrained and advanced toward the image intensifier, access to IV sites is difficult. Direct transduction of arterial pressure is indicated for intracranial embolization procedures, especially with manipulation of systemic pressure with vasoactive agents. Three arterial pressures may easily be monitored from the typical triaxial catheter system used to access the distal cerebral circulation (Fig. 1). Pressure transducers and access stopcocks for
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Figure 1 Representation of a typical arrangement of the transfemoral coaxial catheter and the microcatheter (superselective catheter). Source: From Ref. 43.
blood withdrawal and zeroing are mounted, depending on local preferences, either on the sterile field or toward the anesthesia team. Although some institutions also perform radial artery catheterizations, the femoral artery introducer sheath is easily used to monitor arterial pressure. This process spares the patient from radial artery cannulation. However, it frequently underestimates the systolic and overestimates the diastolic pressure, due to the coaxial catheter passing through the femoral artery sheath. Nonetheless, the mean pressures are reliable and may be used to safely monitor the induction of either hyper- or hypotension. The femoral catheter is continually flushed with an intra-flow device at a rate of 3 mL/hour of heparinized saline, which does not appreciably influence the mean pressure recording. Arterial pressure also may be monitored from the coaxial catheter in the carotid or the vertebral artery and may provide early warning of thrombus formation or vascular spasm at the catheter tip. Catheter migration may be suggested by damping of the waveform. The coaxial catheter is flushed with heparinized saline at a high flow rate, which may artifactually increase the measured pressure. In addition, the pressure at the tip of the superselective catheter may be monitored to gain information about AVM feeding artery pressure. The use of microcatheters for mean pressure measurements has been validated by Duckwiler et al. (44). Other Systemic Monitoring and Patient Preparation Other monitors should include a 5-lead ECG (ideally with automated ST segment trending) and an automatic blood pressure cuff. In patients at risk for myocardial ischemia, a baseline recording of the ECG may be helpful for later comparisons during hemodynamic manipulation. A pulse oximeter probe is placed on the great toe of the leg that will receive the femoral catheters. This probe can give an early warning of femoral artery obstruction or distal thromboembolism. It is also useful when the femoral sheath must be removed and the site compressed for hemostasis, particularly in smaller children in whom over-vigorous compression can lead to permanent occlusion of the vessel.
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O2 (2–4 L/min) is given by nasal cannula with a system to sample and monitor end-tidal CO2 (PetCO2). For the spontaneously breathing patient, an indicator of respiratory rate is recommended if PetCO2 is not available, and may be useful for detecting abnormal respiratory patterns during procedures involving the posterior fossa. Temperature may be monitored in a number of ways, such as with an axillary probe or a bladder catheter thermistor. Shivering is a troublesome problem because it results in patient motion and image degradation, and every effort should be made to keep the patient’s temperature near normal (except in the case of a neurologic catastrophe). Bladder catheters are essential; they assist in fluid management as well as patient comfort. A significant volume of heparinized flush solution may be necessary over the course of the procedure, and radiographic contrast is an osmotic diuretic. The administration of other diuretics such as mannitol or furosemide also may be required for fluid management or in the event of a catastrophe. When the patient’s condition warrants placement of a central venous or pulmonary artery catheter, these catheters may be positioned with fluoroscopy. Similarly, the endotracheal tube position in patients undergoing general anesthesia is easily verified by fluoroscopy of the chest during passage of the coaxial catheters. Intravenous Sedation IV sedation has as its goal the alleviation of pain or discomfort, anxiolysis, and patient immobility, while at the same time allowing for a rapid decrease in the level of sedation when neurologic testing is required. The procedures, in general, are not painful. There may be an element of pain associated with the injection of contrast into the cerebral arteries (burning) and with distention of or traction on them (headache). Discomfort, however, stems from long periods of lying still. The insertion of the bladder catheter and, to a lesser extent, the initial groin puncture for the femoral cannulation are two notable points of discomfort. The procedure is also psychologically stressful. There is a risk of serious stroke or death, which may be particularly important for a patient who has already suffered a preoperative hemorrhage or stroke. Movement by the patient will decrease the usefulness of the digital image subtraction (roadmapping) techniques. For example, a wire or catheter could penetrate a vessel wall and still appear to reside within the lumen. Anesthetic agents are selected to meet the above goals. A combination of midazalam and fentanyl can be used to establish a base of sedation. A propofol infusion can be started at a very low level and then titrated slowly to result in an unconscious patient with a patent airway. The use of propofol gives the anesthesiologist some degree of control when a rapid return to consciousness is needed for neurologic assessment. Various other sedation regimens are certainly possible and must be based on the experience of the practitioner and the aforementioned goals of anesthetic management. Common to all IV sedation techniques is the potential for upper airway obstruction. The placement of nasopharyngeal airways may cause troublesome bleeding in patients treated with anticoagulants and is generally avoided. If the need for a nasopharyngeal airway is expected, it is prudent to place it before anticoagulation and observe meticulous hemostasis. Laryngeal mask airways may have a place in the management of deep IV sedation in these cases. If they are used, care must be taken to insure that there is not excessive motion during the period when the depth of anesthesia is decreased to remove the airway. Coughing or bucking with the large, stiff introducer catheters in the neck vessels may result in vascular injury. Anticoagulation Careful management of coagulation is required to prevent thromboembolic complications during and after the procedures, although algorithms for anticoagulation remain controversial (45–47). Whether heparinization should be used for every case of intracranial catheterization is not clear. Some would argue that anticoagulation increases the risk of intracranial hemorrhage. We feel strongly that heparinization should be routinely performed during any superselective catheterization. In addition to thrombus formation from foreign bodies in the circulation, a considerable amount of thrombogenic endothelial damage may be done by the passage of the superselective catheter.
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After placement of the femoral introducer catheter, a baseline activated clotting time (ACT) is obtained. Heparin is given to a target prolongation of two to three times baseline with hourly monitoring of ACT and supplemental heparin. An occasional patient may be refractory to attempts to obtain adequate anticoagulation. Switching from bovine to porcine heparin or vice versa may be of use. If antithrombin III deficiency is suspected, the administration of fresh frozen plasma may be necessary. Injection of Embolic Material Although any injected embolic material can occlude normal vessels, injection of the glue is fraught with particular hazards. The injection of glue is a critical moment (not unlike the moment when a surgeon closes the clip on the neck of an aneurysm). The catheter may become glued to the vessel. If the catheter cannot be removed by intermittent firm, gentle traction, it may be necessary to leave the catheter intravascularly, where it will eventually endothelialize. Similarly, the catheter, as it is withdrawn, may drag a piece of glue into the proximal part of the artery and occlude it. In this event, territories fed by nutrient vessels distal to the occlusion may become ischemic. Glue that is carried out into the draining vein can cause venous outflow obstruction and result in intracranial hemorrhage. Glue may also pass into the pulmonary circulation. Small amounts (<0.5 mL) may not be clinically significant. Larger amounts, however, may result in a syndrome akin to acute pulmonary thromboembolism. Because the glue is extremely thrombogenic, it may pick up thrombus en route and form more clot once lodged in the pulmonary vasculature. This concern is of particular importance in small children with large AVMs. At the time of gluing, the anesthesiologist must be ready to intervene immediately in the event of catastrophe. Postprocedure Considerations The measurement of immediate postembolization pressures has been suggested as a means of following the course of hemodynamic changes (44) and predicting postprocedure complications, because large increases in feeding artery pressure appear to be associated with intracranial hemorrhage. At the present time, immediate postembolization pressure measurements are practical only with thread, coils, or polyvinyl alcohol particles. When glues such as n-butyl cyanoacrylate are used, currently available superselective catheters must be withdrawn immediately after glue injection (so that they are not cemented into place). It is possible to chase glue from the microcatheter with nonionic solutions, but this reduces the operator control over glue deposition. Typically, the pressures in the proximal feeding artery are quite low, i.e., 40% to 60% of mean arterial pressure (MAP). The proximal portion of the artery usually feeds large areas of functional eloquent brain. The mean pressure in feeding arteries near the entry to a high-flow AVM nidus is usually 15% to 25% of MAP. Pressure may be transmitted to the cerebral venous system and may pressurize normal venous drainage areas. There is not a direct relationship between AVM feeding artery and draining vein pressures; outflow pressure from the nidus is probably primarily determined by the architecture of the venous drainage (10). Because AVM feeding arteries supply variable degrees of normal brain, the abrupt restoration of normal systemic pressure to a chronically hypotensive vascular bed may overwhelm autoregulatory capacity and result in hemorrhage or swelling (NPPB). It is for this reason, in part, that the target range for posttreatment blood pressure is at or slightly below the patient’s normal ward blood pressure. For procedures in the posterior fossa, small degrees of ischemia and swelling from radiocontrast not infrequently result in symptomatic local brain swelling in the postprocedure period. In the more capacious supratentorial compartment, such minor swelling is rarely symptomatic. In the posterior fossa, this swelling may present as delayed deficits or decreased sensorium during the course of the first evening after the procedure, particularly if cerebrospinal fluid pathways become obstructed. This eventuality should be factored into decisions regarding airway management. Complications and Special Considerations Management of Neurologic Catastrophes Complications during instrumentation of the cerebral vasculature can be rapid and dramatic, and they require multidisciplinary collaboration. Having a well-thought out plan for dealing
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with intracranial catastrophe may make the difference between an uneventful outcome and death. If a neurologic catastrophe occurs, rapid and effective communication between the anesthesia and endovascular teams is critical. The primary responsibility of the anesthesia team is to preserve gas exchange and, if indicated, secure the airway. If endotracheal intubation is necessary, a thiopental and relaxant induction should not be avoided because of the possibility of a transient decrease in perfusion pressure. Simultaneous with airway maintenance, the first branch in the decision-making algorithm is for the anesthesiologist to communicate with the interventional neuroradiology (INR) team and determine whether the problem is hemorrhagic or occlusive. In the setting of vascular occlusion, a method to increase distal perfusion is by blood pressure augmentation with or without direct thrombolysis. If the problem is hemorrhagic, immediate reversal of heparin is indicated. Protamine is given as rapidly as possible to reverse heparin without undue regard for the systemic blood pressure. As an emergency reversal dose, 1 mg protamine can be given for each 100 units heparin total dosage during the case. The ACT can then be used to fine-tune the final protamine dose. Bleeding catastrophes are usually heralded by headache, nausea, vomiting, and vascular pain related to the area of perforation. Sudden loss of consciousness is not always due to intracranial hemorrhage. Seizures, as a result of contrast or temporary ischemia, and the resulting postictal state can also result in an obtunded patient. Blood Pressure Augmentation (Deliberate Hypertension) Not infrequently, the patient may experience cerebral ischemia from either a planned or inadvertent vascular occlusion. The systemic blood pressure may be increased to drive adequate flow via collaterals to the area of ischemia as a temporizing measure (7). The primary routes of collateral circulation are the large vessels that make up the circle of Willis (anterior communicating artery and posterior communicating artery and the ophthalmic artery via the external carotid artery) and the surface connections between pial arteries that bridge major arterial territories (anterior cerebral artery–posterior cerebral artery/anterior cerebral artery– middle cerebral artery/middle cerebral artery–posterior cerebral artery). Our first line agent is phenylephrine bolus followed by titrated infusion to increase the pressure up to levels that reverse the neurologic deficit, empirically, 30% to 40% above baseline. The ECG and ST segment monitor should be carefully inspected for signs of myocardial ischemia. Blood pressure goals must be tempered by the patient’s preexisting medical status. Based on the best available evidence, deliberate hypertension in the face of symptomatic cerebral ischemia from vascular occlusion during AVM embolization should not be avoided because of fear of rupturing the malformation (48). If the heart rate is very low to start, e.g., due to preoperative beta blockade or sinus node disease, an alternate choice would be ephedrine or dopamine, with or without phenylephrine. ACKNOWLEDGMENTS The authors thank Joyce Ouchi and Voltaire Gungab for assistance in preparation of the manuscript. Portions of this work were supported by NIH grants NS27713 (WLY), NS34949 (WLY), NS37921 (WLY), NS02091 (WLY), and NS44155 (WLY, TH). REFERENCES 1. Crawford PM, West CR, Chadwick DW, Shaw MD. Arteriovenous malformations of the brain: natural history in unoperated patients. J Neurol Neurosurg Psychiatry 1986; 49:1–10. 2. Halim AX, Johnson SC, Singh V, et al. Longitudinal risk of intracranial hemorrhage in patients with arteriovenous malformation of the brain within a defined population. Stroke 2004; 35:1697–1702. 3. Mast H, Young WL, Koennecke H-C, et al. Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet 1997; 350:1065–1068. 4. Hartmann A, Mast H, Mohr JP, et al. Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformations. Stroke 1998; 29:931–934. 5. Duong DH, Young WL, Vang MC, et al. Feeding artery pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral arteriovenous malformations. Stroke 1998; 29:1167–1176.
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6. Kader A, Young WL, Pile-Spellman J, et al. The Columbia University AVM Study Project. The influence of hemodynamic and anatomic factors on hemorrhage from cerebral arteriovenous malformations. Neurosurgery 1994; 34:801–807 [discussion 807–808]. 7. Young WL, Pile-Spellman J. Anesthetic considerations for interventional neuroradiology (review). Anesthesiology 1994; 80:427–456. 8. DeMeritt JS, Pile-Spellman J, Mast H, et al. Outcome analysis of preoperative embolization with N-butyl cyanoacrylate in cerebral arteriovenous malformations. Am J Neuroradiol 1995; 16: 1801–1807. 9. Sisti MB, Kader A, Stein BM. Microsurgery for 67 intracranial arteriovenous malformations less than 3 cm in diameter. J Neurosurg 1993; 79:653–660. 10. Young WL, Kader A, Pile-Spellman J, Ornstein E, Stein BM. Columbia University AVM Study Project. Arteriovenous malformation draining vein physiology and determinants of transnidal pressure gradients. Neurosurgery 1994; 35:389–395 [discussion 395–386]. 11. Gao E, Young WL, Pile-Spellman J, et al. Cerebral arteriovenous malformation feeding artery aneurysms: a theoretical model of intravascular pressure changes after treatment. Neurosurgery 1997; 41: 1345–1358. 12. Fogarty-Mack P, Pile-Spellman J, Hacein-Bey L, et al. The effect of arteriovenous malformations on the distribution of intracerebral arterial pressures. Am J Neuroradiol 1996; 17:1443–1449. 13. Kader A, Young WL. The effects of intracranial arteriovenous malformations on cerebral hemodynamics. Neurosurg Clin N Am 1996; 7:767–781. 14. Young WL, Pile-Spellman J, Prohovnik I, Kader A, Stein BM. Columbia University AVM Study Project. Evidence for adaptive autoregulatory displacement in hypotensive cortical territories adjacent to arteriovenous malformations. Neurosurgery 1994; 34:601–611. 15. Spetzler RF, Wilson CB, Weinstein P, Mehdorn M, Townsend J, Telles D. Normal perfusion pressure breakthrough theory. Clin Neurosurg 1978; 25:651–672. 16. Nornes H, Grip A. Hemodynamic aspects of cerebral arteriovenous malformations. J Neurosurg 1980; 53:456–464. 17. Mast H, Mohr JP, Osipov A, et al. ‘‘Steal’’ is an unestablished mechanism for the clinical presentation of cerebral arteriovenous malformations. Stroke 1995; 26:1215–1220. 18. Young WL, Kader A, Ornstein E, et al. The Columbia University AVM Project. Cerebral hyperemia after arteriovenous malformation resection is related to ‘‘breakthrough’’ complications but not to feeding artery pressure. Neurosurgery 1996; 38:1085–1095. 19. Batjer HH, Purdy PD, Giller CA, Samson DS. Evidence of redistribution of cerebral blood flow during treatment for an intracranial arteriovenous malformation. Neurosurgery 1989; 25:599–605. 20. Batjer HH, Devous MD Sr. The use of acetazolamide-enhanced regional cerebral blood flow measurement to predict risk to arteriovenous malformation patients. Neurosurgery 1992; 31:213–218. 21. Batjer HH, Young WL, Pile-Spellman J, Prohovnic I, Kader A, Stein B. The Columbia University AVM Study Project: evidence for adaptive autoregulatory displacement in hypotensive cortical territories adjacent to arteriovenous malformations. Neurosurgery 1994; 34:610. 22. Takayasu M, Dacey RG Jr. Spontaneous tone of cerebral parenchymal arterioles: a role in cerebral hyperemic phenomena. J Neurosurg 1989; 71:711–717. 23. Macfarlane R, Moskowitz MA, Sakas DE, Tasdemiroglu E, Wei EP, Kontos HA. The role of neuroeffector mechanisms in cerebral hyperperfusion syndromes (review article). J Neurosurg 1991; 75: 845–855. 24. Macfarlane R, Tasdemiroglu E, Moskowitz MA, Uemura Y, Wei EP, Kontos HA. Chronic trigeminal ganglionectomy or topical capsaicin application to pial vessels attenuates postocclusive cortical hyperemia but does not influence postischemic hypoperfusion. J Cereb Blood Flow Metab 1991; 11:261–271. 25. Ravussin P, Tempelhoff R, Modica PA, Bayer-Berger M-M. Propofol vs. thiopental-isoflurane for neurosurgical anesthesia: comparison of hemodynamics, CSF pressure, and recovery. J Neurosurg Anesth 1991; 3:85–95. 26. Spetzler RF, Martin NA, Carter LP, Flom RA, Raudzens PA, Wilkinson E. Surgical management of large AVMs by staged embolization and operative excision. J Neurosurg 1987; 67:17–28. 27. Todd MM, Warner DS. A comfortable hypothesis reevaluated: cerebral metabolic depression and brain protection during ischemia (editorial). Anesthesiology 1992; 76:161–164. 28. Rosner MJ. Cerebral perfusion pressure: link between intracranial pressure and systemic circulation (Chapter 27). In: Wood JH, ed. Cerebral Blood Flow: Physiologic and Clinical Aspects. New York: McGraw-Hill, 1987:425–448. 29. Zornow MH, Todd MM, Moore SS. The acute cerebral effects of changes in plasma osmolality and oncotic pressure. Anesthesiology 1987; 67:936–941. 30. Warner DS, Boehland LA. The effects of iso-osmolal hemodilution on post-ischemic brain water content in the rat. Anesthesiology 1988; 68:86–91. 31. Trumble ER, Muizelaar JP, Myseros JS, Choi SC, Warren BB. Coagulopathy with the use of hetastarch in the treatment of vasospasm. J Neurosurg 1995; 82:44–47. 32. Lanier WL. Glucose management during cardiopulmonary bypass: cardiovascular and neurologic implications (editorial). Anesth Analg 1991; 72:423–427. 33. Lam AM, Winn HR, Cullen BF, Sundling N. Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg 1991; 75:545–551.
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34. Busto R, Dietrich WD, Globus MY-T, Valdes I, Scheinberg P, Ginsberg MD. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 1987; 7:729–738. 35. Busto R, Dietrich WD, Globus MY-T, Ginsberg MD. The importance of brain temperature in cerebral ischemic injury. Stroke 1989; 20:1113–1114. 36. Clifton GL, Allen S, Barrodale P, et al. A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma 1993; 10:263–271; discussion 273. 37. Marion DW, Penrod LE, Kelsey SF, et al. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med 1997; 336:540–546. 38. Todd MM, Hindman BJ, Clarke WR, Torner JC. Mild intraoperative hypothermia during surgery for intracranial aneurysm. N Engl J Med 2005; 352:135–145. 39. Baker KZ, Young WL, Stone JG, Kader A, Baker CJ, Solomon RA. Deliberate mild intraoperative hypothermia for craniotomy. Anesthesiology 1994; 81:361–367. 40. Frank SM, Beattie C, Christopherson R, et al. The Perioperative Ischemia Randomized Anesthesia Trial Study Group. Unintentional hypothermia is associated with postoperative myocardial ischemia. Anesthesiology 1993; 78:468–476. 41. Chen H, Chopp M. Effect of mild hyperthermia on the ischemic infarct volume after middle cerebral artery occlusion in the rat. Neurology 1991; 41:1133–1135. 42. Porembka D, Ebrahim Z, Bloomfield E, Stuebing R. The postoperative hyperdynamic cardiovascular response following intracranial excision of arterial venous malformation (AVM) (abstract). Anesthesiology 1991; 75:A215. 43. Young WL. Clinical Neuroscience Lectures. Munster, IN: Cathenart Publishing, 1999. 44. Duckwiler G, Dion J, Vinuela F, Jabour B, Martin N, Bentson J. Intravascular microcatheter pressure monitoring: experimental results and early clinical evaluation. Am J Neuroradiol 1990; 11: 169–175. 45. Eskridge JM. Interventional neuroradiology. Radiology 1989; 172:991–1006. 46. Purdy PD, Batjer HH, Samson D. Management of hemorrhagic complications from preoperative embolization of arteriovenous malformations. J Neurosurg 1991; 74:205–211. 47. Vinuela F, Halbach VV, Dion JE. Interventional Neuroradiology: Endovascular Therapy of the Central Nervous System. New York: Raven Press, 1992:209. 48. Szabo MD, Crosby G, Sundaram P, Dodson BA, Kjellberg RN. Hypertension does not cause spontaneous hemorrhage of intracranial arteriovenous malformations. Anesthesiology 1989; 70:761–763.
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Supratentorial Lobar Arteriovenous Malformations John E. Wanebo Department of Neurosurgery, National Naval Medical Center, Bethesda, Maryland, U.S.A.
Jeffrey G. Ojemann Department of Neurosurgery, University of Washington/Children’s Hospital and Regional Medical Center, Seattle, Washington, U.S.A.
Ralph G. Dacey, Jr. Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
INTRODUCTION Supratentorial lobar arteriovenous malformations (AVMs) account for the majority of cerebral AVMs presenting to the neurosurgeon (1). Although variable in size and location, these lesions frequently affect the cortex. The arterial and venous anatomy, involvement of eloquent cortical structures, and paraventricular location determine the strategies and techniques for neurosurgical management. Although natural history data suggest an annual hemorrhage rate of 4%, patients with certain subgroups of AVMs may be at higher or lower risk for hemorrhage (2–7). In addition, the natural history of ischemic regions within AVMs is unclear. The decision for therapy must balance the risks of the natural history of the AVM relative to the risks of treatment, which in turn depend on characteristics of the AVM and on the patient’s general medical condition as well as the experience and skill of the treatment team. Decisions about combinations of therapy for AVMs should be made by neurosurgeons in conjunction with interventional neuroradiologists and stereotactic radiosurgeons. In this chapter, we first present general considerations regarding supratentorial lobar AVMs. We then proceed to specific considerations by anatomic region, specifically, frontal lobe (Fig. 1), temporal lobe (Figs. 2–5), parietal lobe (Figs. 6 and 7), and occipital lobe (Fig. 8). GENERAL CONSIDERATIONS Anatomy Patterns of Cortical AVM Involvement AVMs may be divided into surface lesions (those that are visible on the surface of the brain at exploration) and deep lesions (those that are not visible on the surface at exploration). Surface lesions may present on the dorsal (lateral) surface, the mesial surface, the polar surface, or the basal surface of the cerebral hemispheres. These lesions by definition extend to the cortex and may be variably present extending to the subcortical and subependymal regions. Within the context of lobar AVMs, the deep lesions may be sulcal (appearing in any of the sulci), fissural (appearing in the lateral, interhemispheric, or transverse fissures), or deep within the white matter. AVMs in the sulci may be exposed by dissecting through the arachnoid of the sulcus. AVMs that are deep within the fissures may still be superficial in relation to the corpus callosum and may be exposed with minimum brain retraction by opening the subarachnoid cisterns (10,11). Patterns of AVM Vascular Supply The term nidus describes a conglomerate of vascular loops. The nidus of an AVM may contain two types of connections: the first, a tangle of loops that have some inter-connections (plexiform) and the second, a direct arterial-venous fistula that is a connection of small to large vessels (fistulous).
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Figure 1 Frontal arteriovenous malformation (AVM). (A) Axial T2-weighted MR image demonstrating flow voids of a right frontal AVM. (B) Anteroposterior (AP) and (C) lateral common carotid artery (CCA) angiograms demonstrating middle cerebral artery (MCA), anterior cerebral artery (ACA), and ECA arterial contributions. (D) AP internal carotid artery (ICA) angiogram displaying sump effect with contralateral ICA injection filling AVM ACA feeders. (E) Venous phase of lateral ICA angiogram showing venous drainage to superior sagittal sinus, middle cerebral veins, and vein of Labbe´. This AVM was approached through a large right frontal craniotomy extending past midline with the patient supine. (F) AP and (G) lateral ICA postoperative angiograms showing complete resection.
Brain tissue in the nidus is usually gliotic and may show deposits of hemosiderin from previous hemorrhage. AVMs may have a single or multiple niduses. AVMs may also be diffuse, with pathological arterial-venous connections scattered throughout normal brain parenchyma (11).
Compartmentalization of AVMs Yasargil introduced the idea of compartmentalization of AVMs (11). An AVM compartment is a hemodynamic unit served by one or more feeding pedicles and one or more draining veins. When all the appropriate feeders have been divided, the compartment of interest collapses.
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Figure 2 Cross-sectional anatomy of temporal lobe demonstrating close relationship between superior temporal gyrus and sylvian fissure vessels. Source: From Ref. 8.
If additional compartments of the AVM exist, they will remain as turgid units. A single compact nidus may have one or multiple compartments. Pellettieri et al. proposed the idea of hidden compartments, regions that are not visible at cerebral angiography and may be responsible for AVM regrowth or hemorrhage after a successful operation (12,13).
Figure 3 Drawing displaying relative probability of a given frontotemporal region being critical for language function in 117 patients as assessed by stimulation mapping of left dominant hemisphere. Upper number in circle is the percentage of those patients with sites of significant evoked naming errors in that zone, while the lower number is the number of patients with a site in that zone. Source: From Ref. 9. (See color insert.)
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Figure 4 Lateral temporal arteriovenous malformation (AVM). (A) Anteroposterior (AP) and (B) lateral internal carotid artery (ICA) angiograms of this large right temporal-parietal AVM, which had middle cerebral artery (MCA) and posterior cerebral artery (PCA) supply as well as 2 right MCA aneurysms and a right proximal posterior cerebral artery (P1) segment aneurysm. The patient who presented with intraventricular hemorrhage underwent clipping of both MCA aneurysms followed by serial AVM embolizations and coiling of the P1 aneurysm before definitive AVM resection. (C) Pre- and (D) post-P1 segment aneurysm coiling as viewed on AP vertebral artery (VA) angiograms. Note MCA aneurysm clips. (E) Lateral ICA and (F) AP VA angiograms after six serial embolizations. The AVM was resected via a right pterional craniotomy with the head in a lateral position. (G) Lateral ICA and (H) lateral VA intraoperative angiograms after definitve AVM resection.
AVM Shape and Configuration The classic pyramidal or wedge-shaped AVM occurs in approximately 40% of cases (Fig. 6B, C) (11). Most AVMs, however, are irregular in shape and may be described as oval, globular, or spheroidal. AVM construction may be purely fistulous, purely plexiform, or a mixture of fistulous and plexiform. Elements of an AVM Feeding arteries from lobar AVMs are derived from five main groups including the anterior cerebral artery (ACA), the middle cerebral artery (MCA), the posterior cerebral artery (PCA), the perforating branches of each of these arteries, and the choroidal arteries. Additionally, dural branches of the external carotid arteries (ECAs) may contribute feeding arteries to lobar AVMs (14). Cerebral arteries may be related to the malformation in three ways: as a terminal feeding artery that ends in the AVM, as a transit feeding artery that feeds both normal brain and AVM, and as an artery
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Figure 5 Mesial temporal arteriovenous malformation (AVM). (A) Coronal and (B) axial T1-weighted, gadoliniumenhanced MR images of a mesial left temporal AVM status post-one embolization. (C) Anteroposterior (AP) internal carotid artery (ICA), (D) lateral ICA, and (E) lateral vertebral artery (VA) angiograms demonstrating a mesial temporal AVM with anterior temporal branch feeders from both middle cerebral artery (MCA) and posterior cerebral artery (PCA) distributions. Cortical draining veins emptied into the vein of Labbe´, then into the transverse sinus, and finally into the sigmoid sinus. A left frontotemporal craniotomy and transsylvian approach was used to resect this AVM with the head 20 degrees away from midline. (F) Lateral ICA and (G) lateral VA intraoperative angiograms showing complete resection.
en passage that passes through or near the AVM but serves brain parenchyma, not the AVM. Transit arteries are usually enlarged, whereas arteries en passage are generally normal in caliber (11). Venous drainage starts at the center of the AVM or toward the apex and continues on to one of the sinuses. Large draining veins frequently have a dilated origin with a gradual loss of caliber distally. Draining veins are usually divided into a superficial group, which drain to the sagittal, sphenoparietal, cavernous, transverse, and sigmoid sinuses, and a deep group, which pass to the subependymal collecting systems and subsequently into the internal cerebral veins, basal veins of Rosenthal, internal occipital vein, and the vein of Galen.
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Figure 6 Right parietal arteriovenous malformation (AVM). (A) Sagittal T1-weighted and (B) axial proton density MR images demonstrating flow voids of this parietal AVM with probable involvement of supramarginal gyrus. (C) Anteroposterior (AP) and (D) lateral internal carotid artery (ICA) angiograms showing posterior middle cerebral artery (MCA) feeding arteries and venous drainage into sagittal sinus and into vein of Labbe´, both of which drain into transverse sinus. Temporal branches of PCA also served this AVM. (E) Lateral ICA and (F) vertebral artery (VA) angiograms of AVM after serial embolization. This AVM was approached from a large fronto-temporo-parietal craniotomy with somatosensory and motor mapping (Fig. 7). Intraoperative angiography intitally demonstrated residual AVM with a subsequent intraoperative study demonstrating complete resection.
Clinical Presentation Patients with symptomatic lobar AVMs can present with cranial hemorrhage, epilepsy, headaches, and/or progressive neurological deficits. In addition, an increasing number of
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Figure 7 Right parietal arteriovenous malformation (AVM) resection (same patient as Fig. 6). (A) Use of somatosensory evoked potentials from a hand stimulus site to localize primary somatosensory cortex (C denotes central sulcus). (B) Motor mapping of hand area (H) using a setting of 4 on Ojemann stimulator. (C) Parietal AVM located 1.5 gyri posterior to somatosensory cortex (S). Hand area (H) and central sulcus (C) also labeled. (D) Drawing of circumferential dissection of AVM with isolation, coagulation, clipping, and division of feeding pedicles with Weck clips placed on feeders larger than 0.5 mm. (E) Sundt aneurysm clips used for deep feeders. (F) Clipping and coagulation of final draining vein after inspection confirmed obliteration of all feeders. (See color insert.)
asymptomatic lobar AVMs are discovered incidentally by computed tomography (CT) scans or magnetic resonance imaging (MRI). Specific presentations of each type of lobar AVM will be addressed in later sections. Radiographic and Functional Evaluation CT and MRI Non-contrast enhanced CT scans readily demonstrate basic characteristics of lobar AVMs including the presence of acute or subacute hemorrhage, hydrocephalus, mass effect, and encephalomalacia (15). Hemorrhage usually occurs in the parenchyma or ventricle adjacent
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Figure 8 Occipital arteriovenous malformation (AVM). (A) Anteroposterior (AP) internal carotid artery (ICA), (B) lateral ICA, and (C) AP vertebral artery (VA) angiograms demonstrating parietal-occipital AVM with parietal feeding branches from left middle cerebral artery (MCA) and left posterior cerebral artery (PCA). (D) Lateral VA angiogram demonstrating venous drainage to superior sagittal sinus, straight sinus, and transverse sinus. After two embolizations of PCA feeders, this AVM was approached via a large left occipital craniotomy extending past the midline with the patient prone. (E) Lateral ICA and (F) lateral VA intraoperative angiograms showing complete resection.
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to the AVM, and occasionally, only subarachnoid hemorrhage is found (16,17). In up to 31% of larger AVMs, calcification is evident on non-contrast CT (18). Contrast-enhanced CT scans frequently demonstrate the AVM nidus and the larger feeding arteries and draining veins. MRI surpasses CT scanning in defining the anatomic relationships of AVMs to brain parenchyma (Figs. 1A; 5A,B; and 6A,B). The sensitivity of MRI to flowing blood allows for excellent demonstration of the AVM nidus and its major feeding arteries and draining veins (19–21). T1 imaging in three planes provides excellent delineation of parenchymal and ventricular anatomy relative to AVM flow voids (22). T2 sequences show cerebrospinal fluid (CSF) and any parenchymal edema, while gadolinium enhancement reveals channels of slow flow. The location of the Rolandic fissure and sensorimotor cortex can be reliably identified on axial images (23). Three dimensional reconstruction of MR images can provide excellent delineation of the anatomic complexity of a lobar AVM (24). MRI may also be used to evaluate the changes in an AVM nidus after radiosurgery (25). The anatomic relationship of the AVM to brain structures demonstrated on MRI plays a significant role in the treatment decision process. Angiographic Evaluation and the Role of Embolization Superselective Angiography
Understanding the angioarchitecture of the AVM is essential to guide its management. Superselective catheterizations and digital subtraction angiography techniques can provide a precise understanding of the AVM’s nidus, feeding pedicles, and draining veins (15,26,27). Selective catheterizations and mapping of feeding pedicles is usually required to evaluate the presence of a rapidly filling nidus for aneurysms, fistulas, and vessels en passage. All feeders must be understood, and care must be taken with transit arteries, which may supply both the AVM and normal brain tissue. Large lesions may have feeders from all three major vascular divisions, may reach the ventricular surface, may have both superficial and deep venous drainage, and may be supplied by a ECA. The border zone of the AVM and brain parenchyma may be poorly delimited but should be angiographically defined when possible. Enlarged collaterals at these AVM border zones should not be embolized, since they often serve normal brain parenchyma. Venous drainage should also be evaluated. It is noteworthy that the presence of venous stenosis with associated proximal venous dilation or of arterial aneurysms associated with the AVM are angiographic risk factors for increased hemorrhage. Repeat angiography is important as close to the operation as possible, because the configuration of the AVM may change, including the appearance of new feeders or thrombosis of feeders previously visualized. Role of Embolization
Preoperative embolization has evolved into a standard technique for AVM therapy and augments AVM treatment in several ways (26,28–35). Embolization can significantly devascularize AVM feeders from ECA, internal carotid artery (ICA) and vertebral artery (VA) distributions, often eliminating feeders entirely, (Figs. 4E,F, and 6E,F). Feeder embolization is most helpful in the case of large, complex lobar lesions by reducing overall flow to the AVM and by eliminating specific feeders. A large AVM may be reduced in size to one that is more readily treatable, with either microsurgery or radiosurgery. In certain cases, large, high flow AV fistulas may impair visualization of smaller nearby feeding vessels or may impair superselective Wada testing due to vascular steal. Embolization of these large AV fistulas can facilitate better regional angiography, mini-Wada testing, and additional embolization of nearby feeders. By changing the AVM hemodynamics, preoperative embolization may also reduce the incidence of normal perfusion pressure breakthrough (NPPB) (36). Although serial preoperative embolization can devascularize an AVM, thereby making dissection easier and potentially reducing the risk of NPPB, it is important that the risk of surgery and embolization be lower than the risk of surgery alone, since even in experienced hands, embolization complications can occur. Intraoperative Angiography
Intraoperative angiography has become a common procedure since its initial development in the 1960s (28,37,38). Digital subtraction angiographic techniques were introduced in 1984 and have allowed for the accurate assessment of resection completeness before wound closure. Intraoperative angiography may be particularly helpful for removal of lobar AVMs within
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eloquent cortex, where exposure and resection may be more conservative. Pietilla et al. reported a 19% incidence of residual nidus during the resection of AVMs in the eloquent cortex (39) (Figs. 4G,H, and 5F,G). Functional Evaluation: Mini-Wada Testing Provocative testing, or ‘mini-Wada’ testing, uses superselective catheterization of AVM feeding pedicles with the catheter tip close to the nidus. Sodium amobarbital is administered through the catheter, anesthetizing brain supplied by the catheterized vessel, but sparing other, non-perfused, cortex. Function (e.g., motor and language) is then assessed. Because amobarbital is short-acting, the test can be repeated for different vessels. Thus, unlike the Wada test (40), in which the entire hemisphere is anesthetized, a smaller portion of brain is tested with the so-called mini-Wada test (40). Language is typically assessed by object naming, thus testing both receptive and expressive aphasia. Motor strength is directly assessed while the drug is administered. Errors in the predictive value of the mini-Wada can be both false positive and false negative results. False positives arise from amobarbital perfusion of brain that would be perfused post-operatively. The amobarbital may penetrate small vessels that would normally remain patent by collaterals after resection. Also, the AVM sump effect may pull all the flow to the pedicle of the AVM from normal brain. Therefore, superselective catheterization should be repeated with mini-Wada testing after the flow has been diminished by embolization. High vascular pressures within the feeding pedicles may suggest that these pedicles feed normal brain. False negative results can arise if amobarbital fails to reach areas that will be devascularized or resected. This may be important for AVMs that arise from both anterior and posterior circulations as in the posterior temporal lobe. Intravenous conscious sedation is frequently used for wire-directed systems, since the patient must be absolutely still for angiographic road mapping. However, patients must be able to be awakened for amobarbital testing and follow-up neurological examination. In patients with dominant hemisphere temporo-parietal or fronto-opercular AVMs, superselective Wada testing frequently demonstrates anterior translocation of language function (41). Functional Imaging The usefulness of functional imaging in AVM management is several fold. The variations of language cortex are well described by Ojemann and colleagues, and significant distortion of language cortex location can be found in the presence of lobar AVMs (9,42,43). Pretreatment localization of eloquent cortex can guide the choice of therapy. If surgery is pursued near eloquent cortex, the direction of approach can be chosen appropriately. Accurate identification of eloquent cortex may also allow for more selective use of superselective angiography and can help with the adjustment of isocenters during radiosurgery. Several functional imaging techniques are applicable for use with lobar AVMs. Functional MRI (fMRI) demonstrates increased blood flow to activated eloquent cortex (44). Currently, fMRI can facilitate preoperative identification of speech, motor, and visual functional cortex relative to AVM, but the technique is not accurate enough by itself to guide resections around eloquent cortex (45–48). fMRI of regional brain activity within the confines of an AVM nidus may help to predict the likelihood of post-therapy deficits (45). Preoperative localization of speech, sensory, and motor cortex using fMRI may help in the planning of isodose curves for AVMs treated with radiosurgery (49). Positron emission tomography (PET), like fMRI, can localize functional areas of the brain activated by behavior-specific tasks (50). Preoperative PET scanning has been used to delineate motor cortex in the presence of a lobar AVM with good correlation to intraoperative cortical mapping (51,52). Language cortex can also be mapped by PET in the presence of lobar AVMs, although less reliably than motor cortex (53,54). By delineating the relationship of an AVM to functionally important areas of the brain, these functional studies provide additional data to assess the risks of treatment. Magnetoencephalography (MEG), which evaluates the magnetic effect of currents generated by large neurons, can also be used to identify eloquent motor and speech cortex (43,55). MEG has been used to map out language cortex in the presence of lobar AVMs with good correlation to intraoperative cortical mapping (56). Motor and sensory mapping using MEG has facilitated assignment of patients with eloquent cortex AVMs to surgical or non-surgical
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therapy (57). Preoperative MEG mapping of sensorimotor cortex has been integrated with CT, MRI, and angiographic data and has been used successfully in image-guided resections of lobar AVMs (58). Decision Analysis Decisions about AVM treatment depend on the characteristics of the patient, including age and medical condition, and on characteristics of the AVM, including the natural history of the disease and the risks and success rates of therapy. The potential management options include observation only (including seizure and headache management), microsurgery, radiosurgery, embolization, and combinations of these therapies. Knowledge of the outcome of each therapy is essential for decision making and patient counseling. From Ondra’s AVM natural history data taken from Troupp’s AVM series, we expect a yearly hemorrhage rate of 4% with a yearly morbidity rate of 2% and a yearly mortality rate of 1% (2,5). Certain AVM characteristics are associated with a higher risk of hemorrhage (3,4,6,7). Smaller AVMs are thought to bleed more frequently than medium and large lesions, possibly due to higher feeding artery pressures (59,60). Others report that size does not alter hemorrhage rate (61,62). AVMs with slower arterial filling times based on time to peak angiographic contrast density also have a higher bleed rate, possibly reflecting slow flow, high pressure lesions (7). Impaired venous drainage, venous stenosis, and exclusive deep venous drainage have also been linked to higher rates of hemorrhage (3,6,63,64). Nataf et al. reported that venous recruitment is protective against hemorrhage (6). Other angiographic features associated with a higher AVM hemorrhage rate include AVM-associated arterial or venous aneurysms, periventricular location, and prior embolization (4,65,66). Surgical cure rates approach 100%, and surgical morbidity (8 to 71%) and mortality (0 to 4.8%) rates increase with Spetzler-Martin grade (67–69). The recurrence of AVMs after angiographically confirmed surgical excision is rare, although it has been reported (70). Kader et al. described recurrent AVMs in 5 of 141 children (age under 18) but in none of 667 adults after AVM resection, suggesting that angiographic follow-up after the initial postoperative study should be delayed for at least a year in children with AVMs (60). Radiosurgery cure rates three years after surgery are reported as up to 90% for lesions less than 3 cm, but only 50% for larger lesions, with a morbidity rate of 2% and a mortality rate of 1% (71–74). For embolization therapy alone, a cure rate of 4%, a morbidity rate of 10%, and a mortality rate of 1% are reported (75–79). Embolization alone rarely produces total obliteration, and partial embolization has not been shown to decrease risk of hemorrhage (80). Therefore, embolization alone is reserved for very large lesions causing symptoms of progressive neurologic decline in which neither surgery nor stereotactic radiosurgery, is considered feasible with an acceptable risk of morbidity and mortality. Embolization may reduce the flow enough to improve symptoms, at least temporarily. In an effort to facilitate decision making with this complex set of variables, which in part includes patient condition and age, AVM natural history, and the risks and success rates of embolization, stereotactic radiosurgery, and open microsurgery, several authors advocate decision analysis (81–83). In Fisher’s decision analysis, which used the American Society of Anesthesiologists (ASA) grading scale to classify the patient in one of five groups and the Spetzler–Martin five grade scale to stratify AVM surgical outcomes, open surgery was favored over radiosurgery, delayed therapy, or embolization plus therapy for all Spetzler–Martin grade 1 to 3 AVMs unless the ASA grade was 4 or 5; for the latter cases, radiosurgery was favored (67,84). For ASA grade 3 patients who had AVMs less than 3 cm in diameter, both surgery and radiosurgery were favored and had similar outcomes. Radiosurgery was favored for all Spetzler-Martin grade 4 and 5 lesions despite cure rates of less than 50%. Fisher’s model did not address the circumstances of multiple AVMs or AVMs associated with aneurysm. Radiosurgical Management Lobar AVMs that are not suitable for surgical removal may be considered for radiosurgical management. Radiosurgery can be useful in treating small AVMs less than 3.5 cm diameter in poor surgical candidates. Friedman reported an angiographic obliteration rate of 84% for AVMs less than 10 cm3 treated with radiosurgery but an obliteration rate of only 58% for those
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greater than 10 cm3 (85). Although small AVMs may be treated with radiosurgery, at least two years are required for complete obliteration in most cases, with no additional protection from hemorrhage conferred during this time (66,86). Chang et al. recently reported effective surgical treatment of radiosurgery failures, noting that these lesions were less vascular than expected and easier to resect (87). Significant side effects of radiation have been reported in 3–9% of patients with radiosurgically treated AVMs; these effects include radiation necrosis, cyst formation, and arterial stenosis (88–92). Higher complication rates are associated with higher radiation doses and closer proximity to eloquent cortex (72). With careful dosing and planning, Friedman reports a 1% risk of permanent radiation-induced neurologic deficits with a 3% risk of temporary deficits (84). Radiosurgery is an option for small deep-seated lesions that cannot be reached without prohibitive risk, but it is not generally recommended for the treatment of lobar AVMs unless they are in extremely eloquent cortex where surgery is judged to be associated with prohibitive risk. Surgical Techniques Timing Surgery for AVMs is usually performed on an elective basis. In the case of intraparenchymal hemorrhage with life-threatening mass effect, the hemorrhage may be evacuated, but often the AVM is not resected unless it is simple to remove and easily exposed during craniotomy for removal of the hemorrhage. The decision to remove the AVM at the time of hematoma resection depends on the degree of brain swelling, the size and configuration of the AVM, and the exposure of the AVM that is afforded by the craniotomy. Moderate simple hemorrhages can be treated conservatively in many patients, thereby allowing the clinical condition to improve before surgery. Positioning For cortically presenting AVMs, the head should be positioned so that the surface of the AVM is parallel to the floor; this position enables arterial feeders to be approached in a perpendicular fashion. For large lesions that may have feeders from all three major vascular divisions, may reach the ventricular surface, may have both superficial and deep venous drainage, and may have ECA supply, the head should be positioned so that the most significant feeder can be addressed. Ideally, the head should be positioned also to allow gravity to aid in brain retraction and to avoid compression of neck veins, which would impede venous drainage. Craniotomy A generous craniotomy and dural opening should be performed, exposing a large portion of brain tissue around the nidus and thereby allowing for easier identification of the arterial feeders, draining veins, and cortical landmarks. A generous craniotomy enables the surgeon to map functionally important cortex, permits wider freedom to adjust the microscope angle, and provides the potential to deal with unforseen AVM angioarchitecture or hemorrhage distant to the AVM. When there is significant meningeal supply, extreme caution must be exercised with the craniotomy flap. The creation of multiple holes and the coagulation of any meningeal feeders visible through the burr holes before the bone flap is removed are helpful techniques. The dural opening should commence far from the surface presentation of the AVM to avoid tearing of involved vessels from mengingeal vascular pedicles. Sometimes it is necessary to leave the AVM attached to a segment of free dura to prevent injury to AVM vessels. Occasionally, multiple feeders necessitate the use of several positions to expose and divide these vessels. Microsurgical Equipment The operating microscope should be used for dissection of the arachnoid, and bipolar forceps of multiple lengths and multiple tip diameters should be available for use, as should thumb regulated, graduated suction tips. MRI-compatible titanium permanent hemoclips can be used to occlude large feeding vessels greater than 0.5 mm in diameter. The Sundt microclips are useful for vessels in the depths of the resection, which are often resistant to bipolar cautery and are frequently best managed by clipping. Dissection AVM excision proceeds in several stages including identification of the malformation, elimination of superficial feeding vessels, circumferential dissection, dissection of the apex of the
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lesion, division of the final vascular pedicle and draining vein at the time of complete AVM removal, and, finally, absolute hemostasis. After identification of superficial feeders, the arachnoid can be opened with an arachnoid knife and then followed until it enters the AVM. The feeding vessels may then be divided after first confirming that they do not serve normal brain. The en passage vessels serving normal brain, frequently encountered in perisylvian lesions and in those around the corpus callosum, must be preserved. Occasionally, ultrasound may be used to identify AVMs that are not visible on the surface. Major draining veins associated with the AVM should be preserved until the end of the operation. Management of Arterialized Veins Red veins should not be confused with feeding arteries. Under higher magnification, red veins have thinner walls and are less turgid than the arteries of the same size. Veins also generally have a larger diameter than the arteries. Temporary clip placement will reduce pulsations either away from the AVM, in the case of vein application, or towards the AVM, in the case of arterial feeder application. Veins are easier to compress than arterial feeders using the bipolar cautery. The use of small, quick, bipolar current will shrink a vein much faster than an artery. Circumferential AVM Dissections After all large superficial feeding vessels have been identified and divided, circumferential dissection can proceed around the AVM (Fig. 7D). The smallest amount of brain tissue should be transgressed, and the utilization of cisternal and sulcal anatomy should be maximized. Dissection should be carried out as close to the margin of the lesion as possible to avoid injuring adjacent brain. The plane of dissection can be slightly more peripheral in lesions far from critical areas, such as those in the frontal or temporal poles. Oozing at the margin of the lesion can be controlled with cottonoids compressed under a retractor onto the lesion. Packing bleeding on the brain side can cause intraparenchymal or intraventricular hemorrhage, potentially leading to catastrophic swelling. For convexity lesions, the initial circumferential dissection should proceed to a depth of 2.5 cm, which is the maximum depth of the sulci, and should include all of the superficial arterial feeders. Additional major feeders are usually not encountered until the apex of the AVM. Since these vessels are usually small, subependymal, and resistant to coagulation, hemoclips, small aneurysm clips, or Sundt microclips can be used for control (Fig. 7D–F ). Packing should be avoided. Occasionally, hypotension can be used to control bleeding at this stage. Near the completion of the resection, an AVM should remain attached from one or more venous pedicles. If the veins are still arterialized, it may indicate that small feeders deep to the draining veins may persist. Hemostasis Absolute hemostasis after AVM dissection is essential. Cottonoids placed in the resection cavity to mark planes should be carefully removed, under constant irrigation. The entire wall of the resection cavity should be inspected under high magnification so that bleeding or clotted blood is identified. The walls of the resection bed may be rubbed gently with a cottonoid to expose any residual AVM or microscopic bleeding sites. When the surgeon is certain that the entire AVM has been removed and all hemorrhage is controlled, the cavity is lined with Surgicel. The anesthesiologist then should raise the blood pressure to 20 mmHg above the resting pressure to expose any potential bleeding sites. The surgeon should inspect the AVM cavity for approximately 15 minutes under elevated blood pressure. It is important to ensure that the blood pressure does not rise above this artificial elevation. Intraoperative angiography should be performed before wound closure on complicated AVMs or if there is any uncertainty about completeness of resection. Postoperative Management It is of the utmost importance that these patients are awakened from anesthesia in a smooth fashion without any blood pressure elevations, Valsalva maneuvers, or coughing. Instantaneous control of blood pressure is necessary to keep the value below the level tested intraoperatively for 48 hours postoperatively. After resection of large, high volume AVMs, some patients develop a syndrome of swelling or hemorrhage in the operative bed and the surrounding brain tissue that cannot be explained by residual lesion or by early obstruction or obliteration of draining
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veins (93). This syndrome, termed NPPB, is attributed to the restoration of normal perfusion pressure to the surrounding vascular bed after removal of the shunt, which is thought to be dysautoregulated due to chronic hypoperfusion. Predisposing angiographic characteristics for NPPB include a large nidus, the presence of large caliber and long feeding vessels, and differential shunting into the AVM, possibly filling the vessels in the adjacent brain (35). NPPB may be prevented by the gradual reduction of flow into large AVMs by embolization. FRONTAL LOBE AVMs Anatomy AVMs of the frontal lobe occur in paramedian, lateral, frontobasal, and frontopolar locations. The anatomical location determines the likely arterial supply and venous drainage and the patterns of clinical symptomatology. The anatomical location also determines the surgical approach. Paramedial AVMs occupy the superior frontal gyrus and its interhemispheric medial surface. These lesions may involve or be adjacent to the supplementary motor area. Arterial supply is predominantly from branches of the ACA with additional input from the MCA. Frontal AVMs fed solely by the ACA can be difficult to embolize because feeding vessels from these parent arteries frequently also supply normal brain distal to the AVM. Venous drainage is into the superior sagittal sinus. Anterior AVMs of the corpus callosum may overlap with these lesions. Lateral frontal AVMs are situated in the middle and inferior frontal gyri; in the dominant hemisphere, they may involve motor speech areas (Fig. 3). The predominant arterial supply is from the MCA, but in larger lesions the ACA also may contribute. High-flow lesions may recruit arterial supply from middle meningeal arteries. Venous drainage is into the middle cerebral vein and sphenoparietal sinus. Rarely, some veins drain deeper to the subependymal system or posteriorly to the parietal occipital area. Orbitofrontal lesions are located in the orbital gyri and the gyrus rectus. They receive their arterial supply from the Al and A2 segment branches of the ACA, including the frontopolar branch, from perforators off the Ml and M2 segments of the MCA, and from branches of the ophthalmic artery. Occasionally, frontopolar AVMs can receive contributions from the ethmoidal artery or from the anterior falcine artery, both off the ICA. Venous drainage is usually into the superior sagittal sinus (SSS), the sphenoparietal sinus, the sylvian system, or posteriorly into the basal vein of Rosenthal. Frontopolar AVMs share similar anatomical characteristics. Most frontal AVMs are conical or pyramidal in shape with their broad base at the cortical surface and their apex at the ventricular ependymal surface. Perforating arterial vessels typically supply the apex or deepest part of such lesions and frequently contribute to the difficulty of removing the last parts of the AVM. Clinical Presentation Frontal AVMs, like those in other areas, may present with seizures, hemorrhage, headaches, or progressive neurological deficits. Seizures are a common presentation of frontal lobe AVMs. Frontal cortex is thought to be more epileptogenic than other cortical locations (94). Seizures arising from the frontal lobe often have a rapid onset compared to seizures arising from other regions, such as temporal lobe, where auras or other warnings may precede overt seizure activity. Some typical features of frontal lobe seizures have been described (95). Contraversive head movements (head turning away from the side of seizure focus) classically occur with dorsolateral frontal seizures. Seizures involving medial frontal cortex provoke head and eye turning associated with arm movement. Seizures arising near motor cortex can give rise to focal motor seizures, or to ’Jacksonian’ motor seizure if progression of seizure activity occurs along the motor homunculus. Autonomic manifestations are associated with insular seizure onset but may also appear in some fronto-insular seizures (95). Of Yasargil’s 59 patients with frontal AVMs, 51% presented with seizures (94). The reported range of patients presenting with hemorrhage is from 40% to 70% (5,96–99). Patients with frontopolar and frontobasal AVMs are more likely to present with an intracerebral, subarachnoid, or subdural hematoma, whereas paramedial lesions more often occur in the
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presence of intraventricular hemorrhage. Central venous drainage, intranidal aneurysms, periventricular location, and venous stenosis are all associated with an increased risk of hemorrhage (65). Occasionally, patients with a lobar AVM present with severe hemorrhage that requires emergent evacuation; in these situations an angiogram may not be possible. Only a high index of suspicion will lead to the diagnosis of AVM as cause of the hemorrhage. Three to 23% of patients with AVMs have concomitant aneurysms, which may be the source of the hemorrhage (100,101). Patients with lobar frontal AVMs may also present with progressive neurological deficits, which occurred in 37% of Yasargil’s 59 patients, all of whom had an associated hemorrhage (94). Posterior frontal lesions may cause progressive hemiparesis due to steal and/or mass effect. Lateral lesions may cause aphasia. Headaches are described by 10% of patients (94). Radiographic and Functional Evaluation In addition to the standard radiographic evaluation, attention to the functional anatomy is particularly pertinent to frontal AVMs. In particular, the evaluation of language and motor function can affect surgical management of frontal AVMs. Most (98%þ) right-handed individuals are lefthemisphere dominant for language, and at least 70–80% of left-handed individuals are also left-hemisphere dominant for language (40,102). However, language lateralization must be definitively established, traditionally with the cerebral amobarbital test (or Wada test) (40). Anesthesia of one hemisphere with intracarotid injections of sodium amobarbital can lateralize language function on the basis of the performance of the unanesthetized hemisphere (40,103). Functional imaging (e.g., fMRI or PET) during performance of a language task appears to be another reliable method for language lateralization (102). Additional tools for localizing both language regions and motor cortex include the superselective Wada tests and functional imaging. When AVMs are considered for embolization, a catheter placed into a feeding branch can be used to selectively administer amobarbital, thus anesthetizing a smaller region of cortex. The presence or absence of preserved language or motor function during these injections can aid in localizing critical areas. fMRI shows promise for localizing language function; however, precise agreement with fMRI localization and stimulation mapping (to the resolution of a gyrus, for example) has yet to be achieved. Motor cortex can be better localized than language on preoperative functional imaging (PET, MEG, fMRI), although the gold standard remains intraoperative motor mapping (45,46,48,51,52,57, 104–107). (Speech mapping techniques are described in the temporal AVM section.) We generally perform motor and sensory mapping for posterior frontal and anterior parietal AVMs (Fig. 7A–C) and speech mapping for these lesions in the dominant hemisphere. Intraoperative motor mapping plays an important role in posterior frontal AVM management since in some cases the motor area can be shifted to accessory motor cortex (Fig. 7B) (107). Decision Analysis Proximity of frontal AVMs to eloquent language and motor cortex, size of AVM, angioarchictecture of AVM, and patient medical condition all play a role in the decision for type of therapy. In addition to features discussed earlier (in general decision analysis), the presence of lenticulostriate arterial contribution can significantly influence outcome. In Morgan’s series of 92 patients with surgically treated AVMs with MCA supply, 10 had significant lenticulostriate supply; of those 10, 8 had neurologic complications referable to lenticulostriate distribution (108). As reported by others (109,110), we use a multimodality approach to frontal AVMs that includes nidus embolization, radiosurgery, and microsurgery. Surgical Management Anterior paramedian frontal AVMs are usually approached through a frontal craniotomy with the patient supine and the head straight up; this position facilitates control of interhemispheric feeding vessels. If ACA feeding vessels can be eliminated with preoperative embolization, the head may be turned 90 degrees with the ipsilateral side up. Crossing the midline with the bone flap maximizes the ipsilateral exposure gained by dural reflection at the margin of the sagittal
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sinus. The AVM can then be retracted against the falx as MCA feeders are taken laterally. It can be difficult to expose the arterial feeders yet preserve the venous drainage, particularly with veins traversing the interhemispheric fissure to enter the sagittal sinus. Ideally, preoperative embolization can reduce the number of ACA feeders that need to be accessed. A generous anterior-posterior exposure of the parasagittal area provides the surgeon with several routes of access around obstructing draining veins. On some occasions, when venous drainage cannot be reasonably preserved, one may consider accessing the AVM on its mesial aspect via a parasagittal corticotomy, frequently via a sulcal corticotomy. Occasionally, the medial lesions may also be served by branches extending from the falx, in which case resection of the involved falcine segment can speed the dissection. It is important to avoid damage to the contralateral parasagittal frontal hemisphere, and both ACAs should be identified in parasagittal lesions to ensure that they are preserved. Paramedian AVMs involving the posterior frontal lobe and the parietal lobe are more complex because they usually derive blood supply from more than one arterial distribution, they frequently have large draining veins to the sagittal sinus that limit entry into the interhemispheric fissure, and they are frequently involved with critical primary motor and sensory areas. Preoperative embolization of interhemispheric feeders can be very helpful with these lesions. If embolization is not feasible, the procedure may be staged. In the first surgical stage, the patient is positioned supine with the head straight up to occlude ACA feeders. A broad-based bone flap over the sagittal sinus is used to maximize the approach through the interhemispheric fissure and minimize possible potential damage to interhemispheric arterialized draining veins. These veins often can be dissected from the arachnoid and gently mobilized to one side enough to facilitate access to the medial frontal lobe. In the second stage, the patient is in the supine position, with the head turned 90 degrees, elevated and ipsilateral side up, facilitating occlusion of convexity MCA feeders. To approach AVMs of the lateral frontal cortex, we use a large frontotemporal bone flap, which provides adequate exposure of the sylvian fissure and of the components of the AVM adjacent to the sylvian fissure (Fig. 1A–G). In lesions with significant input from the interhemispheric fissure, the flap is extended to the parasagittal region. Unlike aneurysm surgery, the sphenoid ridge is not resected routinely, and in general the horizontal portion of the sylvian fissure is not opened unless exposure of the Ml is necessary. For posterior frontal lesions involving motor and speech areas, the insular portion of the sylvian fissure is opened widely so that the surgeon can identify the origin of the ascending frontal branches and follow them distally into the AVM. This technique should reduce the incidence of inadvertent damage to vessels en passage serving normal cortex. For large posterior frontal AVMs, we recommend circumferential dissection of the lesion down to the paraventricular margin with sacrifice of the perforating vessels just as they enter the malformation through the deep white matter. Given the proximity of the motor and somatosensory cortex of posterior frontal or anterior parietal AVMs, we generally perform somatosensory and motor mapping to minimize motor and sensory deficits (Fig. 7A–C). Sensorimotor cortex can be identified with intraoperative mapping. Using bipolar stimulation with electrodes 1 cm apart (Ojemann Cortical Stimulator, Radionics, Burlington, MA), current is applied to the cortical surface while the contralateral arm and leg and the bilateral face are observed for movement. Current begins at 2 mA and increases by intervals of 1–2 mA up to 8–10 mA or until an effect is encountered (105). The cooperation of the anesthesiologists is critical, as paralytic agents must not be used, and careful patient observation is required. Profound anesthesia during mapping may also impair evoked motor responses. The operative approach for orbital surface AVMs is generally via the pterional exposure with resection of the lateral sphenoid ridge and wide opening of the sylvian fissure to facilitate early access to branches of the Ml and M2 segments that supply these malformations. These segments can be tracked along the orbital cortical surface until they perforate into the malformation, at which point they can be divided. For dissection of frontal orbital AVMs at the Ml and Al segments, attention should be paid to the region of the subolfactory sulcus, where branches from the A2 segment can dip medially into the sulcus, leave laterally, and subsequently serve the AVM (94). Posterior orbital cortex AVMs require a wide opening of the sylvian fissure and generous subfrontal retraction. Perforating branches of the Ml segment, which are exposed via a corticotomy, are followed into the nidus. Since lenticulostriate
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arteries can be indistinguishable from perforators supplying the AVM, it is essential to identify all vessels in the region of the AVM to preserve the normal perforators that transit the periphery of the AVM. Management of giant frontal AVMs begins with preparing the entire Al and Ml segments, ensuring sufficient proximal control. Feeding branches from the A2 and M2 may be approached through dissection into the sulci which may be up to 5 cm deep. Vessels can be dissected circumferentially as far as the ventricular system. Outcome In Yasargil’s patients with frontal lobe AVMs, seizure incidence fell from 51% preoperatively to 14% postoperatively (94). All patients with normal findings on preoperative mental and neurological examinations had favorable outcomes after frontal lobe AVM resection, whereas only 77% of those with preoperative mental or neurological deficits had favorable outcomes. AVM surgery in the frontal region is associated with relatively low risks of morbidity and mortality (94). Occasional temporary impairment of higher mental function and loss of short term memory is found. With a modern multidisciplinary team approach, even frontal AVMs near functional areas can be effectively treated with a low morbidity rate (87% stable or improved neurological outcomes in Ausman’s series of 34 pericentral AVMs) (109). TEMPORAL LOBE AVMs Anatomy AVMs of the temporal lobe present unique functional considerations in addition to the specific anatomy and vascular supply of the region. Surgically, it is useful to consider separately AVMs of the temporal neocortex from AVMs of the medial temporal region, specifically of the amygdalohippocampal region. A review of the coronal plane anatomy of the temporal lobe demonstrates the close relationship of the superior temporal gyrus to the sylvian fissure and the vessels traveling within (Fig. 2). By following the superior temporal gyrus inferiorly and then medially, the middle and inferior temporal gyri are encountered. The lateral occipito-temporal gyrus separates the inferior temporal gyrus from the parahippocampal gyrus, which, in turn, is contiguous with the hippocampus and, together with the amygdalohippocampal complex and the uncus, constitutes the medial temporal lobe. The hippocampus serves as the inferior wall of the temporal horn, the latter containing the choroid plexus and the choroidal artery traveling within the choroidal fissure. The choroidal artery is a common source of branches to both medial and lateral temporal AVMs. Temporal lobe convexity lesions are usually supplied by distal branches from the MCA and the PCA. Peduncle and temporal branches of the anterior choroidal arteries may also supply temporal lesions. Clinical Presentation Seizures are a common presenting feature. In Yasargil’s series, seizures were present in 40% of all patients with temporal AVMs, and 65% of patients with mediobasal AVMs presented with seizures (94). Seizure type can be somewhat helpful in localization. Although complex partial seizures can occur from foci in many different regions, vertiginous seizures are thought to indicate lateral temporal onset, whereas olfactory, masticatory, absence seizures, or seizures with sexual behavior appear to point toward medial temporal onset. The more common presentations of hallucinations, dyscognitive and affective states, and automatisms can be seen with either medial or lateral seizure onsets. Seizures that affect speech—speech arrest, post-ictal comprehension, or fluency difficulties—suggest involvement of the dominant temporal lobe. Memory deterioration also occurs, especially verbal memory in patients with dominant medial temporal lobe lesions. Visual disturbances are less commonly reported, but superior quadrantanopsia may occur, especially after hemorrhage of a temporal AVM near the visual radiations of Meyer’s loop adjacent to the temporal horn. Of 70 patients in Yasargil’s series with temporal lobe AVMs, 60% presented with hemorrhage alone, 16% had both hemorrhage and epilepsy, and 14% had headaches (94). 39 of 70 (55.7%) had preoperative neurological deficits, and 90% of those patients had hemorrhage (94).
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Functional Evaluation Lateralization In addition to the standard radiographic evaluation (remembering the likelihood of both anterior and posterior circulation supply to temporal AVMs), attention to the functional anatomy is particularly pertinent to temporal AVMs. Evaluation of language and memory function can affect surgical management of temporal AVMs. Determining language lateralization is essential for decision making in temporal lobe AVMs and can usually be accomplished with the cerebral amobarbital test or with functional imaging (e.g., fMRI or PET) during performance of a language task. Superselective Wada for Language Additional tools for localizing language regions include the superselective Wada tests. Especially when AVMs are considered for embolization, a catheter placed into a feeding branch can be used to selectively administer amobarbital, thus anesthetizing a smaller region of cortex. The presence or absence of preserved language function during these injections can aid in localizing critical areas. Although imaging tools such as fMRI show promise for localizing language function, precise agreement with fMRI localization and stimulation mapping (to the resolution of a gyrus, for example) has yet to be achieved. Superselective Wada for Memory The Wada test may also be used to assess dominance for verbal memory. If memory is primarily sustained by the medial temporal regions involved by the AVM (a fortunately rare occurrence), then resection might carry a greater risk of provoking severe memory deficits (111). Cortical Mapping To determine if a specific region is critical for language, elaborate testing appears to be necessary. Although anatomical landmarks can offer some security in avoiding critical language areas, it is known from stimulation mapping of language function that the precise location of language varies across individuals and that sites even within 4 cm of the temporal tip, on superior temporal gyrus, can be critical for language function. The relative probability of a given fronto-temporal region being critical for language is illustrated (Fig. 3). Although some have suggested that staying within the AVM avoids the risk of neurological sequelae, others have reported effective use of cortical localization in planning surgical resection (104,105). Preservation of function in tissue adjacent to AVMs has also been reported. Cortical mapping can be performed either during an awake craniotomy or with placement of subdural grid electrodes that permit mapping to be performed outside of the operating room (112,113). Awake craniotomies can be performed as a staged procedure, thereby allowing for full benefit of anesthesia and brain protection after language sites have been determined. Awake mapping techniques require complete patient cooperation. Patient education about the language tasks must occur pre-operatively (113). Typically, direct naming of objects presented as slide drawings is used to determine language areas. With the use of diprovan, exposure and resection can be performed under anesthesia with the patient awake only for language mapping. Local anesthesia with a field block is used before draping, and the craniotomy is performed in the usual manner. Once the patient has awakened, the dura is opened. Using corticography, the stimulation current is increased until the after-discharge threshold is reached, with subsequent stimulation staying below this threshold current. By applying stimulation during the presentation of slides to the patient, sites where naming is blocked are identified. Good post-operative language function has been found when resections stay at least 1 cm from the sites where naming is blocked (114). Mapping also can be performed as a first stage, with AVM resection performed under general anesthesia at a later time. Decision Analysis The decision to treat a temporal AVM surgically depends on the characteristics of the lesion, its presentation (previous hemorrhage, venous drainage), and its location relative to eloquent cortical regions. Additionally, the presence of seizures, especially intractable seizures, is relevant to the decision process. Most seizures in the setting of temporal AVMs presenting with seizures are controlled medically. However, some seizures prove refractory, and consideration should then be given to more extensive medial temporal resection of potentially epileptogenic
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tissue. Total resection of the AVM offers seizure control in most cases. However, situations in which electroencephalography or electrocorticography (obtained during surgery) suggest that seizure activity exists away from the AVM itself may require more extensive surgery specifically directed at seizure control (115). Both tissue adjacent to the AVM and medial temporal structures can become seizure foci. Especially in the setting of persistent seizures, medial temporal regions can ‘‘kindle,’’ leading to the so-called ‘‘dual pathology,’’ where both lesion and medial temporal structures must be resected to achieve seizure control. Surgical Approaches General surgical techniques that can maximize functional outcome in this critical area, as desribed by Yamada et al. in their series of 22 resected AVMs from the superior temporal gyrus, include avoiding the removal of brain tissue, preserving functional cortex, preserving the microcirculation, compartmental AVM isolation, and preserving major draining vein patency (116). Temporal lobe AVMs can be subdivided by anatomic location. Medial and lateral temporal AVMs are considered separately, inasmuch as the lateral AVMs behave as convexity AVMs but the pattern of drainage in medial temporal AVMs is more typical of central AVMs. Generally, convexity temporal AVMs have arterial supply from MCA and/or PCA branches. AVMs of the inferior temporal and lateral occipitotemporal gyri often extend to the parahippocampus and drain into the vein of Labbe´ as well as to petrosal veins. They are typically supplied by both MCA and PCA branches. The surgical approach to these AVMs (lateral marginal in Yasargil’s terminology) is at the end of the sylvian fissure. After the anterior feeders are identified, the ICA, posterior communicating artery, choroidal and PCA are identified, and the AVM feeders are removed laterally toward the incisura, removing branches from the P2 segment. Polar AVMs can be removed by a pterional craniotomy. Branches of the M1 (temporopolar and anterior temporal) are the primary feeders. Anterior choroidal branches may also feed these lesions, and more anterolateral inferior regions may receive P2 segment branches. Venous drainage is typically to Labbe´ or to the sphenoparietal sinus or basal veins. A more limited surgical resection may be sufficient if seizure control is not a primary goal of the operation. AVMs on the lateral surface of the temporal lobe may also be encountered, either on the superior temporal gyri, extending into the sylvian fissure, or on the middle temporal gyrus, extending into the superior temporal sulcus (117). Arterial supply may be from the temporal horn off of anterior choroidal artery branches, as well as from P2 segment branches. A pterional approach to these lesions permits identification of the feeding vessels (Fig. 4A–G). Amygdalohippocampal AVMs are classified as central AVMs with feeders generally from the anterior choroidal artery and from P2-P3 segments. Venous drainage is deep to the amygdala vein, inferior ventricular vein, longitudinal hippocampal vein, and basal vein. Approaches to amygdalar AVMs and AVMs in the anterior two-thirds of the hippocampus begin with a pterional craniotomy and identification of the Ml, ICA, anterior choroidal artery, and posterior communicating artery. Entering the inferior horn allows access to additional feeders. Access to the posterior third of the hippocampus may require a transcortical approach through the inferior occipitotemporal gyrus to reach the more posterior choroidal feeders and P2 branches (Fig. 5A–G). Outcomes In the series of Yamada et al. of 22 superior temporal gyrus AVMs treated surgically, all but one were completely eliminated, and 19 patients had excellent neurological and occupational recovery (116). Zimmerman et al. evaluated 8 patients with pure sylvian fissure AVMs with pre- and post-operative cognitive testing and found none with significant cognitive deficits; this finding demonstrates the safety of appropriately performed surgical approaches to this region (117). PARIETAL LOBE AVMs Anatomy The lateral surface of the parietal lobe is bounded anteriorly by the central sulcus, posteriorly by a line joining the preoccipital notch to the parietal occipital sulcus, superiorly by the edge of the hemisphere, and inferiorly by a line extending from the posterior aspect of the sylvian fissure. Lateral parietal AVMs usually derive their arterial supply from distal ACA and MCA
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branches. Occasionally, these malformations receive perforators from ventricular branches of the PCA (P2 and P3 segments) and from the lateral posterior choroidal arteries. Parietal lobe AVMs derive their vascular supply from all three major vessels (MCA, ACA, PCA) in 43% of cases (94). The venous drainage for lateral surface parietal AVMs is divided into an ascending group, which empties into the superior sagittal sinus, and a descending group, which drains into the veins along the sylvian fissure. Venous drainage may also include the septal veins and the vein of Labbe´. Yasargil describes parietal AVMs occurring both laterally in a paramedian position near the convexity and in a medial position near the corpus callosum (94). These AVMs frequently are conically shaped and extend to the lateral ventricular surface. Clinical Presentation In 49 parietal AVMs, 47% presented with epilepsy alone, 29% presented with hemorrhage alone, 22% presented with both hemorrhage and epilepsy, and 69% presented with neurological deficits (94). Of 34 patients with neurological deficits, 24 were associated with hemorrhage and 10 (29%) were not (94). Headaches were reported by 22% of these patients (94). Radiographic and Functional Evaluation For a parietal AVM supplied by both the ACA and the MCA, preoperative embolization of the ACA contribution allows the surgeon to address the more accessible superficial MCA feeders. Preoperative fMRI or PET scanning can help to delineate the AVM location relative to the primary motor cortex and speech centers for dominant hemisphere lesions. Decision Analysis Large parietal lobe AVMs usually are associated with a higher risk of surgical morbidity, due to the proximity to eloquent brain and to tortuous and elongated feeding vessels from the MCA, which have fragile walls that are difficult to coagulate. Functional imaging is helpful in the treatment decision and in evaluating the likelihood of postoperative deficits. Depending on the location of a parietal AVM and its relation to the optic radiation, a contralateral inferior quadrant anopsia may be expected. Postoperative neurological abnormalities are frequent with parietal lesions, even in uncomplicated cases, and are thought to be secondary to manipulation of normal brain. Hemiparesis and dysphasia can be encountered. Surgical Approaches Parietal AVMs that involve the central, postcentral, and intraparietal sulci are treated much like those of the sylvian fissure. The sulci are opened, the arterial supply is dissected, and feeders are eliminated, while transit arteries are spared. Paramedian parietal (post-central marginal) AVMs are technically challenging lesions to resect for several reasons. These lesions are frequently supplied by branches from the ACA and the MCA that extend to areas in the deep sulci, including the parieto-occipital sulcus, the cingulate sulcus, and the postcentral sulcus. In addition, draining veins for these lesions frequently impede access to the interhemisphere fissure, which may preclude early dissection of feeders from A4 and P5 branches. Occasionally, dissection necessitates temporary clipping or even sacrifice of these large draining veins. Finally, these AVMs frequently have deep feeders from the PCA and ACA, necessitating dissection down to the ventricular area for vascular control. Approaches to parietal lobe AVMs are similar to those for posterior frontal lobe AVMs (Fig. 6A–F). For large lateral parietal AVMs, exposure should encompass the posterior aspect of the sylvian fissure, and for AVMs extending to the parasagittal region, exposure should extend past midline, allowing the dura to be reflected over the sagittal sinus. As for posterior frontal AVMs, we routinely perform motor and somatosensory mapping for anterior parietal lesions (Fig. 7A–F). Preoperative embolization may enable the elimination of large feeding vessels from one or more arterial distributions. When possible, ACA feeders should be embolized preoperatively, thereby allowing MCA feeders to be approached perpendicularly with the patient in a lateral position. Circumferential dissection proceeds from the surface towards the falx where the ACA feeders can be addressed. It is important to positively identify the arterial feeders and minimize brain retraction. In addition, medial draining veins should be preserved at all costs. As with all lesions near eloquent cortex, it is essential that contributing
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arteries to the malformation be extensively dissected and sacrificed only as they enter the AVM nidus. In this functionally important region of the brain, retracting the AVM away from brain parenchyma can also help minimize retraction injury. Alternatively, for large parietal AVMs with significant feeders from multiple distributions after embolization, surgery can be staged, with the first procedure commencing with the head in the lateral position to employ a subtemporal approach designed to address posterior feeders. A second stage may follow in the supine position to eliminate pericallosal feeders. Outcome In one series, 80% of those with no preoperative neurological deficits had a favorable outcome, whereas only 62% of those with preoperative neurological deficits had a favorable outcome (93). Depending on the location of a parietal AVM and its relation to the optic radiation, a contralateral inferior quadrant anopsia may be expected. Resection of parietal sensory cortex AVMs can produce proprioceptive loss and gait difficulties, although with time most patients overcome these deficits (118). OCCIPITAL LOBE AVMs Anatomy Due to their complex vascular architecture and the intimate relationship of the optic radiation and visual cortex, occipital lobe AVMs are technically challenging. The lateral surface of the occipital lobe is poorly delineated from the parietal lobe. However, the primary visual cortex is located at the occipital pole and the mesial aspect of the occipital lobe along the upper and lower banks of the calcarine fissure, which is one fissure above the lingual gyrus that rests on the tentorium. The further a lesion lies distant from the occipital pole and calcarine sulcus, the less functionally significant the occipital cortex. Occipital lobe AVMs can be located on the medial, lateral, basal, or polar aspects of the occipital lobe. The arterial supply is derived from the distal PCA and MCA branches. If the malformation involves the para-splenial region, there may also be input from the terminal pericallosal branches of the ACA. Up to 20% of occipital AVMs may be fed by the MCA, PCA, and ACA and dural feeders (94). Occipital lobe AVMs often recruit feeders from the external carotid system through the meningeal system, or via direct calvarial perforators. Occipital lobe AVMs can extend into the ventricular system and receive feeders from the posterior choroidal artery. Some inferiorly located mixed pial-dural occipital lesions derive input from tentorial branches of the ICA. Venous drainage for occipital AVMs can be quite complex. In general, lateral occipital lobe lesions drain inferiorly toward the transverse sinus and superiorly into the sagittal sinus. Mesial lesions drain into the galenic system and into the superior sagittal sinus. Venous drainage frequently enters the sagittal sinus relatively far anteriorly, thus facilitating the interhemispheric approach for mesial occipital AVMs. Polar lesions drain into the transverse sinus. Occipital lobe AVMs are associated with a high incidence of venous anomalies including sinus stenosis or occlusion, abnormalities in the vein of Galen, and superficial venous abnormalities (119,120). Clinical Presentation In 30 occipital AVMs treated surgically by Yasargil, 50% presented with hemorrhage alone, 27% with epilepsy alone, 7% with both epilepsy and hemorrhage, and 40% with headaches (94). Of 14 patients who had neurological deficits (47%), 12 patients (86%) had hemorrhage and 2 did not (94). Formal ophthalmologic testing demonstrated homonymous visual field deficits in 35% to 56% of patients treated for occipital AVMs (121,122). Patients with occipital lobe AVMs are particularly prone to present with headaches (123). Troost and Newton noted recurrent headaches in 46% of 26 patients with occipital AVMs; half of these headaches were associated with visual phenomena (124). Radiographic and Functional Evaluation Particular attention should be paid to venous abnormalities commonly associated with occipital AVMs. Preoperative embolization of medial feeders from ACA and PCA and of commonly
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found external carotid can significantly facilitate operative resection. In a recent series of 19 AVMs treated with either radiosurgery or microsurgery, 79% were devascularized with embolization (122). Identification of functional occipital cortex on fMRI by visual field stimulation using light emitting diode goggles is described in the setting of an occipital AVM and may augment anatomic images in the decision process (45). Decision Analysis Excision of occipital lobe AVMs remains quite challenging due to the functional significance of the surrounding brain tissue. The visual cortex and the optic radiations add significant risk to any occipital lobe dissection. Radiosurgery can be performed with low morbidity rates (6%) but only a 65% obliteration rate 26 months after the surgery (25). Surgical Management For exposures of paramedian AVMs, a large flap that crosses the midline allows reflection of the dura across the falx, minimizing brain retraction (Fig. 8A–F). A long parasagittal craniotomy enables the surgeon to work around veins to the sinus. Ideally, preoperative embolization can obliterate medial feeding vessels from the ACA and PCAs. Initially, the distal MCA feeders are identified, dissected, and divided as they enter the nidus. The surgeon can then enter the interhemispheric fissure and identify and occlude the PCA feeders to the AVM. The PCA should be dissected from a proximal location beneath the splenium of the corpus callosum. Due to the overhanging medial posterior temporal lobe, it is usually not possible to visualize the PCA until after the lateral ventricular body within the wing of the ambient cistern is reached. We recommend beginning the dissection by identifying the PCA proximally, then lifting up the occipital lobe gently as the vessel is followed from proximal to distal in its course towards the occipital pole. In this fashion, one can usually identify the abnormal, enlarged feeding arteries along the length of the distal PCA. During identification of these feeding branches, each artery should be dissected into the sulci on the medial aspect of the occipital lobe and then divided at its entry into the nidus of the AVM. Veins traversing the interhemispheric fissure can obscure access to this region, but often these can be mobilized to the side by dissecting off the arachnoid. Circumferential dissection of these medial occipital AVMs not infrequently causes visual field defects, usually due to occipital lobe retraction and rarely due to sacrifice of distal PCA branches. Occipital lobe retraction injury can be minimized by retracting the dura immediately over the sagittal sinus, which should improve the angle of exposure. Spinal fluid drainage and the prone position help to reduce retraction. The AVM itself should be compressed during all phases of dissection and should be delivered into the interhemispheric fissure as it is dissected. This technique should increase the exposure for further dissection without additional brain retraction. In certain cases, coagulation of the malformation may shrink it to sufficient size to facilitate delivery of the lesion into the interhemispheric fissure, and approaching the lesion parallel to the sagittal sinus should also reduce the amount of retraction necessary. Despite these efforts, visual field defects are relatively common with resection of medial occipital lobe lesions. For lateral occipital lobe lesions, we prefer a lateral position. This approach facilitates venous drainage and minimize the effects of gravity and retraction on the occipital lobe. General exposure requires a large craniotomy flap and extensive dural opening. During turning of scalp, bone, and dural flaps, care should be taken to adequately secure any ECA feeders. Care with dural and bone removal is particularly important in occipital AVMs given the higher incidence of meningeal feeders and anomalous superficial venous drainage. Preoperative embolization may reduce these feeders. Isolating the meningeal artery within the dura before reflecting the dura helps to prevent sheering of this vessel from the AVM nidus. Occipital pole AVM resections involve identifying arterial feeders and draining veins, which usually run to the transverse sinus or the tentorial vein. Occasionally, venous drainage is to the vein of Galen or the internal occipital vein. Lobectomy should be reserved only for giant lesions or for patients who already have a dense hemianopsia. Median and paramedian AVMs deep within the parietal occipital sulcus or the calcarine sulcus are approached similar
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to polar lesions. Venous drainage is usually to the sagittal sinus or to the internal occipital vein, culminating in the vein of Galen. Outcome Homonymous hemianopsia is reported in 36 to 69% of patients in the immediate postoperative period but is permanent in only 0 to 25% of cases (119,122,125). Of 4 patients with preoperative visual field deficits, 2 resolved or improved, one was stable, and one was worse after surgery (122). In Yasargil’s series of 30 occipital AVMs, 93% had a favorable surgical outcome, 46% had normal visual fields, 26% were unchanged, and 23% had additional visual field impairment (94). Drake reported 100% resolution of headaches after resecting 7 occipital AVMs, and others reported similar results (121,126). Radiosurgery performed for 34 small AVMs in postgeniculate optic pathways caused additional visual field deficits in only 6%, although this rate was attained in the setting of a 65% angiographic obliteration rate after 26 months of follow-up and a 2.4% hemorrhage rate until obliteration (25).
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Perisylvian Arteriovenous Malformations Harold J. Pikus and Roberto C. Heros Department of Neurological Surgery, University of Miami, Miami, Florida, U.S.A.
INTRODUCTION This chapter covers some considerations specific to the management of arteriovenous malformations (AVMs) in the region of the sylvian fissure, including lesions within the fissure, the adjacent opercular temporal, frontal, and parietal regions, the insula, and the mesial (medial) temporal lobe. AVMs of the sylvian fissure proper and of the surrounding opercular regions will be referred to as sylvian AVMs, while AVMs of the mesial temporal lobe will be designated as such. General information and principles regarding AVMs will not be presented here unless our philosophy or techniques are sufficiently different from others described elsewhere in this volume. The sylvian fissure is formed at the infolding of the frontal, temporal, and parietal operculae. Deep to the fissure lie the insular gyri, beneath which are the basal ganglia. The middle cerebral artery (MCA) enters the sylvian fissure as it curves around the lumen insulae. The M2 branches course over the insula and exit the fissure laterally, generally as the M3 vessels, which then ramify over the adjacent regions of the cerebral hemisphere. These regions include primary motor and sensory areas, language and auditory areas, and subcortical white matter tracts. The complex arterial and venous structures passing through the fissure supply these important areas. Therefore, treatment of lesions in and around the sylvian fissure can be treacherous not only because of the risk of direct injury to adjacent tissue, but also because of the risk of inadvertent injury to en passage vessels. Before treatment, the benefit of any particular therapy or combination of therapies must be weighed against the natural history of the lesion and compared with the risks and benefits of alternative forms of therapies. Perisylvian AVMs are considered separately because of the problems arising as a result of their intricate relationships with the MCA and its branches within and adjacent to the sylvian fissure. Additionally, AVMs in and around the sylvian fissure may be intimately associated with critical regions of cortex. Maintaining the integrity of these structures, vessels, and parenchyma is critical, especially on the dominant side. Drake (1) and Malis (2) used the term ‘‘sylvian fissure AVMs’’ to generally describe these lesions. Heros (3) described surgery of the mesial temporal AVMs. Sugita et al. (4) first provided a detailed description and categorization of the perisylvian AVMs. They described four types of sylvian AVMs: true (those contained by the fissure), medial (those of the medial aspect of the fissure or frontal operculum), lateral (those of the lateral aspect of the sylvan fissure, temporal operculum, or mescal temporal lobe), or deep (those of the insula and deeper structures). The authors grouped these lesions together since they all derive blood supply from the MCA and, in the authors’ opinion, require wide splitting of the sylvian fissure. However, even in this series of 16 patients, these authors had to resort to a mixed classification scheme as some of the lesions did not fit into a single category. We suggest a slightly different approach to categorization of these lesions. The lesions may be thought of as falling into four groups by surgical approach and blood supply. Anterior lesions comprise those true sylvian AVMs of the anterior (horizontal) portion of the fissure, which are intimately related to the main trunk of the MCA and the origin of the main divisions and receive their blood supply from short side branches of these vessels, as well as those of the adjacent operculae and anterior aspect of the mesial temporal lobe. The latter are supplied by anterior temporal branches of the MCA and, when the anteromedial aspect of the temporal lobe is involved, by anterior choroidal branches. These lesions are approached through an extended pterional (combined pterional/anterior temporal) (5) craniotomy and require wide splitting of the fissure. Posterior sylvian lesions comprise those AVMs of the posterior portion of the sylvian fissure and adjacent operculae. They are supplied mostly by the branches of the
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MCA, frequently ‘‘en passage.’’ They are approached through a more posterior craniotomy, and only the lateral (vertical) portion of the fissure needs to be split. Insular AVMs frequently gain supply from the lateral lenticulostriate arteries and from deep branches of the divisions of the MCA as they course through the vertical portion of the fissure; these lesions can extend medially into the basal ganglia. They require wide splitting of the sylvian fissure through a combined pterional/anterior temporal craniotomy. The blood supply from the lenticulostriate branches poses special therapeutic concerns, surgical and endovascular. Finally, posterior mesial temporal AVMs are approached through a low temporal craniotomy that allows both a subtemporal and a transtemporal route. These AVMs frequently get their blood supply from the posterior cerebral artery (PCA) branches and additionally, when they extend more laterally and superiorly, from MCA branches. PRESENTATION Patients with perisylvian AVMs exhibit a spectrum of presenting symptoms. Hemorrhage, seizures, headache, and neurologic deficit are the four most common presenting manifestations of AVMs, in descending order of incidence (6–8). In the senior author’s published series (6), five of six patients with pure sylvian AVMs presented with hemorrhage, while none presented with seizure. Patients with temporal AVMs presented with hemorrhage in over half of cases. Hemorrhage from a sylvian AVM most frequently involves the parenchyma, though subarachnoid and intraventricular hemorrhage may occur, whereas mesial temporal AVMs frequently present with subarachnoid hemorrhage (3,9). Hemorrhage into adjacent brain often meets with devastating neurologic consequences, including pronounced motor and sensory deficits, aphasia, or both. Prognosis for parenchymal perisylvian hemorrhage depends on the precise location and extent of the tissue damaged, as well as the effects of secondary phenomena. Hemorrhage into the dominant angular gyrus, for instance, might leave the patient with a severe aphasia, whereas hemorrhage into the temporal tip might leave no gross residual deficit. Frontal and temporal AVMs appear more likely to cause seizures than AVMs in other cortical areas, with parietal AVMs close behind (6,8,10). Seizures arising from AVMs in the perisylvian region are of several varieties. Patients with temporal AVMs may present with any of the patterns characteristic of mesial temporal seizures, even despite location outside the mesial temporal lobe. Patients with other perisylvian AVMs may present with a spectrum of epileptiform symptoms including focal, secondarily generalized, or primarily generalized seizures. Temporal lobe AVMs are known to generate remote seizure foci in the amygdala and hippocampus, which may confound diagnosis and therapy (11). Headache is a common symptom of patients with AVMs, although it less frequently leads to the diagnosis. Perisylvian AVMs do not seem to have a specific headache pattern. The mechanism of headache associated with an AVM in the absence of intracranial hemorrhage or hydrocephalus is unclear but may be related to abnormal dilation of the more proximal pain-sensitive cerebral vasculature or of meningeal feeders to the AVM. Typical migranous headaches occur not infrequently in patients with AVMs, but most of these patients have AVMs of the occipital lobes (12). Perfusion ‘‘steal’’ due to high flow arteriovenous shunting may also give rise to other presenting symptoms in patients with perisylvian AVMs. Symptoms may fluctuate with changes in various factors affecting the AVM hemodynamics. Ischemia develops when the competence of the collateral circulation and autoregulation is exceeded by the hemodynamic sink due to the arteriovenous shunting within the AVM. This circumstance may cause malfunctioning of the involved brain tissue with neurologic deficit characteristic of that tissue’s function. Frequently, the deficits associated with steal phenomena are slowly progressive and often reversible with treatment of the AVM (13,14). However, the presence of steal phenomenon preoperatively may be a risk for the development of hemorrhagic complications during or after surgery (15). High output cardiac failure is rarely associated with perisylvian AVMs. DIAGNOSTIC STUDIES The diagnostic algorithm for perisylvian AVMs is similar to that for other supratentorial AVMs. For the patient presenting with new neurologic deficit, diminished level of consciousness,
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or severe headache, computed tomography (CT) of the brain is indicated to determine the presence and location of hemorrhage, location of mass, and presence of hydrocephalus. For the patient not in extremis from a clot necessitating emergent surgery, further diagnostic evaluation should be performed. The AVM is usually evaluated with angiography. Conventional catheter angiography provides the best characterization of the lesion’s flow-architecture, that is to say, the arteriovenous anatomy with respect to the volume and velocity of flow. With perisylvian AVMs, it is particularly important to try to sort out which vessels are ‘‘end feeders’’ to the AVM and which are en passage. The angiographer can perform superselective injections to clarify the angioarchitecture of the lesion, which may be critical for safe treatment. Magnetic resonance imaging (MRI) is the best tool for confirmation of the exact spatial location of the lesion. It can also be helpful in clarifying the relationships between the AVM nidus and feeding and draining vessels. MRI is more adept at defining the AVM nidus than are CT or conventional angiography (16). MRI facilitates demonstration of the AVM’s relationship with adjacent gyri and other structures, including deep white and gray matter. CT angiography (CTA) provides three-dimensional views of the lesion and its relation to bony structures that may be helpful at the time of surgery. These images demonstrate the feeding and draining vessels simultaneously, along with the core of the AVM. In our opinion, magnetic resonance angiography (MRA) offers no useful information beyond that obtained by selective angiography, MRI, and occasionally CTA. Another critical aspect of treatment of perisylvian AVMs is understanding not only the spatial location of the lesion but also the functional implications of such location. The margin for error with some of these lesions, depending on location, is small. Therefore, identifying the exact location of major cortical functions such as motor, sensory, and speech areas will facilitate safe treatment of an adjacent lesion. Such a lesion may distort the normal anatomy, thereby misleading the unwary neurosurgeon. Techniques such as functional MRI (FMRI) (17–21), positron emission tomography (PET) (21–23), and magnetic source imaging (MSI) (24,25) allow functional information to be gleaned from the patient and superimposed on the anatomic data. FMRI uses the local increase of oxyhemoglobin concentration in the patient that occurs as a result of the increase in flow rate and blood volume in cortex undergoing stimulation or performing a task. MSI, a form of magnetoencephalography, uses superconducting quantum interference devices (SQUIDs) to detect minute electromagnetic field changes indicative of neuronal activation while a stimulus is applied or the person performs a task. PET uses radiolabeled metabolically active substances to identify metabolically active areas. These data can be superimposed on an anatomic study to yield a three-dimensional model localizing critical functions within the patient’s brain. The surgeon can then develop a better understanding of the juxtaposition of the AVM and these critical tissues. This information may be invaluable in operative, endovascular, and radiosurgical planning. Before the availability of these diagnostic modalities, localization of functional areas relied on interpretation of the anatomy and the use of intraoperative cortical mapping. The latter is still an effective method of localizing or confirming the location of eloquent cortex during the resection of an AVM (11,19,26,27). However, intraoperative cortical mapping requires a different anesthetic technique, and it is of little value once the surgeon begins to resect the AVM because the AVM must be removed completely, as opposed to a tumor where part of the tumor can be left if it impinges on eloquent brain. An additional approach that may be helpful in the identification of function of the brain associated with an AVM is superselective thiopental injection. This technique may be particularly useful for the interventional neuroradiologist about to attempt embolization of an AVM (28). The test can also provide information about the terminal functional distribution of en passage vessels. The traditional intracarotid amobarbital test as described by Wada and Rasmussen (29) may be useful in determining the location of language (26). However, it is unreliable in the presence of an AVM with a significant flow sink (27). Additionally, a large AVM in or adjacent to the speech areas may induce transfer of speech to the non-dominant side. In light of these two observations, better information may be obtained by amobarbital injection of the contralateral carotid. In this situation, a negative result localizes speech to the side of the AVM; a positive result confirms at least partial transfer of speech.
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Preoperative evaluation of patients with intractable seizures should include a comprehensive seizure evaluation. As noted previously, temporal AVMs are capable of generating remote seizure foci in the amygdala and hippocampus. Initial screening surface electroencephalogram (EEG) should be supplemented with video EEG and more aggressive diagnostic maneuvers, if appropriate, to secure the location of the seizure focus. Ictal and inter-ictal metabolic localization techniques, such as single photon emission computed tomography (SPECT), may also facilitate identification of the focus. In these patients, it may be prudent to plan intervention to deal with both the AVM and a seizure generator, if it is remote from the AVM. MANAGEMENT In principle, all therapeutic modalities should be considered in determining the appropriate treatment for each AVM. Such a multidisciplinary approach, with the team led by a neurosurgeon, is likely to yield better treatment outcomes (30–32). Surgery Surgical extirpation of a perisylvian AVM requires planning and preparation on the surgeon’s part. A game plan for the surgery should be developed that includes anesthetic considerations, patient positioning, and possible use of intraoperative diagnostic techniques, such as cortical mapping, ultrasound/Doppler, and digital subtraction angiography. Although not widely available at this time, intraoperative MRI may improve the safety of AVM resection in functional areas when its use becomes more practical and surgeon-friendly. There is considerable literature on complication avoidance and management in the treatment of AVMs (33,34). Several key areas of concern include the surgeon’s judgment regarding patient selection, risk of parenchymal injury, intraoperative hemorrhage, retained AVM, insecure hemostasis, so-called normal perfusion pressure breakthrough phenomenon, retrograde venous occlusion, retrograde arterial thrombosis, postoperative epilepsy, complications of angiography and embolization, and recurrence of the AVM. Aside from considerations specific to operation in and around the sylvian fissure, the more general concepts will not be discussed here, as they are presented thoroughly elsewhere in this volume. Anterior Sylvian and Mesial Temporal AVMs These lesions should be approached through the sylvian fissure to control their blood supply. A combined pterional/anterior temporal transylvian approach is preferred (5) (Fig. 1). The skin flap is taken down superficial to the fascia of the temporalis muscle, and the superficial fascia of the muscle is cut above the zygoma and taken down with the skin flap by interfascial dissection to expose the zygoma and frontozygomatic process, preserving the frontalis nerve. The temporalis muscle is cut superiorly, leaving a cuff for re-attachment at closure, and anteroinferiorly for about 1.5 cm just below the zygoma. This allows posterior retraction of the muscle over the ear, leaving the anterior aspect of the zygoma exposed. The classical pterional bone flap is augmented anteroinferiorly to expose the anterior temporal pole. The pterion and lesser wing of the sphenoid are removed, and the anterior temporal bone is rongeured down to the floor of the anterior temporal fossa. The dura is then opened on a flap based inferiorly, which is tented up to allow a very flat approach along the base. The sylvian fissure and medial cisterns are opened widely. Great care is taken throughout the procedure to avoid excessive retraction on eloquent structures. Frequently, it is possible to use little or no fixed retraction, diminishing the risk of retraction-related injuries. A number of arterialized veins draining the tip of the temporal lobe may be present. It is important to preserve these vessels at this early stage of the operation; non-arterialized bridging veins present at the temporal tip may be taken if necessary. In the situation where multiple venous outflow channels are present, arterialized venous drainage crossing the sylvian fissure may be divided to allow mobilization of the lesion. The MCA is now followed from proximal to distal, with meticulous attention paid to the identification of the proximal MCA branches within the sylvian fissure. With some lesions, it is advantageous to open the lateral aspect of the sylvian fissure and work from distal to proximal toward the lesion. The AVM should be separated from one side of the fissure without
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Figure 1 Left combined pterional/anterior temporal craniotomy. (A) Bony exposure before craniotomy. Note that the temporalis muscle (on the left side) is cut superiorly, leaving a cuff of muscle for later re-attachment, and then under the frontozygomatic process and about half of the zygoma so that it can be retracted backward over the ear, leaving the anterior–inferior aspect of the temporal bone covering the tip of the temporal lobe down to the middle cranial fossa exposed for the craniotomy. Because this case involved an older patient with adherent dura, we used three burr holes, which are marked by the three forceps. The first burr hole on the right anterior aspect of the figure is at the keyhole. The posterior burr hole (inferior aspect of the figure) is on the superior temporal line, and the third burr hole is in the inferior aspect of the temporal bone. Thorough drilling of the pterion and the greater and lesser wing of the sphenoid, sometimes entering the lateral wall of the orbit inferiorly to unlock the superior orbital fissure, provides excellent anterior-inferior temporal exposure. (B) The dura has been opened in a flap based inferiorally, which is tented up to allow a flat approach. Retractors, which usually are not necessary, have been inserted to demonstrate the exposure of the anterior aspect of the middle cranial fossa. The stretched arachnoid between the retractors will be opened to begin the complete opening of the sylvian fissure. Source: From Ref. 5.
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taking any of the feeding vessels until the angioarchitecture is well defined. One of the potential pitfalls of sylvian AVM surgery is the sacrifice of a vessel believed by the surgeon to be terminating within the AVM, but which is actually en passage to its true terminus in the perisylvian regions of the brain. A single such mistake can turn an otherwise flawless resection into a disaster postoperatively, with potentially profound transient or permanent neurologic injury. The key to preservation of these important en passage vessels is meticulous dissection and definition of the angioarchitecture. No vessel should be permanently ligated until it is perfectly clear that it belongs entirely to the AVM. At that point it should be definitively ligated. If the surgeon is unsure of the vessel’s course, a temporary clip may be placed on the major trunk while the small branches that are clearly feeding the AVM are taken. In this manner, the major trunk may be preserved in case it is actually passing by the malformation. Another difficulty of sylvian AVM surgery is the frequent arterial supply from lateral lenticulostriate vessels, more commonly seen with insular AVMs. These vessels are often thin walled, tear easily, and are difficult to coagulate; but the surgeon must carefully define, coagulate, and divide them. The packing of persistent bleeding from one of these vessels that has not been adequately cauterized should be avoided, as it may lead to a deep hemorrhage. When these lesions involve the anterior aspect of the medial temporal lobe, they invariably acquire blood supply from the anterior choroidal artery and frequently from anterior temporal branches of the PCA. These feeders can be controlled sequentially by gradually separating the mesial temporal lobe, with the AVM, from the MCA, from the anterior choroidal artery, and from the posterior communicating artery and PCA (Fig. 2). Posterior Sylvian AVMs These lesions are best approached with a more posterior exposure (13,33,35). The head is placed in the straight lateral position, and the bone flap is more posterior than for the routine pterional craniotomy. The scalp flap is fashioned using the standard temporal horseshoe type of incision centered above the ear. In these cases, it is not necessary to remove the pterion.
Figure 2 Arteriovenous malformation (AVM) of the anteromedial aspect of the right temporal lobe. Through a combined pterional/anterior temporal craniotomy the sylvian fissure has been opened. Retractors have been placed to gently hold the fissure open. The middle cerebral artery (MCA) has been exposed to its bifurcation. Note the AVM under the retractor on the right side on the tip of the temporal lobe and the very large anterior temporal feeder from the MCA. The next artery, going proximal along the internal carotid artery, is the anterior choroidal. After the anterior temporal branch is divided, the branches from the anterior choroidal artery to the AVM can be controlled. This will bring into exposure the small branches from the posterior communicating artery first and then from the posterior cerebral artery (PCA) to the AVM, which can also be controlled through this exposure.
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Likewise, it is not necessary to open the proximal sylvian fissure, although in some cases this may be helpful. Dissection may start in the more distal fissure, working toward the AVM. In cases where the fissure is obscured by the AVM, an arterialized vein usually can be found on the surface that can be followed to the lesion. This requires careful opening of the arachnoid, while respecting the pial boundaries. Damage to the adjacent pial banks may be devastating, particularly in the dominant hemisphere. Temporary occlusion of suspected AVM feeding vessels helps to clarify the architecture of the lesion. If there is no change in the turgor or the color of the lesion, a search is made for deeper branches. After the major feeders are occluded, the AVM coils may be coagulated to shrink them, pulling them away from the critical adjacent brain. Posterior perisylvian AVMs may drain through the vein of Labbe´. The surface anatomy must be thoroughly understood to avert damage to this vein. Dissection within the sylvian fissure puts the deep sylvian vein at risk. Numerous arterialized vessels are frequently found exiting the AVM to this vein. These vessels run parallel to numerous small arterial feeders, making the dissection treacherous. The key to successful resection of these AVMs is the preservation of vessels ‘‘en passage,’’ taking only their side branches to the lesion and true ‘‘end feeders’’ to the AVM (Fig. 3) (36). Insular AVMs These lesions require wide opening of the sylvian fissure which we accomplish through the combined pterional anterior temporal approach (Fig. 4) (5). The problem with these lesions is the control of the lateral lenticulostriate feeders. It is most desirable, but difficult, to obliterate this deep blood supply with preoperative embolization. At surgery, these feeders look different from normal branches to the basal ganglia that must be preserved. When in doubt, we place temporary clips and follow the vessel to the AVM, taking it only when it is positively identified as a feeder. Control of the more distal branches that penetrate the AVM distally from the divisions of the MCA as they turn around the limen insula and distally within the vertical portion of the fissure is more straightforward. Again, the key is the preservation of the branches ‘‘en passage.’’ Posterior Mesial Temporal AVMs A low temporal craniotomy is used for these lesions. The craniotomy is taken down to the floor of the middle fossa, over the petrous pyramid to allow the surgeon to work either subtemporally or through the inferior temporal gyrus (3). Either approach may cause a superior quadrantanopsia. The transtemporal approach has the advantage of decreasing traction on both the vein of Labbe´ and the temporal lobe, which may be problematic with the subtemporal approach. The trajectory of the dissection with the transtemporal route is toward the temporal horn, which serves as a good landmark. Feeding vessels from the anterior choroidal artery can usually be controlled through the choroidal fissure on the medial aspect of the temporal horn. Posterior cerebral feeders are controlled either subtemporally or transtemporally as they enter the AVM. As with the other sylvian AVMs, understanding the angioarchitecture of the mesial temporal AVM is critical before sacrifice of any vessels. Medial branches of the anterior choroidal artery to the brainstem and basal ganglia may appear to be involved in the AVM but must be preserved. Loops of the AVM that are imbedded in the inferolateral portions of the basal ganglia and thalamus can usually be excised safely. In some cases, the choroid plexus of the temporal horn and trigone may be substantially involved and may be removed at the attachment to the AVM. Finally, once the feeding vessels have been interrupted and the turgor and color of the AVM and its draining veins have changed, the venous drainage, which is usually medially toward the basal vein of Rosenthal, may be interrupted and the lesion removed (Fig. 5). Intraoperative Adjuncts Identification of small deep lesions may be facilitated by use of any of a number of localization techniques. There is, however, no substitute for the understanding of the three-dimensional anatomy of the AVM afforded by thorough analysis of the preoperative diagnostic studies. Stereotactic craniotomy can now be facilitated through the use of any of the commercially available cranial frameless stereotaxy packages (37,38). The intraoperative ultrasound may facilitate identification of an elusive, small, deep AVM when frameless stereotaxy was not used or encounters difficulty. Intraoperative angiography is desirable in most cases of AVM
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Figure 3 Posterior sylvian arteriovenous malformation located within the dominant sylvian fissure. Preoperative (A) lateral and (B) anteroposterior (AP) views. Postoperative (C) lateral and (D) AP views. The lesion was removed through a posterior temporal craniotomy with opening of the sylvian fissure and preservation of vessels en passage as demonstrated in (C).
resection (39–41). Only if the lesion is small and the surgery is uncomplicated should angiography be deferred to the postoperative period. Embolization The development of newer embolic materials and endovascular techniques has resulted in somewhat safer and more effective AVM embolization (42–44). Typically, embolization is useful in diminishing the flow to an AVM in preparation for surgery. The procedure minimizes blood loss, reduces the risk of hyperemic complications, and facilitates microsurgical extirpation (31). However, these sylvian AVMs are frequently small, and problems with
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hyperperfusion are unlikely; we find embolization more useful in the elimination of less accessible vascular pedicles such as the lateral lenticulostriate feeders to insular AVMs and the posterior cerebral feeders (which would require subtemporal exposure with risks to the arterialized draining veins and the vein of Labbe´) to posterior mesial temporal AVMs. Leakage of the embolic agent into unintended arteries may have grave consequences (34,45). Likewise, rupture of the feeding artery by puncture with the guidewire may produce subarachnoid or parenchymal hemorrhage with equally grave consequences (44,46). Premature closure of venous drainage to the entire AVM or even to a ‘‘compartment’’ within the AVM can also lead to disastrous hemorrhage (46). In the patient not suitable for microsurgical intervention, embolization may reduce the volume of an AVM enough to allow radiosurgical treatment (47–49). However, the efficacy of this paradigm (making the volume of the AVM permanently smaller and therefore allowing radiosurgery of a lesion that was previously too large for this treatment) has been questioned (50). Staged embolization may be useful in the preparation for surgery of large AVMs (33,51). The technique may carry with it a not inconsequential risk of hemorrhage (46).
Figure 4 (Continued on next page)
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Figure 4 (Continued from previous page) Large sylvian/medial temporal right-sided arteriovenous malformation (AVM). (A) Multiframe magnetic resonance imaging. (B) Lateral and (C) anteroposterior (AP) views of the AVM. (D) Early lateral arterial phase showing multiple feeders from lenticulostriate arteries to the insular portion of the AVM. (E) AP and (F) lateral postoperative views showing complete removal of the AVM. Resection was accomplished in a long one-stage operation through a large combined frontotemporal bone flap. The approach was essentially trans-sylvian with complete opening of the sylvian fissure.
Radiosurgery Radiosurgery of surgically accessible AVMs has a limited role. If an unruptured AVM is within a region of eloquent brain, an argument can be made that radiosurgery would spare the patient the surgical morbidity. However, comparison of the results of radiosurgical and microsurgical series reveals that microsurgery is superior with respect to immediate protection from hemorrhage, AVM obliteration, and neurologic deficits (52–54). Additionally, when the long-term costs of treating a small resectable AVM with surgical excision or with radiosurgery are carefully analyzed, surgical excision emerges as a much more cost-effective therapeutic option (55). Nevertheless, there is a small, but definite morbidity risk associated with microsurgery, which some patients may find undesirable. However, in a multi-institutional review of patients with radiosurgically treated AVMs with a mean radius of 1.1 cm, more than 8% developed late sequelae, most of which were associated with radiation damage to surrounding brain, new cranial neuropathies, and new or worsened seizures (56). Others have found that increasing the AVM treatment volume was associated with an increasing incidence of radiation changes in the surrounding brain in up to 20% of patients (56–58). The factors that have been found to be favorable for radiosurgery (volume, draining veins, age, location) also optimize outcome with microsurgery (57,59–61). The most important application of
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Figure 5 Mid and posterior medial temporal arteriovenous malformation involving the amygdala and inferior aspect of the insula. (A) Lateral view. (B) Postoperative angiogram showing complete removal of the lesion.
radiosurgery is in the treatment of unresectable AVMs. Radiosurgery may be an adjunct to shrink large lesions in the context of a multimodality treatment scheme. Radiosurgery or proton beam therapy may be applied prior to or following other modalities (30,32,42,47,62–67). Intentionally staged radiosurgery has been used before microsurgery to reduce the surgical volume of Spetzler–Martin Grade V AVMs (68). The ideal use of radiosurgery is for small lesions (generally less than 2.5 cm in diameter) that are unresectable because of their location and that can be covered completely in the radiosurgical field (50). There are occasionally patients with resectable AVMs who are unable to tolerate microsurgery. The underlying medical problems must be evaluated carefully. If life expectancy is limited, the risk of AVM-related morbidity and mortality should be weighed against the risk of any proposed treatment. In some instances it is prudent not to treat the patient (69). Other patients with relative contraindications to surgery such as a mechanical heart valve may be better candidates for radiosurgery. Once again, the risk of being off anticoagulants during the procedure and the immediate postoperative period must be weighed against the protracted risk of hemorrhage from an AVM in an anticoagulated patient after radiosurgery but before obliteration.
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RESULTS The results and outcomes of management of perisylvian AVMs, as a specific subset of supratentorial AVMs, are difficult to determine based on the published surgical, radiosurgical, and endovascular series. The numbers of patients are small or the outcome is not classified with respect to location. Likewise, the AVM description is inconsistent from author to author. It is clear that size, location in eloquent brain, and depth of an AVM, as indicated by the presence of deep venous drainage, all contribute independently to risk of surgical treatment of the lesion (6,7,70). High flow, steal, and supply by perforating vessels are also potential surgical risk factors (15,71,72). Sugita et al. (4) reported a series of 16 patients with sylvian AVMs. Thirteen patients were classified as having good or excellent outcomes, and two patients were classified as having fair outcomes. One patient died. Most of these patients were operated on shortly after hemorrhage, thus clouding the true impact of the surgery on the neurologic outcome. Series of mesial temporal AVMs are the most reliable with regard to characterization and consistency from study to study. The senior author has reported a small series of mesial temporal AVMs, describing the approach and radiographic characteristics (3). The results in this small series were good, with all patients returning to their prior occupations within two months of surgery. One patient developed a mild superior quadrantanopsia as a result of surgery. Oka et al. (73) reported on three patients who had undergone operation for mesial temporal AVMs. Two patients recovered well, but one developed a speech disturbance postoperatively. This patient died 22 months postoperatively after rupture of an AVM not demonstrated on the postoperative angiogram. Malik et al. (9) reported on 24 consecutive patients with temporal AVMs. Sixteen of these AVMs were classified as ‘‘convexity,’’ which almost certainly includes many perisylvian AVMs, but the locations of these lesions are not clearly indicated. Six of the lesions were in the mesial temporal lobe. Overall, two patients developed a new hemiparesis and dysphasia, one developed dysphasia and hemianopsia, and three others developed an isolated superior quadrant field deficit. The rate of lasting surgical morbidity, not including isolated field deficits, was 13%. Burchiel et al. (26) reported no new neurologic deficits in seven of eight patients with AVMs in eloquent neocortical areas who were treated surgically. Yamada (74) reported on 22 patients with AVMs of the superior temporal gyrus. In 10 of these, the lesion extended into Broca’s area. Three patients had AVMs involving Wernicke’s area. All 22 involved the lower sensorimotor area. All patients improved postoperatively with respect to the preoperative neurologic status, except one who developed a hemianesthesia syndrome after coagulation of a diffuse AVM involving the thalamus. This patient did, however, return to normal activity. Two patients developed transient worsening of Broca’s aphasia postoperatively. Seven patients in Yamada’s series (74) presented with seizure; they were seizure-free and off anticonvulsants postoperatively. Three patients who presented with hemorrhage and seizures gained seizure control with reduced doses of anticonvulsants. The senior author (6) has also noted, in general, substantial reduction in seizures upon AVM extirpation. Yeh et al. (11) reported excellent or good seizure control in 24 of 27 patients with AVMs who underwent resection aimed both at total excision of the AVM and any associated seizure focus. The authors pointed out that their surgical approach also addressed any remote foci involving the amygdala and hippocampus, a phenomenon common to many superficial or posterior temporal lobe AVMs. Others have corroborated success in seizure reduction with treatment of these AVMs (31,75,76). There is also evidence that radiosurgery may ameliorate seizures associated with AVMs (77–79). REFERENCES 1. Drake CG. Cerebral arteriovenous malformations: considerations for and experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–208. 2. Malis LI. Arteriovenous malformations of the brain. In: Youmans JR, ed. Neurological Surgery. Philadelphia: Saunders 1982:1786–1806. 3. Heros RC. Arteriovenous malformations of the medial temporal lobe. Surgical approach and neuroradiological characterization. J Neurosurg 1982; 56:44–52. 4. Sugita K, Takemae T, Kobayashi S. Sylvian fissure arteriovenous malformations. Neurosurgery 1987; 21:7–14. 5. Heros RC, Lee SH. The combined pterional/anterior temporal approach for aneurysms of the upper basilar complex (Technical report.) Neurosurg 1993; 33:244–251.
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6. Heros RC, Korosue K, Diebold PM. Surgical excision of cerebral arteriovenous malformations: late results. Neurosurgery 1990; 26:570–578. 7. Hamilton MG, Spetzler RF. The prospective application of a grading system for arteriovenous malformations. Neurosurgery 1994; 34:2–7. 8. Woodard EJ, Barrow DL. Clinical presentation of intracranial arteriovenous malformations. In: Barrow DL, ed. Intracranial Vascular Malformations. American Association of Neurological Surgeons, 1990:53–61. 9. Malik GM, Seyfried DM, Morgan JK. Temporal lobe arteriovenous malformations: surgical management and outcome. Surg Neurol 1996; 46:106–114. 10. Waltimo O. The relationship of size, density and localization of intracranial arteriovenous malformations to the type of initial symptom. J Neurol Sci 1973; 19:13–19. 11. Yeh HS, Kashiwagi S, Tew JMJ, Berger TS. Surgical management of epilepsy associated with cerebral arteriovenous malformations. J Neurosurg 1990; 72:216–223. 12. Ojemann RG, Heros RC, Crowell RM. Arteriovenous malformations of the brain. In: Ojemann RG, Heros RC, Crowell RM, eds. Surgical Management of Cerebrovascular Disease. 2nd ed. Baltimore: Williams & Wilkins, 1988. 13. Luessenhop AJ, Rosa L. Cerebral arteriovenous malformations. Indications for and results of surgery, and the role of intravascular techniques. J Neurosurg 1984; 60:14–22. 14. Luessenhop AJ, Presper JH. Surgical embolization of cerebral arteriovenous malformations through internal carotid and vertebral arteries. Long-term results. J Neurosurg 1975; 42:443–451. 15. Batjer HH, Devous MDS, Seibert GB, Purdy PD, Bonte FJ. Intracranial arteriovenous malformation: relationship between clinical factors and surgical complications. Neurosurgery 1989; 24:75–79. 16. Noorbehesht B, Fabrikant JI, Enzmann DR. Size determination of supratentorial arteriovenous malformations by MR, CT and angio. Neuroradiology 1987; 29:512–518. 17. Latchaw RE, Hu X, Ugurbil K, Hall WA, Madison MT, Heros RC. 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Hojo M, Miyamoto S, Nakahara I, et al. A case of arteriovenous malformation successfully treated with functional mapping of the language area by PET activation study. No Shinkei Geka 1995; 23:537–541. 23. Vinas FC, Zamorano L, Mueller RA, et al. [15O]-water PET and intraoperative brain mapping: a comparison in the localization of eloquent cortex. Neurol Res 1997; 19:601–608. 24. Hund M, Rezai AR, Kronberg E, et al. Magnetoencephalographic mapping: basic of a new functional risk profile in the selection of patients with cortical brain lesions. Neurosurgery 1997; 40: 936–942. 25. Rezai AR, Mogilner AY, Cappell J, Hund M, Llinas RR, Kelly PJ. Integration of functional brain mapping in image-guided neurosurgery. Acta Neurochir Suppl (Wien.) 1997; 68:85–89. 26. Burchiel KJ, Clarke H, Ojemann GA, Dacey RG, Winn HR. Use of stimulation mapping and corticography in the excision of arteriovenous malformations in sensorimotor and language-related neocortex. Neurosurgery 1989; 24:322–327. 27. 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Steinberg GK, Chang SD, Levy RP, Marks MP, Frankel K, Marcellus M. Surgical resection of large incompletely treated intracranial arteriovenous malformations following stereotactic radiosurgery. J Neurosurg 1996; 84:920–928. 33. Heros RC, Korosue K. Parenchymal cerebral arteriovenous malformations. In: Apuzzo MLJ, ed. Brain Surgery. Vol. 2. New York: Churchill Livingstone, 1993; 1175–1193.
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34. Heros RC, Korosue K. Complications of complete surgical resection of AVMs of the brain. Barrow DL, ed. Intracranial Vascular Malformations Park Ridge, IL: American Association of Neurological Surgeons 1990:157–168. 35. Heros RC, Morcos JM. Supratentorial arteriovenous malformations. In: Carter LP, Spetzler RF, eds. Neurovascular Surgery. New York: McGraw-Hill, 1995:979–1004. 36. Yasargil MG ed. Microneurosurgery IIIA. Stuttgart: Georg Thieme Verlag, 1987: 408. 37. Zamorano L, Matter A, Saenz A, Portillo G, Diaz F. Interactive image-guided surgical resection of intracranial arteriovenous malformations. Comput Aided Surg 1998; 3:57–63. 38. Zamorano L, Planells ML, Jiang Z, Nolte L, Kadi AM, Diaz F. Vascular malformations of the brain. Surgical management using interactive image guidance. Neurosurg Clin N Am 1996; 7:201–214. 39. Barrow DL, Boyer KL, Joseph GJ. Intraoperative angiography in the management of neurovascular disorders. Neurosurgery 1992; 30:153–159. 40. Derdeyn CP, Moran CJ, Cross DT, Grubb RL, Dacey RG. Intraoperative digital subtraction angiography: a review of 112 consecutive examinations. Am J Neuroradiol 1995; 16:307–318. 41. Pikus HJ, Harbaugh RE, Cromwell L. Intraoperative digital subtraction angiography: implications of initial experience. J Neurovasc Dis 1997; 2:5–12. 42. Wallace RC, Flom RA, Khayata MH, et al. The safety and effectiveness of brain arteriovenous malformation embolization using acrylic and particles: the experiences of a single institution. Neurosurgery. 1995; 37:606–615. 43. Purdy PD, Samson D, Batjer HH, Risser RC. Preoperative embolization of cerebral arteriovenous malformations with polyvinyl alcohol particles: experience in 51 adults. Am J Neuroradiol 1990; 11: 501–510. 44. Aletich VA, Debrun GM, Koenigsberg R, Ausman JI, Charbel F, Dujovny M. Arteriovenous malformation nidus catheterization with hydrophilic wire and flow-directed catheter. Am J Neuroradiol 1997; 18:929–935. 45. Purdy PD, Batjer HH, Risser RC, Samson D. Arteriovenous malformations of the brain: choosing embolic materials to enhance safety and ease of excision [see comments]. J Neurosurg 1992; 77:217–222. 46. Purdy PD, Batjer HH, Samson D. Management of hemorrhagic complications from preoperative embolization of arteriovenous malformations. J Neurosurg 1991; 74:205–211. 47. Gobin YP, Laurent A, Merienne L, et al. Treatment of brain arteriovenous malformations by embolization and radiosurgery [see comments]. J Neurosurg 1996; 85:19–28. 48. Dion JE, Mathis JM. Cranial arteriovenous malformations. The role of embolization and stereotactic surgery. Neurosurg Clin N Am 1994; 5:459–474. 49. Mathis JA, Barr JD, Horton JA, et al. The efficacy of particulate embolization combined with stereotactic radiosurgery for treatment of large arteriovenous malformations of the brain. Am J Neuroradiol. 1995; 16:299–306. 50. Heros RC, Korosue K. Radiation treatment of cerebral arteriovenous malformations. New Engl J Med 1990; 323:127–129. 51. Spetzler RF, Martin NA, Carter LP, Flom RA, Raudzens PA, Wilkinson E. Surgical management of large AVMs by staged embolization and operative excision. J Neurosurg 1987; 67:17–28. 52. Pikus HJ, Beach ML, Harbaugh RE. Microsurgical treatment of arteriovenous malformations: analysis and comparison to stereotactic radiation. J Neurosurg 1998; 88:641–646. 53. Sisti MB, Kader A, Stein BM. Microsurgery for 67 intracranial arteriovenous malformations less than 3 cm in diameter. J Neurosurg 1993; 79:653–660. 54. Schaller C, Schramm J. Microsurgical results for small arteriovenous malformations accessible for radiosurgical or embolization treatment. Neurosurgery 1997; 40:664–672. 55. Nussbaum E, Heros RC, Camarata P. Surgical treatment of intracranial arteriovenous malformations with an analysis of cost-effectiveness. Clin Neurosurg 1994; 42:348–369. 56. Flickinger JC, Kondziolka D, Lunsford LD, et al. A multi-institutional analysis of complication outcomes after arteriovenous malformation radiosurgery. Int J Radiat Oncol Biol Phys 1999; 44:67–74. 57. Aoki Y, Nakagawa K, Tago M, Terahara A, Kurita H, Sasaki Y. Clinical evaluation of gamma knife radiosurgery for intracranial arteriovenous malformation. Radiat Med 1996; 14:265–268. 58. Flickinger JC, Lunsford LD, Kondziolka D, et al. Radiosurgery and brain tolerance: an analysis of neurodiagnostic imaging changes after gamma knife radiosurgery for arteriovenous malformations. Int J Radiat Oncol Biol Phys 1992; 23:19–26. 59. Pollock BE, Flickinger JC, Lunsford LD, Maitz A, Kondziolka D. Factors associated with successful arteriovenous malformation radiosurgery. Neurosurgery 1998; 42:1239–1244. 60. Karlsson B, Lax I, Soderman M. Factors influencing the risk for complications following gamma knife radiosurgery of cerebral arteriovenous malformations. Radiother Oncol 1997; 43:275–280. 61. Yamamoto Y, Coffey RJ, Nichols DA, Shaw EG. Interim report on the radiosurgical treatment of cerebral arteriovenous malformations. J Neurosurg 1995; 83:832–837. 62. Friedman WA, Blatt DL, Bova FJ, Buatti JM, Mendenhall WM, Kubilis PS. The risk of hemorrhage after radiosurgery for arteriovenous malformations. J Neurosurg 1996; 84:912–919. 63. Chang SD, Steinberg GK, Levy RP, et al. Microsurgical resection of incompletely obliterated intracranial arteriovenous malformations following stereotactic radiosurgery. Neurol Med Chir (Tokyo) 98 AD; 38 (suppl):200–207.
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64. Deruty R, Pelissou-Guyotat I, Amat D, et al. Complications after multidisciplinary treatment of cerebral arteriovenous malformations. Acta Neurochir (Wien) 1996; 138:119–131. 65. Benati A. Interventional neuroradiology for the treatment of inaccessible arteriovenous malformations. Acta Neurochir (Wien) 1992; 118:76–79. 66. Caldarelli M, Di Rocco C, Iannelli A, Rollo M, Tamburrini G, Velardi F. Combined management of intracranial vascular malformations in children. J Neurosurg Sci 1997; 41:315–324. 67. Young C, Summerfield R, Schwartz M, O’Brien P, Ramani R. Radiosurgery for arteriovenous malformations: the University of Toronto experience. Can J Neurol Sci 1997; 24:99–105. 68. Firlik AD, Levy EI, Kondziolka D, Yonas H. Staged volume radiosurgery followed by microsurgical resection: a novel treatment for giant cerebral arteriovenous malformations: technical case report. Neurosurgery 1998; 43:1223–1228. 69. Camarata PJ, Heros RC. Arteriovenous malformations of the brain. In: Youmans JR, ed. Neurological Surgery. Vol. 2. Philadelphia: WB Saunders, 1973:1372–1401. 70. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 71. Morgan MK, Drummond KJ, Grinnell V, Sorby W. Surgery for cerebral arteriovenous malformation: risks related to lenticulostriate arterial supply. J Neurosurg 1997; 86:801–805. 72. Batjer HH, Devous MDS, Seibert GB, et al. Intracranial arteriovenous malformation: relationships between clinical and radiographic factors and ipsilateral steal severity. Neurosurgery 1988; 23:322–328. 73. Oka N, Kamiyama K, Nakada J, Endo S, Takaku A. Surgical approach to arteriovenous malformation of the medial temporal lobe–report of three cases. Neurol Med Chir (Tokyo) 1990; 30:940–944. 74. Yamada S. Surgical approach to arteriovenous malformations in functional areas of the brain. In: Yamada S, ed. Arteriovenous Malformations in Functional Areas of the Brain. Yamada S. Armonk, NY: Futura Publishing Company Inc., 1999:1–122. 75. O’Laoire SA. Microsurgical treatment of arteriovenous malformations in critical areas of the brain. Br J Neurosurg 1995; 9:347–360. 76. Pellettieri L, Carlsson CA, Grevsten S, Norlen G, Uhlemann C. Surgical versus conservative treatment of intracranial arteriovenous malformations: a study in surgical decision-making. Acta Neurochir Suppl (Wien) 1979; 29:1–86. 77. Eisenschenk S, Gilmore RL, Friedman WA, Henchey RA. The effect of LINAC stereotactic radiosurgery on epilepsy associated with arteriovenous malformations. Stereotact Funct Neurosurg 1998; 71:51–61. 78. Gerszten PC, Adelson PD, Kondziolka D, Flickinger JC, Lunsford LD. Seizure outcome in children treated for arteriovenous malformations using gamma knife radiosurgery. Pediatr Neurosurg 1996; 24:139–144. 79. Falkson CB, Chakrabarti KB, Doughty D, Plowman PN. Stereotactic multiple arc radiotherapy. III— Influence of treatment of arteriovenous malformations on associated epilepsy. Br J Neurosurg 1997; 11:12–15.
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Supratentorial Periventricular Arteriovenous Malformations Charles J. Prestigiacomo Departments of Neurological Surgery and Radiology, Neurological Institute of New Jersey, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, U.S.A.
Robert A. Solomon Department of Neurological Surgery, New York Neurological Institute, Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
INTRODUCTION Asymptomatic and symptomatic cerebral arteriovenous malformations (AVMs) have a risk of hemorrhage of 2% to 4% per year with a combined morbidity and mortality rate of 50% (1,2). However, the literature suggests that deep paraventricular AVMs may have a higher risk of hemorrhage (and subsequent rebleeding), a higher associated risk of morbidity and mortality, and a significantly higher treatment risk than the more superficial convexity AVMs (3–9). In contrast to convexity lesions, paraventricular AVMs are hidden by normal parenchyma, making their localization and the surgical approach to the feeding and draining vessels more difficult. The management of supratentorial, deep paraventricular AVMs has developed dramatically over the last several decades. In addition to a better understanding of the natural history of the disease, the tremendous growth in the various modalities of treatment has made certain, previously inaccessible, high-risk lesions treatable. The use of endovascular therapy as an adjunct to the treatment of AVMs has helped to improve surgical outcomes by embolizing feeding arteries that can be a significant challenge to the surgeon and thereby reducing overall flow to the AVM. A better understanding of the role of stereotactic radiosurgery in combination with the development of more precise targeting strategies has likewise made the treatment of AVMs safer with this modality. Finally, the many improvements in intraoperative technology such as image-guided stereotaxy and microsurgical instrumentation have enabled surgeons to better approach these lesions with minimal compromise of normal brain parenchyma. Deep AVMs consist of a broad group of lesions, which include callosal, periventricular, paraventricular (basal ganglia, thalamic), and sylvian lesions. Sylvian and callosal AVMs are discussed in chapters 17 and 19, respectively. In this chapter, we will review the anatomy and natural history of periventricular and paraventricular AVMs and the treatment options for them. EPIDEMIOLOGY, PRESENTATION, AND NATURAL HISTORY Periventricular AVMs—AVMs whose nidus is within or on the surface of a ventricle—are rare. Data concerning the frequency of these lesions along with their primary mode of presentation and natural history are significantly biased, since they are usually part of a retrospective analysis of a particular surgeon’s case series. Thus, the true incidence of these lesions may never be clearly known. However, significant trends can be gleaned from evaluating the available data from these retrospective series, which have an impact on how these lesions should be managed. In large case series, these lesions have been found to comprise 4% to 13% of all intracranial AVMs (2,10–16). Whereas patients with convexity AVMs often present with seizures, patients with these deeper lesions present primarily with an intracranial hemorrhage (Table 1). In fact, when the results of these case series are combined, 83% of patients initially presented with hemorrhage. The clinical status of these patients with deep AVMs on presentation varies according to the location and severity of the hemorrhage. Patients have presented in coma
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Table 1 Presentation in Patients with Paraventricular Arteriovenous Malformations Authors (Ref. No.) Barrow and Dawson (6)
No. of Patients 26
Location Trigone
Verheggen et al. (17)
8
Paraventricular
Miyasaka et al. (18)
24
Choroid plexus Paraventricular
U et al. (19)
16
Periventricular
Nagata et al. (5)
21
Lateral ventricle
Malik et al. (20)
6
Basal ganglia
Batjer and Samson (9)
15
Trigone
Solomon and Stein (21)
22
Thalamocaudate
Waga (22)
10
Thalamus Choroids plexus Caudate
Presentation Hemorrhage Seizures Hemorrhage Other (NS) Hemorrhage Hemorrhage Seizures Hemorrhage Seizures Focal deficits Headache Hemorrhage Seizures Tremors Hemorrhage Focal deficits Hemorrhage Seizures Hemorrhage Seizures Hemorrhage Hydrocephalus Hemorrhage Hemorrhage
Number
Percent of Total
20 6 6 2 11 11 2 8 1 6 1 18 2 1 5 1 14 1 21 1 3 1 2 4
77 23 75 25 46 46 8 50 6 38 6 86 10 4 83 17 93 7 95 5 30 10 20 40
with a purely intraventricular hemorrhage, with focal neurological deficits from a combined intraventricular and intraparenchymal hemorrhage, or with severe headaches and nuchal rigidity secondary to a combined intraventricular and subarachnoid hemorrhage. Furthermore, although not clearly documented in the literature, evidence suggests that these lesions carry a higher propensity to rebleed (3,4,6,9) than convexity lesions. This higher propensity for hemorrhage and rehemorrhage can be explained by the lack of parenchymal tissue along one or several of the borders. In addition, peri- and paraventricular AVMs in general have deep venous drainage, which has been independently associated with a hemorrhagic presentation (23,24). Although patients can recover significantly from these potentially devastating hemorrhages (5), evidence suggests that the probability of hemorrhagic complications such as hydrocephalus is higher in this subgroup of patients (2,3,12,22,25–27). The natural history of peri- and paraventricular AVMs can only be surmised. Nagata et al. compared the outcomes in a highly selected population of 12 patients who did not undergo surgical resection for periventricular AVMs to the outcomes in their surgical series of nine patients (5). They concluded that the natural history of the untreated group is not necessarily poor and that therefore conservative management should be strongly considered when evaluating patients with deep intracerebral AVMs. However, this study was confounded by a significant selection bias in that a large proportion of the AVMs in their non-surgical series were >4 cm and most never rebled. Of the three patients in the untreated group whose AVMs rebled, two died from their hemorrhage. In fact, the authors’ data may reflect the natural history of large AVMs in particular, which may well differ from that of smaller AVMs in a similar location. Other studies have demonstrated that hemorrhage from deeply situated AVMs does lead to severe disability and death (28–33). ANATOMICAL CONSIDERATIONS Peri- and paraventricular AVMs are surrounded by eloquent parenchyma, lack a cortical presentation, and may have a complex, deep vascular supply and drainage pattern. Thorough knowledge of these anatomic relationships is critical for the successful management of these lesions, whether it be by surgery, embolization, radiosurgery, or any combination of these modalities. Although these lesions can be segregated by their vascular supply, surgical approaches, when indicated, are determined by the lesion’s accessibility through established
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approaches that minimize retraction or direct parenchymal injury. Therefore, a brief discussion of the topographic and vascular anatomy relating to these lesions is warranted before discussion of therapeutic options. Lesions of the Frontal Horn and Body of Lateral Ventricle The frontal horn of the lateral ventricle lies rostral to the foramen of Monro. It is bounded superiorly by the corpus callosum, its medial surface is formed by the septum pellucidum, and it is bounded laterally by the head of the caudate and a small portion of the genu of the internal capsule. The body of the lateral ventricle begins posterior to the foramen of Monro and extends to the confluence of this part of the ventricle to the occipital and temporal horns, the trigone. It is bounded superiorly and medially by the corpus callosum, and its superolateral margin is formed by the tapetum of the corpus callosum. It is bounded laterally by the body of the caudate nucleus, the stria terminalis, and terminal veins and inferiorly by the crus of the fornix. Thus, AVMs of these regions can involve the lateral aspects of the corpus callosum, the head and body of the caudate nucleus, the choroid plexus, and the fornix. Branches of the ipsilateral pericallosal trunk generally feed AVMs of the superior and anterior portion of the frontal horns and septum pellucidum. AVMs located in the head of the caudate are fed by perforating branches of the anterior cerebral artery and the recurrent artery of Huebner. AVMs that originate in the region of the choroid plexus drain primarily into the subependymal veins of the lateral ventricle and into the internal cerebral veins. Occasionally, drainage occurs through the interhemispheric fissure to the superior sagittal sinus (34). Lesions of the Trigone and Occipital Horn The trigone of the lateral ventricle is bounded primarily by the crossing fibers of the tapetum and splenium of the corpus callosum. The lateral margin contains the tail of the caudate nucleus, whereas the inferior wall contains the crus of the fornix. Medially, the distal segment of the hippocampus and fimbria that lie beneath the ependymal surface bound the trigone. The splenium and tapetum bound the occipital horn superiorly and laterally, whereas the floor of this horn is predominantly formed by the white matter radiations of the occipital lobe. Thus, lesions of this region can involve the fornix, basal ganglia, and lateral portions of the corpus callosum. The vascular supply to AVMs of this region is relatively constant. The predominant arterial contribution to AVMs of the trigone is the lateral posterior choroidal artery, although posterior temporal branches, thalamoperforators, and anterior choroidal arteries in the case of large lesions can provide direct or collateral flow (9,34). Angiographic AP projections of the AVM can help to distinguish whether a specific trigonal lesion is on the lateral or medial ventricular wall, on the basis of whether the nidus is lateral or medial to the P2–P3 junction (9). The wide use of magnetic resonance imaging (MRI) in the assessment of AVMs clearly documents the location of the lesion in relation to the ventricular wall. Large AVMs of the occipital region may also get a significant contribution from the calcarine artery as well as collateral flow from distal middle cerebral artery branches. The drainage pattern for these lesions is primarily the galenic system, though if large, they may drain more superficially. Lesions of the Temporal Horn The tapetum of the corpus callosum, the optic radiations, the tail of the caudate nucleus, and the stria terminalis form the roof and lateral wall of the temporal horn. The floor contains the collateral eminence, which is a reflection of the collateral sulcus. The medial wall contains the fimbria of the hippocampal formation and the hippocampus proper that extends from the tip of the temporal horn (where the amygdala is noted) to the region of the splenium. Malformations of the anterior temporal horn obtain their arterial supply primarily from branches of the anterior choroidal arteries as well as perforators of the posterior communicating artery and usually drain into the basal vein of Rosenthal. These lesions have been known to be contiguous with the choroid plexus, sharing its feeding and draining vasculature (35). Posterior temporal horn AVMs and AVMs involving the inferior surface of the ventricle involve the posterior hippocampus and fusiform gyrus and may be intimate with the tentorium. Because
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of this association, not only may an AVM of this region derive blood supply from the posterior cerebral, anterior choroidal, and lateral posterior choroidal arteries, but it may also derive supply from dural feeding branches along the tentorium (e.g., branches of the artery of Bernasconi and Cassinari). Venous drainage from these lesions is primarily to the basal vein of Rosenthal, although bridging veins extending from the inferior aspect of the temporal lobe to the tentorial surface often make resection of these lesions hazardous. Lesions of the Third Ventricle Superior to the ependymal lining of the roof of the third ventricle are the contents of the velum interpositum and the body of the fornix. Anteriorly, the anterior commissure and the lamina terminalis bound the third ventricle. The floor of the third ventricle lies next to the optic chiasm, the infundibulum, tuber cinereum, mamillary bodies, posterior perforated substance and tegmentum of the midbrain. Posteriorly, the pineal gland and posterior commissure are found. The lateral margins of the third ventricle are the thalami and hypothalamic nuclei. Arteriovenous malformations of the diencephalon or limbic system can present on the surface of the third ventricle or can be purely within these structures, especially the thalamus. The vascular supply to these AVMs varies with their specific points of origin. AVMs with a significant ventricular component have contributions from one or both posterior choroidal arteries, whereas the primary contribution for thalamic AVMs may be thalamoperforate and thalamogeniculate branches. The draining veins of these lesions usually empty into the internal cerebral veins.
EVALUATION OF PATIENTS WITH PERIVENTRICULAR AVMs All patients who are diagnosed with AVMs require MRI as well as angiography to aid in the development of a comprehensive treatment plan. Non-contrast computed tomography best images an acute hemorrhagic event. This study can help to distinguish intraparenchymal from subarachnoid and intraventricular blood and any calcifications within it [noted in up to 25% of AVMs (36)], while contrast helps to demonstrate the nidus. MRI images the flow voids of the nidus as well as the feeding arteries, draining veins, and any aneurysms associated with the AVM. In addition to imaging blood of different ages in the case of a hemorrhage, MRI is able to demonstrate the presence of partly or completely thrombosed aneurysms. The high definition of parenchymal structures afforded by MRI allows accurate anatomical localization of the AVM and surrounding structures, nuclei, and white matter tracts. This information is critical in defining potential surgical corridors and evaluating the suitability for radiosurgical treatment. The use of functional MRI increases the potential of this imaging modality by providing physiologic data, which can be superimposed on high-resolution T1-weighted images, thereby improving the ability to distinguish eloquent from non-eloquent tissue. Magnetic resonance angiography (MRA) technology continues to evolve. Although many feeding arteries and draining veins of an AVM can be imaged, MRA may never be able to achieve the same resolution as conventional angiographic techniques. Furthermore, MRA provides a static image of a dynamic pathological entity, whereas angiography allows the evaluation of the flow dynamics and high-resolution definition of individual feeding vessels. Both are required in planning treatment strategies. Angiography defines the angioarchitecture of the lesion. Selective and superselective angiography help to define the terminal feeding arteries to the AVM, arteries that merely transit by the AVM but are otherwise uninvolved, and the arteries en passage, which provide one or several branches to the AVM but continue distally to supply normal parenchyma. The angiogram also defines the presence of shunts and fistulae, which are demonstrated by short transit times. Collateral supply to the AVM can also be identified in this way, which is of great significance in those lesions that will require embolization as a mode of therapy. Finally, the angiogram demonstrates the presence of aneurysms in the nidus or on the lesion’s arteries or veins, which can significantly increase the risk of hemorrhage and significantly affect the treatment plan.
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In addition to imaging studies, neuropsychometric evaluation of patients with periventricular AVMs may be valuable, especially if elements of the limbic system are involved with the lesion or may be at risk of compromise from any of the treatment modalities. THERAPEUTIC OPTIONS The treatment of periventricular and paraventricular (thalamocaudate) AVMs presents a dilemma. The proximity to eloquent tissue and the lack of cortical presentation make resection difficult. Because most series suggest that these lesions behave more aggressively than the average AVM (i.e., they are more prone to hemorrhage), and because the potential for permanent neurological injury secondary to a hemorrhage from these lesions can be devastating, clinicians have advocated treatment. Factors to be considered in a determination of therapeutic options are presented in Table 2. Before the advent of radiosurgery, patients with lesions in this location were managed either conservatively or with conventional microsurgical techniques. Patients were made fully aware of the risks of either treating these lesions conservatively and dealing with the consequences of a potential catastrophic hemorrhage or of surgically removing these lesions, knowing that the treatment itself might result in significant neurological sequelae. Over the last decades, radiosurgery for AVMs has made significant strides in reducing the complication rate while providing a reasonable cure rate (Fig. 1). With more precise targeting technology, higher radiation doses to the target site, and significant reduction in collateral damage, radiosurgery has become the primary modality for the treatment of small periventricular or paraventricular AVMs. Though long-term outcomes for these lesions using the current technologies have not yet been reported (37), the results of some series compare favorably with those of surgical case series. The major concerns for the treatment of these lesions by radiosurgery remain the long (2–3 years) latency period before the obliteration of the lesion and its attendant risks of hemorrhage during that period and the long-term side effects of radiation to this region of the brain (38–40). The use of embolization to cure AVMs has been limited (41–44). Most literature quotes a 5% to 12% cure rate with embolization, but long-term follow-up is lacking. Earlier reports stated that the use of embolization to treat periventricular AVMs was precluded by the vascular anatomy of these lesions. However, with the advances made in microcatheter technology, embolization has become an important adjunct to the surgical management of periventricular AVMs. Surgical extirpation of paraventricular AVMs, although no longer the primary modality of treatment, still has an important role in the management of these lesions. Malformations that are located on the roof of the lateral ventricle and include the cingulate gyrus or corpus callosum are amenable to surgical resection. Lesions that are greater than 3 cm in size are generally not considered candidates for radiosurgery and are therefore carefully evaluated for embolization and surgical excision. At our institution, lesions of the thalamus and hypothalamus, as well as lesions involving the internal cerebral veins or the vein of Galen are generally referred for radiosurgery. In addition, radiosurgery is the primary mode of therapy for malformations supplied mainly by the anterior choroidal, lenticulostriate, and thalamoperforate arteries.
Table 2 Criteria Involved in Determining the Therapeutic Options for Periventricular Arteriovenous Malformations Surgery Young age (50 yr) Presents with hemorrhage Greater than 3 cm Cortical or ventricular surface representation Radiosurgery Older than 50 yr of age No history of hemorrhage Smaller than 3 cm No cortical or ventricular representation Primarily deep feeding vessels (choroidal/lenticulostriate)
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Figure 1 Left atrial arteriovenous malformation (AVM) with no evidence of hemorrhage in a 20-year-old man who presented with a single seizure. Axial (A) and coronal (B) magnetic resonance images and posterior-anterior (PA) (C) and lateral (D) cerebral angiograms confirmed the presence of the AVM, with primary feeding vessels from the posterior cerebral artery and some pial–pial collateral contribution from distal middle cerebral artery branches. Although resection of this lesion was possible, its size, periventricular location, and presentation, as well as the risk of deficits from surgical resection, made this patient a good candidate for radiosurgery.
SURGICAL APPROACHES Approaches to periventricular AVMs can take advantage of the fact that although these lesions do not come to a cortical surface, they often do come to a ventricular surface. Approaches can be somewhat tangential, as opposed to the perpendicular approaches that are used for AVMs presenting on the convexity surface. This tangential exposure limits the surgeon’s ability to properly identify and obliterate the feeding arteries, but permits avoidance of injury to the draining veins. Thus, surgeons have slightly modified some of the more traditional approaches to the supratentorial ventricular system in order to access and obliterate these lesions. As with all AVMs, the basic tenets of AVM surgery apply: proper positioning of the patient’s head; adequate brain relaxation through the use of mannitol; induced hypotension; and the use of the operating microscope. Endovascular obliteration of select feeding vessels and neuronavigation has made surgical excision, when necessary, safer and more effective. All approaches depend on the relationship of the AVM to the ventricle, the location of its feeding vessels and draining veins, and the eloquence of the overlying cortex and surrounding
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Figure 2 Illustration summarizing the various approaches in the treatment of periventricular arteriovenous malformations (AVMs). Ellipses represent the general location for AVMs that would be best suited to a given approach (as described by the arrow). Note the use of natural fissures and planes in certain approaches as a means of reducing parenchymal damage. In brief, starting with the arrow at the frontal interhemispheric fissure and going clockwise, the exposures illustrated include the anterior transcallosal approach for frontal horn and body of lateral ventricle as well as the anterior third ventricle; the posterior transcallosal approach for lesions near the atrium of the lateral ventricle; the transcortical approach for lesions of the lateral wall of the trigone; the infratentorial supracerebellar approach for lesions of the posterior third ventricle; the subtemporal approach for medial temporal AVMs; and the transsylvian approach for anterior medial temporal lesions.
white matter (Fig. 2). The amount of blood loss within the ventricular system must be minimized; if the blood is not evacuated at the conclusion of the resection, postoperative hydrocephalus may result. We place Gelfoam1 pledgets into the ventricular space during the resection and remove them at the conclusion of the resection. Immediate postoperative angiography is performed while the patient is still under general anesthesia; if any residual is noted, the patient is returned to the operating room for further resection (45). Multiple reports describe the various approaches to the lateral and third ventricles. We briefly describe the more common approaches to lesions in these locations and discuss our preferred approach. Frontal Horn and Body of the Lateral Ventricle Arteriovenous malformations that come to a cortical surface and extend to the ventricle can be approached like cortical AVMs. When they do not present to the cortical surface, there are two main approaches to the frontal horn and body of the lateral ventricle: the transcortical approach and the transcallosal transventricular approach. The transcortical approach usually involves a middle frontal gyrus corticectomy and leukotomy to come upon the lesion. Such an approach can result in the adequate visualization of lesions in the posterior portion of the body of the lateral ventricle. Although the transcortical approach allows resection of these lesions from a more perpendicular route, the cortical resection that is required can result in some memory disturbances, even if performed on the non-dominant hemisphere. The transcallosal approach offers numerous advantages to the treatment of AVMs in this region. Because the arterial supply for these lesions is primarily from branches of the anterior cerebral artery, early identification and control of these feeders is possible. In addition to avoiding the need for cortical resection, mild amounts of retraction and relaxation are required
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via this approach, especially when one enters and decompresses the lateral ventricle. One disadvantage to approaching AVMs from this direction is the fact that the draining veins may cross the ependymal surface of the nidus, making the resection of these lesions somewhat more difficult. The patient is placed in the supine position with the head in a neutral orientation, elevated above the heart. A craniotomy is made centered two-thirds anterior and one-third behind the coronal suture, and the sagittal sinus is exposed (Fig. 3). The dura is opened, pedicled to the sagittal sinus. The frontal lobe is retracted, exposing the pericallosal arteries and the corpus callosum. The anterior body of the corpus callosum is resected for approximately 2 cm, and the frontal horn of the ventricle is entered. The use of frameless stereotaxy in this phase of the procedure aids in minimizing the risk of injury to nearby eloquent tissue. On entering the frontal horn, the foramen of Monro is identified to serve as a principle topographical landmark. Once the AVM is identified, the nidus is carefully resected with the use of bipolar cautery along the interface of the nidus with normal parenchyma. As with all AVM surgery, meticulous hemostasis is imperative. The use of small Gelfoam pledgets placed in the dependent part of the lateral ventricle aids in reducing the amount of blood that enters the ventricular system, which in turn reduces the potential for postoperative hydrocephalus. Arteriovenous malformations located near the body of the lateral ventricle carry some additional risk in that the approaches to these lesions may require significant retraction of the Rolandic cortex. Surgical planning should include a trajectory that minimizes retraction on the Rolandic cortex and preservation of the Rolandic veins. Trigone and Occipital Horn of the Lateral Ventricle Approaches to the trigone in general and the medial aspect of the trigone in particular are difficult and carry significant risk (Fig. 4). Numerous authors have contributed to the literature about how best to approach this ‘‘no man’s land’’ while minimizing the morbidity risk from a successful resection of the lesion. Drake described a superior temporal gyrus approach to the trigone in non-dominant hemisphere lesions (2), whereas Wilson and Martin preferred the middle temporal gyrus approach (26). The use of the superior parietal lobule approach to the trigone has been reported with good results (12,26). Solomon and Stein have advocated an interhemispheric approach to the trigone with the patient in a semi-sitting slouch position (Fig. 5) (21), which they have found to be most beneficial in the resection of peritrigonal AVMs. Each approach has distinct merits and drawbacks. Although the series are difficult to compare, their outcomes are similar.
Figure 3 Illustration demonstrating the interhemispheric approach for arteriovenous malformations of the frontal horn and body of the lateral ventricle and anterior portion of the third ventricle. (A) Head position for this approach. (B) Solid line depicts the skin incision, while the dotted lines depict the craniotomy for this approach. Inset: Visualization of the corpus callosum and pericallosal vessels, with the dashed line delineating the callosal resection.
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Figure 4 Left trigonal arteriovenous malformation presenting with hemorrhage in a 45-year-old man. Axial (A) and coronal (B) T2-weighted magnetic resonance images demonstrate the residual clot cavity extending to the convexity’s surface. Posterior-anterior (C) and lateral (D) angiograms demonstrate primary contribution from the middle cerebral artery. This lesion is amenable to a transventricular approach. However, the post-hemorrhagic gliosis provides an excellent plane of dissection, and it was used to resect this lesion.
The interhemispheric approach to trigonal AVMs provides excellent visualization of the usual primary feeding vessels to these lesions, namely the posterior cerebral artery and choroidal artery branches, and the deep venous drainage system. By approaching the feeders early in the dissection of the AVM, better control of the AVM is achieved, resulting in a safer resection. With cortical retraction, dissection of an AVM in this region can be performed up to but rarely beyond the lateral edge of the trigone. Consequently, large AVMs with a significant inferior or lateral extension may require a staged approach. Staged approaches involving the dissection of the inferior aspect of the AVM via a temporal gyrus approach or the dissection of the lateral component of the AVM via a superior parietal lobule approach followed by the interhemispheric resection of the lesion may rarely be useful. Transcortical approaches for trigonal AVMs are helpful when the malformation extends significantly lateral to the trigone or when a previous hemorrhage offers a plane of dissection to the nidus. Such approaches have proven useful in cases where the AVM is located predominantly on the lateral aspect of the ventricular surface. In performing the transcortical, superior parietal lobule approach the surgeon should approach the ventricle through the white matter tracts that lie medial to the optic radiations, thus minimizing damage to the visual apparatus. In addition, care should be taken to avoid the origin of the calcarine artery so that ischemic damage to the primary visual cortex can be eliminated. Few AVMs in the peritrigonal regions require approaches other than the posterior interhemispheric approach. This technique has proven useful for AVMs located in the thalamus as well as the posterior cingulate gyrus and splenium of the corpus callosum. With the patient in the semi-sitting slouch position, the head is flexed, allowing a two-fingerbreadth distance
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Figure 5 Illustration demonstrating the posterior interhemispheric approach for trigonal arteriovenous malformations. Relationship of the skin incision and bone flap to the anatomy of the skull and ventricles is shown.
between the chin and chest to minimize the risk of jugular venous congestion. Monitoring for air embolism is used in this setting, which includes monitoring expired pCO2 as well as transthoracic Doppler. A U-shaped flap is fashioned over the parietal region that extends across the midline. A bone flap approximately 5 cm 7 cm is fashioned, with the medial extent placed on the other side of the sagittal sinus. The durotomy is performed with the dura pedicled on the sinus, preserving any medially draining veins when possible. The Rolandic veins are identified and preserved. One or two medially draining veins may be sacrificed to provide a 2 to 3 cm corridor for the approach. With a retractor placed on the medial cortical surface, gentle retraction will expose the surface of the splenium of the corpus callosum. With resection of the corpus callosum anterior to the splenium, the trigone and posterior thalamus are identified. Resection of the AVM can proceed at this stage, inasmuch as the feeding arteries usually present on the medial aspect of the lesion. Patients with AVMs of the occipital horn have a high incidence of presenting with intractable headaches that are eliminated or significantly reduced after AVM resection (2). Although primarily galenic in their drainage patterns, larger occipital AVMs or predominantly polar lesions have a significant superficial drainage pattern, which can make resection more hazardous. Most of these lesions can be resected in a similar fashion to that described for trigonal lesions. However, some lesions may require more significant direct occipital lobe retraction, followed by a corticectomy anterior to the calcarine sulcus to avoid permanent visual field deficits.
Temporal Horn of the Lateral Ventricle Although lesions of the temporal horn can be approached directly through a corticectomy of the superior or middle temporal gyrus, the risks of aphasia and visual field deficits are significant (46). In addition, such an approach does not provide early control of the primary feeding vessels. Consequently, posterior temporal lesions have been approached via a parasagittal approach to the trigone (2) as originally described by Kempe and Blaylock (47). In our experience, lesions of the temporal horn and hippocampal region are best divided in two, with a specific approach for each (Fig. 6). Malformations of the anterior temporal horn are best approached from a pterional craniotomy with the head positioned 30 away from the side of the lesion. By splitting the anterior portion of the sylvian fissure, the supraclinoid carotid and its branches can be visualized and traced posteriorly to the AVM. The anterior choroidal artery can be traced to the choroidal
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Figure 6 Right medial temporal arteriovenous malformation (AVM) in a 54-year-old woman who presented with seizures. (A) Axial magnetic resonance image demonstrating the nidus of the AVM in the medial temporal region, adjacent to the temporal horn. Posterior-anterior (B) and lateral (C) angiograms show feeding branches from the posterior cerebral and middle cerebral arteries. The patient underwent two stages of preoperative embolization and temporal craniotomy for resection of this lesion with an inferior temporal gyrus corticectomy to approach the AVM.
fissure, and any branches from the proximal choroidal vessel feeding the AVM can be safely obliterated. For medial anterior temporal AVMs, an anterior temporal lobectomy and opening of the anterior temporal horn provides excellent exposure with minimal neurological consequences. Because the inferior temporal branch of the posterior cerebral artery primarily feeds lesions of the posterior temporal horn, a pterional approach may not provide sufficient exposure to the AVM. Rather, a temporal craniotomy along the floor of the middle fossa can be performed and the lesion visualized and resected from a subtemporal approach. If the vein of Labbe´ is noted to be under significant traction, a small inferior temporal gyrus resection can be performed to maximize the exposure while minimizing the traction on the vein of Labbe´. Third Ventricle Arteriovenous malformations located around the anterior portion of the third ventricle, including the rostrum of the corpus callosum and septal regions, can be approached from an interhemispheric approach similar to that described for frontal horn AVMs. Lesions located in the posterior portion of the third ventricle, near the superior aspect of the vermis, pineal region, and quadrigeminal plate are best approached by the supracerebellar, infratentorial approach (48). This approach permits visualization of the contralateral feeding vessels and minimizes retraction on the temporal lobes. Thalamostriate Regions Lesions of the thalamostriate region can be treated through similar approaches if they interface with one of the ventricular surfaces. The ventricular surface can be used as a localizer that enables the surgeon to carefully dissect along the AVM-parenchymal interface, thus minimizing damage to the surrounding normal parenchyma. In cases where there is no representation of the AVM on a ventricular surface, other approaches, such as transcortical or transsylvian have been used, but with significant morbidity (8,20,49). In our institution, gamma knife radiosurgery is the prime modality of treatment for these lesions. CONCLUSIONS Significant improvements in the fields of neurosurgery, endovascular surgery, and radiosurgery have made treatment decisions increasingly complex. Many additional factors must be considered before a specific mode of therapy is recommended to the patient. Whereas surgical intervention or expectant conservative management were once the only options to be considered when faced with an AVM of this complexity, other possibilities for treatment now exist, each with different risks and benefits. Multiple factors must be considered when determining the best possible therapy for a given patient (Table 2). At times, the need for combined modalities should also be entertained. Although no specific algorithm can be developed, these factors can help the neurosurgeon select between treatment modalities. For instance, periventricular lesions smaller than 3 cm
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in size, with deep feeding vessels and no cortical representation or lesions embedded in the thalamus or basal ganglia and with deep venous drainage are treated by radiosurgery in our institution. If the lesion is larger than 3 cm or if it has a cortical surface representation, then a combination of staged embolization and surgical resection is recommended. In those cases, the surgical approaches described have greatly aided in minimizing the operative morbidity and mortality from surgery. Immediate postoperative angiography while the patient is under anesthesia is used to confirm complete resection of the lesion. With the tools available today, clinicians are better equipped to cure patients with previously untreatable AVMs. Today’s technologies certainly do not render all AVMs curable. They do, however, provide the necessary platforms from which future therapies and a better understanding of these lesions can mature. REFERENCES 1. Ondra SL, Troup H, George ED et al. The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg 1990; 73:387–391. 2. Drake CG. Cerebral AVMs: considerations for and experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–208. 3. Matsushima T, Fukui M, Kitamura K et al. Arteriovenous malformation in the basal ganglia. Surgical indications and approaches. Neurol Med Chir (Tokyo) 1988; 28:49–56. 4. Pellettieri L, Carlson CA, Grevsten S et al. Surgical versus conservative treatment of intracranial arteriovenous malformations. A study in surgical decision-making. Acta Neurochir Suppl (Wien) 1980; 29:1–86. 5. Nagata S, Matsushima T, Fujii K et al. Lateral ventricular arteriovenous malformations: natural history and surgical indications. Acta Neurochir (Wien) 1991; 112:37–46. 6. Barrow DL, Dawson R. Surgical management of arteriovenous malformations in the region of the ventricular trigone. Neurosurgery 1994; 35:1046–1054. 7. Solomon RA, Stein BM. Surgical management of arteriovenous malformations that follow the tentorial ring. Neurosurgery 1986; 18:708–715. 8. U HS. Microsurgical excision of paraventricular arteriovenous malformations. Neurosurgery 1985; 16:293–303. 9. Batjer HH, Samson D. Surgical approaches to trigonal arteriovenous malformations. J Neurosurg 1987; 67:511–517. 10. Waga S, Shimosaka S, Kojima T. Arteriovenous malformations of the lateral ventricle. J Neurosurg 1985; 63:185–192. 11. Juhasz J. Surgical treatment of arteriovenous angiomas localised in the corpus callosum, basal ganglia and near the brain stem. Acta Neurochir (Wien) 1978; 40:83–101. 12. Andoh T, Itoh T, Yoshimura S et al. Peripheral aneurysms of the posterior inferior cerebellar artery; analysis of 15 cases. No Shinkei Geka 1992; 20:683–690. 13. Crawford PM, West CR, Chadwick DW et al. Arteriovenous malformations of the brain: natural history in unoperated patients. J Neurol Neurosurg Psychiatry 1986; 49:1–10. 14. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983; 58:331–337. 15. Morello G, Borghi GP. A report of 154 personal cases and a comparison between the results of surgical excision and conservative management. Acta Neurochir (Wien) 1973; 28:135–155. 16. Perret G, Nishioka H. Report on the cooperative study of intracranial aneurysms and subarachnoid hemorrhage: section VI. Arteriovenous malformations: an analysis of 545 cases of craniocerebral arteriovenous malformations and fistulae reported to the cooperative study. J Neurosurg 1966; 25:467–490. 17. Verheggen R, Finkenstaedt M, Rittmeyer K, Markakis E. Intra- and paraventricular arteriovenous malformations: symptomatology, neuroradiological diagnosis, surgical approach and postoperative results. Acta Neurochir 1994; 131:176–183. 18. Miyasaka Y, Yada K, Ohwada T, et al. Choroid plexus arteriovenous malformations. Neurol Med Chir 1992; 32:201–206. 19. U HS, Kerber CW, Todd MM: Multimodality treatment of deep periventricular cerebral arteriovenous malformations. Surg Neurol 1992; 38:192–203. 20. Malik GM, Umansky F, Patel S, Ausman JI. Microsurgical removal of arteriovenous malformations of the basal ganglia. Neurosurgery 1988; 23(2):209–217. 21. Solomon RA, Stein BM. Interhemispheric approach for the surgical removal of thalamocaudate arteriovenous malformations. J Neurosurg 1987; 66:345–351. 22. Waga S. Surgical treatment of arteriovenous malformations in the lateral ventricle. Neurol Res 1986; 8:18–24. 23. Duong DH, Young WL, Vang MC et al. Feeding artery pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral arteriovenous malformations. Stroke 1998; 29:1167–1176.
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24. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 25. Pia HW. The acute treatment of cerebral arteriovenous angiomas associated with hematomas. In: Pia HW, Gleave JRW, Grote E et al., eds. Cerebral Angiomas. Advances in Diagnosis and Therapy. New York: Springer-Verlag, 1975:155–177. 26. Wilson CB, Martin NA. Deep supratentorial arteriovenous malformations. In: Wilson CB, Stein BM, eds. Intracranial Arteriovenous Malformations. Baltimore, MD: Williams and Wilkins, 1984:184–208. 27. Wilkins RH. Natural history of intracranial vascular malformations: a review. Neurosurgery 1985; 16:421–430. 28. Davis C, Symon L. The management of cerebral arteriovenous malformations. Acta Neurochir (Wien) 1985; 74:4–11. 29. Fults D, Kelly DL. Natural history of arteriovenous malformations of the brain: a clinical study. Neurosurgery 1984; 15:658–662. 30. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983; 58:331–337. 31. Heros RC, Tu YK. Is surgical therapy needed for unruptured arteriovenous malformations? Neurology 1987; 37:279–286. 32. Jomin M, Lesoin F, Lozes G. Prognosis for arteriovenous malformations of the brain in adults based on 150 cases. Surg Neurol 1985; 23:362–366. 33. Luessenhop AJ. Natural history of cerebral arteriovenous malformations. In: Wilson CB, Stein BM, eds. Intracranial Arteriovenous Malformations. Baltimore, MD: Williams and Wilkins, 1984:12–23. 34. Solomon RA, Stein BM. Management of deep supratentorial and brainstem arteriovenous malformations. In: Barrow DL, ed. Intracranial Vascular Malformations. Park Ridge, NJ: American Association of Neurological Surgeons, 1990:125–140. 35. Stein BM. Arteriovenous malformations of the medial cerebral hemisphere and the limbic system. J Neurosurg 1984; 60:23–31. 36. Apuzzo ML, Chikovani OK, Gott PS et al. Transcallosal, interfornicial approaches for lesions affecting the third ventricle: surgical considerations and consequences. Neurosurgery 1982; 10:547–554. 37. Pollock BE, Flickinger JC, Lunsford LD et al. The Pittsburgh arteriovenous malformation radiosurgery (PAR) grading scale. Radiosurgery 1998; 2:137–146. 38. Blonder LX, Hodes JE, Ranseen JD et al. Short-term neuropsychological outcome following Gamma Knife radiosurgery for arteriovenous malformations: a preliminary report. Appl Neuropsychol 1999; 6:181–186. 39. Flickinger JC, Kondziolka D, Maitz AH et al. Analysis of neurological sequelae from radiosurgery of arteriovenous malformations: how location affects outcome. Int J Radiat Oncol Biol Phys 1998; 40:273–278. 40. Riva D, Pantaleoni C, Devoti M et al. Radiosurgery for cerebral AVMs in children and adolescents: the neurobehavioral outcome. J Neurosurg 1997; 86:207–210. 41. Vinuela F, Duckwiler G, Guglielmi G. Intravacular embolization of brain arteriovenous malformations. In: Maciunas RJ, ed. Endovascular Neurological Intervention. Park Ridge, NJ: American Association of Neurological Surgeons, 1995:189–199. 42. Wilkholm G, Lundqvist C, Svendsen P. Embolization of cerebral arteriovenous malformations: Part I. Technique, morphology, and complications. Neurosurgery 1996; 39:448–459. 43. Gobin YP, Laurent A, Merienne M et al. Treatment of brain arteriovenous malformations by embolization and radiosurgery. J Neurosurg 1996; 85:19–28. 44. Valavanis A, Yasargil MG. The endovascular treatment of brain arteriovenous malformations. Adv Tech Stand Neurosurg 1998; 24:131–214. 45. Solomon RA, Connolly ES, Prestigiacomo CJ, Khandji AG, Pile-Spellman J. Management of residual dysplastic vessels after cerebral arteriovenous malformation resection: implications for post-operative angiography. Neurosurgery 2000; 46:1052–1060. 46. Heros RC. Arteriovenous malformations of the temporal lobe. Surgical approach and neuroradiologic characterization. J Neurosurg 1982; 56:44–52. 47. Kempe LG, Blaylock R. Lateral-trigonal intraventricular tumors. A new operative approach. Acta Neurochir (Wien) 1976; 35:233–242. 48. Solomon RA, Stein BM. Management of arteriovenous malformations of the brain stem. J Neurosurg 2000; 64:857. 49. Shi YQ, Chen XC. Surgical treatment of arteriovenous malformations of the striatothalamocapsular region. J Neurosurg 1987; 66:352–356.
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Corpus Callosum Arteriovenous Malformations Vallabh Janardhan Division of Interventional Neuroradiology, Department of Radiology, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
Howard A. Riina Departments of Neurological Surgery, Neurology, and Radiology, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
Philip E. Stieg Department of Neurological Surgery, Weill Medical College of Cornell University, NewYorkPresbyterian Hospital, New York, New York, U.S.A.
INTRODUCTION The location of a brain arteriovenous malformation (AVM) is an important predictor not only of surgical outcome (eloquent location or not) (1), but also of the risk of future hemorrhage (superficial or deep location) (2). Deep-seated AVMs have a higher risk of future hemorrhage compared with AVMs located superficially (2). AVMs of the corpus callosum are one of the deep-seated brain AVMs (2). Despite the potential morbidity risk of these AVMs, they remain poorly understood. In this chapter, we review the available literature on the epidemiology, morphological characteristics, and management of AVMs of the corpus callosum and discuss our own experience with these lesions. AVMs of the corpus callosum, otherwise known as pericallosal AVMs, can be defined as AVMs or pial arteriovenous (AV) fistulae that are located primarily near the corpus callosum or as cortical brain AVMs that extend significantly into the corpus callosum. These AVMs usually are close to the midline and are predominantly fed by arterial feeders from the pericallosal arteries (bilateral supply not uncommonly) or the splenial branches of the posterior cerebral artery. EPIDEMIOLOGY Prevalence The results of two population-based studies and a prospective cohort show that the prevalence of pericallosal AVMs ranges from 1.1% to 3.1% (Table 1) (3–5). By contrast, studies of hospitalbased cohorts suggest a much higher prevalence of pericallosal AVMs, ranging from 6.7% to 14.8% (Table 1) (6–9; Cornell series, unpublished data). A reason for the discrepancy in prevalence rates between population-based studies and hospital-based studies could be referral bias in tertiary level care centers, and attempts to clarify this discrepancy require understanding of the natural history of deep-seated AVMs. Natural History Among 390 patients with brain AVMs (12 pericallosal AVMs) in the University of Toronto AVM Study Group, 37.4% had hemorrhage as the initial presentation (5). However, hemorrhage was the initial presentation in 59.5% of the patients with deep-seated AVMs, which were noted to have a significantly higher risk of hemorrhage as the initial presentation [odds ratio ¼ 3.26; 95% confidence interval (CI) 1.15–9.2; p ¼ 0.03] (5). In addition, among the same cohort, patients with deep-seated AVMs had a significantly higher risk of future hemorrhage (odds ratio 5.56; 95% CI 2.63–12.5; p < 0.0001) (2). The majority of patients with deep-seated AVMs have deep venous drainage. Mast et al. showed that deep venous drainage is a significant risk factor for spontaneous intracranial
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Table 1 Prevalence of Pericallosal AVMs Location
Study Setting
Prevalence (%)a
Population-based Population-based Prospective cohort
1.1 (1/93) 2.1 (5/240) 3.1 (12/390)
1967–1975 1952–1982
Lothian Health Board, Scotland Perth, Western Australia University of Toronto AVM Study Group Zurich, Switzerland Rome, Italy
Hospital-basedc Hospital-basedc
14.8 (18/121) 9 (15/170)
1984–1994 2001–2006
Nancy, France New York, U.S.A.
Hospital-basedc Hospital-basedc
10.2 (43/420) 6.7 (6/90)
Author
Study Period
Al-Shahi et al. (3) ApSimon et al. (4) Stefani et al. (5)
1998b 1972–1996 1989–1997
Yasargil et al. (6,7) Guidetti and Spallone (8) Picard et al. (9) Cornell series (unpublished data) a
Prevalence is reported as percentage of all patients with brain AVMs who have pericallosal AVMs. Point prevalence. c Retrospective single center series. Abbreviation: AVM, arteriovenous malformation. b
hemorrhage in patients with brain AVMs (hazard ratio ¼ 4.1; 95% CI 1.2–14.9; p ¼ 0.029) (10). Vinuela et al. reported in a consecutive series of 53 deep-seated AVMs (12 pericallosal AVMs) that 77.4% of the patients presented with hemorrhage (11). Angiographic studies in these patients revealed the presence of venous vessel wall irregularities and/or stenosis of the deep venous system (Galenic system) in 14 patients and occlusion of the deep venous system in seven patients (11). They suggested that impaired venous outlets in these patients with deep-seated AVMs could be associated with the increased incidence of intracranial hemorrhage (11). Given the natural history of deep-seated AVMs, it is more likely for hospital-based studies to detect and treat patients with a disabling mode of presentation compared with populationbased studies. Therefore, the prevalence of deep-seated AVMs such as AVMs of the corpus callosum will be higher in hospital-based studies compared with population-based studies. Demographic Characteristics In addition to having a higher risk of hemorrhage, deep-seated AVMs tend to present in patients who are younger than those patients with lobar AVMs (12). In a series of 43 patients with AVMs of the corpus callosum, Picard et al. reported the average age at the time of presentation to be 29.6 years (range 6–57 years) (9). In our Cornell AVM database, the average age at the time of presentation for patients with AVMs of the corpus callosum was 23 years (range 2–49 years). The majority of our patients were male (male ¼ 4; female ¼ 2). However, in larger cohorts, no significant sex differences have been noted (9,12). ANATOMY OF THE CORPUS CALLOSUM White matter of the brain is composed of nerve fibers that can be broadly grouped into (i) commissural fibers, (ii) association fibers, and (iii) projection fibers (13). Commissural fibers help to connect corresponding regions in the two cerebral hemispheres in order to integrate the functions of the two halves of the cerebrum (13). The corpus callosum is the largest and perhaps the most important of the commissures uniting the cerebral hemispheres. Anatomically, the corpus callosum can be broadly divided into (i) the rostrum, (ii) the genu, (iii) the body, and (iv) the splenium (Fig. 1) (13). Each of these four regions has fibers extending to different areas of the cortex. Fibers of the genu connect regions of the anterior section of the frontal lobes, whereas the body links the remaining regions of the frontal lobes, in addition to linking the parietal lobes. The splenium connects areas of the temporal and occipital lobes. Callosal fibers that radiate to parts of the frontal lobes form the forceps minor or the anterior forceps, whereas fibers that project to the occipital lobes are the forceps major or the posterior forceps (13). Vascular Anatomy Ture et al. examined the arteries of the corpus callosum in 20 cadaver brains under the operating microscope (14). The pericallosal and posterior pericallosal arteries were found to be the main sources of blood supply to the corpus callosum in all the specimens (14). In 80% of
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Figure 1 Topographic anatomy of the corpus callosum. Sagittal T1-weighted magnetic resonance imaging scan of the brain in a patient with a frontal arteriovenous malformation showing the different segments of the corpus callosum: (1) the rostrum, (2) the genu, (3) the body, and (4) the splenium.
the specimens, the anterior communicating artery gave rise to either a sub-callosal artery or a median callosal artery, each of which contributed substantially to the blood supply of the corpus callosum (14). Examination of the anatomic features of all the main arteries supplying the corpus callosum revealed anastomoses within the callosal sulcus that formed a pericallosal pial plexus. This network supplied the corpus callosum, the radiation of the corpus callosum, and the cingulate gyrus (14). FUNCTIONS OF THE CORPUS CALLOSUM AND CALLOSAL SYNDROMES The principal function of the corpus callosum is to transfer information from one cerebral hemisphere to the other. With the successful transfer of information the two hemispheres are able to cooperate in order to achieve optimal functioning in experimental tasks and everyday life activities (15). The callosal syndrome or split-brain syndrome, a consequence of interhemispheric disconnection, does not interfere with most activities of daily living, but becomes apparent when a left hemisphere–dominant individual attempts to perform certain tasks (Table 2) (15). Although the exact consequences of lesions to the corpus callosum are still under debate, it is generally agreed that lesions of the anterior and middle segments of the corpus callosum (rostrum, genu, and body) give rise to apraxia, anomia, and agraphia (16). Lesions of the posterior segment (splenium) result in visual–verbal and tactile–verbal disconnection (17,18). These clinical manifestations of corpus callosal lesions, however, usually are not seen in patients with brain AVMs of the corpus callosum. CLINICAL PRESENTATION Patients with AVMs of the corpus callosum usually present in three ways: (i) incidental unruptured AVMs (4.6%; 2/43), (ii) symptomatic unruptured AVMs (seizures, focal deficits) (11.6%; 3/43), and (iii) symptomatic ruptured AVMs (84%; 36/43) (23 intraventricular Table 2 Split-Brain Syndrome or Callosal Syndrome Callosal syndrome
Description
Left hemi-alexia Double hemianopia
Inability to name an object in the left hemi-visual field Inability to point to a moving target in the left visual field with the right hand, and inability to point to a moving target in the right visual field with the left hand Inability to write with the left hand Inability to mimic a command such as pretending to open the door knob with the left hand Inability to copy a complex design with the right hand compared with the left hand Occasions when the left hand acts independent of the patient’s volition
Unilateral left hand agraphia Unilateral left hand apraxia Right hand constructional apraxia Alien hand sign
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Figure 2 (Caption on facing page)
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hemorrhages, 10 subarachnoid hemorrhages, and three intracerebral hemorrhages) (9). In the Cornell AVM database of six patients with an AVM of the corpus callosum, one AVM was noted incidentally, one patient presented with seizures, and four patients presented with hemorrhage. CLASSIFICATION/GRADING SYSTEMS FOR AVMs OF THE CORPUS CALLOSUM Topographic Classification of the Nidus Brain AVMs can occur in any region of the corpus callosum and can be divided into four types according to Yasargil’s classification (19): (i) the anterior type (rostrum and genu) (Fig. 2), (ii) the middle type (body) (Fig. 3), (iii) the posterior type (splenium) (Fig. 4), and (iv) the holocallosal type (includes lesions that extend greater than two-thirds the length of the corpus callosum). The holo-callosal type can be further divided into anterior and posterior subtypes. In Picard’s series, the most common type is the posterior type (46.5%; 20/43), followed by the anterior type (25.6%; 11/43), the holo-callosal type (20.9%; 9/43), and finally the middle type (9). The appearance and extent of the nidus also can be divided into three types according to Picard’s classification (9): (i) the compact type (nidus is well demarcated and located within the corpus callosum), (ii) the extensive type (nidus is involving the cingulated gyrus or septum pellucidum, in addition to the callosum), and (iii) the diffuse type (nidus is ill-defined, scattered, and involves the cortical, sub-cortical, and intraventricular regions with extensive dilatation of cortical vessels). These three types also can be associated with a daughter nidus. The compact type is the most common (44.2%, 19/43), and the diffuse type is the least common (23.2%; 10/43). Multi-focal daughter nidi are noted in approximately 20% of the patients (9/43) (9). Angio-Architecture of Pericallosal AVMs and Classification of the Venous Drainage AVMs of the anterior and middle segments of the corpus callosum are most often supplied by branches of the pericallosal and/or calloso-marginal arteries. AVMs of the posterior segment of the corpus callosum usually are fed by splenial branches of the pericallosal artery, and the splenial or posterior choroidal branches of the posterior cerebral arteries (9). Picard classified the venous drainage of pericallosal AVMs into three types (9): (i) Type A: drainage is through the deep venous system via either the internal cerebral vein or the inferior sagittal sinus draining into the straight sinus; (ii) Type B: drainage is through the superficial venous system via cortical veins draining into the superior sagittal sinus, or Type B0 : superficial drainage is through a primitive persistent falcine sinus draining into the superior sagittal sinus; and (iii) Type C: drainage is through the deep venous system via collateral pathways draining into the venous sinuses of the base of the skull. A mixed pattern of venous drainage (Type A and Type B0 ) is the most common type (41%), followed by Type A and Type C (9). Grading System for Surgical Outcome The Spetzler–Martin grading system (Chapter 6) is a grading system for surgical outcome in patients with brain AVMs (1). As deep venous drainage is commonly noted in patients with AVMs of the corpus callosum, these patients with deep venous drainage get a score of 1 for venous drainage. The corpus callosum per se is not considered to be an eloquent location; however, certain cortico-callosal AVMs may extend into eloquent cortex, and in those cases, patients get a score of 1 for location. The Spetzler–Martin grade also takes size into account. Figure 2 (Facing page) Ruptured arteriovenous malformation (AVM) of the anterior segment of the corpus callosum in a 49-year-old male. (A) Sagittal T1-weighted magnetic resonance imaging (MRI) scan of the brain shows the AVM near the genu of the corpus callosum. (B) Axial gradient echo MRI of the brain shows the ruptured AVM with intracerebral and intraventricular hemorrhage. (C–F) Right internal carotid angiogram in the anteroposterior (AP) (C: early arterial phase; D: late arterial phase) and lateral projections (E: early arterial phase; F: late arterial phase) demonstrates a midline AVM near the anterior segment of the corpus callosum with enlarged early draining veins with predominantly deep venous drainage into the internal cerebral vein and the straight sinus. (G) Left internal carotid angiogram in the AP projection (early arterial phase) demonstrates that the midline AVM near the anterior segment of the corpus callosum has bilateral supply from the A2 segment of the anterior cerebral artery and bilateral pericallosal arteries.
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Figure 3 Ruptured pial arteriovenous (AV) fistula of the middle segment of the corpus callosum (posterior body of the corpus callosum) in a 15-year-old male. (A) Sagittal T1-weighted magnetic resonance imaging scan of the brain shows the AV fistula near the posterior body of the corpus callosum with hemorrhage in the posterior parietal lobe. (B–D) Left internal carotid angiogram in the anteroposterior (AP) (B: early arterial phase) and lateral projections (C: early arterial phase; D: late arterial phase) demonstrates the pial AV fistula near the posterior body of the corpus callosum with arterial feeders predominantly from the left pericallosal artery. The venous drainage is into the internal cerebral vein and the straight sinus, and there is also cortical venous drainage into the superior sagittal sinus.
Grading System for Radiosurgical Outcome As grading systems for surgical outcome have been felt not to correlate well with radiosurgical outcome, a radiosurgery-based grading system for brain AVMs has been proposed by Pollock and Flickinger to predict patient outcome (20). An AVM score of 1 is associated with excellent outcome (20). A specific value needs to be entered for AVMs of the corpus callosum, as shown below: AVM score ¼ (0.1) (AVM volume) þ (0.02) (age) þ (0.3) (location of lesion) where AVM volume is measured in cm3; patient age is in years; and different locations have different values: 0 ¼ frontal or temporal, 1 ¼ parietal, occipital, intraventricular, corpus callosum, cerebellum, 2 ¼ basal ganglia, thalamus, brain stem.
TREATMENT Conservative Management A decision not to treat a patient with a pericallosal AVM can be justified if it is better for the patient to be exposed to the natural history of the disease than to the immediate risks of intervention. In patients with ruptured brain AVMs, including pericallosal AVMs, it is generally agreed that the benefits of treatment outweigh the risks despite the lack of large randomized trials. In contrast, in the case of unruptured brain AVMs, the decision about the need to treat versus conservative management is controversial (21). In one study, the annual risk of rupture
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Figure 4 Incidental arteriovenous malformation (AVM) of the posterior segment of the corpus callosum (involving the splenium of the corpus callosum) in a 5-year-old girl with a ruptured thalamic AVM. (A–D) Right internal carotid angiogram in the anteroposterior (AP) (A: early arterial phase; B: late arterial/early venous phase) and lateral projections (C: early arterial phase; D: late arterial phase) demonstrates the AVM near the splenium of the corpus callosum with arterial feeders from the splenial branches of the pericallosal artery. There is predominantly superficial cortical venous drainage into the superior sagittal sinus.
of an unruptured brain AVM without any risk factors for hemorrhage was reported to be 0.9% (21). Study of the natural history of unruptured brain AVMs is underway in a randomized trial of unruptured brain AVMs (21). However, unruptured deep-seated AVMs such as pericallosal AVMs have an increased annual risk of hemorrhage of about 3.1% (21). Given the increased risk of hemorrhage in this subset of patients who are usually in the younger age group with long life expectancy (12), observation may not be justified. Endovascular Treatment The goal of embolization of an AVM in a stepwise manner is to occlude the angio-architectural features that are associated or responsible for hemorrhage and to decrease the volume of the AVM nidus. Currently used agents for brain AVM embolization in the United States include N-butyl-cyanoacrylate (NBCA) and Onyx. Meisel et al. performed partial targeted NBCA embolization of 22 cortico-callosal AVMs and reported that the risk of hemorrhage was significantly decreased after treatment compared with historical controls (only 1/22 AVMs had hemorrhage) (22). The risk of temporary morbidity was 5.7%, and persisting neurologic deficits occurred in 2%. The mortality rates were equivalent to those of historical controls (22). Yu et al. also showed that embolization with NBCA can be used for complete obliteration of brain AVMs (23). Among 27 treated patients, two had callosal AVMs that were completely obliterated after embolization (23). Picard et al., in a series of 43 patients with pericallosal AVMs, reported that considerable occlusion (defined by them to be more than 75% occlusion) was obtained in 33 patients (77%); of these, more than 95% occlusion was obtained in 17 patients (40%) (9). Angio-architectural findings that were associated with difficult embolization included large and giant AVMs, diffuse-type AVMs, and multi-focal AVMs (9). The overall
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Figure 5 (Caption on facing page)
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morbidity rate was 7% and the mortality rate was 2% (9). In our series at Cornell, of six patients with pericallosal AVMs, we treated five patients with embolization. Two of them had complete occlusion of the AVM, and three underwent partial targeted NBCA embolization (Fig. 5) followed by surgical excision. Good outcomes were achieved [modified Rankin score (mRS) 1] in four patients and a mRS ¼ 3 in one patient. Microneurosurgical Treatment One advantage of surgical resection is that it offers complete removal of the AVM in one procedure. The patient is exposed to the immediate and perioperative risk, but there is no long-term risk. Yasargil et al. reported their experience with surgical excision of eight pericallosal AVMs in the anterior and middle portions of the callosum (6). There was no mortality associated with the surgery. One patient developed postprocedural intraventricular hemorrhage that required re-exploration and removal of residual AVM. Two patients developed seizures, and three patients developed hydrocephalus (6). Yasargil et al. also reported their experience with surgical resection of AVMs of the posterior portion of the corpus callosum (7). There was no mortality associated with the procedure. Two patients developed homonymous hemianopia. One patient had postoperative seizures, and one patient required re-exploration for residual AVM (7). Guidetti and Spallone reported their series of 15 patients with pericallosal AVMs; surgical resection was performed in 11 patients (8). One patient had postoperative memory impairment, and two patients had postoperative seizures. There was no mortality. In our experience at Cornell, three of the six patients underwent combined embolization followed by surgery with good outcomes (mRS 1 at three months) (Fig. 5). Surgical Approach Most pericallosal AVMs can be approached through an interhemispheric approach using a unilateral craniotomy. The patient can be positioned reclining (large anterior callosal lesions) or semi-sitting (small anterior callosal lesions or splenial lesions) with the head in the neutral position or slightly rotated so that the hemisphere falls away from midline. Figure 6A shows the markings for the para-sagittal craniotomy. Figure 6B shows the removal of the bone flap. Figure 6C shows the duramater clearly visualized once the bone flap is removed. Figure 6D shows the duramater exposed. After adequate retraction, the pericallosal arteries can be visualized superior to the corpus callosum (Fig. 6E). The AVM can be resected by skeletonizing the pericallosal arteries as they pass through the lesion, being careful to preserve the main trunks, and taking only the side branches to the malformation. Radiosurgical Treatment The success of obliteration of an AVM with radiosurgery is related to the radiation dose to the periphery of the AVM (24). The risk of complications induced by radiation is related to the volume of the AVM and the radiation dose distribution (24). Finally, the risk of hemorrhage during the latency period before obliteration depends on the age of the patient and the volume of the AVM (24). The success of complete obliteration ranges from 47% to 80% (25). In a recent study of 65 patients (median AVM score 1.69, median radiation dose 18 Gy, mean treatment volume 5.2 cm3) with deep-seated AVMs, including AVMs of the corpus callosum, stereotactic linac-based radiosurgery was performed (26). The complete obliteration rate was Figure 5 (Facing page) Ruptured cortico-callosal arteriovenous malformation (AVM) in a 34-year-old woman. (A,B) Sagittal noncontrast T1-weighted brain magnetic resonance imaging (MRI) (A) and axial T2-weighted brain MRI postcontrast (B) demonstrate a cortico-callosal AVM in the right frontal lobe extending into the anterior segment of the corpus callosum and involving the forceps major of the corpus callosum. (C,D) Right internal carotid angiogram in the anteroposterior (AP) (C: early arterial phase) and lateral projections (D: early arterial phase) demonstrate a midline AVM near the anterior segment of the corpus callosum with enlarged early draining veins with predominantly superficial cortical venous drainage into the superior sagittal sinus. (E,F) Left internal carotid angiogram in the AP (E: early arterial phase) and lateral projections (F: early arterial phase) demonstrate that the cortico-callosal AVM near the anterior segment of the corpus callosum has bilateral supply from the A2 segment of the anterior cerebral artery and bilateral pericallosal arteries. (G,H) Right internal carotid angiogram in the AP (G: early arterial phase) and lateral projections (H: early arterial phase) demonstrate a decrease in the size of the nidus after presurgical partial targeted embolization of the AVM. (I,J) Right internal carotid angiogram in the AP (I: early arterial phase) and lateral projections (J: early arterial phase) demonstrate that the AVM is no longer visualized after surgical resection.
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Figure 6 Surgical approach for the treatment of pericallosal arteriovenous malformations. (A) Markings for the parasagittal craniotomy. (B) Removal of the bone flap. (C) Dura mater once the bone flap is removed. (D) Dura mater fully exposed. (E) With adequate retraction, the pericallosal arteries can be visualized superior to the corpus callosum. Source: Courtesy of Antonio Bernardo, Cornell University, New York, New York, U.S.A. (See color insert.)
50% at three years and 60% at five years (26). Complete obliteration rates were significantly higher for AVMs < 3 cm and for doses > 18 Gy. The annual hemorrhage risks were 4.7%, 3.4%, and 2.7% after one, two, and three years, respectively. Risk factors for hemorrhage included AVM size > 3 cm, AVM volume > 4 cm3, and AVM score > 1.5 (26). Picard et al. reported their preliminary experience with combined embolization followed by radiosurgery in nine patients with inoperable pericallosal AVMs. Four patients had complete obliteration, and another five patients are being followed. The authors suggest that combined therapy with maximal intranidal embolization followed by radiosurgery may be the most effective way to treat AVMs of the corpus callosum (9).
SUMMARY AVMs of the corpus callosum are deep-seated AVMs, are not infrequently found, and appear to be associated with a higher risk of rupture. Their location and angio-architectural characteristics pose unique challenges to their management. A multi-modality approach to the management of pericallosal AVMs is needed to best treat these complex lesions with the least risk of morbidity and mortality.
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Arteriovenous Malformations of the Cerebellar Vermis and Hemispheres Andrew D. Fine Neurosurgery and Spine Specialists, Sarasota, Florida, U.S.A.
Curtis L. Beauregard Southeast Neuroscience Center, Houma, Lousiana, , U.S.A.
Arthur L. Day Cerebrovascular Center, Department of Neurological Surgery, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, U.S.A.
INTRODUCTION Infratentorial arteriovenous malformations (AVMs) can be divided into dural, parenchymal, or combination lesions. Parenchymal AVMs can be further separated into those affecting the brainstem and cerebellum. This chapter deals with cerebellar parenchymal AVMs, including those arising within the hemispheres (lobar), vermis, or peduncles dorsal to the brainstem. CEREBELLAR SURFACE ANATOMY AND VASCULAR SUPPLY The cerebellum is roughly spherical in shape, and its surface is characterized by folia and separated into regions by fissures. The cerebellum can be roughly divided into the two lateral hemispheres (or lobes) and the midline vermis. The bony and dural confines of the posterior fossa define three distinct anatomical cerebellar surfaces, the petrosal, tentorial, and suboccipital (Fig. 1). The regional anatomy of these surfaces is critical to the understanding and exposure of infratentorial AVMs. The petrosal surface represents the anterior surface of the cerebellum and is seen best from an anterior or ventral view (Fig. 2). This surface rests against the petrous temporal bone, basilar occipital bone, and dorsum sella of the sphenoid bone. The horizontal fissure is a prominent feature of the petrosal cerebellar surface and extends laterally from the pons and middle cerebellar peduncle to separate the superior from the inferior semilunar lobule (a feature of no functional significance). The anterior inferior cerebellar artery (AICA) provides most of the arterial blood supply to this cerebellar surface, while most of the venous drainage exits via the superior petrosal vein into the superior petrosal sinus. The AICA usually arises near the junction of the middle and lower thirds of the basilar artery (BA). The AICA originates as a single vessel in 60% to 80% of individuals, is duplicated in 20% to 35%, and is absent in 1% to 2%. Crossing over the ventral surface of the brainstem, its anterior and lateral pontine segments provide perforating vessels to the pons. Laterally, near the cerebellopontine angle (CPA), the AICA runs in the horizontal fissure, sharing this territory with the superior cerebellar artery (SCA) (marginal branch). The artery usually bifurcates into two main trunks. The medial (or caudomedial) trunk supplies the inferior petrosal cerebellar surface and sends branches to the choroid plexus. The lateral (or rostrolateral) trunk supplies the CPA, giving off the internal auditory artery and a dural branch, the subarcuate artery, which anastomoses with the stylomastoid artery branches in the petrous temporal bone via the subarcuate canal. The AICA thus has potential collateral communications with other dural vessels and with branches of the posterior inferior cerebellar artery (PICA), especially laterally. The tentorial surface is defined by the tentorium (and its attachments to the transverse sinus, torcula, and superior petrosal sinus) and the posterior incisural space above the quadrigeminal cistern anterior to the straight sinus (Fig. 3). The tentorial cerebellar surface includes the superior half of the vermis and cerebellar hemispheres (Fig. 1). The superior vermis is the highest point of the cerebellum and lies directly below the straight sinus. The anterior and posterior quadrangular lobules and the superior semilunar lobule face the tentorium. The primary
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Figure 1 Surfaces and blood supply of the cerebellum (lateral view). The petrosal, tentorial, and suboccipital surgical anatomic surfaces are shown in relationship to the major vascular and neural structures of the posterior fossa. Note the position of the basilar (BA), posterior cerebral (PCA), superior cerebellar (SCA), anterior inferior cerebellar (AICA), and posterior inferior cerebellar (PICA) arteries relative to the brainstem. Abbreviations: III, oculomotor nerve; V, trigeminal nerve; MCP, middle cerebellar peduncle; Floc, flocculus; VIII, VII, auditory and facial nerves; VI, abducens nerve; IX, X, XI, glossopharyngeal, vagus, and spinal accessory nerves; XII, hypoglossal nerve; HorFiss, horizontal fissure; StrSin, straight sinus; PrimFiss, primary fissure; IV, trochlear nerve; CP, cerebral peduncle. (See color insert.)
fissure separates the anterior and posterior quadrangular lobules laterally, and the culmen and declive medially. Arterial supply to the tentorial cerebellar surface is primarily derived from the SCA. Venous drainage from the lateral tentorial surface proceeds to the transverse and superior petrosal sinuses, while the more medial surface, especially that anterior to the primary fissure, drains into the precentral cerebellar vein and vein of Galen. The deep cerebellar nuclei also drain into the midline galenic system.
Figure 2 The petrosal surface. The cerebellum and brainstem are viewed from a ventral perspective. The right side of the illustration demonstrates the arterial supply to this surface (derived principally from the AICA), while the left side demonstrates the venous drainage (principally via the superior petrosal vein and sinus). Note the main trunk of the AICA, its anterior and lateral pontine segments (relative to the abducens nerve), and the medial (dividing CN VII and VIII) and lateral (proceeding laterally out of the horizontal fissure) trunks. Abbreviations: CP, cerebral peduncle; III, oculomotor nerve; IV, trochlear nerve; BA, basilar artery; V, trigeminal nerve; MCP, middle cerebellar peduncle; HorFiss, horizontal fissure; IX, X, XI, glossopharyngeal, vagus, and spinal accessory nerves; XII, hypoglossal nerve; Medul, medulla; JugV, jugular vein; TransSin, transverse sinus; VII, VIII, facial and auditory nerves; VI, abducens nerve; SupPetSin, superior petrosal sinus; SupPetV, superior petrosal vein; Mesen, mesencephalon. (See color insert.)
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Figure 3 The tentorial surface. The cerebellar surface is viewed from above. The right side of the illustration demonstrates the arterial supply to this surface [derived principally from the SCA, while the left side demonstrates the venous drainage (posterior-laterally to tentorial sinuses and anterior-laterally to the superior petrosal vein and sinus). Note the major bifurcation (rostral and caudal branches) and perforators to the collicular region and deep cerebellar nuclei off the superior cerebellar artery, after the vessel has circled behind the brainstem. Abbreviations: BA, basilar artery; PCA, posterior cerebral artery; Floc, flocculus; PrimFiss, primary fissure; TransSin, transverse sinus; TentSin, tentorial sinuses; SupPetSin, superior petrosal sinus; VII, VIII, facial and auditory nerves; V, trigeminal nerve; IV, trochlear nerve; III, oculomotor nerve; HemisBr, hemispheric branches of SCA; VermBr, vermian branches of SCA; PreCentCblrV, precentral cerebellar vein; CblrMesenFiss, cerebellomesencephalic fissure. (See color insert.)
The SCA usually arises from the terminal BA as a single trunk, just proximal to the posterior cerebral artery (PCA) origin (Figs. 1 and 3). Occasionally, the SCA may originate from the PCA, or may be duplicate or triplicate. The SCA encircles the brainstem at the level of the lower midbrain and upper pons, above the level of the trigeminal nerve, typically at or just below the level of the free tentorial edge of the incisura. The oculomotor and trochlear nerves course between the SCA and PCA: the oculomotor near the midline and the trochlear in the ambient cistern. Perforating branches to the brainstem or deep cerebellar nuclei arise from the SCA until well after the artery reaches the hemispheres. The SCA usually bifurcates near the trigeminal nerve exit zone into caudal and rostral trunks. The rostral trunk typically supplies the superior vermis and a small portion of the superior medial hemisphere, while the caudal trunk supplies most of the tentorial cerebellar hemispheric surface laterally. As the caudal trunk of the SCA enters the quadrigeminal cistern, a marginal artery typically arises which supplies the hemisphere in the region of the horizontal fissure and provides collateral supply to the AICA. Both the vermian and hemispheric branches may give rise to pre-cerebellar arteries in the cerebellomesencephalic fissure which supply the deep cerebellar nuclei, inferior colliculi and superior medullary velum, and are not safe to sacrifice. The suboccipital surface is confined by the occipital squamosa inferior to the transverse sinuses and is separated from the petrosal surface laterally by the sigmoid sinus. The suboccipital cerebellar surface includes the cerebellar hemispheres laterally and midline uvula between the two tonsils (Fig. 4). The suboccipital fissure separates the superior and inferior semilunar lobule. The secondary fissure separates the biventral lobules (lateral and medial bellies) and the vermian pyramid and uvula. The PICA provides the primary source of arterial supply to this surface. Venous drainage from medial regions drains primarily into the posterior straight sinus and torcula, while the lateral surface drains to the sigmoid and transverse sinuses. The PICA is more variable than the SCA or AICA; it typically arises from the distal vertebral artery (VA) within 2 cm of the vertebrobasilar junction (Fig. 1). Occasionally, this vessel may arise extradurally (5–10% of individuals). Initially, the artery wraps around the
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Figure 4 The suboccipital surface. The suboccipital surface of the cerebellum is viewed from inferiorly, as with the head down in the prone position. The right side of the illustration demonstrates the arterial supply to this surface [derived principally from the posterior inferior cerebellar artery (PICA)], while the left side demonstrates the venous drainage (superiorly to tentorial sinuses). Abbreviations: VeA, vermian arteries from PICA that communicate with the superior cerebellar artery; HeA, hemispheric branches of PICA that communicate with the superior and anterior inferior cerebellar arteries; PetFiss, petrosal fissure; SupOccipFiss, suboccipital fissure; X, vagus nerve; VA, vertebral artery; XI, spinal accessory nerve; IntJugV, internal jugular vein; SigSin, sigmoid sinus; TranSin, transverse sinus; VermBr, vermian branches of PICA; HemisBr, hemispheric branches of PICA; VermV, vermian veins; HemisV, hemispheric veins. (See color insert.)
brainstem, at the ponto-medullary level, and then descends slightly toward the foramen magnum. The caudal loop marks the region where the artery has nearly reached the midline dorsally to ascend between the two cerebellar tonsils into the fourth ventricle. The cranial loop marks the roof of the fourth ventricle, and at its apex the vessel gives off branches to the choroid plexus (the choroidal point). The first three PICA segments may give off perforating branches to the medulla. The PICA then turns caudally and distributes blood supply to the tonsillar, vermian, and hemispheric cortex. The size of the cortical distribution of the PICA is closely related to the size of the AICA; when one is large, the other is characteristically small, and there is extensive cortical leptomeningeal communication between the two distributions. The PICA also shares a rich vermian communication, via the inferior vermian arteries, with the superior vermian branches from the SCA. In addition to the three paired arteries (SCA, AICA, and PICA), parenchymal contributions (and their origins) may arise from the posterior spinal artery (VA), meningeal vessels such as tentorial (internal carotid artery) and posterior meningeal (extradural VA) arteries, and the ascending pharyngeal and occipital arteries (external carotid artery). Approximately 10% of posterior fossa AVMs recruit supply from the external carotid circulation. CEREBELLAR FUNCTIONAL ANATOMY The cerebellum can be separated into three phylogenetically and functionally distinct regions: the neo-, paleo-, and archicerebellum. The cerebellum and its connections are necessary for normal movement and motor learning. Cerebellar dysfunction is associated with disturbance in equilibrium and muscle tone, diminished ability to stabilize joints, and motor incoordination (ataxia). The lateral cerebellar hemispheres, unlike the peduncles and deep nuclei, are generally not considered eloquent brain, due in part to their duplication of task and functional recovery ability. The neocerebellum (lateral cerebellar hemispheres and dentate nucleus) is the ‘‘newest’’ portion of the cerebellum. This region receives input exclusively from the cerebral cortex and is supplied predominantly by the SCA. Lesions in these regions primarily affect skilled voluntary movement. The muscles become easily fatigable, the deep tendon reflexes sluggish, and the ipsilateral extremity movement asynergistic. The axial musculature is ataxic, and there is often an intention tremor and coarse nystagmus. Speech may be slow, monotonous or explosive in character. Cerebellar mutism has been reported. Lesions of the superior cerebellar peduncle and dentate nucleus produce the most severe and persistent functional disturbances.
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If the SCA must be sacrificed, it should be done distally beyond the cerebellomesencephalic fissure and the branches to the deep cerebellar nuclei. The archicerebellum (the inferior vermis, nodulus, floculus, and uvula) is the smallest and phylogenetically oldest division. It primarily regulates balance and eye movements. Lesions in the flocculonodular lobe or its nucleus, the fastigial nucleus, impair an individual’s ability to use vestibular information to control eye movements during head rotation and to balance when standing or walking. Primarily supplied by the PICA, clinical signs of dysfunction include truncal ataxia and nystagmus. Gait is uncoordinated and jerky, but there is no tremor and muscle tone is normal. The paleocerebellum is composed of the remainder of the midline vermis and the medial hemispheres. This cerebellar zone receives somatosensory information from the spinal cord, and is frequently referred to as the spinocerebellum. The vermian component governs posture, locomotion, and gaze, while the hemispheric component is important in the unconscious regulation and adjustment of ongoing motor tasks based on feedback from proprioceptive receptors. Lesions in this region or its nuclei result in hypotonia, dysmetria, terminal tremor, and pendular stretch reflexes. CLINICAL PRESENTATION Based on autopsy studies, approximately 5% to 15% of all intracranial AVMs occur in the posterior fossa (1). Most (75–95%) occur in the cerebellum alone, and the rest lie in the brainstem or both the brainstem and cerebellum (2,3). In 50% to 92% of patients, the initial presentation is hemorrhage. Headache alone (in the absence of hemorrhage or hydrocephalus) is an uncommon presenting symptom with cerebellar AVMs, whereas 40% of patients with supratentorial lesions present with this complaint (3,4). Cerebellar AVMs appear to have a greater risk of rupture than those confined to the brainstem. Some believe they also have a higher risk of hemorrhage than supratentorial lesions, although this conviction is controversial (84.2% vs. 60.8% in one series) (5,6). Arterial or venous aneurysms, lesions known to increase the risk of AVM bleeding, have a 10% to 30% reported incidence in cerebellar AVMs, nearly three times higher than for all AVMs combined (7–13). Once bleeding occurs, it is more likely to be fatal than that associated with supratentorial lesions, due to the proximity of critical neural structures and the small volume and tight anatomic constraints of the posterior fossa. Reported mortality rates of 25% to 57% are closer to those associated with aneurysm rupture and are much higher than the overall 10% risk generally attributed to all AVM sites combined. These risks may be even greater in children (14). Presentations such as hydrocephalus, progressive neurological deficit, trigeminal neuralgia, or hemifacial spasm are encountered less frequently. Enlarged draining veins or vascular channels within the nidus may obstruct cerebrospinal fluid (CSF) outflow from the fourth or third ventricle. Thrombosis of one or several venous sinuses combined with high arterial flow from the malformation into the venous system can produce communicating hydrocephalus. Any hydrocephalus may amplify signs of cerebellar dysfunction, particularly gait disturbances. Posterior third ventricle dilation can cause tectal compression, resulting in Parinaud’s syndrome. The presentation of progressive neurological deficit from ‘‘steal’’ in a patient with AVM can clinically mimic the presentation of other conditions such as demyelinating disease (e.g., multiple sclerosis), tumor, or infection/encephalitis (2,4,15). CLASSIFICATION AND RISK STRATIFICATION Since the anatomy, natural history, and treatment risks for AVMs of the cerebellum appear to be quite different from those for AVMs in other locations, the generally accepted guidelines for assessing the risks and benefits of treatment of supratentorial lesions may not apply. The Spetzler–Martin AVM grading system, which grants points for size, eloquence of adjacent brain, and pattern of venous drainage, is designed to delineate surgical risks, which can then be compared to the natural history of AVMs (16). This system does not consider the more complicated venous drainage, higher incidence of feeding artery aneurysms, and increased mortality and morbidity risks from hemorrhage associated with infratentorial AVMs. The operative risks also appear higher, even for smaller lesions, with mortality rates ranging from 7% to 15%, and significant morbidity risk in an additional 13% to 21% (2–4,17).
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We here propose a modified surgical risk stratification scheme for infratentorial AVMs based on the Spetzler–Martin model. In an effort to conform somewhat to their well-established system, we have considered eloquence, size, arterial feeder aneurysms, and venous drainage from a posterior fossa perspective to aid in the derivation of a grading method more appropriate for these malformations. ‘‘Eloquence’’ is easier to define for supratentorial lesions than for those in the posterior fossa. In our opinion, the definition of posterior fossa eloquence should include the brainstem, the deep cerebellar nuclei, and the cerebellar peduncles. The peduncles and deep nuclei are supplied by arterial branches that often arise distal to the origin of cerebellar cortical branches; this anatomic relationship, unique to the cerebellum, increases the hazards of operative intervention. Venous drainage is a major consideration for all AVMs, particularly when operative intervention is considered (18–20). The classification and significance of deep versus superficial venous drainage in the posterior fossa, however, is not nearly so easily defined in this region as it is in the supratentorial compartment. Obstruction of venous outflow, as evidenced by venous aneurysms or stenosis, or diversion of drainage into delicate vessels adjacent to the fourth ventricle, appears more important, at least in terms of risk stratification (5). Superficial veins on the tentorial surface include the superior vermian and superior hemispheric veins. The suboccipital surface includes the inferior vermian, inferior hemispheric veins, retrotonsillar, and medial and lateral tonsillar veins. On the petrosal surface, the anterior hemisphere veins alone are superficial. Deep venous drainage in the posterior fossa includes veins within the brainstem and those deep in the fissures near the walls of the fourth ventricle. Participation of these deep pathways in the venous drainage of an AVM is usually easily clarified on the venous phase of the angiogram by the presence of venous phase contrast adjacent to the fourth ventricle. The smaller posterior fossa compartment and proximity to the brainstem also prompt changes in size considerations when discussing the surgical risks for these lesions. In our opinion, a more accurate size delineation system to reflect posterior fossa AVM surgical risks should be as follows: small—less than 2 cm, intermediate—2–4 cm, and large—greater than 4 cm. Lesions larger than 4 cm invariably involve multiple feeding vessels, require a more extensive exposure, and have greater risks of deep hemorrhage occurring during final stages of AVM removal. A surgical classification system reflecting the differences for posterior fossa AVMs and including factors similar to those considered in the Spetzler–Martin system is outlined in Table 1. TREATMENT As with AVMs elsewhere, the selection of the best treatment of an individual cerebellar malformation requires a careful assessment of the anatomic location and size of the nidus, the Table 1 Surgical Risk Stratification for Infratentorial Arteriovenous Malformations (AVMs): Cerebellar AVM Grading System Factor Eloquence – þ Size (cm) <2 2–4 >4 Venous outlet obstruction – þ Proximal feeding artery aneurysms – þ Risks of surgery (total points) Low Intermediate High
Points 0 2 1 2 3 0 1 0 1 1 2–3 4
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arterial supply, and the venous drainage. Identification of an associated feeding artery or intranidal aneurysm is imperative, as is consideration of other patient-specific factors such as age, medical co-morbidities, and neurological status at presentation. Computerized tomography is best used for identifying recent hemorrhage, either intraparenchymal or subarachnoid. MRI best clarifies other aspects of the AVM including hydrocephalus, parenchymal edema, and ischemia. During angiography, both carotid and vertebral arteries should be analyzed, as either of these sources may contribute substantially to the malformation or harbor flowrelated aneurysms at some distance from the nidus. Treatment options include surgical resection, radiosurgery, and embolization, alone or in combination. The first step in the selection and timing of treatment is the identification and location of coincident aneurysms of the feeding arteries. Their presence in patients presenting with hemorrhage is often an indication that the aneurysm has bled. These aneuryms usually are located more peripherally, away from the BA or VA. If surgery is selected as the best treatment for the AVM, the aneurysms often can be managed by broadening the operative exposure required to visualize the malformation. In surgical candidates of low- to moderate-risk, surgery is the first line of treatment because of its immediate effectiveness. Conventional radiation therapy is of no benefit (21). Radiosurgery offers very effective obliteration rates in many instances but requires 2 to 3 years for the treatment to be curative. As with surgery, the best results are with small lesions. With larger lesions, the dose must be reduced to limit the risk to immediately adjacent brain, particularly if the brainstem is involved (22–25). Cure rates after single treatments are presumably similar to those for supratentorial malformations—69% for lesions less than 10 cm3, but
Figure 5 Midline suboccipital craniotomy: extent of exposure. Note midline incision (top left) extending from several centimeters above the inion to the spinous process of C5. After a Y-shaped dural incision crossing the occipital sinus inferiorly, the entire suboccipital surface can be well visualized. Abbreviations: PICA, posterior inferior cerebellar artery; VA, vertebral artery; XI, spinal accessory nerve; IX, X, glossopharyngeal, vagus nerves; Lig, ligament.
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only 41% for lesions larger than 10 cm3. As with supratentorial lesions, embolization should be viewed as an adjuvant therapy only, as lasting cures are uncommon with this modality alone (26–28). No radiosurgical series, to our knowledge, has specifically addressed results for posterior fossa AVMs. If infratentorial AVMs actually have higher rates of hemorrhage than supratentorial lesions, radiosurgery may carry higher risks due to the latency period before angiographically demonstrated cure. This question needs to be specifically addressed in future
Figure 6 Lateral suboccipital craniotomy: extent of exposure. Note the incisions for a superior (top left) and far lateral (bottom left) inferior exposure of the tentorial surface. The superior portion of the lateral cerebellar hemisphere can be retracted (top right) to expose the superior cerebellar (SCA) and anterior inferior cerebellar (AICA) vascular territories after they have traveled around from the ventral brainstem surface. The far lateral exposure (bottom right) provides an excellent view of the vertebral (VA) and posterior inferior cerebellar arteries (PICA) and their branches. Note the cranial nerve relationships to each vessel. Abbreviations: V, trigeminal nerve; VII, VIII, facial and auditory nerves; IX, X, XI, glossopharyngeal, vagus, and spinal accessory nerves; SigSin, sigmoid sinus; 4thVent, fourth ventricle.
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studies. The reported increased mortality and morbidity rates with surgical intervention are also strong supportive indications that a better method of treatment selection is needed, based on improved understanding of the natural history and specific outcomes of both surgery and radiosurgery. When surgery is selected, the direction and extent of the approach depends on the location of the malformation and the presence or absence of feeding artery aneurysms. Most posterior fossa AVMs are accessible via either a midline or a lateral suboccipital craniotomy. Although the sitting position reduces venous distention and improves anatomic visualization of the tentorial surface, we prefer a prone, lateral, or parkbench position to reduce the risk of air embolism. Midline or paramedian AVMs are best approached with a standard, midline suboccipital craniotomy, particularly if the lesion presents on the suboccipital surface (Fig. 5) (29). This approach can expose the entire suboccipital cerebellar surface from the transverse sinus and torcula superiorly, the sigmoid sinuses laterally, and the foramen magnum inferiorly. The patient can be rotated in either direction to provide greater surgeon comfort and alter the angle of view as necessary. The tonsils may be separated and the inferior vermis split to expose the floor of the fourth ventricle with little risk to the deep nuclei. Removal of the arch of C1 and C2 enhances inferior exposure. Lateral hemispheric lesions are usually best approached via a unilateral suboccipital route (Fig. 6). The lateral junction of the suboccipital and petrosal or tentorial surfaces is facilitated by this approach, but the midline and ventricular surface are less accessible. Lesions
Figure 7 Occipital transtentorial approach: extent of exposure. Note the incision, bone flap (top left), and the superior lateral retraction of the occipital lobe. The anterior tentorial cerebellar surface can be well visualized, particularly in the paravermian region. Abbreviations: IntCerV, internal cerebral vein; BasV, basal vein of Rosenthal; SCA, superior cerebellar artery; StrSin, straight sinus; VGalen, vein of Galen.
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of the petrosal cerebellar surface are also best approached through a lateral suboccipital craniotomy, carrying the bone exposure laterally to visualize the sigmoid sinus (29). This procedure can be combined with a far-lateral approach (foramen magnum and partial occipital condyle removal) if more inferolateral visualization is required, or with a pre-sigmoid lateral petrosectomy if a more superior view is desired (30). These approaches allow exposure of more medial posterior fossa structures, including more proximal portions of the SCA, AICA, and PICA. Tentorial surface AVMs can be accessed with a midline suboccipital craniotomy, taken high to expose the transverse sinuses and allow maximal superior dural retraction. Adhesions of the cerebellum to the inferior sinus wall are detached, with care taken to avoid injury or premature sacrifice of any bridging veins. This approach can be combined with an occipital transtentorial exposure when more visibility of the tentorial surface is required (Fig. 7) (31). The exposure may be further aided by CSF drainage, mannitol, and furosemide to provide additional brain relaxation as necessary. Examples of the judgments for treatment selection based on an assessment of natural history, anatomic characteristics, and surgical risks of an individual AVM are included in Figures 8–10.
Figure 8 Small lateral hemispheric arteriovenous malformation (AVM) with feeding artery aneurysm, presenting with subarachnoid hemorrhage. (A) MRI showing a small AVM in the lateral hemisphere, and several aneurysms (AN) in the cerebellopontine angle arising from an anterior inferior cerebellar artery (AICA) branch. (B) Anteroposterior (AP) angiogram demonstrating AICA arterial supply. (C) Lateral angiogram showing AICA aneurysm and superficial venous drainage to a tentorial sinus. The grading scale score was 1 (one point for feeding aneurysms), indicating a low risk of surgical treatment, while the presence of the multiple feeding artery aneurysms and prior subarachnoid hemorrhage indicated a high risk natural history if the AVM was left untreated. The lesion was approached via a lateral suboccipital craniotomy, with resection of the AVM and clipping of the aneurysms. The aneurysms were the source of hemorrhage. Abbreviation: PICA, posterior inferior cerebellar artery.
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Figure 9 Large paravermian and hemispheric arteriovenous malformation (AVM) presenting with intraparenchymal bleeding. (A) MRI following hemorrhage, during which the patient developed obstructive hydrocephalus following bleeding into the fourth ventricle (4th Vent). The middle cerebellar peduncle is involved with AVM, but the brainstem is spared. Note dilated venous drainage and venous aneurysm near the midline. (B) Lateral angiogram indicating two arterial compartments of the AVM, the posterior inferior cerebellar artery (PICA) and the superior cerebellar artery (SCA). The nidal blush outlines the brainstem and fourth ventricle. Surgery for this lesion is high risk. The grading scale score was 6 (two points for eloquence, three for size, and one for venous outlet obstruction—venous aneurysm). The lesion was treated with radiosurgery, using two separate isocenters.
SUMMARY Infratentorial cerebellar parenchymal AVMs present unique and difficult challenges to neurosurgeons. Knowledge of the natural history, risks of intervention, anatomic features, and surgical approaches to these lesions can optimize treatment for individual patients. Due to the possible higher rates of hemorrhage for these lesions coupled with the increased risks of potentially catastrophic consequences after hemorrhage, surgery should be strongly considered as the first-line treatment in low risk patients.
Figure 10 Small vermian arteriovenous malformation (AVM) with feeding artery aneurysm and deep venous drainage, presenting with cerebellar and intraventricular hemorrhage. (A) Lateral angiogram (arterial phase) indicating arterial supply from the posterior inferior cerebellar artery (PICA), and the AVM nidus in the vermis. Note the peripheral PICA feeding artery aneurysm arising near the choroidal point, near the roof of the fourth ventricle. (B) Lateral angiogram (venous phase) indicating circuitous venous drainage into deep galenic system, extending anteriorly and superiorly around the brainstem and into the supratentorial space via the basal vein of Rosenthal. The grading scale score was 2 (one point for size and one for venous outlet obstruction with diversion of flow into deep veins near the brainstem). The feeding artery aneurysm was peripheral, indicating a low risk of parent vessel sacrifice at that site should trapping become necessary to ensure its obliteration. The lesion was approached via a midline suboccipital craniotomy, with resection of the AVM and clipping of the aneurysm. The aneurysm was the source of hemorrhage.
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ACKNOWLEDGMENT The authors recognize the contributions of David Peace, the medical illustrator at the University of Florida, for his spectacular artwork and contributions to the clarity of this chapter.
REFERENCES 1. Karhunen PJ, Penttila A, Erkinjuntti T. Arteriovenous malformation of the brain: imaging by postmortem angiography. Forensic Sci Int 1990; 48:9–19. 2. Drake CG, Friedman AH, Peerless SJ. Posterior fossa arteriovenous malformations. J Neurosurg 1986; 64:1–10. 3. George B, Celis-Lopez M, Kato T, et al. Arteriovenous malformations of the posterior fossa [review]. Acta Neurochir 1992; 116:119–127. 4. Batjer H, Samson D. Arteriovenous malformations of the posterior fossa. Clinical presentation, diagnostic evaluation, and surgical treatment. J Neurosurg 1986; 64:849–856. 5. Garcia MR, Alvarez H, Goulao A, et al. Posterior fossa arteriovenous malformations. Angioarchitecture in relation to their hemorrhagic episodes. Neuroradiology 1990; 31:471–475. 6. Lobato RD, Rivas JJ, Gomez PA, et al. Comparison of the clinical presentation of symptomatic arteriovenous malformations (angiographically visualized) and occult vascular malformations [see comments]. Neurosurgery 1992; 31:391–396. 7. Azzam CJ. Growth of multiple peripheral high flow aneurysms of the posterior inferior cerebellar artery associated with a cerebellar arteriovenous malformation. Neurosurgery 1987; 21:934–939. 8. Kaptain GJ, Lanzino G, Do HM, et al. Posterior inferior cerebellar artery aneurysms associated with posterior fossa arteriovenous malformation: report of five cases and literature review [review]. Surg Neurol 1999; 51:146–152. 9. Kikuchi K, Kowada M, Yoneya M. Association of arteriovenous malformation and intracranial aneurysm in the posterior fossa. Surg Neurol 1984; 22:499–502. 10. Lin TK, Wai YY, Wang AD. The association of arteriovenous malformation and aneurysm within the posterior cranial fossa—report of a case. Chang Keng Hsueh Tsa Chih 1990; 13:59–64. 11. Mabuchi S, Kamiyama H, Abe H. Distal aneurysms of the superior cerebellar artery and posterior inferior cerebellar artery feeding an associated arteriovenous malformation: case report [review]. Neurosurgery 1992; 30:284–287. 12. McDermott VG, Sellar RJ. Superior cerebellar artery aneurysms associated with infratentorial arteriovenous malformations. Clin Imaging 1994; 18:209–212. 13. Santucci N, Gazzeri G, Tamorri M. Association of two saccular aneurysms of the posterior inferior cerebellar artery with a cerebellar arteriovenous malformation fed by the same artery. Case report. J Neurosurg Sci 1985; 29:109–112. 14. Griffiths PD, Blaser S, Armstrong D, et al. Cerebellar arteriovenous malformations in children. Neuroradiology 1998; 40:324–331. 15. Matsumura H, Makita Y, Someda K, et al. Arteriovenous malformations in the posterior fossa. J Neurosurg 1977; 47:50–56. 16. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 17. Samson D, Batjer H. Arteriovenous malformations of the cerebellar vermis. Neurosurgery 1985; 16: 341–349. 18. Langer DJ, Lasner TM, Hurst RW, et al. Hypertension, small size, and deep venous drainage are associated with risk of hemorrhagic presentation of cerebral arteriovenous malformations. Neurosurgery 1998; 42:481–486. 19. Muller-Forell W, Valavanis A. How angioarchitecture of cerebral arteriovenous malformations should influence the therapeutic considerations. Minim Invasive Neurosurg 1995; 38:32–40. 20. Nataf F, Meder JF, Roux FX, et al. Angioarchitecture associated with haemorrhage in cerebral arteriovenous malformations: a prognostic statistical model. Neuroradiology 1997; 39:52–58. 21. Redekop GJ, Elisevich KV, Gaspar LE, et al. Conventional radiation therapy of intracranial arteriovenous malformations: long-term results. J Neurosurg 1993; 78:413–422. 22. Ellis TL, Friedman WA, Bova FJ, et al. Analysis of treatment failure after radiosurgery for arteriovenous malformations. J Neurosurg 1998; 89:104–110. 23. Flickinger JC, Kondziolka D, Lunsford LD, et al. A multi-institutional analysis of complication outcomes after arteriovenous malformation radiosurgery. Int J Radiat Oncol Biol Phys 1900; 44:67–74. 24. Pollock BE, Flickinger JC, Lunsford LD, et al. Factors associated with successful arteriovenous malformation radiosurgery. Neurosurgery 1998; 42:1239–1244. 25. Steiner L, Lindquist C, Adler JR, et al. Clinical outcome of radiosurgery for cerebral arteriovenous malformations [see comments]. J Neurosurg 1992; 77:1–8. 26. DeMeritt JS, Pile-Spellman J, Mast H, et al. Outcome analysis of preoperative embolization with N-butyl cyanoacrylate in cerebral arteriovenous malformations. Am J Neuroradiol 1995; 16:1801–1807.
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27. Guo WY, Wikholm G, Karlsson B, et al. Combined embolization and gamma knife radiosurgery for cerebral arteriovenous malformations. Acta Radiol 1993; 34:600–606. 28. Livingston K, Hopkins LN. Endovascular treatment of intracerebral arteriovenous malformations [review]. Clin Neurosurg 1992; 39:331–347. 29. Wen DY, Heros RC. Surgical approaches to the brainstem [review]. Neurosurg Clin N Am 1993; 4:457– 468. 30. Heros RC. Lateral suboccipital approach for vertebral and vertebrobasilar artery lesions. J Neurosurg 1986; 64:559–562. 31. Spetzler RF, Daspit CP, Pappas CT. The combined supra- and infratentorial approach for lesions of the petrous and clival regions: experience with 46 cases. J Neurosurg 1992; 76:588–599.
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Infratentorial Cerebellopontine Angle Arteriovenous Malformations Giuseppe Lanzino Departments of Neurosurgery and Radiology, Illinois Neurological Institute, University of Illinois College of Medicine at Peoria, Peoria, Illinois, U.S.A.
L. Nelson Hopkins Departments of Neurosurgery and Radiology, Toshiba Stroke Research Center, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, U.S.A.
INTRODUCTION Arteriovenous malformations (AVMs) of the posterior fossa have been classically divided into cerebellar and brainstem lesions. Intrinsic to this simple classification was the operability of such malformations; cerebellar AVMs were considered in most cases amenable to surgical excision, whereas brainstem AVMs were deemed inoperable. As more experience was gained from direct exploration of these lesions and with the advent of microsurgical techniques, it became apparent that a separate category was necessary for those AVMs located in the cerebellopontine angle (CPA) (1). CPA AVMs may extend along the ventrolateral surface of the brainstem but usually are relatively easy to dissect, inasmuch as a pial–epipial plane of cleavage separates the malformation from the surrounding parenchyma (1). These characteristics allow safe and radical excision from adjacent structures (brainstem, cerebellum) with low rates of mortality but some morbidity related to dysfunction of cranial nerves (CNs) V to XII (1). Other characteristics that differentiate CPA AVMs from other posterior fossa AVMs include the following: unilateral feeders, with the anterior inferior cerebellar artery (AICA) almost invariably involved; superficial venous drainage, usually to the superior petrosal sinus through the petrosal vein; and a close relationship to the nerves in the angle, which makes ipsilateral CN dysfunction (mostly transient) a frequent, sometimes unavoidable consequence of surgical excision (1). Lesions generically described as ‘‘CPA’’ AVMs have been reported in numerous publications. However, in many of the early articles, the lack of adequate imaging correlates and/or surgical confirmation makes it difficult to define correctly the topography of the lesion. Many of these AVMs have been simply referred to as CPA AVMs because of presenting symptoms referable to the CPA (2), despite the location of the bulk of the malformation in adjacent structures such as the cerebellum, the brainstem, or even the supratentorial compartment, and only a small extension actually located in the CPA. According to Verbiest (2), the definition of CPA AVMs should be used exclusively to indicate those malformations entirely or primarily located in the CPA. In this chapter, we focus on AVMs located at the CPA with only minor superficial extension into surrounding structures. As with most other AVMs, the origin of CPA AVMs is unclear. It has been shown that arteriovenous communications occur normally in some regions of the posterior fossa, such as the pia, along the surface of the brainstem (3), and it has been hypothesized that CPA AVMs may represent the pathological counterparts of such arteriovenous communications (4). CPA AVMs are infrequent. In large surgical series, they constitute 0.8% of all parenchymal AVMs (supratentorial and infratentorial) and 9% to 11% of all infratentorial AVMs (5). In a series of 111 infratentorial parenchymal AVMs treated at the University of Texas, 10 (9%) were located at the CPA. Similarly, Drake et al. reported an incidence of 7 of 66 (10.6%) in their experience (5). REGIONAL ANATOMY For safe removal of CPA AVMs, knowledge of the relevant anatomy, particularly the mutual relationships among vascular and neural structures (Figs. 1 and 2), is of utmost importance.
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Figure 1 Anterolateral view of the brainstem and the cerebellopontine angle (artist’s interpretation). Abbreviations: AICA, anterior inferior cerebellar artery; PICA, posterior inferior cerebellar artery.
Figure 2 Posterior view of the neurovascular structures exposed through a retrosigmoid approach. Abbreviations: AICA, anterior inferior cerebellar artery; CN, cranial nerve. Source: From Ref. 10. (See color insert.)
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We briefly describe some of the pertinent anatomy, beginning with a definition of the CPA. For a more detailed description, the reader is referred to some of the excellent published studies (6–10). The fissure surrounding the lateral recess of the fourth ventricle is commonly referred to as the CPA, despite its actual shape being triangular (11). It is bordered medially by the pons and the ventral aspect of the brachium pontis; superiorly and laterally by the posterior quadrangular lobule and superior semilunar lobule; and inferiorly and laterally by the flocculus, inferior semilunar lobule, lubulus gracilis, and biventer lobulus. The apex of the triangle points to the horizontal fissure of the cerebellum (11). The CPA contains the foramen of Luschka and choroid plexus projecting through the foramen. CNs V, VII, and VIII, and the AICA and its branches traverse this fissure. Cranial Nerves CN VI arises in the medial portion of the pontomedullary sulcus. CN VII arises from the brainstem near the lateral portion of the pontomedullary sulcus (Figs. 1 and 2). This sulcus extends along the junction of the pons and medulla and ends immediately in front of the foramen of Luschka and the lateral recess of the fourth ventricle. CN VII arises in the pontomedullary sulcus 1–2 mm anterior to the point at which the vestibulocochlear nerve joins the brainstem at the lateral end of the sulcus. The distance between CNs VII and VIII is greatest at the level of the pontomedullary sulcus and decreases as these nerves approach the internal auditory meatus. CN VII arises anterior–superior to the choroid plexus, protruding from the foramen of Luschka anterior to the flocculus. Two to 3 mm inferior to the origin of CN VII is the origin of the most cranial rootlets participating in the IX–X–XI complex. Foramen of Luschka, Choroid Plexus, and Flocculus The foramen of Luschka is situated at the lateral margin of the pontomedullary sulcus just dorsal to the junction of CN IX with the brainstem and posterior inferior to the junction of nerves VII and VIII with the brainstem (Figs. 1 and 2). The foramen of Luschka is infrequently well visualized. However, there is a consistently identifiable tuft of choroid plexus that protrudes from the foramen of Luschka and sits on the posterior surface of CN IX and X, just inferior to the junction of nerves VII and VIII with the brainstem. Another structure related to the lateral recess of the fourth ventricle is the flocculus, a fan-shaped cerebellar lobule that projects from the margin of the lateral recess into the CPA. The flocculus, together with the nodule of the vermis, forms the primitive flocculonodular lobe of the cerebellum. It is continuous medially with the inferior medullary velum, a butterfly-like sheet of nerve tissue that forms part of the inferior portion of the roof of the fourth ventricle. The flocculus projects into the CPA just posterior to the intersection of CNs VII and VIII with the pontomedullary sulcus. Anterior Inferior Cerebellar Artery The AICA arises from the lower portion of the basilar artery and courses around the pons near the pontomedullary sulcus (Figs. 1 and 2). After providing branches to the nerves running in the internal auditory meatus and the choroid plexus coming out the foramen of Luschka, it passes around the flocculus to reach the surface of the middle cerebellar peduncle and supplies the lips of the cerebellopontine fissure and the petrosal surface of the cerebellum. Near the VII–VIII complex, the AICA usually divides into a rostral trunk that supplies the upper part of the petrosal surface of the cerebellum and a caudal trunk that supplies the lower part. Based on its relationship with the internal auditory meatus, the course of the AICA is usually divided into premeatal, meatal, and postmeatal segments. The premeatal segment is located from the origin to the proximity of the meatus; and in its course, the AICA passes below, above, or between the interstices of CN VI. The meatal segment runs in the proximity of the meatus. The postmeatal segment originates distal to the VII–VIII complex and courses medially above the flocculus to supply the lateral surface of the brainstem and the cerebellum. The meatal segment often forms a loop with a lateral convex that in 54% of specimens either reaches or protrudes into the auditory canal (6).
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In most cases, the AICA passes below CNs VII and VIII as it courses around the brainstem; it may also pass above or between these nerves (8). Near CNs VII and VIII, the AICA gives rise to the following vessels: labyrinthine artery (also called the internal auditory artery), which supplies CNs VII and VIII as well as surrounding structures; the recurrent perforating branches, which originally may course laterally, but then turn medially to supply the lateral portion of the brainstem; and the subarcuate artery, which enters the subarcuate fossa and in some cases may supply the distal territory of the internal auditory artery. Within the CPA, the AICA maintains a constant relationship with the VII–VIII complex, the foramen of Luschka, and the flocculus. CLINICAL PRESENTATION Subarachnoid hemorrhage (SAH) is the most common presentation of CPA AVMs (1,12–15). Typically, these malformations are small (<3.5 cm in diameter); aneurysms are often present on the feeding pedicles; and seizures, a common manifestation of supratentorial AVMs, do not occur in such locations. All these characteristics may explain the increased frequency of hemorrhagic presentation. Recurrent hemorrhages in untreated lesions are common (1,13); one patient reported by Drake suffered as many as four distinct episodes of SAH in a single month (1). In some patients, hemorrhage can be preceded by long-standing trigeminal neuralgia (16–18), hemifacial spasm (19), or both (20). A thorough patient interview often evokes a history of localizing symptoms such as facial pain (5) or a short-lasting unilateral tinnitus (21) that may precede or accompany the hemorrhage. In the presence of associated aneurysms on a CPA AVM feeding pedicle, rapid aneurysm growth at the time of primary (20) or recurrent hemorrhage (Fig. 3) has been documented. In addition to the classical, non-focal signs and symptoms associated with SAH, coexistent localizing signs such as cerebellar (1,5,13,15,17,18,21–24) and/or ipsilateral CN dysfunction
Figure 3 Angiographic study in a 60-year-old man who presented with sudden onset of coma (Hunt–Hess Grade V) and was found on computed tomography to have diffuse subarachnoid hemorrhage with intraventricular extension (mainly fourth and third ventricles). (A) Digital subtraction angiogram, left vertebral artery injection, anteroposterior view, performed on the day of presentation shows an abnormally dilated and tortuous circumferential pontine artery (arrows) feeding a small arteriovenous malformation (AVM) that extends into the left cerebellopontine angle. There is an aneurysm on the feeding pedicle proximal to the AVM nidus. Treatment of the AVM and the aneurysm was delayed due to the patient’s poor clinical condition. However, one month later, while recovering progressively, he suffered a massive rebleed. (B) Repeat angiogram after rebleed, slightly later arterial phase, shows enlargement of the feeding pedicle aneurysm (arrow).
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(1,4,5,14,15,17,21,25), as well as long-tract dysfunction (1,4,5,14,15,17,18,24,25) may be found on clinical examination after bleeding from a CPA AVM. Such findings reflect direct involvement of the CNs, increased pressure on the surrounding structures, and, in some cases, hemorrhage extension within the cerebellar peduncles and/or the ventrolateral portion of the brainstem. Considerable attention has been paid to the occasional association of CPA AVMs with trigeminal neuralgia (4,16–18,20,23,26,27) and hemifacial spasm (19,20,28,29). This clinical association, along with the direct surgical observation of dilated, pulsating AVM vessels compressing CNs V (30) and VII (28) and symptom resolution after simple decompression (28) or AVM excision (30), tends to support the ‘‘neurovascular conflict’’ theory. Trigeminal neuralgia secondary to AVMs has been reported in up to 1.8% of patients undergoing evaluation for percutaneous rhizotomy (31). In patients with CPA AVMs, the trigeminal pain can involve any of the three branches and usually assumes the same character as idiopathic trigeminal neuralgia. When an AVM is responsible, trigeminal neuralgia often manifests at a young age (16–18,20,23,26), suggesting a structural lesion. Before the advent of more sophisticated imaging techniques, multiple failed procedures aimed at pain resolution were not uncommon in patients with CPA AVMs (17,30). These observations stress the importance of adequate axial imaging in patients presenting with hyperactive CN syndromes. Like trigeminal neuralgia, hemifacial spasm has been reported as a rare mode of presentation of a CPA AVM (19,20,28,29). In some patients, hemifacial spasm coexists with trigeminal neuralgia (19,20). In large series, CPA AVMs are responsible for 0.2% of cases of hemifacial spasm (32). The indentation of CN VII by an AVM feeding vessel has been observed at surgery (20). In such cases, decompression (19,20) or ligation of the compressing vessel (29) without AVM excision is followed by lasting relief of hemifacial spasm. Like trigeminal neuralgia, the occurrence of hemifacial spasm isolated in a young patient (29) raises the question of a structural lesion. Hemifacial spasm synchronous with the patient’s pulse rate has been observed in a young patient with hemifacial spasm secondary to a CPA AVM (29). In the pre–computed tomography (CT) era, because of the intermittent course with exacerbation of neurological symptoms (related to recurrent hemorrhages) in patients who were otherwise young and healthy, an erroneous diagnosis of multiple sclerosis was made in some cases of CPA AVMs (22). CPA AVMs have been found in association with other lesions such as Arnold-Chiari malformation (2), CPA epidermoid cyst (4), familial Rendu-Osler disease (4), and a small-vessel AVM of the parietal scalp (1). Siderosis, probably secondary to multiple subclinical hemorrhages, has also been reported in a patient with a CPA AVM (33). DIAGNOSIS Correct localization of the malformation, in particular its superficial location to critical brainstem structures, is of utmost importance to plan a therapeutic approach. A CT scan of the head is useful for patients who present with SAH. In such cases, the CT scan may reveal the presence of diffuse SAH. However, the presence of a prominent clot in the CPA may give a hint as to the location of the lesion. This CT image may be indistinguishable from that of the more common aneurysms of the posterior inferior cerebellar artery (34). A noncontrast head CT scan in patients with hemorrhages is also useful for detecting the presence and degree of associated hydrocephalus that may require prompt attention. In patients without hemorrhage, the AVM may not be readily apparent on noncontrast CT (28); alternatively, it can appear as a nonhomogeneous high-density region in the CPA (18). After contrast administration, a head CT scan can reveal the malformation as a hyperdense area in the CPA (18,28). Postcontrast CT may also show abnormal enhancement of the ipsilateral superior petrosal sinus draining the AVM (18,30). Before the widespread availability of magnetic resonance imaging (MRI), air contrast-enhanced CT cisternography was also used to localize lesions in the CPA cistern (18,30). MRI is the imaging study of choice to show the characteristic flow voids and mutual relationships of the AVM with surrounding structures. Using special MRI sequencing, the anatomy of the CPA and especially the location of the CNs can be defined with high resolution (35). The MRI also helps to visualize rostral extension of the AVM that may require an additional approach (transtentorial) to achieve total resection. Angiography represents the gold standard in the definitive diagnosis of CPA AVMs. It provides invaluable information about feeding arteries, draining veins, characteristics of the nidus (diffuse vs. multifocal), and ‘‘dangerous’’ findings that may suggest a more
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Figure 4 Angiograms in same patient as in Fig. 3 after the rebleed. (A and B) Digital subtraction angiogram, left vertebral artery injection, anteroposterior view, late arterial phases, shows delayed emptying of the aneurysm and drainage of the arteriovenous malformation mainly through superficial cortical cerebellar veins (arrows).
aggressive nature of the malformation and suggest prompt treatment (such as irregular enlarging aneurysms on feeding pedicles, obstruction of venous drainage, or venous dilatations). Multiple angiographic projections are required to better define the geometry and angiographic characteristics of the AVM. Arterial feeders to CPA AVMs originate almost invariably from the AICA (1,4,12,13,15,26,28–30,36–39). When supplying such malformations, the AICA can often be seen coursing to the internal auditory meatus before looping backward to enter the AVM (1). Alternatively, enlarged circumferential pontine branches of the basilar artery may provide the primary supply to these malformations (Fig. 3) (4,14). Although not always apparent on cerebral angiography, small feeders originating from the basilar trunk are frequently visualized during surgical excision (1,14). If the AVM extends further rostrally or caudally, supply can also come from the superior cerebellar artery (4,12,14,23,30) and the posterior inferior cerebellar artery (12,15,21,28), respectively. The venous drainage is more frequently superficial through the superior petrosal vein to the superior petrosal sinus (1,4,13,14,23,30,38,39), although other drainage patterns can be observed (Fig. 4) (4,12,28,37–39).
THERAPY Surgical excision is the mainstay of therapy for CPA AVMs, and the superficial location of these AVMs and the presence of a pial–epipial cleavage plane make total surgical excision possible in most instances. In elderly patients with hemifacial spasm and/or trigeminal neuralgia, treatment of symptoms by microvascular decompression of the involved nerve is a valuable alternative, since these patients are less likely to tolerate even the transient dysfunction of the lower CNs that follows radical surgery of these lesions. Although significant improvements in devices and technique have occurred since the pioneering efforts of Drake et al. with intraoperative embolization of these lesions (5), the role of endovascular therapy in the treatment of AVMs in the CPA is still limited and probably carries a higher risk than it does for AVMs located in other territories. The angle of origin of the vessels feeding CPA AVMs, often a right angle with a short tortuous course (Fig. 3), limits the possibility of distal catheterization proximal to the nidus. The risk associated with infarction of small perforating branches supplying the brainstem in nondistal positions of
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Figure 5 Angiogram in same patient as in Figs. 3 and 4. The aneurysm was treated endovascularly by catheterization of the enlarged circumflex pontine artery and N-butyl-cyanoacrylate (NBCA) embolization of the distal portion of the feeding pedicle with consequent angiographic obliteration. This case exemplifies some of the problems encountered with endovascular treatment of cerebellopontine angle arteriovenous malformations. Because of the angle of origin of the feeding pedicle from the basilar artery and the tortuous proximal course, distal catheterization closer to the aneurysm was impossible. The procedure was complicated by glue reflux with distal embolization to the calcarine branches of both posterior cerebral arteries, resulting in bilateral occipital infarction. Digital subtraction angiogram, left vertebral artery injection, anteroposterior view, arterial phase, following NBCA embolization of the feeding pedicle bearing the ruptured aneurysm shows obliteration of the aneurysm. The stump of the feeding pedicle is visible.
the catheter is another limitation. At present, endovascular therapy has a minor role as an adjuvant to surgery. The goal of preoperative embolization is to reduce the vascularity of the lesion. In the rare CPA AVM with a single feeder, embolization with a permanent agent such as N-butyl cyanoacrylate (NBCA) can be curative, provided that superselective distal catheterization of the feeder is possible. In patients who have presented with SAH secondary to feeding pedicle aneurysms and are poor candidates for surgery, endovascular therapy targeting the ruptured aneurysm is indicated either by Guglielmi detachable coil (Boston Scientific/Target Therapeutics, Fremont, California, U.S.A.) occlusion of the aneurysm or by glue embolization of the proximal pedicle (Fig. 5). If surgical excision is contraindicated, radiosurgery can be considered as an alternative, especially if the nerve structures can be differentiated from the AVM on high-resolution MRI and properly shielded by means of newly available radiosurgery software. SURGICAL TECHNIQUE CPA AVMs are usually approached through a suboccipital craniotomy similar to that used for other lesions located in this area such as acoustic neuromas and hyperactive CN syndromes involving nerves V and VII. Most neurosurgeons are familiar with this approach and the anatomy involved. Minor modifications are required when operating on AVMs in this area. In those rare instances in which the AVM extends rostrally, a combined retrosigmoid–transtentorial approach is used for complete excision of the lesion (1,5). Positioning The sitting position classically used for vascular and neoplastic lesions of the CPA has been progressively abandoned in favor of the lateral or park-bench position (Fig. 6). This position
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Figure 6 Diagrammatic view of bony exposure (left) and positioning for surgery (right).
is preferred by us as well as by several other authors (5,15,37,40). The park-bench position allows adequate relaxation of the cerebellum while avoiding the risks (air embolism, quadriplegia) associated with the sitting position. With the patient in this position, the surgeon can sit comfortably, which is a great advantage in resecting CPA AVMs away from the nerves, a task that might require several hours of tedious dissection under the microscope. A Foley catheter is inserted and antithrombotic stockings are applied before the patient is positioned. If there is no mass effect from recent hemorrhage, the placement of a lumbar drain can help to maximize cerebellar relaxation. The patient is placed in the lateral oblique position (Fig. 6) with the thorax elevated 15 to maximize venous drainage. The head is held in slight lateral extension and immobilized with the Mayfield three-point fixation device (Ohio/Medical Instrument Company, Cincinnati, Ohio, U.S.A.). If intraoperative angiography is anticipated, a radiopaque headrest is utilized. The park-bench position can be optimized by gently flexing the patient’s neck. During the operation, the table can be rotated toward or away from the surgeon to change the angle of the approach as required to enhance visualization of the brainstem or of the more laterally placed CNs. Before the patient is prepped, appropriate padding is placed to protect all bony prominences. An axillary roll is necessary to protect the brachial plexus. The head and neck are inspected for hyperrotation or hyperflexion, which could interfere with ventilation or jugular venous return. Monitoring Dissection of the AVM vessels off the CNs crowding the CPA and surrounding areas is a critical portion of the operation, and CN dysfunction is the most common complication associated with surgical excision of these lesions. CN monitoring is therefore routinely performed during excision of CPA AVMs. Paired electrodes are placed in the lateral rectus, orbicularis oculi and oris, thyroarytenoid, and hypoglossal muscles to monitor the function of the sixth, seventh, and lower CNs, respectively, during dissection. For this reason, anesthetic-induced muscle paralysis must be avoided during excision. Somatosensory and brainstem auditory-evoked responses are also evaluated intraoperatively. Anesthesiology Considerations and Perioperative Care The anesthesiologist is an integral part of the team in the resection of every AVM. Antibiotics (cefazolin sodium) are administered intravenously approximately 30 minutes before the skin incision is made. Hyperventilation is instituted to maintain a PCO2 around 25–30 mmHg. Osmotic diuretics (mannitol, 1 g/kg) are intravenously administered before the dura is opened
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Figure 7 Incision, craniotomy, and designed dural opening. See text for details.
to reduce intracranial pressure. Dexamethasone (6 mg) is administered intravenously at the start of surgery, then intraoperatively every 6 hours, and for 48 hours postoperatively. Induced hypotension, which is essential for control of bleeding and intraoperative brain swelling during AVM resection, can be achieved by titrating a nitroprusside intravenous drip to a mean arterial pressure of 60 mmHg during resection. The drip can be continued for 24 hours postoperatively to avoid dangerous oscillations in systemic blood pressure during the recovery period. Incision and Craniotomy A linear or curvilinear incision is made approximately 2 cm medial to the mastoid process (Fig. 7). The suboccipital muscles and fascial layers are incised parallel to the skin incision and are dissected from the bone in a subperiosteal plane to expose the lateral two-thirds of the suboccipital bone. Frequently, a mastoid emissary vein is seen, which represents the location of the underlying sigmoid sinus. A burr hole is placed medial and inferior to the asterion, the underlying dura is separated from the inner table of bone, and a bone flap is cut (Figs. 6 and 7). The opening is extended laterally with the aid of rongeurs into the mastoid air cells until the sigmoid sinus is visible. Exposed mastoid air cells are meticulously occluded with bone wax. Laterally, the exposure is carried out to the sigmoid sinus to allow for slight elevation of the sinus itself to better expose the CPA cistern (40). The craniotomy is extended superiorly to visualize the edge of the transverse sinus. The inferior margin of the craniotomy is extended to the foramen magnum, allowing opening of the cisterna magna and removal of cerebrospinal fluid (CSF) to enhance cerebellar relaxation. Dura Opening and AVM Exposure The dura is opened in a cruciate fashion, and the dural edges are held back with sutures (Figs. 7 and 8). The cerebellum is elevated and gently retracted medially with a malleable retractor and then is supported with a self-retaining retractor. A small cottonoid is applied between the cerebellum and the retractor for extra protection of the cerebellar hemisphere. The microscope is positioned, and the remaining portion of the procedure is performed with the aid of the magnification provided. If necessary, the flocculus can be resected to allow better visualization and exposure of the lower CNs and the lateral surface of the brainstem.
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Figure 8 Completed dural opening and arteriovenous malformation exposure. See text for details.
Once the CPA is exposed (Fig. 8), the arachnoid overlying the AVM can be incised. The cistern of the CPA is widely opened from the vertebral artery to the petrosal vein (40). CNs VII and VIII are easily identified from their brainstem origin to the internal auditory meatus, and their relationship to the AVM nidus is noted. Hypertrophied feeding arteries tend to be extensively intertwined with nerves V–XII. This association emphasizes the vulnerability of the lower CNs during surgical excision. Excision of the AVM Initially, the lesion is inspected to determine a plane of cleavage and to define the venous drainage. CPA AVMs lie within the angle extrapially or only shallowly subpially within the brainstem. In some cases, although the mass may seem to be buried in the middle cerebellar peduncle or the brainstem, a cleavage plane (usually subpial) can be found, and the mass can be removed without damaging the parenchyma (1). Following the same general principles that govern AVM resection in other areas, the feeding arteries are separated as they enter the malformation, and major draining veins are preserved until the total arterial supply to the malformation has been eliminated (Fig. 9). Difficulty can be encountered while separating the tough abnormal vessels from the fragile CN roots, and a tedious and prolonged dissection is often required. Because of the close relationship of the AVM with the CNs, preliminary circumnavigation of the AVM may not be possible (40). In such cases, excision starts at the posterior aspect of the AVM at the junction of the cerebellum with the brainstem and proceeds with sequential occlusion of the feeding vessels as the AVM is progressively dissected free and elevated from its pial/subpial plane of attachment (40). The strands of the AVM can be separated from the CPA nerves without loss of function, but hearing may not be preserved after dissection along the fragile CN VIII. It is not unusual for the sensory and motor roots of CN V to be separated by abnormal AVM vessels (1,5). When the AVM mingles with the interstices of CN V, the feeding vessels can be sectioned as they enter and leave the nerve (5) so that the trigeminal nerve is left intact, housing short empty strands of AVM. CNs IX and X should be carefully protected below the lower margin of the AVM. While coagulating feeders to the AVM, care must be taken to follow the course of small vessels proximally within the brainstem parenchyma. To avoid brainstem damage, the
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Figure 9 Excision of the arteriovenous malformation. See text for details.
surgeon must coagulate only the tips of these vessels (5). For AVMs that involve the flocculonodular lobe and the lower CNs and are centered around the foramen of Luschka, the lateral recess and floor of the fourth ventricle should be inspected for residual malformation (39), and feeders that may be coming from the fourth ventricle must be carefully coagulated. In such cases, close inspection of the ventricle before closing is of utmost importance because inadequate exposure of this portion of the AVM and consequent inadequate hemostasis in this location has been reported to cause catastrophic bleeding after removal of CPA AVMs (5). Division of the posterior medullary velum further exposes the foramen of Luschka, allowing the traversing AVM vessels to be securely occluded (5). These vessels are the tiny, thin-walled, tortuous, and fragile feeding arteries that are so difficult to seal intraoperatively with bipolar coagulation. Once all feeders have been properly separated from the CNs, coagulated, and sectioned, attention is directed to the venous drainage. Veins that are obstructing mobilization of the AVM during excision should be temporarily occluded with a bayonette forceps before they are ligated. If the AVM swells during temporary occlusion of a particular vein, that vein is providing critical drainage and cannot be safely sectioned at that time (5). After the draining veins have been identified, the AVM is lifted while still anchored to the draining vein or veins (Fig. 10). The vein(s) is resected and the AVM removed en bloc. The bed of the AVM is closely inspected for residual bleeding. The anesthesiologist is then asked to perform a Valsalva maneuver to ensure the effectiveness of the hemostasis achieved. Closure and Postoperative Care After the cerebellar retractors are removed, the underlying surface of the cerebellum is inspected for any retractor-induced contusion or bleeding. The dura is reapposed and closed with sutures in a watertight manner. A fascial or pericranial graft may be required to repair a dural defect. We prefer either to replace the bone (if it was removed as a craniotomy flap in a single large piece) or to fashion an acrylic cranioplasty; these measures tend to prevent muscle adhesions to the dura, which may be one cause of postoperative headaches. The wound is closed in layers. The patient is observed closely in the neurointensive care unit for at least two days and then is transferred to a regular nursing ward. As previously mentioned, induced hypotension can be continued in the postoperative period for 24 hours to avoid dangerous blood pressure oscillation. Ambulation with assistance is started on the second or third postoperative day.
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Figure 10 Removal of the arteriovenous malformation. See text for details.
COMPLICATIONS Because of the close relationship of a CPA AVM with the CNs traversing the CPA and the lower CNs, dysfunction of these nerves (usually transient, but at times permanent) invariably follows excision of these lesions. Dysfunction of CN V, with the resultant ipsilateral hypo/ anesthesia in one or more of the trigeminal branches, is usually well tolerated. However, involvement of the ophthalmic branch with consequent decreased corneal sensation carries the risk of corneal ulcerations and damage. This risk is particularly high for patients who have an ipsilateral CN VII deficit, with the inability to blink and decreased lacrimal production. In such cases, eye care with lubricating eye drops and early temporary tarsorrhaphy, if necessary, must be considered as preventive measures. When involved by AVM tangles, CN VIII can be very difficult to dissect free. The manipulation required to free the nerve can result in permanent hearing loss (5), as the fragile CN VIII can be difficult to preserve. Postoperative deficits of CNs IX, X, and XI usually appear in tandem rather than alone, as these nerves are close together in the posterior fossa. Temporary dysfunction of these nerves is not unusual, and placement of a nasogastric tube until safe and effective swallowing has been documented can prevent life-threatening aspiration pneumonia. When the lower CNs are compromised, gastrostomy and tracheostomy in the early postoperative period may be required for temporary control of pulmonary toilet and nutrition. A CSF leak can occur after a retrosigmoid approach as a result of mastoid air cell violation during lateral extension of the craniectomy. Prevention of this complication includes the use of bone wax, fat, muscle, and fibrin glue to occlude and isolate the exposed air cells. Conservative treatment of the leak with placement of a lumbar drain is attempted at first, provided that a head CT shows no evidence of an expansile mass (hematoma or infarction). If the leak persists, surgical reexploration and repair are performed. Care must be exercised by the operating surgeon to avoid trauma to the cerebellum, as contusion and cerebellar edema may result at the time of surgery. In the immediate postoperative period, cerebellar edema may result from the lack of regional cerebrovascular autoregulation in the parenchyma surrounding larger AVMs. When this is the case, systemic hypotension (mean arterial pressure of 60–70 mmHg) may be maintained for at least 72 hours postoperatively. The occurrence of severe intraoperative cerebellar edema with no apparent
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cause is a well-known phenomenon in acoustic neuroma surgery (41). If this complication occurs during AVM surgery, the operation may need to be aborted or, alternatively, extensive cerebellar resection may be necessary as a life-saving maneuver. Similarly, if infarction or contusion of the cerebellar hemisphere occurs during surgery, it is best to partially resect the lateral cerebellar lobe rather than leave the necrotic tissue. The tight confines of the posterior fossa tolerate little edema, and transient obstructive hydrocephalus may develop. Obstructive hydrocephalus secondary to parenchymal swelling often resolves after temporary external drainage. Even if no obvious hemorrhage or infarction of the cerebellum is noted, postoperative cerebellar edema can compromise the clinical course in a significant number of patients. This problem is prevented by measures aimed at decreasing the need for significant cerebellar retraction, such as hyperventilation, diuretics, perioperative glucocorticoids, the use of a lumbar drain along with opening of the cisterna magna to enhance cerebellar relaxation, and slight head-up position. Operative vascular complications can also result from parenchymal ischemia secondary to inadvertent obliteration of normal arteries or veins. Development of an infarction in the territory of the vessels feeding the AVM (such as the circumflex pontine arteries, the AICA, posterior inferior cerebellar artery, and superior cerebellar artery) can also be related to decreased blood flow in the enlarged feeder as the AVM is resected with retrograde thrombosis. Clearly, infarction of an artery in this area results in brainstem compromise and even death. Postoperative hemorrhage from incomplete hemostasis, uncontrolled blood pressure, or residual malformation is the most devastating consequence of AVM surgery in the CPA. Coagulation studies after surgery must be carefully reviewed to exclude consumption or dilutional coagulopathy. Tenuous hemostasis is responsible for postoperative bleeds. These events seem to occur more frequently in patients operated on in the sitting position when the cranial arterial pressure is about 20 mmHg lower than the pressure measured in the extremity. Drake therefore suggested that the patient be nursed in this same position for at least 24 hours before the head is lowered to decrease such pressure gradients (1). A hematoma in the resection bed requires prompt return to the operating room and evacuation. Special attention must be given to those AVMs in which the nidus is seen on the angiogram or during operation to be surrounded by several small fragile corkscrew-shaped feeding vessels. These small vessels may be extremely fragile, and great care is needed in their coagulation and clipping to prevent them from tearing and retracting into the depths of the normal parenchymal tissue (5). When posterior fossa hemorrhage develops from a resected CPA AVM, usually the clinical course is rather rapid with sudden coma and respiratory arrest. The warning signs are minor, such as brief elevation of blood pressure, slowing of respiration, and lessening of consciousness, and can be overlooked easily in the postoperative patient (5). During evacuation of the clot, often no single vessel seems to be responsible; instead, several small vessels may be actively bleeding from the wall of the cavity, ‘‘some waving around like small unrestrained hoses’’ (5).
SUMMARY CPA AVMs are an uncommon but definite subcategory of AVMs of the posterior fossa with peculiar characteristics. The most common clinical presentation is SAH, but several cases presenting with hemifacial spasm or trigeminal neuralgia, often clinically indistinguishable from their idiopathic counterparts, have been reported. Characteristic of AVMs in this location is the presence of unilateral arterial feeders, with the AICA most commonly involved. The AVM may also be supplied by abnormally enlarged circumflex pontine arteries arising from the basilar trunk. Participation of the ipsilateral superior cerebellar artery or the posterior inferior cerebellar artery is common. Drainage is usually superficial through the superior petrosal vein or, less commonly, through superficial cortical cerebellar veins. Surgical excision is the mainstay of therapy. The AVM is centered in the CPA and, as such, can be entirely exposed and excised through a classic retrosigmoid approach. Identification of the pial–epipial plane of cleavage allows excision of the AVM from the adjacent cerebellum and lateral brainstem with minimal or no trauma to these structures. The AVM vessels are closely attached to the nerves traversing the CPA, so that the separation of these vessels from the nerves almost invariably results in some CN morbidity.
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ACKNOWLEDGMENTS We thank Paul H. Dressel for preparing the illustrations and the medical library staff at Millard Fillmore Hospital for assistance with the literature searches.
REFERENCES 1. Drake CG. Surgical removal of arteriovenous malformations from the brainstem and cerebellopontine angle. J Neurosurg 1975; 43:661–670. 2. Verbiest H. Arteriovenous aneurysms of the posterior fossa. Prog Brain Res 1968; 30:383–396. 3. Tschabitscher M, Perneczky A. Arterio-venous communications in the posterior cranial fossa. Anatomical study. Adv Neurosurg 1977; 4:266–269. 4. Viale GL, Pau A, Viale ES, Turtas S. Angiomas of the cerebellopontine angle. J Neurol 1981; 225: 259–267. 5. Drake CG, Friedman AH, Peerless SJ. Posterior fossa arteriovenous malformations. J Neurosurg 1986; 64:1–10. 6. Martin RG, Grant JL, Peace D, Theiss C, Rhoton AL. Microsurgical relationships of the anterior inferior cerebellar artery and the facial-vestibulocochlear nerve complex. Neurosurgery 1980; 6:483–507. 7. Matsushima T, Rhoton AL, de Oliveira E, Peace D. Microsurgical anatomy of the veins of the posterior fossa. J Neurosurg 1983; 59:63–105. 8. Rhoton AL. The three neurovascular complexes in the posterior fossa and vascular compression syndromes. Clin Neurosurg 1993; 41:112–149. 9. Rhoton AL Jr., Tedeschi H. Microsurgical anatomy of acoustic neuroma. Otolaryngol Clin North Am 1992; 25:257–294. 10. Seoane E, Rhoton AL. Suprameatal extension of the retrosigmoid approach: microsurgical anatomy. Neurosurgery 1999; 44:553–560. 11. Yasargil MG. Microneurosurgery. Vol. IV A. New York: Thieme Medical Publishers, Inc., 1996:86. 12. Matsumura H, Makita Y, Someda K, Kondo A. Arteriovenous malformations of the posterior fossa. J Neurosurg 1977; 47:50–56. 13. Mount LA. Arteriovenous angioma derived from the anterior inferior cerebellar artery: its diagnosis and treatment. J Neurosurg 1965; 22:612–615. 14. Russo RH, Dicks RE. Arteriovenous malformations of the brainstem in childhood. Surg Neurol 1977; 8:167–170. 15. Solomon RT, Stein BM. Management of arteriovenous malformation of the brainstem. J Neurosurg 1986; 64:857–864. 16. Eisenbrey AB, Hegarty WM. Trigeminal neuralgia and arteriovenous aneurysm of the cerebellopontine angle. J Neurosurg 1956; 13:647–649. 17. Johnson MC, Salmon JH. Arteriovenous malformation presenting as trigeminal neuralgia. Case report. J Neurosurg 1968; 29:287–289. 18. Kawano H, Kobayashi H, Hayashi M, Tsuji T, Kabuto M, Nozaki J. Trigeminal neuralgia caused by arteriovenous malformation of the cerebellopontine angle—report of two cases. No To Shinkei 1984; 36:1175–1179. 19. Gardner WJ, Sava GA. Hemifacial spasm—a reversible pathophysiologic state. J Neurosurg 1962; 19:240–247. 20. Nagata S, Fujii K, Nomura T, Matsushima T, Fukui M, Yasumori K. Hemifacial spasm caused by CP angle AVM associated with ruptured aneurysm in the feeding artery—case report. Neurol Med Chir 1991; 31:406–409. 21. Green JR, Vaughan RJ. Blood vessel tumors and hematomas of the posterior fossa in adolescence. Angiology 1972; 23:474–487. 22. Dereux J, Dereymaeker A, Delberghe P, Deberdt R. Aneurysme arterio-veineux de la fosse posterieure angle pontocerebelleux. Rev Neurol 1959; 100:56–58. 23. Dereux J, Nayrac P, Laine E, et al. Neuf aneurysmes arteria-veineux de la fosse posterieure. Etude clinique et therapeutique. Neurochirurgie 1959; 5:257–279. 24. Hoare RD. Arteriovenous aneurysm of the posterior fossa. Acta Radiol 1953; 4:96–102. 25. Verbiest H. Arterio-venous aneurysms of the posterior fossa, analysis of six cases. Acta Neurochir (Wien) 1961; 9:171–195. 26. Figueiredo PC, Brock M, de Oliveira AM Jr., Prill A. Arteriovenous malformation in the cerebellopontine angle presenting as trigeminal neuralgia. Arq Neuropsiquiatr (Sao Paulo) 1989; 47:61–71. 27. Laine E, Galibert P. Aneurysmes arterio-veineux et cirsoedes de la fosse posterieure: a propos de quarante observations. Rev Neurol 1967; 115:276–288. 28. Kim Y, Tanaka A, Kimura M, Yoshinaga S, Tomonaga M. Arteriovenous malformation in the cerebellopontine angle presenting as hemifacial spasm. Neurol Med Chir (Tokyo) 1991; 31:109–112. 29. Pierry A, Cameron M. Clonic hemifacial spasm from posterior fossa arteriovenous malformation. J Neurol Neurosurg Psychiatry 1979; 42:670–672.
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30. Kawano H, Hayashi M, Kobayashi H, Tsuji T, Kabuto M, Kubota T. Gas CT cisternography of trigeminal neuralgia caused by AVM of the cerebellopontine angle. Am J Neuroradiol 1987; 8:161–162. 31. Lundsford LC, Bennet MH. Percutaneous retrogasserian glycerol rhizotomy for tic doloureux. Part 1: Technique and result in 112 patients. Neurosurgery 1984; 14:424–435. 32. Loeser JD, Chen J. Hemifacial spasm: treatment by microsurgical facial nerve decompression. Neurosurgery 1983; 13:141–146. 33. Schott B, Garde A, Tommasi M, Bady M, Michel D, Rochet H. Siderose marginale du nevraxe: malformation vasculaire de l’angle ponto-cerebelleux. Rev Neurol 1968; 118:222–230. 34. Kallmes DF, Lanzino G, Dix JE, et al. Patterns of hemorrhage with ruptured posterior inferior cerebellar artery aneurysms: CT findings in 44 cases. Am J Roentgenol 1997; 169:1169–1171. 35. Mitsuoka H, Arai H, Tsunoda A, Okuda O, Sato K, Makita J. Microanatomy of the cerebellopontine angle and internal auditory canal: study with new magnetic resonance imaging technique using three-dimensional fast spin echo. Neurosurgery 1999; 44:561–567. 36. Gewirtz RJ, Steinberg GK. AVMs of the posterior fossa: evaluation and treatment. Contemp Neurosurg 1996; 18:1–6. 37. Lewis AI, Tew JM Jr., Management of thalamic-basal ganglia and brain-stem arteriovenous malformations. Clin Neurosurg 1994; 41:83–111. 38. Martin NA, Stein BM, Wilson CB. Arteriovenous malformations of the posterior fossa. In: Wilson CB, Stein BM, eds. Intracranial Arteriovenous Malformations. Baltimore Williams & Wilkins, 1984: 209–221. 39. Batjer H, Samson D. Arteriovenous malformations of the posterior fossa. Clinical presentation, diagnostic evaluation, and surgical treatment. J Neurosurg 1986; 64:849–856. 40. Samson DS, Kopitnik TA Jr., Batjer HH, Purdy PD. Technical features of the management of arteriovenous malformations of the brainstem and cerebellum. In: Batjer HH, ed. Cerebrovascular Disease. Philadelphia: Lippincott-Raven Publishers, 1997:811–821. 41. Wiet RJ, Teixido M, Liang JG. Complications in acoustic neuroma surgery. Otolaryngol Clin North Am 1992; 25:389–412.
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Brainstem Arteriovenous Malformations Steven D. Chang and Gary K. Steinberg Department of Neurosurgery and the Stanford Stroke Center, Stanford University School of Medicine, Stanford, California, U.S.A.
INTRODUCTION Brainstem arteriovenous malformations (AVMs) consist of malformations in the midbrain, pons, and medulla; they are either superficial pial AVMs or deep AVMs located within the brainstem parenchyma. These lesions previously were considered to be generally untreatable based on anatomic location. However, over the last two decades, approaches to some of these AVMs that allow treatment with an acceptable risk have been developed and used. Microinstrumentation and the neurosurgical microscope, along with stereotaxis, electrophysiologic monitoring, and preoperative embolization, have enabled neurosurgeons to resect some of these lesions safely. Stereotactic radiosurgery also has allowed treatment of many ‘‘inoperable’’ lesions. While the basic principles of AVM physiology apply to brainstem AVMs, a fundamental knowledge of the anatomy of midline and deep neurologic structures of the posterior fossa is critical for the cerebrovascular surgeon to treat these lesions with minimal risk of patient morbidity.
NATURAL HISTORY The natural hemorrhage rate for brainstem AVMs and the percentage of patients with those lesions who present with hemorrhage are not well documented, in part due to the rarity of brainstem AVMs and the lack of large clinical series. In one reported series (1) of 12 patients with brainstem AVMs, 92% (11 of 12) presented with an acute hemorrhage, as compared to approximately 50% of patients with supratentorial AVMs (2). The higher percentage of patients presenting with hemorrhage is thought to be due to the lack of seizures observed with brainstem AVMs, and the belief by some that smaller AVMs, of which brainstem AVMs are largely comprised, have a higher hemorrhage rate than larger malformations (86% vs. 46%) (3). In one series of seven patients with brainstem AVMs, a hemorrhage rate of 72% (5 of 7) was found (4). In two larger series of posterior fossa AVMs, hemorrhage was the presenting symptom in 92% (61 of 66) (5) and 72% (23 of 32) (6) of patients; but neither of these studies analyzes the actual hemorrhage rates for AVMs located exclusively in the brainstem.
CLASSIFICATION OF BRAINSTEM AVMs Although brainstem AVMs can be grouped according to multiple parameters, the most clinically relevant classification system involves dividing these lesions into those that are superficial or pial-based and those that are deep-seated within the parenchyma. This distinction is of significance as the superficial group is often resectable, whereas those that are deepseated generally cannot be resected without unacceptable risks of morbidity and mortality. Deep brainstem AVMs are usually better treated with other modalities such as radiosurgery or embolization followed by radiosurgery. Pial-based AVMs include those on the surface of the tectal plate, middle or inferior cerebellar peduncles, superficially on the floor of the fourth ventricle, or anterolateral midbrain, pons, and medulla. They are often located within cisterns, including the quadrageminal plate and ambient cisterns, and the cerebellopontine angle. The resectability is based on their superficial arterial supply; they are not supplied by deep penetrating arteries. Deep AVMs, in contrast, are located within the parenchyma of the brainstem itself and often are supplied by deep perforating arteries, making resection difficult without significant parenchymal injury.
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ARTERIAL SUPPLY AND VENOUS DRAINAGE The arterial supply and venous drainage of brainstem AVMs is largely based on their location, and a critical understanding of these vascular pathways is necessary to ensure successful resection with minimal risk of morbidity. AVMs within the parenchyma of the brainstem are often supplied by paramedian or circumferential perforating arteries from the basilar artery, vessels that often supply normal brainstem parenchyma. Venous drainage from these parenchymal AVMs is generally through the mesencephalic and pontomesencephalic veins to the galenic system or the petrosal sinus. Posterior pial brainstem AVMs are supplied by branches of the superior cerebellar artery (SCA), anterior inferior cerebellar artery (AICA), or the posterior inferior cerebellar artery (PICA), with the feeding arteries often dilated. Drainage is through intraventricular ependymal veins to the galenic system or petrosal sinus. AVMs located along the lateral medulla and pons, including the cerebellopontine angle AVMs are generally supplied by the AICA, with occasional feeding arteries from the SCA and PICA. Venous drainage is variable and can involve the vein of Galen, the petrosal vein, the superior petrosal sinus, the pontomesencephalic system, or combinations of the venous systems. AVMs along the anterior or anterolateral brainstem are usually fed directly by perforators off the basilar artery and drain into either the cavernous sinus or petrosal sinus. AVMs of the tectal plate are usually supplied by branches of the SCA or the posterior cerebral artery, with drainage into the vein of Galen and/or the straight sinus. CLINICAL PRESENTATION With respect to brainstem AVM hemorrhage, subarachnoid hemorrhage occurs more frequently than intra-axial hematomas (4), but both generally cause significant neurologic deficits. Less frequently, brainstem AVMs can manifest as progressive neurologic deficits in the absence of hemorrhage, possibly due to a vascular steal phenomenon, venous hypertension, or local mass effect (4). In some cases, after hemorrhage the patients may be stuporous or comatose on presentation, with blood in the brainstem parenchyma and subarachnoid space of the posterior fossa. For smaller hemorrhages, cranial nerve deficits or motor/sensory deficits of the extremities may be present. In some instances, the clinical symptoms can mimic either brainstem neoplasms or demyelinating diseases (4,7), and brainstem AVMs have been misdiagnosed and mistreated as these lesions, particularly in the pre–magnetic resonance era. INDICATIONS AND CONTRAINDICATIONS FOR SURGERY Many angiographically demonstrable brainstem AVMs are candidates for resection if they have hemorrhaged and are localized to a pial or ependymal surface at a surgically accessible region. Progressive neurologic deficit is also an indication for resection. The risk of surgical resection for AVMs is related in part to AVM size, location, and the complexity of arterial feeders and venous drainage (8). Brainstem AVMs are generally smaller than their cortical counterparts but are located in significantly more eloquent regions, thereby increasing risk. Pial or superficial AVMs can be safely resected in some cases, particularly when small. Deep parenchymal AVMs with associated deep perforating arterial supplies are generally not resectable. Large brainstem AVMs are not usually considered for surgery unless their size is first reduced substantially by embolization and/or radiosurgery. Finally, the lack of experience of most neurosurgeons in resecting brainstem AVMs may also increase the risk of surgery, particularly at centers with a low volume of AVM surgery. The clinical condition of the patient also has a bearing on surgical resection. Patients in poor clinical condition as a result of hemorrhage may not be ideal operative candidates unless significant recovery occurs. However, patients with significant mass effect and deteriorating neurologic condition from a hemorrhagic clot after brainstem AVM rupture should be considered for emergent evacuation of the hemorrhage, with AVM resection reserved for a later date. The timing of resection of brainstem AVMs is similar to that of other AVMs, i.e., resection should be planned under nonemergent conditions. Resection of the AVM three to four weeks after hemorrhage, when the blood is liquefied, may improve the ease of resection, permitting the brain to regain more normal hemodynamic autoregulation and allowing for neurologic recovery (9–12).
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Failure of stereotactic radiosurgery and embolization are other indications for surgical resection. Partial obliteration after radiosurgery does not confer protection from AVM rehemorrhage (10,13–16), and hence an alternative therapy should be sought for residual brainstem AVMs still present more than three years after radiosurgery treatment. Embolization is a useful treatment for large supratentorial AVMs, but it is less useful in the treatment of brainstem AVMs (9). These malformations are generally supplied by small perforating arteries that primarily arise from parent vessels at right angles, have small lumens, and thus are difficult to cannulate. Furthermore, arterial feeders to brainstem AVMs often also supply critical brainstem parenchyma or cranial nerves. Nonetheless, in selected cases, embolization is helpful with partial obliteration of brainstem AVMs. Contraindications to surgical resection of brainstem AVMs include poor clinical condition of the patient as a result of AVM hemorrhage, medical conditions that preclude surgery, elderly patients, and brainstem AVMs that either are large or have a significant deep parenchymal component. Often, patients in poor neurologic condition may improve over time or with minor procedural interventions, such as a ventriculostomy or ventriculoperitoneal shunt for hydrocephalus, and may then be candidates for surgical resection.
POTENTIAL RISKS The potential risks of any AVM resection depend on the size, location, and venous drainage of the lesion; the clinical condition and age of the patient; and the experience of the surgeon (8,17). Due to the nature of their location and high incidence of deep venous drainage, brainstem AVMs are associated with greater risks of resection than their supratentorial or cerebellar counterparts. Possible complications of surgery include motor, sensory, and cranial nerve deficits, as well as less common complications such as respiratory or cardiac abnormalities when surgery is within the medulla. Younger patients have a better benefit/risk ratio for resection of AVMs for two reasons. First, the brain of a young patient can better tolerate resection of the vascular malformation and has improved recovery following surgery (18). Second, a younger patient translates into longer AVM-free survival after resection (18).
PREOPERATIVE PREPARATION We routinely use glucocorticoids during resection of all AVMs, including those in the brainstem. Some authors advocate the use of high-dose methylprednisolone 24 hours before treatment (spinal cord injury protocol) in an attempt to maximize the patient’s tolerance to the surgical trauma (12). Prophylactic antibiotics are administered at the start of the operative procedure. Mannitol is used in individual cases if cortical or cerebellar relaxation is required, and a lumbar drain can be used in cases where additional relaxation is required. Brainstem AVMs may bleed into the ventricular system, placing the patients at risk for hydrocephalus. In these circumstances, a ventriculostomy can be placed and is usually maintained during the acute postoperative course. Patients with chronic hydrocephalus as a result of hemorrhage benefit from placement of a ventriculoperitoneal shunt once they have recovered from the initial resection.
ANESTHETIC TECHNIQUE General anesthesia with judicious control of blood pressure is used. Patients are operated under normotensive conditions. Several large-bore IV cannulas are required to allow rapid infusion of fluids and blood products if necessary. An indwelling arterial line is required to monitor blood pressure. Mild brain hypothermia is used, with the core body and brain temperatures dropped to 32–33 C by application of a cooling blanket (Polar Bair; Augustine Medical, Inc., Eden Prairie, Minnesota, U.S.A.). On completion of the procedure and during emergence from anesthesia, the patient’s arterial blood pressure should be controlled to avoid hypertensive episodes, particularly during extubation. Likewise, coughing, bucking, or episodes of venous hypertension should be prevented to decrease the risk of cerebral edema, swelling, or bleeding.
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SURGICAL APPROACHES AND POSITIONING The surgical approach is chosen according to the site where the AVM presents to the pial or ependymal surface. For AVMs in the midline medulla or pons that are situated superficially on the fourth ventricular surface, a midline suboccipital approach is utilized, with the patient positioned prone. If the medullary or pontine AVM is located laterally or anteriorly and presents to one of these pial surfaces, but not to the fourth ventricular surface, the far lateral suboccipital approach is used (Fig. 1). The patient is positioned laterally or supine with the head turned. The midbrain or pontomesencephalic AVMs are exposed through a subtemporal, a subtemporal transpetrosal, or an orbitozygomatic pterional approach if they present to the lateral or anterior surface of these structures. The patient is positioned supine with a shoulder roll and the head turned or operated in the lateral position. Some of the midline pontomesencephalic AVMs can also be approached through a midline suboccipital exposure if they present to the fourth ventricle or the cerebral aqueduct. If the mesencephalic AVMs are located in the tectal plate region, a supracerebellar, infratentorial exposure is used (Figs. 2 and 3). We prefer the sitting position to allow easier positioning of the microscope and facilitate venous drainage. Others use the supracerebellar, infratentorial approach in the Concorde position. Suboccipital Midline Approach Opening and Exposure For AVMs in the midline medulla or pons that are situated superficially on the fourth ventricular surface, the suboccipital midline approach is used. The skin incision is made with a No. 10 blade, and bipolar coagulating forceps are used to cauterize any bleeding scalp vessels. Dissection is carried through the subcutaneous tissue, galea and/or muscle with a No. 15 blade or electrocautery, and retraction exposes the bone. A perforator and craniotome are used to perform the craniotomy. Bone wax is used to control bleeding along the bone edges, dural tack up sutures are placed, and Surgicel is used to line the bone–dural interface. The dura is opened with dural forceps and a No. 15 blade. For AVMs in the midline medulla or pons that present to the fourth ventricular surface, a suboccipital craniotomy, removing the foramen magnum but not usually the posterior arch of C1, is performed. The cerebellar tonsils are retracted, and the inferior midline vermis is sectioned to facilitate exposure to the floor of the fourth ventricle. The AVM can then be visualized on the floor of the ventricle. Venous drainage of these lesions is most commonly through intraventricular ependymal veins into the galenic system (12). Microsurgical Technique Once identified, the AVM is resected in a systematic fashion with the use of the microscope; systemic mean blood pressure is lowered to 60 mmHg. Microsurgical resection is performed under high-power magnification with very fine bipolar irrigating coagulation forceps and using low coagulation power. Feeding arteries are located, coagulated, and cut. Draining veins are often encountered before the feeding arteries are identified and controlled. It is imperative to preserve the venous drainage until all the arterial feeders are transected and the nidus is dissected out. Before transecting a vein, it is wise to first temporarily occlude it with an aneurysm clip and observe the nidus. If the nidus begins to swell or bleed, then the vein must be preserved until the final stages of resection. In some cases, the Charbel Micro-flowprobe1 (Transonic Systems, Inc., Ithaca, New York, U.S.A.) is extremely useful in differentiating feeding arteries from arterialized veins. It is critically important to perform the dissection on the edge of the AVM, leaving any hemosiderin-stained parenchyma intact. Extreme caution must be exercised to avoid excessive coagulation with spread of current to surrounding brainstem tissue. It is safer to dissect close to the AVM, even encroaching on the nidus, rather than risk Figure 1 (Figure on facing page) Arteriovenous malformation (AVM) on the surface of the left medulla in a 56-yearold male who presented with a two-year history of tinnitus in his left ear and mild ataxia. Magnetic resonance imaging scan, coronal view (A). Pretreatment vertebral angiogram showing the AVM fed by branches of the left anterior inferior cerebellar artery and posterior inferior cerebellar artery on lateral (B) and anteroposterior (C) views. Microsurgical resection was performed using a far lateral suboccipital approach. Postoperative vertebral angiograms showing complete AVM resection in lateral (D) and anteroposterior (E) views. Postoperatively, the patient’s tinnitus and ataxia resolved, and he was neurologically normal.
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Figure 2 Midbrain arteriovenous malformation (AVM) in a 44-year-old female who became acutely comatose after AVM hemorrhage. Sagittal T1-weighted magnetic resonance imaging scan (A). After treatment with a ventriculoperitoneal shunt for hydrocephalus, the patient recovered rapidly but had a mild residual left hemiparesis, left facial numbness, and both vertical and horizontal nystagmus. Vertebral angiography showing a midbrain AVM, filling from the right posteriomedial choroidal artery in lateral (B) and anteroposterior (C) views. Microsurgical resection was performed using a supracerebellar infratentorial midline approach. Postoperative vertebral angiography showing complete AVM resection in the lateral (D) and anteroposterior (E) views. The patient had no further neurologic deficits after surgery and continued to improve clinically.
injury to the surrounding brain. It is essential to resect the entire AVM, since any residual has a high chance of rebleeding. Meticulous hemostasis must be maintained throughout the resection. A self-irrigating bipolar coagulation unit is extremely useful during the dissection. Fragile arteries that are resistant to coagulation can be occluded with Sundt micro-AVM clips. Care must be taken at all times to preserve any en-passage vessels. Judicious use of Surgicel, Gelfoam, Avitene, and small pieces of bulk cotton can also be helpful. Venous drainage for brainstem AVMs is
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Figure 3 Brainstem arteriovenous malformation (AVM) in a 32-year-old female presenting with a total of seven intraventricular hemorrhages, which resulted in bilateral partial third nerve palsies and have quadraparesis. Magnetic resonance imaging scan, coronal view (A). Pretreatment vertebral angiogram showing the AVM filling in the anteroposterior (B) and lateral (C) views from the left posterior cerebral artery, left superior cerebellar artery, and feeders off the basilar artery (angiograms show aneurysm clips from prior surgical for clipping of a left posterior communicating artery aneurysm and a basilar apex aneurysm). Three courses of embolization and two courses of stereotactic radiosurgery (one helium ion and one linear accelerator) were performed. Vertebral angiogram after these treatments showing a modest reduction in AVM volume on anteroposterior (D) and lateral (E) views. Partial-microsurgical resection then was performed using a supracerebellar infratentorial approach. Post-surgical resection vertebral angiography showing a significant reduction in the volume of AVM in anteroposterior (F) and lateral (G) views. The patient continued to have bilateral third nerve paresis and weakness in all four extremities following surgery, and she died five months later from sepsis secondary to pneumonia. (Fig. 3E–G on next page.)
deep, usually to the galenic system or the petrosal sinus. Draining veins should be sacrificed last, immediately before the nidus is removed; smaller draining veins may have to be sacrificed during AVM resection to facilitate removal. When working within the fourth ventricle, cotton patties or bulk cotton should be carefully placed along the nonoperative region of the ependyma to prevent accumulation of blood.
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Figure 3 (E–G). (Caption on previous page.)
On completion of AVM resection, the microscope should be used to inspect the resection bed for any signs of residual AVM and to achieve hemostasis. It is important to check for hemostasis at normotension or even mild hypertension. An intraoperative angiogram can be performed to ensure complete resection of the nidus, but due to the lower quality of these intraoperative images, a conventional angiogram in the radiology suite should be performed in the postoperative period. Far Lateral Approach Opening and Exposure For brainstem AVMs located in the lateral or anterior medulla or pons, a far lateral suboccipital approach is used. Meticulous drilling of bone up to the transverse and sigmoid sinuses maximizes exposure. Once the craniotomy is complete, the dura is opened, with care taken to preserve the transverse and sigmoid sinuses. Retractor blades are used to gently retract the cerebellum, expose the brainstem, and allow identification of the AVM. The arachnoid cistern over the lateral brainstem should be widely opened to maximize exposure. Cranial nerves and vascular branches of the basilar and vertebral artery that are not direct AVM feeding vessels are meticulously avoided. Microsurgical Technique Once identified, the lateral brainstem AVM is resected in a systematic fashion with the use of the microscope. Dissection usually proceeds along the lateral border. Feeding arteries are located, cauterized, and transected. The primary pitfall in this situation is the difficulty in identifying which arteries are pure AVM feeders and which are normal arterial channels supplying the brainstem; a careful inspection of the anatomy is required at this point to avoid catastrophic brainstem ischemia (17). Circumferential dissection is performed around the AVM, with care taken to stay within the gliotic plane immediately outside the AVM. Venous drainage for lateral brainstem AVMs is usually deep, and these veins should be sacrificed last after all arterial feeders have been taken. The microscope should be used to inspect the resection bed for any signs of residual AVM, which should be resected if found. Hemostasis is also
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achieved under the microscope. Other aspects of microscopic technique for resection of these AVMs are similar to those described for the suboccipital approach. Infratentorial Supracerebellar Approach AVMs in the tectal plate or posterior mesencephalon are approached using a suboccipital craniotomy, and generally a supracerebellar infratentorial exposure is utilized (Figs. 2 and 3). This approach may require dissection (with bipolar electrocautery and microsuction resection) of the superior cerebellar vermis and superior medullary velum. The precentral cerebellar vein is usually sacrificed to improve exposure. Retractor blades are used to gently retract the cerebellar hemispheres and maximize exposure. Care must be taken to avoid injury to the vein of Galen, the two draining veins of Rosenthal, and the straight sinus. Hemostasis is maintained at all times to reduce blood clots within the fourth ventricle to minimize postoperative hydrocephalus. Once the AVM location is identified, microsurgical resection proceeds as described previously. Subtemporal and Orbitozygomatic Approach Anterior and anterolateral pontomesencephalic AVMs are generally exposed through either a subtemporal or an orbitozygomatic approach. After the craniotomy is completed, the dura is reflected. For subtemporal approaches, retractors are used to elevate the temporal lobe to expose the tentorial ring. The tentorium can be divided and/or the petrosal bone drilled down extradurally if additional exposure is needed. For the orbitozygomatic approach, the sylvian fissure is opened under the microscope and the frontal and temporal lobes are retracted to expose the anterior mesencephalon. Once the AVM location is identified, careful bipolar electrocautery is used to resect the AVM. Microdissection is performed similarly to that for other brainstem AVMs. The numerous perforating arteries from the internal carotid artery and the middle cerebral artery should be avoided if they do not directly feed the AVM. Venous drainage is toward either the cavernous sinus or the petrosal sinus. CLOSURE TECHNIQUES AND POSTOPERATIVE MANAGEMENT Meticulous hemostasis is obtained in the resection bed of the AVM, and a final inspection is performed to ensure that the entire malformation has been completely removed. Transient induced mild hypertension is used to test hemostasis, and the resection bed is then lined with Surgicel. The dura is closed in the standard fashion with 4–0 nylon suture, and the bone is replaced to complete the craniotomy. The scalp incision is closed in layers, with approximation of the subcutaneous layer using 3–0 Dexon sutures, and skin with staples. A sterile head dressing is applied. In the intensive care unit, hypotension should be maintained for 48 hours to prevent rebleeding. The mean arterial pressure is maintained between 65 and 75 mmHg for the first 24 hours and relaxed to 75–85 mmHg for the second 24 hours. For cases that involve significant bleeding or swelling, the mean arterial pressure can be maintained lower (60–65 mmHg) for 48 to 72 hours. Coagulation should be monitored and corrected if abnormal. A routine postoperative computed tomography (CT) scan is performed to evaluate for edema within the posterior fossa, any hydrocephalus, and the extent of residual blood in the resection bed. Any changes in neurologic examination should be evaluated with emergent CT. A postoperative angiogram is obtained in the first week after surgery unless an intraoperative angiogram was performed with adequate angiographic resolution to confirm complete AVM resection. SPECIAL PERIOPERATIVE EQUIPMENT/TECHNIQUES Intraoperative Monitoring Electrophysiologic monitoring during resection of AVMs is a valuable intraoperative aid and improves clinical results (19). For brainstem AVMs, we have found both somatosensory evoked potential (SSEP) and brainstem auditory evoked potential (BAEP) to be useful and have found further benefit from mapping brainstem motor nuclei. Thus, monitoring for brainstem surgery routinely consists of bilateral SSEPs, bilateral BAEPs, and bilateral fifth nerve, seventh nerve, eleventh nerve, and twelfth nerve motor function. Continuous monitoring of
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these sensory pathways and motor nuclei allows early detection of excessive retraction or manipulation of critical structures and permits more precise planning of the circumferential dissection of brainstem AVMs. Frameless Image-Guided Stereotaxis Intraoperative stereotaxis helps to localize portions of the deep AVMs not presenting directly to the ependymal or pial surface. The Cosman-Roberts-Wells (CRW) frame was previously used but was found to be somewhat cumbersome. We routinely use the Medtronics Stealth Station, which maintains a precision of a few millimeters. This stereotactic approach helps to confirm complete resection of all components of larger brainstem AVMs that may have irregular configurations. Mild Hypothermia Mild brain hypothermia can be used for cerebroprotection. The core body and brain temperature is reduced to 33 C by applying a cooling blanket or intravascular controlled temperature system (Innercool System). This degree of mild brain hypothermia has been shown to provide excellent protection against experimental ischemic and traumatic cerebral injury (20,21). We have now used mild brain hypothermia in over 2000 patients undergoing intracranial surgery for vascular malformations, aneurysms, and tumors. Under operative conditions of AVM resection, this hypothermic technique is safe, feasible, and economical with good clinical outcomes overall (21). Intraoperative Angiogram Intraoperative angiograms became possible with the advent of high-resolution portable angiography and allow the surgeon to determine the completeness of AVM resection. If residual AVM is present, the surgeon can complete the resection before wound closure. At least two studies have shown that patients are not protected from hemorrhage after partial resection of AVMs (22,23), so complete resection remains the goal for all AVMs. We routinely use intraoperative angiography for many brainstem vascular malformations to confirm complete resection. STEREOTACTIC RADIOSURGERY The eloquent location of brainstem AVMs and their generally small, compact nidus make them excellent candidates for stereotactic radiosurgery (12,16). The primary drawback to this form of treatment is the latent period between radiosurgery and AVM obliteration. Patients with asymptomatic brainstem AVMs or deep AVMs completely within the brainstem parenchyma, as well as those patients whose medical condition precludes surgical treatment are optimal candidates for radiosurgery (Fig. 4). Additionally, patients with large AVMs of the brainstem may have less risk of morbidity when treated with stereotactic radiosurgery as opposed to microsurgical resection. Patients with hemorrhages (especially multiple), progressive neurologic deficits, and those for whom radiosurgery fails are candidates for treatment with surgery as long as their lesions are superficial and surgically accessible, and the operative risk is acceptable. Due to the relatively uncommon occurrence of brainstem AVMs, no large radiosurgical series exists that reports outcome. However, there is no reason to believe that brainstem AVMs would respond to radiosurgery differently from their supratentorial counterparts. Stereotactic radiosurgery also plays a role in the multimodality treatment of brainstem AVMs (Fig. 3). Larger AVMs can be treated initially with radiosurgery; and if the follow-up angiograms several years later indicate a smaller AVM, then the malformation may be easier to resect with surgery (15). Alternatively, residual brainstem AVMs after surgical resection or embolization procedures can be treated with radiosurgery; results are generally good due to the relatively small size of these malformations. EMBOLIZATION Preoperative embolization can be a useful adjunct in the treatment of brainstem AVMs (Fig. 3). The primary difficulty with brainstem AVMs of the anterior basis pontis and the medullary and pontine floor of the fourth ventricle is that they are often supplied by small perforating
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Figure 4 Midbrain arteriovenous malformation (AVM) in an 11-year-old female who presented with a six-month history of severe headaches and left eye strabismus. Magnetic resonance imaging scan, sagittal view (A). Vertebral angiography showing the AVM filling from branches off of the left posterior cerebral and superior cerebellar arteries in lateral (B) and anteroposterior (C) views. The patient was treated with linear accelerator stereotactic radiosurgery. Vertebral angiography 22 months after treatment showing complete obliteration of the AVM in lateral (D) and anteroposterior (E) views. The patient’s strabismus resolved, and she remained neurologically normal.
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arteries that arise from parent vessels at right angles (12), and they are thus difficult if not impossible to cannulate. Arterial feeders to brainstem AVMs may also supply important brainstem structures or cranial nerves. In some cases, feeding vessel cannulation can be achieved, thereby allowing embolization of the AVM. Brainstem AVMs of the lateral pons generally derive their arterial supply from enlarged branches of the anterior inferior cerebellar artery (12), and may be easier to embolize. Residual brainstem AVMs after embolization can be treated with either microsurgery or stereotactic radiosurgery. CLINICAL OUTCOME Stanford Series Over the last 12 years, 28 patients with brainstem AVMs have been treated. These malformations were located in the midbrain (16), pons (five), midbrain and pons (four), medulla (two), and midbrain, pons, and medulla (one). The clinical status of these patients at presentation is shown in Table 1, with many patients having debilitating neurologic deficits. Many of these brainstem AVMs were treated with a multimodality approach to minimize the risk of morbidity; treatment modalities are shown in Table 2. In general, small infratentorial brainstem AVMs are treated either with surgery (if they are pially based or in a subarachnoid cistern) or with stereotactic radiosurgery alone. Occasionally, a small brainstem AVM that is supplied by a single arterial feeder may be cured by embolization. For moderate- to large-size AVMs, embolization is performed first to reduce the size and extent of blood flow through the malformation, followed by either microsurgical resection or stereotactic radiosurgery. In cases of AVMs in which there is residual AVM after initial embolization and either surgery or radiosurgery, additional treatment in the form of further surgical resection (i.e., resection of residual malformation after embolization and radiosurgery) or stereotactic radiosurgery is utilized. The post-treatment long-term clinical results are shown in Table 1, with many patients improving from their status at presentation. Only two patients in this series died, one from rehemorrhage after a single course of embolization before any further treatment, and another from complications of surgery to resect a residual malformation after three courses of embolization and two stereotactic radiosurgery treatments. Of the 21 post-treatment patients with angiography available for review and who are at least three years out from radiosurgery if treated in part by that modality, 13 had a complete angiographic cure, four had 75% to 90% obliteration, three had 50% to 75% obliteration, and one (following radiosurgery) had no obliteration. Other Published Series There are few published series that consist exclusively of patients with brainstem AVMs. Most authors include these vascular malformations in larger series of posterior fossa vascular malformations. Solomon and Stein published a series of 12 patients with brainstem AVMs in which nine were treated surgically, and complete resection was achieved in eight (1). Two patients (22%) were worse from surgery, but there were no deaths. Chyatte reported seven patients with AVMs of the brainstem; six were treated surgically and complete resection was achieved in five (4). There were no operative deaths and no permanent morbidity. Kashiwagi et al. reported a series of five patients with brainstem AVMs; three were treated surgically and all three improved postoperatively (24). Drake et al. reported a series of 66 posterior fossa AVMs treated with surgical resection, with 15 located in the brainstem (5). Only two brainstem AVMs were completely resected, and four patients died after exploration of their AVMs. Batjer and Samson reported a series of 32 posterior fossa AVMs of which four Table 1 Pre-Treatment and Post-Treatment Clinical Grades for 28 Patients with Brainstem Arteriovenous Malformations Treated at Stanford
Pre-treatment Post-treatment a
Excellenta
Goodb
Poor c
Deceased
11 17
7 8
10 1
0 2
Absent or minimal neurological deficits. Able to function independently. Moderate neurological deficits. Requires minimal to some assistance. c Severe neurological deficits. b
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Table 2 Treatment Modality for 28 Patients with Brainstem Arteriovenous Malformations Treated at Stanford Treatment modality Surgery Stereotactic radiosurgery Embolization þ radiosurgery þ surgery Embolization þ radiosurgery Radiosurgery þ surgery Embolization
No. of Patients 6 13 4 1 2 2a
a
One patient died from rehemorrhage after embolization before any further treatment; the other patient achieved an angiographically demonstrated cure after a single course of embolization.
were located in the brainstem (6). The outcome of these four patients after surgery is difficult to determine because all patients were grouped together; one patient died in the immediate postoperative period. COMPLICATIONS AND COMPLICATION AVOIDANCE Hemorrhage—Postoperative Control of Blood Pressure The most devastating complication is perioperative hemorrhage, which, fortunately, is extremely rare. This complication can be due to either lack of adequate hemostasis or failure to completely resect the AVM, and it emphasizes the importance of removing the entire malformation, including any irregular extensions. Perioperative hemorrhage can be minimized by careful inspection and hemostasis of the resection bed after removal of the AVM and by a short period of induced hypertension after resection but before closure to check for breakthrough bleeding. Imageguided navigational systems can also aid in confirming complete AVM resection. Hydrocephalus Postoperative hydrocephalus is a complication in patients with significant intraventricular blood. Any fourth ventricular clot secondary to prior hemorrhage should be aspirated before AVM resection. In addition, meticulous hemostasis should be maintained throughout the procedure to minimize acute ventricular blood. If significant intraventricular blood is present, a ventriculostomy can be placed before closure. Chronic hydrocephalus is treated with a ventriculoperitoneal shunt. SUMMARY Superficial brainstem AVMs can be resected in some cases with acceptable risks of morbidity and mortality. With careful preoperative planning and operative positioning, meticulous surgical technique, and compulsive perioperative management, excellent results can be obtained. A fundamental knowledge of the anatomy of midline and deep neurological structures is critical to resect these lesions with minimal risk of morbidity. For deep or complex AVMs of the brainstem, multimodality treatment wih embolization, stereotactic radiosurgery, and microsurgery may produce the optimal results. ACKNOWLEDGMENTS This work was supported in part by funding from Bernard and Ronni Lacroute, and Russell and Elizabeth Siegelman. We also thank Beth Hoyte for assistance with the figures. REFERENCES 1. Solomon RA, Stein BM. Management of arteriovenous malformations of the brainstem. J Neurosurg 1986; 64:857–864. 2. Mohr JP. Neurologic manifestations and factors related to therapeutic decisions. In: Wilson CB, Stein BM, eds. Intracranial Arteriovenous Malformations. Baltimore: Williams and Wilkins, 1984:1–11.
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3. Morello G, Borghi GP. Cerebral angiomas. A report of 154 personal cases and a comparison between the results of surgical excision and conservative management. Acta Neuorchir 1973; 28:135–155. 4. Chyatte D. Vascular malformations of the brainstem. J Neurosurg 1989; 70:847–852. 5. Drake CG, Friedman AH, Peerless SJ. Posterior fossa arteriovenous malformations. J Neurosurg 1986; 64:1–10. 6. Batjer H, Samson D. Arteriovenous malformations of the posterior fossa. Clinical presentation, diagnostic evaluation, and surgical treatment. J Neurosurg 1986; 64:849–856. 7. Stahl SM, Johnson KP, Malamud N. The clinical and pathological spectrum of brain-stem vascular malformations. Long-term course stimulates multiple sclerosis. Arch Neurol 1980; 37:25–29. 8. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 9. Gewirtz RJ, Steinberg GK. AVMs of the posterior fossa: evaluation and management. Contemp Neurosurg 1996; 18:1–6. 10. Lewis AI, Tew JM Jr. Management of thalamic-basal ganglia and brain-stem vascular malformations. Clin Neurosurg 1994; 41:83–111. 11. Perret G, Nishioka H. Report on cooperative study of intracranial aneurysms and subarachnoid hemorrhage. Section VI: Arteriovenous malformations. Analysis of 545 cases of cranio-cerebral arteriovenous malformations and fistulae report to cooperative study. J Neurosurg 1966; 25:467–490. 12. Samson DS, Batjer HH. Posterior fossa arteriovenous malformations. In: Carter LP, Spetzler RF, Hamilton MG, eds. Neurovascular Surgery. New York: McGraw Hill, Inc., 1995:1005–1015. 13. Betti OO, Munari C, Rosler R. Stereotactic radiosurgery with the linear accelerator: treatment of arteriovenous malformations. Neurosurgery 1989; 24:311–321. 14. Kjellberg RN, Hanamura T, Davis KR, Lyons SL, Adams RD. Bragg-peak proton-beam therapy for arteriovenous malformations of the brain. N Engl J Med 1983; 309:269–274. 15. Steinberg GK, Chang SD, Levy RP, Marks MP, Frankel K, Marcellus M. Surgical resection of large incompletely treated intracranial arteriovenous malformations following stereotactic radiosurgery. J Neurosurg 1996; 84:920–928. 16. Steinberg GK, Fabrikant JI, Marks MP, et al. Stereotactic heavy-charged-particle Bragg-peak radiation for intracranial arteriovenous malformations [see comments]. N Engl J Med 1990; 323:96–101. 17. Steinberg GK, Marks MP. Intracranial arteriovenous malformations: therapeutic options. In: Batjer HH, Caplan LR, Friberg L, Greenlee RG, Kopitnik TA, Young WL, eds. Cerebrovascular Disease. Philadelphia: Lippincott-Raven, 1997:727–742. 18. Heros RC, Tu Y-K. Unruptured arteriovenous malformations: a dilemma in surgical decision making. Clin Neurosurg 1986; 33:187–212. 19. Chang SD, Lopez JR, Steinberg GK. The use of electrophysiologic monitoring during resection of arteriovenous malformations and angiographically occult vascular malformations. J Neurosurg 1997; 86:400A. 20. Maier CM, Ahern KV, Cheng ML, Lee JE, Yenari MA, Steinberg GK. Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and inflammation. Stroke 1998; 29:2171–2180. 21. Steinberg GK, Grant G, Yoon EJ. Deliberate hypothermia. In: Andrews RJ, ed. Intraoperative Neuroprotection. Baltimore: William and Wilkins, 1996:65–84. 22. Drake CG. Cerebral arteriovenous malformations: considerations for and experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–208. 23. Forster DMC, Steiner L, Hakanson S. Arteriovenous malformations of the brain. A long term clinical study. J Neurosurg 1972; 37:562–570. 24. Kashiwagi S, van Loveren HR, Tew JM Jr., Wiot JG, Weil SM, Lukin RA. Diagnosis and treatment of vascular brain-stem malformations. J Neurosurg 1990; 72:27–34.
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Intraoperative and Postoperative Angiography Michael A. Lefkowitz Long Island Neurological Associates, New Hyde Park, New York, U.S.A.
Fernando Vinuela Department of Radiological Sciences, Endovascular Therapy Service, UCLA School of Medicine, University of California–Los Angeles, Los Angeles, California, U.S.A.
Neil Martin Division of Neurosurgery, UCLA School of Medicine, University of California–Los Angeles, Los Angeles, California, U.S.A.
INTRODUCTION Cerebral angiography is one of the oldest tools in the neurosurgical armamentarium, yet technological and treatment advances have allowed it to become an increasingly valuable asset in the modern cerebrovascular operating room. In addition, the treatment options available for the management of arteriovenous malformations (AVMs), ranging from open surgery to endovascular therapy to stereotactic radiosurgery, have mandated the need for accurate intraprocedural and postprocedural studies. Egas Moniz first described cerebral angiography in 1934. In his monograph, L’Angiographie Cerebral: Ses Applications et Resultants en Anatomie, Physiologie et Clinique, Moniz presented five cases of cerebral AVMs, thereby becoming the first physician to document the angiographic appearance of this lesion (1). In 1960, Leussenhop and Spence described a procedure that was both the first intraoperative cerebral angiogram and the first embolization of a cerebral AVM (2). The patient, a 47-year-old woman, presented after the rapid onset of headache, drowsiness, and expressive dysphasia. Physical examination revealed the presence of expressive dysphasia, a right hemiparesis, and a systolic bruit over the left eye. The cerebral angiogram demonstrated a large AVM in the left sylvian region. During the procedure, the left common carotid artery bifurcation was exposed surgically, and four spheres of methyl methacrylate measuring between 2.5 and 4.2 mm in diameter were introduced with successful subtotal embolization of the malformation. After the treatment, the patient’s dysphasia and hemiparesis resolved. Follow-up angiography showed excellent filling of normal vessels and only a small remnant of the malformation. In 1996, Loop and Foltz were the first to report the use of angiography during a craniotomy for resection of an AVM (3). Intraoperative angiography was performed via direct puncture of the carotid artery, and imaging was obtained with rapid serial-film cassettes. Bauer first used a portable C-arm for intraoperative angiography in 1984 (4). Portable digital subtraction angiography (DSA) in the operating room was first used by Foley et al. in 1986 (5). DSA represented an advance because it allowed for immediate image processing, subtraction of bony artifact, roadmapping, and the more efficient use of intravascular contrast. INTRAOPERATIVE ANGIOGRAPHY Rationale Indications are numerous for the use of intraoperative angiography in the treatment of AVMs. First and foremost, the technique allows the surgeon to verify whether or not the surgical objective of nidus excision has been met. If residual nidus is identified, it can be removed during the same operation. The need for an additional operation as well as the risk of postoperative hemorrhage from a residual nidus is thereby eliminated. The latter issue is
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important because studies suggest that incompletely resected AVMs are at continued risk of hemorrhage, at a rate that is probably no different from the natural history of the lesion (6,7). By allowing for the rapid identification or exclusion of nidus during a surgical procedure, intraoperative angiography directs the surgeon to the nidus and prevents the need for unnecessary surgical manipulation in searching for nidus in locations where residual AVM is not present (8). In addition to allowing for the determination of the presence or absence of residual nidus during surgery, intraoperative angiography allows for the distinction between AVM vessels and vessels ‘‘en passage,’’ the normal parenchymal vessels that pass through an AVM nidus. It may also assist in the localization of small, deeply situated malformations. Current portable DSA units allow the visualization of vessels as small as 400 mm in diameter, approximately the diameter of the lenticulostriate arteries (4). The technique may also help to identify technical errors other than incomplete nidus resection, such as inadvertent normal vessel occlusion or compromise. Finally, intraoperative angiography may assist the surgeon by providing the adjunct of intraoperative embolization. Review of the Literature Multiple studies have reported on the usefulness of intraoperative cerebral angiography for AVMs in the last three decades. These studies report on the use of diagnostic intraoperative angiography in the treatment of 330 AVMs. Table 1 summarizes the results of these studies. For all the studies reported, the results of the intraoperative angiogram altered the management of the case an average of 15% of the time (range: 5.6–57%). Not all of the reported series compared the results of the intraoperative angiogram with a conventional postoperative angiogram. In those studies where such a comparison was described, a false negative result was obtained 4.4% of the time. In these situations, the intraoperative angiogram failed to demonstrate residual nidus that was ultimately detected on the postoperative angiogram. A false positive result was reported in 1.7% of the studies performed. In these instances, the intraoperative angiogram was suggestive of residual nidus that was not seen on the postoperative angiogram. The reported technical failure rate for intraoperative cerebral angiography was 2.5%. Four technical failures were described: two occurred because of an inability to selectively catheterize a desired vessel, one occurred because the patient had been placed on a radiopaque table, and one occurred because of an electrical power failure. The reported complication rate was 3.1%. A total of 10 complications were reported: in one patient, a cerebral embolus resulted in occlusion of the anterior branch of a left middle cerebral artery and a permanent mild dysphasia. This was the only permanent neurologic deficit attributed to an intraoperative cerebral angiogram. In another patient, a femoral artery thrombus developed in a femoral artery sheath that was also used for pressure monitoring and was inadvertently flushed with heparinized saline during surgery. This patient also developed a femoral artery occlusion at the site of sheath insertion after a subsequent surgery for AVM excision. In this instance, the femoral artery was presumably damaged during sheath insertion. In the earliest study, two patients developed cerebral edema requiring termination of the surgery after cerebral angiography. In each instance, the patient received less than 25 mL of contrast agent. Technical Aspects Currently available portable DSA systems consist of three primary components: the C-arm fluoroscope which consists of a radiation source and an image intensifier, the digital processing and storage unit, and the video monitor. Typical systems allow for fluoroscopy with last-image hold and real-time digital image acquisition with playback in normal, slow, or frame-by-frame modes. Provisions should be available to make hard copies for permanent records. Anticipating the need for intraoperative angiography can save time and effort. Although the technical aspects of the procedure are not difficult, they can become inconvenient and time consuming within the confines of the operating room. Preoperative placement of a 5 French femoral sheath is desirable, as occasionally the patient will be in a position that is awkward for intraoperative sheath placement, such as the prone, lateral, and sitting positions. The presence of a femoral sheath should not interfere with most surgical positions. Femoral sheaths are available that allow as much as 60 of hip flexion. Another reason for preoperative placement of a femoral sheath is that hypotension may be induced in some patients who are undergoing
12
48
5
39
13
18
21
15
93
25
5
18
330
Hieshima et al. (10)
Martin et al. (11)
Meguro et al. (12)
Barrow et al. (8)
Anegawa et al. (13)
Derdeyn et al. (14)
Pietila et al. (15)
Ghosh et al. (16)
Vitaz et al. (17)
Munshi et al. (18)
Hashimoto et al. (19)
Yanaka et al. (20)
Total
49 (15)
1 (5.6)
0 (0)
2 (8.0)
8 (8.6)
3 (20)
4 (19)
5 (28)
3 (23)
7 (18)
1 (20)
5 (10)
3 (25)
3 (27)
4 (57)
Management Altered by Angiogram Results (%)
12/269 (4.4)
0/17 (0)
0/5 (0)
3/17 (18)
3/76 (3.9)
0/3 (0)
0/21 (0)
2/18 (11)
2/13 (100)
1/39 (2.6)
N/R
1/48 (2.0)
0/12
N/R
N/R
False Negative (%)
3/174 (1.7)
0/17 (0)
N/R
N/R
N/R
0/15 (0)
0/21 (0)
0/18 (0)
0/13 (0)
0/30 (0)
N/R
3/48 (6.3)
0/12 (0)
N/R
N/R
False Positive (%)
4/161 (2.5)
0/18 (0)
N/R
N/R
N/R
N/R
N/R
2/18 (11)
0/13 (0)
0/34 (0)
N/R
0/48 (0)
2/12 (17)
0/11 (0)
0/7 (0)
Technical Failures (%)
Note: For total calculations, the denominator used to calculate the percentages was based only on those cases where the particular event was reported. Abbreviation: N/R, not reported.
7
11
Bauer et al. (4)
No. of Angiograms
Smith et al. (9)
Reference
Table 1 Intraoperative Angiogram Clinical Series
10/325 (3.1)
0/18 (0)
1/5 (20)
0/25 (0)
3/93 (3.1)
1/15 (6.7)
0/21 (0)
0/18 (0)
0/13 (0)
0/39 (0)
N/R
3/48 (6.3)
0/12 (0)
0/11 (0)
2/7 (29)
Complications (%)
30–120
N/R
N/R
N/R
N/R
43
N/R
N/R
N/R
30–60
N/R
45–60
60–120
N/R
N/R
Time for Study (min)
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AVM resection to minimize intraoperative bleeding. Hypotension may make it difficult to palpate the femoral pulse to insert an arterial sheath, especially if the patient is in a position other than the supine position. If a femoral artery sheath is to be placed, the anesthetist may wish to use this line for intraoperative monitoring. If this is the case, the sheath must be flushed with pressurized heparinized saline (1000 IU heparin/L of saline infused at 3–5 mL/hr) to prevent thromboembolic complications to the lower extremity. However, the femoral sheath may be unavailable for continuous monitoring during the performance of the angiogram. The operating room should be arranged to allow adequate space for placement of the C-arm fluoroscope near the operating table. Easily moved Mayo stands should be used for surgical instrument trays rather than large instrument tables that may be draped in conjunction with the patient. Finally, cables and cords in the path of the C-arm and digital image processor should be taped to the floor so that these units, which are both unwieldy to move, may be maneuvered about the operating room without excessive disruption and inconvenience. The X-ray technologist should be experienced in the performance of intraoperative angiograms because special skills are required for the procedure. Minimization of the placement of radiopaque objects near the anticipated angiographic site as well as near the patient’s chest, neck, and head (e.g., connection box for electroencephalography and somatosensory evoked potential electrodes, anesthesia cables and cords, surgical retractors, and towel clamps) will improve image quality and reduce the amount of time required to obtain useful images. A radiolucent operating room table facilitates placement of the angiography catheter into the aortic arch. A radiolucent head holder/operating room table attachment system is useful in this regard (21). Systems are commercially available in which all components of the head holder are radiolucent except the skull fixation points. For the performance of an intraoperative angiogram, it is recommended that highdensity contrast (300 osmolarity nonionic) be used for maximal vessel visualization on the portable fluoroscope (22). Because the performance of an intraoperative angiogram may disrupt the aseptic technique of a craniotomy, care must be taken to maintain sterile conditions during the procedure (4). In those situations where an angiogram is being performed on a malformation that is visible in the operative field, no localizing markers should be necessary. However, when an angiogram is being performed either to localize a deep malformation before corticotomy or to look for residual nidus after resection, it is useful to place an opaque marker close to the presumed location of the vessel and finding, by angiography, precisely where the vessel is located (23).
Study Interpretation Because of positioning limitations, standard angiographic views are rarely obtained with intraoperative studies. As a result, the intraoperative studies usually have a different projection from that of their preoperative counterparts. Close attention must be given to the study orientation when interpreting the images. Because the most important study interpretation will occur at the time of the performance of the angiogram, all pertinent preoperative studies must be available for review in the operating room. Limitations in equipment resolution also mandate caution in interpretation of intraoperative studies. Residual nidus should not be identified by parenchymal blush alone because this finding cannot reliably be distinguished from normal tissue with portable equipment. It is necessary to visualize an early draining vein along with the parenchymal blush in order to diagnose residual nidus (14). Parenchymal blush in the absence of an early draining vein may be due to hyperperfusion in adjacent normal vessels (11). These scenarios are the likely cause of false positive results for the intraoperative studies previously described.
Figure 1 (Figure on facing page) Confirmatory operative angiogram. Cerebral angiogram [right internal carotid artery (A) and left vertebral artery (B) injections, lateral projections] demonstrating arteriovenous malformation arising from the pericallosal and posterior cerebral arteries. Postembolization cerebral angiogram [right internal carotid artery (C) and left vertebral artery (D) injections, lateral projections]. Intraoperative cerebral angiogram [right internal carotid artery (E) and left vertebral artery (F) injections, lateral projections] demonstrating complete excision of nidus. Postoperative cerebral angiogram [right internal carotid artery (G) and left vertebral artery (H) injections, lateral projections] confirming complete excision of nidus.
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Figure 1 (Caption on facing page)
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Illustrative Cases Confirmatory Operative Angiogram A 23-year-old woman was diagnosed with an AVM after sustaining a single seizure. Cerebral angiography demonstrated a Spetzler–Martin Grade II (24) AVM with feeding arteries arising from the right pericallosal artery and parieto-occipital branches of the right posterior cerebral artery (Fig. 1A and B). The plan of treatment was to embolize the lesion and then attempt microsurgical resection. Embolization of the lesion resulted in an approximately 80% reduction in the size of the nidus of the malformation (Fig. 1C and D). The malformation was resected via a right parieto-occipital craniotomy under general anesthesia. An intraoperative cerebral angiogram demonstrated no evidence of residual AVM (Fig. 1E and F). This finding was confirmed by the postoperative conventional angiogram (Fig. 1G and H). Aneurysm Associated with AVM A 43-year-old woman with a known right frontoparietal/basal ganglia Spetzler–Martin Grade III AVM sustained three subarachnoid hemorrhages over a two-month period. The patient had undergone partial embolization of the AVM followed by radiosurgery in the year before the hemorrhages. Figure 2A and B demonstrates the lesion with feeder arteries arising from the anterior cerebral, middle cerebral, and lenticulostriate arteries. A small feeding artery aneurysm arises from the lenticulostriate artery. Because the recent hemorrhages were subarachnoid in nature, it was thought that they might be due to rupture of the feeding artery aneurysm. Because the AVM was close to the motor cortex and basal ganglia and the patient was unwilling to accept the neurologic deficit that might be associated with microsurgical resection, an attempt was made to embolize the feeding artery giving rise to the flow-related aneurysm. Because attempts to catheterize the lenticulostriate artery were unsuccessful, a decision was made to attempt to trap the feeding artery aneurysm surgically. The aneurysm was exposed via a right frontotemporal craniotomy and clipped. An intraoperative angiogram verified that the aneurysm had been trapped (Fig. 2C and D). Trapping of the aneurysm was confirmed on a postoperative conventional angiogram (Fig. 2E and F). The patient made an excellent recovery. Residual AVM Nidus Detected on Intraoperative Angiogram A 45-year-old man developed progressive ataxia. Imaging studies including cerebral angiography demonstrated a Spetzler–Martin Grade III AVM of the right cerebellar hemisphere (Fig. 3A). During surgical resection, an intraoperative angiogram (Fig. 3B) revealed residual nidus arising from the superior cerebellar artery. After further surgical resection, a repeat intraoperative angiogram demonstrated no residual nidus (Fig. 3C). False Negative Intraoperative Cerebral Angiogram A 32-year-old-man sustained a thalamic hemorrhage. Imaging studies including cerebral angiography demonstrated a Spetzler–Martin Grade III thalamic AVM supplied by thalamo-perforating arteries and the medial posterior choroidal artery (Fig. 4A). The AVM was approached by the posterior transcallosal approach, and an intraoperative angiogram revealed no evidence of residual nidus or early draining vein (Fig. 4B). However, a conventional postoperative angiogram did reveal a small residual nidus and early draining vein (Fig. 4C), which were successfully removed during a second procedure. Alternatives to Intraoperative Angiography Technical advances in several areas of intraoperative imaging have provided alternatives to intraoperative angiography. One area involves the use of color Doppler flow ultrasound (25,26). One advantage of this relatively noninvasive technique is that it may be used continuously throughout the case with little difficulty. The technique may be used at the beginning of a case for localization of lesions that are not visible on the cortical surface and may be used at the end to inspect the deep aspects of the resection cavity for unseen nidus. Deep lesions with niduses of 6 mm in diameter have been identified with this technology. However, poor resolution, depth limitation to 4–5 cm, and the relatively large size of the scanning probe face limit the effectiveness of this technique. Other modalities that may be useful in the resection of AVMs include frameless stereotaxis and microscope-linked systems that fuse diagnostic images with the images of the operative field seen through the microscope. Although these systems are becoming increasingly easy to
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Figure 2 Aneurysm associated with arteriovenous malformation (AVM). Cerebral angiogram [right internal carotid artery injection, lateral (A) and oblique (B) projections] demonstrating an AVM with feeder arteries arising from the anterior cerebral, the middle cerebral, and the lenticulostriate arteries. A small feeding artery aneurysm is located on one of the lenticulostriate vessels. Intraoperative cerebral angiogram [right internal carotid artery injection, lateral (C) and oblique (D) projections] demonstrating successful trapping of the feeding artery aneurysm. Postoperative cerebral angiogram [right internal carotid artery injection, lateral (E) and anteroposterior (F) projections] also demonstrating successful trapping of the feeding artery aneurysm.
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Figure 3 Residual nidus detected on intraoperative angiogram. (A) Cerebral angiogram (right vertebral artery injection, oblique projection) demonstrating cerebellar arteriovenous malformation. (B) Intraoperative cerebral angiogram (right vertebral artery injection, oblique projection) demonstrating residual nidus (arrows) arising from superior cerebellar artery. (C) Later intraoperative cerebral angiogram (right vertebral artery injection, oblique projection) demonstrating resection of the nidus.
use, they are expensive and do not offer the real-time, dynamic visualization of AVMs that is so important during resection. Another technique that might be effective in the intraoperative management of AVMs involves the use of intraoperative magnetic resonance imaging (MRI). This process would enable the real-time intraoperative visualization of the nidus of an AVM, although it would not allow particularly useful visualization of the feeding arteries and the draining veins. This process would require an open-field MRI situated in a room suitable for surgery and would require the use of nonferromagnetic instruments during surgery.
INTRAOPERATIVE EMBOLIZATION In the past, direct intraoperative catheterization and embolization of AVM feeding arteries was performed for vessels that were inaccessible by conventional angiographic techniques (10,27,28). However, advances in catheter and guidewire technology have reduced the need for intraoperative embolization of AVMs. Nevertheless, it remains an additional tool for the treatment of AVMs in specific situations. When intraoperative embolization was performed
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Figure 4 False negative intraoperative cerebral angiogram. (A) Cerebral angiogram (left vertebral artery injection, lateral projection) demonstrating thalamic arteriovenous malformation arising from thalamo-perforating arteries and the medial posterior choroidal artery. (B) Intraoperative cerebral angiogram (left vertebral artery injection, lateral projection) demonstrating no evidence of residual nidus or early draining vein. (C) Postoperative conventional cerebral angiogram (left vertebral artery injection, lateral projection) demonstrating residual nidus and an early draining vein (arrows).
as definitive therapy, either by itself or as an adjunct to microsurgery, it was successful in 9/24 cases (38%). Intraoperative embolization has also been used in an attempt to ameliorate a specific symptom such as weakness, seizures, or headaches that were related to an AVM considered to be surgically unresectable (29,30). Intraoperative embolization can be effective, but the technique has unpredictable success and a high rate of morbidity. Table 2 summarizes the results of several intraoperative embolization series. POSTOPERATIVE ANGIOGRAPHY Rationale A postoperative cerebral angiogram is indicated after every resection of an AVM. The risk/ benefit ratio for postoperative cerebral angiography clearly favors its use. Several large studies of the complications of cerebral angiography have demonstrated that the risk of permanent neurological deficit ranges from 0.3% to 0.5% (32–36). Studies of the natural history of AVMs suggest that the incidence of hemorrhage ranges from 2% to 4% per year (37,38). In these studies, the risk of mortality or major morbidity after a hemorrhage ranged from 28% to
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Table 2 Intraoperative Embolization Clinical Series Reference
No. of Cases
Embolic Agents
Girvin et al. (30)
14
IBCA
Van Alphen et al. (27)
19
IBCA
Hieshima et al. (10)
5
Molsen et al. (28)
19
Jizong et al. (31)
50
PVA, IBCA
Gelfoam, PVA, Histoacryl, Balloons IBCA
Outcomes
Complications
Headaches in 2 pts, " motor strength # Motor strength in 4 pts, language in 3 pts, # seizures in 2 pts impairment in 1 pt, " seizures in 1 pt 100% embolization/resection in 4 pts, 8 pts had # motor/speech/sensory 100% embolization in 3 pts, 90– function, but 6 of these pts also 99% embolization in 5 pts, < 90% had # in seizures embolization in 7 pts None Complete resection in 2 pts, anticipated subtotal resection in 3 pts N/R None
Complete resection in all patients
Hemiparesis in 6 pts, aphasia in 3 pts
Abbreviations: PVA, polyvinyl alcohol; IBCA, isobutyl-2-cyanoacrylate; N/R, not reported; pt(s), patient(s).
52%. The limited studies of patients with incompletely resected AVMs demonstrate that the risk of morbidity and mortality from hemorrhage from a residual nidus is comparable to the risk of morbidity and mortality from hemorrhage from an untreated AVM (6,7). Some authors have suggested that the risk of morbidity and mortality from a residual nidus may be greater than that of an untreated AVM because it is possible that the draining veins of the residual AVM may have been compromised during surgery (39). Few studies have investigated the incidence of residual nidus after surgical resection of an AVM. In one large series, 324 patients underwent craniotomy for AVM resection, followed by immediate cerebral angiography (39). Six patients (1.8%) were found to have residual lesions on postoperative angiography. All six patients underwent immediate surgical reexploration with complete resection of the residual nidus. Study Interpretation A number of factors must be considered when interpreting postoperative angiograms. Residual AVM nidus must be distinguished from the dysplastic or angiomatous vessel changes that may characterize feeding arteries either before or after nidus resection. These changes are manifest as abnormal-appearing vessels that initially have a tortuous and dilated appearance but return to normal over time. This issue is germane when a postoperative angiogram is obtained in the first few days after surgery. If there is concern about the appearance of vessels on an early postoperative angiogram, then another angiogram approximately one month later may be helpful. Another important distinction between dysplastic or angiomatous vessels and residual nidus involves the presence of an early draining vein, which is associated only with residual nidus. In addition, the hyperperfusion of normal vessels surrounding an AVM resection cavity may be mistaken on postoperative angiogram for the blush of a residual nidus. As with the angiomatous changes, the hyperperfusion surrounding the AVM resection cavity is transient and is not associated with an early draining vein. In one series that examined the relevance of dysplastic vessels on postoperative angiography, 86 consecutive patients with AVMs underwent surgical resection followed by
Figure 5 (Figure on facing page) Angiomatous changes on a postoperative angiogram. Cerebral angiogram [right internal carotid artery injection; anteroposterior (AP) (A) and lateral (B) projections] demonstrating arteriovenous malformation with feeding arteries arising from the right anterior and middle cerebral arteries. Postembolization cerebral angiogram [right internal carotid artery injection, AP (C) and lateral (D) projections] demonstrating reduction in the nidus. Cerebral angiogram [right internal carotid artery injection, AP (E) and lateral (F) projections] performed one day after surgery demonstrating angiomatous changes to the feeding arteries (arrows). There is no obvious nidus or early draining vein. Cerebral angiogram [right internal carotid artery injection, AP (G) and lateral (H) projections] performed four months after surgery demonstrating resolution of the angiomatous changes to the feeding arteries.
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Figure 5 (Caption on facing page)
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postoperative angiography under the same general anesthetic (40). Seventy-eight of the patients (91%) had angiograms that suggested complete AVM resection. Two patients (2.3%) had angiograms that revealed residual AVM—one patient had a persistent early draining vein and a second patient had residual dysplastic vessels. One patient was felt to have dysplastic vessels without evidence of a draining vein. Forty-eight hours after surgery, that patient had a postoperative hemorrhage. The patient was returned to the operating room for removal of the clot, and dilated AVM vessels were encountered and resected. Subsequent review of the postoperative angiogram revealed an initially undetected draining vein. Six additional patients had dysplastic vessels on postoperative angiography without evidence of a draining vein. These patients were managed conservatively, and delayed angiography revealed spontaneous involution of these abnormal vessels. A final issue to consider in the interpretation of postoperative angiograms regards the retrograde thrombosis of feeding vessels, which occurs 5% to 10% of the time after embolization or surgical ligation of an AVM feeding artery. Retrograde thrombosis of feeding vessels is a potential cause of postoperative neurological deterioration, and the phenomenon occasionally prompts a postoperative angiogram. Illustrative Case Angiomatous Changes on a Postoperative Angiogram A 29-year-old woman presented with a seizure. Cerebral angiography demonstrated a Spetzler–Martin Grade III AVM in the right parietal region. Feeding arteries arose from the anterior and middle cerebral arteries (Fig. 5A and B). Multiple stages of embolization were performed with a total of eight pedicles being embolized. The embolization resulted in a reduction in the volume of the nidus by 50% to 60% (Fig. 5C and D). Surgery was scheduled with motor cortex mapping. The AVM was approached through a right frontoparietal craniotomy. The anterior margin of the malformation was adjacent to the central sulcus. The primary motor cortex for the left upper extremity was identified with cortical mapping anterior to the malformation. The primary sensory cortex for the hand area was noted to be slightly anterior and inferior to the malformation. The AVM was resected completely without change in motor or sensory function. No intraoperative angiogram was performed. The following day, a conventional angiogram showed numerous dilated anterior and middle cerebral artery branches with stagnant flow. There was no evidence of arteriovenous shunting or an early draining vein (Fig. 5E and F). Four months after the surgery, a second postoperative angiogram demonstrated resolution of the abnormal appearance of the anterior and middle cerebral artery branches. No arteriovenous shunting or early draining vein was noted (Fig. 5G and H). Alternatives to Postoperative Angiography Although the cerebral angiogram is the definitive means of evaluation of AVMs, it is a labor-intensive, invasive procedure that carries a small but definite risk of morbidity. Thus, alternative modes of follow-up evaluation have been proposed. In the stereotactic radiosurgery literature, MRI has been evaluated as a means to determine if AVM obliteration has occurred after treatment. This modality has been able to predict obliteration with a high degree of success. Pollack et al. reviewed 164 pairs of angiograms and MRIs that were performed a median of 24 months after stereotactic radiosurgery (41). They found that MRI correctly predicted angiographic AVM patency in 64 of 80 patients (80%) and correctly predicted angiographic AVM obliteration in 84 of 84 patients (100%). In 7 of the 16 patients whose AVMs had false negative imaging results, the AVMs ultimately thrombosed without further treatment. When this fact is taken into account, the predictive value of MRI for AVM status was found to be 91%. There are, however, significant differences between the follow-up for patients undergoing radiosurgery and those undergoing conventional surgery. Postmicrosurgical MRIs have the following limitations in terms of interpretation: metallic clip artifact that can be mistaken for flow voids, enhancement of draining veins and of the margins of the surgical resection cavity, and variable appearance of postoperative encephalomalacia and blood products. Furthermore, because of the latency period between radiosurgery and thrombosis, which typically is one to two years, it is reasonable to employ a noninvasive method to assess AVM status. This slightly less reliable imaging technique is also appropriate given the fact that the patient and the clinician have already accepted the risk of AVM hemorrhage during the lengthy and indeterminate period between radiosurgery and thrombosis. When an AVM is
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resected microsurgically, the goal is complete resection. Therefore, it is reasonable to determine the status of the AVM in a rapid and definitive manner so that further treatment may be undertaken if necessary. REFERENCES 1. Moniz E. L’Angiographie Ce´re´bral: Ses Applications et Re´sultats en Anatomie, Physiologie et Clinique. Paris: Masson & Cie, 1934:247–266. 2. Leussenhop AJ, Spence WT. Particle embolization of cerebral arteries. Report of use in a case of arteriovenous malformation. JAMA 1960; 172:1153–1155. 3. Loop JW, Foltz EL. Applications of angiography during intracranial operation. Acta Radiol (Scand) 1966; 5:363–367. 4. Bauer BL. Intraoperative angiography in cerebral aneurysm and AV-malformation. Neurosurg Rev 1984; 7:209–217. 5. Foley DT, Cahan LD, Hieshima GB. Intraoperative angiography using a portable digital subtraction unit. Technical note. J Neurosurg 1986; 64:816–818. 6. Forster DMC, Steiner L, Hakanson S. Arteriovenous malformations of the brain. A long-term clinical study. J Neurosurg 1972; 37:62–70. 7. Drake CG. Cerebral arteriovenous malformations: considerations for an experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–208. 8. Barrow DL, Boyer KL, Joseph GJ. Intraoperative angiography in the management of neurovascular disorders. Neurosurgery 1992; 30:153–159. 9. Smith RW. Intraoperative intracranial angiography. Neurosurgery 1977; 1:107–110. 10. Hieshima GB, Reicher MA, Higashida RT, et al. Intraoperative digital subtraction neuroangiography: a diagnostic and therapeutic tool. Am J Neurorad 1987; 8:759–767. 11. Martin NA, Bentson J, Vinuela F, et al. Intraoperative digital subtraction angiography and the surgical treatment of intracranial aneurysms and vascular malformations. J Neurosurg 1990; 73:526–533. 12. Meguro K, Tsukada A, Matsumura A, Matsuki T, Nakada Y, Nose T. Portable digital subtraction angiography in the operating room and intensive care unit. Neurol Med Chir (Tokyo) 1991; 31:768–772. 13. Anegawa S, Hayashi T, Torigoe R, Harada K, Kihara S. Intraoperative angiography in the resection of arteriovenous malformations. J Neurosurg 1994; 80:73–78. 14. Derdeyn CP, Moran CJ, Cross DT, Grubb RL Jr., Dacey RG Jr. Intraoperative digital subtraction angiography: a review of 112 consecutive examinations. Am J Neuroradiol 1995; 16:307–318. 15. Pietila TA, Stendel R, Jansons J, Schilling A, Koch HC, Brock M. The value of intraoperative angiography for surgical treatment of cerebral arteriovenous malformations in eloquent brain areas. Acta Neurochir (Wien) 1998; 140:1161–1165. 16. Ghosh S, Levy ML, Stanley P, Nelson M, Giannotta SL, McComb JG. Intraoperative angiography in the management of pediatric vascular disorders. Pediatr Neurosurg 1999; 30:16–22. 17. Vitaz TW, Gaskill-Shipley M, Tomsick T, Tew JM Jr. Utility, safety, and accuracy of intraoperative angiography in the surgical treatment of aneurysms and arteriovenous malformations. Am J Neuroradiol 1999; 20:1457–1461. 18. Munshi I, Macdonald RL, Weir BK. Intraoperative angiography of brain arteriovenous malformations. Neurosurgery 1999; 45:491–499. 19. Hashimoto H, Iida J, Hironaka Y, Sakaki T. Surgical management of cerebral arteriovenous malformations with intraoperative digital subtraction angiography. J Clin Neurosci 2000; 7:33–35. 20. Yanaka K, Matsumara Y, Okazaki M, et al. Intraoperative angiography in the surgical treatment of cerebral arteriovenous malformations and fistulas. Acta Neurochir (Wien) 2003; 145:377–383. 21. Hecht ST, Kemp SS, Kerber CW. Technical note: radiolucent operating room table extension to facilitate intraoperative angiography. Am J Neuroradiol 1991; 12:130. 22. Morris P. Practical Neuroangiography. Williams & Wilkins, 1997:47. 23. Mullen JF. Comment. Neurosurgery 1992; 30(2):159. 24. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 25. Black KL, Rubin JM, Chandler WF, McGillicuddy JE. Intraoperative color-flow Doppler imaging of AVMs and aneurysms. J Neurosurg 1988; 68:635–639. 26. Rubin JM, Hatfield MK, Chandler WF, Black KL, DiPietro MA. Intracerebral arteriovenous malformations: intraoperative color Doppler flow imaging. Radiology 1989; 170:210–222. 27. Van Alphen HAM. Intraoperative embolization of cerebral arteriovenous malformations. Neurosurg Rev 1986; 9:77–85. 28. Molsen HP, Grawe A, Nisch G, Rost H, Siedschlag WD. Intraoperative angiography and embolization in intracranial AVM’s and aneurysms. Neurosurg Rev 1992; 15:285–288. 29. Fox AJ, Girvin JP, Vinuela F, Drake CG. Rolandic arteriovenous malformations: improvement in limb function by IBC embolization. Am J Neurorad 1985; 6:575–582. 30. Girvin JP, Fox AJ, Vinuela F, Drake CG. Intraoperative embolization of cerebral arteriovenous malformations in the awake patient. Clin Neurosurg 1984; 31:188–247.
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31. Jizong Z, Shuo W, Jingsheng L, Dali S, Yuanli Z, Yan Z. Combination of intraoperative embolisation with surgical resection for treatment of giant cerebral arteriovenous malformations. J Clin Neurosci 2000; 7 Suppl 1:54-9. 32. Grzyska U, Freitag J, Zeumer H. Selective cerebral intraarterial DSA. Complication rate and control of risk factors. Neuroradiology 1990; 32:296–299. 33. Heiserman JE, Dean BL, Hodak JA, et al. Neurologic complications of cerebral angiography. Am J Neurorad 1994; 15:1401–1411. 34. Mani RL, Eisenberg RL, McDonald EJ Jr., et al. Complications of catheter cerebral angiography: analysis of 5,000 procedures. I. Criteria and incidence. Am J Rad 1978; 131:861–865. 35. Mani RL, Eisenberg RL. Complications of cerebral arteriography: analysis of 5,000 procedures. II. Relation of complication rates to clinical and arteriographic diagnoses. Am J Rad 1978; 131:867–869. 36. Waugh JR, Sacharias N. Arteriographic complications in the DSA era. Radiology 1992; 182:243–246. 37. Fults D, Kelly DL Jr. Natural history of arteriovenous malformations of the brain: a clinical study. Neurosurgery 1984; 15:658–662. 38. Brown RD Jr., Wiebers DO, Forbes G, et al. The natural history of unruptured intracranial arteriovenous malformations. J Neurosurg 1988; 68:352–357. 39. Hoh BL, Carter BS, Ogilvy CS. Incidence of residual intracranial AVMs after surgical resection and efficacy of immediate surgical re-exploration. Acta Neurochir (Wien) 2004; 146:1–7. 40. Solomon RA, Connolly ES Jr., Prestigiacomo CJ, Khandji AG, Pile-Spellman J. Management of residual dysplastic vessels after cerebral arteriovenous malformation resection: implications for postoperative angiography. Neurosurgery 2000; 46:1052–1062. 41. Pollack BE, Kondziolka D, Flickinger JC, Patel AK, Bissonette DJ, Lunsford LD. Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery. J Neurosurg 1996; 85:1044–1049.
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Associated Aneurysms Bernard R. Bendok, Christopher C. Getch, and H. Hunt Batjer Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A.
INTRODUCTION The association of arteriovenous malformations (AVMs) with aneurysms became apparent soon after cerebral angiography was introduced in 1929 by Egas Moniz (1). This association has raised many intriguing questions regarding the pathophysiology of aneurysms as they relate to AVMs. Moreover, their association has often created management dilemmas that have been resolved in different ways by various cerebrovascular specialists. Studies suggest a possible effect of associated aneurysms on the natural history of AVMs (2–5). In this chapter we present a classification scheme for associated aneurysms, discuss their incidence, review hypotheses on their pathophysiology (5,6), and address the patient management issues they raise. CLASSIFICATION Flow-related aneurysms can be subdivided into two groups: those that are related to the AVM hemodynamically, and those that are not on vessels directly feeding the AVM. It is helpful initially to think of these aneurysms in this way because the management of hemodynamically unrelated aneurysms can be different from the management of those that are directly related. AVM-related arterial aneurysms may be further subdivided into proximal aneurysms, pedicle aneurysms, and intranidal aneurysms (7). Proximal aneurysms are located proximally on the circle of Willis on large vessels that are hemodynamically related to the AVM. Pedicle aneurysms are located often more distally along feeding vessels. Intranidal aneurysms are located, as the name implies, within the nidus of the AVM (7).
INCIDENCE Of patients who present with an intracranial aneurysm, roughly 1% also harbor an intracranial AVM (8). Of patients who present with an AVM, approximately 10% have one or more intracranial aneurysms (8). The incidence of this association varies widely in the literature. Most series report percentages between 2.7% and 16.7% (9). In a recent series, superselective angiography identified an associated aneurysm in 58% of the patients with AVMs (10). In prospective angiography studies, the incidence of intracranial aneurysms is 6% (11). With superselective techniques and more intense scrutiny, however, it is likely that the actual incidence will be found to be much higher. Thus, the association of AVMs and aneurysms is more than would be expected by chance alone. The distribution of aneurysms associated with AVMs also differs from aneurysms without AVMs in the general population. The vast majority of associated aneurysms are on vessels that relate anatomically and hence hemodynamically to the AVM. In a recent report on 632 patients with AVMs, Redekop et al. found that 35 (5.5%) patients had intranidal aneurysms, 71 (11.2%) had flow-related aneurysms, and 0.8% had hemodynamically unrelated aneurysms (12). Patient age, size of the AVM, and increased flow are believed to influence the incidence of the association of AVMs and aneurysms. Gender appears to have no influence on the incidence (13). The incidence of this association has been noted to increase significantly with age (13,14). In Berenstein and Lasjaunias’s series of 101 patients with AVMs and associated aneurysms, the frequency of associated aneurysms with AVMs increased with patient age. Associated aneurysms were present in 8% of patients less than 25 years of age, 24% of the patients between 25 and 49, and 37% of patients age 50 and over, a fourfold increase in
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frequency between the age of 10 and 50 (14). The mean age of presentation was 37 years in one large series (12). Definitive studies on the effect of flow on the coincidence of AVM and aneurysms are not available, but it does appear that larger AVMs are more likely to have associated aneurysms (15). Multiple aneurysms appear to occur more frequently when an AVM is present. In one series, 17% of 132 patients with AVMs were found to have associated aneurysms, and of these patients 41% had multiple aneurysms (16). PATHOPHYSIOLOGY Three main hypotheses have been put forth to explain the association of AVMs and aneurysms (5,6): 1. The coexistence of aneurysms and AVM is coincidental. 2. A common developmental vascular abnormality predisposes to both lesions. 3. Abnormal flow dynamics due to the AVM lead to aneurysm formation. The first theory may apply to the hemodynamically unrelated aneurysms, as their incidence appears to be equal to that of aneurysms in the general population. The high incidence of proximal, pedicular, and intranidal aneurysms in patients harboring an AVM cannot be accounted for by this theory. The second theory, that a common developmental vascular abnormality predisposes to both lesions, is intuitively attractive because AVMs are congenital lesions. However, the authors are unaware of any abnormalities that have been identified to directly link the two. The third theory is currently the most favored as an explanation for the increased frequency of aneurysms on proximal and pedicular vessels that feed an AVM. Support comes from several clinical observations. Angiographic follow-up of patients treated with carotid ligation for intracranial aneurysms has been notable for the development of new aneurysms. It is thought that the hemodynamic stress placed on the circle of Willis after carotid ligation leads to these ‘‘iatrogenic’’ aneurysms. The hemodynamic stress placed by an AVM on the circle of Willis may also predispose to aneurysm formation. This phenomenon has been attributed to changes in flow patterns in the circle of Willis (17). The observation by various authors that resection of an AVM can result in a decrease in size or disappearance of a proximal or pedicular aneurysm lends more support to the hemodynamic theory (18,19). Changes in all layers of cerebral vessels, termed ‘‘high flow angiopathy,’’ have been demonstrated in a rabbit model when a carotid jugular shunt is created after ligation of the proximal carotid (20). The fact that associated aneurysms increase in frequency with age also lends support to the hemodynamic theory. NATURAL HISTORY Patients who have an AVM associated with one or multiple aneurysms appear to have a higher risk of intracranial hemorrhage than patients who have either lesion independently (5). In a series of 91 patients with AVMs (21), the yearly risk of hemorrhage for AVMs associated with aneurysms was 7% per year compared with 1.7% per year for AVMs without associated aneurysms. In a recent series by Redekop et al., patients who had intranidal aneurysms had a 9.8% yearly risk of hemorrhage that is higher than the generally reported figure for AVMs (22). These data may be confounded by the fact that pseudoaneurysms may be mistaken for intranidal aneurysms. There is no information about the effect of an AVM on the natural history of aneurysms that occur on unrelated vessels. MANAGEMENT Unrelated Aneurysms The management of a patient harboring both an AVM and an intracranial aneurysm can be divided generally into two strategies depending on whether the aneurysm is on vessels not directly associated with the AVM or is directly related to feeding arteries. In patients with an AVM and an aneurysm not located on a direct feeding artery, the surgeon is confronted with a difficult decision analysis as to which lesion, if any, should be treated. The natural history of both lesions must be carefully reviewed as they relate to patient age, medical
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condition, clinical presentation, specific anatomical features of the aneurysm or AVM such as size and location, risks associated with specific treatments, and patient wishes for treatment. Theoretically, the natural history of each lesion is unaffected by the other lesion. Small aneurysms in the circle of Willis contralateral to the AVM may be managed conservatively if asymptomatic. The authors, however, have a lower threshold for treating aneurysms located in the circle of Willis that are directly hemodynamically related to the AVM. When an aneurysm reaches the clinical threshold for treatment, the aneurysm should be treated first because resection of the AVM may increase the risk of rupture of the aneurysm by increasing distal resistance and transmural gradient (23). Conversely, at the time of the aneurysm repair, care must be taken with fluid and blood pressure management, as AVM rupture has been reported after aneurysm surgery (5). Proximal and Pedicular Aneurysms The management of pedicular and proximal aneurysms is controversial. Suzuki and Onuma in 1979 advocated treating both lesions simultaneously (24). Concern about the increased risk of morbidity with this approach has led other authors to advocate a staged approach. The clinical observation that some ‘‘flow-related’’ aneurysms decrease in size or disappear after the AVM is treated has led some authors to favor treating the AVM first (Fig. 1). Some authors favor treating the lesion that is thought to have bled first. It is often difficult, however, to accurately assess the source of hemorrhage with computed tomography (CT), particularly when the aneurysm and AVM are in close proximity. In situations where the source of the hemorrhage is unclear, it is our philosophy to secure the aneurysm first, because of the more aggressive early natural history of a ruptured aneurysm versus an AVM and because of the possible increases in transmural pressure on a proximal aneurysm after AVM resection (Figs. 2 and 3). In situations where neither vascular lesion has bled, immediate rupture of an aneurysm after AVM resection has occurred (23). In a recent series of 45 AVMs associated with aneurysms, three aneurysms bled during or within three weeks of AVM treatment (5). Furthermore, even when the AVM is treated first, not all aneurysms will regress or disappear (Fig. 4). In a series of 632 AVMs in which 23 proximal aneurysms were identified, 18 were unchanged, 4 were smaller, and one disappeared after AVM treatment (21). Of the five pedicular aneurysms in this series, four regressed completely and one was unchanged at follow-up after AVM treatment.
Figure 1 Flow-related aneurysm that thrombosed after arteriovenous malformation (AVM) excision. A 57-year-old man presented with acute onset of severe headache and was found to have a vermian posterior fossa hemorrhage. Exploratory craniotomy for evacuation of hematoma demonstrated a superior medial cerebellar hemispheric AVM. (A) Left vertebral injection demonstrated a medial superior left cerebellar hemispheric AVM with a small flow-related aneurysm on the left posterior inferior cerebellar artery (PICA) (arrow). (B) Lateral vertebral injection postoperatively demonstrates complete surgical excision of the AVM nidus. The left PICA arterial supply has thrombosed in a retrograde fashion to a point proximal to the flow-related aneurysm.
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Figure 2 Proximal aneurysm treated with Guglielmi detachable coil (GDC) embolization. A 25-year-old woman presented with a six-month history of progressive facial pain. (A) Left vertebral injection demonstrates a vermian arteriovenous malformation with arterial contribution predominantly from the right superior cerebellar artery. Of note is a broad-based flow-related aneurysm at the origin of the right superior cerebellar artery (arrow). (B) and (C) Anteroposterior and lateral left artery injections demonstrating obliteration of proximal flow-related aneurysm with GDC endovascular coiling.
Intranidal Aneurysms Advances in superselective angiography have allowed for improved visualization of intranidal aneurysms (Fig. 5) (25). The significance of intranidal aneurysms has not been completely defined. The understanding of this entity is confounded by the fact that it can be difficult to distinguish pseudoaneurysms from intranidal aneurysms. Nevertheless, intranidal aneurysms appear to be a frequent site of hemorrhage from AVMs, and their presence may increase an AVM’s risk of hemorrhage (3). For patients with significant intracerebral or intraventricular hemorrhage in whom an intranidal aneurysm is a likely cause, successful selective embolization of the aneurysm in the early postbleeding period can eliminate the rebleeding risk and allows the patient to recover before surgical or radiosurgical treatment of the AVM (Fig. 6). Furthermore, embolizing the portion of an unruptured AVM with an intranidal aneurysm when stereotactic radiosurgery is contemplated is a reasonable consideration because of the latency period
Figure 3 Two related aneurysms treated before arteriovenous malformation resection. A 59-year-old male experienced sudden onset of headache with loss of consciousness. Computed tomography scan demonstrated diffuse subarachnoid hemorrhage with an increased density of blood in the left ambient cistern and cerebellar pontine angle. (A) and (B) Cerebral angiogram (A, lateral; B, anteroposterior) demonstrated a small irregular posterior inferior cerebellar artery (PICA) aneurysm on the left (larger arrow) and a larger smooth aneurysm located on a posterior cerebral artery (smaller arrow) feeding a left occipital AVM. The posterior cerebral artery aneurysm was obliterated by Guglielmi detachable coil (GDC) coiling. Direct surgical clipping of the ruptured PICA aneurysm was required because its neck precluded GDC coiling.
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Figure 4 Residual flow-related aneurysm after arteriovenous malformation (AVM) resection. A 56-year-old woman presented with loss of consciousness and cardiac arrest. Computed tomography scan demonstrated acute hydrocephalus and a midline posterior fossa hematoma. (A) Preoperative left lateral vertebral artery injection demonstrated a small posterior medial left hemispheric AVM. Arterial supply to the vascular malformation is predominantly from the left superior cerebellar artery. Flow-related aneurysms are noted on both feeding vessels (arrows). The angiographic appearance of the superior cerebellar artery aneurysm suggests that it was the site of the cerebellar hemorrhage. (B) Postoperative lateral vertebral artery injection demonstrates complete surgical excision of AVM. Despite clipping of the superior cerebellar artery aneurysm with preservation of the parent artery, retrograde thrombosis of the artery (that was noted intraoperatively after resection of the AVM) resulted in angiographic loss of the blood vessel. The small posterior inferior cerebellar artery aneurysm was not easily accessible during the surgical excision and persistently fills on the postoperative angiogram (arrow). A follow-up angiogram will be performed at six months to assess for disappearance of this aneurysm.
associated with radiosurgery (25). This approach may lessen the risk of hemorrhage during the period of time before AVM thrombosis. Finally, embolization may be helpful in the case of an otherwise untreatable—either surgically or radiosurgically—AVM by securing intranidal aneurysms and theoretically lowering the natural history hemorrhage risk of that AVM.
Figure 5 Intranidal aneurysm. A 30-year-old female presented with acute onset headache. (A) Computed tomography scan without contrast demonstrates a right trigonal intraventricular hemorrhage. (B) Vertebral injection demonstrates a right trigonal arteriovenous malformation (AVM) supplied predominantly by the right posterior cerebral artery. There are two intranidal aneurysms contained within the AVM nidus (arrows).
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Figure 6 Endovascularly treated flow-related aneurysm. A 58-year-old female with a large left frontal arteriovenous malformation (AVM) had two intraventricular hemorrhages in less than a month. (A) Coronal computed tomography angiography demonstrates an intraventricular hemorrhage associated with an AVM aneurysm. (B) Left carotid angiogram revealed a large flow-related aneurysm projecting into the ventricle. (C) Left carotid angiogram after embolization of the aneurysm and vascular pedicle feeding the aneurysm.
Infundibula Little has been written on the association of AVMs and infundibula and the clinical significance. Most retrospective series eliminate infundibula from analysis. In one series by Miyasaka and colleagues that included 132 patients with AVMs, 34 infundibula were present in 30 patients (22.7%) (16). In 16 of these patients, the bases of the infundibula were 3 mm or greater. In 8 of these 16 patients, saccular aneurysms coexisted. In 14 patients, the infundibula were less than 3 mm, and only 2 of these 14 patients harbored coexisting saccular aneurysms. The relationship between infundibular size and the presence of an aneurysm was statistically significant. Furthermore, the authors noted that infundibula were more likely to exist in older patients and in patients with larger AVMs, and 92% of the infundibula were anatomically related to the AVM’s feeding vessels. In four patients the infundibula decreased in size after treatment of the AVM. CONCLUSIONS The association of an aneurysm with an AVM appears to be a source of potential increase in the risk of morbidity and mortality in patients harboring both lesions. The high incidence of this association merits thorough and superselective cerebral angiography during the evaluation of a patient with an intracranial AVM. For patients with unruptured AVMs in whom treatment is recommended, consideration should be given to treating anatomically unrelated aneurysms before the AVM because of the potential risk of aneurysmal rupture from the hemodynamic
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changes and stress imposed on the circulation during or after AVM resection. Careful consideration should be given to treating pedicular aneurysms at the time of AVM embolization or directly addressing them at the same time through the same craniotomy approach prior to AVM resection. Pedicular aneurysms that are small or remote and cannot be safely treated with endovascular strategies or surgically during AVM resection should be followed closely with angiography, as it is possible that these aneurysms will not resolve and may eventually require treatment. Symptomatic intranidal aneurysms may be addressed by selective embolization of the portion of the nidus containing the aneurysm before surgery or radiosurgery of the entire AVM or in untreatable AVMs where securing the intranidal aneurysm may lower the natural history risk of hemorrhage of the AVM. Ultimately, treatment strategies must be individualized. The close collaboration of cerebrovascular and endovascular specialists is critical to assure optimum patient care. In all cases, the best information available regarding the natural history and the risk for the specific patient must be weighed against the potential risk of therapeutic morbidity in the individual surgeon’s own practice history.
REFERENCES 1. Moniz E. Cerebral angiography. Its application in clinical practice and physiology. Lancet 1933; 225:1144–1147. 2. Kim EJ, Halim AX, Dowd CF, et al. The relationship of coexisting extranidal aneurysms to intracranial hemorrhage in patients harboring brain arteriovenous malformations. Neurosurgery 2004; 54:1349– 1357; discussion 1348–1357. 3. Meisel HJ, Mansmann U, Alvarez H, Rodesch G, Brock M, Lasjaunias P. Cerebral arteriovenous malformations and associated aneurysms: analysis of 305 cases from a series of 662 patients. Neurosurgery 2000; 46:793–800; discussion 800–802. 4. Stapf C, Mohr JP, Pile-Spellman J, et al. Concurrent arterial aneurysms in brain arteriovenous malformations with haemorrhagic presentation. J Neurol Neurosurg Psychiatry 2002; 73:294–298. 5. Thompson RC, Steinberg GK, Levy RP, Marks MP. The management of patients with arteriovenous malformations and associated intracranial aneurysms. Neurosurgery 1998; 43:202–211; discussion 211–202. 6. Nornes H, Grip A, Wikeby P. Intraoperative evaluation of cerebral hemodynamics using directional Doppler technique. Part 1: Arteriovenous malformations. J Neurosurg 1979; 50:145–151. 7. Perata HJ, Tomsick TA, Tew JM Jr. Feeding artery pedicle aneurysms: association with parenchymal hemorrhage and arteriovenous malformation in the brain. J Neurosurg 1994; 80:631–634. 8. Fox JL. Associated conditions. In: Fox JL, ed. Intracranial Aneurysms. New York: Springer-Verlag, 1983:396–398. 9. Yasargil MG. Association of aneurysm and AVM. In: Yasargil MG, ed. Microneurosurgery. Stuttgart, New York: Georg Thieme Verlag, Thieme Medical Publishers, 1987:182–189. 10. Turjman F, Massoud TF, Vinuela F, Sayre JW, Guglielmi G, Duckwiler G. Correlation of the angioarchitectural features of cerebral arteriovenous malformations with clinical presentation of hemorrhage. Neurosurgery 1995; 37:856–860; discussion 860–862. 11. Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke 1998; 29:251–256. 12. Redekop G, TerBrugge K, Montanera W, Willinsky R. Arterial aneurysms associated with cerebral arteriovenous malformations: classification, incidence, and risk of hemorrhage. J Neurosurg 1998; 89:539–546. 13. Reyes Rdl, Fink M. Special problem: AVM associated with aneurysm. In: Batjer HH, ed. Cerebrovascular Disease. Philadelphia: Lippincott-Raven, 1997:743–747. 14. Berenstein A, Lasjaunias PL. Surgical neuroangiography. Berlin, New York: Springer-Verlag, 1992. 15. Kondziolka D, Nixon BJ, Lasjaunias P, Tucker WS, TerBrugge K, Spiegel SM. Cerebral arteriovenous malformations with associated arterial aneurysms: hemodynamic and therapeutic considerations. Can J Neurol Sci 1988; 15:130–134. 16. Miyasaka K, Wolpert SM, Prager RJ. The association of cerebral aneurysms, infundibula, and intracranial arteriovenous malformations. Stroke 1982; 13:196–203. 17. Somach FM, Shenkin HA. Angiographic end-results of carotid ligation in the treatment of carotid aneurysm. J Neurosurg 1966; 24:966–974. 18. Hayashi S, Arimoto T, Itakura T, Fujii T, Nishiguchi T, Komai N. The association of intracranial aneurysms and arteriovenous malformation of the brain. Case report. J Neurosurg 1981; 55:971–975. 19. Shenkin HA, Jenkins F, Kim K. Arteriovenous anomaly of the brain associated with cerebral aneurysm. Case report. J Neurosurg 1971; 34:225–228. 20. Pile-Spellman JM, Baker KF, Liszczak TM, et al. High-flow angiopathy: cerebral blood vessel changes in experimental chronic arteriovenous fistula. Am J Neuroradiol 1986; 7:811–815.
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21. Brown RD Jr., Wiebers DO, Forbes GS. Unruptured intracranial aneurysms and arteriovenous malformations: frequency of intracranial hemorrhage and relationship of lesions. J Neurosurg 1990; 73:859–863. 22. Ondra SL, Troupp H, George ED, Schwab K. The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg 1990; 73:387–391. 23. Batjer H, Suss RA, Samson D. Intracranial arteriovenous malformations associated with aneurysms. Neurosurgery 1986; 18:29–35. 24. Suzuki J, Onuma T. Intracranial aneurysms associated with arteriovenous malformations. J Neurosurg 1979; 50:742–746. 25. Marks MP, Lane B, Steinberg GK, Snipes GJ. Intranidal aneurysms in cerebral arteriovenous malformations: evaluation and endovascular treatment. Radiology 1992; 183:355–360.
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Arteriovenous Malformations in Pregnancy Eli M. Baron Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania, U.S.A.
Sumon Bhattacharjee Neuroscience Group of Northeast Wisconsin, Neenha, Wisconsin, U.S.A.
Robert Wienecke Neuroscience Specialists, Oklahoma City, Oklahoma, U.S.A.
Christopher M. Loftus Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania, U.S.A.
INTRODUCTION Although rare, subarachnoid hemorrhage (SAH) is the most common non-obstetric cause of maternal death (1). Some estimate that approximately one-quarter of these hemorrhages are due to rupture of an arteriovenous malformation (AVM) (2). The presence of an AVM, whether ruptured or not, significantly complicates the management of pregnancy. In this chapter, the epidemiology, physiologic considerations, and management of AVMs in pregnancy are reviewed. EPIDEMIOLOGY The incidence of AVMs in unselected populations has been estimated to be between 0.89 and 1.34 per 100,000 person-years (3,4). The prevalence of AVMs in unselected populations has been estimated at 18 per 100,000 (5). Epidemiologic numbers are less clear with regard to AVMs in pregnant women. Whether pregnancy actually increases the risk of AVM rupture is controversial. While indirect evidence suggests that there may be a higher risk of AVM rupture with pregnancy (6,7), Horton et al., in a large retrospective analysis of women with known AVMs, found a 3.5% risk of hemorrhage during pregnancy, consistent with the expected hemorrhage rate in the non-pregnant population (8). Overall, the data regarding increased risk of AVM hemorrhage during pregnancy are inconclusive (9). Additionally, rupture appears likely to occur throughout pregnancy, with only a slight preponderance toward the third trimester, as opposed to cerebral aneurysms (10). Dias and Sekhar (2) reported a series of 154 pregnant women who suffered an intracranial hemorrhage: 23% of the hemorrhages were secondary to rupture of an AVM. The mean age of the patients in their series was 26.7 years, and the mean gestational age at hemorrhage was 30 weeks. Maternal mortality exceeded fetal mortality (28% vs. 14%). Pregnancy seemed to increase the lethality of AVM rupture, and poor outcome was correlated with a moribund or comatose condition at presentation. PHYSIOLOGIC CHANGES ASSOCIATED WITH PREGNANCY Major physiologic changes occur within the cardiovascular system during pregnancy, including changes in blood volume, blood pressure, cardiac output, and vasculature. In some instances, pathologic changes occur as well. We review these changes and consider their impact on pregnant women with AVMs. Whole blood is comprised of both plasma and a cellular mass, and both components undergo expansive changes during pregnancy. Whole blood volume increases by 40% to 55% due to a disproportionate increase in plasma volume over the increase in red blood cell mass
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(11,12). These changes lead to the physiologic anemia of pregnancy, which may protect against hemorrhage and help fill the expanded vascular system created by vasodilation and the low resistance vasculature of the uteroplacental unit (13). Systemic arterial blood pressure typically declines during pregnancy. The drop in blood pressure is partially explained by an increase in circulating prostaglandins, particularly prostacyclin, resulting in decreased systemic vascular resistance (14). Decreased blood returned to the heart from compression of the inferior vena cava may also contribute to a decline in blood pressure during pregnancy, particularly when the patient is recumbent. The pulse pressure actually rises because the decrease in diastolic blood pressure is greater than the decrease in systolic blood pressure. Systemic vascular resistance reaches its nadir at midpregnancy but begins to gradually rise until term; nevertheless, it remains on average 21% lower than prepregnant values (13). In several pathologic conditions, the systemic arterial blood pressure is elevated during pregnancy. Preeclamptic and eclamptic syndromes are defined in part by a pathologic elevation of blood pressure (15). In some instances, this elevation in blood pressure results in intracranial hemorrhage, at times secondary to the rupture of an AVM. Transient hypertension of pregnancy, chronic preexisting hypertension, and preeclampsia/eclampsia superimposed on chronic hypertension are other categories of hypertension in pregnancy. Hypertension from any cause increases the risk of AVM rupture (16). Maternal cardiac output increases by 30% to 50% in pregnancy (17). Both stroke volume and heart rate increase to produce this change in cardiac output. By the time of the first stage of labor, cardiac output during a contraction is 51% greater than baseline pregnancy values. Cardiac output reaches its maximum in the immediate postpartum period, with a further 10% to 20% rise. It then progressively declines after the first postpartum day and returns to normal two to four weeks after delivery (13). The hormonal changes of pregnancy impact the peripheral vascular system. Generalized vasodilatory changes are most profound in the kidney, uterus, and skin (18). Besides physiologic changes at the smooth muscle level, anatomic changes in the vessel walls also occur. Intimal hyperplasia is thought to occur secondary to an increase in circulating estrogen and loss of elastin, along with fragmentation of reticular fiber, which can be found in the tunica media. Some investigators have attributed the increased rate of aortic and renal artery dissection associated with pregnancy to these vascular wall changes (19). Similar vasodilatory changes are seen in vessels in the central nervous system (7). These changes can occur in both normal and abnormal vessels. Circulating estrogens may also contribute to increased flow within AVM vessels, increasing their likelihood of rupture (20). Additionally, hormonal changes with myometrial involution after delivery may result in structural alterations of AVM vessels (21). Studies of changes in cerebral blood flow associated with pregnancy have yielded conflicting results. Ikeda et al. noted increases in maternal regional cerebral blood flow (5.6–16.7%) using a xenon SPECT technique (22). The greatest increase was in cerebellar blood flow followed by the temporal, parietal, and frontal lobes. A minimal increase in blood flow occurred in the occipital lobes. Cerebral blood flow was increased despite the progesteroneinduced hypocapnia of pregnancy. In a study using velocity-encoded phase-contrast magnetic resonance imaging (MRI), Zeeman et al. found middle cerebral artery blood flow to be decreased during pregnancy (23). Bergersen et al. noted that during standardized handgrip exercise mean arterial pressure showed a statistically significant increase during pregnancy that did not affect cerebral blood flow when internal carotid velocities were assessed with ultrasound (24). They concluded that pregnancy had no effect on cerebral autoregulation. Using transcranial Doppler ultrasonography, Franco-Macias et al. noted low cerebral vasculature mean velocities and a low pulsatility index consistent with cerebral vasodilatation in pregnant women from 33 weeks to term (25). This finding may explain the proclivity of aneurysmal SAH to occur in the third trimester (10). Nevertheless, others have noted that half of all AVM ruptures in pregnant women occur early during pregnancy (2); thus, other mechanisms likely come into play. RADIOLOGIC DIAGNOSIS OF AVM IN PREGNANCY When a pregnant patient presents with signs and symptoms that suggest the possible presence of an AVM, such as sudden severe headache, headache with sudden onset of a hemiparesis,
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decreased mentation, or new onset seizure, a computed tomographic (CT) scan of the head without contrast is the initial study of choice. In the setting of intracerebral hemorrhage, CT scanning has sensitivity between 50% and 77% and specificity between 84% and 99% for the detection of an AVM when compared with arteriography (4). Four-vessel digital subtraction arteriography should then follow. MRI may be useful for surgical planning; it is unclear what its role is as a diagnostic test with regard to sensitivity and specificity in detecting AVMs compared with other imaging modalities (4). The risk of radiotoxicity to mother and fetus must be considered when evaluating possible or known AVMs during pregnancy. Central nervous system malformations are among the most common teratogenic effects of ionizing radiation, including microcephaly and mental retardation. These were seen in World War II after the bombing of Hiroshima and Nagasaki, where survivors in utero were exposed to radiation doses of 10–150 cGy (26). Depending on the timing of the insult during fetal development, different effects may appear. During the first two weeks of pregnancy (embryogenesis), radiation exposure may result in fetal wastage. During two to seven weeks (organogenesis), radiation damage may result in congenital anomalies. Exposure to radiation during weeks 8 to birth may result in growth retardation and microcephaly. During weeks 8 to 15, the risk of neuronal depletion is highest, as neuroblast proliferation and migration to the cerebral cortex occur (27). Generally, fetal risk is considered negligible at doses of 5 cGy (rad) or less, and the risks of malformations significantly increase at doses above 15 cGy. Estimated fetal radiation exposure for a maternal head CT scan is <0.05 cGy. Thus, >100 studies would have to be performed for there to be significant risk to the fetus (28). Studies of radiation exposure of the gravid uterus during digital subtraction cerebral angiography have not been performed. Nevertheless, information regarding skull radiography is available. Feygelman et al. reported an absorbed dose equivalent of 10 mSv for patients undergoing digital subtraction angiography, the equivalent of five to eight CT scans of the head [the Sievert (Sv) is the SI unit measuring the biologic impact of radiation] (29). Marshall et al. (30) reported a dose of 3.6 mSv, less than half the dose reported by Feygelman et al. (29). Nevertheless, these numbers are difficult to extrapolate to absorbed fetal dose as a result of scatter from the cranium. With a standard reference phantom regarding radiation exposure of the uterus and fetus, when four-image radiographic skull imagery was performed on a gravid mother, the actual exposure was less than 0.0001 cGy (31). In short, the amount of radiation to which a leadshielded uterus and fetus are likely to be exposed when a pregnant women undergoes standard neuroradiologic evaluation is minimal and is unlikely to result in any untoward teratogenic or oncologic effects; any possible risk is outweighed by the potential benefit for mother and fetus of diagnosis and treatment of an intracerebral hemorrhage and/or AVM (27). The effect of MRI on the fetus is less clear. While MRI is being used more frequently as a diagnostic test for the fetus itself and appears safe, more information about magnetic fields and acoustic exposure of the fetus is necessary before a generalized statement about MRI and pregnancy can be made (32). MEDICAL MANAGEMENT The medical management of a pregnant woman with an AVM is not very different from the management of a non-pregnant patient with an AVM. Strict control of hypertension and seizure activity is the cornerstone of AVM management during pregnancy. After rupture of an AVM, the risk of rehemorrhage and vasospasm is less of a consideration than with aneurysmal SAH. The greatest concern is of mass effect and neurologic compromise due to the primary rupture. Measures to reduce these risks are appropriate, such as standard measures to reduce intracranial pressure, including ventricular drainage, and potentially definitive hematoma evacuation with or without AVM resection if the mass is life-threatening. As with AVMs in non-pregnant patients, management and neurologic recovery take precedence over the need for emergency or early surgery in most cases, since the potential for repeat hemorrhage is less than that for post-aneurysmal SAH. A rational surgical plan, including preoperative embolization where necessary, is most important. The institution of a low-stimulation environment with limited visitation and low noise and light is generally accepted for the pregnant patient after AVM rupture. Laxatives, anti-tussives, analgesics, sedatives, and antiemetics should all be used in moderation. While
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the patient is in bed, the left lateral decubitus position minimizes aortic and vena cava obstruction, thereby preventing maternal hypotension and placental hypoperfusion (33). Invasive and non-invasive monitors should be used to ensure that both mother and fetus are constantly assessed, and appropriate steps should be taken to maximize fetal viability and minimize the risk of maternal rehemorrhage and vasospasm. Nimodipine carries with it the risk of potential teratogenicity, and because of the low risk for vasospasm in AVM rupture, is not customarily administered. Anticonvulsants also carry a potential risk for congenital malformation, but the risk of seizure and a concomitant increased risk of hemorrhage and hypoxia overshadow the potential drawbacks (2,34). Antifibrinolytic agents such as epsilon-aminocaproic acid have been shown to decrease the risk of rehemorrhage in patients with aneurysmal SAH, but the hypercoagulable state in pregnancy increases the risk for morbid side effects associated with antifibrinolytics (35). There is no role for them in the treatment of patients with ruptured AVMs, whether pregnant or not. SURGICAL MANAGEMENT Women with AVMs in pregnancy may be divided into two groups. The first group includes those pregnant women in whom a previously unrecognized AVM ruptures. The second group includes those women who become pregnant after having been diagnosed with an AVM; these women may or may not experience SAH during pregnancy. Some of these patients may have had previous successful pregnancies before the AVM was discovered, and others (more common with modern imaging) may be nulliparous. In either group, the decision to surgically resect an AVM during pregnancy should be based primarily on neurosurgical rather than obstetric considerations. Although resection of an AVM during pregnancy eliminates the risk of hemorrhage, no definitive studies support such an approach with respect to maternal and fetal mortality risk. When a woman with a known AVM considers pregnancy for the first time, her physician should inform her of possibly increased morbidity and mortality risks associated with an AVM rupture during pregnancy. When feasible, the treatment plan for AVM obliteration may be instituted and completed before pregnancy, if the surgical risk is acceptable. Grading the AVM with the Spetzler–Martin scale (36) is crucial in assessing these risks. In those pregnant women with a ruptured AVM, hematoma causing significant mass effect and/or hydrocephalus may require emergent surgical intervention. Regarding the AVM itself, a strategy of surgery during pregnancy is taken by some neurosurgeons because of an assumed high rate of rehemorrhage in this population (7). After resection, the pregnancy may be carried to term with obstetric management being dictated by the clinical situation. Women giving birth with an intracranial AVM, ruptured or not, may deliver either by C-section or vaginally. Many, however, advocate an alternative approach of waiting until delivery to plan surgical excision of the AVM based on the idea that there is minimal evidence to suggest a higher rehemorrhage rate during pregnancy (37). If conservative management is chosen, delivery ensues either with caesarian section or vaginally with a shortened second stage of labor to minimize hemodynamic/cerebral perfusion fluctuations (7). Once the decision is made to operate on a pregnant patient, the neurosurgeon must carefully consider intraoperative positioning. The supine position is poorly tolerated during pregnancy because of vascular congestion. Positioning should be planned to minimize compression of the aorta and vena cava. For right-sided craniotomies, rolls placed under the right shoulder and hip are usually adequate. However, given the right paramedian position of the inferior vena cava, a right lateral decubitus position should be considered for left-sided craniotomies. Similarly, for posterior fossa exposure, a park-bench position may be used to maximize venous return to the maternal heart. With any operative positioning, sequential compression devices and compression tracking should be used to prevent lower extremity venous pooling and deep venous thrombosis. These principles of position should extend from the operative suite to the pre- and postoperative care of the pregnant patient. Additionally, displacement of the uterus laterally may help minimize aortocaval compression (38). The effectiveness of the displacement can be assessed by palpation of the right femoral pulse or monitoring right lower extremity pulse oximetry (39). Fetal heart rate monitoring may be useful in detecting impairment of uteroplacental blood flow and fetal oxygenation. Monitoring is easily performed with commercially available external sensors. The normal fetal heart rate is 120 to 160 beats/min with 3 to 7 seconds
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of variability. Hypoxia and sedation are among the intraoperative factors that may reduce variability. Additionally, as the fetus has minimal ability to adjust its stroke volume, fetal bradycardia is associated with significant reductions in cardiac output, with rates less than 60 beats/min suggesting that the fetus is in jeopardy. Fetal tachycardia may be related to maternal drug administration, fever, or sepsis (39). Additionally, maternal hypothermia may cause decreased fetal heart rate and variability. Fetal heart rate decelerations, however, are suggestive of fetal stress such as hypoxemia (38). In addition to heart rate monitoring, monitoring of uterine contractions with an external tocodynomanometer will allow detection of premature labor and permit tocolysis, if necessary, to prevent premature birth (39). Modification of common cranial surgery practices may be considered when AVM surgery is performed on the gravid mother. Excessive hyperventilation may result in decreased placental oxygen transfer and umbilical vessel vasoconstriction. Nevertheless, it should not be a problem for the healthy fetus if the mother receives moderate hyperventilation. Fetal heart rate monitoring would show evidence of compromise in fetal oxygenation, thereby allowing the anesthesiologist to make changes as needed. Maternal hypothermia usually causes fetal bradycardia, which reverses with maternal rewarming, and is not known to cause any harmful effects. Diuresis may create significant fluid shifts for the fetus that are potentially detrimental. Thus, mannitol and furosemide should be administered judiciously during craniotomy in pregnant women (39). EMBOLIZATION AND RADIOSURGICAL PROCEDURES With the possible exception of rare cases, glue embolization and/or vascular techniques are inadequate treatments to eliminate (cure) parenchymal AVMs. Endovascular strategies remain primarily an adjunct to surgical resection. This situation is no different for pregnant women. Preoperative embolization is performed at the surgeon’s discretion, both to reduce operative hemorrhage and to reduce the risk of cerebral edema secondary to sudden flow shifts in the brain with occlusion of the feeding arteries. Neuroendovascular procedures have been successfully performed in pregnant patients without evidence of adverse effect to the fetus (27). Radiosurgery is appropriate for certain AVMs, whether by the patient’s choice or by the surgeon’s judgment of unacceptable surgical risk or inaccessibility of the lesion. There is no role for radiosurgery in the treatment of pregnant women, whether the AVM is ruptured or unruptured. Because of the two-year average latency period from radiosurgical treatment to AVM obliteration, radiosurgery does not protect the patient from primary rehemorrhage during the confinement; the risk of radiation exposure, although theoretically minimal, would probably be unacceptable to most patients and physicians. ETHICAL CONSIDERATIONS The treatment of pregnant women rendered unconscious, vegetative, or brain dead by AVM hemorrhage warrants a brief discussion. Ethical considerations extend beyond the life of the mother: decisions must be made about the possibility of pregnancy termination, the continued support of the pregnant mother, whether the primary interest is that of the fetus or the mother, and the power of a surrogate to render decisions for the pregnant woman. Few women of childbearing age actually have an advanced directive. Additionally, many states have limitations on advanced directives and on power of attorney privileges in the presence of pregnancy (40). There are numerous case reports of brain-dead pregnant women being sustained on life support, from 36 hours to weeks, with healthy delivery following (41–43). Decision-making about mother and fetus may be practically tempered by local practice, and consultation with local judicial authorities is indicated. Finnerty et al. conclude on the topic, ‘‘We believe that evaluation and treatment of the arteriovenous malformation may be undertaken without regard for the pregnancy and that the pregnancy should progress without concern for the arteriovenous malformation’’ (40). CONCLUSIONS Despite modern diagnostic and therapeutic modalities, SAH secondary to AVM rupture remains a major cause of non-obstetric morbidity and mortality in pregnant women. Aggressive medical and surgical management of pregnant women with AVMs is indicated to minimize the
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impact on mother and child. Pregnancy should not be a deterrent to aggressive diagnostic and therapeutic management of ruptured AVMs that are otherwise amenable to surgery. For women with AVMs who are considering pregnancy for the first time, surgical extirpation is reasonable on a preventative basis. For patients with ruptured AVMs who present for the first time while pregnant, the best management strategy is unclear. Our policy would be to bring those patients to term without intervention unless hemorrhage forces a surgical hand. Others might adopt a more aggressive stance. In either case the patient should be educated about the increased risk of hemorrhage during term, and ultimately the decision regarding surgery must come through an informed partnership with the patient and her family. REFERENCES 1. Barno A, Freeman DW. Maternal deaths due to spontaneous subarachnoid hemorrhage. Am J Obstet Gynecol 1976; 125(3):384–392. 2. Dias MS, Sekhar LN. Intracranial hemorrhage from aneurysms and arteriovenous malformations during pregnancy and the puerperium. Neurosurgery 1990; 27(6):855–865; discussion 865–866. 3. ApSimon HT, Reef H, Phadke RV, et al. A population-based study of brain arteriovenous malformation: long-term treatment outcomes. Stroke 2002; 33(12):2794–2800. 4. Choi JH, Mohr JP. Brain arteriovenous malformations in adults. Lancet Neurol 2005; 4(5):299–308. 5. Al-Shahi R, Warlow C. A systematic review of the frequency and prognosis of arteriovenous malformations of the brain in adults. Brain 2001; 124:1900–1926. 6. Bevan H, Sharma K, Bradley W. Stroke in young adults. Stroke 1990; 21(3):382–386. 7. Trivedi RA, Kirkpatrick PJ. Arteriovenous malformations of the cerebral circulation that rupture in pregnancy. J Obstet Gynaecol 2003; 23(5):484–489. 8. Horton JC, Chambers WA, Lyons SL, et al. Pregnancy and the risk of hemorrhage from cerebral arteriovenous malformations. Neurosurgery 1990; 27(6):867–871; discussion 871–872. 9. Ogilvy CS, Stieg PE, Awad I, et al. AHA Scientific Statement: recommendations for the management of intracranial arteriovenous malformations: a statement for healthcare professionals from a special writing group of the Stroke Council, American Stroke Association. Stroke 2001; 32(6):1458–1471. 10. Sadasivan B, Malik GM, Lee C, et al. Vascular malformations and pregnancy. Surg Neurol 1990; 33(5):305–313. 11. Granger JP, Alexander BT, Bennett WA, et al. Pathophysiology of pregnancy-induced hypertension. Am J Hypertens 2001; 14:178S–185S. 12. Wadsworth GR. Blood-volume: a commentary. Singapore Med J 2002; 43(8):426–431. 13. Gordon MC. Maternal physiology in pregnancy. In: Gabbe SG, Niebyl JR, Simpson JL, eds. Obstetrics—Normal and Problem Pregnancies. London: Churchill Livingstone, 2002:63–92. 14. Carbillon L, Uzan M, Uzan S. Pregnancy, vascular tone, and maternal hemodynamics: a crucial adaptation. Obstet Gynecol Surv 2000; 55(9):574–581. 15. Henry CS, Biedermann SA, Campbell MF, et al. Spectrum of hypertensive emergencies in pregnancy. Crit Care Clin 2004; 20(4):697–712, ix. 16. Barrow DL, Reisner A. Natural history of intracranial aneurysms and vascular malformations. Clin Neurosurg 1993; 40:3–39. 17. van Oppen AC, Stigter RH, Bruinse HW. Cardiac output in normal pregnancy: a critical review. Obstet Gynecol 1996; 87(2):310–318. 18. Buster JE, Carson SA. Maternal physiology in pregnancy. In: Gabbe SG, Niebyl JR, Simpson JL, eds. Obstetrics—Normal and Problem Pregnancies. London: Churchill Livingstone, 2002:3–36. 19. Nolte JE, Rutherford RB, Nawaz S, et al. Arterial dissections associated with pregnancy. J Vasc Surg 1995; 21(3):515–520. 20. Elliott JA, Rankin RN, Inwood MJ, et al. An arteriovenous malformation in pregnancy: a case report and review of the literature. Am J Obstet Gynecol 1985; 152(1):85–88. 21. Donaldson JO. Cerebrovascular disease. Neurology of Pregnancy. London: WB Saunders, 1989: 137–184. 22. Ikeda T, Ikenoue T, Mori N, et al. Effect of early pregnancy on maternal regional cerebral blood flow. Am J Obstet Gynecol 1993; 168(4):1303–1308. 23. Zeeman GG, Hatab M, Twickler DM. Maternal cerebral blood flow changes in pregnancy. Am J Obstet Gynecol 2003; 189(4):968–972. 24. Bergersen TK, Hartgill TW, Pirhonen J. Cerebrovascular response to normal pregnancy. A longitudinal study. Am J Physiol Heart Circ Physiol 2006; 290(5): H1856–61. 25. Franco-Macias E, Quesada CM, Miranda-Guisado ML, et al. Transcranial Doppler velocimeter in pregnant and later normotensive puerperal women. Rev Neurol 2004; 38(11):1006–1008. 26. Blot WJ, Miller RW. Mental retardation following in utero exposure to the atomic bombs of Hiroshima and Nagasaki. Radiology 1973; 106(3):617–619. 27. Meyers PM, Halbach VV, Malek AM, et al. Endovascular treatment of cerebral artery aneurysms during pregnancy: report of three cases. Am J Neuroradiol 2000; 21(7):1306–1311.
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28. Toppenberg KS, Hill DA, Miller DP. Safety of radiographic imaging during pregnancy. Am Fam Physician 1999; 59(7):1813–1818, 1820. 29. Feygelman VM, Huda W, Peters KR. Effective dose equivalents to patients undergoing cerebral angiography. Am J Neuroradiol 1992; 13(3):845–849. 30. Marshall NW, Noble J, Faulkner K. Patient and staff dosimetry in neuroradiological procedures. Br J Radiol 1995; 68(809):495–501. 31. Gorson RO, Lassen M, Rosenstein M. Patient dosimetry in diagnostic radiology. In: Waggener RG, Kereiakes JG, Shalek RJ, eds. CRC Handbook of Medical Physics. Boca Raton: CRC Press, 1984. Vol. II:467–526. 32. De Wilde JP, Rivers AW, Price DL. A review of the current use of magnetic resonance imaging in pregnancy and safety implications for the fetus. Prog Biophys Mol Biol 2005; 87(2–3):335–353. 33. Pedersen H, Finster M. Anesthetic risk in the pregnant surgical patient. Anesthesiology 1979; 51(5): 439–451. 34. American Academy of Pediatrics Committee on Drugs. Anticonvulsants and pregnancy. Pediatrics 1979; 63(2):331–333. 35. Kassell NF, Torner JC, Adams HP Jr. Antifibrinolytic therapy in the acute period following aneurysmal subarachnoid hemorrhage. Preliminary observations from the Cooperative Aneurysm Study. J Neurosurg 1984; 61(2):225–230. 36. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65(4):476–483. 37. Fujita K, Tsunoda H, Shigemitsu S, et al. Clinical study on the intracranial arteriovenous malformation associated with pregnancy. Nippon Sanka Fujinka Gakkai Zasshi 1995; 47(12):1359–1364. 38. Rosen MA. Management of anesthesia for the pregnant surgical patient. Anesthesiology 1999; 91(4): 1159–1163. 39. Kuczkowski KM. Nonobstetric surgery during pregnancy: what are the risks of anesthesia? Obstet Gynecol Surv 2004; 59(1):52–56. 40. Finnerty JJ, Chisholm CA, Chapple H, et al. Cerebral arteriovenous malformation in pregnancy: presentation and neurologic, obstetric, and ethical significance. Am J Obstet Gynecol 1999; 181(2):296–303. 41. Bernstein IM, Watson M, Simmons GM, et al. Maternal brain death and prolonged fetal survival. Obstet Gynecol 1989; 74:434–437. 42. Vives A, Carmona F, Zabala E, et al. Maternal brain death during pregnancy. Int J Gynaecol Obstet 1996; 52(1):67–69. 43. Heikkinen JE, Rinne RI, Alahuhta SM, et al. Life support for 10 weeks with successful fetal outcome after fatal maternal brain damage. Br Med J (Clin Res Ed) 1985; 290(6477):1237–1238.
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Diagnosis and Management of Pediatric Arteriovenous Malformations Jeffrey P. Greenfield and Mark M. Souweidane Department of Neurological Surgery, Weill Medical College of Cornell University, NewYork-Presbyterian Hospital, New York, New York, U.S.A.
INTRODUCTION The management of pediatric arteriovenous malformations (AVMs) has evolved over the last two decades into a highly individualized treatment paradigm for the children diagnosed with these vascular anomalies. Urgent neurosurgical care and pediatric intensive care management are the backbone of the emergent management of the lesions at time of presentation, often with life-threatening hemorrhage and raised intracranial pressure. Once the patients have been stabilized, however, multidisciplinary care involving neurological surgery, interventional neuroradiology, and radiation therapy is required for the management and treatment of these sometimes incurable lesions to obtain the optimal result with a minimum risk of morbidity. In this chapter we discuss the unique features of AVMs in children and highlight how they differ from similar lesions in adults. Sections on surgical, interventional neuroradiological, and radiosurgical management will follow a discussion on the presentation and evaluation of the AVMs. Vein of Galen aneurysmal malformations (VGAM) reflect a choroidal arteriovenous disease and, unlike pial AVMs, the actual vascular shunt lies in the subarachnoid space. The clinical presentation, natural history, treatment, and complications of VGAMs are entirely separate from pial AVMs and will not be considered in this chapter. For this reason, AVM, in this chapter, refers to pial AVMs specifically. EPIDEMIOLOGY The prevalence of cerebral AVMs in the overall population is less than 1%, with roughly 10% to 20% occurring in children (1). Thus, the overall prevalence in children is between 0.014% and 0.028% (2). There does not appear to be a gender predilection (3). Most AVMs in children occur sporadically without any familial history, although there are reports (4) of familial cases. Several syndromes have been associated with vascular malformations, including AVMs. In particular, children with Osler–Weber–Rendu disease have a 7.9% risk for developing a symptomatic AVM (5) and potentially multiple AVMs, and the presentation of a visual pathway or midbrain AVM along with ipsilateral facial nevi should suggest the possible presence of Wyburn–Mason syndrome (6). Overall, multiple AVMs, even in the absence of a recognized syndrome, are more common in children than adults, as is a predilection for the posterior fossa, with up to 25% of pediatric AVMs occurring below the tentorium (Fig. 1) (7). Finally, it has been suggested that pediatric AVMs are larger on average than adult AVMs (8), although a pathophysiological basis for this finding remains unclear. It has been posited that expression of vascular endothelial growth factor (VEGF) may play a role in determining the size of AVMs (9) and perhaps in explaining some of the difference between pediatric and adult lesions. DEVELOPMENTAL BIOLOGY OF AVMs IN CHILDREN Although the past decades have witnessed an explosion in the technology available to treat AVMs, progress in understanding the molecular mechanisms that regulate their development has been less rapid. As scientists begin to elucidate the mechanisms of normal vasculogenesis and angiogenesis, the manner in which those pathways relate to abnormal vessel development will undoubtedly become clearer. VEGF and fibroblast growth factor-2 (FGF2) are expressed at high levels during embryonic development but are normally absent in adult cerebral vasculature. VEGF, FGF2, and transforming growth factor-b1 expression in cerebral vascular
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Figure 1 Arteriovenous malformation (AVM) at the cortical surface of the right cerebellar hemisphere. Pediatric AVMs have a propensity for occurrence at infratentorial locations, in contrast to AVMs in adults. (See color insert.)
malformations may be regulated by proliferation of new vessels, hemodynamic stress, ischemia, or hemorrhage (10). VEGF is expressed in the subendothelial layer and media of vessels comprising AVMs, whereas FGF2 is expressed in the media of AVM vessels. The receptors for these factors are also found to be in a tightly regulated pattern within and around cerebral AVMs. In one study, abnormally low levels of endothelial cell-specific receptor tyrosine kinases, Tie-2 and VEGF-R2, were found in pathologic AVM specimens, perhaps contributing to their aberrant vasculature phenotype. Low Tie-2 expression may explain poor periendothelial cell support structures in AVMs—a factor that could explain their unregulated size and propensity to hemorrhage (11). VEGF receptors are highly expressed during embryonic vascular development and are down-regulated in adult vasculature, including the cerebral vasculature. VEGF binding to VEGF-R2 induces the endothelial cells to proliferate and migrate. VEGF expression and AVM growth are related, and VEGF expression may even correlate with the recurrence of AVMs in the pediatric population (9). Because proper vascular growth requires ordered arrangements of endothelial and perivascular cells, it is not hard to hypothesize that AVM formation and perhaps the continued growth of these lesions may be strongly influenced by disordered pathways involving VEGF and its downstream receptors. These growth factor receptors could conceivably be therapeutic targets within the endothelial or perivascular layers of developing AVMs. Unresectable, complex, or large AVMs may be approached with molecular targeting, perhaps in combination with endovascular or open surgical delivery techniques.
NATURAL HISTORY The origin of AVMs has for the most part been considered to be congenital, although this issue cannot be considered without controversy. A recent report on the de novo presentation of a Spetzler–Martin Grade II AVM in a seven-year-old child four years after a mild head injury with a negative MRI at the time of injury (12) demonstrates that AVMs are not necessarily present at the time of birth. Almost all children with AVMs present with either a hemorrhage and the resultant neurologic sequelae or, less commonly, a first-time seizure (13). By contrast, hemorrhage is a less frequent presentation in adults. Up to 75% of children with AVMs present with hemorrhage, and 15% present with seizures (14). Infants with AVMs can present with high-output heart failure when there is a large arteriovenous shunt, as is often the case with vein of Galen malformations. In addition, infants may present with increasing head circumference or signs of raised intracranial pressure from hydrocephalus. This phenomenon is believed to be secondary to the high venous pressures caused by the AVM, precluding an adequate gradient to allow cerebrospinal fluid absorption across the arachnoid granulations. Children also can present with neurologic symptoms referable to mass effect from a large venous draining vein or varix (Fig. 2), an uncommon presentation in adults.
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Figure 2 Internal carotid artery injection indicating an early draining venous outflow into the sagittal sinus. Complex variceal formation is seen (A) immediately past the nidus. These varices can obtain very large sizes and result in neurologic symptoms secondary to mass effect in children. A combination of embolization and surgical excision resulted in an angiographic cure (B) at early follow-up.
In addition to hemorrhage being the most common presentation of AVM rupture, spontaneous intracranial hemorrhage is most often caused by a ruptured AVM, and a child with new intracranial hemorrhage is presumed to have an underlying vascular anomaly until proven otherwise. This presumption is crucial in the early management of these children because attempts to decompress a clot in the face of uncontrollable intracranial pressure must be performed with full expectation of finding an AVM. A recent addition to most tertiary care centers with neurosurgical care is computed tomography angiography (CTA), which can be done expediently whenever a CT is being performed. While not as detailed as MRI or catheter angiography, CTA may be quite useful in safely guiding a life-saving clot evacuation before the lesion can be further characterized and embolized. When the risks and benefits of AVM management are weighed in adults, advanced age and medical comorbidities often guide surgeons away from aggressive management of higher-grade lesions. In children, medical comorbidities are not usually present. The natural history of AVMs with associated risk factors has not been determined specifically for children. With a risk of hemorrhage in adults of 2% to 4% per year (15), the risk of recurrent hemorrhage and progressive disability or death usually directs the management toward an attempted cure, when possible. The risk of a rebleed is also believed to be slightly higher in the first year after the initial presentation, with rates quoted as high as 6% for the first year for all AVMs taken together, although many factors to be discussed subsequently, such as AVM size, venous drainage, depth in the brain, and associated aneurysms, all factor into the rebleed rate (16). Subsequent hemorrhages carry grave consequences: a 50% morbidity rate and a 10% mortality rate (17). Further differentiating AVM management in adults and children is the plasticity that the developing central nervous system demonstrates in cases of trauma or hemorrhage. For example, the proposed resection of a dominant parietal lobe lesion in an adult may cause serious consternation for fear of sacrificing venous drainage from well-established cortical regions subserving language. However, the same lesion may be more aggressively approached in a five-year-old child in whom language may yet have time to lateralize to the contralateral hemisphere. In summary, the very high likelihood of repeated hemorrhages and progressive neurologic decline dictates a more aggressive management paradigm in children than in adults that is imperative to integrate into the interdisciplinary treatment plan.
PRESENTATION AND EVALUATION OF AVMs IN CHILDREN Physicians who are treating children with suspected AVMs usually obtain a noncontrast head CT in the emergency room at the time of presentation (Fig. 3). Their primary objective is to stabilize the child with respect to airway management and hemodynamic resuscitation if
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Figure 3 Noncontrast head computed tomography scan demonstrating prototypical axial image of a child with a newly discovered arteriovenous malformation (AVM). Children who present with new intracranial hemorrhage are likely to harbor an AVM, and appropriate imaging should be performed to diagnose the lesion before intervention unless the clot requires emergent evacuation.
necessary. Therefore, children often are transferred to tertiary care centers after the imaging has been completed, or the pediatric neurosurgery team is called to the emergency department to evaluate the child after the CT has been completed. Although CT images of AVMs are not ideal, they often provide substantial information. It may be possible to see hemorrhage obviously, as well as calcifications and dilated vessels such as a large draining vein, and even to define the nidus if contrast is given. Once the child has been evaluated, it must be decided whether the child has an emergent neurosurgical need such as ventriculostomy placement or evacuation of the intracranial hemorrhage. The responding physicians are responsible for initiating antiepileptic medication and strict blood pressure control with arterial line monitoring to prevent further seizures or hemorrhage; these measures will directly assist in controlling the intracranial pressure (ICP). If the child is hemodynamically and neurologically stable, several other imaging options are available with which to better define and evaluate the malformation including magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), CTA, and catheter angiography. MRI with MRA is often the study of choice because it offers excellent information about the architecture of the feeding vessels, nidus, and early draining vein, but the study is often difficult to obtain in children without sedation. It also is sensitive enough to identify the age of blood products (Fig. 4). Despite the amount of information that can be obtained with MRI and CTA, these studies still are not as useful as formal catheter angiography (Fig. 5),
Figure 4 Axial magnetic resonance imaging images from the same patient in Figure 3. As can be seen on the T1FLAIR (A), gradient-echo (B), and magnetic resonance angiography (C), a large, acute clot in the temporal lobe is due to the rupture of an underlying vascular malformation with deep venous drainage.
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Figure 5 Preembolization (A) and postembolization (B) of a right posterior cerebral artery-fed arteriovenous malformation. The vertebral artery injection shows a nidus and early draining vein from the malformation before embolization, and an angiographic cure immediately following the procedure.
which requires sedation and general anesthesia. Besides the need for anesthesia, the other minimal risks include the use of the femoral artery for cannulation, which can be quite small in children and at risk for occlusion, and the need for a dye load with its associated risks.
CONSIDERATIONS FOR INTERVENTION Surgical intervention in a child with an angiographically proven AVM must be dictated by an understanding of the goals of surgery because they pertain to the natural history of the lesion. There are several therapeutic goals. The most important is to prevent recurrent hemorrhage. Controlling symptoms related to vascular steal or AVM-related seizures are also legitimate goals of surgery in this population, even when complete surgical excision cannot be safely attempted. Surgery remains the cornerstone of pediatric AVM management, although the outcomes depend very much on the surgical risks for each patient (18,19). The Spetzler–Martin scheme has been widely adopted as the best predictor of the risk of surgical morbidity (20,21). In this system, points are assigned to lesions according to their size, pattern of venous drainage, and proximity to eloquent parenchyma. When the points are summed, the system yields five possible grades of lesions. The largest lesions combined with deep venous drainage near eloquent areas of the brain receive a grade of V. This system translates practically into being able to assign a risk of morbidity—in the case of grade V lesions, approximately 20% major morbidity—to undergoing surgical resection of the lesion. In adults, a basic division occurs between grades III and IV, with vascular surgeons recommending intervention for AVMs with grades of I to III. In children, this division is not as clear, as the lifetime morbidity risk associated with not operating on a higher grade AVM in a child may outweigh the risks associated with surgery even on complex deep lesions. While the Spetzler–Martin grading scheme may accurately represent the architecture of AVMs in both children and adults, it has been shown to be a predictor of outcome only in adults.
TIMING OF INTERVENTION The presentation of the AVM to clinical attention is the primary determinant of the temporal management. A child who presents with a superficial lesion in the left temporal lobe that is causing seizures and speech arrest would benefit from seizure control, functional mapping of language areas, and outpatient angiography followed by planned resection. By contrast, a child who presents with depressed mental status, hemiparesis, and a sluggish pupil requires urgent decompression of a hematoma without the benefits of anything beyond a CT, perhaps with contrast but certainly without time devoted to angiographic evaluation of the presumed underlying AVM.
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At the time of surgery, an experienced pediatric surgeon may feel that the lesion is selfevident and that resection is warranted without further imaging. An equally valid approach would be decompression of the hematoma and stabilization of ICP before complete evaluation of the lesion and subsequent possible resection. The latter approach allows for thorough angiographic evaluation and possible embolization. For lesions that are larger than grade II, preoperative embolization is becoming a routine part of pediatric AVM management at many tertiary care centers with on-call interventional neuroradiologists. PREOPERATIVE EMBOLIZATION The evolution of AVM treatment to include preoperative embolization was natural. As angiographic evaluation became the standard of care, the benefits of operating on a partially embolized lesion, namely better hemostasis and less blood loss, became evident as well (22,23). In a 20-kg child, the amelioration of intraoperative blood loss is far more important than in an adult who has a several-fold greater circulating blood volume. When the risks and benefits of preoperative embolization and surgery are discussed with parents of children with AVMs, the question of whether embolization alone is sufficient to control the lesion should be expected. The simple answer is that the success rate of embolization alone does not nearly approach that of embolization and surgery to prevent further hemorrhage or to achieve a radiographic cure (24). Retrospective studies have placed the cure rate of embolization (Fig. 6) without further adjuvant treatment at less than 10% (21,25). Thus, the neo-adjuvant nature of the procedure to facilitate, not replace, surgery must be emphasized to parents, along with the risks of rebleeding from incompletely embolized AVMs.
Figure 6 Cerebral angiography showing a typical pial arteriovenous malformation (A) with residual nidus visible after intravascular treatment (B). Selective catheterization shows recurrent vascular malformation 18 months following primary embolization (C).
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In addition to routine preoperative embolization of lower grade AVMs, staged embolization of larger and more complex lesions may also be within the AVM treatment paradigm in children. Staged procedures usually are performed in nonoperative lesions such as deep thalamic AVMs, but they may play a role in large superficial lesions as well. Blood hydrodynamics through a residual AVM may be altered when feeding vessels are sacrificed during intra-arterial embolization. The residual abnormal vessels may inherit a volume of blood flow per minute that they were not previously encountering, making these leaky vessels more prone to hemorrhage. Thus, for large complex, AVMs, one or two large feeders are embolized per treatment. The lesions then tend to undergo some degree of remodeling with changed blood flow dynamics. A close working relationship between the pediatric neurosurgeon and the interventional neuroradiologist is essential to optimizing the results obtained from preoperative embolization. Another role for partial embolization is as an adjunct to stereotactic radiosurgery (SRS), a nonoperative modality. We discuss this treatment at length below.
STEREOTACTIC RADIOSURGERY The goal of SRS in treating pediatric AVMs is the complete obliteration of the lesion with preservation of neurological function. During the last decade, accumulating experience has placed SRS firmly within the acceptable treatment paradigm for pediatric AVMs. The remaining questions relate to the associated risks and the long-term obliteration rates. Three recent large retrospective studies have focused on the complication and obliteration rates for AVMs in patients under the age of 18 years (26–28). In the largest study of 53 children with AVMs treated with SRS and followed for at least three years, Levy et al. reported a 74% complete AVM obliteration rate. The obliteration rates, defined by MRI or angiography, were best for lesions smaller than 3 cm. In one-third of the patients, radiosurgery was performed as an adjunct to surgery or embolization, supporting the growing experience of multimodality treatment of AVMs. The obliteration of pediatric AVMs must not be taken entirely literally, however, as an infrequent but well-recognized phenomenon of recurrent AVMs in children mandates that they be monitored for many years after successful obliteration of their lesions (29). This phenomenon does not appear to be related to the modality of treatment, but rather appears to be an inherent propensity for regrowth, because pediatric AVMs have recurred after angiographically confirmed surgical cures as well (30). We advocate yearly MRI and angiography at five years, or sooner if the MRI results suggest recurrence. The only significant morbidity reported for the largest series occurred in a child with a brain stem AVM who experienced posttreatment edema and worsening of gait ataxia. Such low rates of morbidity are noteworthy, especially in light of the fact that 75% of the malformations were complex (Spetzler–Martin Grades III/IV) and presumably could not be surgically treated with equally low risks. However, the use of any form of radiation for young children is associated with risk because of ongoing cerebral development and maturation. With respect to efficacy, four children experienced hemorrhage during the follow-up period. One of the episodes resulted in death 40 weeks after treatment. Rebleeding during the period after SRS remains a concern when the optimal therapy is being chosen. Therefore, although early studies seem to support the use of SRS for complex AVMs in children, similar justification may not exist for using SRS to treat less complex malformations (Spetzler–Martin Grades I/II) where the risk to rebleed while waiting for complete obliteration of the lesions may outweigh the risks of surgery. Other possible complications that do not occur with embolization and surgery, including radiation-induced secondary tumors, radiation necrosis, and vasculopathies, are all valid concerns in a population of children with otherwise normal life expectancies. In only 17 patients treated at the University of Pennsylvania with a linear accelerator, two developed radiation necrosis and two developed vasculopathies (24). It appears that for most radiation-based treatments, the best outcomes are for the smallest lesions, which are similarly curable with surgical resection, and the most complications occur with those lesions not amenable to safe resection. Thus, the niche for radiosurgery in the treatment of pediatric AVMs appears to be still defining itself, although it does seem likely that for some percentage of unresectable AVMs, a combination of embolization and SRS, perhaps even intensity-modulated radiosurgery (31), will become standard treatment.
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Figure 7 Intraoperative photograph demonstrating a pial arteriovenous malformation on the cortical surface of the right parietal lobe in a seven-year old child. Arterial feeders (A), a tangled vascular nidus (N), and large arterialized venous outflow (V) are all visible through this dural opening. (See color insert.)
SURGICAL TECHNIQUE Planning for complete surgical excision of parenchymal pediatric AVMs usually involves preoperative angiography, frameless stereotaxy, and coordination with neuroanesthesia. Due to the fragile hemodynamics of small children with limited intravascular reserves, an arterial line, a central venous line, and electroencephalography leads all are placed in anticipation of possible blood loss and the need for burst suppression for cerebral protection. Mild intraoperative hypothermia is often used for the same reason. The child is positioned in either an adult or pediatric three-pin head fixation, depending on age and weight, or on a simple padded headrest in the case of an infant. We routinely use a horseshoe headrest for children under two years of age and at least a four-pin fixation for slightly older children. Frameless navigation cannot be performed in children too young for skull fixation. These children are also not candidates for functional MRI or intraoperative corticography, making a complex resection in a young child a treacherous undertaking. The opening is no different than that for any pediatric craniotomy with the one caveat of being cognizant of the possible contributions of meningeal vessels to the vascular malformation. Microsurgical dissection of the AVM is performed under the operating microscope and proceeds circumferentially around the lesion in the plane between parenchyma and abnormal vasculature (Fig. 7). It is of utmost importance during surgery to be certain that feeding vessels planned for sacrifice are not feeding normal parenchyma, and that all of the draining veins are not sacrificed until the AVM’s arterial supply has been extirpated completely. These lesions are often extremely fragile and subject to hemorrhage with even minor manipulation. Teflon-coated, irrigating bipolar cautery is essential along with topical hemostatic agents and patience. COMPLICATIONS AVOIDANCE Hemorrhage is certainly the most feared complication before, during, and after AVM resection. Intraoperative blood loss, even if not from frank uncontrollable hemorrhage is crucial to limit in small children whose hemodynamic reserves are limited. Hemodynamic shock can ensue after one-quarter of a child’s blood volume has been lost, an amount that is very small in infants and small children. Blood volume in milliliters can be roughly calculated by multiplying the child’s weight in kilograms by 80, and thus a 10-kg one-year-old child can go into shock after losing as little as 200 mL of blood.
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Although avoiding hemorrhagic complications is the responsibility of the surgeon, the anesthesia team must alert the surgical team to blood loss and, more importantly, to any hemodynamic consequences, including tachycardia or hypotension, which may necessitate temporary cessation of dissection or abortion of the case entirely. Attempts to minimize blood loss during the scalp opening, craniotomy, and dural reflection must be rigorous, as must meticulous circumferential dissection and avoidance of premature sacrifice of draining veins. In conjunction with preoperative embolization, these techniques will help to avoid catastrophic hemorrhage. Aside from hemorrhage, the major complications involve injury or resection of surrounding parenchyma, either through direct resection or, more commonly, due to sacrifice of vessels that partially supplied those territories. Attention to the preoperative MRI and angiogram will help to define the limits of resection along with intraoperative stereotaxy and visual guidance. Resecting unnecessary cortex is often balanced against leaving behind residual AVM. The surgeon should not hesitate to perform an intraoperative angiogram if there is concern about leaving residual AVM that may necessitate future surgery. In the immediate postoperative setting, several complications may arise. Postoperative hematomas, either from poor resection cavity hemostasis or from residual AVM, are possible surgical emergencies requiring reoperation. Of less obvious but equally dangerous concern is swelling or hemorrhage in surrounding brain due to redistribution of vascular flow. Blood that was being directed through a very high flow malformation is now redirected into smaller vessels. The parenchyma supplied by these vessels is not only used to such high flow, it likely has been the victim of vascular steal from the adjacent malformation. When the hyperperfusion of that tissue outstrips the autoregulatory mechanisms of the vessels, infarct, edema, and hemorrhage all may result over a period of hours to days (32). Seizures also may occur postoperatively, and care must be taken to ensure strict control of blood pressure in these instances. It has been calculated that new onset seizures occur in more than 10% of children after AVM resection, although less than half of them will require chronic seizure control (33). Vasospasm, stroke, and vascular thrombosis are rare but reported complications in children. In summary, the postoperative patient’s complications will depend almost entirely on the extent of resection and the ability of the brain to compensate for new blood flow dynamics. However, the intensive monitoring of these children with arterial lines and frequent neurologic checks will detect any complications early and allow prompt intervention. OUTCOMES The exact basis for judging neurosurgical success in children with AVMs may differ from series to series, but the most important factors are prevention of further hemorrhage, control of seizures, and avoidance of neurologic decline. On the basis of these criteria, it now appears appropriate to quote a 95% success rate, with angiographic obliteration rates nearly matching that (34). The rate of severe morbidity is close to 10%, and the mortality rate approximates 5% depending on the size of the series and the average grade of the lesions resected (7,16,35). DiRocco et al. (36) suggest that of all prognostic factors, neurologic status may be the best predictive factor of good outcome. Children with devastating hemorrhages may eventually recover to a degree not possible in adults with similar hemorrhages and neurologic grades. In one study, more than 50% of comatose children who survived a ruptured AVM had a good functional outcome (37). With respect to seizure control, more than half of the children who present initially with seizures are seizure-free without antiepileptic medication (29) after resection. Early surgery and a younger age prognosticate better long-term seizure control in children (30). Because of the possibility of AVM recurrence (26,37,38), children must be followed for several years after treatment for AVM irrespective of the mode of treatment. We favor yearly MRIs due to ease and noninvasiveness when compared with angiography, but angiography must be done at some point within the first several years after resection to confirm obliteration. We also perform an angiogram at a five-year interval from a suspected cure to evaluate for subclinical recurrence. For unknown reasons, likely related to continued secretion of growth factors, AVMs in children seem to be at the highest risk of recurrence after apparent obliteration (29). Over the last 25 years, the management of pediatric AVMs has evolved into a multidisciplinary art requiring the close interaction of neurological surgeons, interventional
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neuroradiologists, and radiation oncologists as well as neuroanesthesiologists and pediatric intensivists. To optimize the neurologic and angiographic outcomes, each child presenting with an AVM must have an individualized treatment paradigm designed with those goals as primary endpoints. As embolization, surgery, and SRS become further refined, and indications for each better defined, we will be able to offer children with these lesions an increasingly excellent chance for a complete recovery and angiographic cure. REFERENCES 1. Millar C, Bissonnette B, Humphreys RP. Cerebral arteriovenous malformations in children. Can J Anesth 1994; 41:321–331. 2. Garza-Mercado R, Cavazos E, Tamez-Montez D. Cerebral arteriovenous malformations in children and adolescents. Surg Neurol 1987; 27:131–140. 3. Itoyama Y, Uemura S, Ushio Y, et al. Natural course of unoperated intracranial arteriovenous malformations: study of 50 cases. J Neurosurg 1989; 71:805–809. 4. Aberfeld DC, Rao KR. Familial arteriovenous malformations of the brain. Neurology 1981; 31:184–186. 5. Roman G, Fisher M, Perl DP. Neurological manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): report of 2 cases and review of the literature. Ann Neurol 1978; 4:130–144. 6. Wyburn-Mason R. Arteriovenous aneurysms of midbrain and retina, facial naevi and mental changes. Brain 1943; 66:12–203. 7. Humphreys RP, Hendrick BE, Hoffman HJ. Arteriovenous malformations of the brainstem in childhood. Childs Brain 1984; 11:1–11. 8. Yasargil MG. AVM of the brain, clinical considerations, general and special operative techniques, surgical results, nonoperated cases, cavernous and venous angiomas, neuroanesthesia. Microneurosurgery. Vol 3B. New York: Thieme, 1988. 9. Sonstein WJ, Kader A, Michelsen WJ, Llena JF, Hirano A, Casper D. Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study. J Neurosurg 1996; 85(5):838–845. 10. Gault J, Sarin H, Awadallah NA, Shenkar R, Awad IA. Pathobiology of human cerebrovascular malformations: basic mechanisms and clinical relevance. Neurosurgery 2004; 55:1–16. 11. Hashimoto T, Emala C, Joshi S, et al. Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations. Neurosurgery 2000; 47:910–917. 12. Gonzalez LF, Bristol RE, Porter RW, Spetzler RF. De novo presentation of an arteriovenous malformation. Case report and review of the literature. J Neurosurg 2005; 102:726–729. 13. Hofmeister C, Stapf C, Hartmann A, et al. Demographic, morphological and clinical characteristics of 1289 patients with brain arteriovenous malformations. Stroke 2000; 31:1307–1310. 14. Celli P, Ferrante L, Palma L, Cavedon G. Cerebral arteriovenous malformations in children. Acta Neurochir (Wein) 1984; 142:145–158. 15. Brown RD Jr., Wiebers DO, Forbes G. The natural history of unruptured intracranial arteriovenous malformations. J Neurosurg 1988; 68:352–357. 16. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983; 58:331–337. 17. Ondra SL, Troupp H, George ED. The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg 1990; 73:387–391. 18. Caldarelli M, Di Rocco C, Iannelli A, Rollo M, Tamburrini G, Velardi F. Combined management of intracranial vascular malformations in children. J Neurosurg Sci 1997; 41:315–324. 19. Humphreys RP, Hoffman H, Drake M, Rutka J. Choices in the 1990s for the management of pediatric cerebral arteriovenous malformations. Pediatr Neuosurg 1996; 25:277–285. 20. Hamilton MG, Spetzler RF. The prospective application of a grading system for arteriovenous malformations. Neurosurgery 1994; 34:2–7. 21. Spetzler RF, Martin NA. A proposed grading system of arteriovenous malformations. J Neurosurg 1986; 65:476–483. 22. Spetzler RF, Martin NA, Carter LP, et al. Surgical management of large AVMs by staged embolization and operative excision. J Neurosurg 1987; 67:17–28. 23. Wikholm G, Lundqvist C, Svendsen P. Embolization of cerebral arteriovenous malformations, I: technique, morphology and complications. Neuosurgery 1996; 39:448–459. 24. Frizzel RT, Fisher WS III. Cure, morbidity, and mortality associated with embolization of brain arteriovenous malformations: a review of 1246 patients over a 35-year period. Neurosurgery 1995; 37:1031–1040. 25. Guo WY, Karlsson B, Ericson K, Lindqvist M. Even the smallest remnant of an AVM constitutes a risk for further bleeding. Acta Neurochir (Wein) 1993; 121:212–215. 26. Levy EI, Niranjan A, Thompson TP, et al. Radiosurgery for childhood intracranial arteriovenous malformations. Neurosurgery 2000; 47:834–842.
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27. Maity A, Shu HG, Tan JE, et al. Treatment of pediatric intracranial arteriovenous malformations with linear accelerator-based stereotactic radiosurgery: the University of Pennsylvania experience. Pediatr Neurosurg 2004; 40:207–214. 28. Nicolato A, Foroni R, Seghedoni A, et al. Leksell gamma knife radiosurgery for cerebral arteriovenous malformations in pediatric patients. Childs Nerv Syst 2005; 21:301–307. 29. Kader A, Goodrich JT, Sonstein WJ, Stein BM, Carmel PW, Michelsen WJ. Recurrent cerebral arteriovenous malformations after negative postoperative angiograms. J Neurosurg 1996; 85:14–18. 30. Ali MJ, Bendok B, Rosenblatt S, Rose JE, Getch CC, Batjer HH. Recurrence of pediatric cerebral arteriovenous malformations after angiographically documented resection. Pediatr Neurosurg 2003; 39:32–38. 31. Fuss M, Salter BJ, Caron JL, Vollmer DG, Herman TS. Intensity-modulated radiosurgery for childhood arteriovenous malformations. Acta Neurochir (Wein) 2005; 147:1141–1150. 32. Heros RC, Korosue K, Diebold PS. Surgical excision of cerebral arteriovenous malformations: late results. Neurosurgery 1990; 26:570–578. 33. Yeh Hs, Tew JM, Gartner M. Seizure control after surgery on cerebral arteriovenous malformations. J Neurosurg 1993; 78:12–18. 34. Hoh B, Ogilvy C, Butler W, Loeffler J, Putnam C, Chapman P. Multimodality treatment of nongalenic arteriovenous malformations in pediatric patients. Neurosurgery 2000; 47:346–357. 35. Fong D, Chan S. Arteriovenous malformations in children. Childs Nerv Syst 1988; 4:199–203. 36. DiRocco C, Tamburrini G, Roolo M. Cerebral arteriovenous malformations in children. Acta Neurochir (wein) 2000; 142:145–158. 37. Meyer PG, Orliaguet GA, Zerah M, et al. Emergent management of deeply comatose children with acute rupture of cerebral arteriovenous malformations. Can J Anaesth 2000; 47:758–766. 38. Gabriel EM, Sampson JH, Wilkins RH. Recurrence of cerebral arteriovenous malformations after surgical excision: case report. J Neurosurg 1996; 84:879–882.
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Management of Residual Arteriovenous Malformations Daniel P. McCarthy, Stefan A. Mindea, Bernard R. Bendok, Christopher C. Getch, and H. Hunt Batjer Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A.
INTRODUCTION Intracranial arteriovenous malformations (AVMs) are relatively uncommon, with incidence estimates generally on the order of 1 to 100 per 100,000 person-years. Thus it is not surprising that the literature has few articles about the management and outcomes of residual AVMs. Primary treatment modalities include microsurgery, radiosurgery, embolization, and various combinations of these techniques as described throughout this book. Despite the paucity of evidence, several basic principles guide the decision-making process for an AVM that was not fully obliterated by initial treatment. Many of these principles are identical to the ones applied during the management of the primary lesion. This principled framework can then be adapted to the context of the individual case. Average obliteration rates have been estimated at 10% to 20% for embolization, 65% to 85% for radiosurgery, and 89% to 100% for surgery on lesions of Spetzler–Martin Grades I to III (1–3). It is difficult to directly compare these treatments, since a considerable amount of selection bias goes into the initial choice of treatment strategy. Nevertheless, the presence of a residual lesion is a serious problem. The natural history after incomplete obliteration is considered to be no better than that of an untreated lesion. Hemodynamic rearrangement and potential venous occlusion secondary to intervention may even make the natural history of a residual AVM worse than that of an untreated lesion. Incompletely obliterated lesions are therefore almost always corrected by further intervention. It is important to first consider exactly what is meant by the term ‘‘residual AVM.’’ This classification is not monolithic; rather, the term has different implications in different contexts. The classic definition of a residual AVM is remaining nidus with demonstrated arteriovenous shunting. Yet some pathological tissue characteristics, such as dysplastic vessels, may persist in the absence of a classically defined residual AVM (4,5). There are also times when complete obliteration is not the intended endpoint. The treatment objective may be only a reduction in nidus volume or flow rate to halt a progressing neurological deficit in an elderly patient. In this case, a classically defined residual lesion does not carry the implication of treatment failure. Furthermore, the very nature of a nidus may change due to therapy. The nidal remnant encountered after radiosurgery has vascular characteristics that are significantly different from those of a nidus after embolization. The relevant features of a residual lesion are thus determined by context and must be evaluated with reference to the objective and effects of initial treatment. A common feature of all residual lesions is the morphologic diagnosis. Angiography is the gold standard for AVM detection; magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) do not yet have the ability to reliably visualize the subtle angioarchitecture that often occurs with these lesions. Additional clues specific to each modality may indicate the continued presence of an AVM, such as the red arterialized veins seen during surgery. Yet a definitive diagnosis can be made only with angiography, as these ‘‘red’’ veins may simply represent sluggish outflow (or no outflow) of previously shunted blood. If, however, early venous drainage is detected with angiography, residual AVM is present. The process of evaluating the treatment risk of a residual lesion is not as starkly circumscribed. Most factors relevant to the treatment of primary AVMs, such as proximity to eloquent tissue, remain pertinent. Other characteristics are unique to residual lesions. A residual lesion may have partial occlusion of its venous outflow, or the nidus may be fibrotic because of
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radiation. These features are not seen with untreated AVMs but are of considerable importance in managing residual lesions. The evaluation of a residual AVM is as much dependent on objective criteria as it is on sound surgical judgment. Multiple variables must be integrated in deciding whether the lesion can be conceptualized as merely a remnant of the initial AVM or whether it is significantly different to warrant complete reevaluation. This chapter discusses the major factors and decision-making processes used to determine case-specific management strategies. RESIDUAL MALFORMATIONS AFTER ENDOVASCULAR EMBOLIZATION The field of endovascular intervention has undergone rapid advancement in recent years. Embolization is now a versatile, strategic tool. Since it is used to achieve different goals, the concept of a ‘‘residual’’ lesion after embolization is particularly diverse. In some cases, the objective of embolization is not complete obliteration. Here, the traditional definition of a residual lesion is the intended endpoint. Embolization may also be used to effect a cure, in which case any remaining nidus with shunting will constitute failed treatment. Finally, embolization is more prone than other modalities to leave a particularly dangerous remnant: a residual nidus with venous occlusion. After Adjunctive or Palliative Embolization Some cases call for endovascular intervention in which the objective of treatment is not complete obliteration. Large AVMs are often accompanied by high flow rates that make surgical management difficult. Here a staged approach may use embolization to reduce flow before microsurgery is attempted. Staged embolization may also be used to occlude deep arterial feeders that are difficult to reach surgically until the last phase of the dissection. Nidus volume, a predictor of radiosurgical failure, can be reduced endovascularly. In some cases, severe headache due to external carotid and dural feeders may lead to external carotid embolization as the primary treatment modality (Fig. 1). Finally, a patient’s advanced age, comorbidities, or the extreme operative risk of the lesion itself might indicate that the risks of complete obliteration outweigh the risks of conservative therapy. In this case, partial obliteration may protectively eliminate weak points prone to hemorrhage such as nidal aneurysms (Fig. 2). In addition, partial obliteration may also resolve symptoms stemming from nidus-related steal phenomena in the surrounding tissue by sequential flow reduction and perfusion redistribution. When successful treatment intentionally leaves a residual AVM, management of the remaining malformation is dictated by the original treatment plan. The success of palliative embolization is pragmatically defined by the elimination of symptoms: pain, progression of deficits, or repetitive bleeding. A reasonable follow-up strategy includes future angiography to detect recanalization, periodic magnetic resonance imaging (MRI) to detect changes in the surrounding brain tissue, and periodic clinic visits to identify a change in neurological status. Planning angiographic follow-up after any embolization treatment raises the question of when and how often it should be performed. Totally obliterated nidi can reappear on follow-up angiograms (6). At least one group has reported recanalization occurring two years after polyvinyl alcohol embolization in a patient who demonstrated angiographic obliteration postoperatively and again nine months later (7). Recanalization does not necessarily determine failure, however, since the objective of palliative embolization is a reduction of symptoms regardless of the presence of a residual lesion. If symptoms persist, recur, or become worse, then the surgical team must work with the patient to decide on a management strategy. The endovascular surgeon must decide whether further embolization-induced flow reduction is feasible and offers a reasonable expectation of relief. The risks and benefits of repeat embolization or radiosurgery must be evaluated. The patient’s level of tolerance for current symptoms and potential treatment-related complications will determine an action threshold in the context of the surgical team’s risk–benefit analysis. Failure of adjunctive embolization is more manageable. The inability to reduce the volume or flow rate as much as desired might be considered failure. Causes of failure may relate to tortuosity of access vessels, inability to navigate into the nidus, or inability to catheterize a problematic feeding perforating vessel such as an anterior or posterior choroidal, lenticulostriate, or ophthalmic perforator. Adjunctive therapy reduces the risks involved with curative radiosurgery or microsurgery. It typically is not an absolute requirement in the sense that
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Figure 1 Right temporal–parietal–occipital arteriovenous malformation (AVM) in a 10-year-old boy who presented with severe headaches. (A) Magnetic resonance imaging scan of the brain. (B), (C), and (D): Left external carotid artery angiogram demonstrated a right temporal–parietal–occipital AVM with robust dural-arterial supply from the contralateral external carotid artery. These vessels were successfully embolized with subsequent amelioration of the headache.
curative therapy can still proceed after failed embolization, albeit at a higher risk than would be expected with successful adjunctive treatment. This contingency in particular reveals how a classically defined residual AVM can have little effect on subsequent management strategy. After Curative Embolization Occasionally embolization is used to provide complete obliteration of an AVM. Since the rate of cure is low (8–20%), there are relatively few cases where primary embolization is the most attractive strategy (1). A ‘‘control’’ angiogram can be done while the patient is still catheterized to examine the treated feeders, collaterals, and surrounding normal vessels. As noted before, follow-up angiography is necessary to detect delayed recanalization or reconstitution and to see if occlusion improves with time. If the intervention is not completely successful, there are two types of outcomes: incomplete arterial occlusion with residual shunting and venous compromise. Embolization may fail to achieve total occlusion for a variety of reasons. Tortuosity or constriction of the vasculature may be more challenging than it appeared preoperatively. The size and flow of a fistula might prevent the embolic agent from safely obliterating the arteriovenous connection. Reconstitution of the nidus may occur if flow increases through previously minor feeders. Once the incomplete obliteration is confirmed angiographically, the
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Figure 2 Large right frontal arteriovenous malformation in a 51-year-old male that hemorrhaged on presentation and necessitated an emergent hematoma evacuation. (A) Cerebral angiogram and (B) computed tomographic angiography. A nidal aneurysm was discovered (arrow) on the medial bank of the lesion that received vigorous high flow from multiple lateral lenticulostriate branches.
situation must be reevaluated in order to gain an appreciation of how the malformation has changed. If the intervention had only a minimal impact, then repeat embolization may still be the best option. The endovascular surgeon who performed the initial procedure is in the best position to judge the likely outcome of a second attempt. Even if a second embolization is feasible, reduced flow may now make surgical resection the preferable choice of management. One important new consideration is flow redistribution. Autoregulation in the lesion and surrounding tissue may be defective due to chronic high flow conditions. Flow dynamics in surrounding brain may not be properly stabilized after embolization, and the residual malformation may be destabilized by altered perfusion sources. However, the effects of flow redistribution are typically less important for management considerations than issues like proximity to eloquent tissue, and the AVM can otherwise be surgically evaluated as if it were untreated. Finally, radiosurgery may be an option after embolization when microsurgery is contraindicated. This strategy is reasonable since the factors that initially excluded microsurgery may still be present. Furthermore, lesion volume has been cited as a predictor of radiosurgical success (8), and volume may have been reduced by the initial endovascular treatment. Although embolization for nidus volume reduction has shown some success in combination with radiosurgery (9), controversy remains because these results seem to conflict with other reports indicating that prior embolization is a predictor of radiosurgery failure (8). This correlation has not been thoroughly investigated and must be interpreted with caution. Careful prospective studies are needed to clarify the value of preradiosurgery embolization. Flow redistribution may also play a role, in that it may increase the chance of hemorrhage in the interval between radiosurgical intervention and cure. It is not clear what other factors might make the radiosurgical management of partially embolized AVMs significantly different from that of untreated lesions. The most serious residual lesion after embolization involves venous obstruction. Occlusion in the arterial system can be tolerated because arteries are designed to withstand high transluminal pressures. Venous occlusion exposes relatively thin-walled vessels to an increasing pressure head, resulting in transmural forces that can rupture the vessel wall within the nidus. The danger of venous occlusion is particularly pronounced in AVMs with a single source of venous outflow; multiple draining veins provide alternate routes of exit. It is critical to identify venous occlusion as soon as possible. Ideally, detection would occur during the control angiogram conducted during and after embolization. If significant venous occlusion is discovered, hypotension may be induced while the patient is prepared for emergency surgical treatment. While further embolization to obliterate the AVM completely is an option,
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our experience has proven that even angiographically complete embolization may be followed by hemorrhage in the face of outflow obstruction. In general, it is our recommendation that inadvertent venous embolization that is hemodynamically significant constitutes a surgical emergency, and a craniotomy should be performed immediately. RESIDUAL MALFORMATIONS AFTER RADIOSURGERY The failure to achieve complete obliteration with radiosurgery presents several unique challenges for determining an effective management strategy. The rates of both obliteration and complications are dependent on dosing strategy (10). Because of its increasing use and potential for objective comparison between institutions, lesions not completely obliterated by radiosurgery have been discussed in the literature more than any other type of residual AVM (Fig. 3). The first issues confronted revolve around defining outcomes. Unless it is part of a multimodal approach, the objective of radiosurgery is nearly always complete obliteration. In contrast to primary embolization, computed tomography (CT) and MRI during follow-up are more important with radiosurgery because they can detect and predict tissue necrosis or other radiation-induced complications (11,12). This necrosis has been attributed to local ischemia produced by radiation-induced endothelial and smooth muscle cell proliferation, which progressively occludes the vasculature (13,14). MRI can be suggestive of cure or failure, but angiography still is needed. The question of when exactly angiography can determine treatment failure is controversial. The latency to angiographic cure is generally cited as 24 to 36 months, although the exact follow-up strategy varies with regard to when and how often angiography is conducted. Increased procedures confer greater risk due to the invasive nature of angiography. Angiography at 24 months may underestimate obliteration in a lesion that is still actively progressing. Angiography at 36 months may confer an extra year of increased hemorrhage risk before a patient with truly failed radiosurgical treatment receives further intervention. At least one study has found that radiosurgery decreases the risk of hemorrhage even before complete obliteration is achieved (15). To further complicate matters, it has been reported that a very small percentage of patients with angiographically defined cures experienced hemorrhage or recanalization after more than three years (12,15,16). Dosing parameters must also be taken into account, since there is evidence that they can affect the latency interval to complete obliteration (17). The ideal diagnostic strategy probably involves a combination of angiography and MRI or CT. Angiographic documentation of residual nidus with shunting is clear evidence of failure. Once it is determined that residual nidus with shunting is present, there are two main options for further management: microsurgery or repeat radiosurgery. This decision is largely based on the extent and location of impact the first treatment had on the AVM angioarchitecture and the physiologic eloquence of the AVM site. Initial radiosurgical treatment may have eliminated some risk factors of surgical resection such as the fragile deep periventricular arterioles. In our experience, radiation-induced endothelial damage and intimal thickening render an AVM substantially more manageable by microsurgery. Penetrating arterioles with a proclivity to rupture during deep dissection are usually fibrotic and forgiving after radiosurgery. Microsurgical treatment after failed radiosurgery has been documented as effective, and the lesion has been noted as less vascular and more easily resected (18). However, the residual lesion may still possess characteristics that complicate surgical success. In this case, it is important to understand exactly what caused radiosurgery to fail. Pollock et al. identified reasons for failure in 45 radiosurgical cases (19). The vast majority of failures in this study were related to getting a complete angiographic picture of the lesion and its three-dimensional configuration. Other centers have reported targeting error, which can be related to imaging problems, as a common cause of failure (9,20,21). If radiosurgery is to be repeated, it is essential to be able to overcome the imaging-related problems responsible for initial failure. One interesting finding from the study by Pollock et al. is that in 38% (17/45) of their cases, they attribute failure to potential ‘‘radiobiological resistance’’ (19). Further investigation is warranted to determine how prevalent this phenomenon is and also to identify possible predictors through molecular imaging techniques so that resistant patients are not selected for this therapy. Assuming the cause of initial failure can be overcome, repeat
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Figure 3 Right temporal–polar arteriovenous malformation in a 37-year-old man who was initially treated with radiosurgery. The patient returned with significant edema and residual AVM 1.5 years after radiosurgery. (A) and (B): Original pretreatment magnetic resonance imaging (MRI) and angiogram. (C) and (D): Post-treatment MRI and angiogram. Note the significant edema that persisted in addition to the incompletely treated AVM.
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Figure 4 Right temporo-parietal-occipital arteriovenous malformation (AVM) (A) in a 20-year-old female who presented with seizures but was neurologically intact. She was followed for several years without any change in her neurologic condition. She then developed a homonymous hemianopsia with an acquired Chiari malformation and progressive venopathy as seen on magnetic resonance imaging (MRI) (B). The postembolization angiogram (C) highlights the three-compartment AVM [anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) supply]. Following preoperative embolization, an en-bloc resection was performed uneventfully. No evidence of residual nidus was appreciated during surgical dissection, but the postoperative angiogram demonstrated residual AVM in the superior temporal gyrus and splenium of the corpus callosum (D). These areas had preserved venous drainage and have been treated with radiosurgery.
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radiosurgery may be reasonable. It has been reported that the probability of cure for repeat radiosurgery is no different than the probability calculated for the initial treatment (22). Many centers have reported good success with repeated intervention (11,23,24), and we have had some success using a staged approach with multiple radiosurgical treatments. RESIDUAL MALFORMATIONS AFTER MICROSURGICAL RESECTION In the treatment of AVMs, microsurgery has the longest history and the highest documented cure rate. If resection is the selected form of treatment, then the intention is to remove the entire AVM—a residual lesion will confer no protection against subsequent hemorrhage. However, complete obliteration is not guaranteed. Angiomatous changes in the AVM and extensive leptomeningeal collateralization are the most frequent causes of dissection errors leading to residual nidus. Even the most meticulous preoperative imaging requires the interpretation of a skilled and experienced operator. The complicated mass of vessels can be confusing, efferent and afferent structures are visually similar, and the threat of unnecessarily damaging perinidal tissue is ever-present. Generally, if any nidus remains, either the remnant resembled normal circumferential tissue or the complex, three-dimensional structure of the lesion was difficult to appreciate intraoperatively. Microsurgery provides the luxury of direct visualization of the brain, and in this sense a residual lesion is usually more easily detectable. Nidus tissue may appear visually distinct from nearby functional brain. An even more pronounced indicator is the presence of arterialized veins, which appear red and perhaps thin or dilated. Yet residual lesion may be present despite a lack of visible clues (Fig. 4). At least one group recommends intraoperative imaging in almost all cases to detect a residual AVM (25–27). This strategy allows the surgeon to remove any remaining nidus before the surgery is concluded. An even greater benefit is protecting the patient from the risk of postoperative hemorrhage during the time it takes to detect a residual lesion and return the patient to the operating room. Fritsch and Heros report that before they began regular use of intraoperative angiography, their group experienced two postoperative hemorrhages that might have been avoided if the lesion had been imaged intraoperatively (26). Other groups do not recommend intraoperative angiography (28). They point out that the imaging quality is often poor and the table can prevent getting all the angles necessary to make a thorough examination. In our practice, we have developed a compromise system that functions reasonably well. If the surgeon has any suspicion that residual AVM is present after surgical extirpation, intraoperative angiography is performed. If the surgeon believes that a complete resection has been performed, surgery is concluded. The patient is taken to the intensive care unit with cautious blood pressure control (peak systolic of 110–120) overnight and is kept sedated and on an antihypertensive medication drip. The next morning, a definitive angiogram is performed. When more sophisticated angiographic capability is developed in our operating room, we will perform intraoperative angiograms on all patients before closing. It is important to emphasize the critical importance of high-quality angiographic dynamic imaging as well as experienced interpreters, as the angioarchitecture can be extremely deceptive after resection of complex AVMs. Interpretation is a joint activity between an experienced neuroradiologist and the operating surgeon who has experienced the nuances of the dissection planes. If any nidus or early drainage remains after resection, then it is necessary to intervene. The most common management strategy is repeat surgery. Since surgery was selected as the initial treatment modality, it should still be safe. Most of the lesion has already been resected, so access to vessels in the residual lesion is greatly improved. The one exception is a residual lesion that is extremely close to eloquent tissue (Fig. 5). This piece may remain because of conservative resection during the initial operation. If microsurgery cannot safely remove this remnant, embolization or radiosurgery might be considered. It must be determined, however, whether the risk of surgical resection is higher than the net risk of hemorrhage until endovascular or radiosurgical cure, plus the risk inherent to whichever of these treatments is chosen. In eloquent tissue, the decision is influenced by the preservation, or lack thereof, of acceptable venous drainage. As a general rule, remaining AVMs post-surgery should be immediately resected as venous drainage has been compromised. Given this calculation, careful microsurgery is often warranted in lieu of these alternatives.
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Figure 5 Perirolandic arteriovenous malformation (AVM) in a 45-year-old male that was treated ten years earlier with embolization. The patient presented with progressing hemiparesis. (A) and (B): preoperative magnetic resonance imaging and AP and lateral carotid angiogram. Functional MRI suggested that the motor cortex resided immediately posterior to the AVM. At surgery, a very clean posterior dissection plane was noted. Angiography demonstrated a residual cluster of AVM vessels with early drainage (C) through the Vein of Trolard. The patient came through surgery without worsening of the hemiparesis, and we elected to manage this residual portion of the AVM by maintaining the patient in induced hypotension. Angiography one week later (D) showed the residual tuft of nidus but no venous drainage. Within three months, all evidence of the residual cluster had vanished (E).
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CONCLUSION The management of a residual AVM depends on context, but an optimal treatment strategy can be determined by applying several principles to each unique situation. First, the surgeon must understand the objective and selection criteria used in the initial treatment. It is then important to consider why treatment failed, and how exactly failure has been defined and diagnosed in this case. Since any intervention will have some effect on the AVM, the surgeon must evaluate how the lesion has changed and which characteristics remain the same. Finally, the risks and benefits of each treatment option must be weighed against the natural history of not treating the residual lesion. This analysis will provide an optimum projected outcome that helps to determine whether the residual lesion should be managed with embolization, radiosurgery, microsurgery, a combination of these techniques, or medical therapy. Further investigation must be undertaken with regard to both residual lesions and staged treatment so that surgeons will be better able to formulate their treatment decisions according to an evidence-based approach.
REFERENCES 1. Choi IS, Chavali R, Tantivatana J, Kim SJ. Neuroendovascular surgical procedures for cerebral arteriovenous malformations. In: Batjer HH, Loftus CM, eds. Textbook of Neurological Surgery: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins, 2003:2578–2590. 2. Fleetwood IG, Steinberg GK. Arteriovenous malformations. Lancet 2002; 359:863–873. 3. Ogilvy CS, Stieg PE, Awad I, et al. AHA Scientific Statement: recommendations for the management of intracranial arteriovenous malformations: a statement for healthcare professionals from a special writing group of the Stroke Council, American Stroke Association. Stroke 2001; 32:1458–1471. 4. Solomon RA, Connolly ES Jr., Prestigiacomo CJ, Khandji AG, Pile-Spellman J. Management of residual dysplastic vessels after cerebral arteriovenous malformation resection: implications for postoperative angiography. Neurosurgery 2000; 46:1052–1060; discussion 1060. 5. Stapf C, Connolly ES, Schumacher HC, et al. Dysplastic vessels after surgery for brain arteriovenous malformations. Stroke 2002; 33:1053–1056. 6. Sorimachi T, Koike T, Takeuchi S, et al. Embolization of cerebral arteriovenous malformations achieved with polyvinyl alcohol particles: angiographic reappearance and complications. AJNR Am J Neuroradiol 1999; 20:1323–1328. 7. Standard SC, Guterman LR, Chavis TD, Hopkins LN. Delayed recanalization of a cerebral arteriovenous malformation following angiographic obliteration with polyvinyl alcohol embolization. Surg Neurol 1995; 44:109–112; discussion 112–113. 8. Pollock BE, Flickinger JC, Lunsford LD, Maitz A, Kondziolka D. Factors associated with successful arteriovenous malformation radiosurgery. Neurosurgery 1998; 42:1239–1244; discussion 1244. 9. Foote KD, Friedman WA, Buatti JM, Bova FJ. Radiosurgical procedures for arteriovenous malformations. In: Batjer HH, Loftus CM, eds. Textbook of Neurological Surgery: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins, 2003:2591–2611. 10. Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD. An analysis of the dose-response for arteriovenous malformation radiosurgery and other factors affecting obliteration. Radiother Oncol 2002; 63: 347–354. 11. Levegrun S, Hof H, Essig M, Schlegel W, Debus J. Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: correlation with dose distribution parameters. Int J Radiat Oncol Biol Phys 2004; 59:796–808. 12. Shin M, Kawahara N, Maruyama K, Tago M, Ueki K, Kirino T. Risk of hemorrhage from an arteriovenous malformation confirmed to have been obliterated on angiography after stereotactic radiosurgery. J Neurosurg 2005; 102:842–846. 13. Niranjan A, Gobbel GT, Kondziolka D, Flickinger JC, Lunsford LD. Experimental radiobiological investigations into radiosurgery: present understanding and future directions. Neurosurgery 2004; 55:495–504; discussion 504. 14. Schneider BF, Eberhard DA, Steiner LE. Histopathology of arteriovenous malformations after gamma knife radiosurgery. J Neurosurg 1997; 87:352–357. 15. Maruyama K, Kawahara N, Shin M, et al. The risk of hemorrhage after radiosurgery for cerebral arteriovenous malformations. N Engl J Med 2005; 352:146–153. 16. Lindqvist M, Karlsson B, Guo WY, Kihlstrom L, Lippitz B, Yamamoto M. Angiographic long-term follow-up data for arteriovenous malformations previously proven to be obliterated after gamma knife radiosurgery. Neurosurgery 2000; 46:803–808; discussion 809–810. 17. Shin M, Maruyama K, Kurita H, et al. Analysis of nidus obliteration rates after gamma knife surgery for arteriovenous malformations based on long-term follow-up data: the University of Tokyo experience. J Neurosurg 2004; 101:18–24.
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18. Chang SD, Steinberg GK, Levy RP, et al. Microsurgical resection of incompletely obliterated intracranial arteriovenous malformations following stereotactic radiosurgery. Neurol Med Chir (Tokyo) 1998; 38(suppl):200–207. 19. Pollock BE, Kondziolka D, Lunsford LD, Bissonette D, Flickinger JC. Repeat stereotactic radiosurgery of arteriovenous malformations: factors associated with incomplete obliteration. Neurosurgery 1996; 38:318–324. 20. Ellis TL, Friedman WA, Bova FJ, Kubilis PS, Buatti JM. Analysis of treatment failure after radiosurgery for arteriovenous malformations. J Neurosurg 1998; 89:104–110. 21. Gallina P, Merienne L, Meder JF, Schlienger M, Lefkopoulos D, Merland JJ. Failure in radiosurgery treatment of cerebral arteriovenous malformations. Neurosurgery 1998; 42:996–1002; discussion 1002–1004. 22. Morgan MK. Classification and decision making in treatment and perioperative management, including surgical and radiosurgical decision making. In: Winn HR, Youmans JR, eds. Youmans Neurological Surgery. Philadelphia: Saunders, 2004:2185–2204. 23. Pollock BE, Kline RW, Stafford SL, Foote RL, Schomberg PJ. The rationale and technique of stagedvolume arteriovenous malformation radiosurgery. Int J Radiat Oncol Biol Phys 2000; 48:817–824. 24. Maesawa S, Flickinger JC, Kondziolka D, Lunsford LD. Repeated radiosurgery for incompletely obliterated arteriovenous malformations. J Neurosurg 2000; 92:961–970. 25. Anegawa S, Hayashi T, Torigoe R, Harada K, Kihara S. Intraoperative angiography in the resection of arteriovenous malformations. J Neurosurg 1994; 80:73–78. 26. Fritsch MJ, Heros RC. Surgical management of supratentorial arteriovenous malformations. In: Winn HR, Youmans JR, eds. Youmans Neurological Surgery. Philadelphia: Saunders, 2004:2231–2249. 27. Yanaka K, Matsumaru Y, Okazaki M, et al. Intraoperative angiography in the surgical treatment of cerebral arteriovenous malformations and fistulas. Acta Neurochir (Wien) 2003; 145:377–382; discussion 382–383. 28. Hoh BL, Carter BS, Ogilvy CS. Incidence of residual intracranial AVMs after surgical resection and efficacy of immediate surgical re-exploration. Acta Neurochir (Wien) 2004; 146:1–7; discussion 7.
Section V
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Critical Care Management Mark R. Harrigan Department of Neurosurgery, University of Alabama, Birmingham, Alabama, U.S.A.
B. Gregory Thompson Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, U.S.A.
INTRODUCTION The critical care management of patients with an intracerebral arteriovenous malformation (AVM) is uniquely challenging. Patients with AVMs typically present in young or middle adulthood and do not usually have many coexisting health problems. However, the hemodynamic properties of AVMs, the wide variety of vascular configurations and locations of AVMs, and the potential severity of angiomatous hemorrhage and treatment complications require an aggressive and knowledgeable critical care approach. This chapter reviews aspects of critical care management of patients with AVMs. NEUROLOGICAL MONITORING AND IMAGING Many neurosurgeons prefer to wait for one to three weeks after angiomatous hemorrhage to operate in order to allow the hematoma to be resorbed and the surrounding brain to recover from the initial insult. Much of the role of critical care management between hemorrhage and craniotomy in this situation is to monitor for evidence of rehemorrhage, cerebral edema, or any other neurologic change that may prompt earlier intervention. In the postembolization or postsurgical period, the primary purpose of neurologic monitoring is to predict or identify any of a wide variety of complications. Potential complications of angiomatous hemorrhage include cerebral edema, cerebral ischemia and stroke, seizures, hydrocephalus, electrolyte disorders, and, rarely, vasospasm. Complications associated with AVM surgery include retraction injury, nutrient-artery occlusion, hemorrhage (spontaneous or resulting from inadequate hemostasis or residual AVM), and cerebral edema. General complications of craniotomy include infection, cerebrospinal fluid (CSF) leak, deep venous thrombosis, and pulmonary embolism. The cornerstone of neurologic monitoring in the intensive care unit is the examination. Performed hourly by the nursing staff and at least twice a day by the neurosurgical team, the surveillance neurologic examination must assess mental status and evaluate for focal neurologic deficits. A brief cranial nerve examination and a peripheral motor and sensory examination are usually sufficient, with emphasis on certain aspects of the examination depending on where in the brain the AVM is located. Intracranial Pressure Monitoring Intracranial pressure (ICP) monitoring or ventriculostomy should be considered for patients with angiomatous hemorrhage and coma, hydrocephalus, or significant perioperative cerebral edema. Ventriculostomy is nearly always preferable to permit CSF drainage, if necessary. The authors also use ICP monitoring after resection of large AVMs (5 cm, or Spetzler–Martin Grades IV and V). Patients who harbor large AVMs are generally at higher risk for postoperative edema, seizures, and even normal perfusion pressure breakthrough (NPPB) bleeding (1). Computed Tomography Computed tomography (CT) is fast and inexpensive. A CT scan should be obtained after any significant perioperative change in the patient’s neurologic status. Acute infarction typically is
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not identified on CT for 6 to 12 hours after the event, which is a major limitation of CT. CT angiography can be a useful alternative to conventional angiography in assessing AVM anatomy and identifying residual AVM after treatment. Magnetic Resonance Imaging Magnetic resonance imaging (MRI) is useful in a number of situations. Cerebral edema, venous congestion, and infarction can frequently be differentiated by T2-weighted imaging (2) and diffusion scanning. A delayed, low-grade communicating hydrocephalus, which may be subtle and frequently occurs after intraventricular AVM hemorrhage, is also more readily demonstrated on T2-weighted MRI images than on conventional CT scans. Magnetic resonance angiography can be an effective noninvasive technique to characterize AVMs and also to identify residual AVM after treatment, although catheter angiography is still the ‘‘gold standard’’ for assessment of the presence of a fistula as evidenced by an ‘‘early draining vein.’’ MRI is contraindicated in patients bearing some ferromagnetic materials or cardiac pacemakers and is cumbersome for some critically ill patients. Xenon CT Cerebral Blood Flow Measurement Xenon CT uses nonradioactive xenon gas as a contrast agent in the CT scanner to obtain highresolution, accurate, quantitative images of cerebral blood flow. Xenon CT is useful for preoperative evaluation of patients with AVMs who are suspected of having cerebral steal. Xenon CT studies performed before and after the administration of acetazolamide, a cerebral vasodilator, can identify areas in the brain with abnormal CO2 reactivity. Both supranormal and impaired CO2 reactivity may indicate increased risk of perioperative cerebral edema or NPPB (1). Xenon CT is also useful to assess potential complications after treatment of the AVM. For instance, hypodense areas on postoperative CT can be difficult to explain; they can be caused by intraoperative retraction, venous congestion, or infarction. Xenon CT cerebral blood flow imaging can differentiate these entities. Transcranial Doppler Ultrasonography Transcranial Doppler ultrasonography (TCD) is a noninvasive method to measure blood velocity in intracranial vessels at the level of the circle of Willis. Feeding arteries of AVMs usually have elevated blood velocities and diminished pulsatility indexes; these measurements tend to normalize after treatment (3). Postembolization or postsurgical TCD may be useful to identify blood velocity changes indicative of alterations in cerebral blood flow. Although elevated TCD velocities have been described in hyperperfusion syndrome after carotid endarterectomy (4), published experience with posttreatment TCD as a method to monitor cerebral hyperemia or ischemia is lacking. PERIOPERATIVE CEREBRAL EDEMA Surgical excision or embolization of an AVM can lead to fulminant cerebral edema and intracerebral hemorrhage (1,5–7). Perioperative cerebral edema is an uncommon but potentially catastrophic complication of AVM treatment. Effective management of patients with this phenomenon depends on an understanding of the hemodynamic changes that can occur with obliteration of some AVMs. The hemodynamic effects of AVMs are not completely understood, and existing theories are controversial. AVMs shunt high-flow arterial blood into the low-resistance venous system. There is evidence that some AVMs cause neurologic symptoms by diverting blood away from surrounding brain tissue. The concept of cerebral steal rests on the assumption that cerebral vessels adjacent to an AVM are in competition for blood flow with the AVM, and are thus maximally dilated in an effort to deliver as much flow as possible to their respective regions of brain. Transient ischemic attacks and ischemic stroke in some patients with untreated AVMs are presumed to occur because of steal of cerebral blood flow by the AVM, that is, blood flow in brain tissue falls below the autoregulatory and ischemic thresholds because of diversion into the AVM (8,9). The concept of steal in AVMs began with the observation that brain structures adjacent to AVMs frequently do not opacify with contrast angiography (10). Regional cerebral blood flow adjacent to AVMs is significantly reduced and returns to normal
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after excision of the AVM (11). However, Mast et al. found that progressive focal neurologic deficits are rare in AVM patients, occurring in only 1.3% of cases (12). Thus, the actual contribution of cerebral steal to neurologic deficits in patients with AVMs remains unclear. There is some evidence that chronic maximal arteriolar vasodilation in brain tissue surrounding AVMs can result in vasomotor paralysis. That is, resistance vessels lose their ability, over time, to vasoconstrict in response to elevated perfusion pressure. The existence of maximally dilated resistance vessels surrounding the AVM forms the basis for NPPB, or circulatory breakthrough. According to this view, in rare cases when normal perfusion is suddenly reestablished after resection of an AVM, vessels in the chronically ischemic tissue are unable to vasoconstrict in response to the new (higher) pressure, resulting in capillary breakthrough, cerebral edema, and hemorrhage. In their original report proposing NPPB theory, Spetzler et al. described two patients who suffered brain edema and hemorrhage after surgery or embolization of an AVM (1). In an experimental model of arteriovenous fistula in the cat, the same authors demonstrated that occlusion of the shunt led to a loss of CO2 reactivity and autoregulation. NPPB theory is supported by observations that cerebral blood flow can increase markedly after treatment of AVMs. Intraoperative and postoperative studies with cortically applied thermistors (13), laser Doppler velocimetry (14), SPECT (15), and intravenous 133Xe (16) demonstrated that regional cerebral blood flow increases significantly after the obliteration of AVMs. In a subset of patients, Batjer and Devous found enhanced vasodilation with acetazolamide challenge testing in vessels around AVMs, possibly indicating a heightened risk of posttreatment hyperemia by failure to respond to increased tissue perfusion with protective vasoconstriction (8). If cerebral blood vessels surrounding AVMs are abnormal, then, on a theoretical basis, the modern microsurgical era may bring greater risk of postoperative cerebral edema. Whereas in earlier decades neurosurgeons often removed a margin of brain tissue surrounding an AVM during the resection, today AVM vessels are carefully dissected away from the surrounding brain, leaving as much neural tissue as possible. This change in technique, while maximizing the amount of brain tissue preserved, may carry a higher risk of NPPB, as the chronically impaired resistance vessels in the adjacent brain tissue are also preserved. There is, however, evidence that autoregulation is preserved in brain tissue adjacent to AVMs (12,17). Angiographic examination of patients with perioperative cerebral edema demonstrated venous obstruction in a significant proportion (74%) of cases (5). An emerging alternative explanation for perioperative cerebral edema is occlusive hyperemia (5). According to this view, brain edema and hemorrhage after treatment of AVMs are due to obstruction of venous outflow, with associated passive hyperemia and vascular engorgement, and to sluggish arterial flow in former AVM feeders with worsening of preexisting hypoperfusion, ischemia, and hemorrhage. Wilson and Hieshima reported that interference with venous drainage accounts for most significant complications of AVMs (2). In fact, perioperative cerebral edema may represent a spectrum of fairly uncommon disorders, ranging from arteriolar dysautoregulation to venous occlusion, all presenting as fulminant cerebral edema following treatment of an AVM. Perioperative cerebral edema is uncommon, occurring in 3% or less of cases (5,18–22). It may first present in the operating room or up to 11 days after treatment (5). Cerebral edema may follow embolization as well as AVM excision (2) and usually occurs in higher-grade (Spetzler–Martin Grades IV or V) AVMs (23). Surgical factors that may indicate elevated risk of perioperative cerebral edema include a prolonged and difficult dissection, intraoperative brain swelling, or difficult hemostasis (20). Clinical features can include seizures (5), severe headache (5), focal neurologic deficits (5), abrupt neurologic deterioration (24), and elevated ICP (20,24). Intracerebral hemorrhage may be apparent in the operating room (1) or on radiographic imaging. An early postoperative CT scan should be obtained whenever a patient is felt to be at high risk of cerebral edema or hemorrhage (20). MRI T2-weighted images may also show cerebral edema (2). The management of perioperative cerebral edema includes measures to control brain edema, offer cerebral protection, and manage elevated ICP (24). The head and neck should be kept in a neutral position to minimize jugular vein compression and obstruction of CSF outflow. Glucocorticoids may have some beneficial effect on cerebral edema and provide neural protection. Ventriculostomy to allow measurement of ICP and CSF drainage is useful. Intracranial pressure should be maintained below 20–25 mmHg and cerebral perfusion pressure above 60–70 mmHg. The judicious use of hyperventilation may be effective, as cerebrovascular reactivity to CO2 remains intact after the excision of AVMs (8,25). Osmotic
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diuretics, such as mannitol, are effective; however, serum osmolality should be followed closely when these agents are used. Their use should be suspended if serum osmolality rises above about 310 mosm/kg; serum osmolality above 320 mosm/kg is associated with acute tubular necrosis and renal failure. High-dose barbiturate anesthesia (pentobarbital, 10 mg/kg IV loading dose followed by 5 mg/kg/hr) may help to control elevated ICP and offer some neuroprotective effect (24). Indomethacin, a potent vasoconstrictor, has also been used to control cerebral edema in this setting (26). Aggressive control of blood pressure and avoidance of systemic hypertension are recommended. This regimen of supportive care may suffice to permit reoperation on patients with intracerebral hematoma to be delayed for several days to a time when hemostasis is improved and brain injury associated with reoperation is reduced (6). CARDIOVASCULAR MANAGEMENT Most patients with AVMs do not have preexisting cardiovascular disease. However, angiomatous hemorrhage, craniotomy, and the stress of a prolonged ICU course places a burden on the cardiovascular system, and optimal cardiovascular functioning is necessary to provide adequate cerebral perfusion. Management begins with knowledge of the patient’s medical history and a thorough workup, including a chest X-ray and electrocardiogram. Cardiac monitoring in the ICU permits identification of cardiac arrhythmias, and an in-dwelling arterial catheter is mandatory to monitor blood pressure continuously. Blood Pressure Control Blood pressure alterations can occur in patients with AVMs due to elevated sympathetic tone associated with intracranial hemorrhage, intravascular fluid shifts, and postoperative pain and neurologic changes. Systemic hypotension places the brain at risk of ischemia, and severe hypertension carries the risk of intracerebral hemorrhage; patients are at greatest risk in the first 16 hours after surgery (27). Systolic blood pressure should be kept about 10% below the patient’s baseline blood pressure for at least the first 24 hours after surgery (20). Transient elevations in blood pressure can be managed with intermittent doses of labetalol, a combined alpha and beta antagonist (5–20 mg IV as needed) (28). Labetalol should not be used in patients with bradycardia or asthma. Hydralazine, a direct vasodilator (20–40 mg IV as needed), is useful in patients with bradycardia but carries the potential to increase ICP due to vasodilation. For sustained or refractory elevations in blood pressure, sodium nitroprusside, also a vasodilator, is effective (0.25–8 mg/kg/min IV drip). Nitroprusside may also elevate ICP and carries the additional risk of cyanide toxicity. If nitroprusside is used for more than 24 hours, daily thiocyanate levels should be obtained; the drug should be discontinued when the serum thiocyanate level exceeds 10 mg/100 mL. Hypotension may occur in patients with injury to brainstem regulatory centers (29). Colloids, such as IV solutions containing 5% albumin, may be sufficient to maintain blood pressure at adequate levels. Dopamine, a combined alpha and beta agonist (10–20 mg/kg/min), is useful as a first-line agent. Tachycardia may be associated with dopamine due to its alpha agonist effects; dobutamine, primarily a beta agonist (5–25 mg/kg/min), is a good alternative. Ischemic Injury and Arrhythmias Angiomatous hemorrhage can lead to hypothalamic injury and cause profound catecholamine release. The resulting increase in sympathetic tone can produce subendocardial tissue injury, cardiac conduction abnormalities, and myocardial infarction. These changes can occur in the absence of any preexisting cardiac disease. Electrocardiographic abnormalities associated with intracranial hemorrhage include T-wave inversion, QT segment prolongation, ST elevation or depression, U-waves, and various dysrhythmias (30). Arrhythmias may also be caused by adverse effects of ICP control such as hypokalemia, hypomagnesemia, hypocalcemia, and respiratory alkalosis from hyperventilation (31). A patient who develops electrocardiographic changes should undergo continued cardiac monitoring, aggressive control of blood pressure, and evaluation for myocardial infarction by serial electrocardiograms and serum cardiac enzyme levels. Although depolarization and repolarization changes after intracranial hemorrhage do not necessarily indicate myocardial ischemia, a minority of patients will develop an acute myocardial infarction. Patients with
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myocardial infarction can be given oxygen, intravenous morphine, nitroglycerin, and antiarrhythmics, if needed. Systemic anticoagulation is relatively contraindicated after an intracranial hemorrhage or craniotomy. PULMONARY MANAGEMENT A number of factors can complicate the pulmonary status of patients with AVMs. Altered mental status, preexisting pulmonary conditions, and neurogenic pulmonary disorders can lead to insufficient ventilation or oxygenation. Mechanical ventilation is indicated when spontaneous breathing is inadequate to maintain gas exchange or when the effort required to maintain gas exchange is exhausting the patient. General guidelines for consideration of mechanical ventilation include a respiratory rate greater than 40, vital capacity less than one liter, maximal negative inspiratory pressure less than 20 mmHg, arterial oxygen saturation less than 90%, and paCO2 greater than 45 mmHg (32). Orotracheal intubation is preferred over nasotracheal intubation to minimize the chance of sinusitis and subsequent pneumonia (33). For alert patients, the ventilator should be set on assist-control mode at a low sensitivity. In this setting, the patient breathes at a rate that autoregulates the paCO2 at a normal level, but each breath is mechanically assisted, providing maximal inflation. The volume of each breath is set by limiting the maximal pressure or maximal volume of each breath. The peak inspiratory pressure should generally not exceed 40 cmH2O. If the patient is obtunded or chemically paralyzed, the assist-control mode cannot be used, and the rate is set in addition to the volume (controlled mechanical ventilation or intermittent mandatory ventilation) (33). For patients for whom a long course of mechanical ventilation is anticipated, early (first or second day) tracheostomy is recommended (33). Tracheostomy eliminates problems associated with other forms of intubation such as nasopharyngeal irritation and breakdown, sinus obstruction, sinusitis, and contamination of the lower airway. Weaning is accomplished by progression from assist-control mode to spontaneous breathing with continuous gas flow. Respiratory parameters that indicate successful weaning include a negative inspiratory force of greater than 20 mmHg, a vital capacity of greater than 10 mL/kg/min, ventilation less than 10 L/min, arterial oxygen saturation greater than 90%, and paCO2 less than 45 mmHg (32). The most common pulmonary abnormality in neurologically impaired patients is atelectasis resulting in a ventilation–perfusion mismatch (29,34). Impaired mobility, unchanging position, sedation, aspiration, and preexisting conditions, such as a history of smoking, can all contribute to alveolar collapse. Aggressive pulmonary toilet, regular position changes, and positive pressure ventilation will oppose the formation of atelectasis. Positive end expiratory pressure (PEEP) is also an effective method to open alveoli. However, PEEP should be used with caution in any patient with intracranial vascular disease, as it increases intrathoracic pressure, diminishes venous return, and may increase ICP. Keeping the head of the bed at 30 may minimize the effect of PEEP on ICP (35). Neurogenic pulmonary edema may occur after intracranial hemorrhage. Although the mechanism of this disorder is not completely understood, it is believed that an abrupt intracranial insult leads to an explosive sympathetic discharge, resulting in an increase in pulmonary blood flow, blood pressure, and capillary permeability. Pulmonary edema is accompanied by an inflammatory response. Treatment is essentially supportive. Diuresis with furosemide or ethacrynic acid may promote oxygeneration (29). Positive pressure ventilation with PEEP may also be necessary; this is best done in combination with ventriculostomy or ICP monitoring to avoid excessive elevation of ICP due to the use of PEEP. A pulmonary artery catheter is also useful to guide treatment. Neurogenic pulmonary edema is usually self-limited. FLUIDS AND ELECTROLYTES Patients should be kept euvolemic. Adequate hydration is important to maintain intravascular volume, optimize cerebral perfusion, and avoid cerebral venous thrombosis. Isotonic intravenous fluids containing potassium, run at a maintenance rate, are usually sufficient. Glucose-containing solutions should be avoided because of the tendency of hyperglycemia to exacerbate brain injury (36). Patients may require additional fluid supplementation when osmotic or loop diuretics are used to treat elevated ICP. In uncomplicated patients, the
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monitoring of fluid balance and daily weight is adequate; more complicated patients should undergo central venous pressure monitoring or pulmonary artery catheter monitoring. Hyponatremia (serum sodium <135 mEq/dL) is a common complication of intracranial disease, including angiomatous hemorrhage. This is usually caused by cerebral salt wasting (CSW), in which a renal loss of sodium leads to hyponatremia and a decrease in extracellular fluid volume (37). The mechanism by which this syndrome occurs is not understood. The brain influences renal sodium reabsorption via both humoral and neural mechanisms, and a derangement of either system, or both, may lead to CSW. The other most common cause of hyponatremia in critically ill patients is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). CSW is characterized by a decrease in intravascular fluid volume, whereas SIADH is a euvolemic or hypervolemic state. These conditions may be differentiated by attention to the patient’s fluid volume status. The diagnosis of CSW is indicated by dehydration and decreases in plasma volume, body weight, pulmonary capillary wedge pressure, and central venous pressure, in addition to increases in hematocrit and the blood urea nitrogen:creatinine ratio. Serum osmolality and potassium concentrations may be increased or unchanged. In contrast, SIADH is characterized by increased plasma volume; weight, pulmonary capillary wedge pressure, and central venous pressure may be increased or unchanged. Appropriate treatment for CSW is fluid replacement and maintenance of a positive salt balance. Water and salt supplementation is usually sufficient. Intravenous hydration with normal saline or hypertonic saline, or oral salt may be used alone or in combination, depending on the severity of the hyponatremia. Treatment of SIADH consists of fluid restriction to less than one liter per day (pediatric patients <1 L/m2). Severe hyponatremia due to SIADH calls for salt supplementation with sodium tablets or hypertonic saline. It is critical to differentiate CSW from SIADH; fluid restriction in a patient with CSW will further exacerbate intravascular depletion, diminish cerebral perfusion, and place the patient at risk of cerebral ischemia. Rapid correction of hyponatremia has been associated with pontine myelinolysis, but the optimal rate of correction is unclear. A cautious approach is to raise serum sodium no faster than 0.5 mEq/L/hr (12 mEq/L/day). Diabetes insipidus (DI) may occur with severe brain injury due to angiomatous hemorrhage or a more limited injury to the pituitary stalk. Phenytoin and glucocorticoids may exacerbate DI by inhibition of antidiuretic hormone release. The diagnosis of DI can be made in a patient with intracranial disease when polyuria (urine output >250 mL/hr) is present, hypotonic urine (urine osmolality 50–150 mosm/L or specific gravity 1.005) is present, and serum sodium is normal or elevated (>148 mEq/L). Fluid input and output, as well as serum electrolytes and osmolality, should be followed closely. Intravenous fluids containing free water (e.g., 1/2 normal saline) should be given at a maintenance rate, in addition to urine output replacement on a mL per mL basis. For DI that continues beyond about 12 hours despite fluid replacement, intranasal desmopressin [10 mg (0.1 mL) every 12 hours as needed] is effective. Potassium disorders are relatively infrequent among neurosurgical patients. Serum potassium levels should be checked periodically in patients undergoing prolonged ICU stays. Hypokalemia (serum potassium < 3.5 mEq/L) may be due to gastrointestinal or renal losses or to acute alkalosis. Intravenous potassium chloride replacement should be given no faster than 10 mEq/hr to avoid cardiac arrhythmias. Hyperkalemia (serum potassium >5.0 mEq/L) occurs in renal failure, acute acidosis, and with the use of potassium-sparing diuretics. Intravenous 10% calcium gluconate (5–10 mL) reverses cardiac and neuromuscular toxicity. Sodium bicarbonate (1 amp IV) and regular insulin (5–10 units IV) with glucose (D50, 1 amp IV) cause potassium to be shifted into cells. Cation-exchange resins (e.g., kayexalate 20–50 g oral or 50 g rectal) remove potassium from the body. NUTRITION AND DIABETIC MANAGEMENT Postoperatively, patients with AVMs are systemically hyperdynamic (38). This condition, combined with the catabolic state induced by glucocorticoids, accounts for their elevated nutritional needs. Adequate nutritional support is vital to promote wound healing, prevent catabolism, and optimize immune system and neurologic functioning. Patients who are unable to achieve adequate oral caloric intake should receive supplementation. The authors prefer to administer enteral feedings to ventilated patients and others unable to tolerate oral intake
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beginning approximately 24 hours after surgery. The availability of various enteral formulas permits selection according to the individual needs of the patient. Nutritional needs can be estimated on the basis of height, weight, age, and gender; a stress factor must be added to account for the increased demands associated with the AVM. The caloric requirements of ventilated patients can be determined with more precision using the resting energy expenditure (REE), which employs measurement of exhaled CO2 to determine caloric consumption. An REE should be obtained every other day for patients on prolonged mechanical ventilation, to follow often-changing nutritional needs. Stress-ulcer prophylaxis with H2 blockers, usually for the duration of the ICU stay, is important. Diabetic patients call for particular vigilance. Hyperglycemia has adverse effects on the central nervous system and impairs wound healing; hypoglycemia can impair neurologic functioning and cloud the neurologic examination. Moreover, brittle diabetics can topple into diabetic ketoacidosis with a relatively modest impetus; this state, in turn, can worsen neurologic functioning. Most insulin-requiring diabetic patients need some basal level of exogenous insulin, whether they are ‘‘NPO’’ or not. A common error in surgical ICUs is to relegate the diabetic management of such patients to a universal ‘‘insulin sliding scale,’’ in which the patient is given a standardized dose of insulin only for blood glucose levels above the normal range. This approach fails to take into account the individual needs of the patient and to provide insulin dosing before blood glucose derangements. The following strategy is an effective alternative. Insulin-requiring patients are maintained on half of their regular subcutaneous insulin regimen while they are taking nothing by mouth (e.g., prior to surgery and immediately afterward). As soon as oral intake or enteral feedings are begun, the regular insulin regimen is restored. Blood glucose levels are checked four times a day, and the regimen is modified as needed. If glucose levels remain consistently elevated (>200 mg/dL) despite subcutaneous insulin, an insulin drip is run. An insulin drip permits very tight control of blood glucose levels, and, after 24 hours, allows calculation of the daily insulin requirement for conversion back to a subcutaneous regimen. INFECTIOUS DISEASE Critical illness, immunosuppressant effects of glucocorticoids, and the presence of numerous catheters and lines all place patients at risk of infection. Mechanically ventilated patients are at particular risk of sinusitis and pneumonia. Infectious disease management begins with efforts to diminish risk. Aggressive pulmonary toilet is important for all ventilated patients. In patients for whom a prolonged ventilator-dependent course is anticipated, tracheostomy should be performed early. Vascular access catheters should be changed every three to five days to avoid progression from bacterial colonization to infection. Patients with ventriculostomy or an ICP monitor should be given a broad-spectrum antibiotic for prophylaxis; the authors prefer cefazolin (1 g IV every eight hours). Infections are relatively common in critical care patients. A fever or elevated white blood cell count should prompt a meticulous workup for a source of infection. Blood, sputum, urine cultures, and a chest X-ray are usual screening tests. The risk of ventriculitis or meningitis ranges as high as 8.9% in patients with ventriculostomy (39); CSF analysis and cultures should be ordered for any patient suspected of having an intracranial infection. A head CT with intravenous contrast is also useful to rule out ventriculitis, brain abscess, and sinusitis. Once an infectious source is identified, the antibiotic regimen should be correlated with the culture sensitivities. Fever of unknown origin is a periodic problem in neurosurgical critical care patients. Elevations in brain temperature exacerbate ischemic injury (40) and should be avoided. Multiple possible causes of fever should be investigated, such as infections, deep venous thrombosis, atelectasis, and drug fever. Patients who continue to be febrile despite a negative fever workup should be treated with acetaminophen (650 mg every four hours) and cooling blankets to maintain the body temperature in the normal range. The fever workup should be repeated daily or every other day, if needed, to ensure that a treatable fever source is not overlooked. SEDATION AND ANALGESIA Sedation is necessary for mental status changes related to neurologic injury and anxiety. Adequate analgesia and sedation are also important to avoid wide fluctuations in blood pressure. The
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authors prefer intermittent doses of morphine (2–6 mg IV as needed) and midazolam (1–2 mg IV as needed). The minimal dose of each drug should be given so as not to cloud the neurologic examination. Propofol (continuous IV infusion) is a useful alternative, particularly in patients with elevated ICP. Propofol has a very short half-life, which permits fine-tuning of the dose and frequent interruptions of the infusion for neurologic assessment. Propofol is carried in a lipid-based solution with a relatively high caloric content. This should be taken into consideration when nutritional needs are calculated. In addition, with prolonged infusions, the increased lipid metabolic load can lead to a compensatory respiratory alkalosis, as the patient seeks to blow off the added CO2. Propofol infusion should not be used in children for longer than 24 hours; propofol infusion for more than 48 hours in children is associated with fatal myocardial failure (41). GLUCOCORTICOIDS Glucocorticoids inhibit vasogenic cerebral edema and may be helpful for short-term use in patients with AVMs. The authors use dexamethasone (10 mg IV) at the time of surgery, followed by a short course (6 mg IV every six hours) in the ICU, then a taper. Gastrointestinal protection with an H2 blocker is necessary during treatment with glucocorticoids. THROMBOTIC COMPLICATIONS Neurologically impaired patients are at risk of deep venous thrombosis (DVT), primarily because of immobility. Synchronized compression devices, applied continuously to the lower extremities, prevent lower-extremity DVTs in the majority of cases. The lower extremities of patients at risk of DVT should be examined daily; evidence of DVT includes lower-extremity swelling or discoloration, or fever. A patient suspected of having a DVT should undergo Doppler ultrasonography. Patients with intracranial vascular disease and a DVT are at significant risk of pulmonary embolism. Patients in the perioperative period who are unable to undergo systemic anticoagulation should be considered for placement of a vena cava filter. SEIZURE PROPHYLAXIS AND TREATMENT Seizures are a common presenting feature of patients with AVMs. Patients presenting with angiomatous hemorrhage should be treated with anticonvulsants. The authors prefer to give a loading dose of phenytoin (17 mg/kg IV) on admission, followed by a maintenance regimen of 100 mg IV three times a day. Serum phenytoin levels are checked only in the event of seizure or suspected phenytoin toxicity. Patients undergoing elective resection of an AVM are frequently already on an anticonvulsant regimen. For patients not already being treated with an anticonvulsant, the loading dose of phenytoin can be given before treatment. A seizure in a patient with an AVM is a neurologic emergency. Attention to the airway is critical for nonventilated patients. A seizure in progress can be treated with lorazepam, 4 mg IV over two minutes, and repeated every five minutes up to a maximum dose of 9 mg (42). For seizures refractory to lorazepam, phenobarbital (20 mg/kg IV infused <100 mg/min) is an alternative; hypotension due to myocardial depression is a possible hazard. A new seizure in a patient with AVM during the postoperative period can represent the presence of another complication, such as hemorrhage, infarction, an electrolyte disorder, or a subtherapeutic anticonvulsant level, and thus requires an appropriate workup, including a CT and blood work. REFERENCES 1. Spetzler R, Wilson C, Weinstein P, Mehdorn M, Townsend J, Telles D. Normal perfusion pressure breakthrough theory. Clin Neurosurg 1978; 25:651–672. 2. Wilson C, Hieshima G. Occlusive hyperemia: a new way to think about an old problem. J Neurosurg 1993; 78:165–166. 3. Petty G, Massaro A, Tatemichi T, et al. Transcranial Doppler ultrasonographic changes after treatment for arteriovenous malformations. Stroke 1990; 21:260–266. 4. Powers A, Smith R. Hyperperfusion syndrome after carotid endarterectomy: a transcranial Doppler evaluation. Neurosurgery 1990; 26:56–60.
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5. Al-Rodhan N, Sundt TJ, Piepgras D, Nichols D, Rufenacht D, Stevens L. Occlusive hyperemia: a theory for the hemodynamic complications following resection of intracerebral arteriovenous malformations. J Neurosurg 1993; 78:167–175. 6. Day A, Friedman W, Sypert G, Mickle J. Successful treatment of the normal perfusion pressure breakthrough syndrome. Neurosurgery 1982; 11:625–630. 7. Mullan S, Brown F, Patronas N. Hyperemic and ischemic problems of surgical treatment of arteriovenous malformations. J Neurosurg 1979; 51:757–764. 8. Batjer H, Devous MS. The use of acetazolamide-enhanced regional cerebral blood flow measurement to predict risk to arteriovenous malformation patients. Neurosurgery 1992; 31:213–218. 9. Mohr J. Neurological manifestations and factors related to therapeutic decisions. In: Wilson C, Stein B, eds. Intracranial Arteriovenous Malformations. Baltimore: Williams & Wilkins, 1984:1–11. 10. Feindel W, Perot P. Red cerebral veins: a report on arteriovenous shunts in tumors and cerebral scars. J Neurosurg 1965; 22:315–325. 11. Okabe T, Meyer J, Okayasu H, et al. Xenon-enhanced CT CBF measurements in cerebral AVM’s before and after excision: contributions to pathogenesis and treatment. J Neurosurg 1983; 59:21–31. 12. Mast H, Mohr J, Osipov A, et al. "Steal" is an unestablished mechanism for the clinical presentation of cerebral arteriovenous malformations. Stroke 1995; 26:1215–1220. 13. Barnett G, Little J, Ebrahim Z, Jones S, Friel H. Cerebral circulation during arteriovenous malformation operation. Neurosurgery 1987; 20:836–842. 14. Rosenblum B, Bonner R, Oldfield E. Intraoperative measurement of cortical blood flow adjacent to cerebral AVM using lase Doppler velocimetry. J Neurosurg 1987; 66:396–399. 15. Batjer H, Devous MS, Meyer Y, et al. Cerebrovascular hemodynamics in arteriovenous malformation complicated by normal perfusion pressure breakthrough. Neurosurgery 1988; 22:503–509. 16. Young W, Prohovnik I, Ornstein E. Monitoring of intraoperative cerebral hemodynamics before and after arteriovenous malformation resection. Anesth Analg 1988; 67:1011–1014. 17. Young W, Pile-Spellman J, Prohovnik I, Kader A, Stein B. Evidence for adaptive autoregulatory displacement in hypotensive cortical territories adjacent to arteriovenous malformations. Neurosurgery 1994; 34:601–611. 18. Drake C. Cerebral arteriovenous malformations: considerations for and experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–208. 19. Heros R, Korosue K, Diebold P. Surgical excision of cerebral arteriovenous malformations: late results. Neurosurgery 1990; 26:570–578. 20. Kader A, Young W. Arteriovenous malformations: considerations for perioperative critical care monitoring. In: Batjer H, ed. Cerebrovascular Disease. Philadelphia: Lippincott-Raven, 1997. 21. Morgan M, Johnston I, Hallinan J, Weber N. Complications of surgery for arteriovenous malformation of the brain. J Neurosurg 1993; 78:176–182. 22. Yasargil M. AVM of the Brain, History, Embryology, Pathological Considerations, Hemodynamics, Diagnostic Studies, Microsurgical Anatomy. Microneurosurgery, Vol. IIIA. New York: Thieme Medical, 1988:221–226. 23. Spetzler R, Martin N. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 24. Awad I, Magdinec M, Schubert A. Intracranial hypertension after resection of cerebral arteriovenous malformations: predisposing factors and management strategy. Stroke 1994; 25:611–620. 25. Young W, Prohovnik I, Ornstein E, et al. The effect of arteriovenous malformation resection on cerebrovascular reactivity to carbon dioxide. Neurosurgery 1990; 27:257–267. 26. Hansen P, Knudsen F, Jacobson M, Hasse J, Bartholdy N. Indomethacin in controlling ‘‘normal perfusion pressure breakthrough’’ in a case of a large cerebral arteriovenous malformation. J Neurosurg Anesth 1995; 7:117–120. 27. Stein B, Kader A. Intracranial arteriovenous malformations. Clin Neurosurg 1992; 39:76–113. 28. Orlowski J, Shiesley D, Vidt D, et al. Labetalol to control blood pressure after cerebrovascular surgery. Crit Care Med 1988; 16:765–768. 29. Giannotta S, Schneider J. Perioperative management of patients with intracranial arteriovenous malformations. In: Barrow D, ed. Intracranial Vascular Malformations. Park Ridge, IL: American Association of Neurological Surgeons, 1990:99–109. 30. Ramani A, Shetty U, Kundaje G. Electrocardiographic abnormalities in cerebrovascular accidents. Angiology 1990; 41:681–686. 31. Mokhtar S, Weil M, Shubin H. Risks of alkalosis in critically ill patients and their relationship to ventricular arrhythmias. Chest 1975; 68:421. 32. Geisler F, Salcman M. Respiratory system: physiology, pathophysiology, and management. In: Wirth F, Ratcheson R, eds. Neurosurgical Critical Care. Baltimore: Williams & Wilkins, 1987. 33. Bartlett R. Critical care. In: Greenfield L, Mulholland M, Oldham K, Zelenock G, eds. Surgery: Scientific Principles and Practice. Philadelphia: JB Lippincott, 1993. 34. Schumacker P, Rhodes G, Newell J, et al. Ventilation–perfusion imbalance after head trauma. Am Rev Respir Dis 1979; 119:33–43. 35. Garretson H. Intracranial vascular malformations. In: Wilkins R, Rengachary S, eds. Neurosurgery. Baltimore: Williams & Wilkins, 1985:1448–1458.
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36. Lanier W. Glucose management during cardiopulmonary bypass: cardiovascular and neurologic implications [editorial]. Anesth Analg 1991; 72:423–427. 37. Harrigan M. Cerebral salt wasting: a review. Neurosurgery 1996; 38:152–160. 38. Porembka D, Ebrahim Z, Bloomfield E, Stuebing R. The postoperative hyperdynamic cardiovascular response following intracranial excision of arterial venous malformation (AVM)[abstr]. Anesthesiology 1991; 75:A215. 39. Mayhall C, Archer N, Lamb V. Ventriculostomy-related infections: a prospective epidemiologic study. N Engl J Med 1984; 310:553–559. 40. Ginsberg M, Sternau L, Globus M-T, Dietrich W, Busto R. Therapeutic modulation of brain temperature. Relevance to ischemic brain injury. Cerebrovasc Brain Metab Rev 1992; 4:189–225. 41. Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth 1998; 8:491–499. 42. Levy R, Krall R. Treatment of status epilepticus with lorazepam. Arch Neurol 1984; 41:605–611.
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Surgical Complications Sean D. Lavine Departments of Neurological Surgery and Radiology, Columbia University, College of Physicians and Surgeons, New York Neurological Institute, New York, New York, U.S.A.
Steven L. Giannotta Department of Neurosurgery, University of Southern California, Los Angeles, California, U.S.A.
INTRODUCTION Complications related to the surgical management of intracranial arteriovenous malformations (AVMs) are best thought of in a categorical fashion, broadly divided into preoperative, intraoperative, and postoperative considerations. Proper surgical judgment may be reached only after consideration of a multiplicity of factors in each of these general areas. Appropriate planning and adherence to known surgical principles can avoid many pitfalls of AVM-related surgery. PREOPERATIVE CONSIDERATIONS Medical Condition A complete medical evaluation must be performed on each patient directed to specific body systems as they relate to surgical and anesthetic risk factors. Failure to do so may result in major surgical morbidity or death, simply due to the fact that surgery was recommended for a patient who was medically unable to tolerate the procedure. Particular attention must be given to cardiovascular, pulmonary, renal, liver, and hematologic systems, given the potential for prolonged anesthesia, significant blood loss, and need for fluid and blood product replacement. Electrolyte shifts must be anticipated, evaluated, and treated in a timely and appropriate manner. Investigation for bleeding diatheses should be performed preoperatively, and correction performed before embarking on any surgical procedure. Heros reported a surgical death secondary to underestimation of liver damage in a patient who underwent surgery for an AVM and succumbed to hepatic coma (1). The surgeon also must explore the potential for hormone deficiencies such as thyroid or cortisol when the suspicion arises. The lack of systemic infection should be confirmed as well. The appropriate management of any threatening medical condition should take precedence over surgical planning. In the absence of a life-threatening clot or ruptured feeding artery aneurysm, the delay of definitive AVM treatment is warranted until medical comorbidities have been evaluated and appropriately managed. Given the low acute rerupture rate of cerebral AVMs, the surgical treatment of the lesion may be reasonably postponed until the successful resolution of a pulmonary embolism or myocardial infarction. Neurological Condition Hematoma The timing of AVM surgery after intracranial hemorrhage (ICH) requires careful consideration. A hematoma secondary to AVM rupture of significant size or precarious location may result in mortality or permanent morbidity due to primary or secondary (edema) mass effect (2,3). Although many small hematomas and, occasionally, large (usually lobar) collections can be managed nonsurgically, those that produce significant obtundation and/or herniation syndromes should be urgently evacuated. Simultaneous removal of the AVM should be considered only when the lesion is small and is located immediately adjacent to the clot cavity. With an aggressive approach to AVM resection after acute hemorrhage, reversible neurological deficits may become permanent, as the surrounding parenchyma is more vulnerable to injury in this setting. Once the intracranial dynamics are normalized, proper preoperative radiographic evaluation, surgical planning, and endovascular intervention can proceed in an organized fashion.
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In a study of 10 patients with acute ICH from AVM rupture (two spontaneous and eight secondary to an embolization procedure), eight patients underwent simultaneous hematoma evacuation and AVM resection in the acute phase. Four of these patients were reported to have an ‘‘excellent’’ outcome, three had a ‘‘good’’ outcome, and one had a ‘‘poor’’ outcome; therefore, 50% of these patients were without significant neurological sequelae. Given these results and drawing from extensive experience with AVM treatment, the reviewers of this article, Heros and Samson, recommended that control of intracranial pressure (ICP) with careful hematoma evacuation and delayed AVM resection continue to be the preferred treatment (4). In the case of small hemorrhages or neurological deficit, a delay of several weeks may be indicated before an attempt is made at AVM resection (5,6). This interval allows resolution of brain edema, plateau of recovery from neurological deficit, and liquefaction of the hematoma, leading to both improved radiological evaluation and ease of surgery. Hydrocephalus Acute hydrocephalus secondary to AVM rupture should be managed with external ventricular drainage. A cerebrospinal fluid (CSF) absorption problem in this setting usually represents a posthemorrhagic phenomenon due to intraventricular or subarachnoid blood and may be a temporary condition. Rarely, the location of the AVM may create an obstructive hydrocephalus, which frequently resolves with judicious use of ventricular drainage. Occasionally, permanent CSF diversion systems are required either before or after definitive surgical removal. Steal Phenomenon Occasionally, patients present with a progressive neurological deficit with no radiographic evidence of hemorrhage or increased size of the AVM. These patients may benefit from a more urgent approach to AVM management, especially partial embolization. Failure to respond quickly may result in an irreversible deficit that could have been prevented. These deficits have been attributed to a ‘‘steal phenomenon’’ as the AVM theoretically recruits arterial flow away from normal brain. Partial embolization is the preferred initial step in management in this situation. Steal symptoms usually are ameliorated temporarily, and the potential for postresection perfusion problems minimized (7,8). Venous hypertension may be responsible for neurological symptoms in the absence of hemorrhage. Venous outlet obstruction is more commonly associated with hemorrhage. Neurological symptoms and irreversible cerebral damage could theoretically result from mass effect or ischemia caused by high arterial flow with limited venous drainage, and/or venous arterialization, stenosis, or occlusion (9). Figure 1 demonstrates an AVM with an associated varix closely opposed to the midbrain in a patient who presented with the acute onset of contralateral hemiparesis without evidence of hemorrhage. The likely etiology of her symptoms is the mass effect from the varix on her cerebral peduncle.
Figure 1 Magnetic resonance image (A) and angiographic (B) views of an arteriovenous malformation (AVM) in a patient who presented with the acute onset of contralateral hemiparesis without evidence of hemorrhage. The AVM nidus is within the frontal lobe, representing a resectable lesion; however, an associated varix of significant size (black arrows) is closely opposed to the cerebral peduncle and is the likely cause of her symptoms.
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Intracranial Pressure Control In the case of ruptured AVMs, aggressive control and management of ICP may be required before the patient can undergo definitive treatment of the lesion. Intubation with hyperventilation, mannitol, and glucocorticoids in association with critical care monitoring may salvage a poor-grade patient. Resuscitative measures should always take precedence over surgical planning for patients in poor neurological condition. Special attention is given to blood pressure control and adequate seizure prophylaxis before the surgical procedure. Radiographic Evaluation In the setting of acute hemorrhage from an AVM, a noncontrast computerized tomography (CT) scan provides the most useful initial information about preoperative complications, including the size and location of hemorrhage, amount of mass effect, presence or absence of intraventricular or subarachnoid blood, and presence or absence of hydrocephalus. Serial scans assist in the determination of the appropriate timing for surgical intervention. Resolution of mass effect and surrounding edema is associated with improved surgical results, suggesting again that judicious timing of treatment modalities is an important factor in outcome. Cerebral angiography allows for pathological identification, assessment of the safety of removal, and assessment of the need for/safety of endovascular therapy. The timing of the angiogram is very important, as a study performed long before the time of surgery may not adequately demonstrate the true anatomy encountered during the resection (10). The AVM may spontaneously thrombose either partially or completely, or it may actually increase in size (11–13). As the clot resorbs from a hemorrhage, the configuration of the AVM may change, requiring a different treatment strategy. The presence or absence of aneurysms and their size and location must be confirmed. To circumvent the catastrophic consequences of aneurysm rupture surgical planning may be altered. Occasionally, separate craniotomy or embolization procedures may be required to secure aneurysms before AVM resection (14). However, not all aneurysms require direct treatment, as flow-related aneurysms might regress after AVM resection (Fig. 2). The failure to define the anatomical relationship between the vascular malformation and eloquent brain structures is a major cause of morbidity in the surgical resections of AVMs. Although surgery for lesions in the brain stem is more likely to produce neurological deficit, the surgeon must factor the potential consequences of operating in other regions as well (15). The sensorimotor cortex, internal capsule, speech areas, and optic radiations are often situated near these vascular lesions and must be localized during the surgical planning phase (16). Occasionally, these areas are intimately involved with the AVM and the decision to proceed with surgery must be contrasted against radiosurgery or no therapy at all. Magnetic resonance imaging (MRI) is valuable in identifying the precise anatomical location of the lesion and the proximity of the AVM to eloquent areas. The path of feeding arteries and draining veins frequently is confused with the nidal portion of the lesion, thereby leading to an artificially pessimistic assessment of treatment morbidity. Because it is the nidus that is dissected, only it and the pathway to access it should be considered in risk assessment. Figure 3 demonstrates a lesion that at first may be considered unresectable. However, this lesion has a nidus distinctly separate from eloquent regions, and it is the varix that is closely associated with the brain stem. Functional MRI can identify motor, speech, and visual areas, thereby adding to the information available for surgical planning (17). Xenon CT is used by some groups to assess flow patterns within the AVM and surrounding brain to help predict the likelihood of perioperative perfusion-related complications (18,19). INTRAOPERATIVE CONSIDERATIONS Localization The localization of cortical lesions or lesions that come to a surface is a simple matter. However, deeply situated lesions may require adjunctive measures for selection of the least risky pathway. Stereotactic localization with framed devices such as the Cosman-Roberts-Wells or Leksell system is beneficial for some small and deep lesions (20). Newer frameless stereotactic devices can also assist with both localization and evaluating completeness of resection (21).
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Figure 2 Flow-related aneurysm of the PCA (A and B, black arrows) in a patient with an associated arteriovenous malformation (AVM). Regression of the aneurysm (C, white arrow) after resection of the AVM.
Others use intraoperative hemoclip placement and plain skull roentgenograms, Doppler ultrasound flowmeters, and intraoperative angiography to assist with localization (22,23). Failure to localize the AVM appropriately could result in damage to normal parenchyma or vascular injury while searching for the malformation. Operative Approach Positioning Every attempt should be made to maximize venous drainage of the brain during AVM surgery. The head should be elevated above the heart, and care should be taken not to flex, extend, or rotate the head excessively to avoid the possibility of jugular venous compression. Failure to do so could result in excessive bleeding, brain swelling, and damage to normal parenchyma during resection in a less-than-ideal operative surgical bed. Further details related to positioning can be found in other chapters devoted to AVMs in specific locations. Exposure Supratentorial AVMs are usually cone-shaped, with the widest diameter most superficial. Thus, wide exposure is a surgical necessity from the standpoints of both craniotomy and dural openings. Evaluation of the true anatomy is possible with this approach in terms of arterial
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Figure 3 Arteriovenous malformation that is at high risk for normal perfusion pressure breakthrough. Note the presence of high-flow arterial feeders to this lesion, with paucity of filling of arteries to the surrounding brain.
feeders, draining veins, and anatomical features of the surrounding intracranial structures. Wide exposure also allows for adequate retraction and visualization both with and without the operating microscope. During resection, bleeding occasionally occurs at sites remote from the nidus such as damaged draining veins, and lack of access to these areas complicates control. Major external carotid supply to the AVM may travel through the dural arteries. Bleeding in this area can be managed by preemptive bipolar cautery of the dura, placement of vascular clips, and tacking of the dura against the inner table of the skull at the craniotomy edge. Surgical Technique Immediately after dural opening and an evaluation of the AVM features, the arachnoidal dissection is performed under the magnification and illumination afforded only by the microscope. Failure to adequately visualize the plane of the AVM leads to one of the most common surgical complications—parenchymal damage from a wide margin of resection. Although there is much discussion about the margin of gliotic brain around an AVM, a surgical plane directly on the nidus, while somewhat more technically challenging due to bleeding, reduces the chance of neurological deficit from damage to normal brain. This concern is more important for AVMs closer to eloquent regions than for frontal and temporal pole lesions. While the general principles of AVM surgery are presented in other chapters, it is important to remember that whenever possible, working in fissures and sulci helps to reduce brain injury (24). Additionally, insulated bipolar forceps reduce the chance of nontarget cautery. Some AVMs are described as diffuse, filamentous, or lacy because they contain brain tissue interspersed between fine vascular channels. No specific surgical technique can effectively preserve the intervening brain tissue during the removal of this type of malformation. Luxurious leptomeningeal collateral supply can make a small AVM look quite large and forbidding. In some circumstances, the nidus of the lesion can be isolated from much of its supply by simply bipolar coagulating the leptomeningeal vessels, leaving the underlying cortex intact. A more focused resection of the underlying AVM can then be undertaken with less risk of morbidity. Preoperative decision making must respect the high likelihood of neurological deficit, should resection of such a lesion be attempted in an eloquent area. Avoidance of injury to, or resection of, normal vasculature associated with an AVM is essential to reducing the complications of AVM surgery. Feeding arteries may contain important branches proximal to entering the nidus and, therefore, must be taken only as they
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directly enter this portion of the lesion to avoid brain injury. Wide arachnoid dissection in the sulci and fissures surrounding the AVM enables the surgeon to determine the course of the vasculature near the malformation and take only those vessels that terminate in the nidus (25). ‘‘Vessels of passage’’ are well described in association with cerebral AVMs. These arteries are often small branches of parent arteries that pass through or near the AVM and supply normal, often eloquent, brain beyond the lesion. Although these arteries may be small, they must be followed to and beyond the nidus. Only those branches that feed the nidus should be taken, while preserving the main lumen that extends beyond the malformation and supplies normal brain. Failure to do so could result in both incomplete resection of AVM feeding vessels as well as stroke in a region remote from the malformation. Stein reported outcomes for 180 patients who underwent AVM surgery and attributed postoperative neurological deficit in 27 (15%) of them to the compromise of normal arteries at the time of surgery. Deficits included hemianopsia (16 patients), hemisensory or hemiparesis (8 patients), aphasia (2 patients), and akinetic mutism (1 patient) (26). Intraoperative Hemorrhage General Principles/Venous Injury/Retraction Injury While most surgeries for AVM resection are fraught with some form of bleeding due to the nature of the lesions, some problems are avoided with careful planning and technique. Endovascular embolization techniques can be judiciously used in selected AVMs to reduce the risk of bleeding complications and to assist in surgical removal. AVM embolization is discussed at length in Chapters 12, 30, and 32. Injury to a major venous drainage pathway of the AVM may require an attempt to repair the vein, particularly in those lesions lacking major alternative venous drainage. Bipolar cautery, clip placement, or gentle tamponade alone or in combination may be required to preserve venous drainage until major sources of arterial flow can be isolated and occluded. In cases where substantial blood loss is anticipated, the use of a cell saver may be helpful. Arterialized veins are differentiated from feeding arteries by high magnification inspection for the thickness of the vessel wall and degree of pulsations, often higher in arteries. The vessels can be temporarily occluded with the bipolar or temporary clips to assess for distal collapse or color change (vein) versus continued pulsation (artery). Significant retraction of the brain in parasagittal approaches must be avoided to reduce the likelihood of injury to draining veins. Venous infarction, hemiplegia, and parietal lobe syndromes will likely result from sacrifice of posterior draining veins. Excessive retraction of the temporal lobe near the vein of Labbe´ could also result in venous-related parenchymal damage and serious neurological sequelae. Heros recommends brain resection to access lesions in two specific regions: corpus callosum for deep parasagittal malformations and inferior temporal gyrus for deep temporal AVMs (27). We do not routinely employ hypotension during resection to control bleeding, as we feel that many normal parenchymal vessels may already be maximally dilated to counteract the arteriovenous (AV) shunting from the AVM, and hypotension would result in ischemia. Others believe moderate hypotension is helpful; for example, Sugita and Takayasu recommend induced systolic pressure of 85–90 mmHg during AVM resection (22). In extreme circumstances during an episode of high-flow, poorly controlled bleeding, it may be necessary to use this strategy. Bleeding During AVM Resection Technical Principles
Arterial bleeding from the AVM is usually controllable with judicious bipolar use and gentle tamponade, either manually or with a self-retaining retractor. As dissection of the AVM proceeds into deeper portions of the lesion, persistent bleeding may indicate that the nidus has been violated. Reevaluation of the true plane between the malformation and brain and widening the diameter of dissection will permit control of this type of bleeding. Control of deep perforating vessels near the end of the dissection is the most difficult task in AVM surgery. Maximally dilated with very thin walls, these arteries are fragile and resistant to bipolar cautery. Tamponade is generally ineffective and may obscure deep bleeding into the parenchyma or ventricular system. Patience and clear identification of the margins of the vessels are the keys to hemostasis in this area, as premature vessel rupture leads to retraction into the white matter with continued bleeding. Following these vessels for some distance may
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reveal a portion of the vessel that is more amenable to cautery. An array of maneuvers may be necessary for achieving control of these vessels including the use of routine microaneurysm clips, specially designed microclips, clip occlusion followed by cautery, bipolar cautery of an exposed length of vessel, and tangential cautery of the exposed length of vessel (6,22,28,29). In a series of 112 patients undergoing surgical resection of AVMs, Morgan et al. identified 24 patients with complications (30). Operative deaths occurred in four of these patients; three deaths were reported as secondary to intraoperative hemorrhage, while the fourth was attributed to normal perfusion pressure breakthrough (NPPB). One additional patient had a a nonfatal intraoperative hemorrhage. Therefore, intraoperative hemorrhage accounted for 4/24 (17%) of their total complications (30). Yasargil reported the need for blood transfusion in 124/414 (30%) patients. Of the 124 patients requiring transfusion, 63 (51%) required up to 500 mL, 38 (31%) required 500 to 1500 mL, and 23 (19%) required more than 1500 mL. Six patients were described as having bleeding that was out of control, with a transfusion requirement >5 liters; two patients died and four had ‘‘rewarding results’’ (24). Residual AVM
Occasionally, a daughter nidus may be ‘‘disconnected’’ from the major nidus during the course of AVM resection. This retained malformation may be the cause of persistent intraoperative bleeding. Although intraoperative angiography is the best way to detect residual nidus, this study is not always available or feasible. Doppler sonography is helpful for identifying retained AVM (29,31). Usually, the daughter nidus is hidden in a sulcus closely related to the main nidus and is connected by one or two vessels. Thorough inspection of the resection cavity after the surgeon feels the AVM has been completely removed occasionally reveals a swollen, tense, or deformed margin that usually represents residual malformation. Routine elevation of the patient’s blood pressure 10–15 mmHg above preoperative levels and inspection for 15 minutes before dural closure may also identify retained AVM and prevent complications or the need for additional AVM therapy. Samson and Batjer advocate immediate postoperative angiography under the same anesthetic and return to the operating room for immediate reexploration if the angiogram reveals evidence of persistent arterial to venous shunting (6). Because the resolution of portable intraoperative angiography is not always sufficient to identify retained elements, careful exploration of the resection cavity before closing will improve results. Brain Swelling Although brain swelling during the course of a neurosurgical operation is by no means unique to surgery performed for AVMs, the specific pathophysiology of these lesions presents additional challenges. General causes such as hypercapnia from obstruction of the endotracheal tube or ventilator disconnection must be ruled out first. Venous drainage compromise must also be ruled out by checking the patient’s head, neck, and body position. Once these causes are ruled out, the specific complications of AVM surgery must be explored, including occult bleeding, intraventricular hemorrhage causing acute obstructive hydrocephalus, and cerebral edema from dysautoregulation. Occult Bleeding Whereas an intraparenchymal hematoma of significant size is unlikely to be completely hidden from the surgeon’s view, a portion of the AVM may become isolated from the surgical exposure and bleed when its venous drainage is disconnected. Significant brain swelling may ensue with no immediately apparent cause. Often, this rapidly expanding hematoma will rupture into the previous plane of resection. The plane of resection must be expanded to include the hematoma cavity, and a circumferential dissection must continue after the hematoma has been evacuated. The potential consequences of such a hemorrhage include parenchymal damage from compression and vascular injury during evacuation and control of bleeding. There is also the potential for rupture into the ventricle (see below). Obstructive Hydrocephalus The ventricle is routinely entered on many AVM resections, and proper precautions can be taken in most instances to prevent the complications of expected bleeding into the ventricular
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system. Effective measures include the placement of cotton sponges to block exposed entry points during resection and removal of all identifiable intraventricular clot with extensive irrigation of the exposed ventricular system before closure. Occasionally, bleeding into the ventricle may be occult, and present only as global or focal brain swelling, accompanied by bradycardia, sudden hypertension, or no change in the vital signs. Premature entry into the ventricle secondary to deep dissection with inadequate circumferential exposure of the AVM is the likely source of such bleeding. When suspected, the ventricle must be immediately exposed through the ependymal wall and the clot evacuated. The site of bleeding must be methodically identified and secured. Normal Perfusion Pressure Breakthrough/Occlusive Hyperemia Once all of the previously mentioned causes of swelling have been ruled out during a period of unexplained intraoperative cerebral edema, NPPB must be considered. This condition, originally described by Spetzler and Wilson, has been reported by several other experienced cerebrovascular neurosurgeons and challenged by others (22,32–37). It is characterized by acute massive brain swelling with a firm, distended, herniating margin of brain around the malformation with multiple bleeding points that are resistant to coagulation. The theory states that the brain around the AVM was subjected to prolonged ischemic steal, resulting in chronic dilatation and loss of autoregulation of the brain’s arteries in an attempt to divert blood from the AVM. These vessels are putatively unable to autoregulate when normal perfusion is reestablished by virtue of resection of the AV shunt. The adjacent brain capillary ‘‘breakthrough’’ results in edema and hemorrhage. Figure 3 demonstrates an AVM that is at high risk for NPPB. When NPPB occurs intraoperatively, it usually appears toward the end of the resection when the high flow shunt has been removed. Treatment consists of immediate brain protection from elevated cerebral perfusion pressure (CPP) by EEG burst-suppressive anesthesia with pentobarbital and systemic arterial blood pressure reduction (systolic 80–90 mmHg) with sodium nitroprusside or nicardipine (33). This approach usually arrests the spread of cerebral edema, allowing for craniotomy closure. Hemorrhagic brain tissue may need to be resected as well as residual AVM. This surgery must be performed with absolute hemostasis. An ICP monitor should be placed, and the patient should be taken for immediate cerebral angiography to verify complete AVM resection. Drake reported the occurrence of NPPB in 4/166 (2%) patients undergoing surgery for AVMs, and all four patients died (38). Heros reported the occurrence of NBBP in only 4/300 (1.3%) patients in his surgical series; good outcomes were achieved in three of them (34). Day et al. successfully treated NPPB that began intraoperatively in three patients with three to five days of the regimen described above, including return to the operating room for evacuation of delayed hematomas (33). The ICP should be lowered by pharmacological means over the next 24 hours under barbiturate coma, and head CT scans should be performed for any unexplained alteration. If the surveillance CT scans demonstrate no progression, the patient can be weaned from the antihypertensive agent over the next 12 to 24 hours provided that the ICP remains controlled and systemic blood pressure does not rise inappopriately. The patient can then be weaned from the barbiturate over the following 24 hours (it may take a few days to metabolize and clear systemically). Prevention of NPPB is the best form of treatment. High fistula flow with a paucity of flow entering the immediately adjacent brain is the angiographic hallmark predicting this condition. Staging AVM treatment with repeat operative approaches and/or endovascular embolization techniques can be effective prophylaxis. This approach theoretically allows autoregulation to be restored at a gradual pace, as the high-flow shunting is methodically reduced.
POSTOPERATIVE CONSIDERATIONS Postoperative Hemorrhage/Cerebral Edema Residual AVM is the most common cause of postoperative hemorrhage, and a daughter nidus is one of the most frequent causes of retained lesion. These are often small remnants of malformation left on the wall or within an adjacent sulcus to the main area of nidus resection. These portions are transected from the bulk of the nidus during the attempt to follow a plane of resection along the vascular coils of the lesion.
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In a series of 414 operations reported by Yasargil for cerebral AVM and vein of Galen aneurysms, reexploration for ICH was required in 29 (7%) instances. Twelve of these 29 patients (41%) had residual AVM, nine of which were completely resected. Of the 12 patients who had residual AVM at the second surgery, six had good outcomes and six died (24). Drake reported that of 105 patients studied with postoperative angiograms, 18 (17%) showed residual AVM. Five of these underwent immediate reresection, although one had an early rehemorrhage. With reoperation, two had a good result, one died, and two did poorly due to large hemorrhages. Fourteen other patients had known incomplete resections and did not undergo immediate reoperation. Five of these had delayed rehemorrhages (38). NPPB is a rare but potential cause of postsurgical bleeding. The Mayo Clinic group uses the term ‘‘occlusive hyperemia’’ to describe the phenomenon of otherwise unexplained brain edema and hemorrhage that occasionally occurs in the postoperative period after resection of a high-flow AVM resection. They analyzed 295 cases of AVM resection over a 20-year period and found the most common cause of postoperative neurological deterioration (15/34 cases) was incomplete AVM resection (36). Of the 19 other patients with deterioration, 13 had hemorrhage and edema, and six had edema alone. Postresection angiography revealed that these 19 patients consistently demonstrated slow flow in former AVM feeders and their parenchymal branches, and impaired venous drainage in the region of resection in 14/19 of these patients. They theorize that stagnant flow in arterial feeders produces hypoperfusion significant enough to cause ischemia, with resultant hemorrhage and/or edema, further complicated by venous outflow obstruction; this leads to hyperemia, engorgement, and worsened arterial stagnation. Early diagnosis and aggressive medical and surgical management of these hemorrhagic complications of AVM surgery are essential to preserve the lowest rates of morbidity and mortality that are possible with the treatment of cerebral AVMs. Vascular Thrombosis Similar to the occlusive hyperemia theory, delayed postoperative neurological deficit can result from parenchymal damage secondary to stasis or true occlusion of veins exposed to arterialized blood before AVM resection. Retrograde thrombosis of major arterial feeders back to the point of a proximal major branch has been reported (39). Old age, larger AVM size, and marked dilatation and elongation of feeders were identified as potential risk factors for this complication. This group treated the complication with intra-arterial urokinase infusion and achieved dramatic clinical and angiographic improvement. Dense hemiplegia and aphasia developed acutely, 30 minutes postoperatively after left frontotemporal AVM surgery, and an angiogram revealed occlusion of the M1 segment of the middle cerebral artery (MCA) The patient had a partially retained microcatheter in the MCA feeding the AVM from a previous embolization procedure that was likely the nidus for postoperative thrombosis. After selective M1 urokinase infusion, the MCA recanalized and the patient recovered to have only a mild expressive aphasia and arm and hand apraxia with normal strength (39). Delayed hemorrhagic venous infarction has been reported after AVM resection, presumed secondary to thrombosis of draining veins, and requiring reoperation and evacuation. The patient in this report had a right temporal lesion and achieved a good outcome, with return to the usual occupation, although suffering from a quadrantanopsia (40). Epilepsy A review of the literature reveals that 27% to 38% of patients with AVMs have epilepsy before treatment, and 4% to 30% develop new seizures after treatment (1,41). Most seizure disorders associated with AVMs are effectively controlled with antiepileptic medications, and patients with malformations in epileptogenic regions should routinely be treated prophylactically with these agents. The reduction or elimination of seizure activity in patients with AVMs and pretreatment epilepsy is a separate issue. Seizures were eliminated in roughly 18% of patients in whom arterial feeders were eliminated by ligation or embolization (8,42). AVM resection increases seizure-free outcome to approximately 56% of patients (43,44). Approximately 50% of 55 patients with preoperative epilepsy in a series of 153 patients operated on for AVM were
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seizure free after AVM surgery (45). Directed seizure surgery with AVM resection can result in as much as a 75% chance of seizure-free outcome (46–48). Cerebrospinal Fluid Absorption Most patients who undergo cerebral AVM surgery do not require permanent CSF diversion. However, temporary ventricular dilatation is a frequent complication of both AVM rupture and surgery due to the presence of blood in the ventricular and subarachnoid spaces after these events. External ventricular drainage usually allows for control of ICP as well as removal of bloody CSF during the time that normal absorption pathways recover. Yasargil found that 8.4% of his 414 patients required shunt operations for hydrocephalus, 4.1% before and 4.3% after AVM resection (24). General Medical Issues Awareness of potential complications, proper monitoring for their development, and prophylactic and therapeutic intervention are basic tenets of postsurgical care. Detailed description and management strategies are beyond the scope of this chapter; however, certain conditions are highlighted briefly. Prolonged immobilization will occasionally follow complicated AVM surgery, and the potential complications of deep venous thrombosis and atelectasis can be reduced with appropriate intermittent compression stockings and pulmonary toilet procedures. Early mobilization, incentive spirometry, and involvement of speech, occupational, and physical therapists will also assist with these potential problems. Residual AVM/Regrowth In Yasargil’s series of 414 surgeries for AVM, residual AVM was the cause of postoperative bleeding in the acute phase in twelve patients (24). Three of these patients had bilateral thalamic AVMs that could not be eliminated, and they died. Three patients whose residual AVMs were completely resected at the second surgery also died. Six others made a good recovery. Yasargil identified 10 other patients whose postoperative angiograms showed incomplete removal. Three of these patients refused surgery, and one of these later died of a rebleed.
Figure 4 Regrowth of an arteriovenous malformation (AVM). Postoperative angiogram after resection of an AVM showing complete resection (A), and repeat angiogram in the same patient after the delayed rebleed demonstrating AVM regrowth (B).
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Of the other seven patients, one had a mesencephalic remnant that was deemed inoperable, one died of a postoperative complication, one died of AVM rebleed, and four were considering radiation versus reexploration at the time of publication (24). Yasargil identified five patients who had complete AVM resection and documented regrowth of the AVM that requires additional surgery one to seven years after the first surgery (24). Four of these suffered rehemorrhage before the regrowth was discovered. Paterson and McKissock reported an additional patient who had a rebleed from a completely excised AVM two years after surgery (49). Forster et al. also reported one case of delayed rebleeding in 49 patients who had complete excision of the AVM (50). We have seen this phenomenon in two patients who presented with rebleeds. Both underwent repeat resection and made good recoveries. Figure 4 demonstrates the initial postoperative angiogram of one of the patients, revealing complete AVM resection, and a repeat angiogram after the delayed rebleed demonstrating AVM regrowth. This patient had abused cocaine and metamphetamines in the interim, and it is possible that this behavior affected her vascular system. SUMMARY The management of cerebral AVMs requires the neurosurgeon to draw from all aspects of his/ her training and skill in terms of proper judgment and microsurgical technique. Perhaps the most difficult decision is to determine which patients and lesions are appropriate for surgical intervention. Systematic analysis of pre-, intra-, and postoperative factors will enable the clinician to recommend appropriate evaluation and intervention for these challenging lesions. With the correct approach, many of these malformations can be safely and completely resected surgically with minimal risk of permanent sequelae. Complications are to be expected, however, even in the hands of the most skilled cerebrovascular surgeons who deal with a large number of cerebral AVMs. Appropriate recognition and management of these complications are essential to achieve the excellent outcomes that are possible with surgical treatment of these lesions. REFERENCES 1. Heros RC. Surgery for arteriovenous malformations of the brain. In: Ojemann RG, Ogilvy CS, Crowell RM, Heros RC, eds. Surgical Mangement of Neurovascular Disease. Baltimore: Williams and Wilkins, 1995:419–474. 2. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations. J Neurosurg 1983; 58:331–337. 3. Ondra SL, Troupp H, George ED, Schwab K. The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg 1990; 73:387–391. 4. Jafar J, Rezai A. Acute surgical management of intracranial arteriovenous malformations. Neurosurgery 1994; 34:8–13. 5. Camarata PJ, Heros RC. Arteriovenous malformations of the brain. In: Youmans, ed. Neurological Surgery. Philadelphia: WB Saunders, 1996:1372–1404. 6. Samson DS, Batjer HH. Surface lesions: lobar arteriovenous malformations. In: Apuzzo MLJ, ed. Brain Surgery. Complication Avoidance and Management. New York: Churchill Livingstone, 1990: 1142–1175. 7. McCormick WF. Pathology of vascular malformations of the brain. In: Wilson CB, Stein BM, eds. Intracranial Arteriovenous Malformations. Baltimore: Williams and Wilkins, 1984:44–65. 8. Kusske JA, Kelly WA. Embolization and reduction of the ‘‘steal’’ syndrome in cerebral arteriovenous malformations. J Neurosurg 1974; 40:313–321. 9. Vinuela F, Nombela L, Roach MR, Fox AJ, Pelz DM. Stenotic and occlusive disease of the venous drainage system of deep brain AVMs. J Neurosurg 1985; 63:180–184. 10. Newton TH, Troost BT, Moseley I. Angiography of arteriovenous malformations and fistulas. In: Wilson CB, Stein BM, eds. Intracranial Arteriovenous Malformations. Baltimore: Williams and Wilkins, 1984:64–104. 11. Nornes H, Grip A. Hemodynamic aspects of cerebral arteriovenous malformation. J Neurosurg 1980; 53:456–464. 12. Spetzler RF, Wilson CB. Enlargement of an arteriovenous malformation documented by angiography. J Neurosurg 1975; 43:767–769. 13. Parkinson D, Bachers G. Arteriovenous malformations. J Neurosurg 1980; 53:285–299. 14. Batjer H, Suss RA, Samson D. Intracranial arteriovenous malformations associated with aneurysms. Neurosurgery 1986; 18:29–35.
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15. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 16. Korosue K, Heros RC. Complications of complete surgical resection of AVMs of the brain. In: Barrow DL, ed. Intracranial Vascular Malformations. Neurosurgical Topics. Chicago: AANS Publications, 1990:157–168. 17. Hinke RM, Hu X, Stillman AE. Functional magnetic resonance imaging of Broca’s area during internal speech. Neuroreport 1993; 4:675–678. 18. Tarr RW, Johnson DW, Rutigliano M, et al. Use of acetazolamide-challenge xenon CT in the assessment of cerebral blood flow dynamics in patients with arteriovenous malformations. Am J Neuroradiol 1990; 11:441–448. 19. Batjer HH, Devous MD. The use of acetazolamide-enhanced regional cerebral blood flow measurement to predict risk to arteriovenous malformation patients. Neurosurgery 1992; 31:213–218. 20. Sisti MB, Solomon RA, Stein BM. Stereotactic craniotomy in the resection of small arteriovenous malformations. J Neurosurg 1991; 75:40–44. 21. Golfinos JG, Fitzpatrick BC, Smith LR, Spetzler RF. Clinical use of a frameless stereotactic arm: results of 325 cases. J Neurosurg 1995; 83:197–205. 22. Sugita K, Takayasu M. Arteriovenous malformations: general considerations. In: Apuzzo MLJ, ed. Brain Surgery. Complication Avoidance and Management. New York: Churchill Livingstone, 1990:1114–1117. 23. Martin N, Doberstein C, Bentson J. Intraoperative angiography in cerebrovascular surgery. Clin Neurosurg 1991; 37:312–331. 24. Yasargil MG. Microneurosurgery IIIB: AVM of the Brain. New York: Thieme Medical Publishers, 1988. 25. Yasargil MG. Microneurosurgery IIIA: AVM of the Brain. New York: Thieme Medical Publishers, 1987. 26. Stein BM. Arteriovenous malformations of the cerebral convexities. In: Wilson CB, Stein BM, eds. Intracranial Arteriovenous Malformations. Baltimore: Williams and Wilkins, 1984:156–183. 27. Heros RC. Brain resection for exposure of deep extracerebral and paraventricular lesions. Surg Neurol 1990; 34:188–195. 28. Woodard EJ, Barrow DL. Clinical presentation of intracranial arteriovenous malformations. In: Barrow DL, ed. Intracranial Vascular Malformations. Neurosurgical Topics. Chicago: AANS Publications, 1990:53. 29. Hassler W, Steinmetz H. Cerebral hemodynamics in angioma patients: an intraoperative study. J Neurosurg 1987; 67:822–831. 30. Morgan MK, Johnston IH, Hallinan JM, Weber NC. Complications of surgery for arteriovenous malformations of the brain. J Neurosurg 1993; 78:176–182. 31. Martin N, Doberstein C, Bentson J. Intraoperative angiography in cerebrovascular surgery. Clin Neurosurg 1991; 37:312–331. 32. Spetzler RF, Wilson CB, Weinstein P, Mehdorn M, Townsend J, Telles D. Normal perfusion pressure breakthrough theory. Clin Neurosurg 1978; 25:651–672. 33. Day AL, Friedman WA, Sypert GW. Successful treatment of the normal perfusion pressure breakthrough syndrome. Neurosurgery 1982; 11:625–630. 34. Heros RC, Korosue K. Deep parenchymous lesions. In: Apuzzo MLJ, ed. Brain Surgery. Complication Avoidance and Management. New York: Churchill Livingstone, 1990:1175–1193. 35. Young WL, Kader A, Prohovink I, et al. Pressure autoregulation is intact after arteriovenous malformation resection. Neurosurgery 1993; 32:491–497. 36. Al-Rodan NRF, Sundt TM, Piepgras DG, Nichols DA, Rufenacht D, Stevens LN. Occlusive hyperemia: a theory for the hemodynamic complications following resection of intracerebral arteriovenous malformations. J Neurosurg 1993; 78:167–175. 37. Wilson CB, Hieshima G. Occlusive hyperemia: a new way to think about an old problem. J Neurosurg 1993; 78:165–166. 38. Drake CG. Cerebral arteriovenous malformations: considerations for and experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–208. 39. Sipos EP, Kirsch MJR, Debrun G, Ulatowski JA, Bell WR. Intra-arterial urokinase for treatment of retrograde thrombosis following resection of an arteriovenous malformation. Case report. J Neurosurg 1992; 76:1004–1007. 40. Miyasaka Y, Yada K, Ohwada T, et al. Hemorrhagic venous infarction after excision of an arteriovenous malformation: case report. Neurosurgery 1991; 29:265–268. 41. Weinand ME. Arteriovenous malformations and epilepsy. In: Carter LP, Spetzler RF, Hamilton MG, eds. New York: McGraw-Hill, 1995:933–956. 42. Lussenhop A, Presper J. Surgical embolization of cerebral arteriovenous malformations through internal carotid and vertebral arteries. J Neurosurg 1975; 42:443–451. 43. Adelt D, Zeumer H, Wolters J. Surgical treatment of cerebral arteriovenous malformations. Follow-up study of 43 cases. Acta Neurochir 1985; 76:45–49. 44. Nornes H, Lundar T, Wikeby P. Cerebral arteriovenous malformations: results of microsurgical management. Acta Neurochir 1979; 50:243–257. 45. Heros RC, Korosue K, Diebold PM. Surgical excision of cerebral arteriovenous malformations: late results. Neurosurgery 1990; 26:570–578.
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Endovascular Therapy: Indications, Complications, and Outcome Adnan H. Siddiqui and P. Roc Chen Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A.
Robert H. Rosenwasser Department of Neurosurgery, Division of Cerebrovascular Surgery and Interventional Neuroradiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A.
INTRODUCTION Embolization of arteriovenous malformations (AVMs) has developed over the last four decades from an experimental treatment reported by Lussenhop and Spence in 1960 (1), to a standard component of the multimodal armamentarium used for the treatment of AVMs (2). Initial therapies were developed to embolize feeding arterial pedicles during surgery. Subsequently, plastic microsphere embolics were developed and delivered through a transcervical carotid route. Since then, principles of embolization have evolved in tandem with the development of endovascular technologies. Flow-directed microcatheters provide for routine deployment of embolic material close to or within the nidus. Embolic material science has allowed for a transition from solid and particulate materials to liquid embolics. Embolization is a vital modality either separately or as an adjunct to radiosurgery or microsurgery for treatment and hence obliteration of AVMs. In this chapter we provide an overview of the indications, techniques, complications, and outcomes of endovascular management of AVMs. CEREBROVASCULAR MALFORMATIONS Cerebrovascular malformations are classified as (i) AVMs, (ii) cavernous angiomas (cavernomas, cavernous malformations), (iii) capillary telangiectasias, and (iv) venous angiomas (developmental venous anomalies) (3,4). In an autopsy series of 5743 consecutive patients, venous angiomas were present in 3%, capillary telangiectasias in 0.9%, AVMs in 0.5%, and cavernomas in 0.3% (3). Of this myriad group of essentially congenital vascular anomalies, only AVMs and cavernomas present with hemorrhage, seizures, or other neurological manifestations that require treatment. AVMs are considered congenital, arising from primitive arteriovenous communications that unlike their developmental counterparts fail to regress and hence are present from the very first few weeks of central nervous system (CNS) development. These lesions typically consist of multiple arterial pedicles that feed a dysplastic nidus, which drains without any intervening capillary network through one or more draining veins into major venous sinus systems. Because there is no intervening capillary filter, AVMs are considered high-flow as opposed to cavernomas, which are dilated venous sinusoids and hence low-flow. Although most AVMs are present within pial margins, they do not contain within them functional brain; instead they have dysplastic neuroepithelial rests intertwined between the vascular channels. This neuroepithelial tissue many times provides a compact circumferential plane of dissection around the AVM during surgery distinct from functional neuronal tissue. Angiographically, AVMs are easily identified by the presence of hypertrophied arterial feeders and a compact or diffuse nidus. The hallmark, however, is the identification of an early-draining vein or veins in the arterial phase of the angiogram. The ability to angiographically visualize the AVM enables us to devise endovascular strategies to treat the lesion either as a single modality or as an adjunct to microsurgical resection or stereotactic radiosurgery.
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NATURAL HISTORY OF AVMs Intracerebral and/or subarachnoid hemorrhage is the most common and the most devastating presentation for up to 50% of patients with AVMs (5–7). Seizures are the next most common presentation for supratentorial AVMs (30%) (7). There is a fair amount of uniformity in the results of multiple studies that have been undertaken to estimate the natural history of AVMs. There is consensus that the risk of hemorrhage is between 2% and 4% per year (8–14). The 24-year prospective follow-up study of 166 symptomatic patients by Ondra et al. remains the most quoted, with an annual hemorrhage rate of 4%, mortality rate of 1%, and severe morbidity or mortality rate of 2.7% (13). It is unclear if there is a difference in hemorrhage rates between symptomatic and asymptomatic patients, or between patients presenting with seizures and those presenting with hemorrhage (8,15). It is also controversial whether the risk of subsequent hemorrhages after a hemorrhage increases and whether this risk declines after a latency period. Ondra et al. did not report any such increases, but subsequent reports suggest an increase, which declines to baseline after a year (9–12,14). Regardless, each event of hemorrhage has a well-established 10% risk of mortality and 30% risk of severe morbidity (14,16). A variety of patient characteristics and structural and angiographic features have been investigated to further stratify the risk of hemorrhage. Evidence exists to suggest an inverse relationship between the size of the nidus and the risk of hemorrhage (12,17–23). This inverse relationship is speculated to be related to higher transmittal of arterial pressures onto the draining veins (24,25). However, other evidence suggests that the risk of hemorrhage increases with increasing nidus size (26,27) and still other evidence suggests no relationship (18,28–31). Venous anatomical features that have been suggested to warrant concern for increased risk of hemorrhage are deep venous drainage, venous outflow stricture, and presence of a venous varix (32–37). Location has also been suggested to be a factor, with evidence supporting a higher risk of hemorrhage with deep periventricular and infratentorial lesions (7,15,34,38). The association of aneurysms and AVMs has been reported to be between 2.7% and 14% (18,39–43). Hemodynamic factors play a large role in the development of these aneurysms, often on the feeding arterial pedicles or in the nidus itself. Developmental factors may be at play with aneurysms evident in circulations removed from the AVM. The presence of an associated aneurysm, particularly intranidal, appears to increase the risk of hemorrhage. The management of AVM-associated aneurysms has been the subject of much discussion. The hemodynamic genesis of these aneurysms is supported by the regression of some AVM-associated aneurysms after treatment of the AVM (42); other factors lend support to strategies for early intervention. In particular, in instances of intracranial hemorrhage when both an AVM and an aneurysm are present, the aneurysm is the lesion most likely to have bled (15). This fact, combined with the higher rates of morbidity and mortality associated with an aneurysm hemorrhage, has led many to recommend that the aneurysm be treated first, if at all possible. Patient characteristics that influence the risk of AVM hemorrhage are less well understood. Increasing age may increase risk of hemorrhage (44). However, other patient characteristics such as gender, hypertension, pregnancy, and tobacco use, although associated with aneurysmal hemorrhage, have not been shown to be associated with AVM hemorrhage. Various grading scales for cerebral AVMs have been proposed to aid in the prediction of patient morbidity and/or mortality either with or without treatment. The most commonly employed grading scale is that proposed by Spetzler and Martin in 1986 (see Table 3 in Chapter 6) (45), which was designed to predict the risk of operative treatment. Because this grading scale was based on patients who were treated primarily with surgical resection, its applicability to endovascular therapy is questionable. However, at present there is no widely accepted grading scale for the endovascular treatment of cerebral AVMs. INDICATIONS FOR TREATMENT Based on the established natural history of AVMs, the undertaking of treatment is frequently recommended, particularly in patients who are relatively young, symptomatic, and/or have angiographic or clinical risk factors that predispose to hemorrhage. The rationale for treatment is to reduce the risks of hemorrhage, morbidity, and mortality from those associated with the
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natural history of the disease (14,16). Treatment is also undertaken to improve current neurological status when symptoms can be attributed to venous hypertension or steal phenomenon. The goal of any single treatment modality or combination of modalities is the ultimate obliteration of the AVM. However, each individual treatment modality may have its own specific role in the overall treatment plan. Endovascular embolization as a treatment modality usually assumes one of three roles: (i) adjunctive, (ii) curative, or (iii) palliative. Adjunctive Embolization Before Microsurgery The most common role of endovascular embolization is as an adjunct to either microsurgical resection or stereotactic radiosurgery. For patients with surgically accessible lesions (Spetzler– Martin Grades I and II), microsurgical removal can provide an immediate cure with minimal risk of morbidity and mortality (45,46). However, a large nidus, deep feeding vessels, and high-flow shunts increase the operative risk (45,46). In such patients, the added risks of endovascular treatment may compare favorably to the risks of surgery alone (Figs. 1–4). In a comparison of patients undergoing AVM embolization with N-butyl-cyanoacrylate (NBCA) before surgical resection versus patients undergoing surgery alone, Jafar et al. found that rates of complications and of good or excellent outcomes were similar for both groups despite the fact that the patients undergoing embolization had higher Spetzler–Martin grade lesions (47). Embolization shortened operative time and reduced blood loss. Similar findings have been reported by others (48–55). The degree of preoperative AVM volume reduction necessary to actually effect a difference in surgical resection has been contested. It has been suggested that while elimination of over 75% of the AVM nidus facilitates surgical resection, occlusion of less than 50% does little to aid operative removal (56). The advantage of preoperative embolization is the possible elimination of deep arterial (perforator) feeders, which will not be encountered during surgery until the penultimate phase of resection. Thus, elimination of the superficial arterial supply does nothing to aid surgery, because these are easily addressed during the initial approach. However, embolization of these vessels does expose the patient to the risks of embolization. Therefore, in general, the risks of embolization for surgically accessible small AVMs (Spetzler–Martin Grade I or some Grade II) probably do not outweigh the benefits. An additional benefit of endovascular embolization before surgery is in the management of AVM-associated aneurysms, particularly if they are on deep pedicles or are the source of a recent hemorrhage. In large high-flow AVMs with robust arteriovenous shunting, a gradual reduction of flow through staged embolization may also potentially decrease the risk of postoperative perfusion breakthrough hemorrhage through gradual restoration of vascular reactivity. Some have suggested the use of preoperative embolization of AVMs in eloquent or deep areas to induce either a reduction in flow or elimination of the perforator supply before surgery. If embolization successful, then the decision is made to proceed with surgery; otherwise, the patient is treated with stereotactic radiosurgery (57). Adjunctive Embolization Before Stereotactic Radiosurgery In patients with AVMs located in eloquent cortex or deep structures, stereotactic radiosurgery may be a preferable alternative to microsurgical resection, because the associated risks of morbidity and mortality may be unacceptably high (Fig. 5). In such patients, endovascular embolization may be used to reduce the size of the AVM before radiosurgery or to eliminate certain angiographic features such as intranidal aneurysms, which may provide for elevated risk while the patient awaits AVM obliteration after radiosurgery. The AVM cure rate after stereotactic radiosurgery is inversely proportional to the size of the AVM (58–65). Therefore, the role of endovascular embolization in this setting is to reduce the nidus size so that a cure after radiosurgery will become more likely (59,62,66). This presumption is supported by case series, which have shown an improvement in radiosurgical cure for patients with postembolization reduction in AVM volume to below 10 cm3 (67,68). The volume of an AVM is calculated in similar fashion to that of a sphere (4/3pr3). Therefore, a 2-cm nidus has a volume of 4.18 cm3, while a 3-cm nidus has a volume of 6.3 cm3. The rationale for preradiosurgery embolization is based on the findings that a 1 cm3 AVM has a 100% cure rate, while this drops to 85% for lesions 1 to 4 cm3 in size and further declines to 58% for lesions larger than 4 cm3. In preradiosurgery patients, it is helpful but not essential for the AVM nidus
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to be reduced to a smaller single focus. If this is not possible, a volume-staged approach may be used to treat two or more areas of residual AVM separately (69,70). Alternatively, when stereotactic radiosurgery does not produce complete obliteration, repeated embolization or surgical resection may still be used, often with greater success (71,72).
Figure 1 (Continued on facing page) An axial noncontrast computed tomography scan (A, B) performed on a 27-year-old male who presented with the sudden onset of a severe headache and right hemiparesis shows an acute left intracerebral hemorrhage with associated mass effect and shift. A subsequent angiogram (C, D) demonstrates an arteriovenous malformation (AVM) in the right posterior temporal lobe fed by branches of the right middle cerebral artery (MCA). Note medial and upward displacement of the MCA from the hematoma. (E, F) Emergent embolization resulted in obliteration of AVM. Also note the presence of a distal anterior cerebral artery aneurysm. The patient was taken to the operating room, and the hematoma was evacuated and the AVM resected. (G) The distal anterior cerebral artery aneurysm was clipped. (H, I) Intraoperative angiogram reveals complete excision of the AVM and exclusion of the aneurysm.
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Issues have been raised with preradiosurgical embolization because of concerns for delayed recanalization of a portion of AVM that was embolized and therefore not included in the radiosurgical plans (63,73). This may be partly related to the embolic materials used because particulate materials are associated with a 15% to 20% recanalization rate as compared to liquid embolics (68). In addition, postradiosurgical follow-up by magnetic resonance imaging (MRI) alone may potentially underreport the persistent presence of an AVM. We therefore follow up patients after radiosurgery with sequential MRI scans, and when there is MRI evidence of obliteration of AVM, we perform cerebral angiograms of all six cranial vessels to confirm complete obliteration. In our experience, this approach has resulted in the identification of AVMs requiring repeat treatments that in some cases would have been considered obliterated based on MRI alone. Curative Embolization The primary goal of AVM treatment is complete obliteration of the lesion and its arteriovenous shunt. Only after complete obliteration is the patient’s future risk of hemorrhage eliminated. For endovascular embolization to be curative, there must be no residual filling of the nidus, and the angiographic shunt or abnormal early venous drainage must be eliminated (Figs. 6–8). For most cerebral AVMs, endovascular embolization alone is unable to provide complete obliteration. Probably the most common reason for this subtotal obliteration is the inability to catheterize and thereby embolize many of the small arterial feeders associated with the majority of brain AVMs. Published endovascular cure rates are difficult to interpret. Because embolization evolved primarily as an adjunctive therapy, many published series suffer from considerable referral bias, whereby only ‘‘large’’ AVMs, which are incapable of being treated with radiosurgery or open microsurgery alone, are the ones referred for embolization, and smaller lesions with only one or two feeding pedicles are treated without endovascular intervention. In addition, the lack of a widely accepted endovascular grading scale makes comparison between various studies problematic. Frizzel and Fisher reviewed 1246 patients who underwent embolization for AVMs in 32 series over a 32-year period and found cure rates between 5% and 18% (74). In a series of 465 patients, Vinuela et al. reported a 9.7% rate of complete AVM occlusion with embolization alone (75). Gobin et al. reported a similar cure rate of 11.2% in a cohort of
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Figure 2 (Continued on facing page) Initial magnetic resonance imaging scan (A, B) from a 20-year-old female who presented with a small intraparenchymal hemorrhage shows an arteriovenous malformation (AVM) in the inferior portion of the left cerebellar hemisphere. (C, D) Preembolization angiogram reveals the AVM supplied primarily by the left PICA. Control angiogram performed after a single session of N-butyl-cyanoacrylate embolization (E, F) shows a considerable reduction in the nidus size. Given the patient’s previous history of hemorrhage, the small size of the residual AVM and the surgically accessible location, the patient underwent microsurgical excision of the lesion. (G, H) The patient was positioned in a lateral decubitus position to allow for an intraoperative angiogram. (I, J) The lateral skull film and intraoperative angiogram reveal no residual nidus and no persistent early venous drainage.
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Figure 2 (Continued from previous page)
patients scheduled for radiosurgery who had undergone prior embolization as an ‘‘adjunctive’’ therapy (67). Both series found cure to be more likely in patients with small AVMs. Gobin et al. also found that the rate of cure was inversely related to the number of feeding pedicles. In contrast, other authors have reported much higher rates of cure with endovascular therapy when patients were selected specifically for embolization as a primary modality. After selecting a subgroup of patients based on angiographic features they felt were likely to promote endovascular obliteration, Valavanis and Yasargil noted a cure rate of 74% (or 35% of their overall series) with embolization alone (76). Factors that predisposed to complete occlusion included the presence of dominant feeders without perinidal angiogenesis, a single nidus, and a more fistulous than plexiform nidus. Yu et al. reported on a series of 27 patients from whom 10 were selected for curative embolization on the basis of AVM size less than 3 cm, fewer than three arterial feeders, and the ability to catheterize up to the nidus (77). Their cure rate was 60% for such a select subgroup, with overall cure rate of 22%. Most recently, Haw et al. reported on their embolization experience of 18 years on 306 patients (2). Their cure rate was 9.1% for the entire cohort, but for the subgroup of 55 patients for whom the primary intent was cure through embolization, the rate increased to 31%. Palliative Embolization It is unclear if partial treatment of AVMs alters the natural history of the disease, particularly in regard to the risk of hemorrhage (78,79). Although only complete elimination of the AVM constitutes a true cure, in selected cases palliative treatment may be justified. Specifically, patients who are symptomatic because of large and/or deep-seated AVMs that are unlikely to be cured with any combination of treatments may benefit from subtotal endovascular embolization. Embolization to reduce the arteriovenous shunt and thereby decrease the amount of ‘‘steal’’ and/or venous hypertension associated with a lesion has been reported to cause clinical improvement (80,81). In patients with repeated AVM-related hemorrhages, embolization may be used to eliminate angiographic risk factors for hemorrhage, such as intranidal aneurysms. However, the risk of hemorrhage from the AVM has been suggested to increase after partial treatment as compared to conservative management. Miyamoto et al. reported on 46 patients
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Figure 3 (A) During surgery the glue cast is visible in the nidus on the cortical surface. (B) Post-resection arteriovenous malformation (AVM) filled with glue. (C) Intraoperative angiogram revealing complete absence (excision) of the AVM.
whose AVMs were palliatively treated because of size and/or location (82). They reported an increase in the rate of annual hemorrhage from 2.6% in untreated patients to 14.6% in the partially treated patients. Kwon et al. reported on 27 patients with Spetzler–Martin Grade III AVMs, of which 11 were partially embolized and 16 were managed conservatively (83). Although the incidences of clinical deterioration in the follow-up period were similar, the rate of hemorrhage was 45.5% in the embolized group versus 25% in the conservatively managed group. Evidence to the contrary has been provided by Meisel et al., who reported on the partial embolization of AVMs in 450 patients that were deemed to have angiographically identified high-risk features and be otherwise incurable (84). The annual rate of hemorrhage in the untreated group was 8.9%, and this rate declined to 3.6% after partial targeted embolization to address the angiographic high-risk features. Al-Yamany et al. also reported on patients who presented with progressive neurological decline without evidence of hemorrhage; partial embolization halted the progression of symptoms in over 90% of patients (85). The role of partial embolization remains unclear. However, we believe that there are certain narrow roles by which this modality can help decrease the risk of hemorrhage and effect clinical benefit by addressing specific angiographic attributes or through reduction of flow and correspondent improvement in steal and or venous hypertension. Furthermore, as newer applications of radiosurgery such as volume staging are developed, there may be a shrinking population of AVMs considered to be incurable (70). Modality-Driven Perspectives on the Management of AVMs Controversy exists between neurosurgeons and interventional neuroradiologists in their approach to the indications for AVM treatment (2,67,78,86). As neurosurgeons who perform all three of the major modalities of AVM treatment, we prefer to view indications for treatment from a multidisciplinary perspective with treatment tailored to the individual patient and his/her AVM. The first decision for the treating physician should be whether or not the AVM needs to be treated. This question is answered through analysis of patient factors such as age and symptomatology of the lesion as well as angiographic factors such as size, location, eloquence, venous drainage, and associated high-risk features such as aneurysms and venous outflow obstruction. Once these factors have been assessed, we consider the established natural history of the disease. If intervention provides an improvement in the natural history
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Figure 4 This patient presented with seizures and a right temporal arteriovenous malformation (AVM). (A) Magnetic resonance imaging shows AVM flow void. (B) The angiogram revealed filling principally from the right MCA branches. (C) Microcatheter runs prior to glue embolization reveal the angioarchitecture, flow patterns, and fistulous components of the nidus. (D) Postembolization. Note the absence of the rostrosuperior aspect of the nidus. The patient underwent a surgical excision, and (E) intraoperative angiogram reveals the absence of the AVM.
without exposing the patient to inordinate risk, we proceed to design a tailored treatment plan. This treatment plan usually consists of a multimodal approach to most patients. For patients who have sustained a hemorrhage, every effort is made to eliminate the risk of future bleeding as soon as possible. For such patients this may mean a combination
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Figure 5 Pretreatment angiogram (A) performed on a 56-year-old woman with new onset seizures reveals a left frontal arteriovenous malformation (AVM) fed by branches of the left ACA. (B, C) After the nidus volume was reduced with multiple sessions of glue embolization, an angiogram was performed and the patient underwent volume-staged gamma knife stereotactic radiosurgery. An angiogram performed approximately three years after two stages of radiosurgery (D, E) shows no persistent filling of the AVM. A glue cast is still visible in the left frontal lobe.
of surgical resection and/or endovascular embolization. However, if the risk of morbidity/ mortality associated with these treatments is likely to be greater than that of the natural history of the untreated AVM over the next few years, then a combination of stereotactic radiosurgery and/or embolization may be desirable. Traditionally, surgical resection alone has been favored for patients with mass-effect symptoms from a sizable acute intracerebral hemorrhage. However, even in many of these patients, we have either used emergent aggressive embolization preoperatively to reduce intraoperative blood loss or simply evacuated the hematoma, leaving the AVM for later treatment with any combination of modalities. In general, though, because our institution is a tertiary care referral center, the majority of AVMs that we see are large and arise either within or partially within eloquent brain. As a result, more than 50% of the patients with AVMs treated in the senior author’s series underwent stereotactic radiosurgery and embolization. More recently, we as well as others (70,73) have begun to utilize volume-staged radiosurgery for addressing otherwise incurable or high-interventional-risk AVMs. In the end, success is most likely to be achieved with a multidisciplinary approach tailored to both the individual patient and the characteristics of the lesion itself.
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Figure 6 A high-flow arteriovenous malformation (AVM) fed principally by the left ICA with a prominent fistulous component was embolized. (A, B) Preembolization films reveal the fistulous component. After N-butyl-cyanoacrylate embolization under roadmap (‘‘mask’’) conditions (C), a glue cast can be seen within the AVM nidus. (D, E) Postembolization angiogram reveals complete shutdown of the high-flow fistulous connection and obliteration of the AVM.
Such an approach is best delivered at a tertiary care institution where practitioners experienced in the latest microsurgical, radiosurgical, and endovascular techniques are readily available. MANAGEMENT PRINCIPLES FOR ENDOVASCULAR TREATMENT The first reports of the endovascular treatment of AVMs involved the nonselective use of particles (1). It was not until 1972 that Zanetti and Sherman reported the use of a liquid embolic
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Figure 7 This patient presented with seizures. (A, B) The initial angiogram revealed a medial right frontoparietal arteriovenous malformation (AVM) fed by the right pericallosal artery. (C, D) Postembolization there is minimal flow in the nidus. (E, F) Angiography six weeks postembolization confirms the complete obliteration of AVM.
acrylate polymer to treat cerebral AVMs (87). Today liquid cyanoacrylate glue derivatives delivered through superselective microcatherization are the most commonly used embolic agents for the treatment of cerebral AVMs. At our institution, almost all AVM embolizations are performed under general endotracheal anesthesia with pharmacological paralysis (Fig. 9). This essentially eliminates patient movement and facilitates roadmapping for radiographic intravascular navigation. Rigorous blood pressure control is maintained throughout the procedure and in the postoperative period. To minimize the risk of a neurological deficit in patients treated under general anesthesia, we routinely use intraoperative neurophysiological monitoring in the form of somatosensory evoked potentials and electroencephalography, while brainstem auditoryevoked responses are monitored for lesions requiring access through the posterior circulation. Arterial access is generally achieved through a transfemoral route. In adults, a 7 F sheath is placed in the femoral artery. The use of a 7 F sheath with a 6 F guide catheter allows for continuous blood pressure monitoring through the sheath, thereby eliminating the need for a separate arterial line. In addition, the 6 F guide provides for easy contrast injection such that
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Figure 8 This patient presented with seizures. (A) Magnetic resonance imaging revealed a right temporal arteriovenous malformation (AVM). (B, C) Preembolization angiogram revealed filling principally from the right MCA. Following staged embolization, the AVM nidus was completely occluded. (D, E) Complete occlusion was confirmed through an intraoperative angiogram.
a selective angiogram may be performed even with a microcatheter in place. In addition, a 6 F guide allows for continuous flush through pressurized lines around the microcatheter, eliminating the need for systemic intraprocedural anticoagulation. Flow-directed microcatheters, rather than braided, wire-driven catheters are optimal for accessing distal AVM pedicles and delivering liquid embolic agents. Commonly used brands approved for use in the United States include the Spinnaker Elite (1.5 or 1.8 F) from Boston Scientific (Neurovascular, Fremont,
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Figure 9 The interventional neuroradiology or endovascular suite. (A) Biplane fluoroscopy is critical for intracranial vascular navigation. (B) Electrophysiologic monitoring is utilized for all interventional cases. (C) Sterile technique is used for all procedures. (D) Anesthesia is used for almost all diagnostic angiography with monitored anesthesia care. General anesthesia with pharmacologic paralysis is used for all cases of embolization.
California, U.S.A.) and the Regatta (1.8 F) manufactured by Cordis Neurovascular (Miami, Florida, U.S.A.). Although these catheters are flow-directed, a hydrophilic guidewire (usually 0.10-in. diameter) is still required to facilitate the flow-independent movements often required for selecting a specific arterial pedicle. Aggressive manipulation with the wire, however, should be avoided to minimize the risk of vascular perforation. After the appropriate first- or second-order vessel is selected and catheterized, a pretreatment biplane angiogram including capillary and venous phases should be obtained to serve as a reference for comparison with the postembolization angiogram to quantify the extent of embolization as well as to ensure the patency of all identifiable arterial branches. We attempt to place our guide catheter as distal as is safely possible to provide added support for the microcatheter. This is routinely at the cervicopetrous junction of the internal carotid artery for the anterior circulation and at the V3 segment of the vertebral artery in cases requiring access to the posterior circulation. A digital roadmap is then created and used to navigate the flow-directed microcatheter into an appropriate arterial pedicle. Larger pedicles are usually selected during initial sessions, because smaller pedicles may subsequently dilate as the flow characteristics of the AVM change with treatment. Once a specific pedicle has been selected, contrast injection through the microcatheter is used to judge flow rate through the nidus, assess the proximity of the draining vein(s), and determine whether any normal arterial branches are being supplied distal or adjacent to the nidus, particularly in the case of en passant branches. In some instances, particularly in awake patients, selective barbiturate injections through the microcatheter may be used to assess the eloquence of brain served by the arterial pedicle in question (‘‘amobarbital testing’’) (44,88–90). For patients under general anesthesia, superselective barbiturate injection may lead to changes in neurophysiological parameters. However, the lack of certainty with regard to flow distribution of the barbiturate in the presence of an AVM may limit the usefulness of this method. As a result, a negative amobarbital test does not necessarily guarantee a good outcome. In this regard, newly developed microcatheters allow for catheterization essentially up to the nidus, thus obviating the need for pharmacologic testing in most cases.
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Actual AVM occlusion is achieved with an embolic agent. Over the years, various types of embolic agents have been employed to treat cerebral AVMs. Many earlier treatments were performed with particles, particularly polyvinyl alcohol (PVA). Today, liquid embolic derivatives of cyanoacrylate have largely supplanted PVA as the agent of choice. A prospective, randomized trial comparing NBCA to PVA for the preoperative embolization of cerebral AVMs demonstrated equivalence for both agents, at least in terms of percent nidus reduction and number of pedicles embolized (91). However, PVA particles are unlikely to provide permanent arterial occlusion and should be used only as an adjunct to timely surgical extirpation (92,93). Occasionally, in lesions with fistulous components, the injection of glue may be facilitated by the use of platinum coils that can be pushed to reduce flow (94). Several liquid embolics have been used in the endovascular occlusion of cerebral AVMs. The most popular liquid embolic agents are cyanoacrylate derivatives, including Trufill (Cordis Neurovascular, Miami, Florida, U.S.A.) and Histocryl (Braun-Aesculap, Tuttlingen, Germany). Absolute ethyl alcohol has also been used as an embolic agent for vascular malformations, primarily of the extracranial circulation. The treatment of cerebral AVMs with absolute alcohol has been reported, but its use remains controversial (95). Currently, the only ‘‘glue’’ that the Food and Drug Administration (FDA) approved for use in cerebral AVMs in the United States is Trufill (NBCA). NBCA glue is a clear, colorless, and radiolucent liquid that comes packaged in single concentration 1-ml vials (Fig. 10). The glue begins to polymerize immediately on contact with ionic materials such as blood, saline, and ionic contrast media. To alter the polymerization properties of the glue and make it visible during injection on angiography, NBCA is combined with ethiodol (oil based nonionic contrast), nonionic water-soluble contrast, or tantalum powder.
Figure 10 (A) N-butyl-cyanoacrylate or Trufill is the only Food and Drug Administration-approved liquid embolic material for arteriovenous malformations and comes with provided tantalum powder and nonionic contrast. (B) The glue tray is set up in a stereotypic fashion with compulsory use of specific color-coded syringes, needles, and other equipment.
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Trufill is packaged with ethiodol for dilution, although many have found the behavior of various ethiodol–NBCA concentrations to be inconsistent in terms of viscosity and polymerization. Nevertheless, NBCA concentrations of between 20% and 70% are commonly used depending on the proximity of the microcatheter to the nidus and the rapidity of the arteriovenous shunt. Some authors have advocated the use of glacial acetic acid as the diluting agent for NBCA, feeling that its effects are more reproducible (54). Because acetic acid is also radiolucent, the glue must be combined with tantalum powder (also packaged with Trufill) to make it radioopaque. Tantalum, however, adds to the viscosity of the mixture. With the microcatheter in optimal position, the embolic agent may then be prepared. The appropriate glue concentration should be mixed on a separate table to avoid contamination with blood or other ionic substances that may cause premature polymerization. Determining the appropriate glue concentration is not an exact science. Observation of the AVM’s flow characteristics and angioarchitecture during contrast injection through the microcatheter is critical. In the end, there is no substitute for experience with a specific embolic agent. At our institution moderate hypotension (mean arterial pressure approximately 50 mmHg) is induced before embolization. The microcatheter is repeatedly flushed with 5% dextrose water solution to prevent premature polymerization in the catheter, and the glue is then injected under roadmapping to enhance visualization. After glue administration, the microcatheter must be rapidly pulled from the site of injection to prevent the catheter from being glued in place. The anesthesiologist is forewarned to be prepared to provide a valsalva maneuver to increase venous pressure to prevent or at least retard the progression of embolic material toward the draining vein(s). After glue injection and removal of the microcatheter, the microcatheter should be inspected to ensure that the entire catheter has been removed. Because of the possibility of residual glue in the catheter, we prefer to discard the microcatheter after every glue injection. The guide catheter should be thoroughly flushed before being reused. A postembolization angiogram should be performed to assess the degree and location of AVM obliteration obtained during the embolization as well as to inspect the venous drainage pattern of the residual AVM to ensure there is no venous engorgement and for patency of the arterial tree. Postoperatively, our patients are observed in a monitored intensive care or intermediate care unit. Mild hypotension (MAP <80 mmHg) is maintained for approximately 24 hours to minimize the risk of breakthrough hemorrhage. Dexamethasone is administered preoperatively to control the inflammatory response that may occur secondary to the NBCA. We do not routinely use anticoagulation during the procedure. Femoral sheaths usually are removed the evening after embolization, and most patients are discharged home the following day. There are no specific guidelines as to the percent-volume or number of pedicles that should be embolized at one time. It has been suggested that major alterations in the hemodynamic characteristics of an AVM may occur after the rapid occlusion of a large percentage of its volume, thus increasing the risk of a hemorrhagic complication. This conclusion, however, continues to be controversial. We prefer to take a very conservative approach to endovascular AVM treatment, and we frequently embolize only one pedicle at a given session. Larger AVMs may therefore require three or more sessions of embolization, usually spaced four to five weeks apart. COMPLICATIONS: AVOIDANCE AND MANAGEMENT The risks of endovascular embolization of AVMs are well established. It is therefore incumbent on the endovascular surgeon to evaluate the particular role embolization will play in the cure of each lesion. This role is then weighed against risk–benefit ratios for embolization as opposed to radiosurgery and/or microsurgery. Once embolization has been chosen as an approach, either alone or as part of a multimodal management of the AVM, we have to be cognizant of the possible complications of this technique. Complications related to endovascular AVM treatment usually fall into one of two broad categories: ischemic or hemorrhagic. Either can have serious consequences from transient to permanent neurologic deficit and even death. Frizzel and Fisher reviewed in 32 reports spanning the period from 1969 to 1993 the morbidity and mortality rates for 1246 AVMs. The mortality was 1% and permanent morbidity was 8% (74). Subsequent reports have suggested mortality rates between 1% and 3.7%, and permanent morbidity rates between 3.8% and 14% (48,76,84,91,96,97).
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Recently, Haw et al. evaluated their complications from embolization over an 18-year period (2). They had a permanent morbidity, including mortality, rate of 3.9%. They divided their complications into three categories based on the timing of the inciting event: (i) during the endovascular approach to the AVM, (ii) during embolization, or (iii) in the postembolization period. This approach is useful for analyzing complications because it allows construction of potential strategies for complication avoidance. The endovascular approach to the AVM was the cause of 16% of their complications (2). Most prominently, this group consisted of vascular injury during approach to the AVM with vessel perforation. Vessel dissection with guide catheter and wire also falls into this category. The availability of highly flexible variable stiffness microcatheters with very soft 0.10 in. guide wires has made this injury less likely. Avoidance of dissection and thromboembolic episodes is based on good endovascular technique with careful advancement of the guide wire, use of road mapping whenever possible in the cervical vasculature, and presence of a continuous pressurized bubble-free flush system. Vascular injury at the level of the arterial pedicles is best prevented by careful catheterization of the proximal pedicles with the soft 0.10 in. guide wire followed by utilizing the flow-directed catheter’s innate ability to advance. Wire manipulation in these distal vessels is likely a major cause for arterial perforations. Haw et al. also reported on a single case where a basilar terminus flow-related aneurysm ruptured during the approach, causing death despite immediate placement of an external ventricular drain (2). In cases of arterial perforation, anticoagulation should be reversed if it has been employed. We do not routinely use anticoagulation during embolization of AVMs. Arterial pressures should be dropped. If there is active extravasation with the microcatheter in the extravascular space, an attempt should be made to deploy a coil as the catheter is retrieved back into the intravascular space to plug the hole. An emergent computed tomography (CT) scan should be obtained and an external ventricular drain placed. Complications during embolization were the most common (61%) in the series of Haw et al. (2). The vast majority of complications in this group were secondary to ischemic injury. Ischemic injury can be secondary to arterial occlusion or from venous congestion secondary to thrombosis of the draining venous structures. If the microcatheter is proximal to the nidus, injection of glue can occlude normal arterial branches that are not appreciated secondary to high flow proximal to the nidus or occlude en passant vessels distal to the nidus. This may be categorized as anterograde arterial occlusion and can potentially be circumvented by newer, more flexible catheters that can be wedged in an intranidal location. Reflux of the glue can also lead to the retrograde occlusion of arterial branches proximal to the catheter tip (76). Picard et al. reported that a volume of glue injected greater than 1 ml was associated with arterial and venous thrombosis and subsequent hemorrhage (98). Similarly, flow of the glue into the venous drainage system has been repeatedly shown to be a major factor associated with venous congestion, thrombosis, and hemorrhage (48,98,99). The important factor identified in all these studies was the visualization of glue cast in the major draining vein or postembolization venous stasis. Another factor associated with posttreatment hemorrhage is the presence of either a direct fistulous component in the nidus or a very high flow state within the plexiform component of the nidus. We address this risk by performing multiple contrast injections under continuous fluoroscopic guidance with a road map mask before glue injection to assess the flow dynamics as well as evaluate for en passant arterial branches and fistulous components of the nidus. This allows for development of a ‘‘feel’’ for the amount and pressure required to glue the nidus as well as the speed of the glue injection. For instance, the higher the flow noted, the higher the concentration of glue used and the slower the speed of injection. We also routinely drop the mean arterial pressure to 50 mmHg and ask the anesthesiologist for a valsalva maneuver to prevent venous injection for high-flow or fistulous states. Another risk during embolization relates to the fact that if the microcatheter is not removed swiftly, it may be glued inside the vessel and potentially cause arterial rupture or occlusion. The microcatheters are routinely examined after removal for intactness. The person pulling the microcatheter must be acutely aware of when and how the catheter is to be pulled. Duckwiler et al. also pointed out the risk of aggressive multiple pedicle embolizations during single sessions by suggesting that venous congestion and neurologic decline with hemorrhage may occur because of sudden marked reduction in arterial flow through the nidus with resultant venous stasis and subsequent thrombosis (100). We stage our embolizations, with only rare occasions when more than one pedicle is embolized during a single session.
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The third category in terms of timing of complications is during the postembolization recovery period. Patients awaken from anesthesia without deficits and then in the ensuing hours to days, sometimes weeks, they develop progressive neurologic symptoms. Haw et al. reported this subgroup as 23% of all complications (2). In most cases, there was evidence of encroachment of the glue cast in the venous structures draining the nidus. This finding essentially indicates that the AVM compensates for the postglue hemodynamic changes and venous hypertension up to a point and then becomes symptomatic with venous congestion, stasis, thrombosis, and eventually hemorrhage. The most important factors identified to date that increase risk of embolization are glue penetration and thrombosis of the AVM venous drainage system (48,74,99), presence of a fistulous component, eloquent cortex location (2), injected glue volume greater than 1 ml (98), and increasing patient age (96). THE JEFFERSON HOSPITAL FOR NEUROSCIENCE EXPERIENCE In the senior author’s personal series covering a period from October 1995 to December 2005, a total of 448 AVMs were embolized, 225 underwent gamma knife radiosurgery, and 135 were surgically removed. An additional 164 patients had no treatment and are being followed due to age or medical comorbidities. In a series of 170 patients treated with endovascular embolization and with complete follow-up at 36 months, permanent morbidity was noted in only 7 patients (4.1%). In this group, there were no cases of postembolization hemorrhage and no deaths after embolization. The majority of patients (125, 73%) underwent one or two sessions of embolization. Twenty-six (15%) and 9 (5%) had three and four sessions, respectively, while 10 patients underwent five or more embolizations. The overall cure rate to date, including all modes of treatment, is 24.7%. The cure rate for patients treated with endovascular embolization alone (49 patients, 28.8% of total series) stands at 14.3% (7 patients). Those cured with embolization alone all harbored AVMs with Spetzler–Martin grades of three or lower. None of these lesions had a maximal dimension over 6 cm. As discussed previously, cure rates after endovascular embolization are difficult to interpret. This is at least partially due to the lack of prospective randomized controlled studies comparing various treatment modalities. Given the current trend toward the multidisciplinary treatment of AVMs, it is doubtful that such studies will ever be performed. A multidisciplinary approach must therefore be critically compared to the natural history of these lesions, and attention must be paid to clinical outcome in terms of functional status, quality of life, and patient satisfaction. Summary Untreated cerebral AVMs carry a significant risk of long-term morbidity and mortality. Endovascular embolization has evolved into an important treatment option for the majority of AVMs, whether it is utilized as an adjunct or as the primary therapy. Although sometimes a challenge to use, liquid cyanoacrylate derivatives have become the material of choice for most practitioners performing endovascular AVM embolization. In addition, advances in flow-guided microcatheter technology have enabled safer access to ever more hard to reach areas of the cerebral vasculature. In the current era, the treatment of cerebral AVMs is best approached from a multidisciplinary standpoint at facilities where the major treatment modalities of microsurgery, stereotactic radiosurgery, and endovascular embolization are all available. REFERENCES 1. Lussenhop A, Spence W. Artificial embolization of cerebral arteries: report of use in a case of arteriovenous malformation. J Am Med Assoc 1960:172. 2. Haw C, et al. Complications of embolization of arteriovenous malformations. J Neurosurg 2006; 104(2):226–232. 3. McCormick W. The pathology of vascular malformations of the brain. In: Wilson C, Stein B, eds. Intracranial Vascular Malformations. Baltimore: Williams and Wilkins, 1984:44–63. 4. McCormick WF. The pathology of vascular (arteriovenous) malformations. J Neurosurg 1966; 24(4):807–816.
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Rolandic arteriovenous malformations: improvement in limb function by IBC embolization. AJNR Am J Neuroradiol 1985; 6(4):575–582. 81. Kusske JA, Kelly WA. Embolization and reduction of the ‘‘steal’’ syndrome in cerebral arteriovenous malformations. J Neurosurg 1974; 40(3):313–321. 82. Miyamoto S, et al. Posttreatment sequelae of palliatively treated cerebral arteriovenous malformations. Neurosurgery 2000; 46(3):589–594; discussion 594–595. 83. Kwon OK, et al. Palliatively treated cerebral arteriovenous malformations: follow-up results. J Clin Neurosci 2000; 7(suppl 1):69–72. 84. Meisel HJ, et al. Effect of partial targeted N-butyl-cyano-acrylate embolization in brain AVM. Acta Neurochir (Wien) 2002; 144(9):879–87; discussion 888. 85. Al-Yamany M, et al. Palliative embolisation of brain arteriovenous malformations presenting with progressive neurological deficit. Interventional Neuroradiology 2000; 6:177–183. 86. Baskaya M, Heros RC. Indications for and complications of embolization of cerebral arteriovenous malformations. J Neurosurg 2006; 104(2):183–187. 87. Zanetti PH, Sherman FE. Experimental evaluation of a tissue adhesive as an agent for the treatment of aneurysms and arteriovenous anomalies. J Neurosurg 1972; 36(1):72–79. 88. Moo LR, et al. Tailored cognitive testing with provocative amobarbital injection preceding AVM embolization. AJNR Am J Neuroradiol 2002; 23(3):416–421. 89. Rauch RA, et al. Preembolization functional evaluation in brain arteriovenous malformations: the ability of superselective Amytal test to predict neurologic dysfunction before embolization. AJNR Am J Neuroradiol 1992; 13(1):309–314. 90. Rauch RA, et al. Preembolization functional evaluation in brain arteriovenous malformations: the superselective Amytal test. AJNR Am J Neuroradiol 1992; 13(1):303–308. 91. n-BCA Trial Investigators: N-butyl cyanoacrylate embolization of cerebral arteriovenous malformations: results of a prospective, randomized, multi-center trial. AJNR Am J Neuroradiol 2002; 23(5):748–755. 92. Rosenwasser RH, et al. Safety of embolic materials. J Neurosurg 1993; 79(1):153–155. 93. Sorimachi T, et al. Embolization of cerebral arteriovenous malformations achieved with polyvinyl alcohol particles: angiographic reappearance and complications. AJNR Am J Neuroradiol 1999; 20(7):1323–1328. 94. Richling B, Killer M. Endovascular management of patients with cerebral arteriovenous malformations. Neurosurg Clin N Am 2000; 11(1):123–145, ix. 95. Yakes WF, et al. Ethanol endovascular management of brain arteriovenous malformations: initial results. Neurosurgery 1997; 40(6):1145–1152; discussion 1152–1154. 96. Hartmann A, et al. Risk of endovascular treatment of brain arteriovenous malformations. Stroke 2002; 33(7):1816–1820. 97. Taylor CL, et al. Complications of preoperative embolization of cerebral arteriovenous malformations. J Neurosurg 2004; 100(5):810–812. 98. Picard L, et al. Acute spontaneous hemorrhage after embolization of brain arteriovenous malformation with N-butyl cyanoacrylate. J Neuroradiol 2001; 28(3):147–165. 99. Deruty R, et al. Complications after multidisciplinary treatment of cerebral arteriovenous malformations. Acta Neurochir (Wien) 1996; 138(2):119–1131. 100. Duckwiler GR, et al. Delayed venous occlusion following embolotherapy of vascular malformations in the brain. AJNR Am J Neuroradiol 1992; 13(6):1571–1579.
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Radiosurgical Complications Alan C. Hartford Section of Radiation Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire, U.S.A.
Paul Chapman Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
Philip E. Stieg Department of Neurological Surgery, Weill Medical College of Cornell University, NewYorkPresbyterian Hospital, New York, New York, U.S.A.
Christopher S. Ogilvy Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
Jay S. Loeffler Department of Radiation Oncology, Northeast Proton Therapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
HISTORICAL BACKGROUND In 1928, Harvey Cushing was the first to treat arteriovenous malformations (AVMs) using sources of ionizing radiation. Cushing summarized his experience with the statement that radiation therapy for AVMs ‘‘if persisted in, offers considerable promise of amelioration or possibly of cure’’ (1). Although the orthovoltage radioactive sources caused fibrotic and necrotic changes in AVMs, doses to normal brain were high, yielding extensive areas of brain necrosis and significant clinical sequelae. At Stockholm’s Karolinska Hospital in 1951, Leksell introduced stereotactic radiosurgery: noninvasive technology designed to produce a precisely located, well-defined area of necrosis within the brain using a single fraction dose of ionizing radiation (2). This original work included both orthovoltage radiation generators as well as proton beam irradiation. More than a decade later, in 1965, Kjellberg et al. at the Massachusetts General Hospital combined the two approaches and used proton beam irradiation at the Harvard Cyclotron Laboratory (HCL) to perform the first stereotactic radiosurgical treatment of a patient with an AVM (3). Early success with the proton beam, with helium ions, and with the Leksell gamma unit, including treatment of unresectable AVMs as well as tumors such as acoustic neuromas, craniopharyngiomas, pituitary lesions, and pineal tumors (3–9), led to the dissemination and increased popularity of radiosurgery (10). With the success of these technologies, modern linear accelerators were adapted to produce similar, precise dose distributions with single fraction treatments (11–16), and in 1986, the first stereotactic linear accelerator radiosurgical treatment of an AVM in the United States was performed at the Brigham and Women’s Hospital (17,18). Thus, the armamentarium of stereotactic radiosurgery treatments for AVMs expanded over time to include proton and charged particle beams, the gamma knife, cobalt units, and dedicated linear accelerators. By the 1990s, more than 6000 patients with AVMs had been treated with stereotactic radiosurgery in centers around the world. With the accrual of technological sophistication and patient numbers came increased experience with radiosurgical complications. Early experimental and theoretical models as well as experience with clinical complications after radiosurgery treatment led Kjellberg to develop dose–volume isoeffect curves that predicted the likelihood of brain necrosis as a function of the dose and volume irradiated, with logarithmic scales for field diameter and dose (Fig. 1)
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Figure 1 Distribution of posttreatment complications among 74 patients with arteriovenous malformations treated with proton beam irradiation at the Harvard Cyclotron Laboratory between 1965 and 1978 by Kjellberg. The upper and lower slanted lines represent, respectively, the isoeffect dose– volume combinations resulting in 99% and 1% radionecrosis probabilities, per Kjellberg’s estimates. Open circles indicate the first four, comparatively serious complications, and cross-hatched circles the next four complications, which were comparatively mild; solid circles indicate patients without complications. Source: From Ref. 3.
(3,19–21). Through the late 1980s, while several centers were developing large clinical experiences, little more was published on the relationships between dose, volume, and types of complications. In 1990, Steinberg et al. reported a series of 86 symptomatic patients treated with heavycharged-particle (helium ion) radiation through a collaboration between Lawrence Berkeley Laboratory and Stanford University Medical Center (8,22). The authors were among the first to distinguish adverse outcomes clearly between posttreatment bleeding risk and radiosurgery-related complications. Ten patients (12%) bled from residual AVMs between 4 and 34 months after treatment, seven of whom had bled prior to treatment, whereas no patient with a completely obliterated AVM subsequently hemorrhaged. On the basis of imaging studies and angiography, the authors found that white-matter changes occurred between 4 and 26 months after treatment in about half the studied patients, but nearly two-thirds of these patients remained asymptomatic. The authors concluded that estimating the likelihood of a clinical complication arising for a given patient required understanding the relationship between complication rates, types of complications, and underlying doses and treatment volumes. This history serves as backdrop for the classification of radiosurgical complications into four categories (23). First, hemorrhage may occur before AVM obliteration. Second, transient radiation-related effects may arise in the perioperative period. Third, permanent radiationinduced complications can result within the surrounding normal brain parenchyma and vasculature. Fourth, there is a low, long-term risk of radiation-induced neoplasia resulting from stereotactic radiosurgery. In this chapter, we will examine each of these complications. RISK OF HEMORRHAGE Considerable controversy exists about the risk of hemorrhage after stereotactic radiosurgery for an AVM. Several studies suggest that this risk is reduced, others argue that the risk mirrors the risk before radiosurgery, and a few believe that the risk may be increased in selected instances. However, all agree that the risk drops to zero once the AVM has been obliterated completely, defined by Lindquist and Steiner as ‘‘normal circulation time, absence of former nidus vessels, and disappearance or normalization of draining veins’’ (24). The baseline annual risk of hemorrhage for an AVM lies between 2% and 6%, and the risk may increase with each additional hemorrhage (25–29). One excellent estimate of 4% per year was derived from a study that followed a homogeneous group of patients for 24 years and systematically recorded the annual incidence of hemorrhage (30). The rate of further
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Figure 2 Risk of hemorrhage for a series of 316 patients with arteriovenous malformations, according to the presence or absence of hemorrhage at initial presentation. The annual rate of rehemorrhage was 18% for patients presenting with hemorrhage, whereas the annual rate of hemorrhage was 2% among patients without prior bleeding history (p < .001). Source: From Ref. 37.
bleeding in patients with a history of hemorrhage has been reported to be significantly higher, averaging between 4% and 10% per year, and as high as 18% for the first year after hemorrhage (Fig. 2) (25,31–37). Besides previous bleeding history, the risk of hemorrhage may increase with small AVM size, deep venous drainage, intranidal and feeding proximal aneurysms, high feeding artery pressures, and the patient’s age, reflecting the natural history of the malformation (25,26,28,29,33,35,38–42). Radiosurgery as Protective Before AVM Obliteration Several studies argue for a decreased bleeding risk after radiosurgery. Summarizing experience with 709 treated patients, of whom 389 were followed for more than two years, Kjellberg described a risk of rebleeding for patients presenting with hemorrhage that declined from 7.2% per year to 2.4% per year after two years; however, total obliteration of the AVM was achieved in only 20% of patients (34). Because the AVMs were not completely obliterated in more than 300 patients at the two-year mark but the rebleeding rate was cut by more than threefold, the results suggested there was a protective effect even for incompletely obliterated lesions. Kjellberg argued this decline in hemorrhage risk followed a one-year ‘‘incubation period,’’ after which clinical improvement became evident. Even this one-year estimate for the latency period might be too high for some cases (43,44). Likewise, Forster noted no instances of hemorrhage among 15% of 615 patients who had persistence of abnormal venous drainage but with partial reduction in AVM nidus flow two years after radiosurgery treatment (45). Similar results were reported by Steiner et al., who found no instances of rebleeding in patients whose AVMs achieved ‘‘subtotal’’ obliteration, meaning that the nidus was no longer visualized but that an early draining vein demonstrated the continued presence of shunting (44). This finding might represent a reduced risk of hemorrhage, although the authors noted this conclusion would depend on assumptions about the number of years the patient could be considered to be at risk before AVM obliteration after the last angiogram. In contrast, in a separate analysis summarizing data for 247 consecutive cases treated from 1970 to 1983, Steiner et al. documented a rebleeding rate between 1.9% and 6.5% per year that continued at least from two years through five years after treatment of partially (but not ‘‘subtotally’’) obliterated lesions (46). Further analysis and longer follow-up suggested the risk of hemorrhage for an untreated AVM might be higher than previously thought; the Karolinska group estimated an annual risk of 5% at age 25 years, increasing to an annual risk as high as 8% at age 50 years (47). Karlsson et al. reevaluated the issue in an enlarged series of 1604 patients, among whom 49 hemorrhages
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occurred during the first two years (risk of bleeding 3% per year per patient at risk), and 41 occurred more than two years after treatment (risk of bleeding 2.1% per year per patient at risk) (48). Higher doses (correlated with smaller AVM volumes) and younger ages were found to be associated with a decreased risk of hemorrhage; in particular, six months after radiosurgery, no hemorrhage occurred in the patients whose AVMs received 25 Gy or more to the periphery. By comparing these risks with the baseline estimates, the authors argued that a protective effect could be detected even within six months after treatment. More recently, Maruyama et al. analyzed a large retrospective series of 500 patients treated with gamma knife radiosurgery and found a decline in the risk of hemorrhage across three time periods: before radiosurgery, between radiosurgery and AVM obliteration, and after angiographic obliteration (49). Across all 500 treated patients, 42 hemorrhages were observed shortly before radiosurgery, 23 occurred during the period between treatment and obliteration, and six occurred after obliteration, yielding an estimated 54% decrease of hemorrhage risk in the latency period and an estimated 88% decreased risk after obliteration. The risk reduction was noted to be greater for those patients who presented with hemorrhage than for those who did not. For the 310 patients presenting with hemorrhage, the authors estimated the annual rate of repeated hemorrhage before radiosurgery at slightly more than 6% per year. Radiosurgery as Not Protective Before AVM Obliteration Several investigators have found that partial obliteration of the AVM does not provide a protective effect from hemorrhage risk. Steinberg et al. found no measurable effect on the likelihood of posttreatment hemorrhage during the time prior to obliteration, with (nonactuarial) 12% of treated patients bleeding between 4 and 34 months after treatment (8). The authors noted that they needed more data to show that there was a protective effect (if any) from radiosurgery during the latency period before AVM obliteration. Similarly, in a series of 158 patients with unresectable, Spetzler–Martin Grades I–IV AVMs followed for a mean of 30 months after linear accelerator-based treatment, Friedman et al. reported that six patients (4%) had posttreatment hemorrhages, but all occurred within one year of the radiosurgery (50). The authors concluded that some risk of hemorrhage remained during the latency interval before AVM ablation, but that more data would be needed to show a reduced risk. Kondziolka et al. analyzed the occurrence of postprocedure hemorrhage among 348 patients treated with the gamma knife at the University of Pittsburgh between 1987 and 1992 (51). Under the assumption of obliteration rates of 40% at one year and 80% at two years and an underlying yearly hemorrhage risk of 4%, the authors predicted that 16 patients would suffer hemorrhages during the latency period; however, the actual number was 18 patients. The authors concluded that there was no evidence for ascribing a protective effect to radiosurgery for lesions not totally obliterated. It should be noted, however, that even a 50% decline (e.g., from 4% to 2%) in the annual hemorrhage rate would not be easily detectable without follow-up longer than two years for a larger series of patients. After two years, if 20% of the AVMs in a group of 400 patients remained partially obliterated, then 80 patients would be at risk of bleeding, and a decline in annual risk from 4% to 2% would be statistically undetectable without several years of follow-up. Pollock et al. provided an in-depth analysis with longer follow-up of a similar series of 315 patients with AVMs treated before 1992, with a longer mean follow-up of 47 months (28). Analysis of the available 10,939 patient-years before radiosurgery revealed an annual nonfatal hemorrhage rate of 2.4%. This result might be interpreted as an argument for a total (fatal and nonfatal) annual risk of (pretreatment) hemorrhage not in excess of 5% (an estimate that likely should be lower given the biases inherent in AVM recognition and patient selection). After radiosurgery, the actuarial, annual hemorrhage rate until AVM obliteration was 5% in this study, without a significant change between time periods zero to two years and two to five years postprocedure. In contrast with other studies suggesting there might be a baseline tendency for rebleeding at a higher rate during the first year after the initial hemorrhage, the authors concluded there was no evidence for an increased risk of bleeding during the latency interval the first year after radiosurgery. Given the continuing actuarial risk of hemorrhage at least through five years of follow-up, the authors also concluded there was no evidence for a decreased risk of bleeding in incompletely obliterated AVMs beyond two years after radiosurgery. Multivariate analysis of risk factors for postradiosurgical hemorrhage,
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including clinical presentation; prior embolization or incomplete resection; AVM volume, size, location, morphology, and venous drainage characteristics; related aneurysms; and dose, revealed only the presence of an unsecured proximal aneurysm as predictive for subsequent hemorrhage, with a relative risk of 4.56 (p < .001). The authors defined an early draining vein without residual nidus as a successful obliteration. In this group of 19 patients (whose lesions other authors would describe as ‘‘subtotally’’ obliterated) Pollock et al. observed no instances of subsequent hemorrhage. Repeat angiography on 7 of these 19 patients at 10 to 29 months (median 12 months), showed complete obliteration of the AVM. Among the other 12 without angiographic follow-up, there were no instances of clinically evident hemorrhage with median follow-up of 27 months. The inclusion of these patients among the group whose AVMs were considered incompletely obliterated would lower the observed bleeding rate and throw into question this paper’s conclusion that there is no decline in bleeding risk. In contrast, some have suggested that, under some circumstances, incomplete treatment with radiosurgery might entail some increased risk of hemorrhage after the procedure. However, no data exist to support this hypothesis for AVMs whose volumes have been fully treated. Steinberg et al. speculated that partial thrombosis of vessels in a nidus might predispose to hemorrhage, due to increased outflow resistance in the remaining abnormal vessels (8). Consistent with this hypothesis, Lo et al. developed mathematical and experimental models that suggested partial volume treatment might yield permanent pressure and flow increases within other parts of the AVM (52,53). Colombo et al. reported a series of 180 patients treated with linear accelerator radiosurgery (54). Fifteen patients had posttreatment hemorrhages, which yielded an actuarial risk of 8.4% for the first year after radiosurgery and a risk of 4.0% for the second year. Partial-volume irradiation was associated with a higher rate of hemorrhage than irradiation covering the entire AVM; however, the 27 patients who received partial-volume irradiation had AVMs with large and/or threedimensionally irregular target volumes, and these AVMs were thought to have a greater risk of bleeding at baseline. To work around this problem, the authors made an intertemporal comparison: the bleeding risk for these partial-volume cases was 4% for the first six months, increased to 10% for the seventh through the 18th month, declined to 6% for the 19th through the 24th month, and then dropped to zero. However, with a total of only 27 cases at risk, these differences in fact are indistinguishable. Similarly, Gallina et al. reviewed 17 cases of AVMs that were not cured three years after radiosurgical treatment (55), and found two large AVMs that bled 36 and 39 months after receiving irradiation, respectively. Both of these had received partial-volume irradiation. The authors reported that for these two cases the angiograms at the time of bleeding showed changes in blood flow, reduction of the number and of the caliber of the draining veins, and increased tortuosity, which they ascribed to increased pressure gradients through the malformations. In all, these data suggest that partial-volume irradiation may be associated with increased bleeding risk. Does Radiosurgical Treatment Affect Bleeding Risk? In summary, the evidence is mixed about whether radiosurgery affects the risk of posttreatment bleeding, but certain conclusions are reasonable. These may be viewed from the perspective of the time intervals that mark the natural progression of the AVM nidus and vessels in response to radiosurgical treatment: (i) latency, (ii) incomplete obliteration, (iii) subtotal obliteration, and (iv) total obliteration. We define the ‘‘latency interval’’ as that time during which little change would be clinically evident if angiography were to be repeated (an interval that might extend from several weeks to perhaps about one year). No clear evidence currently exists for radiosurgery causing either a decrease or an increase in the risk of bleeding during this initial period. After the latency interval, the nidus begins to be obliterated. For large AVMs not completely irradiated, some theoretical and experimental models suggest that vessels not in the irradiated portion of the nidus may suffer increased pressure and flow with increased likelihood of rupture, whereas the irradiated portion of the nidus becomes obliterated (8,52–55). However, clinical evidence supporting this hypothesized increased risk is only anecdotal and not conclusive.
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For completely irradiated AVMs, several studies suggest the risk of bleeding decreases as the nidus is obliterated (34,45,48,49). Other experiences suggest there is a continuing bleeding risk prior to obliteration (8,28,50,51). However, Steinberg et al. and Friedman et al. only demonstrated the continued existence of hemorrhage risk prior to obliteration (which is not controversial) (8,50). Pollock et al. did not include ‘‘subtotally obliterated’’ lesions as being at risk (28). Inclusion of these lesions as at-risk for bleeding would lower the posttreatment hemorrhage rates and thereby would suggest a decrease in risk as obliteration progresses. On balance, for patients whose AVMs were completely irradiated, the evidence favors a decrease in risk of hemorrhage when incomplete obliteration is observed on angiogram. ‘‘Subtotal’’ obliteration, defined by Steiner et al. as the disappearance of the nidus on angiogram but with the continued presence of an early draining vein, appears associated with a decreased risk of hemorrhage (44). Pollock et al. reported 19 such patients with median followup in excess of two years following the angiogram, with no instances of bleeding (28). The experiences of Forster et al. (45) and Steiner et al. (44) were similar, with no patient with a subtotal obliteration experiencing a subsequent hemorrhage. Nevertheless, the existence of an early draining vein is evidence for the existence of continued shunting, even if no nidus is visible. In conjunction with shunting and continued elevated pressures in the nonarterial vasculature, hemorrhage is possible. There is some evidence that such subtotal lesions are obliterated fairly rapidly (median 12 months) without further intervention (28); however, as long as an early draining vein is present, there is some residual degree of risk. Steinberg et al. noted the occurrence of bleeding 34 months after treatment in one patient who had 95% obliteration of the AVM on angiography (8). This finding argues that there is a continued risk of hemorrhage, even when the nidus is nearly obliterated. Complete obliteration of the AVM, with no evidence of continued shunting, should be the ultimate goal of radiosurgical treatment. Very few instances of bleeding have been reported in lesions that have been completely obliterated, defined by normal circulation time, absence of former nidus vessels, and disappearance or normalization of draining veins (24). However, Maruyama et al. documented six patients with hemorrhages in 250 patients whose AVMs had been obliterated with median follow-up of 5.4 years (49). This represented a reduction in the risk of hemorrhage by 88% after obliteration compared to the time period before treatment, and a reduction in risk of 74% compared to the time period between treatment and obliteration. Shin et al. estimated the risk of rebleeding following complete nidus obliteration at 0.3% per year (56). TRANSIENT EFFECTS ON NORMAL BRAIN TISSUE Many authors divide the reactions of brain tissue to radiation treatment into three categories according to their time of appearance: (i) acute reactions, (ii) early-delayed reactions, and (iii) late-delayed reactions (57–59). Reactions in the first two categories are generally selflimited and transient, disappearing even without therapy; reactions in the third category are generally permanent and often are associated with central necrosis. Although these clinical distinctions are based on patients treated primarily with fractionated treatments, these categories are helpful in categorizing the responses of normal tissues to stereotactic radiosurgery. Acute Reactions to Radiation Treatment Acute side effects arising from radiosurgery are caused either by worsening intracranial edema or by the exacerbation of ectopic electrochemical activity in the brain. These situations may result in new or worsening headaches, nausea, visual changes, ataxia, focal neurological deficits, seizures, or other neurological symptoms or signs, which may be so mild as to be clinically negligible or so severe as to require hospitalization (60). Management of new or worsening symptoms requires ruling out other possible causes, particularly AVM hemorrhage, and identifying the underlying etiology. Postprocedure Intracranial Edema Rubin and Casarett described cerebral edema as a very early or immediate form of acute radiation injury (61). Most acute reactions in response to brain irradiation are likely due to edema, and such reactions usually respond to glucocorticoid therapy (59). Such edema may be
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manifested as generalized symptoms of increased intracranial pressure, or as a more focal intensification of the existing neurological symptoms that arise from the underlying lesion. In general, the occurrence of symptomatic edema is related to both the dose and volume of brain irradiated. In one study, patients received doses of 6.0 Gy to the whole brain twice a week to a total of 30 Gy; this regimen was well tolerated (62). However, in another study, two fractions of 7.5 Gy to the whole brain resulted in an acute complication rate of 49%, with complications including headaches, nausea, vomiting, temperature elevation, and even cerebral herniation (63). Although total dose and target volume are important in assessing the likelihood of acute side effects for hypofractionated radiation treatments, no study to date has related the dose and volume of irradiation delivered using stereotactic radiosurgery to the incidence of acute side effects for patients with AVMs. Werner-Wasik et al. found an overall incidence of 36% (4 of 11 patients) for immediate side effects after AVM stereotactic radiotherapy. However, only five of these patients were treated with radiosurgery, while the remainder received fractionated stereotactic treatment; and patients treated with radiosurgery were routinely premedicated with a single dose of glucocorticoids before the procedure (60). The location of the radiosurgery may influence the occurrence of postoperative symptoms. In 22 (11%) of 196 patients treated for intracranial metastases, nausea and/or vomiting developed within 24 hours of radiosurgery (64). All but one had a metastasis within millimeters of the area postrema (the vomiting center at the floor of the fourth ventricle). The incidence and severity of symptoms were directly correlated with the dose delivered to the area postrema; all patients who received greater than 2.75 Gy at the area postrema developed symptoms, whereas only one of 174 patients who received less than 2.56 Gy to the area developed symptoms (65,66). Similarly, in the radiosurgical experience reported by Loeffler and Alexander, four patients with metastatic lesions in the motor cortex experienced weakness within 36 hours of stereotactic radiosurgery, but these symptoms resolved within 24 hours without glucocorticoid therapy (64). One patient with a recurrent glioma developed aphasia two hours after treatment to the left temporal lobe, but this effect cleared within 12 hours of radiosurgery (66). Such acute events appear to be self-limited and related to the dose and area of brain treated. The clinical management of short-term effects of radiosurgery focuses on control of cerebral edema as well as the management of symptoms. Some transient edema is anticipated; therefore, some centers start low-dose oral dexamethasone therapy the day of radiosurgery and taper the steroid over the ensuing two weeks (50). In response to clinical or radiographic evidence of worsening edema, the oral steroid dose may be increased and the taper prolonged. Although glucocorticoid therapy may be helpful in terms of preventing or ameliorating shortterm symptoms, there is no evidence of long-term benefit. Some centers do not routinely premedicate patients with glucocorticoids. We premedicate patients with glucocorticoids and an antiemetic agent one hour before radiosurgery if the dose calculated to be delivered to the area postrema is greater than 4.0 Gy. Premedication with intravenous ondansetron, a 5-HT3 receptor antagonist thought to block serotonin-mediated pathways, with or without glucocorticoids, decreases the incidence and severity of nausea and vomiting in this subset of patients (67). Postprocedure Seizure Activity In their series of 158 patients treated between 1988 and 1993, Friedman et al. noted that seven patients (4.6%) experienced seizures within 48 hours of radiosurgery (50). All these patients had originally presented with a seizure disorder. In the series treated by Loeffler and Alexander, seizures developed in 12 of 196 patients (6%) within 24 hours of radiosurgery for intracranial metastases. All 12 patients had a history of seizure, and 10 were being treated with anticonvulsants (64). The incidence of seizures after radiosurgery for AVMs, however, may be somewhat higher. Reporting on 247 patients with AVMs who were treated between 1970 and 1983, Steiner et al. noted 29 patients (12%) with uncontrolled seizures following radiosurgery, although the timeline after treatment was not detailed (46). Of the 188 patients without a history of seizures before treatment, 11 patients (6%) developed new-onset seizures following radiosurgery; of the 59 patients with a history of epilepsy, 18 patients (31%) continued to have uncontrolled seizures after treatment. Similarly, Kjellberg et al. reported that 5 of 24 patients (21%) with a pretreatment history of seizures continued to have seizures after radiosurgery (3).
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In short, seizures may arise within 48 hours after radiosurgery in 5% or more of patients with a history of seizures. Therefore, in our practice blood levels of anticonvulsants for patients with a seizure history are optimized before radiosurgery. These patients are not hospitalized after the procedure, but safe proximity to a medical facility is assured. For patients without a seizure history, antiepileptic medications are not administered routinely. The literature shows these patients have little risk of the induction of seizure activity by radiosurgical treatment in the absence of a predisposing history, although there are a few reports of new-onset seizures after radiosurgical treatment (46,68). Early-Delayed Reactions to Radiation Treatment Early-delayed reactions to brain irradiation appear clinically from a few weeks to a few months after treatment, are transient, and usually disappear without therapy (59). The first studies documenting early-delayed clinical effects included primarily patients treated with fractionated radiation to relatively large volumes of the brain (69–73). Although many of these patients improved spontaneously without changes in therapy, a few deteriorated, eventually to die of brain damage. It is, therefore, important to distinguish early-delayed reactions, which are self-contained and transient, from the late-delayed, usually permanent reactions, which evidence underlying, long-term, usually progressive brain necrosis. Early-delayed reactions arise a few weeks to several months after brain irradiation (58). These reactions may be clinically asymptomatic, may be associated with generalized somnolence or other nonspecific symptoms, or may even include severe neurological sequelae. Histopathologically, in all these patients areas receiving radiation may develop disseminated plaques of demyelination, at times associated with central necrosis and petechial hemorrhages. As early as 1964, Lampert and Davis emphasized this early-delayed reaction as a separate, characteristic clinical and pathologic entity (57). Hoffman et al. speculated that demyelination might be the cause of this syndrome, with the latent period corresponding to the turnover time for myelin (73). However, noninflammatory microangiopathy with varying amounts of adjacent necrosis and microcalcifications, along with macroscopic changes of ventricular dilatation, widening of subarachnoid spaces, decreased attenuation coefficient, and intracerebral calcifications also have been documented in some cases (74,75). Van der Kogel and Barendsen described two types of injury appearing in rat spinal cord, the earlier (within seven months) appearing to be a result of demyelination and the later appearing to be a result of vascular damage (76,77). It is tempting to speculate that demyelination changes are more transient, whereas vasculopathies may lead to frank necrosis; however, no study to date has clarified this association. Both types of changes, transient demyelination and microvasculopathies, are associated with similar changes on imaging studies. For example, prolongation of the T2 signal on magnetic resonance imaging (MRI) is suggestive of increased regional proton content, likely indicating cerebral edema. Increased extracellular fluid with resulting edema arises from regional blood–brain barrier disruption, which might well be the result of direct cytotoxicity, demyelination, or disruption of vasculature. Due to this lack of radiographic specificity, most clinical distinctions in the literature center on the timeline and outcome of observed neuroradiologic findings to determine whether a given finding is transient or whether it will progress to worsening, long-term, permanent damage. Types of Imaging Changes Attempts have been made to correlate various radiologic findings with clinical outcomes. In one study, 60 patients with AVMs who had been treated in 1994 and 1995 with linear accelerator-based radiosurgery were followed up with detailed MRI imaging (78). Patients were sorted into four categories: grade 1, those with no parenchymal findings on MRI; grade 2, those with hypersignal on T2 imaging; grade 3, those also with contrast-enhancement on T1 imaging; and grade 4, those also with central hyposignal (suggesting necrosis) and with peripheral hyposignal on T1-weighted sequences. With very short (one year) follow-up, the only patients with clinical symptoms were grade 4 patients, and most of these symptoms responded to treatment with glucocorticoids. However, at one year the AVM obliteration rates also correlated very strongly with MRI findings: 12.5% for grade 2 and up to 82.2% for grade 4.
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It is open to question whether these particular correlations of MRI findings with clinical symptoms and with AVM obliterations will be maintained with longer follow-up. Data from a study by Lunsford et al. partly address this question (79). MRI findings in 2344 patients (including 646 patients with AVMs) treated with the gamma knife were categorized as ‘‘white dwarfs,’’ ‘‘black holes,’’ or ‘‘supernovas.’’ With pathologic correlations for these MRI findings from animal models, the authors used this typology to characterize patients’ responses to treatment. ‘‘White dwarfs’’ showed dramatic radiologic response consisting of involution of the lesion with residual small volume contrast enhancement. Among a subset of 140 patients with angiographic follow-up, such small ‘‘white dwarfs’’ at the AVM target site correlated with total angiographic AVM obliteration with greater than 90% accuracy two years after treatment (80% sensitivity, 100% specificity) (80). In animal models such white dwarfs were characterized by fibrosis, gliosis, vessel hyalinization, and luminal vascular obliteration (81). ‘‘Black holes’’ on MRI showed central loss of contrast enhancement in lesions (thought to represent central necrosis), as well as overall volume loss for AVM targets. Such findings were similar to what Nataf et al. ranked as a ‘‘grade 4’’ response to radiosurgery at one year follow-up. However, Lunsford et al. observed that development of a ‘‘black hole’’ portended progression to a ‘‘white dwarf’’ in more than 70% of patients over the ensuing 12 months (79). Therefore, a ‘‘black hole’’ likely would correlate best with direct or induced cell death (apoptosis) along with vascular obliterative events—early stages of the histopathological changes seen with ‘‘white dwarfs’’—rather than with early signs of tissue necrosis involving normal brain. ‘‘Supernovas’’ showed imaging changes that greatly exceeded the expected response based on lesion histology or treatment volume (79). Lunsford et al. found these rare events were characterized by diffuse T2 signal abnormality, at times associated with diffuse irregular contrast enhancement in the perilesional target volume. These were related to dose, volume, and (to some extent) location of the AVM, potentially correlating with blood–brain barrier breakdown (particularly in cavernous malformations). The authors speculated that these effects might be due to release of a vasoactive substance, thus leading to long-term imaging changes as a result of blood leakage or hemosiderin deposition. Incidence of Imaging Changes The Lawrence Berkeley Laboratory’s experience with heavy-charged particles was one of the earliest studies systematically documenting radiographic imaging findings after radiosurgery for AVMs (8,82). MRI or computed tomography (CT) scans every six months and angiograms once a year showed that half (33 of 65) of the patients studied with MRI or CT developed white-matter changes between 4 and 26 months after treatment (mean 15.3 months). Twenty (61%) of these patients remained asymptomatic. Vasogenic edema on imaging studies occurred more commonly among those radiosurgery patients receiving higher doses of helium ions to their AVMs (in excess of 25 GyE), and this effect seemed to be more common with treatment volumes located within the substance of the central white matter. The edema usually resolved spontaneously over six months, but in some cases it persisted with limited effects for between one and two years. Complete resolution could take up to 36 months after treatment. Similar high rates of imaging changes were found in a study of 135 lesions treated with stereotactic radiosurgery between 1990 and 1994 by Voges et al. (83). With a median follow-up of 28.1 months, radiation-induced tissue changes documented on CT or MRI or by clinical symptoms occurred more frequently for AVMs (37.5%) than for skull base tumors (14.6%), with the vast majority occurring within the first 20 months after treatment. Furthermore, the risk for the development of clinically symptomatic neuroradiologic changes was 25.5% at two years for intraparenchymal (mostly AVM) lesions, but only 1.5% for skull base tumors. Multivariate Cox regression analysis of these 56 AVM lesions revealed only the total volume covered by the 10-Gy isodose line (median 25.4 cm3, range 1.2–81.9 cm3), as having statistically significant impact on the occurrence of radiation-induced tissue changes. No radiation-induced tissues changes occurred in patients with less than 10 cm3 volume receiving more than 10 Gy irradiation, whereas the incidence for the group receiving more than 10 Gy to more than 10 cm3 volume was 37.5%. Flickinger et al. did serial postirradiation MRI imaging of 72 patients with AVMs between 1987 and 1993 (84). Twenty developed imaging changes, and 9 of these 20 patients
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Figure 3 Actuarial incidence of developing postradiosurgery imaging changes (any new T2 changes) and symptomatic imaging changes (symptomatic T2 changes) in 307 patients with arteriovenous malformations treated at the University of Pittsburgh between 1987 and 1993, with a minimum follow-up period of 24 months (median followup 44 months). Source: From Ref. 85.
developed clinical symptoms, for an actuarial risk two years after radiosurgery of 31% for all imaging changes and 14% for symptomatic imaging changes. Symptoms were more common for imaging changes in the brainstem (six of seven patients) than for changes in the cerebral cortex or cerebellum (3 of 13). However, in multivariate analysis, treatment volume was the only factor that was significantly associated with the development of imaging changes. This series was expanded in three subsequent publications (85–87). In 307 patients with AVMs treated between 1987 and 1993 with gamma knife radiosurgery, postradiosurgical imaging (PRI) changes developed in 30.5%—defined as new regions of T2 imaging changes on follow-up MRI scans (85). At seven years follow-up, 10.7% of patients had experienced symptomatic PRI changes, with no new cases after 30 months (Fig. 3).These changes resolved within three years of development in 94.5% of patients with asymptomatic PRI changes, but in only 52.8% of patients with symptomatic PRI changes (Fig. 4). The seven-year actuarial rate for developing persistent, symptomatic PRI changes was 5.05%. In a paper analyzing 332 patients with AVMs treated between 1987 and 1994, Flickinger et al. developed a ‘‘postradiosurgery injury expression’’ (PIE) score for AVM location that categorized risk into four groups: 1—frontal lobe; 2—cerebellum and temporal and parietal lobes; 3—occipital lobe and basal ganglia; 4—medulla, pons, thalamus, corpus callosum, and intraventricular areas (85). This score, along with the 12-Gy volume (the total volume receiving 12 Gy), predicted development of symptomatic PRI sequelae on multivariate analysis, with relative risk increasing by a factor of 3.4 per unit PIE score (Fig. 5). In 30 patients, the risk of
Figure 4 Comparison of actuarial rates of resolution for postradiosurgery imaging changes for 56 asymptomatic and 29 symptomatic patients with arteriovenous malformations treated at the University of Pittsburgh between 1987 and 1993. Source: From Ref. 85.
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Figure 5 Likelihood of symptomatic sequelae as a function of radiosurgery volume receiving at least 12 Gy for different postradiosurgery injury expression scores. Estimates were derived from multivariate logistic regression analysis of 30 patients with symptomatic postradiosurgery sequelae, among 332 patients with arteriovenous malformation treated at the University of Pittsburgh between 1987 and 1994. Source: From Ref. 86.
these symptomatic PRI changes persisting for more than two years (i.e., the clinical definition of radionecrosis) was predicted by PIE score as well as by whether the entire AVM nidus (and, hence, the surrounding normal tissues) received a minimum of at least 20 Gy. However, the 12-Gy volume did not prove to be a significant predictor for persistence of symptoms. Flickinger et al. expanded this series into a multi-institutional study of 85 patients with AVMs who developed symptomatic complications, 38 of whom were classified as having permanent sequelae (necrosis), along with a control group of 337 patients without complications (87). The authors found that the 12-Gy volume along with the AVM location could be modeled as a ‘‘significant postradiosurgery injury expression’’ (SPIE) score (0–10). The SPIE score along with the 12-Gy volume significantly predicted risk of permanent symptomatic sequelae, whereas inclusion of prior hemorrhage, marginal dose, or marginal 12-Gy volume (the volume receiving 12 Gy but excluding the target) did not significantly improve the risk-prediction model. Therefore, PRI changes do not all represent postradiation injury but, for instance, may include parenchymal hemodynamic changes or signals from damaged shunting vessels, that portend AVM obliteration. The likelihood of permanent, symptomatic radionecrosis is not simply a reflection of the incidence of PRI changes (whether symptomatic or not); rather, additional factors are important. These include, at the very least, further information about regions of high dose delivered to surrounding normal brain tissue (86,87). Definition of Volume at Risk It is unclear whether the irradiated volume contributing to the risk for complications includes the entire volume irradiated (including the AVM nidus), whether it excludes the entire volume of the AVM, or whether it includes only part of the AVM volume—considerations that are relevant especially for larger malformations. Flickinger originally hypothesized that the volume of the AVM should be excluded (88), while Lax and Karlsson included the entire volume in their calculations (89). Addressing this issue, Flickinger et al. used multivariate analysis to study several parameters as potential predictors of PRI changes for patients with treated AVMs, including volume receiving 12 Gy, the number of isocenters, the minimum and maximum doses to the target volume (Dmin, Dmax), treatment volume, nontreatment volume receiving more than 8 Gy, dose rate, and target dose inhomogeneity (85). However, of these parameters, the only significant independent variable associated with PRI changes was the 12-Gy volume, and this finding was true for the entire patient population as well as for the subgroup of patients treated with a single isocenter. Because inclusion of the target AVM nidus within the volume contributing to risk of complications was a better predictor of PRI changes than was exclusion of the target from this volume, the authors argued the AVM nidus target tissue contributed to radiosurgery complications. This finding was subsequently confirmed in a large, multiinstitutional analysis (87).
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Similarly, in an earlier study of 250 patients treated with the gamma knife, with a minimum follow-up of two years, Flickinger et al. observed PRI changes in 54 patients (22%) (90). These changes occurred more frequently in patients with AVMs (31%) than in patients with vestibular schwannomas or meningiomas (8%). Step-wise multivariate logistic regression showed that the only significant factor affecting the likelihood of a PRI change was the treatment volume (p ¼ .029); however, the difference between patients with AVMs and those with benign tumors was nearly statistically significant when treatment volume was controlled for (p ¼ .052), with a relative risk of 8.6 for an AVM (95% confidence limits: 0.98–75.8). Although this study was not conclusive due to the small number of PRI changes available, the results were consistent with the hypothesis that, above and beyond volume effects on normal brain tissue, target volume within the AVM nidus contributed to the observed PRI changes. Dose Inhomogeneity Nedzi et al. performed a retrospective analysis of 60 patients with 64 primary gliomas or cerebral metastases (no AVMs in the population studied), who were treated between 1986 and 1989 with stereotactic linear accelerator radiosurgery (91). Fourteen patients developed symptomatic complications related to treatment. Although several other variables were highly correlated with dose inhomogeneity, including tumor volume, number of isocenters, maximum normal tissue dose, and maximum tumor dose, in a multivariate logistic analysis of symptomatic complications the authors found that tumor dose inhomogeneity had the highest log-likelihood of the variables analyzed. This finding suggested that dose inhomogeneity arising in the target volume might be related to the risk of symptomatic radiosurgical complications. However, no AVMs were included in the analysis, and the tight correlations between the variables suggested these distinctions were less than conclusive. In contrast, in their study comparing 250 patients treated with the gamma knife, including 144 AVMs, 69 vestibular schwannomas, and 37 meningiomas, Flickinger et al. found that neither minimum treatment dose, maximum dose, tumor dose inhomogeneity (that varied from 2.2 up to 40 Gy), treatment isodose, nor the use of single versus multiple isocenter plans were significant predictors of PRI changes (90). Likewise, more extensive analysis of 307 patients with AVMs did not find dose inhomogeneity to be a significant predictor of PRI changes (85), nor was dose inhomogeneity significant in a subsequent multivariate model of complications in 1255 gamma knife treatments for AVMs (87). Similarly, in their analysis of 133 patients treated with linear accelerator radiosurgery, Voges et al. found no statistically significant effect relating the number of isocenters to PRI changes (83). Conclusions About Imaging Changes and Symptomatic Complications In summary, the likelihood of a PRI change is a function of the treatment volume (defined as the volume receiving at least 10 or 12 Gy) and lies between 30% and 50% in most series. In a subset of these patients, the PRI changes are symptomatic, with the likelihood of symptoms being a function, not just of treatment volume, but also of anatomical location. Most PRI changes resolve, but about one-third to one-half of symptomatic changes do not. The volume of the AVM appears to contribute to the likelihood of a PRI change; however, beyond this effect there is no strong evidence at present for dose inhomogeneity contributing additionally to the risk of a PRI change. Progression to frank radionecrosis (clinically defined as long-term, symptomatic sequelae) depends on factors in addition to those contributing to PRI risk. These factors are not yet identified clearly but may be related to the dose levels delivered to surrounding normal brain. RADIONECROSIS AND OTHER LONG-TERM EFFECTS Modeling Radionecrosis Risk As classically described, late-delayed reactions have a latent interval from irradiation to the appearance of symptoms or signs ranging from a few months to several years (59). These reactions are characterized as irreversible and frequently progressive, and they usually indicate underlying radiation necrosis. White matter appears more sensitive than gray matter. In their seminal review, Sheline et al. studied the world literature and found 80 evaluable patients with radiation-induced brain necrosis (58). In their analysis of total dose (D), overall treatment time (T), and number of fractions (N), with dose and number of fractions plotted on a log–log
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plot, they found the data to be consistent with the ‘‘neuret’’ formulation of equivalent dose: neuret ¼ D N0.41 T0.03, with about 1000 neuret representing a cut-off below which radionecrosis is very rare (59). Compared with the ‘‘nominal standard dose’’ of the Ellis formula for late radiation effects, their use of the 0.41 exponent emphasized particularly the importance of fraction number (N) in the determination of the likelihood of late necrosis and was based both on their review of the clinical data as well as on the animal models of van der Kogel and Barendsen (76,77). In a review of 139 irradiated patients, seven of whom developed proven brain necrosis, Marks et al. reached similar conclusions (92). These estimates, however, were based on clinical experiences with multiple fraction treatments. It would not be warranted to apply these equations directly to the extremes posed by stereotactic radiosurgery, by which a single fraction delivers the entire treatment dose. Instead, in developing their isoeffect curves, Kjellberg et al. used these equations as a baseline, but supplemented them with further modeling and experimental animal data to derive estimates of dose–volume isoeffects for radionecrosis risk (3,20). After the 1983 publication by Kjellberg et al. of 1% and 99% isoeffective lines for radiation necrosis with logarithmic scales for field diameter and dose (3,20), several groups adapted the 1% isoeffect curve for making decisions about treatment doses for various collimator sizes and treatment doses, although these curves had limitations. First, they were based primarily on animal models and theoretical constructs with little available clinical experience. It was not until 1983 that sufficient numbers and follow-up had accrued to enable publication of treatment results and clinical complications for the first 75 patients with AVMs treated at the HCL with proton radiosurgery (3). Second, these predictions did not account for differences in the dose distributions outside the treatment volume. These differences varied across both patients and centers: with the type of beam employed (e.g., protons, heavy ions, and various photon energy distributions), with the specific beam arrangements and techniques used (e.g., fixed beams, arcs, and beam widths), and with the anatomical relationship of the treatment volume to critical brain structures (e.g., brainstem, optic tracts, and corticospinal pathways). Third, early clinical data suggested that the isoeffect lines might underestimate observed clinical experience. By the mid-1980s one clinical series of 600 patients with AVMs treated with the Leksell gamma unit reported a 3.3% rate of transient radiation-related complications and a 3.1% risk of permanent, radiation-related symptomatic brain necrosis. However, without a dose–volume analysis it was unclear whether all patients included in the study were treated to the 1% isoeffect line (9,93). Fourth, not all complications associated with radiosurgical treatment of AVMs were necessarily a function of the risk of radiation necrosis. Given these limitations, along with the need to be able to predict isoeffects when fractionated large field irradiation is combined with single fraction radiosurgical boosts, Flickinger developed the integrated logistic formula for predicting complications resulting from radiosurgery (88). This expression assumed a logistic equation for the dose–response curve for complications within the reference volume: PðD; 1Þ ¼ ð1 þ ðD50 =DÞk Þ1 ; and it relied on clinical parameters (D50, k) that Flickinger estimated using data from whole brain irradiation (for D50) and from several clinical and experimental sources (for k). Values for k were then checked and refined using a 600 patient clinical data base that had a 3% complications rate (9,93). Probabilities of brain necrosis for volumes including and excluding the 70% isodose value were modeled to be functions of the Dmax delivered and the collimator size, and these yielded complication probabilities predicted for single fraction radiosurgery with the Leksell gamma unit using 4-, 8-, 14-, and 18-mm diameter collimators, as well as for whole brain irradiation combined with a radiosurgical boost (Table 1). The Flickinger integrated logistic model with an isoeffect complication rate of 3% continues to be used as a guideline for estimating the likelihood of symptomatic brain necrosis. Lax and Karlsson went through a similar process to develop a double-exponential model (89), which assumed a dose–response curve for the reference volume to take the form: PðD; 1Þ ¼ expðN0 expðD=D0 ÞÞ: D0 and N0 were empirically determined from clinical data of 862 patient treatments with an overall complications rate (edema or radionecrosis) of 5%. In comparison with the results of
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Table 1 Complication (Radionecrosis) Probabilities for the Leksell Gamma Unit for Various Collimator Sizes and the Maximum Dose (Dmax) Based on the Exponential Version of the Integrated Logistic Model Collimator (mm) 4 8 14 18 18
Dmax (Gy)
Pr[0–70%] (%)
Pr[0–100%] (%)
50.0 50.0 50.0 40.0 62.0a
0.2 0.8 4.0 4.3 4.2
0.3 1.6 7.9 14.2 10
Note: Probability of radionecrosis was calculated for two separate sets of parameters, either with exclusion of the high-dose volume receiving more than 70% of Dmax, Pr[0–70%], or with inclusion of the entire volume treated, Pr[0–100%]. a The 62.0 Gy value includes 30.0 Gy in 12 fractions irradiation to the whole brain followed by a single fraction radiosurgical boost of 16 Gy to the 50% isodose volume. Source: From Ref. 88.
Flickinger, these authors found complication probability values that were slightly higher at all dose levels, but that were clinically notable only at high dose levels (e.g., a difference appearing for a 100 cm3 target volume only at doses yielding more than 15% to 20% chance of a complication) (Fig. 6). Given the slight difference between the two studies in terms of the definition of a complication event and given that the two approaches were based on entirely separate data sets and on different underlying mathematical structures, the similarities between the results of the two models appear mutually reinforcing over clinically relevant dose ranges. The Harvard Cyclotron Laboratory Experience: 37 Years of Follow-up Between 1965 and 1993, Kjellberg treated 1329 patients with AVMs at the HCL using proton beam stereotactic radiosurgery (94). Through concurrent clinical records, questionnaires, and contacts with referring physicians, follow-up was obtained for 1250 patients (94.5%) with a median follow-up time of 6.5 years. Doses and volumes for each patient were obtained from HCL records. The median dose was 10.5 Gy, and the median volume was 33.7 cm3, both calculated at the 90% isodose line. Of these lesions, 23% had volumes less than 10 cm3. Doses had been selected on the basis of Kjellberg’s estimates of complication risk, a model that included only dose and beam diameter. Using these data, Barker et al. found that permanent neurological complications were most likely to arise within the first few years after radiosurgery (Fig. 7) (94). Among the
Figure 6 Lack of significant difference in radionecrosis risk estimates over clinically relevant dose ranges between the Flickinger logistic model and the Lax/Karlsson double exponential model. The two sigmoidal curves to the left represent the dose–response curves for a reference volume equal to the whole brain, with the dashed line representing the logistic model and the solid line representing the double exponential model. The two curves to the right show the dose–response curves for a volume equal to 100 cm3, with the upper curve representing the double exponential model, and the lower curve the logistic model. Source: From Ref. 89.
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Figure 7 Survival plot showing incidence of permanent complications after arteriovenous malformation radiosurgery in 1250 patients treated by Kjellberg at the Harvard Cyclotron Laboratory between 1965 and 1993. Dotted lines represent the 95% CIs; numbers over the plot indicate the number of patients still under observation 1, 2, 5, and 10 years posttreatment. Source: From Ref. 94.
1250 patients, 51 experienced permanent neurological deficits (4.1%). Complications occurred between 0.2 and 6.8 years after treatment, but no further complications were reported during 2311 additional patient-years of follow-up beyond 6.8 years. The authors found that Kjellberg’s model underestimated risk of permanent neurological injury, particularly at higher doses (Table 2). Of 1043 patients treated using a Kjellberg radiation isoeffective centile less than 1% (patients predicted to have less than 1% complication risk), 1.8% suffered radiation-related complications, while complication rates for 128 patients treated at Kjellberg centile of 1% to 1.8% were 4.7%, and complication rates for 61 patients treated at Kjellberg centile of 2% to 2.5% were 34%. Analysis of results for the 293 patients with lesions less than 10 cm3, thereby normalizing for treatment volume, showed a similar pattern, with complication rates higher than those predicted by the Kjellberg centile formula, particularly for patients treated at centiles 2% or above. Multivariate modeling demonstrated significance for four variables: larger treatment dose and volume, older age, and central lesion location (in the thalamus or brainstem). Also, an interaction term between dose and volume proved significant (p ¼ 0.01) because complications occurred more frequently than otherwise expected when both dose and volume were large. More modern series have considered both dose and volume in the prescribing of radiosurgical treatments, resulting in a strong colinearity between the two variables. In contrast, the
Table 2 Permanent Radiosurgery-Related Complications for 1250 Patients with Arteriovenous Malformations Treated by Kjellberg at the Harvard Cyclotron Laboratory Between 1965 and 1993 Kjellberg’s Model—Estimated Complication Risk Less than 1% 1–1.8% 2–2.5% Among 293 lesions with less than 10 cm3 volumes: Less than 1% 1–1.8% 2% or greater Source: From Ref. 94.
Actual Complications
No. of Evaluated Patients
No.
(%)
1043 128 61
19 6 21
1.8 4.7 34
230 44 19
11 1 3
5.4 2.2 15.8
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HCL experience provided a unique data set, with its unusually broad range of doses and volumes. These data reinforced the importance of dose, volume, and central location in assessing the risk of permanent sequelae following radiosurgical treatment of an AVM. Univariate logistic modeling showed the best cutoff point for a threshold dose effect at 13.49 Gy, with complications occurring in five (0.6%) of 905 treatments at or below this dose and in 46 (13.3%) of 345 treatments above this dose. However, in multivariate models, dose as a continuous variable yielded a consistently better fit than did dose as a threshold effect. Treatment of Radionecrosis In some circumstances, glucocorticoids and/or resection may ameliorate symptoms of radionecrosis. In their definitive review, Edwards and Wilson concluded that resection of focal necrosis may be life saving and is often efficacious in improving functional outcome (95). Sheline et al. found that 35 of 80 patients with brain necrosis underwent surgical intervention (58). Of the 19 (24% of necrotic lesions) who were reported to benefit from the surgery, nine (47%) had superficial necrosis (these nine previously had been irradiated for skin cancers). However, with current neurosurgical techniques, more patients are likely to benefit from the resection of surgically accessible necrotic lesions. Other Long-Term Effects on Brain Tissues Symptoms in the Absence of Evident Parenchymal Damage Flickinger et al. described a multi-institutional series of 1255 patients with AVMs among whom 102 developed neurological sequelae, but with a relatively short median follow-up of 34 months (96). Of these 102 patients, 22 had no evidence on imaging studies of injury to brain arenchyma: 12 presented with isolated cranial neuropathies, and 10 with new or worsened seizures. Multivariate analysis of these 102 symptomatic patients identified significantly greater resolution of symptoms among patients with no prior history of hemorrhage (p ¼ .015) and in patients with headache or seizure as the only sequelae of radiosurgery (p < .0001). However, the study did not specifically examine whether patients with radiologic evidence of parenchymal damage had a lower rate of symptom resolution. Nevertheless, these data argue strongly that symptoms due to lesser degrees of underlying tissue injury are more likely to resolve over time. There have been a few cases of long-term symptoms that persist after the PRI changes resolve. Friedman et al. reported two patients (1.3%) who experienced permanent radiation-induced complications, with onset of symptoms at 11 and 14 months, respectively, but both of whom had areas of edema on neuroimaging that gradually resolved after months of steroid therapy (50). Both had documented cures by angiography. Nonsymptomatic Permanent Imaging Changes Not all long-term changes related to radiosurgical treatment lead to frank necrosis, with its worsening edema, mass effect, and functional debilitation. Some PRI changes, although not significantly symptomatic, may persist indefinitely. Kihlstro¨m et al. reported on 18 AVM patients treated with radiosurgery who had follow-up MRI scans an average of 10 years (range 4–17 years) after confirmed nidus obliteration (97). A significant number (12 of 18) had signal changes up to 23 years after gamma knife radiosurgery. All were asymptomatic, yet 28% had cyst formation (defined as CSF signal with a well-demarcated margin), 61% showed gadolinium enhancement (but without evidence of recanalization on angiogram), and 17% showed increased T2-weighted signal, all at the obliterated AVM site. These results could not be clearly related to the treatment dose (other than that higher doses correlated with increased T2-weighted signal). The authors suggested that increased vascularity and/or blood–brain barrier breakdown could explain gadolinium enhancement in the treated area, observed as long as 16 years after radiosurgery, whereas cyst formation might be a consequence of AVM destruction or of normal tissue response to irradiation, and increased T2-weighted signal was most likely related to demyelination or gliosis. In contrast, Yamamoto et al. reported three radiation-related symptomatic morbidities and an additional four asymptomatic imaging changes, arising at or beyond five years of followup, among 53 patients followed for more than 40 months after gamma knife treatment; however, a clear dose–volume–location analysis was lacking that might help explain this
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unusually high rate of late-occurring effects (98). Of note, 8 of these 53 patients received ‘‘less than complete nidus coverage,’’ while 29 of these patients received more than 25 Gy to the periphery—either of which might help explain the discrepancy. For comparison, among 607 patients with AVMs treated by Kihlstro¨m et al. between 1970 and 1987, only two (0.3%) had onset of symptoms more than four years after radiosurgery treatment, one at five years, and the other at 10 years (97). The latter case showed cyst formation on MRI. Similarly, in their analysis of 1255 patients, Flickinger et al. found that only 6% of symptomatic complications arose more than five years after radiosurgery, yielding an overall rate of late-occurring symptomatic complications of about 0.5% (96). Thus, long-term imaging changes are frequent but are rarely symptomatic. Radiosurgical treatment of AVMs can result in long-term imaging changes up to 23 years after treatment. In the absence of associated symptoms, the clinical significance of these changes is debatable. The Risk of Radiation-Induced Malignancy In 1948, Cahan et al. proposed criteria to determine whether a tumor had been induced by radiation treatment. These included (i) tumor arising within the irradiated tissues, (ii) a latency interval between treatment and tumor occurrence, (iii) documented absence of the tumor at time of radiation treatment, (iv) difference in histology between the new tumor and the previously treated tissues, and (v) absence of a cancer-prone syndrome, such as Li–Fraumeni syndrome (99). In 2000, Yu et al. provided the first report of a glioma arising within radiosurgically treated brain tissue that met the Cahan criteria (100). Shortly thereafter, Kaido et al. reported a case of glioma associated with prior AVM radiosurgery in a 20-year-old patient who had been treated six years previously for a cerebral AVM (101). There have been several other case reports of radiation-related tumors arising in brain tissue previously treated with radiosurgery for a variety of other conditions, including one cavernous angioma (102), two vestibular schwannomas (of which only one was histologically confirmed) (103,104), two pituitary adenomas (105), and one metastatic melanoma (106). Estimating the relative risk of radiosurgery-associated tumors is difficult. One may attempt to extrapolate this risk from long-term data from fractionated radiotherapy applied to larger fields. In the 1940s and 1950s, for example, more than 10,800 children in Israel received radiation to the scalp (mean dose 1.5 Gy) to induce alopecia as part of the treatment of tinea capitis (107). With a 30-year cumulative risk of 0.8% for development of neural tumors, these individuals had a relative risk of 8.4 for neural tumors of the head and neck, with the association strongest for nerve-sheath tumors (relative risk 18.8) and meningiomas (relative risk 9.5) but somewhat lower for other tumor types. A significant dose–response was observed, with relative risk approaching 20 with doses at 2.5 Gy and above. In this experience the mean interval for tumor occurrence was 21 years for meningiomas, 15 years for schwannomas, and 14 years for gliomas. A subsequent paper described 253 patients who developed meningiomas after radiation for tinea capitis in childhood (108). The mean latency period from exposure to meningioma diagnosis was about 36 years, emphasizing the importance of very long-term follow-up. Brada et al. reported a long-term study (3760 person-years) of a cohort of 334 patients with pituitary adenoma who were treated with conservative surgery and external beam radiotherapy (109). This study may be especially important in considering the potential risk of malignancy following radiosurgery, because the target volumes were similar to those often used in radiosurgery treatment, and because the doses were near (though somewhat lower) in terms of biological effectiveness to those typically used in the treatment of patients with AVMs. The authors identified five patients who developed second tumors (two meningiomas, two gliomas, one sarcoma), with a latency interval of 6 to 21 years. Relative risk of a second tumor was 9.38 compared with the normal population, with a cumulative risk, 20 years after treatment, at 1.9%. Although the doses in this study (median 45 Gy) were substantially higher than those in the tinea capitis experience, the relative risk values were not too dissimilar, suggesting a trade-off effect between dose and volume in the long-term risk of malignancy. On the basis of these studies, one may conclude that the risk of radiation-related malignancy is a function of both dose and volume irradiated, although the relationship between dose and risk is ill-defined and likely complex (105). The case reports demonstrate that radiosurgery-related tumors can arise within the full-dose region as well as in low-dose peripheral regions. Furthermore, the latency periods observed in the case reports are not dissimilar to
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those observed for malignant tumors in the Brada study and the tinea capitis experience, suggesting that very long-term surveillance strategies are prudent for all surviving patients. Lastly, although the risk of radiation-related malignancy is low, these studies and case reports demonstrate that this risk is real; therefore, patients with AVMs who are considering radiosurgery should be advised about this possibility. The Re-Treatment Problem Some centers have reported significant experience with re-treatment of incompletely obliterated AVMs. Steinberg et al. described re-treating 17 patients with helium ions three to five years after their initial radiosurgery, in cases of partial or no angiographic obliteration; with short follow-up, they reported complete obliteration in several patients while achieving a low complication rate (22). Kihlstro¨m et al. noted that of the 18 patients in their study of long-term MRI changes, six had been treated twice (97); however, they found no correlation between one or two treatments and the long-term observed MRI changes, a lack the authors thought might be explained by differences in treatment volumes or by fractionation effects. Pollock et al. reported on 45 patients with continued follow-up who underwent repeat radiosurgery 39 months (median) after the initial procedure (110). Two (4.4%) of these patients had AVM hemorrhages at 6 and 21 months, respectively, after the second procedure; whereas at two years after repeat radiosurgery, 6 of 14 patients with angiographic follow-up had complete obliteration, two had early draining veins only, and six had residual nidus. Hemorrhage risk for re-treated patients thus appeared to be similar to the risk for any patient treated with radiosurgery who still had a residual AVM nidus. Foote et al. reported similar results. The authors reviewed 52 patients who underwent repeated radiosurgery for residual AVM, in whom residual shunting had persisted longer than 36 months after the initial treatment (111). Treatment volumes were significantly smaller at the time of re-treatment: mean 13.8 cm3 compared with mean 4.7 cm3, for an average volume reduction of 66% following the first radiosurgical procedure. Consequently, doses were higher at the time of re-treatment, median 12.5 Gy for the first procedure, as compared to median 15.0 Gy for the second. Ten patients were either lost to follow-up or refused further neuro-imaging. Angiographic obliteration of the residual nidus was seen in 60% of the remaining 42 patients. One patient died of hemorrhage five months after re-treatment, and three other patients developed posttreatment complications, two transient and one permanent. In contrast, with longer follow-up (minimum greater than two years after the second treatment), Karlsson et al. found a higher-than-predicted number of complications (14 actual vs. 5 predicted) for 112 re-treated AVM gamma knife patients who had previously received conventional radiotherapy or prior radiosurgery (112). However, when the risk from the preceding radiation treatment was added, the observed number of complications was similar to the predicted number. Taken together, these studies demonstrate that more long-term data are needed to assess the efficacy and complication rates related to re-treatment of incompletely obliterated AVMs.
CONCLUSIONS Complications after radiosurgical management of AVMs mirror the patterns seen with more traditional forms of radiation therapy to the brain. If anything, radiosurgery’s precise localization of target volume and of dose distribution provides useful, novel information about the clinical tolerances of various areas of the brain in response to radiation treatment. Radiation effects, whether acute, transient, or permanent, are functions of both the dose and volume treated. The location of the target, exemplified by the PIE index, significantly influences clinical tolerance. As we learn more from increasingly detailed and sophisticated imaging and metabolic studies, the link between short-term parenchymal changes and long-term permanent sequelae will become increasingly clear. Continued improvements in our ability to assess the radiographic, pathophysiologic, and clinical effects of treatment, in conjunction with further improvements in targeting and delivering radiation dose, will enable us to minimize longterm complications and to enhance ever further this valuable technology.
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Section VI
FUTURE CONSIDERATIONS
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Endovascular Techniques Harry J. Cloft Departments of Radiology and Neurosurgery, Mayo Clinic College of Medicine, Rochester, Minnesota, U.S.A.
Jacques E. Dion Departments of Radiology and Neurosurgery, Emory University Hospital, Atlanta, Georgia, U.S.A.
INTRODUCTION The ideal treatment for arteriovenous malformations (AVMs) would achieve immediate obliteration while minimizing the risks of morbidity and mortality. Unfortunately, this ideal cannot yet be achieved for all patients. The marked heterogeneity of cerebral AVMs and the various advantages and disadvantages of the available treatment modalities necessitate a cooperative multidisciplinary approach by the vascular neurosurgeon, radiosurgeon, and interventional neuroradiologist. The overall treatment strategy is tailored to each patient on the basis of the patient’s condition and the anatomy of the AVM. Because of this multidisciplinary approach, future developments of endovascular techniques will occur in conjunction with future developments in neurosurgical and radiosurgical techniques. Pre-operative embolization is not needed for small AVMs in noneloquent areas because these lesions can generally be resected with low risk of morbidity and mortality (1). The risk of embolization becomes acceptable only when the size or anatomy of the AVM adds to the surgical risk, and it is expected that embolization will substantially alter the unfavorable anatomy. The goal of preoperative embolization is to reduce blood loss and to occlude vessels that may be difficult to control surgically, such as deep feeding arteries and large intranidal arteriovenous fistulae. Embolization can be performed before radiosurgical treatment of large AVMs to reduce the size of the nidus to less than 10 cm3, inasmuch as lesions larger than 10 cm3 have a lower cure rate with radiosurgery alone (2). Embolization to reduce the size of the nidus in preparation for radiosurgery must be performed with a permanent agent because the goal of embolization is to permanently obliterate a portion of the nidus that will not be included in the radiosurgery target. Curing AVMs with embolization is unusual. Therefore, curing the AVM is generally not the primary intention for embolization at most institutions. Cure with embolization can be achieved only with a permanent embolic material, such as N-butyl cyanoacrylate (NBCA) (3) or ethanol (4). Only small AVMs are potentially curable with NBCA. The overall cure rates have been reported to be 6% (3), 13% (5), and 14% (6) with NBCA and 40% with ethanol (4). A majority of the AVMs that might be curable with embolization are not embolized because they are generally easy surgical targets and are frequently operated on without preoperative embolization. Therefore, the reported cure rates with NBCA may be lower than what is actually achievable. Also, older literature (7) before the development of distal microcatheter access techniques described by Aletich et al. (8) may report lower cure rates than are currently achievable, because distal perinidal access is generally essential to the degree of nidus penetration required for cure. It is generally believed that partial treatment does not generally alter the natural history of brain AVMs (9,10). Therefore, partial embolization without an overall treatment plan with cure as the goal usually is not a sensible strategy. Exceptions to this dictum include the following: (i) targeted embolization of an intranidal aneurysm or pseudoaneurysm that may be a potentially high-risk element within the AVM, (ii) embolization of dural blood supply to reduce headaches in a patient with an otherwise incurable AVM, or (iii) embolization of a large incurable AVM to reduce symptoms due to a vascular ‘‘steal’’ phenomenon or venous congestion.
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The multiple roles of embolization in the multidisciplinary treatment of AVMs must be kept in perspective as the development of new endovascular techniques is pursued. Additionally, improvements in endovascular techniques will likely be driven by progress in the disciplines of neurosurgery and radiosurgery. MICROCATHETERS An ideal microcatheter would have the following properties: (i) easy achievement of very distal access in small arteries, (ii) minimal risk of perforation, and (iii) compatibility with all desirable embolic materials. The development of any embolic material and microcatheter systems are actually intertwined, because the performance of embolic materials depends on the distal access achievable with the microcatheter as well as on potential physical and chemical interactions between the embolic material and the microcatheter. Therefore, advances in embolic materials may stimulate advances in microcatheter technology and vice versa. Two basic types of microcatheters are currently available: ‘‘over-the-wire’’ microcatheters and flow-directed microcatheters. ‘‘Over-the-wire’’ microcatheters require the use of a microguidewire to direct them through the vasculature. Manipulation of the microcatheter and microguidewire carries a small risk of vascular perforation. The flow-directed catheters have a soft distal segment that is carried through an artery by flowing blood and generally can be positioned close to or within an AVM nidus with little risk of perforation. The size of the AVM arterial feeders that can currently be catheterized is limited by the diameter of the distal tip of the available microcatheters (1.5 French or 0.5 mm). While it might be possible to develop still smaller microcatheters, it is doubtful that they would make a significant impact on the embolization of AVMs, because it is probably not practical to superselectively catheterize and embolize a large number of tiny feeding arteries. The size of the microcatheters that can be developed is also limited by the minimum size of the lumen necessary to inject embolic materials without excessive resistance. Arterial perforations during superselective catheterizations for AVM embolization are usually caused by a microguidewire during manipulations of an over-the-wire microcatheter system. Perforations will decrease with more widespread use of flow direction. Hydrophilic catheters help to prevent NBCA from inadvertently gluing the catheter in situ (11). With the dilute mixtures of glue now commonly used (3), in conjunction with hydrophilic microcatheters, it is quite uncommon to inadvertently glue the microcatheter in situ. An additional advantage of hydrophilic catheters is that they are less thrombogenic and therefore may result in fewer thromboembolic complications (12). An alternative approach to avoid catheterization of innumerable tiny arteries feeding an AVM would be to use a transvenous approach, as has been used successfully in treating dural arteriovenous fistulae and vein of Galen malformations. The transvenous approach has not been developed for cerebral AVMs, however, because of the risk of hemorrhage associated with the occlusion of draining veins (13). The flow-directed microcatheters currently available allow experienced operators to achieve access to feeding arteries at the AVM nidus consistently and safely (8). While microcatheter technology will undoubtedly continue to improve, the currently available microcatheters are quite good and generally are not the limiting factor in our failures to successfully treat brain AVMs with endovascular techniques. EMBOLIC MATERIALS The basic requirements for embolic materials are that they have minimal local or systemic toxicity and are deliverable through a microcatheter system. The perfect embolic material would be permanently occlusive, easy to deliver in a controlled fashion to the nidus, nontoxic, nonadherent to the microcatheter, readily available, and inexpensive. Embolic materials can be divided into two basic categories: liquid agents and solid agents. Various embolic materials are currently being used in clinical practice. Only liquid agents achieve permanent nidus occlusion. The large solid agents can cause permanent occlusion but generally do not reach the nidus, and therefore they occlude feeding arteries proximal to the nidus. Polyvinyl alcohol (PVA) particles are solid and do reach the nidus, but they do not result in permanent occlusion. Because the solid agents do not cause permanent occlusion of the nidus, they are
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generally reserved for presurgical embolization rather than preradiosurgical embolization. An exception to this generalization is the occasional use of coils in occlusion of large arteriovenous fistulae before radiosurgery. Just as some combination of surgery, radiosurgery, and embolization is necessary to treat AVMs, a combination of embolic materials must be chosen with regard to the therapeutic goals and the anatomy of the AVM. Liquid Agents Isobutyl cyanoacrylate (IBCA) was first used in AVM embolization 20 years ago (14,15). Since the late 1980s, NBCA (Histoacryl, Braun, Melsungen, Germany; and Trufill1, Cordis Neurovascular Inc., Miami Lakes, Florida, U.S.A.) has replaced IBCA for AVM embolization (16). NBCA polymerizes when it comes into contact with blood, but its polymerization rate can be adjusted by dilution with ethiodized oil or glacial acetic acid (16). NBCA is not radiopaque and is opacified either by mixing with tantalum powder or diluting with ethiodized oil. New techniques that use a mixture of one part of NBCA diluted with three parts of ethiodized oil (resulting in a slow polymerization rate) (3) and very distal catheter access with ‘‘wedging’’ of the microcatheter in an AVM feeder or nidus (8) have created renewed interest in AVM embolization with NBCA. Allowing the microcatheter tip to ‘‘wedge’’ in an arterial feeder close to the nidus or in the nidus itself occludes flow distally. Because blood flow is no longer able to carry off the embolic agent, hydrostatic pressure from the injection can be used to push a prolonged, large-volume injection of NBCA to fill a large portion of the nidus. Neuracryl M (Prohold Technologies, Inc., El Cahon, California, U.S.A.) is a new cyanoacrylate (2-hexyl cyanoacrylate) proposed for use in AVMs. It is reported to have better cohesiveness than NBCA, resulting in improved penetration in an in vitro AVM model (17). Animal and human testing needs to be performed, however, before this agent can be added to the armamentarium for AVM therapy. Ethylene–vinyl alcohol copolymer (EVAL) (Onyx, Micro Therapeutics Inc., Irvine, California, U.S.A.) (18–20) has recently become available for AVM embolization. EVAL is dissolved in the organic solvent dimethyl sulfoxide (DMSO). On contact with blood, the DMSO rapidly diffuses into the blood, and the EVAL forms an elastic solid that obstructs the vessel lumen. The polymeric solid is less adhesive to the injecting microcatheter than NBCA, so untoward catheter retention due to adhesion of glue to the catheter is not as much of a concern as it is with NBCA. DMSO, however, is not compatible with the plastics used to make some microcatheters. Microcatheters compatible with DMSO have been developed to allow injection of EVAL into distal arteries for AVM embolization. Another relatively nonadhesive polymer is a mixture of methyl butyl methacrylate with dimethylaminoethyl methacrylate dissolved in ethanol and iopamidol (Eudragit-E) (21). This agent precipitates rapidly upon contact with blood and has been investigated thus far only in animals. Development and refinement of liquid polymers for embolization of AVMs will likely continue in the future in efforts to improve safety and ease of use. Ethanol has been proposed as an effective embolic agent for AVM therapy (4). It causes denudation of the endothelium and thrombosis. Because absolute ethanol is extremely toxic to normal brain tissue (22), careful, superselective injection is essential. Embolization with ethanol requires invasive hemodynamic monitoring with a Swan–Ganz catheter because it can cause critical elevation of pulmonary artery pressures. Ethanol may become more widely used for AVM embolization and may effect a higher cure rate than other embolic materials. In a series of 17 patients, Yakes et al. reported curing seven, including Spetzler–Martin Grade III and IV AVMs (4). However, experience with ethanol is much more limited than with NBCA. Solid Agents Solid embolic agents are not likely ever to be curative for AVMs, but they will likely continue to have an adjunctive role in the treatment of AVMs. Pushable microcoils have been used to embolize AVMs for many years with limited success. New developments in coil technology promise to be more useful. Berenstein liquid coils (Target Therapeutics, Boston Scientific Corporation, Natick, Massachusetts, U.S.A.) are perhaps the most useful coil for the treatment of AVMs. The Berenstein liquid coils are actually made of platinum wire but are designated as ‘‘liquid’’ because they are extremely soft and therefore can conform to the shape of their container. The Berenstein liquid coils can be used alone or in combination with NBCA for the
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occlusion of large arteriovenous fistulae. The electrolytically detachable Guglielmi detachable coil (GDC, Target Therapeutics, Boston Scientific Corporation, Natick, Massachusetts, U.S.A.) was designed for aneurysm therapy, but small GDCs can be useful in occluding large arteriovenous fistulae within AVMs. The GDCs can be used alone or in combination with NBCA. Small, electrolytically detachable coils specifically designed to be placed directly in an AVM nidus have been used in an animal model but have not been tested in humans (23). PVA microparticles have been used to embolize AVMs prior to surgery (24). Because microparticles do not effect permanent occlusion, they are not useful before radiosurgery or in an attempt to cure with embolization. The use of microparticles also is limited by their relative incompatibility with the smaller, flow-directed catheters. Larger, over-the-wire microcatheters that often cannot be placed very close to the AVM nidus are generally required. Some experienced endovascular therapists continue to use particles for preoperative AVM embolizations, but most now use NBCA or EVAL. As experience with liquid embolization techniques continues to grow, it is likely that the use of microparticles will decline. Biologically Active Materials Embolic agents in the future could be modified to be biologically active rather than just mechanically occlusive. These agents might be liquid or solid and might be made from naturally occurring polymers such as fibrin (25). Gene therapy (26) is an evolving field that might have applications to the treatment of AVMs with biologically active materials. The basic premise of gene therapy is that genetic material is transferred to a patient (either locally or systemically) in such a way that the gene’s product (a protein) will be produced and be available to treat the patient’s condition. Genetic material can be delivered to the host in a number of ways, including with viral and liposomal vectors and through the implantation of cells that were genetically modified in vitro. Gene therapy techniques might be useful in inciting a proliferative response within the AVM nidus or, perhaps, in making AVMs more sensitive to radiation. Gene therapy agents could potentially be delivered via endovascular techniques. However, the high flow of AVMs will make it difficult to achieve the endoluminal exposure time that would be necessary for the gene vector to accomplish gene transfer. Gene therapy is a rapidly developing field, and such challenges may be overcome soon. The implantation of genetically altered cells is a form of gene therapy that has been proposed as a technique that could facilitate intraluminal fibrosis of cerebral aneurysms (27). Such cell implantation might also have applications in producing intraluminal fibrosis in an AVM nidus. The strategy for gene therapy can be guided by advances in the understanding of the genetic basis of AVMs. Molecular biological studies are helping us to understand the molecular and genetic basis of cerebral AVMs. Vascular endothelial growth factor (28,29) and endothelial cell-specific tyrosine kinase are overproduced in AVMs (29). The protein endothelin-1 is not expressed in intracranial AVMs, indicating that endothelial dysfunction may contribute to the formation of AVMs (30). Although these molecular abnormalities in AVMs are currently incompletely understood, continued advances in molecular biology may ultimately lead to improvements in AVM therapy. The development of embolic materials is somewhat limited by the lack of a realistic animal model. The development of an AVM model in animals will hopefully be realized in the near future. REDUCTION OF COMPLICATIONS In improving the contribution of endovascular therapy to the rate of cure of AVMs, it is important to reduce the risk of endovascular therapy to the lowest possible point. This goal can be achieved in a number of ways, including the development of new catheters and embolic agents as described above. A better understanding of the natural history of AVMs relative to various anatomical and epidemiological parameters may help in selecting patients for embolization. Additionally, diagnostic information obtained before and during an embolization procedure can potentially reduce complications. Pressure monitoring techniques have been developed that allow measurement of pressure changes in arterial feeders as the AVM is embolized (31–33). Embolization increases the vascular resistance and thereby results in increased pressure in the feeding arteries and
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the portions of the nidus that have not been embolized. Although these pressure increases might be predictive of an increased risk of hemorrhage as the embolization progresses, the actual clinical situations and associated pressure values that are predictive of hemorrhage, which would make such pressure measurements useful, remain to be determined. Superselective amobarbital injections have been used as a pre-embolization functional evaluation to determine if eloquent brain is fed by an artery (34). Because current microcatheters can be positioned immediately next to or within the AVM nidus fairly routinely, inadvertent embolization and infarction of adjacent brain is now much less likely. Provocative testing requires that the patient be awake and therefore precludes the use of general anesthesia. General anesthesia, however, permits superb imaging during injection of embolic materials and improves patient comfort during long procedures. Many operators now feel that the advantages of general anesthesia outweigh the advantages of provocative testing. The use of provocative testing has therefore become less common and will probably continue to decline. Functional magnetic resonance imaging may be useful in the accurate localization of eloquent brain before embolization, surgery, or radiosurgery. AVMs can cause shifting of functional regions of the cerebral cortex away from typical anatomic locations (35). Techniques are currently available to localize primary somatosensory, motor, speech, and visual cortex (35,36). Localization of eloquent cortex may allow operators to embolize more aggressively in noneloquent areas and less aggressively in eloquent areas. Localization of eloquent cortex may also allow the safer creation of an overall treatment plan for many patients, such as in deciding if an AVM is amenable to surgery or not. CONCLUSION The treatment of AVMs is likely to remain a multidisciplinary endeavor. The continued development of specialized centers with a multidisciplinary team consisting of neurosurgeons, neuroradiologists, neurological intensive care specialists, and anesthesiologists, all with extensive experience in treating patients with AVMs, is an important element in improving the outcome for these patients. Without excellence in all of the disciplines involved in AVM therapy, the treatment options and follow-up care for many patients may be compromised. Those involved in developing new endovascular techniques for AVM therapy must keep this multidisciplinary approach in perspective and stay abreast of developments in all aspects of AVM therapy. REFERENCES 1. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–483. 2. Dion JE, Mathis JM. Cranial arteriovenous malformations. The role of embolization and stereotactic surgery. Neurosurg Clin N Am 1994; 5:459–474. 3. Debrun GM, Aletich V, Ausman JI, Charbel F, Dujovny M. Embolization of the nidus of brain arteriovenous malformations with n-butyl cyanoacrylate. Neurosurgery 1997; 40:112–120. 4. Yakes WF, Krauth L, Ecklund J, et al. Ethanol endovascular management of brain arteriovenous malformations: initial results. Neurosurgery 1997; 40:1145–1152. 5. Wikholm G, Lundqvist C, Svendsen P. Embolization of cerebral arteriovenous malformations: Part I— Technique, morphology, and complications. Neurosurgery 1996; 39:448–457. 6. Fournier D, TerBrugge KG, Willinsky R, Lasjaunias P, Montanera W. Endovascular treatment of intracerebral arteriovenous malformations: experience in 49 cases. J Neurosurg 1991; 75:228–233. 7. Vinuela F, Dion JE, Duckwiler G, et al. Combined endovascular embolization and surgery in the management of cerebral arteriovenous malformations: experience with 101 cases. J Neurosurg 1991; 75:856–864. 8. Aletich VA, Debrun GM, Koenigsberg R, Ausman JI, Charbel F, Dujovny M. Arteriovenous malformation nidus catheterization with hydrophilic wire and flow-directed catheter. AJNR Am J Neuroradiol 1997; 18:929–935. 9. Forster DM, Steiner L, Hakanson S. Arteriovenous malformations of the brain. A long-term clinical study. J Neurosurg 1972; 37:562–570. 10. Drake CG. Cerebral arteriovenous malformations: considerations for and experience with surgical treatment in 166 cases. Clin Neurosurg 1979; 26:145–208. 11. Mathis JM, Evans AJ, DeNardo AJ, et al. Hydrophilic coatings diminish adhesion of glue to catheter: an in vitro simulation of NBCA embolization. AJNR Am J Neuroradiol 1997; 18:1087–1091.
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12. Kallmes DF, McGraw JK, Evans AJ, et al. Thrombogenicity of hydrophilic and nonhydrophilic microcatheters and guiding catheters [published erratum appears in AJNR Am J Neuroradiol 1997; 18: 1800]. AJNR Am J Neuroradiol 1997; 18:1243–1251. 13. Duckwiler GR, Dion JE, Vinuela F, Reichman A. Delayed venous occlusion following embolotherapy of vascular malformations in the brain. AJNR Am J Neuroradiol 1992; 13:1571–1579. 14. Zanetti PH, Sherman FE. Experimental evaluation of a tissue adhesive as an agent for the treatment of aneurysms and arteriovenous anomalies. J Neurosurg 1972; 36:72–79. 15. Bank WO, Kerber CW, Cromwell LD. Treatment of intracerebral arteriovenous malformations with isobutyl 2-cyanoacrylate: initial clinical experience. Radiology 1981; 139:609–616. 16. Brothers MF, Kaufmann JC, Fox AJ, Deveikis JP. n-Butyl 2-cyanoacrylate—substitute for IBCA in interventional neuroradiology: histopathologic and polymerization time studies. AJNR Am J Neuroradiol 1989; 10:777–786. 17. Kerber C, Connors J, Knox K. Behavior of Neuracryl M, a new liquid embolic agent. American Society of Therapeutic and Interventional Neuroradiology, Nashville, 1999. 18. Jahan R, Murayama Y, Gobin YP, Duckwiler GR, Vinters HV, Vinuela F. Embolization of arteriovenous malformations with Onyx: clinicopathological experience in 23 patients. Neurosurgery 2001; 48:984–997. 19. Taki W, Yonekawa Y, Iwata H, Uno A, Yamashita K, Amemiya H. A new liquid material for embolization of arteriovenous malformations. AJNR Am J Neuroradiol 1990; 11:163–168. 20. Chaloupka JC, Vinuela F, Vinters HV, Robert J. Technical feasibility and histopathologic studies of ethylene vinyl copolymer (EVAL) using a swine endovascular embolization model. AJNR Am J Neuroradiol 1994; 15:1107–1115. 21. Yamashita K, Taki W, Iwata H, Kikuchi H. A cationic polymer, Eudragit-E, as a new liquid embolic material for arteriovenous malformations. Neuroradiology 1996; 38(suppl 1):S151–S156. 22. Sampei K, Hashimoto N, Kazekawa K, Tsukahara T, Iwata H, Takaichi S. Histological changes in brain tissue and vasculature after intracarotid infusion of organic solvents in rats. Neuroradiology 1996; 38:291–294. 23. Massoud TF, Ji C, Guglielmi G, Vinuela F. Endovascular treatment of arteriovenous malformations with selective intranidal occlusion by detachable platinum electrodes: technical feasibility in a swine model. AJNR Am J Neuroradiol 1996; 17:1459–1466. 24. Purdy PD, Samson D, Batjer HH, Risser RC. Preoperative embolization of cerebral arteriovenous malformations with polyvinyl alcohol particles: experience in 51 adults. AJNR Am J Neuroradiol 1990; 11:501–510. 25. Nagino M, Hayakawa N, Kitagawa S, et al. Interventional embolization with fibrin glue for a large inferior mesenteric-caval shunt. Surgery 1992; 111:580–584. 26. Thomas JW, Kuo MD, Chawla M, et al. Vascular gene therapy. Radiographics 1998; 18:1343–1372. 27. Kallmes DF, Williams AD, Cloft HJ, Lopes MB, Hankins GR, Helm GA. Platinum coil-mediated implantation of growth factor–secreting endovascular tissue grafts: an in vivo study. Radiology 1998; 207:519–523. 28. Sonstein WJ, Kader A, Michelsen WJ, Llena JF, Hirano A, Casper D. Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study. J Neurosurg 1996; 85:838–845. 29. Hatva E, Jaaskelainen J, Hirvonen H, Alitalo K, Haltia M. Tie endothelial cell-specific receptor tyrosine kinase is upregulated in the vasculature of arteriovenous malformations. J Neuropathol Exp Neurol 1996; 55:1124–1133. 30. Rhoten RL, Comair YG, Shedid D, Chyatte D, Simonson MS. Specific repression of the preproendothelin-1 gene in intracranial arteriovenous malformations. J Neurosurg 1997; 86:101–108. 31. Duckwiler G, Dion J, Vinuela F, Jabour B, Martin N, Bentson J. Intravascular microcatheter pressure monitoring: experimental results and early clinical evaluation. AJNR Am J Neuroradiol 1990; 11: 169–175. 32. Jungreis CA, Horton JA. Pressure changes in the arterial feeder to a cerebral AVM as a guide to monitoring therapeutic embolization. AJNR Am J Neuroradiol 1989; 10:1057–1060. 33. Chaloupka JC, Vinuela F, Kimme-Smith C, Robert J, Duckwiler GR. Use of a Doppler guide wire for intravascular blood flow measurements: a validation study for potential neurologic endovascular applications. AJNR Am J Neuroradiol 1994; 15:509–517. 34. Rauch RA, Vinuela F, Dion J, et al. Preembolization functional evaluation in brain arteriovenous malformations: the ability of superselective Amytal test to predict neurologic dysfunction before embolization. AJNR Am J Neuroradiol 1992; 13:309–314. 35. Schlosser MJ, McCarthy G, Fulbright RK, Gore JC, Awad IA. Cerebral vascular malformations adjacent to sensorimotor and visual cortex. Functional magnetic resonance imaging studies before and after therapeutic intervention. Stroke 1997; 28:1130–1137. 36. Turski PA, Cordes D, Mock B, et al. Basic concepts of functional arteriovenous MR imaging malformations. Neuroimaging Clin N Am 1998; 8:371–381.
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Radiosurgery Douglas Kondziolka, L. Dade Lunsford, and John C. Flickinger Departments of Neurological Surgery and Radiation Oncology, The Center for Image Guided Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A.
INTRODUCTION Stereotactic radiosurgery has become an important and widely used treatment technique for the management of cerebral arteriovenous malformations (AVMs). The first AVM radiosurgery procedure was performed by Kjellberg in 1965 using protons (P. Chapman, personal communication). He did not perform another procedure until years later, after Steiner et al. had reported their initial case (1). Since that time, ongoing analyses of results have led to refinements in technique and a better understanding of both the vascular malformation response and the normal surrounding brain response (2–16). Increased knowledge has led to improved clinical results. Although radiosurgery is a minimally invasive technique, it is not risk-free. Most patients will enjoy long-term survival if their AVM is obliterated. Therefore, both short- and long-term outcomes after radiosurgery must be evaluated rigidly. In this chapter, we discuss the results from our 17-year experience with the radiosurgical treatment of patients with AVMs at the University of Pittsburgh, and we discuss the continuing and future role of radiosurgery in AVM management. RADIOBIOLOGY OF VASCULAR MALFORMATION RADIOSURGERY For almost 50 years, radiation oncologists have advocated fractionated external beam radiotherapy to treat cancer. Fractionation relied on the goal of reduced adverse radiation effects (for late-reacting normal tissue) compared to the more rapid and early response expected for malignant cells included in the treatment field. This concept improved the ‘‘therapeutic window’’ so that tumor control and complication rates remained balanced. When both the target tissue and the surrounding normal brain tissue have similar types of response (both may be late-responding tissues), little is gained by fractionation (17). Such a situation is relevant in AVM radiosurgery because the target is a collection of abnormally constructed blood vessels with relatively long cell cycle times. A similar situation exists for most benign brain tumors. The actual alpha:beta ratio for AVM tissue, a measure of cell turnover rapidity, is not known. Radiosurgery is preferred because single-fraction irradiation is powerful and causes significant injury to the blood vessels that comprise the AVM (18–21). To confine the radiobiologic effects of radiosurgery to the AVM, stereotactic definition of the target volume is necessary. Conformal radiosurgery allows radiation on only a small volume of the surrounding normal tissues in the region of radiation dose fall-off (10,22). Dose-prescription formulae assist in the selection of the dose depending on imaging and clinical factors (23–25). The immediate effect of radiosurgery is damage of the endothelial cells of the AVM vessels. Release of tissue-specific cytokines common to other forms of radiation-induced injury, such as basic fibroblast growth factor, interleukin-2, and platelet-derived growth factor, is likely to mediate such acute effects. Inflammatory cells mediate tissue repair in response to irradiation. Later, chronic inflammation consists of the ingrowth of granulation tissue that contains fibroblasts and new capillaries. Szeifert et al. identified the presence of actin-producing fibroblasts, the so-called myofibroblasts, that are hypothesized to exert contractile properties that facilitate AVM obliteration (26). Involution of the irradiated mass is the final stage of the healing response as well as the final stage of inflammation. At this time, the AVM vessels are occluded, and the AVM volume is reduced. Magnetic resonance imaging (MRI) studies of patients after radiosurgery often show a diminished AVM target mass with expansion of the surrounding brain into the volume previously occupied by the AVM (27). It is also common that contrast-enhanced MRI studies at this late stage after obliteration show enhancement of
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the obliterated AVM. This finding does not indicate a ‘‘patent’’ AVM but rather is a marker for the newly formed capillary network within the scar tissue of the AVM mass. Reports have noted the rare, late finding of cyst formation at the AVM site, which probably represents expansion of the extracellular fluid space within the fibrotic remnant (28,29). Our understanding of the biologic effects of radiosurgery for AVMs may lead to improvements in the obliteration rate. It may soon be possible to up-regulate the response rate by delivering cytokines already active in the response. By intravenous or intra-arterial delivery of the cytokines noted above during irradiation, we may be able to increase the initial endothelial response that later causes luminal closure. INDICATIONS FOR AVM RADIOSURGERY The treatment of AVMs by radiosurgery facilitated its application to other neoplastic and functional conditions. Between 1971 and 1986, data obtained from the management of AVMs were disseminated widely. A large number of studies indicated that radiosurgery provided satisfactory AVM cures with few complications. Surgical resection, endovascular embolization, and radiosurgery, alone or in combination, are valuable strategies to treat patients with AVMs (10,30). Conservative management may be appropriate for elderly patients or patients with large, nonhemorrhagic AVMs. Radiosurgery is most appropriate for patients with small- or medium-sized AVMs, especially those AVMs in brain locations associated with high risk for surgical resection. Natural history data indicate that most patients who have a brain AVM should be treated if feasible. Patients with a previous hemorrhage appear to have an increased risk for rebleeding (31). The goal of radiosurgery is to obliterate the lumen of the AVM vessels and prevent hemorrhage. Relief from headaches and cessation of seizures are also desirable (32). The risk of hemorrhage does not change until obliteration has occurred (33). After radiosurgery, MRI and angiographic imaging are used to assess the brain and AVM response (34). A secondary and important potential benefit of radiosurgery is its effect on seizure control. Several series reported cessation of seizures at a rate similar to that observed after AVM resection (32,35,36). CLINICAL EXPERIENCE At the University of Pittsburgh, 1068 AVM patients had gamma knife radiosurgery during a 17-year interval. The mean patient age was 36 years (range 2–82). Previous intracranial hemorrhage was reported in 46% of the patients, headaches in 37%, and seizures in 28%. Intravascular embolization was performed on 182 patients (17%) before radiosurgery. One hundred seventeen patients (11%) had undergone one or more surgical procedures before radiosurgery. For some of these patients, the goal of surgery had been AVM resection, while for others, the goal was hematoma removal. The mean AVM volume was 2.5 mL (range .03–24 mL). The 50% isodose was used as the margin isodose in 79% of the patients. Only 0.7% of the patients were treated below the 50% isodose. The Spetzler–Martin grading system was used to classify all AVMs according to size, critical location, and venous drainage. Twenty-seven patients (2.5%) had AVMs that were Grade I (small, superficial, and noncritical in location). The most frequent AVM grade managed was Grade III (n ¼ 397, 37%). Thirteen percent of the patients (n¼104) had Grade VI AVMs. The AVM was located totally within the parenchyma of the brainstem or thalamus. The mean dose delivered to the AVM margin was 20 Gy and the mean maximum dose 32 Gy. Staged procedures were performed in 102 patients (10%). The primary locations of the intracerebral AVMs in this series are listed in Table 1. STEREOTACTIC RADIOSURGERY TECHNIQUE On the day of radiosurgery, we begin with attachment of the stereotactic frame to the head using buffered local scalp anesthesia (5% marcaine and 1% xylocaine) supplemented with mild sedation when needed. In children under 13 years of age, general anesthesia is preferred. Since 1992, all eligible patients undergo intraoperative MRI, which includes a sagittal scout sequence followed by a contrast-enhanced axial volume acquisition (37). On this spoiled grass gradient recombinant scan we use a low TE to enhance blood vessel definition. A magnetic
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Table 1 Locations of Intracerebral Arteriovenous Malformations Managed with Stereotactic Radiosurgery (n ¼ 1029) Location Frontal lobe Parietal lobe Temporal lobe Occipital lobe Intraventricular Basal ganglia Thalamus Cerebellum Pons/midbrain Corpus callosum Medulla Other
No. of Patients 211 208 107 153 22 48 99 80 63 22 3 13
resonance angiography (MRA) reconstruction is then obtained. The patient next undergoes conventional transfemoral stereotactic angiography. MRI studies are transferred to the gamma knife work station by ethernet, and a scanner is used to digitize the magnification subtraction angiograms (Fig. 1). Precise definition of the AVM nidus is of utmost importance in radiosurgery planning. It is important to exclude draining veins, normal arterial vessels outside the nidus, and normal brain tissue. We aim to construct a conformal radiosurgery volume that irradiates only the AVM nidus (the pathological shunt between afferent arteries and efferent veins) (Fig. 2). Irradiation of the smallest appropriate target volume increases the success rate, in part because a higher marginal dose can be delivered to a smaller target. Planning is first carried out on axial MR images, which are reformatted into coronal and sagittal planes as well. A conformal plan is generally achieved using 1 to 12 isocenters of different diameters. After finalizing the plan with the digitized angiographic images, we use the integrated logistic formula for
Figure 1 Gamma knife radiosurgery planning for a 25-year-old man who sustained an intraventricular hemorrhage from a right thalamic arteriovenous malformation (AVM). Angiographic and magnetic resonance images are shown. Two 8-mm isocenters were used to create a dose plan that fits the AVM margin well at the 50% line. A margin dose of 25 Gy and a maximum dose of 50 Gy were delivered. (See color insert.)
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Figure 2 Anteroposterior and lateral vertebral angiograms in an eight-year-old girl with headaches (A). An arteriovenous malformation of the left middle cerebellar peduncle was found. Radiosurgery was performed with two 8-mm and two 4-mm isocenters to deliver a margin dose of 20 Gy (50%) and a maximum dose of 40 Gy. The contrastenhanced volume acquisition magnetic resonance imaging scan at 1-mm intervals is shown (B). (See color insert.)
a 3% probability of permanent radiation-related complications to guide dose selection. The expected obliteration rate based on margin dose is also checked (38). The patient next undergoes radiosurgery with the gamma knife. All patients receive a 40-mg dose of methylprednisolone at the conclusion of irradiation. Patients with subcortical
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lobar AVMs are considered at risk for perioperative seizures. We achieve therapeutic anticonvulsant levels in such patients. After the stereotactic frame is removed, a light compression bandage is applied, which is then removed after a few hours. Patients are observed overnight and discharged the next morning. Patients are monitored with MRI scans at 6, 12, 24, and 36 months. Angiography is performed at three years if the MRI suggests complete obliteration. In our experience, MRI accurately predicts obliteration and can be used as a guide for deciding the timing of final angiography. We request postradiosurgery angiography in all patients (Fig. 3). Future radiosurgery planning may more frequently incorporate functional imaging into the dataset. By determining the location of cortical tissue for motor function, vision, or language, we can block the fall-off in the radiation dose outside those areas and place the fall-off into less critical areas. We have performed such cases on a pilot basis. AVM OBLITERATION Successful AVM obliteration depends on proper stereotactic nidus definition and delivery of an adequate radiosurgery dose (38,39). A complete analysis of 197 patients with AVMs with up to three-year angiographic follow-up showed an overall complete obliteration rate of 72% after a single procedure. These results were stratified by volume. In 20 of the 197 patients (10%), the targeted AVM nidus failed to be obliterated totally. The most important reason for lack of complete obliteration was improper targeting (40). An additional 35 patients (18%) had a residual AVM that was not included in the original treatment volume. Important obliteration factors were identified in this study: incomplete imaging definition of the AVM, reappearance of AVM after initial compression by hematoma, and recanalization of a previously embolized nidus. We and others advocate the use of multimodality imaging (MRI, MRA, and conventional stereotactic angiography) to obtain the best results (8,37). Table 2 shows the obliteration results stratified by volume. For the smallest AVM (less than 1.3 mL), 90% of patients had complete obliteration (45 of 50), and 98% had obliteration of the target (49 of 50). For AVMs between 1.4 and 3 mL, 41 of 49 patients had complete obliteration (84%), and 47 of 49 had obliteration of the included target (96%) (Fig. 4). In a separate analysis of our data, we reported a multivariate analysis of AVM obliteration as related to dose and volume (38). A clear dose response up to 25 Gy was identified. We concluded that large AVMs have low obliteration rates because of the combination of lower treatment doses used and the greater problems encountered with target definition. An analysis of 95 patients with thalamic or basal ganglia AVMs found similar obliteration rates when stratified by volume; overall, 80% of the patients were cured after a single procedure (unpublished results). POSTRADIOSURGERY EFFECTS Immediate postradiosurgery complications are rare. To reduce seizure risks, we administer anticonvulsant medications to patients with supratentorial lobar AVMs. The potential risk of morbidity due to radiosurgery is delayed and corresponds with the time course for AVM obliteration as well as for the inflammatory-mediated effects discussed above. We found that the rate of developing any postradiosurgery imaging change between two and seven years after radiosurgery is 30% (41). We believe that the majority of these changes are hemodynamic or inflammatory. Most do not cause neurologic symptoms. Symptomatic imaging changes are found in 10%. These changes resolve in half the patients within three years of onset as compared to a 95% resolution rate in patients with asymptomatic imaging findings. Parenchymal long TR imaging changes may be related to regional hemodynamic effects as the AVM obliterates, cerebral edema, ischemia, astrocytosis, or radiation necrosis. Contrast enhancement at the target is consistent with obliteration and should not automatically be considered an indication of adverse radiation effects (27). In a multivariate analysis of imaging changes with various radiosurgical parameters, the only significant independent correlation was the total volume of tissue that received a dose greater than or equal to 12 Gy. We have termed this the ‘‘12 Gy volume’’ (24). Symptomatic imaging changes were correlated with both the ‘‘12 Gy volume’’ and location (brainstem vs. non-brainstem). Critical structures in the brainstem are more sensitive to adverse radiation effects.
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Figure 3 Lateral and anteroposterior angiograms in a 51-year-old man who sustained his second hemorrhage from a thalamic arteriovenous malformation (AVM) (A). Radiosurgery was performed with one 14-mm and three 8-mm isocenters to deliver a margin dose of 20 Gy and a maximum dose of 40 Gy. Serial magnetic resonance scans showed progressive obliteration of the flow-void signal. Four years later, repeat carotid and vertebral angiograms confirmed total AVM obliteration (B and C).
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Table 2 Arteriovenous Malformation Obliteration After Radiosurgery: Targeting and Volume Volume Range (mL) 0.06–1.3 1.4–3.1 3.2–5.5 5.5–18
No. of Cases
No. (%) with Complete AVM Obliteration
50 49 49 49
45 41 35 20
(90%) (84%) (71%) (41%)
No. (%) with Targeted AVM No. (%) with Part of AVM Obliterated Left Untargeted 49 47 44 37
(98%) (96%) (90%) (76%)
1 2 5 12
(2%) (4%) (10%) (25%)
Abbreviation: AVM, arteriovenous malformation.
Although Karlsson et al. reported protection from rehemorrhage in the interval before complete obliteration, neither the Pittsburgh nor the University of Florida series identified such a benefit (33,42,43). In our experience, the hemorrhage rate after radiosurgery remains the same as the hemorrhage rate before radiosurgery until the AVM obliterates. We have never observed a hemorrhage after obliteration. REPEAT RADIOSURGERY The first radiosurgery procedure may not lead to complete elimination of the arteriovenous shunt. If after three to four years, a residual AVM nidus with early venous drainage remains, then a second radiosurgical procedure should be performed (40). We do not recommend additional management for patients who harbor only an early draining vein as this feature resolves over an additional observation interval (44). In addition, we know of no patient who sustained a later hemorrhage when only an early draining vein was present. In some patients, the angiogram may show some abnormal-appearing vessels in the region of the irradiated AVM, without early venous drainage. This fine vascular blush may indicate the neocapillary network within the scarred malformation. Such findings also require no additional therapy. For patients who have a persistent AVM nidus, additional management options include repeat radiosurgery or resection (45). If only a small AVM remnant remains and the AVM was not well suited to resection initially, we perform repeat radiosurgery. We consider retreating the incompletely obliterated nidus at three to four years because few additional patients have obliteration beyond this time. Retreatment is associated with a 70% probability of obliteration (46). At the second procedure, only the small remnant needs to be irradiated, usually at a dose lower than the first dose delivered (though sometimes greater if the initial AVM was large and the remnant is small, depending on location). In our thalamic and basal ganglia AVM series, 5 of 14 retreated AVMs showed complete obliteration within three years of the second procedure. STAGED VOLUME RADIOSURGERY We now consider prospective staged radiosurgery for larger AVMs (volume staging), especially for patients who present with hemorrhage and whose AVMs are not suitable for resection. With this approach, the AVM volume is divided up volumetrically to allow radiosurgery of smaller components at higher and more tolerable doses. Irradiation of an entire large AVM at a low dose (below 15 Gy to the AVM margin) has such a low obliteration rate that it is probably not worthwhile. Dividing the AVM into volumes that could receive higher and more effective doses may lead to a significantly higher rate of obliteration. We separate the AVM radiosurgeries by four to six months to allow repair of sublethal deoxyribonucleic acid damage in normal brain. With this strategy, we hope to obliterate large, symptomatic AVMs that were not treatable in the years past. Evidence suggests that even incompletely obliterated AVMs may become easier to resect after a period of several years. Perhaps prophylactic staged radiosurgery may facilitate eventual resection of AVMs previously considered untreatable (47). FUTURE ROLES FOR AVM RADIOSURGERY As the least invasive form of AVM management, radiosurgery is particularly attractive to patients. Currently, radiosurgery is used mainly to treat deep or critically located AVMs for
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which resection poses a high risk. Will radiosurgery become the treatment of choice for all small- or medium-sized AVMs, regardless of brain location? Some information suggests that this is already happening. The use of radiosurgery for polar AVMs (Spetzler–Martin Grade I) appears to be increasing, especially in the absence of previous hemorrhage. The benefits of radiosurgery for deep AVMs are more obvious, but well-designed clinical trials will be necessary to define the role of radiosurgery in settings where resection can be performed successfully. Perhaps the issues of cost, prompt return to employment, and the avoidance’ of craniotomy will become relevant to patients and payors. The role of radiosurgery for dural AVMs and fistulas has not been large. Many of these lesions are difficult to define anatomically and can be cured by endovascular or microsurgical techniques. Radiosurgery may become more important for these disorders as an alternative to resection if superselective catheterization provides more adequate nidus definition. It appears that endovascular approaches provide reasonable short-term solutions to these problems. We await long-term angiographic data that support permanent obliteration of these malformations without recanalization or symptomatic recurrence using the current embolic agents. The biologic effect of radiosurgery may prove to be the best permanent solution to these malformations and, increasingly, may be used together with endovascular approaches. How can radiosurgery become even less invasive? Elimination of conventional angiography during the procedure would be one way. For the last six years we have used MRI and MRA for AVM targeting along with angiography. Should stereotactic computed tomography (CT) angiography provide high-resolution imaging of AVMs, this would be another important improvement. Many centers currently use standard CT imaging for planning. Because all AVMs are different, especially with regard to the compactness of the nidus and the imaging appearance, we must use all available information sources alone or in combination and tailored to individual patients for providing the best result. SUMMARY AVM radiosurgery has been in practice for over 30 years and is now a common method for managing brain AVMs in properly selected patients. The techniques have been refined along with our understanding of the expected response. Radiosurgery causes vascular obliteration. To obtain complete AVM obliteration, exquisite image guidance is necessary. Some patients require staged procedures in a fashion similar to staged embolization or staged resection. Some patients require multimodality approaches. All patients with AVMs should seek to understand whether stereotactic radiosurgery is an appropriate option for their problem. REFERENCES 1. Steiner L, Leksell L, Greitz T, et al. Stereotaxic radiosurgery for cerebral arteriovenous malformations. Report of a case. Acta Chir Scand 1972; 138:459–464. 2. Betti O, Munari C, Rosler R. Stereotactic radiosurgery with the linear accelerator: treatment of arteriovenous malformations. Neurosurgery 1989; 24:311–321. 3. Colombo F, Benedetti A, Pozza F, et al. Linear accelerator radiosurgery of cerebral arteriovenous malformations. Neurosurgery 1989; 24:833–840. 4. Colombo F, Pozza F, Chierego G, et al. Linear accelerator radiosurgery of cerebral arteriovenous malformations: an update. Neurosurgery 1994; 34:14–21. 5. Duma C, Lunsford LD, Kondziolka D, et al. Radiosurgery for vascular malformations of the brain stem. Acta Neurochir 1993; 58(suppl):92–97. 6. Engenhart R, Wowra B, Debus J, et al. The role of high-dose, single-fraction irradiation in small and large intracranial arteriovenous malformations. Int J Radiat Oncol Biol Phys 1994; 30:521–529. 7. Friedman W, Bova F. Linear accelerator radiosurgery for arteriovenous malformations. J Neurosurg 1992; 77:832–841. 8. Friedman W, Bova F, Mendenhall W. Linear accelerator radiosurgery for arteriovenous malformations: the relationship of size to outcome. J Neurosurg 1995; 82:180–189.
Figure 4 (Figure on facing page) (A) Computed tomography (left) and magnetic resonance imaging (right) scans showing a hemorrhage from a right internal capsule arteriovenous malformation (AVM) in a 26-year-old woman. Angiograms before (B) and after (C) radiosurgery using two 8-mm and two 4-mm isocenters (AVM margin dose of 22 Gy to the 50% isodose) confirmed complete obliteration at 24 months. No neurologic deficits occurred after radiosurgery.
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9. Kemeny A, Dias P, Forster D. Results of stereotactic radiosurgery of arteriovenous malformations: an analysis of 52 cases. J Neurol Neurosurg Psych 1989; 52:554–558. 10. Lunsford LD, Kondziolka D, Flickinger J, et al. Stereotactic radiosurgery for arteriovenous malformations of the brain. J Neurosurg 1991; 75:512–524. 11. Pollock BE, Lunsford LD, Kondziolka D, et al. Stereotactic radiosurgery for postgeniculate visual pathway arteriovenous malformations. J Neurosurg 1996; 84:437–441. 12. Pollock BE, Lunsford LD, Kondziolka D, et al. Patient outcomes after stereotactic radiosurgery for ‘‘operable’’ arteriovenous malformations. Neurosurgery 1994; 35:1–8. 13. Souhami L, Olivier A, Podgorsak E, et al. Radiosurgery of cerebral arteriovenous malformations with the dynamic stereotactic irradiation. Int J Radiat Oncol Biol Phys 1990; 19:775–782. 14. Steinberg G, Fabrikant J, Marks M, et al. Stereotactic heavy-charged-particle Bragg-peak radiation for intracranial arteriovenous malformations. N Eng J Med 1990; 323:96–101. 15. Yamamoto M, Jimbo M, Kobayashi M, et al. Long-term results of radiosurgery for arteriovenous malformation: neurodiagnostic imaging and histological studies of angiographically confirmed nidus obliteration. Surg Neurol 1992; 37:219–230. 16. Yamamoto Y, Coffey R, Nichols B, et al. Interim report on the radiosurgical treatment of cerebral arteriovenous malformations. J Neurosurg 1995; 83:832–837. 17. Redekop G, Elisevich K, Gaspar L, et al. Conventional radiation therapy of intracranial arteriovenous malformations: long-term results. J Neurosurg 1993; 78:413–422. 18. Flickinger J, Kondziolka D, Kalend AM, et al. Radiosurgery-related imaging changes in surrounding brain: multivariate analysis and model evaluation. Radiosurgery 1995; 1:229–236. 19. Larsson B, Leksell L, Rexed B, et al. The high-energy proton beam as a neurosurgical tool. Nature 1958; 182:1222–1223. 20. Schneider B, Eberhard D, Steiner L. Histopathology of arteriovenous malformations after gamma knife radiosurgery. J Neurosurg 1997; 87:352–357. 21. Wu A, Lindner G, Maitz A, et al. Physics of gamma knife approach on convergent beams in stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 1990; 18:941–949. 22. Kondziolka D, Lunsford LD. Intraparenchymal brainstem radiosurgery. Neurosurg Clin N Amer 1993; 4:469–479. 23. Flickinger JC. An integrated logistic formula for prediction of complications from radiosurgery. Int J Radiat Oncol Biol Phys 1989; 17:879–885. 24. Flickinger JC, Kondziolka D, Pollock B, et al. Complications from arteriovenous malformation radiosurgery: Multivariate analysis and risk modeling. Int J Radiat Oncol Biol Phys 1997; 38:485–490. 25. Flickinger JC, Lunsford LD, Kondziolka D. Dose prescription and dose volume effects in radiosurgery. Neurosurg Clin North America 1992; 3:51–59. 26. Szeifert GT, Kemeny AA, Timperley W, et al. The potential role of myofibroblasts in the obliteration of arteriovenous malformations after radiosurgery. Neurosurgery 1997; 40:61–66. 27. Guo WY, Lindquist C, Karlsson B, et al. Gamma knife surgery of cerebral arteriovenous malformations: serial MR imaging studies after radiosurgery. Int J Radiat Oncol Biol Phys 1993; 25:315–323. 28. Hara M, Nakamura M, Shiokawa Y, et al. Delayed cyst formation after radiosurgery for cerebral arteriovenous malformation: two case reports. Minim Invas Neurosurg 1998; 41:40–45. 29. Yamamoto M, Jimbo M, Hara M, et al. Gamma knife radiosurgery for arteriovenous malformations: long-term follow-up results focusing on complications occurring more than 5 years after irradiation. Neurosurgery 1996; 38:906–914. 30. Mathis J, Barr J, Horton J, et al. The efficacy of particulate embolization combined with stereotactic radiosurgery for treatment of large arteriovenous malformations of the brain. AJNR 1995; 16:299–306. 31. Pollock BE, Flickinger JC, Lunsford LD, et al. Factors that predict the bleeding risk of cerebral arteriovenous malformations. Stroke 1996; 27:1–6. 32. Steiner L, Lindquist C, Adler JR, et al. Clinical outcome of radiosurgery for cerebral arteriovenous malformations. J Neurosurg 1992; 77:1–8. 33. Pollock BE, Flickinger JC, Lunsford LD, et al. Hemorrhage risk after radiosurgery for arteriovenous malformations. Neurosurgery 1996; 38:652–661. 34. Pollock BE, Kondziolka D, Flickinger J, et al. Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery. J Neurosurg 1996; 85:1044–1049. 35. Gerszten PC, Adelson PD, Kondziolka D, et al. Seizure outcome in children treated for arteriovenous malformations after gamma knife radiosurgery. Ped Neurosurg 1996; 24:139–144. 36. Huang CF, Somaza S, Lunsford LD, et al. Radiosurgery in the management of epilepsy associated with arteriovenous malformations. Radiosurgery 1996; 1:195–200. 37. Kondziolka D, Lunsford LD, Kanal E, et al. Stereotactic magnetic resonance angiography for targeting in arteriovenous malformation radiosurgery. Neurosurgery 1994; 35:585–591. 38. Flickinger JC, Pollock BE, Kondziolka D, et al. A dose–response analysis of arteriovenous malformation obliteration after radiosurgery. Int J Radiat Oncol Biol Phys 1996; 36:873–879. 39. Petereit D, Mehta M, Turski P, et al. Treatment of arteriovenous malformations with stereotactic radiosurgery employing both magnetic resonance angiography and standard angiography as a database. Int J Radiat Oncol Biol Phys 1993; 25:309–313. 40. Pollock BE, Kondziolka D, Lunsford LD, et al. Repeat stereotactic radiosurgery of arteriovenous malformations: factors associated with incomplete obliteration. Neurosurgery 1996; 38:318–324.
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41. Flickinger JC, Kondziolka D, Maitz A, et al. Analysis of neurological sequelae from radiosurgery of arteriovenous malformations: how location affects outcome. Int J Radiat Oncol Biol Phys 1998; 40: 273–278. 42. Friedman W, Blatt D, Bova F, et al. The risk of hemorrhage after radiosurgery for arteriovenous malformations. J Neurosurg 1996; 84:912–919. 43. Karlsson B, Lindquist C, Steiner L. Effect of gamma knife surgery on the risk of rupture prior to AVM obliteration. Minim Invas Neurosurg 1996; 39:21–27. 44. Karlsson B, Lindquist M, Lindquist C, et al. Long-term angiographic outcome of arteriovenous malformations responding incompletely to gamma knife surgery. Radiosurgery 1996; 1:188–194. 45. Guo WY, Karlsson B, Ericson K, et al. Even the smallest remnant of an AVM constitutes a risk of further bleeding. Acta Neurochir 1993; 121:212–215. 46. Karlsson B, Kihlstrom L, Lindquist C, et al. Gamma knife surgery for previously irradiated arteriovenous malformations. Neurosurgery 1998; 42:1–6. 47. Steinberg G, Chang S, Levy R, et al. Surgical resection of large incompletely treated intracranial arteriovenous malformations following stereotactic radiosurgery. J Neurosurg 1996; 84:920–928.
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Molecular Biology of Arteriovenous Malformations Michael L. DiLuna Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
Turker Kilic Vascular and Oncological Neurosurgery, Gamma-Knife Radiosurgery, Marmara School of Medicine, Istanbul, Turkey
Issam A. Awad Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, and Evanston Northwestern Healthcare, Evanston, Illinois, U.S.A.
Murat Gunel Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
INTRODUCTION The past two decades have seen an exponential increase in information from molecular studies of human and vertebrate pathobiology. Bioinformatics and high-throughput screening of genes, proteins, and their interactions have allowed the physician-scientist, for the first time, to shift gears from understanding the pathology of disease to the potential biological treatment of disease based on underlying molecular pathways. The genetic data from Mendelian forms of human disease have led to the discovery of novel gene pathways for complex developmental pathways including angiogenesis, organogenesis, and vertebrate patterning. For neurovascular diseases such as arteriovenous malformations (AVMs) and vascular malformations of the brain as a whole, we are now in the process of identifying novel molecular targets. The future will see a shift in paradigm to the manipulation of these targets to modify the natural history of human diseases. In this chapter, we review the process by which blood vessels form under physiological conditions (vasculogenesis and angiogenesis), present seminal examples of molecular advances in Mendelian and non-Mendelian diseases, and discuss novel molecular approaches to neurovascular diseases. AVMs of the brain are pathological direct communications between arteries and veins, with normal vessel wall elements. These abnormal connections create a high-flow state predisposing the adjacent tissues to vascular recruitment, arterialization of venous structures, and gliosis of intervening and adjacent brain tissue. These lesions are prone to hemorrhage not only from the AVM itself, but also from the so-called high-risk features (direct fistulas, venous obstruction, and aneurysms) that can develop, with time, due to the behavior and nature of these lesions. Little is known about the underlying molecular mechanisms that predispose individuals to developing AVMs. Instead, researchers have looked to vertebrate models of normal vasculogenesis and angiogenesis, and then to Mendelian forms of human disease that have phenotypic qualities similar to those of AVMs in the brain. ANGIOGENESIS AND VASCULOGENESIS Embryologic Vasculogenesis The process by which the circulation of the central nervous system (CNS) forms, namely the interplay between vasculogenesis and angiogenesis, plays an important role in the development of cerebrovascular pathology and our understanding of it. The two processes are integral to the developing embryo, where it is argued that the process of vasculogenesis stops and angiogenesis continues throughout the organism’s life. Vasculogenesis specifically refers
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to the process by which primitive blood vessels (endothelial cell tubes) form. Beginning with the embryologic heart, a vascular plexus or tree begins to sprout and initiates connections with the extraembryonic tissues (yolk sac, placenta) through which the embryo will draw energy for continued growth. Stem cells from the mesenchyme expand, differentiate, and divide. Primitive tubes form at this stage as endothelial cells divide and mature. Eventually, smooth muscle cells and pericytes, also from the mesoderm and mesenchyme, are recruited to give added support to the na€ve vessels, a process thought to be triggered by the beginnings of circulation. Numerous signals initiate and stimulate this process, including the highly studied vascular endothelial growth factor (VEGF), its splice variants and receptors, and angiopoietin (ANG) 1–4 and their receptors TIE-1 and -2. Angiogenesis At this point, with the beginnings of the maturation of these primitive vessels, vasculogenesis stops and angiogenesis begins and continues throughout the life of the organism. It is important to note that this process parallels the development of the embryologic endoderm and ectoderm. VEGF expression and its receptors are found in numerous tissues during embryogenesis, not just within the developing vascular tree. Neural tube development is also occurring in a synchronous fashion with vasculogenesis and development of the cerebrovasculature. As a part of the angiogenesis phase in the embryo, the primitive carotid arteries sprout from the aortic arch, and subsequently these vessels migrate to the ventral neural tube to form a primitive vascular plexus. Vessels originating from this plexus sprout and enter the brain parenchyma to form the microvasculature. VEGF appears to be a key central signaling peptide throughout this process; its expression in the subependymal layer is accompanied by high levels of expression of VEGF receptors (Flk-1 and Flt-1) on the surface of invading and proliferating endothelial cells (1). Angiogenesis can be simply divided into three processes described as initiation, proliferation and division, and maturation. The initiation phase calls upon stem cells not only from the surrounding connective tissue, but also from within the circulation, to divide into cells to become the building materials (endothelial cells, pericytes, and fibroblasts) important for angiogenesis. As this process takes place, the cells begin to organize within the extracellular matrix. The matrix is broken down by a set of enzymes known as membrane-associated matrix metalloproteinases, which digest proteins such as type IV collagen and laminin. The early vessels now invade the tissue and branch into increasingly complex networks. Lastly, as these networks mature, the lumens of these vessels are supported by pericytes and vascular smooth muscle and more endothelial cells through cell division. Venous versus arterial circulation also appears to be decided at this stage as the proliferating and migrating endothelial cells express markers, specifically Ephrin-B2 and Ephrin-B4, each of which appears to direct the fate of the circulation (2). As angiogenesis begins, paracrine signaling involving the endothelium and other vessel wall elements begins to play an important regulatory role, through both inhibition and stimulation as the process, progresses through the three outline stages of angiogenesis. Four paracrine growth factor systems [VEGF, angiopoietins, ephrins, and transforming growth factor-beta (TGF-b)] are integral to this process and will be outlined further. Angiogenesis initiation begins with paracrine signaling through the receptor tyrosine kinase (RTK) pathway and its associated ligands and cofactors. To date, four RTKs have been proven as integral to early phases of angiogenesis, although novel pathways are constantly being discovered and tangentially linked to early angiogenesis: VEGF-R1 and VEGF-R2 (VEGF receptors known as Flt-1 and Flk-1, respectively, in the molecular genetics literature), and TIE-1 and TIE-2 (receptors for the proteins ANG-1 and ANG-2) (3). A stem cell from within the circulation or the extracellular matrix differentiates through paracrine signaling by VEGF and Flk-1. The early blood vessels (endothelial cell tubes) that are formed are TIE-1, TIE-2, and Flt-1 positive. As these receptors are activated by their respective ligands, complex inhibitory and stimulatory processes begin, leading to the second phase of angiogenesis: proliferation and division. During this next phase of angiogenesis, endothelial cells must divide and migrate through the extracellular matrix (basal lamina) to the new and growing tissues requiring a blood supply. A host of digestive enzymes such as urokinase (u-PA), tissue-type (t-PA) plasminogen activators, and matrix metalloproteinases break down matrix proteins and allow for these activated endothelial cells to migrate, form tubes, and begin organizing new vessels. The process by which the endothelial cells are recruited and migrate through the extracellular
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matrix is an important discovery that plays a large role in our understanding of aging, tumor angiogenesis and metastatic behavior, and apoptosis. Transforming growth factor-b acts in a similar fashion on the newly developed vessel and the proliferating endothelial cells within the mesenchyme. The TGF-b superfamily (including TGF-bs, activins, bone morphogenic proteins, and Mullerian-inhibiting substance) are embryologically vital cytokines that regulate many aspects of cellular function such as proliferation, death, differentiation, adhesion, migration, and organization (4). TGF-b, specifically, subtype TGF-b1, signaling in angiogenesis induces differentiation of mesenchymal cells into pericytes and smooth muscle cells that surround the nascent tubes and stabilize them within the extracellular matrix (5,6). At the same time, TGF-b1 dimers inhibit endothelial cell proliferation. The role this plays in cerebrovascular pathology will be discussed in the section on hereditary hemorrhagic telangiectasia or HHT. TGF-b1 signaling is also thought to act in concert with a number of branching-directed proteins to enable the differentiation of the venous and arterial sides of circulation. The final stage, the maturation phase, is aimed at organizing the pericytes and smooth muscle within the walls of the new vessels to ensure vessel integrity, structure, and strength in response to the pending circulating plasma. MENDELIAN FORMS OF AVMs Angiogenesis is a process that must continue throughout the life of an organism. Responses to illness, injury, cell death, and turnover all require the growth and differentiation of new blood vessels. Understanding the process by which angiogenesis occurs under normal physiological conditions enables us to understand how this process potentially fails in human disease. Specifically, AVMs lie where the boundary between normal and pathological angiogenesis occurs. Discoveries made at the research bench in Mendelian models of AVM have permitted the understanding of how sporadic disease occurs and have enabled us to predict the biology of these lesions. The Mendelian forms of AVMs are listed in Table 1. Venous Malformations Venous malformations (VMs), the most common errors of vascular morphogenesis in humans, are composed of dilated, serpiginous channels (7). The walls of the channels have a variable thickness of smooth muscle; some mural regions lack smooth muscle altogether. In families demonstrating the inherited phenotype of VMs, termed venous malformations, multiple cutaneous and mucosal (VMCM), Vikkula et al. identified a genotype, specifically missense arg849-to-trp mutation, in the active kinase domain of TIE-2 that cosegregated with the disease phenotype (8). The locus for this gene is within a 24-cM interval on 9p, specifically 9p21, defined by the markers D9S157 and D9S163. TIE-2 or TEK RTK is expressed exclusively by endothelial cells in mammals, and its disruption in knockout studies is embryonically lethal as the embryos do not develop endothelium. It has since been shown that the mutation in families with the autosomal dominant venous malformation disease, VMCM1, activates the TIE-2 receptor. The TIE-2 receptor, which is acted on by the ANG-1 and -2 cytokines, is expressed by stem cells within the marrow and circulation, thought to be endothelial precursors. The action of TIE-2 within these cells maintains them in a quiescent state until they are recruited Table 1 Mendelian Forms of AVMs Disease Allele
Gene
Locus
Protein Function ANG-1 receptor p120-RasGAP protein Integrin binding and microtubule associated protein Unknown Unknown Type III TGF-bb receptor Endothelial cell receptor for members of the TGFbb superfamily
VMCM1 CMAVM CCM1
TIE-2 RasA1 Krit1
9p21 5q13.3 7q11-q21
CCM2 CCM3 HHT1 HHT2
MGC4607 PDCD10 Endoglin Acvrl1
7p13 3q26.1 9q34.1 12q11-q14
Abbreviations: VMCM, venous malformation, multiple cutaneous and mucosal; CMAVM, capillary malformation arteriovenous malformation; CCM, cerebral cavernous malformation; HHT, hereditary hemorrhagic telangiectasia; TGF, transforming growth factor; PDCD, programmed cell death.
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for angiogenesis (9). It is believed that the activating mutations within TIE-2 disrupt the normal communication between the proliferating and differentiating endothelial cells within the extracellular matrix leading to abnormal and disorganized vessel formation and the disease phenotype. The majority of the lesions in this disease are found on the mucosal surfaces and extremities, with multiple lesions on visceral structures including vascular tumors on the spleen, stomach, pancreas, and liver (7). Although not a direct CNS phenotype, the ultrastructure of these lesions is quite similar to that of CNS AVMs. Sporadic cerebral AVMs demonstrate abnormal expression of numerous angiogenesis cytokines and receptors, specifically, the expression of TIE-2 and the VEGF receptors 1 and 2 (Flt-1 and Flk-1) is significantly lower in the lesions when compared with normal brain (10). (See section below, ‘‘Molecular Information on Sporadic AVMs.’’) Capillary Malformation-AVM Capillary malformations of the skin, otherwise known as ‘‘port-wine stains,’’ are very common and are thought to be benign, pigmented lesions that change with age and hormone cycles. These lesions appear with other known diseases of vascular development including Sturge–Weber, Klippel–Trenaunay, and Parkes–Weber syndromes. Multiple families were recently reported with capillary malformations associated with either AVM or arteriovenous fistula (11). The gene was later cloned, and the phenotype is associated with mutations in RASA1. RASA1, a p120-RasGAP protein, is important for signaling in multiple cell types, controlling proliferation, mitosis, cell differentiation, and programmed cell death, including vascular endothelial cells (11). The RAS family of proteins are membrane-associated, guanine nucleotide-binding proteins (p21). The role of RAS1A and RasGAP proteins as a whole in vascular morphogenesis and angiogenesis is yet to be determined, although there is some crossover in the cavernous malformation phenotype. Cerebral Cavernous Malformations Cerebral cavernous malformations (CCMs) are characterized by caverns that are filled with blood or thrombus, which are lined by a single layer of endothelial cells separated by a dysmorphic connective tissue matrix (collagen) (12,13). These lesions do not contain any intervening neural parenchyma or identifiable mature vessel wall elements (12,13). Furthermore, gaps exist between the endothelial cells, devoid of tight junctions that would normally create the blood–brain barrier, allowing for the leakage of red blood cells into the surrounding brain parenchyma and leading to heavy hemosiderin deposits (12). Unlike the disease phenotypes previously mentioned, CCMs are confined to the skin, retina, and, primarily, the CNS. This disease has been recognized to be a common clinical entity since the advent of magnetic resonance imaging (MRI), which demonstrates characteristic lesions of variable signal intensity surrounded by a dark ring attributable to hemosiderin (14). Both MRI and autopsy studies suggest a prevalence of cavernous malformation of 0.5%, although the prevalence of symptomatic disease is much lower (15,16). Symptomatic patients typically present in the third through the fifth decades of life (17,18). Treatment ranges from therapy with antiepileptic drugs in patients with seizures to surgical excision of accessible lesions in patients who suffer from hemorrhage or intractable seizures (17–20). CCM is a familial disorder (21–23,27). Several large kindreds affected with CCM have been reported, and all of these have shown patterns of transmission consistent with autosomal dominant inheritance. However, the proportion of at-risk offspring of affected subjects developing clinical disease is often less than 50%, suggesting incomplete penetrance of the trait (21). Genome-wide linkage analysis of affected families and positional cloning eventually identified three loci, CCM1 on 7q11.2-q21, CCM2 on 7p13, and CCM3 on 3q26.1 that linked to disease phenotype (24–26). Familial cases are particularly evident among Hispanic-Americans of Mexican descent, with over 50% of affected individuals having an affected relative (27). This disproportionate number of familial cases raises the possibility that a common mutation inherited from a shared ancestor (a founder mutation) accounts for the higher disease prevalence in this group. This analysis revealed that all Hispanic patients with familial CCM have inherited the same set of genetic markers, or haplotype, in the portion of 7q linked to CCM (28). This founder mutation found within the gene KRIT1 (Q455X), inherited from a common ancestor, is responsible for CCM1 in the majority of cases. Subsequently, numerous other mutations within
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the KRIT1 gene were found in families with CCM1. The manner by which mutations in the KRIT1 gene lead to a loss of function and disease phenotype is thought to be through a Mendelian two-hit model where patients with the inherited form of CCM1 are born with one mutant KRIT1 allele and one wild-type allele and lose the second allele through a somatic mutation, ultimately leading to complete loss of KRIT1 expression. In contrast, it is believed that patients with the sporadic form of CCM are born with two normal copies of the KRIT1 gene and have to acquire two independent somatic mutations within one or more of the CCM genes to form CCM lesions. To date, little is known about the KRIT1 protein. KRIT1 was found initially through a Yeast-2-hybrid screen using Krev1/Rap1A as bait (29). Krev1 is a member of the RAS family of GTPases; and in assays with RAS-activating proteins (GAP), Krev1 is not activated by GAP but is bound tightly to GAP and thereby competitively inhibits GAP-mediated RAS-GTPase activity (29). Thus, Krev1 acts as a tumor suppressor gene in RAS signaling. The role of KRIT1, RAS, and angiogenesis in the development of the cerebrovasculature is unknown. The interaction between KRIT1 and Krev1 implicates potential importance of RAS signaling in angiogenesis, coupled with data from patients with capillary malformation-AVM (CMAVM) and the molecular data from CCM. Indeed, one study suggests that GAP proteins (like RAS) are phosphorylated in response to VEGF in cultured endothelial cells to stimulate proliferation and angiogenesis (30). Thus, the KRIT1 functional data and previous work done on RAS and angiogenic factors suggest a novel involvement of the RAS signal transduction pathway in angiogenesis. Other investigations aimed at understanding the function of KRIT1 protein, using molecular genetic and yeast two-hybrid technologies, demonstrated that it encodes a microtubule-associated protein (31) that also interacts with integrin cytoplasmic domainassociated protein-1a (ICAP-1a) (32–34). Furthermore, this interaction is mediated specifically by an N-terminal KRIT1 NPXY amino acid sequence, a motif critical for ICAP-1 binding to b1-integrin (32). Knockout studies in mice demonstrate that KRIT1 is ubiquitously expressed early in embryogenesis and is essential for vascular development. Homozygous mutant embryos die in mid-gestation; and the first detectable defects are exclusively vascular in nature, where the precursor vessels of the brain become dilated starting at E8.5, reminiscent of the intracranial vascular defects observed in the human disease (35). These results implicate KRIT1 in focal cell adhesion. Under this model, loss of function mutations in KRIT1 would have predictable consequences in endothelial cell morphology and performance during angiogenesis directed by b1-integrin signaling. Using similar positional cloning and molecular biochemical techniques, Liquori et al. found mutations in an unknown gene, MGC4607 or malcavernin, in families with CCM2 (36). This gene encodes a putative phosphotyrosine-binding domain, which is the same domain found in ICAP-1a, KRIT1’s binding partner. Little is known about the function of this gene. Histopathology analysis of CCM2 revealed similar patterns of expression in similar cell subtypes as seen with KRIT1, specifically within arterial endothelium, but not in vascular wall elements such as smooth muscle cells or the venous circulation (37). Mutations in the gene Programmed Cell Death-10 (PDCD10) link to the CCM3 phenotype (38–40). PDCD10 is an unknown protein without any functional domain found through sequence analysis. The role of this peptide in CCM disease is yet to be determined. Because the disease phenotypes caused by mutations in either gene are clinically and pathologically indistinguishable, the significant overlap in expression pattern supports the hypothesis that the three proteins are involved in the same pathway important for CNS vascular development. Hereditary Hemorrhagic Telangiectasia One example of how Mendelian forms of human vascular disease have redefined all elements of translational research from angiogenesis and the development of the normal cerebrovasculature to patient care is hereditary hemorrhagic telangiectasia (HHT) or Rendu–Osler–Weber syndrome. Much of what is understood today about the process of angiogenesis and how errors in this delicate balance of positive and negative signaling can result in human disease has come from studies of patients with HHT. HHT is an autosomal dominant form of vascular dysplasia that is characterized by the appearance of telangiectases and AVMs in multiple tissues such as the skin, mucosa, and viscera, including the lung, liver, and brain.
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The clinical diagnosis of HHT requires the presence of any two of the following: a pattern of autosomal dominance inheritance, telangiectases in the nasal mucosa, recurrent epistaxis, and visceral telangiectases. The risk of intracranial hemorrhage among people with HHT is believed to be low, and patients have a good functional outcome after hemorrhage (41). HHT lesions within the CNS are mostly low-grade AVMs (Spetzler–Martin Grade I or II) and are frequently multiple. About 7% to 12% of patients with HHT have CNS lesions, and females are affected more often than males (42–44). Controversy exists as to whether or not patients with HHT should undergo frequent screening for CNS lesions. By comparison, pulmonary arteriovenous fistulae are a much more frequent cause of neurological symptoms in this population through embolic stroke. HHT was first described by Osler in 1901 as a ‘‘family form of recurring epistaxis, associated with multiple telangiectases of the skin and mucous membranes’’ (45). Histopathological and ultrastructural analyses of telangiectases from the skin and mucosa reveal focal dilations of postcapillary venules composed of prominent stress fibers and pericytes along the adluminal border (46). There is no reported difference between mucosal and cutaneous telangiectases and those found in the viscera (47) or the neurovasculature (48). As the pathologic AVM develops, the abnormal vessels have multiple layers of smooth muscle, often without an elastin component, and connect through one or more capillaries to dilated arterioles (46). The first gene, HHT1, was mapped to 9q34.1 (49), and a second group of families showed linkage to a second locus, HHT2, on 12q11-q14 (50). A third locus was later shown within a 5.4-cM disease interval at 5q31.3-5q32 (51). Similar to CCM, linkage and positional cloning techniques showed that a gene coding for endoglin, a TGF-b binding protein, was mutated in affected individuals with HHT1 (52). In a similar fashion, loss-of-function mutations were found in the activin receptor-like kinase 1 gene, Acvrl1, a type I serine-threonine kinase receptor for the TGF-b superfamily of growth factors within the HHT2 locus on 12q11-q14 (53). These proteins are expressed extensively in the vascular endothelium and play an important role in vasculature repair and angiogenesis. The gene that is mutated in HHT3 is not known at this time. Both Acvrl1 and endoglin are required as receptor-partners for TbRI, II, and III to maintain the balance between the positive and negative biphasic effect that TGF-b signaling has on angiogenesis (54). Endoglin Endoglin, a type III TGF-b receptor, is a member of a family of cell surface receptors that are among the most densely expressed receptors across a given cell’s surface (55). Endoglin is a membrane glycoprotein expressed in limited amounts in organ tissues but is found in high levels predominately in vascular endothelial cells and in hematopoietic cell types (56). The endoglin gene codes for a 561-amino acid protein, including the cell localization signal peptide, multiple extracellular N- and O-linked glycosylation sites, and a 47-amino acid cytoplasmic domain that can vary in length due to alternative splicing events (57). The native protein exists as a homodimer linked by multiple cysteine–cysteine bonds (58). Endoglin-null mice (–/–) do not survive past E11.5 (11.5 days after fertilization); these knockout mice are three times smaller and exhibit a profound absence of vascular organization (56). Interestingly, in the absence of endoglin expression, Flk-1, Flt-1, TIE-1, and TIE-2, in addition to TGF-b expression, are all unchanged. This finding implies that endothelial cell differentiation from precursor cells is not solely regulated by endoglin, but given the severity of the phenotype in the null mice, each piece of the angiogenesis puzzle is vital to vascular organization in the developing embryo. As expected, the vascular structures in the knockout mice are deficient in the maturation stage of angiogenesis, as vascular smooth muscle precursors were absent from supporting structures of the nascent capillary networks. Activin Receptor-like Kinase (Acvrl1) Acvrl1, similar to endoglin, is an endothelial cell receptor for members of the TGF-b superfamily. Acvrl1 shows little or no activity in response to all TGF-b protein subtypes. However, when bound as a chimeric heterodimer to the TGF-b type I receptor, Acvrl1 signaling activity markedly increases in response to TGF-b1 and -b3 but not -b2 (4). Cellular signaling dependent on heterodimer binding specificity with TGF-b type I receptors is a result seen in functional experiments with endoglin, lending further support to the notion that endoglin and Acvrl1 are in the same molecular and developmental pathway and that each is able to
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keep TGF-b positive and negative angiogenic signaling in check. Similar to the CCM phenotypes, the HHT phenotypes are indistinguishable, and these results support both proteins playing a role in the same angiogenesis pathway. The results from the functional studies of these proteins suggest that the quiescent state of mature, adult blood vessels is regulated by endogenous negative effectors, acting through endoglin and Acvrl1 signaling. Acvrl1-null (–/–) mice were also embryonic lethal mutants (59,60). At E9.5, the knockout mice had yolk sacks that failed to form distinct vitelline vessels and remained a meshwork of interconnected and homogeneous endothelial tubes. Furthermore, the mice showed primary arterial-venous shunting of the central vascular tree with subsequent disruption of endothelial remodeling and vascular smooth muscle cell development (59,60). Combined with the endoglin data, the process of angiogenesis and early vascular development can be broken down into two distinct but critical processes. First, proteins like VEGF and other growth factors must differentiate the angioblasts and vascular stem cells into the endothelial tubes that form the vitelline capillary plexus of the yolk sac and the central vascular tree (61). Secondly, the assignment of arterial-venous identity must occur to create the mature circulatory system, a process dependent on Acvrl1 and TGF superfamily cytokines (60). Acvrl1, similar to endoglin, plays a crucial role in angiogenesis, vessel turnover, and venous-arterial designation through the maturation of new blood vessels, again supporting theories about the formation of AVMs. MOLECULAR INFORMATION ON SPORADIC AVMs The wealth of information gained from the data on Mendelian forms of vascular malformations has been applied to studies of sporadic cases. Starting with the receptors, their ligands, and cytokines expressed throughout vasculogenesis and angiogenesis, investigators have looked at differences between normal and abnormal vasculature of the brain (Fig. 1). For example, we discussed the fact that VEGF and its receptors are highly expressed by precursor cells and throughout angiogenesis early in the embryo state. VEGF in the adult is typically expressed only by tissues in a pathological state (stress, ischemia, and neoplasm). In AVMs, VEGF and FLT-1 expression is high compared to that of normal brain (48,62). Dynamic angiogenesis studies showed that, of the three cerebrovascular malformation types, AVMs showed the highest angiogenic activity, CCMs exhibited some degree of angiogenic activity (less than AVMs but more than normal brain artery tissue), and angiogenesis induction by venous angiomas was comparable to that of normal brain artery tissue (63). Ultrastructural histopathological analysis of AVMs yielded results that could be expected of a normal, mature vessel altered by arterialized flow and general intimal stress. These lesions maintain relatively normal, identifiable vessel structures with relative structural integrity (tight junction and pericyte preservation) (13). Proteins found within vessels that maintain their presence within the extracellular matrix as well as solidify vessel wall strength, such as laminin, type IV collagen, actin, and smoothelin, are expressed intensely by AVMs (13,62,64,65). This separates these lesions from others such as CCMs, which tend to have leaky or defective tight junctions. Other than structural proteins, extracellular molecules, growth factors (and their receptors), intercellular molecular signaling proteins such as integrins (integrin avb1, avb3, and avb5) are expressed in AVMs and CCMs in different patterns, possibly linked to stages of angiogenic maturation. Integrin avb1 is expressed more strongly in endothelium and subendothelium/media of AVMs than in the corresponding layers of CCMs (Fig. 2). Conversely, integrins avb3 and avb5 are expressed more strongly in CCM endothelium than in AVM endothelium (Fig. 3). Another example of how molecular technology has furthered our understanding of neurovascular disease is the use of microarrays. AVMs analyzed by gene expression micorarray for the differential expression of genes important in angiogenesis revealed upregulated expression for endoglin mRNA. Additionally, gene expression of ANG-1, TIE-1, TEK, and PECAM1 mRNAs are downregulated in AVMs while FLT-1 (VEGF receptor) is upregulated (66,67). All in all, over 100 genes were found to be differentially expressed by AVMs when compared with other CNS vascular lesions and normal controls. Although the data gained from microarrays can be vast and often difficult to interpret, they might be useful in understanding the role that these molecules play in angiogenesis and vessel remodeling.
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Figure 1 Graphs summarizing the immunohistochemical data showing the differential intensity of selected groups of molecules during the process of angiogenic maturation and their relative presence in the AVMs, CCMs, and VAs. (A) Structural proteins forming the vascular wall, (B) extracellular proteins, (C) integrins. Abbreviations: AVM, arteriovenous malformation; CCM, cerebral cavernous malformation; VA, venous angioma. (See color insert.)
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Figure 2 Illustrative sections of the AVM sections stained with integrin amb1 (A–C), integrin amb3 (D–F), and integrin amb5 (G–I) antibodies, The three integrins were expressed in different ways in the AVMs versus the CCMs. The differences relate to the stages of angiogenic maturation exhibited by these lesions. All the histological layers of the AVMs showed stronger expression of integrin amb1 than the corresponding layers of the CCMs. Integrin amb3 was expressed more strongly in CCM endothelium than in AVM endothelium. Integrin amb5 was expressed more strongly in CCM endothelium and subendothelium than in AVM endothelium and subendothelium/media. Abbreviations: AVM, arteriovenous malformation; CCM, cerebral cavernous malformation. (See color insert.)
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Figure 3 Illustrative sections of the cerebral cavernous malformation (CCM) sections stained with integrin avb1 (A–C), integrin avb3 (D–F), and integrin avb5 (G–I) antibodies. (See color insert.)
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FUTURE RESEARCH Much remains to be understood about cerebrovascular disease as a whole, but specifically with respect to vascular malformations. The pathways by which angiogenesis is altered early in life to lead to the foundation of an AVM are still unknown. Moreover, a novel angiogenesis and vascular remodeling pathway needs further clarification with the understanding of the mechanism of action of the CCM2 and -3 proteins. Currently, we can counsel our patients harboring a severe phenotype of vascular malformation at a young age through the screening of potentially affected relatives. As we expand our ability to diagnose and treat these lesions, not only through surgical means but also with minimally invasive techniques like stereotactic radiosurgery and endovascular technologies, the molecular data will enhance our knowledge of how these lesions grow and change through the life of a patient. We soon will enter an era of biological treatment of these lesions through either gene delivery or gene modification. The goal will be not only to prevent lesion formation, but more likely, to alter the natural history of these lesions to reduce the risks of morbidity and mortality for our patients.
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51. Cole SG, Begbie ME, Wallace GM, Shovlin CL. A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5. J Med Genet 2005; 42(7):577–582. 52. McAllister KA, Grogg KM, Johnson DW, et al. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 1994; 8(4):345–351. 53. Berg JN, Gallione CJ, Stenzel TT, et al. The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am J Hum Genet 1997; 61(1):60–67. 54. Shovlin CL, Hughes JM, Scott J, Seidman CE, Seidman JG. Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia. Am J Hum Genet 1997; 61(1): 68–79. 55. Massague J. Receptors for the TGF-b family. Cell 1992; 48:409–415. 56. Li DY, Sorensen LK, Brooke BS, et al. Defective angiogenesis in mice lacking endoglin. Science 1999; 284(5419):1534–1537. 57. Gougos A, Letarte, M. Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 1990; 265:8361–8364. 58. Barbara NP, Wrana JL, Letarte M. Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor- beta superfamily. J Biol Chem 1999; 274(2):584–594. 59. Srinivasan S, Hanes MA, Dickens T, et al. A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2. Hum Mol Genet 2003; 12(5):473–482. 60. Urness LD, Sorensen LK, Li DY. Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet 2000; 26(3):328–331. 61. Pepper MS. Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev 1997; 8(1):21–43. 62. Kilic T, Pamir MN, Kullu S, Eren F, Ozek MM, Black PM. Expression of structural proteins and angiogenic factors in cerebrovascular anomalies. Neurosurgery 2000; 46(5):1179–1191; discussion 91–92. 63. Konya D, Yildirim O, Kurtkaya O, et al. Testing the angiogenic potential of cerebrovascular malformations by use of a rat cornea model: usefulness and novel assessment of changes over time. Neurosurgery 2005; 56(6):1339–1345; discussion 45–46. 64. Kilic T, Sohrabifar M, Kurtkaya O, et al. Expression of structural proteins and angiogenic factors in normal arterial and unruptured and ruptured aneurysm walls. Neurosurgery 2005; 57(5):997–1007; discussion 997–1007. 65. Seker A, Yildirim O, Kurtkaya O, et al. Expression of integrins in cerebral arteriovenous and cavernous malformations. Neurosurgery 2006; 58(1):159–168; discussion 159–168. 66. Shenkar R, Elliott JP, Diener K, et al. Differential gene expression in human cerebrovascular malformations. Neurosurgery 2003; 52(2):465–477; discussion 77–78. 67. Shenkar R, Sarin H, Awadallah NA, Gault J, Kleinschmidt-DeMasters BK, Awad IA. Variations in structural protein expression and endothelial cell proliferation in relation to clinical manifestations of cerebral cavernous malformations. Neurosurgery 2005; 56(2):343–354.
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Surgical Approaches Daniel P. McCarthy, Bernard R. Bendok, Christopher C. Getch, and H. Hunt Batjer Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, U.S.A.
INTRODUCTION The surgical treatment of intracranial arteriovenous malformations (AVMs) has advanced tremendously since Cushing and Bailey wrote in 1928, to ‘‘extirpate one of these aneurysmal angiomas in its active state would be unthinkable’’ (1). As recently as the late 1970s, the senior author had the opportunity to watch Dr. Duke Samson resect a large and complex AVM. It appeared at that time that we simply did not have the appropriate technologies to deal with the fragility of the vasculature surrounding these lesions. Only high levels of surgical skill and extensive experience enhanced the patient’s chance for a good outcome by overcoming technological limitations. Progress in surgical management has been driven by two broad trends: technological development and interdisciplinary coordination. Endovascular and radiosurgical therapies have expanded the therapeutic arsenal, while the operating microscope has refined the surgical option. Advances in our understanding of the pathobiology and natural history of the disease have reshaped anesthetic and postoperative care of patients with AVMs. Neuroradiologists now provide surgeons with exceptional imaging capabilities. In the near future, we may see even tighter collaboration between disciplines. AVM surgery will likely be conducted in a modified operating room that permits simultaneous endovascular and microsurgical intervention. The increased interdisciplinary cohesion in combating AVMs has had a significant impact on surgical outcomes. These collaborative strategies are examined in more detail in other chapters. This chapter describes another factor that will continue to transform surgical approaches to AVM management—technological development. Innovations in local drug delivery, neuroanesthesia, neurological critical care, instrumentation, imaging, and real-time data management will allow surgeons to achieve a new level of technical proficiency and safety. These advances should expand the universe of patients who can be cured of this disease. Furthermore, these breakthroughs will enable strategies that were previously impractical or inconceivable. In this chapter we attempt to identify innovations, currently available or visible on the horizon, that are poised to have a lasting impact on the surgical treatment of AVMs and on patient outcomes. DRUG DELIVERY SYSTEMS Many of the nonhemorrhagic complications during and after AVM surgery lend themselves to medical treatment. For example, cerebral hyperemia can be treated with cerebral vasoconstrictors and metabolic suppression, vasospasm by calcium channel blockers or endothelin receptor antagonists, and seizures by anticonvulsants. Yet these interventions can be limited by side effects resulting from systemic delivery or the inherent complexity of pharmacological action regarding vasoactivity and metabolic impact. For example, a drug used to increase systemic blood pressure with the goal of augmenting cerebral blood flow (CBF) may have the paradoxical effect of actually decreasing CBF by cerebral vasoconstriction. Novel drug delivery systems offer the advantage of direct application to the target tissue. Local application allows a higher concentration of therapeutic agent at the desired site, while maintaining an absence of drug in the systemic circulation. The rate of release can also be controlled to optimize a variety of parameters (e.g., time period of drug release). Perhaps most importantly, direct application to the brain tissue can circumvent the blood–brain barrier (BBB). This could allow the delivery of proteins and other molecules that do not normally cross the BBB. In many respects we have failed, to date, to take advantage of the fact that we actually expose vessels and brain tissue during surgery.
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Although much of the research on novel drug delivery systems involves extracranial uses, some reports have been published on the use of microparticles in the brain (2). Artificial biodegradable microparticles have been designed to deliver chemotherapeutics to brain tumors via stereotactic implantation. Evidence demonstrates the biocompatibility of these microparticles in the rat brain (3). In addition to microparticle suspensions, drugs can be conjugated directly to gel-polymers. Even something as simple as an irrigation solution containing the selected drug could be applied directly to the target site, although this mode would most likely not provide the same long-term delivery as a gel. These delivery systems can easily be applied to the resection bed and surrounding tissue, and they might offer more effective prevention of common AVM complications. Other substances may present additional methods of hemostasis during AVM surgery. The SURGIFOAM1 (Johnson & Johnson) absorbable gelatin powder can be mixed with saline to form a hemostatic paste useful for dealing with the irregular shape of the resection bed, where it may be difficult to apply conventional hemostatic techniques. This technique is already used by some surgeons in AVM surgery. SURGIFOAM does not contain any active therapeutics, but it illustrates the advantages of using novel materials in AVM surgery. Hemostatic foams, with or without the addition of therapeutic agents, might be used to stop elusive minor bleeds without requiring further dissection to reach the bleed with a bipolar or cotton. The last decade has seen welcomed advances in neuroanesthesiology and neurocritical care. It is now possible to keep patients intubated and essentially under full anesthesia with barbiturate-induced cerebral vasoconstriction for many days. Cerebral protectant strategies enable the use of intraoperative temporary arterial occlusion during episodes of hemorrhage without risking ischemic sequelae. Although the authors have not used transient pharmacologically induced circulatory arrest in AVM surgery, there is no reason that it should not be a useful adjunct to the armamentarium. During periods of serious intraoperative bleeding, an immediate arrest of blood flow could allow salvage of an otherwise very difficult situation. Further types of pharmacological agents will also hopefully be much more refined, with highly predictable regional vasoactivity to help protect patients during endovascular and microsurgical interventions. SURGICAL INSTRUMENTATION Advanced instrumentation is another area that will change the future surgical treatment of AVMs. Innovations will include both refinements in existing instruments and the creation of entirely new implements. AVM surgery presents specific problems that either are unique or are encountered more frequently as compared with other neurovascular procedures. Most of these difficulties relate to the hemodynamic abnormalities and high flow states induced by the AVM. Microsurgical AVM management involves the dissection of highly vascularized tissue with abnormally high flow rates and low run-off resistance. Many of the vessels encountered must be sacrificed, while others are manipulated so that resection can be accomplished without their disruption (vessels en passage). Clips play a vital role in this process. They can be applied quickly and safely for temporary occlusion of sizable feeding trunks and to facilitate coagulation by reducing flow. The problematic arterioles in the periventricular region carry such a rapid blood flow that bipolar cautery simply cannot heat the luminal blood adequately for protein coagulation. Applying a small clip stops the flow and enables coagulation to occur. The clip can then be removed if the surgeon desires. The development of clips designed specifically for use in AVM surgery has been a welcome advance. The clips themselves are effective, but work must be done regarding the shape of clips, their size, and the clip applier technology. The clip appliers themselves must be redesigned to allow more versatile application in hard to reach areas in which the target vessel may be oriented at complex angles with respect to the available surgical corridor. Moreover, visual obscuration by the clip applier and an open clip is an aspect that requires innovation in these precarious surgical corridors often compromised by ongoing hemorrhage. One potential solution might involve clip appliers that allow independent surgeon-driven control of all angles of the clip and its parent applier. Such appliers would provide the surgeon with a finer degree of control than merely increasing options of clip size and shape. Once in place, the clips themselves can hinder further dissection if they
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are not tiny. The type of material used to make AVM clips should also be studied. As advanced intraoperative imaging progresses (see below), the presence of any material creating a magnetic resonance (MR) or computed tomography (CT) artifact will be problematic. The rapidly evolving field of biomedical engineering will likely come up with appropriate materials that are compatible and durable. AVM surgery could also benefit from the use of an advanced microDoppler to ensure the patency and direction of flow in involved vasculature. Branches, en passage vessels, and draining veins must be preserved to permit perfusion and drainage of the normal tissue surrounding the resection bed. Minimally invasive techniques would be very beneficial to allow evaluation of these vessels for potential accidental occlusion. The current generation of microDopplers is limited by the need to apply the device at a 45 angle to get an accurate reading. This requirement is a hindrance in AVM surgery because of the narrow corridors and tortuous vascular supply. The next generation of microDopplers should be able to reliably detect blood flow within the vessel when applied at a wide range of angles and in extremely narrow confines. One of the most important devices in AVM surgery is the bipolar cautery. Hemorrhage develops frequently during dissection, and fast and effective hemostasis is required. Current bipolar forceps designs are plagued by a variety of limitations during these procedures. Their tips become coated with sticky, charred tissue because of extensive use in these long procedures. Once charred, the forceps are disabled and must be removed from the field for cleaning, during which time further bleeding may occur. Despite attempts to solve this problem, a bipolar less susceptible to such accumulation remains desirable. In addition, there are potentially more important changes needed to enhance bipolar efficacy. AVMs nearly always have high flow rates through the arterial feeders and nidal vessels. At such high flow velocity and low outflow resistance, the thermal energy imparted by the electrical discharge of the bipolar is limited in its ability to coagulate. Future bipolars could deal with this problem in a variety of ways. One solution would be simply to increase their electrical strength. Another answer might be to create a bipolar with a tip shape that more effectively deals with high flow rates and the tortuous vascularity intrinsic to AVMs. Such a solution might be a right-angled tip so that more of the vessel wall could be included in contact with the forceps. Effort should be devoted to looking at new electrical wave characteristics and wider arc of electrical discharge. AVMs provide an opportunity for the development of novel instrumentation. The intricate nidal tangling of vessels complicates identification of specific vessels of interest. Surgeons commonly expend time and effort just to determine whether a vessel is entering or exiting the nidus or an adjacent sulcus. A simple and very small probe that can indicate the directionality of flow within a vessel would prove useful in this circumstance. Recently, a transit-time ultrasonic flowmeter was designed to measure changes in arterial flow (4). This probe has two small transducers and a reflector, which are positioned around the vessel of interest. Ultrasonic waves are bounced in opposite directions off the reflector. The wave traveling upstream takes slightly longer to travel the same distance as the downstream wave, thus allowing detection of flow directionality. This probe offers the additional advantage of being able to measure blood flow. Another novel device might help preserve vessels during arterial manipulation. For example, these vessels could potentially be mobilized and rolled out of the way with such precision that flow is not compromised. Other potential innovative solutions might make AVMs more amenable to resection. For example, an endovascular device could facilitate transient venous suction decompression. By temporarily occluding inflow with clips and aspirating the blood out of the nidus transvenously, the surgeon could more easily manage the collapsed vessels. Immediately reinstating flow and restoring venous drainage would prevent ischemia to the adjacent brain tissue. The senior author had intraoperative experience in which the sole draining vein of a sizable AVM was transected by the craniotome during craniotomy. Consideration was given to a direct anastomosis. However, the power instrument badly damaged the venous wall, and it would have been difficult to repair with microsutures. With the insertion of the suction directly into the draining vein’s stump, the bleeding ceased and the AVM collapsed. The resident held the suction in place, and the AVM was quickly and bloodlessly resected. Finally, a tool that would substantially improve AVM microsurgery is one that could simultaneously cut and coagulate a vessel. Transection and coagulation are currently separate
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steps, sometimes facilitated by application of a clip. This multistaged process with instrument exchange increases operative time. The disadvantages of the current technique are especially problematic in the case of a bleed deep from the nidus that can be reached only by first dissecting through intervening tissue. Judicious use of clips on afferent vessels for temporary hemostasis may reduce the time it takes to reach the deep bleeding. This method is still hindered by switching between multiple instruments and clip appliers. Bipolars with the ability to cut through tissue are available, but these are not designed to allow simultaneous cutting and coagulation of fragile vasculature. Whatever form it takes, a single device for concurrent transection and coagulation could substantially decrease bleeding and operative time in AVM surgery. ANATOMICAL, PHYSIOLOGICAL, AND OPERATIVELY INTEGRATED IMAGING No matter how effective instrumentation becomes, a surgeon’s technique is only as good as the information he or she has at hand to navigate the tortuous three-dimensional (3-D) maze of an AVM. Imaging technology has had a major impact on the neurosurgeon’s ability to plan and execute the complex procedure required for AVM resection. Progress in both anatomical and functional imaging has revolutionized the preoperative evaluation of patients with AVMs, allowing an experienced surgeon to fairly quickly assess which AVMs should be treated and how to proceed. Postoperative evaluation also has improved greatly, with neuroimaging allowing the acquisition of quickly developed data to prove that resection is complete and permitting assessment of the surrounding brain. These techniques clearly have improved surgical outcome and decreased complications. However, the translation and direct application of these advanced techniques to the operative environment have been notably absent. Even the highest resolution, 3-D preoperative imaging is usually reduced to a static printout that sits on a back wall in the operating room. In the near future, we will see a proliferation of technologies that enable the operator to optimize use of all relevant imaging data without removing himself or herself from the operative field. Data storage will no longer be in monitors, which are very space-expensive, but will be placed on flat screens that fill the walls of the operating suite. The new challenge, of course, will be to get that data directly into the surgeon’s domain. Several of these technologies are commercially available, albeit in a relatively primitive form. Furthermore, intraoperative imaging modalities will allow surgeons to gain 3-D information about the AVM during the dissection at real time. These information streams will be readily available and integrated within the surgeon’s visual field. The military has developed these technologies for use by fighter pilots. Data are downloaded in real time to the goggles, and the pilot can access information in various areas of his or her visual field. Excellent data have been gathered on how much information is too much and can actually lead to confusion due to data overload. Our surgical environment is quite primitive in this regard. We rely on surgical expertise, experience, and instincts instead of real data enabling the surgeon to ‘‘see’’ the lesion in 3-D and ‘‘see’’ where persistent feeding is coming from. Both CT and magnetic resonance imaging (MRI) give precise and useful anatomic information, and this precision will likely increase over time. This information has high relevance to AVM surgery. These images help identify structures that may be involved in the lesion itself. Anatomic information also helps in planning the surgical approach and suggests visible landmarks that can guide resection. Anatomic data go hand in hand with functional imaging. Both positron emission tomography and functional MRI (fMRI) convey the functional status of the perinidal tissue seen in anatomical images. These anatomical and functional imaging technologies will continue to offer higher and higher spatial resolution. MR imaging is the single most important modality in allowing the surgeon to determine whether a lesion should be treated or not and in planning a surgical route or corridor of access. The specific details and strategies of the detailed surgical dissection, however, are dependent on precise angiographic characterization of the lesion. With the advent of CT angiography (CTA) and MR angiography (MRA), noninvasive modalities are able to provide detailed images of cerebral vasculature, although for now digital subtraction angiography (DSA) remains the gold standard. Novel processes for acquisition of highly accurate vascular data through MRA have recently demonstrated exquisite comparability to DSA (T. Carroll, personal communication). Superselective angiography can be used to examine the subtlest
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aspects of AVM angioarchitecture. As with anatomical imaging, our ability to image the cerebral vasculature will continue to improve. The availability of high-quality, 3-D, real-time angiography to detect deep bleeding, residual AVM, or remaining feeding pedicles would clearly advance the field. An important new trend in DSA, MRA, and CTA is the processing of radiographic datasets to generate 3-D representations. These rendered images can be manipulated on workstations to allow examination from any angle. Future surgeons will be able to access and interact with such 3-D images in the operating room to examine the AVM from any angle necessary. Algorithms have also been created that depict the vasculature from new perspectives. One example is the ability to generate images that give luminal detail of feeders from an intravascular point of view. This perspective can help identify true vessel branches and fistulas, and illustrate when two vessels come in close approximation but do not have luminal communication. Other imaging methods are providing information on shear stress experienced by vessels. These data might help identify weak points in the nidus and thus aid in the selection of patients who are at higher risk of hemorrhage than their cohort. Quantification of the mechanical and hemodynamic stress of the vessel system can also better enable the surgeon to predict and anticipate particularly dangerous areas of resection. Where direct imaging data on the hemodynamics of an AVM are not available, computational flow dynamics may be able to provide predictive support (5). The next generation of computational modeling may allow surgeons to test different strategies preoperatively. For example, modeling may indicate that the elimination of several specific feeding arteries through staged embolization or in the initial steps of microsurgery will render the remaining lesion much more manageable than by the traditional circumferential dissection. At the very least, modeling may help predict the effects of flow redistribution caused by progressive surgical eradication of the components of AVM angioarchitecture. Taken as a whole, a surgeon will have increasingly sophisticated resources for evaluating the anatomy, vasculature, and functional characteristics of an AVM and adjacent tissue. Yet we remain confronted with two major problems that limit the use of these technologies. First, the advances have been made largely outside of the operating room; the surgeon must still rely on his or her experience and intuition to apply the static preoperative images to the dynamic intraoperative environment. Few tools are used to update and augment this information quickly. A second and related difficulty is in the integration of the disparate sources of imaging information into the surgical field. The solutions to these two dilemmas are coming in the form of intraoperative imaging and integrated microsurgery systems. Intraoperative imaging is only beginning to become commonplace in neurosurgery. Optical imaging is a potentially useful tool for intraoperative evaluation of functional tissue, but it is still used more for research than for clinical decision-making. Intraoperative MRI has been used by some centers, although cost and conversion to an MRI-compatible operating room are significant obstacles to adoption. One asset of intraoperative MRI in AVM resection, as well as other areas of neurosurgery, is in its ability to demonstrate the shifting of structures due to surgical intervention. This intraoperative information enables surgeons to more accurately estimate how the subtle structures depicted on high-resolution preoperative imaging may have changed with positioning and the evacuation of cerebrospinal fluid. While most intraoperative MR imaging systems currently suffer from poor image quality, newer devices will offer higher resolution, as well as the capability to conduct fMRI, MRA, and diffusionweighted scans while the patient is on the table. Preliminary reports of these intraoperative MR imaging modalities have already surfaced, although not in patients with AVMs (6,7). The ability to collect intraoperative vascular data will have a substantial impact on AVM microsurgery. Many of the commonly encountered problems in AVM surgery have to do with proper characterization of vessels. A surgeon must be able to identify en passage vessels, decide whether a vessel has important perinidal branches, locate the border between nidussupplied tissue and normal brain, determine the direction of flow within a vessel, and distinguish vessel borders underneath an arachnoid layer that may be considerably thickened due to previous hemorrhage or other effects of these congenital lesions. All of these issues can be sorted out, at least hypothetically, by extracting a signal intrinsic to the AVM vasculature or abnormal nidus tissue. It is well known that nidus tissue lacks capillary beds and is nonfunctional; these and other characteristics differentiate it from the normal tissue surrounding the lesion. Intraoperative optical imaging allows mapping of active brain regions by measuring
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changes in cortical light reflectance caused by activity-dependent perfusion and metabolic alterations. It seems reasonable that a future optical imaging system could detect intrinsic signal differences between normal tissue and abnormal nidal tissue on the basis of the metabolic and perfusion profiles of these tissues. Furthermore, it may be possible for optical imaging to eventually distinguish reflectance differences between blood vessels laid against a background of nidus tissue. An innocuous agent with reflectance-changing properties, unable to cross the BBB, might even be used to accentuate the intrinsic signal differences between the vessels and tissue in an AVM. As optical imaging begins to move into the clinical arena, infrared imaging is being examined as an intraoperative tool for AVM surgery. At temperatures greater than absolute zero, all matter emits electromagnetic radiation (photons) at wavelengths within the infrared spectrum. The intensity of this infrared radiation is proportional to temperature. Although it first emerged in the 1960s, medical infrared imaging has been limited by poor resolution and temperature discrimination. Technological advances are finally allowing this methodology to find practical clinical applications. Recent studies have provided evidence for the viability of infrared imaging as an intraoperative tool in neurosurgery (8–11). This technique has several assets. Circulating blood is maintained at a relatively consistent temperature. Therefore, blood vessels will continually emit infrared radiation. The perfusion of warm blood through capillary beds maintains tissue temperature. Thus adequately perfused tissue will also emit a consistent infrared signal. Infrared imaging has many potential uses in AVM resection. It provides a tool for examining cerebrovasculature in real time during the procedure. It can be used to demonstrate occlusion of a vessel (reduced flow causes a decrease in vessel temperature) and also will reveal any tissue regions with compromised flow (they will demonstrate gradual decreases in temperature when perfusion is reduced). Furthermore, infrared imaging can help map out the margins of an AVM, since the lesion itself is slightly cooler than the well-perfused perinidal tissue. Finally, this imaging modality has the potential to demonstrate hyperemia in adjacent tissue. All of these applications have been demonstrated to be feasible in animal research. ADVANCED OPERATING SUITE With the inexorable proliferation of data, a necessary goal for the future will be organizing that data to maximize its surgical usefulness without creating information overload. This objective can be achieved through seamless, dynamic integration of information directly into the surgical microscope. The surgical microscope will be considered not only a tool, but also a platform for the deployment of imaging technologies and presentation of imaging data directly to the operator. A surgeon who wants to consult the radiographic images during a procedure currently must disengage from the surgical field to view them. A much more effective system would allow imaging data to be seen directly within the eyepieces of the operating microscope. The exact presentation of these images could take several forms. First, a static display of images could be displayed in the periphery. There would also be a mechanism for the surgeon to scroll through the available scans to find the appropriate image. A more sophisticated system might allow presentation of dynamic 3-D images. In this case, the surgeon might be able to rotate the 3-D image to select the most useful perspectives. Furthermore, instead of (or perhaps in addition to) the peripheral display, an ‘‘augmented reality’’ system could be used. Augmented reality is the idea of superimposing transparent 3-D images over the actual view of the surgical field (12). Computer software is responsible for the accurate registration of the image. The benefit of augmented reality is that such a system could highlight structures that are not visible in the surgeon’s line of sight or that are hidden beneath the tissue surface. Obviously, considerable technological hurdles must be overcome for augmented reality to become feasible. The operating microscope will also be a platform for deploying and displaying real-time intraoperative imaging. The intraoperative imaging systems discussed earlier could be mounted directly onto the microscope and targeted along the surgeon’s current line of sight. This imaging data could then be viewed within the microscope’s eyepiece. Positional information from navigation-integrated tools could also be fed into the eyepiece. These surgical instruments would be tagged so that their position in space could be tracked. The position
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of the instruments is then compared to fiducials placed around the patient’s skull. The fiducials are used as landmarks to allow registration with imaging data. This process will allow the surgeon to view the position of his or her instrument mapped onto whatever imaging data is available. Such subtle understanding of instrument position allows increased precision, helping to avoid accidental vessel injury when structures are hidden from view. These predictions are not unbridled futurism. Microscope-integrated navigation systems, navigationintegrated instrument tracking, and microscope-mounted intraoperative imaging hardware already exist. Companies such as Medtronic, BrainLAB, Leica, GE Healthcare, and others have developed commercially available versions of one or more of these systems. Preliminary reports of novel image-guided AVM surgeries have been published (13–15).
CONCLUSION Although technological progress will spur the continued evolution of AVM surgery, this progress comes with a price. All new technology is associated with significant costs. It is likely that this factor will lead to further centralization of care for these complex patients. Fewer centers will be able to develop the financial resources to purchase the advanced operating suite with integrated imaged guidance and navigation including instrument tracking. This problem also raises the question of whether untested technologies should be purchased before thorough testing to determine their efficacy. Historically, new technologies are adapted into the therapeutic armamentarium well before definitive impact on the disease under attack is demonstrated. This approach may no longer be tolerable given the financial constraints in medicine. Moreover, an AVM is a relatively rare lesion, and it is unlikely that even the busiest neurovascular centers will have more than 50 AVMs treated microsurgically each year. Does this kind of volume justify the kind of expense that may be posited? It will be critical to ensure that the surgical advances have applicability to other aspects of neurosurgery as well as to other surgical disciplines. Flexibility will have to be established in the way imaging devices are managed so that they can be used productively throughout the day for outpatients or inpatients when they are not being deployed in the operating room. The use of tracks to either move the imaging device or move the patient under anesthesia will facilitate this efficiency. Finally, it is worth reflecting on how these technological advances will affect the training of future cerebrovascular surgeons. While these new innovations will provide surgeons with reproducible, objective, and precise information, can they serve as proxies for the decades of experience a senior surgeon might have in dealing with the vagaries of AVM physiology? Will we create surgeons who rely too heavily on technology and lose the hard-earned ‘‘intuitive sense’’ that something is beginning to go wrong? During this transitional period, it will be critical for a senior surgeon to embrace the new technology but to ensure that these new tools supplement, not supplant, the essential components of surgical teaching experience and intuition born from years and decades of trials and tribulations with occasional victories.
REFERENCES 1. Cushing H, Bailey P. Tumors Arising from the Blood Vessels of the Brain: Angiomatous Malformations and Hemangioblastomas. Springfield (IL), Baltimore: C. C. Thomas, 1928. 2. Benoit JP, Faisant N, Venier-Julienne MC, Menei P. Development of microspheres for neurological disorders: from basics to clinical applications. J Control Release 2000; 65(1–2):285–296. 3. Veziers J, Lesourd M, Jollivet C, Montero-Menei C, Benoit JP, Menei P. Analysis of brain biocompatibility of drug-releasing biodegradable microspheres by scanning and transmission electron microscopy. J Neurosurg 2001; 95(3):489–494. 4. Nakayama N, Kuroda S, Houkin K, Takikawa S, Abe H. Intraoperative measurement of arterial blood flow using a transit time flowmeter: monitoring of hemodynamic changes during cerebrovascular surgery. Acta Neurochir (Wien) 2001; 143(1):17–24. 5. Hademenos GJ, Massoud TF. The Physics of Cerebrovascular Diseases: Biophysical Mechanisms of Development, Diagnosis, and Therapy; with foreword by Fernando Vinuela. New York: Springer, 1998. 6. Gasser T, Ganslandt O, Sandalcioglu E, Stolke D, Fahlbusch R, Nimsky C. Intraoperative functional MRI: implementation and preliminary experience. Neuroimage 2005; 26(3):685–693.
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7. Sutherland GR, Kaibara T, Wallace C, Tomanek B, Richter M. Intraoperative assessment of aneurysm clipping using magnetic resonance angiography and diffusion-weighted imaging: technical case report. Neurosurgery 2002; 50(4):893–897; discussion 897–898. 8. Ecker RD, Goerss SJ, Meyer FB, Cohen-Gadol AA, Britton JW, Levine JA. Vision of the future: initial experience with intraoperative real-time high-resolution dynamic infrared imaging. Technical note. J Neurosurg 2002; 97(6):1460–1471. 9. Gorbach AM, Heiss JD, Kopylev L, Oldfield EH. Intraoperative infrared imaging of brain tumors. J Neurosurg 2004; 101(6):960–969. 10. Okudera H, Kobayashi S, Toriyama T. Intraoperative regional and functional thermography during resection of cerebral arteriovenous malformation. Neurosurgery 1994; 34(6):1065–1067; discussion 7. 11. Watson JC, Gorbach AM, Pluta RM, Rak R, Heiss JD, Oldfield EH. Real-time detection of vascular occlusion and reperfusion of the brain during surgery by using infrared imaging. J Neurosurg 2002; 96(5):918–923. 12. Shuhaiber JH. Augmented reality in surgery. Arch Surg 2004; 139(2):170–174. 13. Coenen VA, Dammert S, Reinges MH, Mull M, Gilsbach JM, Rohde V. Image-guided microneurosurgical management of small cerebral arteriovenous malformations: the value of navigated computed tomographic angiography. Neuroradiology 2005; 47(1):66–72. 14. Unsgaard G, Ommedal S, Rygh OM, Lindseth F. Operation of arteriovenous malformations assisted by stereoscopic navigation-controlled display of preoperative magnetic resonance angiography and intraoperative ultrasound angiography. Neurosurgery 2005; 56 (suppl 2):281–290; discussion 290. 15. Zamorano L, Matter A, Saenz A, Portillo G, Diaz F. Interactive image-guided surgical resection of intracranial arteriovenous malformations. Comput Aided Surg 1998; 3(2):57–63.
Index
Activin receptor-like kinase (Acvrl1), 474 angiogenesis, 475 Akinetic mutism, 398 Amobarbital testing, 222–224 Analgesia, for AVM patients, 389–390 Anatomic parameters, of AVMs, 11–18, 83–84 basal ganglia region, 11–18 callosal region, 9–11 frontal lobe, 1–2 mediobasal temporal lobe, 5–9 occipital lobe, 4–5 parafalcine, 9–11 parietal lobe, 2–3 temporal lobe, 3 Anesthetic management, during neuroradiological procedures, 206–211 anticoagulation, 209 blood pressure augmentation, 211 complications, 210–211 embolic material injection, 210 intravenous vs. general anesthesia, 207, 209 Anesthetic management, during surgery, 201–206 intraoperative, 203–206 postoperative, 206 preoperative, 203 Aneurysms abnormal flow dynamics, 344 arachnoidal phase of, 153 arterial, 289, 343 associated, 343–348 AVMs, 347 classification, 343 electrophysiological monitoring, 150 embolization, 149, 346 flow-related, 343 formation of, 34–35 frameless stereotactic guidance systems, 148 functional magnetic resonance imaging (FMRI), 147 intracerebral hematoma, 151–152 intranidal, 346 parenchymal dissection, 154 pathophysiology of, 344 polyvinyl alcohol (PVA), 192 proximal and pedicular, 345 stereotactic radiosurgery, 346 symptomatic intranidal, 349 time-of-flight (TOF) images, 104 unrelated, 344–345 venous outflow obstruction, 146 Angioarchitecture, of AVMs, 21–23, 77 Angiogenesis, 469–470 vascular endothelial growth factor (VEGF), 47 Angiography alternatives to, 334–335 cerebral, 329 evaluation of, 223, 262 intraoperative, 329–336 postoperative, 337–341 Angiomatous hemorrhage, 383 by cerebral salt wasting (CSW), 388
[Angiomatous hemorrhage] complications cerebral edema, 383 cerebral ischemia, 383 hydrocephalus, 383 hypothalamic injury, 386 Anterior paramedian frontal AVMs, 229 Anticoagulation, thromboembolic complications of, 166 Archicerebellum nystagmus, 289 truncal ataxia, 289 Aphasia, 398 Arnold-Chiari malformation, 303 Arrhythmias, management of, 386–387 Arterio-capillary-venous hypertensive syndromes, 41–42 Arteriovenous malformations (AVMs), cerebral asymptomatic, 259 classification of, 81, 162, 290, 299 clinical trials designing, 59 complications, 383, 390 computed tomography (CT) and, 385 congenital, 117 definition, 49 embolization. See also Embolization of AVMs. feeding artery pressure, 55 genetic syndromes Bannayan syndrome, 26 Sturge-Weber syndrome, 26 Wyburn-Mason syndrome, 27 grading scales for, 408 grading systems, 85–87, 90–91, 162 Drake, 85 Ho¨llerhage, 90–91 Luessenhop and Gennarelli, 84–85 Luessenhop and Rosa, 86–87 Malik, 91 Pelletieri, 85 Pertuiset, 90 Shi and Chen, 88–89 Spetzler and Martin, 87, 128–129, 225 Tamaki, 89–90 hemianopsia, 400 hemiparesis, 400 hemorrhage, 408. See Hemorrhage hemorrhagic presentation, 66 hemorrhagic risk estimation, 57 hyperemia, 55 infratentorial, 187, 299 intracranial pressure (ICP) monitoring, 383 ischemic injury and arrhythmias, 386 magnetic resonance imaging (MRI), 146, 384 Mendelian forms of, 471 midbrain/pontomesencephalic, 319 models, 51, 60–62 morbidity rate, 259 mortality rate, 259 occipital transtentorial approach, 293 paraventricular, 259 pericallosal, 273
492 [Arteriovenous malformations (AVMs), cerebral] perisylvian, 243 pregnancy, AVM during, 77, 351–355 regrowth, 402 residual, 78, 371, 399, 487 Rolandic cortex, 266 rupture risk estimation, 57 steal phenomenon, 31, 384, 394 stereotactic radiosurgery. See Stereotactic radiosurgery suboccipital craniotomy, 293 supratentorial, 245, 259, 315 surgical grading system, 96–97 surgical treatments of, 127–128, 399–400 decision analysis tree, 129 Spetzler-Martin grade system, 127 stereotactic radiosurgery (SRS), 128 treatment options, 96–97, 290–295 symptomatic, 259 transcranial Doppler ultrasonography (TCD), 384 vascular stress, 67 xenon CT, 385
Bannayan syndrome, 26 Basal ganglia region AVMs, anatomy of, 11–12 anteroinferior limit, 12 lateral limit, 13–14 medial limit, 16–18 superior limit, 18 Blood flow analysis, 117 MRA techniques, 120 Blood pressure augmentation, during surgery, 211 control, during surgery, 386 in patients with AVMs, 119, 388 Bonnet-Blanc-Dechaume syndrome. See Wyburn-Mason Syndrome Brainstem AVMs anesthetic technique, 317 angiography, 316 circumferential dissection, 323 classification, 315 clinical grades, 326 hydrocephalus, 327 infratentorial supracerebellar approach, 323, 326 lateral suboccipital approach, 322 microsurgical resection, 326 perioperative complications, 326 perioperative equipment/techniques, 323–324 postoperative management, 323 preoperative embolization, 324 preoperative preparation, 317 stereotactic radiosurgery, 324 suboccipital midline approach, 319 subtemporal and orbitozygomatic approach, 323 surgical candidacy, 316–317 sylvian fissure, 323 See also Surgical approaches Brainstem auditory evoked potential (BAEP), 323 Brain swelling, 399–400 obstructive hydrocephalus, 402–403 occlusive hyperemia, 402–403 occult bleeding, 402 Broca’s aphasia, 254 Bucrylate (isobutyl–2–cyanoacrylate), 25
Index Cahan criteria, 445 Calcitonin gene-related peptide, 203 Calibrated leak balloon technique, 160 Callosal region AVMs, anatomy of, 9–11 Callosal syndrome.See Split-brain syndrome. Cebellopontine angle AVMs, 302 Cerebellar vermis and hemispheres, AVMs of, 285–295 anatomy, 285–289 clinical presentation, 289 classification, 289–290 treatment, 290–295 Cerebellopontine angle (CPA) AVMs, 285, 299, 303–305 diagnosis, 303 excision of, 304, 306 subarachnoid hemorrhage (SAH), 302 surgical techniques, 305–307 vascular complications, 310 Cerebral angiography, 329 carotid artery bifurcation, 329 cerebral edema, 330 complications of, 336 intraoperative, 330 microsurgical resection of, 332 postoperative, 337 Cerebral arterial hypotension, 202 Cerebral blood flow (CBF), 116, 202–203, 483 brain AVMs on, 37 measurements techniques, 37 Cerebral blood volume (CBV), 119 Cerebral cavernous malformations (CCMs), 473, 472, 477–478 Cerebral edema, perioperative, 384–386 Cerebral hyperemia, 55 Cerebral hyperperfusion, 204 Cerebral ischemia, regional, 205 Cerebral perfusion pressure (CPP), 400 Cerebral salt wasting (CSW), 388 Cerebral vascular anomalies, 21 classifications, 407 Cerebrovascular steal, 31, 95–96, 108–109 Charbel Micro-flowprobe1, 319 Choroid plexus, 301 Chromosome 9q33–q34, 26 Clopidogrel bisulfate, 173 Columbia-Presbyterian AVMs study project, 76 Corpus callosum AVMs, 273–282 anatomy, 274–275 classification systems, 277–278 surgical outcome, 277–278 topographic, 277 venous drainage, 277 clinical presentation, 275 epidemiology, 273–274 function of, 275 grading system, 277–278 modified Rankin score (mRS), 281 Picard’s classification, 277 treatment, 278–282 Yasargil’s classification, 277 Cosman-Roberts-Wells system, 395 Craniotomy, 226, 383 Cyanoacrylate, 421
Deep venous thrombosis (DVT), 390 Deliberate hypertension, during surgery, 211 Dexamethasone, 307 Diabetes insipidus (DI), with brain injury, 388 Diabetic management, of AVM patients, 388–389
493
Index Digital subtraction angiography (DSA), 329, 330, 486 Draining vein pressure (DVP), 53 Drake grading scale, 85
Edema, post-radiosurgery, 434–435 Electrolyte management, in AVM patients, 38 Embolization, 409 adjunctive, 372–373 arterial, 182, 223, 336 brainstem AVMs, 324–326 complications, avoidance, 425–426 curative, 373–372, 411–413 embolic agents, 421–422, 452–454 hemorrhage, 410 intraoperative, 336–337 N-butyl-cyanoacrylate (NBCA), 409 palliative, 372–373, 413–414 pediatric, 364–365 treatment, 411, 413, 421, 424 Endoglin, 474 Endovascular embolization, residual malfomations and, 372–375 Endovascular principles, 159–172 Endovascular techniques, 451–455 Endovascular therapy, 407–424 Epilepsy, in AVMs, 76 Ethylene vinyl alcohol copolymer (Onyx), 160, 172
Feeding mean arterial pressure (FMAP), 53, 66 Femoral artery sheath, 332 Fibroblast growth factor–2 (FGF2), 359 Flickinger logistic equation, 441 Flow-directed microcatheters, 160 Flow-related aneurysms, 343 Flow-related enhancement (FRE), 104 Fluid and electrolyte management, of AVM patients, 387 Fluorodioxyglucose (FDG), 116 Fractionated stereotactic radiotherapy, 183. See also Radiotherapy; Stereotactic radiotherapy. Frontal horn lesions, 261 Frontal lobe AVMs anatomy, 3, 228 presentation, 228–229 radiographic evaluation, 229 surgical management, 229–231 Furosemide, 355
Gamma knife radiosurgery, 177, 182, 459 Gelfoam1, 265 Genetic factors, 25–26, 471–478 Glucocorticoids, 183, 205, 390 Gradient-recalled echo (GRE) imaging, 100 Gravity and retraction, on occipital lobe effects, 236 Guglielmi detachable coil, 306
Harvard cyclotron laboratory experience, 442, 443 Hemifacial spasm, 303 Hemorrhage, 168, 182, 225 incidence, 74 intraventricular, 260 morbidity and mortality, 75 radiosurgery and, 430–434 risk of, 74, 182, 225, 430, 431 subarachnoid, 260
Hemorrhagic telangiectasia (HHT), 22 Hemosiderin pigment, 24 Hereditary hemorrhagic telangiectasia (HHT), 473, 474 Hippocampal vein, longitudinal, 234 Ho¨llerhage grading scale, 90–91 Homonymous hemianopsia, 237 Hydrophilic catheters, 452 Hyperemia, 41, 401 complications, postoperative, 204 Hyperkalemia, 388–389 Hypoglycemia, 205 Hyponatremia, 388 Hypothermia, for cerebroprotection, 324
Infectious diseases, in patients with AVMs, 389 Inferior temporal gyrus, 231 Inferior ventricular vein, 233 Infratentorial cerebellopontine angle AVMs, 299–311 anatomy, 299–302 clinical presentation, 302–303 diagnosis, 303–304 surgical complications, 310–311 surgical technique, 305–309 therapy, 304–305 Infundibula, 348 Internal carotid (ICA) arteries, 83, 216 Interstices AVMs, 32 Intracranial hemorrhage (ICH), 394 Intracranial pressure (ICP), 203, 394–395 Intranidal aneurysms, 346–348 Intranidal model, of AVMS, 53 Intraoperative angiography, 223, 251 advantages of, 334 applications of, 329 color Doppler flow ultrasound, 334 frameless stereotaxis resection, 334 Ischemic injury, management of, 386
Karnofsky scale, 89 Kjellberg’s series, 447 Krit1 protein, 473
Leksell system, 395 Linear accelerators (LINACs), 177 Lipiodol, 171 Lobectomy, 236 Lorazepam, 180 Luessenhop and Gennarelli grading scale, 85 Luessenhop and Rosa grading scale, 86, 301
Magnetic resonance imaging (MRI), 177 for AVMs, 117, 303, 340 black holes on, 437 characteristic flow voids, 303 functional, 117 high-resolution, 305 phase contrast (PC), 104 postmicrosurgical, 340 time-of-flight (TOF), 104 types of, 436 Magnetoencephalography (MEG), 224 for AVMs, 117 functional imaging modality, 118 Malignant brain swelling, 202 Malik grading scale, 91
494 Mannitol, 355 Markov modeling of AVMs, 124–125 definition, 125 sensitivity testing, 127 Maximum intensity projection (MIP) reconstructions, 104 Mayfield three-point fixation device, 306 McNemar’s test, 67 Mediobasal temporal lobe AVMs, anatomy of, 5–9 Meningioma, 445 Mesencephalooculo-facial angiomatosis. See Wyburn-Mason syndrome. Mesial lesions drain, 235 Mesial temporal AVM, 219 Microcatheters, 168, 452 development of, 169 flow-directed, 160, 407 types of, 452 wire-guided, 160 Microcoils, 170 Microsurgery for direct visualization of brain, 378 equipment, 227 residual malformations after, 378–379 Microvessel groups (MVGs), 50 Midbrain AVM, 320 Mild hypothermia, 205 effect of, 206 Mini-Wada testing, 224
Natural history of AVMs, 73–78 N-butyl-cyanoacrylate (NBCA), 279, 409, 451 with ethiodol, 422 tantalum powder, 421, 422 Neuret formulation, 441 Nicardipine, 400 Nidus, recurrent, 183 Nidus, residual, 185, 224 Nidus tissue, 378 Nimodipine, 207, 354 Normal perfusion pressure breakthrough (NPPB) bleeding, 223, 383 Nutrition, of patients with AVMs, 388–389 Nystagmus, 289
Occipital horn lesions, 261 Occipital lobe AVMs anatomy of, 4–5, 235 clinical presentation, 235 evaluation, 235–236 surgical management, 236–237 Occipital lobe retraction injury, 236 Occipitotemporal gyri, lateral, 233 Oligodendrogliomas, 22 Ondansetron, 435 Orbitofrontal lesions, 228 in children, 359
Parafalcine AVMs, anatomy of, 9–11 Paraffin-petrolatum mixture, 159 Parahippocampal gyrus, 231 Paramedial lesions, 228 Parasagittal corticotomy, 230 Paraventricular AVMs frontal horn, 265
Index [Paraventricular AVMs] temporal horn lesions of, 268 thalamostriate regions, 269 third ventricle, 269 trigone and occipital horn, 266 Parenchymal perisylvian hemorrhage, 244 Parietal lobe AVMs anatomy of, 3–4, 233–234 evaluation, 234 presentation, 234 surgical approaches, 234–235 Parinaud’s syndrome, 289 Pathology, 21–24 Pediatric AVMs, 359–368 clinical signs, 359–360 developmental biology, 359–360 embolization, preoperative, 364–365 epidemiology, 359 evaluation techniques, 361–363 FGF2 expression in, 360 intervention criteria, 363–364 management, 359 natural history, 360–361 outcomes, 367–368 presentation and evaluation, 361–363 Spetzler-Martin grading scheme, 363 surgical techniques, 366 transforming growth factor-b1 expression, 360 treatment, 364–365 VEGF expression in, 360 Pedicular aneurysms, 343 for AVMs, 85 endovascular strategies, 349 management of, 345 Pericallosal AVM angio-architecture of, 277 definition, 273 Picard’s classification, 277 prevalence of, 273, 274 radiosurgical treatment, 281 Periembolic inflammation, 173 Perioperative prophylactic anticonvulsants, 183 Perisylvian AVMs, 243 diagnostic techniques, 245–246 electroencephalogram (EEE), 246 pterional/anterior temporal craniotomy, 247 pterional/anterior temporal transylvian approach, 246 stereotactic craniotomy, 251 superconducting quantum interference devices (SQUIDs), 245 sylvian fissure, 243 symptoms, 244 treatment, 245 Periventricular AVMs frontal horn, 261 occipital horn, 261 surface anatomy, 260 temporal horn, 261 therapeutic treatment of, 263 third ventricle, 262 trigone and occipital horn, 261 Pertuiset grading scale, 90 Phase contrast (PC) magnetic resonance imaging, 104 Poiseuille’s equation, 33 Polyvinyl alcohol, 160, 170, 372 Positron emission tomography (PET), for AVM, 115, 117, 224 Postembolization angiogram, 162
Index Posterior cerebral artery (PCA), 50, 145, 218 cortical distribution, 288 occlusion of, 150 Postoperative angiography, 265, 337–338 dysplastic vessels, 338 hemorrhage, 338 hyperperfusion, 338 noninvasive method, 340 Postradiosurgery injury expression (PIE) score, 438 Pregnancy, AVMs in, 351–356 cerebral blood flow, 352 embolization procedures, 355 epidemiology, 137 ethical considerations, 355 hormonal changes, 352 medical management, 353–354 pathologic conditions, 352 physiologic changes, 351–352 prevalence of, 351 radiologic diagnosis, 352–353 radiosurgical procedures, 352–353, 355 radiotoxicity, 353 Spetzler-Martin scale, 354 surgical management, 354–355 symptoms of, 352 Propofol infusion, in children, 390 Proximal aneurysms, 345, 347 Pseudoaneurysm, 162
Radiation, 226 necrosis, 184 side effects of, 226, 435, 440 Radiation-induced neurologic deficits, permanent, 226 Radionecrosis, 440–446 Harvard cyclotron experience, 442–444 Treatment of, 444 Radiosensitizers, 184 Radiosurgery. See Stereotactic radiosurgery Rayleigh distribution function, 65–66 Receptor tyrosine kinase (RTK), 470 Rendu-Osler-Weber syndrome, 473 Residual AVMs, 371–374 definition, 371 diagnosis, 371 endovascular embolization and, 372 management, 369–380 retreatment for, 446 Reynold’s shear stress measurement, 32
Sedation, of AVM patients, 389–390 Seizures, in AVM patients, 76, 390 post-radiosurgery, 435–436 Seldinger technique, 168 Sensorimotor cortex, 230 Shi and Chen grading scale, 88–89 Siderosis, 303 Significant postradiosurgery injury expression (SPIE), 439 Sodium nitroprusside (SNP), 167 Somatosensory evoked potential (SSEP), 323 Spetzler-Martin grading, 124, 128–129, 225 brain AVMs, 140 and stereotic radiosurgery (SRS), 128 Sphenoid ridge, lateral, 230 Sphenoparietal sinus, 233
495 Sporadic AVMs, 475 Staged volume radiosurgery, 463 with hemorrhage, 463 sub-lethal deoxyribonucleic acid, 463 Stereotactic headframe, placement of, 180 Stereotactic linear accelerator radiosurgery, 440 Stereotactic magnetic resonance imaging (MRI), 180 Stereotactic radiosurgery, 177–183, 429–440, 457–463 application of, 201 brainstem AVMs, 324, 461 cerebral AVMs, 128, 457 complications, 429–446 brain tissue effects, 434–440 hemorrhage, 430–434 radionecrosis, 440–446 cyberknife, 178 gamma knife, 459 image-guidance system, 178 imaging changes, 436–439 indications for, 458 magnetic resonance angiography (MRA), 459 magnification subtraction angiograms, 459 management of, 435 pathologic changes, 178 in pediatric patients, 365 post-radiosurgery complications, 461 prophylactic, 469–471 radiobiology, 177–178, 457–458 radionecrosis, 440–446 repeat radiosurgery, 463 residual malformations after, 375–378 single-fraction irradiation, 457 Spetzler-Martin grade for, 128, 458, 465 staged volume radiosurgery, 463 Sturge-Weber syndrome, 25 characterization, 26 clinical manifestations, 27 pathological examination, 27 Subarachnoid hemorrhage (SAH), 201, 252, 351 Suboccipital craniotomy, 291–293 Superior sagittal sinus (SSS), 228 Superior temporal gyrus, 231 Superselective angiography, 262 Superselective catheterizations, 452 Supratentorial lobar AVMs, 215–237 anatomy, 215–220 clinical presentation, 220–221 decision analysis, 225 evaluation, 221–225 radiosurgical management, 225–226 surgical techniques, 226–228 Supratentorial periventricular AVMs, 259–270 anatomy, 260–261 epidemiology, 259–260 patient evaluation, 262–263 surgical approaches, 264–269 therapy, 263 Surgical approaches, 483–489 brainstem AVMs far lateral approach, 322–323 infratentoprial supracerebellar approach, 323 orbitozygomatic approach, 323 suboccipital midline approach, 319–322 subtemporal approach, 323 frontal lobe AVMs, 229–231 infratentorial cerebellopontine angle AVMs, 305–309 occipital lobe AVMs, 235–236 parietal lobe AVMs, 234–235 pediatric patients, 366
496 [Surgical approaches] supratentorial lobar AVMs, 226–228 supratentorial periventricular AVMs, 264–269 temporal lobe AVMs, 232 Surgical principles, 145–157 Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), 388
Tamaki grading scale, 89 Tantalum powder, 171, 421, 422 Temporal horn lesions, 261–262 Temporal lobe AVMs anatomy, 3, 231 clinical presentation, 231–232 evaluation, 232 surgical approaches, 232 Third ventricle lesions, 262 Three-dimensional rotational angiography, 160 Thrombogenic endothelial damage, 166 Thrombotic complications, in AVM patients, 390 Time-of-flight (TOF) magnetic resonance imaging, 104 Tocodynomanometer, 355 Transcranial Doppler ultrasonography, 384 Transfemoral coaxial catheter, 208 Transforming growth factor–b (TGF–b), 471 Trigeminal neuralgia, 302, 303 Trigone lesions, 261 Trufil, 421, 422. See also N-butyl-cyanoacrylate (NBCA) Truncal ataxia, 289
Index Vascular endothelial growth factor (VEGF), 24,359, 360 Vascular malformation radiosurgery, 457 Vascular thrombosis, 401 Vasculogenesis, 469 Vasoparalysis, 202 Vein of Galen aneurysmal malformations (VGAM), 359 Venous drainage, 219, 290, 380 in posterior fossa, 290 sagittal, 219 sigmoid sinuses, 219 sphenoparietal, 219 transverse, 219 Venous malformations, cutaneous and mucosal (VMCM) AVMs, 471, 472 Venous occlusion, 374 Venous stenosis, 223 Venous thrombosis, 173 Vermian AVMs, 18 Vessel dissection, 169
Wire-guided microcatheters, 160 Wyburn-Mason syndrome, 25, 359
Xenon CT, 384
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Figure 1.1 (A) Anatomical venous dissection of the right cerebral hemisphere: 1. Vein of Trolard; 2. superficial sylvian vein; 3. vein of Labbé. (C) Intraoperative view of the same patient showing the enlarged superficial veins that drain the AVM.
Figure 1.2 (A) Anatomical dissection of the brain with the frontal lobes removed to the level of the anterior perforated substance to expose the anterior portion of the poligone of Willis: 1. Corpus callosum; 2. lateral ventricle; 3. basal ganglia; 4. M2 branches of the middle cerebral artery; 5. anterior communicating artery; 6. recurrent artery of Heubner; 7. lenticulostriate arteries; 8. M4 segment of the middle cerebral artery; 9. M1 segment of the middle cerebral artery; 10. A1 segment of the anterior cerebral artery; 11. Internal carotid artery.
Figure 1.3 (A) Anatomical dissection of the posterior cerebral artery and its branches (viewed from the basal surface of the brain): 1. Internal carotid artery; 2. posterior communicating artery; 3. anterior choroidal artery; 4. posterior cerebral artery; 5. Posterior thalamoperforating artery; 6. medial posterior choroidal artery; 7. anterior temporal artery; 8. medial temporal artery; 9. posterior temporal artery; 10. parietooccipital artery; 11. calcarine artery. (D) Digital vertebral angiogram of a right-sided posterior mediobasal temporal lobe AVM.
Figure 1.4 (A) Anatomical dissection of the medial aspect of the left cerebral hemisphere. 1. Cingulate gyrus; 2. body of corpus callosum; 3. splenium of corpus callosum; 4. genu of corpus callosum; 5. rostrum of corpus callosum; 6. body of lateral ventricle; 7. fornix; 8. internal cerebral vein; 9. vein of Galen; 10. third ventricle; 11. anterior cerebral arteries.
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Figure 1.5 (A) Anatomical dissection of the right cerebral hemisphere. 1. Cingulate gyrus; 2. body of corpus callosum; 3. genu of corpus callosum; 4. rostrum of corpus callosum; 5. fornix; 6. splenium of corpus callosum; 7. right anterior cerebral artery; 8. third ventricle; 9. internal cerebral vein; 10. vein of Galen; 11. straight sinus. (C) Anatomical dissection of the brain where both hemispheres were separated in the midline to show the interhemispheric course of the anterior cerebral arteries. The optic chiasm was displaced inferiorly to show the anterior communicating-anterior cerebral artery complex. 1. Orbital surface of the frontal lobe; 2. olfactory nerve; 3. gyrus rectus; 4. corpus callosum; 5. right anterior cerebral artery; 6. anterior communicating artery; 7. right middle cerebral artery; 8. internal carotid artery; 9. optic chiasm; 10. posterior cerebral artery.
Figure 1.6 (A) Anatomical dissection of the neural and arterial structures of the interhemispheric aspect of the right cerebral hemisphere: 1. Superior frontalgyrus; 2. cingulate gyrus; 3. precuneus; 4. corpus callosum; 5. fornix; 6. splenium of the corpus callosum; 7. parietooccipital sulcus; 8. cuneus; 9. anterior cerebral artery; 10. lamina terminalis; 11. third ventricle; 12. posterior medial choroidal artery; 13. parietooccipital artery; 14. calcarine artery; 15. calcarine fissure; 16. optic chiasm; 17. cerebral peduncle; 18. internal carotid artery; 19. posterior cerebral artery.
Figure 1.7 (A) Anatomical dissection of the brain where the right frontal lobe was removed at the level of the anterior perforated substance in order to expose the basal ganglia. In the left cerebral hemisphere the frontal and the parietal lobes have been removed, and the insula and basal ganglia were sectioned along the choroidal fissure to expose the course of the posterior cerebral artery and of the vein of Labbé in the ambient cistern: 1. Calcarine artery; 2. choroid plexus; 3. M2 branches of the middle cerebral artery; 4. fimbria of the fornix; 5. temporal horn; 6. posterior cerebral artery; 7. basal vein of Rosenthal; 8. middle cerebral artery; 9. internal carotid artery; 10. anterior cerebral artery; 11. lenticulostriate arteries; 12. lenticular nucleus; 13. internal capsule; 14. caudate nucleus; 15. vein of Galen. (C) Medial anterior basal ganglia AVM. Right side (anteroposterior) digital carotid angiogram showing a basal ganglia AVM located in the head of the right caudate nucleus.
Figure 1.8 (A) Anatomical dissection showing the venous drainage pattern of the right cerebral hemisphere. 1. Body of corpus callosum; 2. body of lateral ventricle; 3. splenium of corpus callosum; 4. internal cerebral vein; 5. vein of Galen; 6. straight sinus; 7. basal vein of Rosenthal (cut); 8. third ventricle; 9. posterior cerebral artery.
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Figure 2.1 Gross appearance of a cerebral arteriovenous malformation in the occipital lobe. Source: Courtesy of Dr. J.H. Kim.
Figure 2.2 Histologic appearance of cerebral arteriovenous malformation nidus. Hematoxylin and eosin stain, 40x. Thrombosed red blood cells (red); arterialized vessel walls (purple); gliotic brain (blue). Source: Courtesy of Dr. J.H. Kim.
Figure 2.3 Histologic demonstration of elastic fibers in the arterialized vessels of a cerebral arteriovenous malformation. Elastic von Gieson stain, 40x. Source: Courtesy of Dr. J.H. Kim.
Figure 2.4 Immunohistochemical analysis of arteriovenous malformation (AVM) vessels. (A) Laminin (a component of the basement membrane that regulates vessel wall stability) immunoexpression in an AVM vessel, 20x. (B) VEGF immunoexpression in an arterialized draining vein of an AVM specimen, 40x. (C) Flk-1 (an endothelial-specific receptor tyrosine kinase) immunoexpression in the endothelium of an AVM vessel, 40x.
Figure 3.1 Profile of the pressure along the length of the vascular pathway in the brain. The maximal deviation from the normal is where resistance in the AVM is no greater than that of the arterial system (straight fistula). The vasculature within the sphere of influence of the AVM will deviate from normal and toward this curve. On occlusion of the fistula, the curve will move towards the maximal response anticipated, which will be above the normal curve, because the arteries have a larger diameter than is normal (see text). In addition, the pulsatility will increase above normal because of the increased reflectance. Abbreviations: AVM, arteriovenous malformation; lCA, intemal carotid artery; A1, M1, P1, pressure in these arteries; AVM or capillary, pressure at the level of the AVM or capillary.
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Figure 3.2 Model of possible arterio-capillary-venous units coming under the influence of an AVM. (A) The pressure within the artery and vein of the AVM drop over a short distance at the point of turbulence within the AVM and at the point of venous stenosis (if this exists). (B) The quantification of this pressure drop is variable. As shown in (A) parenchymal arteries and veins can arise at a distance (1 = artery branch; 4 = venous tributary) or in close proximity (2 = artery branch; 3 = venous tributary) to the fistula, producing the four classes of arterio-capillary-venous units: A, B, C and D. Pressure profiles will be determined by the specific parenchymal vascular pathway, and many such profiles will be present around an AVM. Examples of such profiles are illustrated by the pressure profiles between points 1 and 3, points 1 and 4, points 2 and 3, and points 2 and 4, representing the various arterio-capillary-venous units, shown in (B). With occlusion of the fistula the pressure profile within the arterio-capillary-venous units will rise towards the line indicating “profile from maximal effect from fistula ablation,’’ which is higher on the arterial side and lower on the proximal venous side than normal because of the dilatation of the vasculature (see text). Thus, at any one point in the arterio-capillary-venous unit, the pressure after ligation can be traced with a vertical line from the arterio-capillary-venous unit to the post-ligation pressure. It should also be remembered that these lines represent mean pressures and peak pressures, and the increase in pulsatility will be even greater. Abbreviations: AVM, arteriovenous malformation; ICA, internal carotid artery; A1, proximal anterior cerebral artery; M1, proximal middle cerebral artery; P1, proximal posterior cerebral artery.
Figure 8.1 Functional MRI and PET scan. (A) Two T1-weighted axial MR images, of which the second image shows the nidus as a faint area of increased signal intensity to the right of midline in the frontal lobe. The colored pixels represent areas of activation from left foot motion. (B) Four axial images from an FDG-PET study with increased metabolic activity medially adjacent to the arteriovenous malformation generated by left foot motion. Together these studies confirm the close approximation of the nidus to eloquent cortex. Abbreviations: PET, positron emission tomography; MRI, magnetic resonance imaging; FDG, fluorodioxyglucose.
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Figure 8.2 Magnetoencephalography. The image depicts magnetic mapping points superimposed on the patient’s T1-weighted magnetic resonance image. The indicated activity was derived from somatosensory stimulation of the left second toe and is marked as a solid square. The surrounding circle represents a statistical confidence volume (closer to the square being greater confidence). Thus, the nidus straddles not only the anatomic central sulcus, but also the functionally defined one shown here, centered over the leg region. Source: Courtesy of Howard A. Rowley, UCSF Medical Center.
Figure 11.1 (A) Intraoperative view of right insular cortical arteriovenous malformation demonstrating multiple middle cerebral artery branches.
Figure 11.4 (A) Intraoperative view demonstrating thickened arachnoid overlying a cortical arteriovenous malformation (AVM). The arachnoidal phase of dissection begins by defining the feeding arterial supply and pial margins if the AVM has cortical representation. (B) Intraoperative view of an AVM with no direct cortical representation demonstrating the value of utilizing the major draining vein as a guide to reach the AVM nidus.
Figure 11.2 (B) Intraoperative view demonstrating a Gug-lielmi detachable coil mass in an anterior cerebral feeding artery placed in anticipation of surgical resection of the AVM. Intraoperative identification of embolized arteries can be useful for intraoperative orientation.
Figure 11.5 Functional magnetic resonance imaging study in a patient with a left hemispheric AVM (small arrow) with displacement of primary motor hand function to the collateral hemisphere (large arrow). Abbreviation: AVM, arteriovenous malformation.
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Figure 11.7 (A) Intraoperative frameless stereotactic guidance can be utilized for optimal bone flap design and selection of the optimal trajectory for surgical resection of an AVM. Abbreviation: AVM, arteriovenous malformation.
Figure 11.11 Intraoperative view of left frontal arteriovenous malformation (AVM) with cortical representation demonstrating circumferential pial coagulation defining the resection margins of the AVM prior to beginning the parenchymal dissection phase.
Figure 11.12 (A) Schematic diagram illustrating systemic parenchymal dissection phase of the arteriovenous malformation (AVM) nidus based on arterial pedicles. (B) Intraoperative view of a cortical AVM with a parenchymal dissection plane (multiple small arrows) developed circumferentially around the AVM nidus, which is still connected via a vascular pedicle consisting of the major draining vein (large arrow).
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Intraoperative views (A and B) demonstrating use of tapered Telfa pledgets to mark dissection planes.
Figure 11.14 (A) Intraoperative view of deep insular AVM with representation to the lateral ventricular surface (arrow). (B) Surgical view after removal of insular AVM, demonstrating the ependymal window into the lateral ventricle (arrow). (C) Schematic diagram of AVM with ventricular representation and periventricular vascular supply. Periventricular vessels can be controlled by circumferentially coagulating the tissue in the ventricular wall. Abbreviation: AVM, arteriovenous malformation.
Figure 12.1 N-butyl-2-cyanoacrylate, Trufill (Cordis Neurovascular Corp., Miami, Florida, U.S.A.). The packaged kit includes lipiodol, which serves as a hydrophobic contrast agent that also delays polymerization time on the basis of the relative concentration of lipiodol to Trufill. A 2:1 lipiodol:Trufill concentration (v:v, or 33%) is a relatively standard concentration, although polymerization time can be made faster or slower by decreasing or increasing the amount of lipiodol added.
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Figure 12.2 Ethylene vinyl alcohol copolymer, Onyx (Micro Therapeutics, Irvine, California, U.S.A.). Currently, two viscosities are approved for the treatment of arteriovenous malformations, Onyx 18 and Onyx 34. Both are prepackaged and require vigorous agitation for 20 minutes to resuspend the tantalum, which serves as the opacifying agent.
Figure 12.5 Guiding catheters. Unlike diagnostic catheters, guiding catheters designed for neurovascular use are specifically made with soft, pliable tips and a braided internal design to provide the necessary pushability and trackability to the catheter, while minimizing the risk of vessel dissection or spasm. Artist rendition of the Envoy guiding catheter exhibiting variable areas of stiffness (Cordis Neurovascular Corp., Miami, Florida, U.S.A.).
Figure 12.6 Microcatheters. Polymer science has resulted in the development of microcatheters that can be safely navigated by over-the-wire techniques or by the flow of blood to distal targets along the cerebral arterial circulation, changing the art and science of AVM embolization. (A) Artist rendition of a Marathon microcatheter, compatible with Onyx use (Micro Therapeutics). (B) Magic microcatheters are the only truly flow-guided microcatheters that can achieve distal positioning in tortuous vasculature (Balt, Montmorency, France). Several varieties of microcatheters exist and are compatible with N-butyl-2-cyanoacrylate.
Figure 13.1
Gamma knife headframe placement.
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Figure 13.2 Arteriovenous malformation radiosurgery treatment plan.
Figure 13.3
Gamma knife radiosurgery treatment delivery.
Figure 16.3 Drawing displaying relative probability of a given frontotemporal region being critical for language function in 117 patients as assessed by stimulation mapping of left dominant hemisphere. Upper number in circle is the percentage of those patients with sites of significant evoked naming errors in that zone, while the lower number is the number of patients with a site in that zone. Source: From Ref. 9.
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Figure 16.7 Right parietal arteriovenous malformation (AVM) resection (same patient as Fig. 6). (A) Use of somatosensory evoked potentials from a hand stimulus site to localize primary somatosensory cortex (C denotes central sulcus). (B) Motor mapping of hand area (H) using a setting of 4 on Ojemann stimulator. (C) Parietal AVM located 1.5 gyri posterior to somatosensory cortex (S). Hand area (H) and central sulcus (C) also labeled. (D) Drawing of circumferential dissection of AVM with isolation, coagulation, clipping, and division of feeding pedicles with Weck clips placed on feeders larger than 0.5 mm. (E) Sundt aneurysm clips used for deep feeders. (F) Clipping and coagulation of final draining vein after inspection confirmed obliteration of all feeders.
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Figure 19.6 Surgical approach for the treatment of pericallosal arteriovenous malformations. (A) Markings for the parasagittal craniotomy. (B) Removal of the bone flap. (C) Dura mater once the bone flap is removed. (D) Dura mater fully exposed. (E) With adequate retraction, the pericallosal arteries can be visualized superior to the corpus callosum. Source: Courtesy of Antonio Bernardo, Cornell University, New York, New York, U.S.A.
Figure 20.1 Surfaces and blood supply of the cerebellum (lateral view). The petrosal, tentorial, and suboccipital surgical anatomic surfaces are shown in relationship to the major vascular and neural structures of the posterior fossa. Note the position of the basilar (BA), posterior cerebral (PCA), superior cerebellar (SCA), anterior inferior cerebellar (AICA), and posterior inferior cerebellar (PICA) arteries relative to the brainstem. Abbreviations: III, oculomotor nerve; V, trigeminal nerve; MCP, middle cerebellar peduncle; Floc, flocculus; VIII, VII, auditory and facial nerves; VI, abducens nerve; IX, X, XI, glossopharyngeal, vagus, and spinal accessory nerves; XII, hypoglossal nerve; HorFiss, horizontal fissure; StrSin, straight sinus; PrimFiss, primary fissure; IV, trochlear nerve; CP, cerebral peduncle.
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Figure 20.2 The petrosal surface. The cerebellum and brainstem are viewed from a ventral perspective. The right side of the illustration demonstrates the arterial supply to this surface (derived principally from the AICA), while the left side demonstrates the venous drainage (principally via the superior petrosal vein and sinus). Note the main trunk of the AICA, its anterior and lateral pontine segments (relative to the abducens nerve), and the medial (dividing CN VII and VIII) and lateral (proceeding laterally out of the horizontal fissure) trunks. Abbreviations: CP, cerebral peduncle; III, oculomotor nerve; IV, trochlear nerve; BA, basilar artery; V, trigeminal nerve; MCP, middle cerebellar peduncle; HorFiss, horizontal fissure; IX, X, XI, glossopharyngeal, vagus, and spinal accessory nerves; XII, hypoglossal nerve; Medul, medulla; JugV, jugular vein; TransSin, transverse sinus; VII, VIII, facial and auditory nerves; VI, abducens nerve; SupPetSin, superior petrosal sinus; SupPetV, superior petrosal vein; Mesen, mesencephalon.
Figure 20.3 The tentorial surface. The cerebellar surface is viewed from above. The right side of the illustration demonstrates the arterial supply to this surface [derived principally from the SCA, while the left side demonstrates the venous drainage (posterior-laterally to tentorial sinuses and anterior-laterally to the superior petrosal vein and sinus). Note the major bifurcation (rostral and caudal branches) and perforators to the collicular region and deep cerebellar nuclei off the superior cerebellar artery, after the vessel has circled behind the brainstem. Abbreviations : BA, basilar artery; PCA, posterior cerebral artery; Floc, flocculus; PrimFiss, primary fissure; TransSin, transverse sinus; TentSin, tentorial sinuses; SupPetSin, superior petrosal sinus; VII, VIII, facial and auditory nerves; V, trigeminal nerve; IV, trochlear nerve; III, oculomotor nerve; HemisBr, hemispheric branches of SCA; VermBr, vermian branches of SCA; Pre-CentCblrV, precentral cerebellar vein; CblrMesenFiss, cerebellomesencephalic fissure.
Figure 20.4 The suboccipital surface. The suboccipital surface of the cerebellum is viewed from inferiorly, as with the head down in the prone position. The right side of the illustration demonstrates the arterial supply to this surface [derived principally from the posterior inferior cerebellar artery (PICA)], while the left side demonstrates the venous drainage (superiorly to tentorial sinuses). Abbreviations: VeA, vermian arteries from PICA that communicate with the superior cerebellar artery; HeA, hemispheric branches of PICA that communicate with the superior and anterior inferior cerebellar arteries; PetFiss, petrosal fissure; SupOccipFiss, suboccipital fissure; X, vagus nerve; VA, vertebral artery; XI, spinal accessory nerve; IntJugV, internal jugular vein; SigSin, sigmoid sinus; TranSin, transverse sinus; VermBr, vermian branches of PICA; HemisBr, hemispheric branches of PICA; VermV, vermian veins; HemisV, hemispheric veins.
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Figure 21.2 Posterior view of the neurovascular structures exposed through a retrosigmoid approach. Abbreviations: AICA, anterior inferior cerebellar artery; CN, cranial nerve. Source: From Ref. 10.
Figure 26.1 Arteriovenous malformation (AVM) at the cortical surface of the right cerebellar hemisphere. Pediatric AVMs have a propensity for occurrence at infratentorial locations, in contrast to AVMs in adults.
Figure 26.7 Intraoperative photograph demonstrating a pial arteriovenous malformation on the cortical surface of the right parietal lobe in a seven-year old child. Arterial feeders (A), a tangled vascular nidus (N), and large arterialized venous outflow (V) are all visible through this dural opening.
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Figure 33.1 Gamma knife radiosurgery planning for a 25-year-old man who sustained an intraventricular hemorrhage from a right thalamic arteriovenous malformation (AVM). Angiographic and magnetic resonance images are shown. Two 8-mm isocenters were used to create a dose plan that fits the AVM margin well at the 50% line. A margin dose of 25 Gy and a maximum dose of 50 Gy were delivered.
Figure 33.2 Anteroposterior and lateral vertebral angiograms in an eight-year-old girl with headaches (A). An arteriovenous malformation of the left middle cerebellar peduncle was found. Radiosurgery was performed with two 8-mm and two 4-mm isocenters to deliver a margin dose of 20 Gy (50%) and a maximum dose of 40 Gy. The contrast enhanced volume acquisition magnetic resonance imaging scan at 1-mm intervals is shown (B) .
Figure 34.1 Graphs summarizing the immunohistochemical data showing the differential intensity of selected groups of molecules during the process of angiogenic maturation and their relative presence in the AVMs, CCMs, and VAs. (A) Structural proteins forming the vascular wall, (B) extracellular proteins, (C) integrins. Abbreviations: AVM, arteriovenous malformation; CCM, cerebral cavernous malformation; VA, venous angioma.
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Figure 34.2 Illustrative sections of the AVM sections stained with integrin ανβ1 (A–C), integrin ανβ3 (D–F), and integrin ανβ5 (G–I) antibodies. The three integrins were expressed in different ways in the AVMs versus the CCMs. The differences relate to the stages of angiogenic maturation exhibited by these lesions. All the histological layers of the AVMs showed stronger expression of integrin ανβ1 than the corresponding layers of the CCMs. Integrin ανβ3 was expressed more strongly in CCM endothelium than in AVM endothelium. Integrin ανβ5 was expressed more strongly in CCM endothelium and subendothelium than in AVM endothelium and subendothelium/media. Abbreviations: AVM, arteriovenous malformation; CCM, cerebral cavernous malformation.
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Figure 34.3 Illustrative sections of the cerebral cavernous malformation (CCM) sections stained with integrin ανβ1 (A–C), integrin ανβ3 (D–F), and integrin ανβ5 (G–I) antibodies.