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ISSN 0929-6743
Differential Diagnosis in Neurology
By
Robert Jay Schwartzman Drexel University College of Medicine, Philadelphia, PA, USA
Amsterdam • Berlin • Oxford • Tokyo • Washington, DC
© 2006 The author. All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without prior written permission from the publisher. ISBN 1-58603-624-6 Library of Congress Control Number: 2006927014 Publisher IOS Press Nieuwe Hemweg 6B 1013 BG Amsterdam Netherlands fax: +31 20 687 0019 e-mail:
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LEGAL NOTICE The publisher is not responsible for the use which might be made of the following information. PRINTED IN THE NETHERLANDS
DEDICATION to my wife, Denise
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Preface Differential Diagnosis in Neurology grew out of my taking daily morning report with neurology residents and examining patients in front of colleagues over the last 30 years. Dr. Eugene Stead, who was Chairman of Medicine for many years at Duke, taught me the importance of the fine points of the history and the significant details of the examination that separate one disease from another. Dr. G. Milton Shy was a master diagnostician melded each disease with its scientific basis and proposed diagnostic possibilities. It was a great privilege rounding with both and I hope a trace of their medical knowledge and scholarship comes through in these pages. The essence of “differential diagnosis” is “splitting” rather than “lumping”. It requires bringing knowledge to the table and then adding experience. The book is meant to be a skeleton that will give the clinician a general background with regard to the disease at hand. Molecular genetics, physiology and biochemistry will uncover mechanisms and associations that will further expand differential diagnosis of all neurological disease. There is no bibliography as it would be grossly out-of-date within one year. The reader is expected to utilize digital libraries to augment the basic information with the latest mechanism and treatment. It is hoped that the clinician will use the volume as a workbook in which new entities are added or older classifications revised. A possible strength of the volume is that one person wrote it and therefore it is somewhat uniform. Its glaring weakness is that one person can not know the depth of information needed to be comprehensive for each entity described.
Acknowledgment
I gratefully acknowledge my present and former colleagues, fellows, residents and students who have enriched my career in medicine. I thank my administrative assistants, Janet McCracken and Barbara Romm for helping me in all aspects of the project. I am delighted that I actually finished the project Yale Altman suggested many years ago and Anne Marie de Rover saw through to completion. I am especially pleased to acknowledge the support of Amy and Mark Tilly who made the volume possible.
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Contents Preface
vii
SECTION I. VASCULAR DISEASE Chapter Chapter Chapter Chapter Chapter Chapter Chapter
1. 2. 3. 4. 5. 6. 7.
Ischemic Stroke Venous Strokes Medical Causes of Stroke Cerebral Emboli Hypoxic-Ischemic Encephalopathy Chronic Small Vessel Disease Hemorrhagic Vascular Disease
3 51 54 96 108 113 115
SECTION II. EPILEPSY Chapter Chapter Chapter Chapter Chapter Chapter Chapter Chapter Chapter
1. 2. 3. 4. 5. 6. 7. 8. 9.
Introduction Generalized Seizures Progressive Myoclonic Epilepsy Partial Seizures Status Epilepticus Pseudoseizure Genetic Aspects of Seizures Unusual Seizures and Concomitant Medical Conditions Differential Diagnosis of Seizure Disorder vs Syncope
149 150 156 158 170 172 173 179 182
SECTION III. ANTERIOR HORN CELL DISEASE THAT AFFECTS ADULT PATIENTS Chapter Chapter Chapter Chapter Chapter
1. 2. 3. 4. 5.
Spinal Muscular Atrophies Linked to Chromosome 5q11.12–13.3 Immune Mediated and Genetic Lower Motor Neuron Syndrome Motor Neuron Disease Associated with Physical Agents Rare Causes of Motor Neuron Disease Amyotrophic Lateral Sclerosis
189 192 195 195 196
SECTION IV. SPINAL CORD DISEASE Chapter 1. Chapter 2. Chapter 3. Chapter 4. Chapter 5. Chapter 6. Chapter 7. Chapter 8. Chapter 9. Chapter 10.
Introduction Congenital Defects of the Spinal Cord Vertebral Column Bony Trauma Vascular Anatomy of the Spinal Cord Spastic Paraparesis Enzyme and Metabolic Disorders Affecting the Spinal Cord Autoimmune Causes of Spinal Cord Dysfunction Infections Affecting the Spinal Cord Tumors of the Spinal Cord Vascular Disease of the Spinal Cord
203 207 211 215 222 228 230 233 240 253
SECTION V. CRANIAL NERVES Chapter 1. Cranial Nerve I Chapter 2. Cranial Nerve II
263 264 ix
Contents
x
Chapter 3. Chapter 4. Chapter 5. Chapter 6. Chapter 7. Chapter 8. Chapter 9. Chapter 10. Chapter 11. Chapter 12. Chapter 13.
Cranial Nerve III Cranial Nerve IV Cranial Nerve V Cranial Nerve VI Cranial Nerve VII Cranial Nerve VIII Cranial Nerve IX Cranial Nerve X Cranial Nerve XI Cranial Nerve XII Multiple Cranial Neuropathy
284 289 290 293 294 299 308 310 313 314 316
SECTION VI. RADICULOPATHY Chapter Chapter Chapter Chapter Chapter Chapter Chapter
1. 2. 3. 4. 5. 6. 7.
Introduction Disc Disease Cervical Root Disease Thoracic Root Disease Lumbosacral Root Disease L1–L5; S1–S5 Epidural and Vertebral Metastasis Differential Diagnosis of Radiculopathy
319 320 325 329 332 334 338
SECTION VII. BRACHIAL PLEXUS Chapter Chapter Chapter Chapter Chapter Chapter
1. 2. 3. 4. 5. 6.
Introduction Differential Diagnosis by Plexus Component Traumatic Brachial Plexus Injury Differential Diagnosis of Thoracic Outlet Syndromes Neoplasms Affecting the Brachial Plexus Unusual Causes of Brachial Plexus Pathology
345 346 347 351 354 356
SECTION VIII. CERVICAL PLEXUS Chapter 1. Introduction Chapter 2. Clinical Presentations of C1–C4 Lesions Chapter 3. Pharyngeal Plexus
361 361 362
SECTION IX. LUMBOSACRAL PLEXUS LESIONS Chapter Chapter Chapter Chapter Chapter Chapter
1. 2. 3. 4. 5. 6.
Introduction Trauma of the Lumbosacral Plexus Tumors of the Lumbosacral Plexus Medical Causes of Lumbosacral Plexopathy Retroperitoneal Hemorrhage Immune Mediated/Toxic and Anesthetic Causes of Lumbosacral Plexopathy
365 366 367 368 370 371
SECTION X. DIFFERENTIAL DIAGNOSIS OF PERIPHERAL NEUROPATHY Chapter Chapter Chapter Chapter
1. 2. 3. 4.
Introduction Acute Predominately Small Fiber Sensory and Autonomic Neuropathy Dorsal Root Ganglion Disorders Differential Diagnosis of Symmetric Sensory Polyneuropathies
375 376 381 383
Contents
Chapter 5. Chapter 6. Chapter 7. Chapter 8. Chapter 9. Chapter 10. Chapter 11. Chapter 12. Chapter 13. Chapter 14. Chapter 15. Chapter 16. Chapter 17. Chapter 18. Chapter 19. Chapter 20.
Inherited Peripheral Neuropathies The Neuropathies of Disordered Lipid Metabolism Neuropathies of Disorders of Defective DNA Repair The Neuropathy of Heavy Metals and Industrial Agents Nutrition Associated Neuropathies Immune Mediated Neuropathies Vasculitic Peripheral Neuropathy and Neuropathies Associated with Connective Tissue Disorders Neuropathies Associated with Infection Diabetic Neuropathy Neuropathies Associated with Tumors Neuropathies Associated with Medical Illness Tumors of Peripheral Nerves Traumatic and Compressive Neuropathy Nonvasculitic Ischemic Nerve Injury Differential Diagnosis of Neuropathy by Pathology, Evolution Overtime and Precipitating Cause Differential Diagnosis of Neuropathy by Predominant Symptom, Hereditary or Feature
xi
386 396 399 400 416 418 425 434 440 443 448 453 456 476 479 482
SECTION XI. NEUROMUSCULAR JUNCTION DISORDERS Chapter Chapter Chapter Chapter Chapter Chapter
1. 2. 3. 4. 5. 6.
Introduction Myasthenia Gravis (Acquired and Congenital) Lambert Eaton Syndrome (LEMS) Drugs/Toxins that Alter Neuromuscular Transmission Botulism Tetanus
493 493 497 497 501 502
SECTION XII. MUSCLE DISEASE Chapter 1. Chapter 2. Chapter 3. Chapter 4. Chapter 5. Chapter 6. Chapter 7. Chapter 8. Chapter 9. Chapter 10. Chapter 11. Chapter 12. Chapter 13.
Inherited Myopathies Congenital Myopathies Myotonic Disorders of Muscle Periodic Paralysis Disorders with Continuous Motor Unit Activity (CMUA) Ryanodine-Receptor/Calcium Channel Disease Inflammatory Myopathy Metabolic Muscle Disease Mitochondrial Myopathies Malignant Hyperthermia Rhabdomyolysis and Myoglobinuria Myopathy Caused by Nutritional Deficiency Endocrine Myopathy
507 521 531 535 538 539 541 554 563 578 580 587 595
SECTION XIII. CEREBELLAR DISEASE Cerebellar Disease The Afferent and Efferent Cerebellar Pathways of Clinical Relevance Specific Anatomically Based Cerebellar Syndromes The Autosomal Recessive Ataxias Friedreich’s Ataxia Ataxia Telangiectasis (A-T) Rare AR Cerebellar Ataxias Autosomal Dominant Ataxias Episodic Ataxia (EA1)
605 605 606 607 607 608 609 611 613
Contents
xii
Rare Dominant Ataxias Unusual Genetic Ataxia Mitochondrial Ataxias Metabolic Ataxias Differential Diagnosis of Cerebellar Diseases An Overview of Non-Vascular Cerebellar Disease Infections Differential Diagnosis of Episodic Ataxia
614 615 615 617 618 619 622 623
SECTION XIV. BASAL GANGLIA AND MOVEMENT DISORDERS Chapter Chapter Chapter Chapter Chapter Chapter Chapter
1. 2. 3. 4. 5. 6. 7.
Bradykinetic Disorders Hyperkinetic Disorders Dystonia Myoclonus Tic Disorders Miscellaneous Movement Disorders Differential Diagnosis of Hyperkinetic Movement Disorders
628 637 649 652 656 657 658
SECTION XV. THE CEREBRAL CORTEX / BEHAVIORAL NEUROLOGY Chapter Chapter Chapter Chapter Chapter Chapter Chapter
1. 2. 3. 4. 5. 6. 7.
The Left Frontal Lobe The Parietal Lobe The Temporal Lobe The Occipital Lobe Arousal Memory and Amnesia Aphasia and Apraxia
663 665 666 667 669 671 674
SECTION XVI. DEMENTIA Chapter 1. Chapter 2. Chapter 3. Chapter 4. Chapter 5. Chapter 6. Chapter 7. Chapter 8. Chapter 9. Chapter 10. Chapter 11. Chapter 12.
Introduction Alzheimer’s Disease and Dementia with Lewy Bodies Fronto Temporal Dementias (FTDs) Prion Disease Hereditary Dementias Secondary Dementias Adult Lysosomal Disorders with Dementia Peroxisome Single Enzyme Defects of Adolescence and Adulthood Toxic Disorders with Dementia Neoplasms Causing Dementia Head Trauma as a Cause of Dementia Vasculitic and Microangiopathic Forms of Dementia
683 684 688 695 698 702 707 716 718 720 722 722
Section I VASCULAR DISEASE
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Chapter 1. Ischemic Stroke
Chapter 1 Ischemic Stroke General Features of the Differential Diagnosis of Ischemic Stroke, Embolus, and Intracranial Hemorrhage
Cerebral thrombosis occurs most frequently in the early morning hours during sleep. Patients frequently awaken and fall as they are unaware of their deficits. Transient ischemic episodes occur prior to thrombotic stroke in approximately 30% of patients and TIA’s precede 50% of strokes in the posterior circulation. They are almost always atherosclerotic in origin. TIA’s are usually emboli that arise either from the heart or intraarterial vessels (carotid, arch of the aorta or vertebral arteries to distal smaller branches). They occasionally occur from distal field ischemia due to compromised vessels and decreased cerebral perfusion or vasospasm (migraine). They may cause symptoms at each level of the brain as they progress through the circulation. They often occur in showers so that a number of vessels may be occluded simultaneously. The symptoms of intra arterial vessel to vessel emboli are usually <2 minutes. Longer TIA’s suggest a cardiac origin. TIA’s may occur only a few times or up to several times a day or on rare occasions in a rapid series (crescendo TIA). They often are stereotypical, but careful exam may reveal a new sign or symptom with each TIA. If an infarction follows the first TIA, it will be within one month in 20% of patients and within one year in 50%. Anterior TIA’s involve the cerebral hemisphere and the eye. Visual loss in the ipsilateral eye is usually characterized by transient monocular blindness. A shade may descend over the eye uniformly or more rarely there is a wedge of visual loss, sudden blurring or bright scotomata (This finding is often noted with concomitant carotid stenosis). The visual deficit clears painlessly and uniformly. Often ocular attacks precede hemispheric attacks. Hollenhorst plaques (yellow, birefringent, cholesterol particles) are rarely noted at branch points of the retinal arterioles. Rarely the pupil is paralyzed from ischemia of the ciliary body. Hemispheric attacks are most often characterized by face and arm weakness with concomitant sensory loss. The face and lips may be involved together or singly, a cheiro-oral presentation. The sensory loss involves the corner of the mouth and usually the C6 and C8 hand sensory root distribution: Most hemispheric TIA’s cause aphasia, heaviness, weakness and numbness of the face and arm (brachiocephalic) or of the arm, face and leg (internal capsule distribution). Rarely dysarthria leg weakness may predominate. A pseudo radial palsy of the arm suggests ischemia of the “knuckle” of the motor cortex. Simultaneous eye and hand involvement from a carotid embolus is extremely rare. Anterior TIA’s may cause: dizziness, confusion, both anterior or posterior aphasia, higher cortical sensory and cognitive deficits, and neglect to contralateral space with
3
nondominant hemispheric involvement. Headaches are common and usually ipsilateral. The usual manifestation of TIA’s in the posterior circulation (includes the vertebral, basilar and posterior cerebral arteries) are: bilateral visual field loss, dizziness, perioral numbness, ataxia, diplopia, dysphagia, dysarthria and bilateral motor or sensory symptoms. A crural hemisensory deficit (ipsilateral face and contralateral body below the clavicle) is pathognomic of brainstem involvement but is extremely rare. Dizziness alone is rare as a posterior TIA symptom but has been described with posterior inferior cerebellar artery involvement. Unusual signs and symptoms of posterior circulation TIA’s are: veering to one side (PICA at the level of the inferior olive), staggering (PICA territory), lateral pulsion (PICA territory, medial branch), a feeling of crossed eyedness, bilateral dark vision, noise or pounding in the head or ear, unusual cephalic sensations, pain in the face or head. Drop attacks, sudden loss of tone with falling may occur and are unaccompanied by loss of consciousness. The patients are stunned or slightly confused. Impaired hearing (sounds are faint or distant); deafness, forced eye deviation, hemiballismus, and a feeling of moving of a part and choreoathetosis have rarely been described. Peduncular hallucinosis has recently been demonstrated to occur from hippocampal formation ischemia. Forced eye deviation is encountered from unilateral para pontine reticular formation ischemia. Basilar artery ischemia may cause alternate hemiparesis. The affected extremities may be simultaneously weak or there is spread of weakness over 10 to 60 seconds which is much longer than expected from seizure activity. A basilar TIA may resolve suddenly or gradually. Posterior TIA’s have a higher incidence of headache than anterior TIA’s. In general, ipsilateral carotid disease causes face and parietal headache. Vertebral artery involvement refers pain to the retroauricular area whereas basilar artery disease produces occipital and C2 distribution (forehead) pain. Posterior cerebral artery ischemia refers to the lateral eyebrow. The major risk factors for thrombotic stroke are an important diagnostic feature. Hypertension, diabetes mellitus, cigarette smoking, prior stroke, heart and peripheral vascular disease are most common in older patients. Stroke in the young is embolic from the heart or secondary to dissection, collagen vascular disease, hypercoagulable states, genetic diseases or associated medical conditions. Development of neurologic deficits in thrombotic strokes occur in several ways: (1) single attack with the full deficit evolving over hours; (2) stuttering or intermittent progression that may continue over hours to 1–2 days; (3) a partial deficit that may improve and then progress to a completed stroke; (4) fleeting deficits may be followed by a longer episode and then a major stroke that occurs within days. The deficits may be regional at onset or evolve in a steplike pattern. Intermittent progression is a characteristic of thrombotic stroke. Rarely there is an apparent gradual progression of the deficit over 1–2 weeks which is most common in pure motor strokes.
4
SECTION I. Vascular Disease
In general, thrombotic strokes of the large conducting vessels of the middle cerebral artery (M1 and M2 components) reach maximum disability in three days which is dependent on consequent edema. Carotid occlusion, particularly if there is a fetal origin of the posterior cerebral artery (from the carotid artery) results in maximum edema and disability within 24 hours. Death is usually from transtentorial herniation at midbrain levels. Posterior fossa strokes, particularly of the vertebral artery, (the most common site of origin of PICA), may have delayed cerebral edema (4–7 days) and produce tonsillar herniation at this time (tonsillar coning). Particular arteries thrombose with different diseases. Diabetic patients suffer infarction of PICA and the thalamogeniculate and thalamoperforate arteries from the PCA to a greater extent than expected. Young hypertensive women on birth control pills infarct PICA. Lipohyalinosis and focal atheromatous plaques at the origin of penetrating arteries (lacunar strokes) occur most frequently in diabetic hypertensive patients. Dissection of the vertebral or carotid arteries usually causes stroke by emboli from the site of dissection but less commonly by decreased flow. Dissection of the vertebral artery is common in the horizontal component of the artery at C2. This frequently causes neck pain and may be followed by chiropractic manipulation which extends the dissection. Diabetes accelerates atherosclerosis by approximately 10 years. Radiation therapy in the neck induces a vasculopathy that accelerates atherosclerosis and causes proliferative endarteritis over long segments of the artery. If the brain is involved, small vessels occlude in the cortex with focal deficits and strokes. In the spinal cord, the perforating sulcal arteries are involved which produces a Brown Sequard Syndrome. Polycythemia most often affects the posterior circulation. The vasculopathy of sickle cell disease affects large and small vessels. The usual sites of atherosclerotic disease are the carotid bifurcation, siphon and the intracavernous portion of the artery. Rarely there may be isolated stenosis of superficial branches as well as the M1 and M2 segments of the middle cerebral artery. In the posterior circulation, the origin of the vertebral arteries, mid and top of the basilar artery, as well as the junction of the vertebral and basilar arteries, are major sites of disease. Stenosis may be seen singly or in tandem. Anomalies of arteries from their embryological origin may be important in determining the extent of thrombotic stroke. Poor development of the anterior and posterior communicating arteries may isolate one cerebral hemisphere. In general, the right vertebral artery is atretic or smaller than the left. Atherosclerosis of the left vertebral artery may induce severe basilar symptoms because of lack of circulatory support from the right vertebral artery. Occlusion of a vertebral artery may occur with prolonged abnormal head positions during surgical procedures as the artery on the side of the ipsilaterally turned head is occluded. If it is the predominant artery, there is no effective basilar flow. Similarly, a single thalamic peduncle (Percheron’s artery) at the top of the basilar may cause bilateral thalamic infarction as it will be the origin of the paired
interpeduncular arteries that usually arise separately from the top of the basilar artery. Failure of regression of the 4 major embryologic connections between the carotid and basilar artery (persistent trigeminal, otic, hypoglossal and proatlantal) may allow an embolus from the anterior circulation to infarct posterior circulation territory or vice versa. A fetal origin of the posterior cerebral artery arising from the carotid may be the cause of complete hemispheric infarction following carotid occlusion. A lacune is an area of infarction within the territory of a single perforating artery. The basic clinical syndromes associated with these lesions are: pure motor stroke, pure sensory stroke, homolateral ataxia and crural paresis, dysarthria – clumsy hand syndrome, ataxic hemiparesis and sensorimotor stroke. Approximately 80% of lacunes may be clinically silent. The temporal profile of a lacunar infarct may evolve over hours or rarely days in contradistinction to a cortical infarct. Lacunar strokes do not present with loss or impairment of consciousness, headache, seizure or higher cognitive deficits. Approximately 20% have TIA’s at the time of incipient occlusion and may be embolic. Often several perforating arteries are occluded in the latter circumstance. The capsular warning syndrome describes a crescendo of lacunar TIA attacks prior to completion of internal capsule infarction. A cerebral embolus strikes suddenly during wakefulness and frequently has a suggestive underlying cause. It may involve superficial surface cortical vessels giving pure cortical symptoms such as aphasia or hemianopia, or it may occlude stem arteries such as the M1 segment of the middle cerebral artery. This location causes deep internal capsular as well as surface hemispheric symptoms. Seizures occur in at least 15% of patients, and a similar number appear stunned and mute (stem MCA territory and rarely supplementary motor area). A small percentage of patients lose consciousness. Smaller emboli characteristically are cholesterolplatelet-fibrin in origin and give shorter symptoms (minutes). Larger red emboli from the heart clear more slowly (hours). The deficit following an embolus is most severe at onset and then clears over time. Most emboli occur in the MCA territory as this vascular territory receives the most blood flow. There may be evidence at presentation of prior embolic events in other vascular territories. Approximately 30% of cerebral emboli are associated with blood in the CSF(100 RBC/mm3 ). The setting for a cerebral embolus is a cardiac arrhythmia of which atrial fibrillation is by far the most common. A patient with AF that has the onset of an acute isolated Wernicke’s aphasia has almost certain embolization to the temporo-occipital branch of the inferior division of the MCA. Brady-tachy arrhythmia is the second most common arrhythmia causing cerebral embolus (usually during the tachy phase). A myocardial infarction, subacute bacterial endocarditis, artifical heart valve, perforated foramen ovale (20% of patients), aneurysm of the atrial septum, cardiomyopathy, lower extremity thrombophlebitis (paradoxical emboli) and cancer (nonbacterial thrombotic endocarditis) all
Chapter 1. Ischemic Stroke
suggest an embolus as the cause of stroke. Newer transthoracic echo-cardiographic techniques have demonstrated the importance of the aortic arch as a source of emboli (approximately 15–25%). The brain is the first clinical herald of systemic emboli from the heart in the overwhelming majority of patients. Recent diffusion/perfusion MRI studies confirm the diagnosis particularly if two circulations are involved. Arteries to artery emboli are smaller than those from the heart and often involve several territories in the posterior circulation. It is not unusual to have a vertebral artery embolus produce lower brainstem, pontine, midbrain, thalamic and cortical symptoms and signs as it moves up the posterior circulation. Carotid artery emboli to ophthalmic and central retinal arteries frequently produce amaurosis fugax, a shade descending in the involved eye that lasts for 1–2 minutes. It is coincident with a Hollenhorst plaque at a retinal artery bifurcation. The embolic deficit from a carotid or vertebral artery dissection may be associated with sympathetic ocular paralysis in the former and lateral neck pain in the latter. The clinical deficits caused from these events are from emboli at the site of dissection rather than CBF limitation. Embolic disease both from artery to artery and from the heart may occur as a shower with several circulations affected. Characteristically, emboli may affect the same territory with each event, which is thought to be due to laminar flow characteristics of that circulation. In the vertebrobasilar system, the top of the basilar artery is narrowest and is most often occluded from emboli. Rarely, emboli occur in a stepwise fashion that simulates distal field ischemia. The use of transesophageal echocardiography has demonstrated the root of the aorta as a rich source of emboli (15–25% of all emboli). Grade V (pedunculated) atherosclerosed material is most likely to cause a clinical problem. The recent application of transcranial Doppler techniques during carotid endarterectomy and other procedures has demonstrated that emboli may be asymptomatic. The from high frequency “hits” noted are smaller platelet fibrin emboli while lower frequency “hits” clots favor the heart. Lacunar disease of the basal ganglia and subcortical white matter are most often due to lipohyalinosis or atheromatous plaques at the origin of the penetrating vessels. If a group of these small penetrating vessels is occluded simultaneously emboli are the most likely cause. Persistent embryological arteries (trigeminal, otic, and hypoglossal) may allow an anterior embolus to infarct the posterior circulation or vice-versa. Hemorrhagic vascular disease can easily be divided by location, age of the patient, underlying medical disease, iatrogenic factors and clinical features. In general, hemorrhagic vascular disease occurs when the patient is awake and active. The exceptions may be aneurysms and cavernous hemangiomas that may rupture while the patient is asleep. The usual pattern of cerebral hemorrhage is the apoplectic onset of severe neurologic deficits with gradual headaches. Occasionally, the headache is severe, the patient vomits once (pressure on the floor of the IV
5
ventricle followed by compensating mechanisms), and there are focal neurologic deficits and loss of consciousness. Specific clinical points allow differentiation of the location and the most likely pathogenesis of the hemorrhage. Hypertensive hemorrhages occur in the setting of sustained hypertension that is then exacerbated by Kocher–Cushing reflexes (increased activity of the vasomotor center) which come into play to insure cerebral perfusion. The most common locations for hypertensive hemorrhages are the basal ganglia (40%), the thalamus (20%), the cerebellum 10%, lobar 10%, the pons 5%, and infrequently the medulla 1%. Hemorrhages in the white matter of the centrum semiovale suggest platelet and clotting disorders. Several areas of hemorrhage in different lobes that have mixed MRI signals (old and new blood surrounded by a dark hemosiderin ring) are suggestive of cavernous hemangioma. Blood in the suprachiasmatic cistern is often noted with P-COM, carotid and anterior communicating artery aneurysms. Blood tracking anteriorly between the hemispheric fissures is most characteristic of ACom aneurysms. Blood in the Sylvian fissure on one side suggests MCA aneurysm. Perimesencephalic prepontine blood in a patient with little or no focal abnormality is probably venous. Cavernous sinus aneurysms decompress into the sinus and are associated with cranial nerve abnormalities (III, IV, VI). Approximately 50% of aneurysms have a short episode of loss of consciousness at the ictus. A small percentage has seizures. Almost all have EKG changes. The neck is stiff, and Brudzinski’s and Kernig’s signs are positive. Frequently hydrocephalus is noted on the initial CT scan. Dural irritation from blood may be associated with tender eyes, a retinal hemorrhage on the side of the lesion (Torsten’s syndrome) and sore neck and shoulder muscles (meningeal irritation). Rarely, pain in the lower back is the major manifestation. Irritation of lower back meninges without headache should always raise the suspicion of a spinal AVM. Each aneurysm has its own clinical profile. P-COMs are associated with a pupil involving III nerve palsy A-COM show little focal neurological deficit (weak leg) but prominent personality defects. MCA aneurysms may have a prominent hemiparesis. Carotid aneurysms may be associated with a contralateral hemiparesis and III nerve palsy. Ophthalmic artery aneurysms cause unilateral visual loss. Parenchymal vascular malformations most often present with seizures rather than overt bleeding. These emanate from abnormal glial and neuronal tissue within the malformation. Migraine-like headaches are also common. Hemorrhage clearly can present with focal neurologic signs depending on the affected lobe. Arteriovenous malformations are associated with phakomatoses such as Von Hippel Lindau, Cobb’s, Sturge Weber, Wyburn–Mason, Klippel–Feil–Trenaunay, syndromes. There are genetic chromosomal defects with AVMs and cavernous hemangiomas (Krit1gene). Elderly patients presenting with single or multiple lobar hemorrhages suffer congophilic angiopathy. Gradient Echo
6
SECTION I. Vascular Disease
MRI sequences demonstrate prior bleeds because this technique is very sensitive to hemosiderin deposition. Traumatic hemorrhages may be associated with blood in the subarachnoid space, a coup contra coup location (frontal lobe coup and contra coup in occipital lobe) with contusion of the crown of the gyrus. They may be delayed for four to seven days after the injury. If severe, the hemorrhage may be associated with loss of autoregulation, severe cerebral edema and “commotio retinae” (an increased light streak from the retinal blood vessels). Venous hemorrhages occur in association with sinus thrombosis (particularly the superior sagittal sinus). They present with seizures, headache and focal deficits. They are accompanied by bilateral basal ganglia or thalamic hemorrhages. If cortical, they also are frequently seen in the middle cerebral artery territory. In the setting of pre or post partum, they frequently present with seizures in a lower extremity that generalizes, associated with bloody spinal fluid. Venous malformations are linear and often connect to a ventricle. They seldom bleed spontaneously but will cause infarction and hemorrhage into the drained territory if they are clipped. The use of TPA causes 6–16% of hemorrhage into the occluded territory. Hyperextension, the size of the infarcted area and age are risk factors similar to that which is seen with anticoagulation. Transformed hemorrhage which occurs in a previously infarcted area often is petechial but may be massive. Hemorrhage from anticoagulants usually is nonhomogeneous on MRI scan (swirling effect). Arteriograms following infarction may appear to be hemorrhages. Twenty percent of patients that have suffered a cerebral hemorrhage from cocaine abuse have an underlying vascular malformation. Rarely, propanethanolamine and dexedrine may cause cerebral hemorrhage from hypertensive mechanisms. Hereditary congophilic superficial hemorrhages are noted in Dutch, Swedish and Icelandic patients. Cavernous hemangiomas may be most common in Mexican Americans. The history and physical examination should localize vascular disease. The medical setting and this localization generates the differential diagnosis. Imaging proves the diagnosis, uncovers unsuspected pathology and allows insight into the basic mechanisms that are involved. There is no substitute for the history, physical examination, interpretation of the imaging studies and clinical judgment. The rapid advance of interventional radiological techniques, thrombolytic and possibly neuroprotective agents have made stroke neurology very therapeutic.
American and Asian ancestry (intracranial greater than extra cranial vascular disease) and family history are immutable. Specific secondary risk factors are associated with specific arterial size and distribution of infarction. Hypertension is associated with accelerated atherosclerosis of large extracranial vessels particularly the arch of the aorta, the carotid bifurcation, systemic and intracranial large vessel stenosis as well as atheromata at the mouth of penetrating small vessels of the brain. The lacunar hypothesis is generally, but not totally, accepted. Diabetes mellitus is concomitant with atherosclerosis but also is a risk factor for infarction of the posterior inferior cerebellar arteries, the thalamogeniculate and the thalamoperforate arteries. It is also associated with the lacunar state. Smoking is a clear risk factor for cerebral and extracranial atherosclerosis. Most patients with extracranial carotid disease from atherosclerosis associated with smoking die of coronary artery disease. The major risk factors for embolic stroke are cardiac and intravascular (artery to artery). Cardiac arrhythmia, particularly atrial fibrillation and tachybrady arrhythmias are the most serious. Ejection fractions of less than 30% from dilated cardiomyopathy of any cause are highly associated with embolic disease. Mitral valve disease from rheumatic involvement, prolapse, valve replacement or infection is the most common valvular cause of embolic stroke. The aortic valve is more prone to calcification from a bicuspid congenital defect than rheumatic disease (in the present era). Patent foramen ovale with or without atrial septal aneurysm is gaining increasing attention as a cause of embolic disease. Valve lesions are now very well visualized by transesophageal echocardiography. Thickening of valve cusps and myxomatous degeneration of the chordae tendinea are now being evaluated as a source of emboli. Left ventricular aneurysms and thrombi, as well as akinetic heart segments, have clearly been identified as risk factors for stroke following myocardial infarction. The arch of the aorta is now visualized with TEE and is a source of artery to artery emboli in approximately 30% of posterior circulation embolic strokes. Special risk factors for ischemic stroke include asymptomatic large vessel atherosclerosis (particularly the carotid bifurcation), but also the origin of the great vessels from the aorta and initial segments of the anterior cerebral, middle and posterior cerebral arteries. This stenosis can now be addressed by angioplasty and stenting. Catheter related emboli are special risks of CABG surgery.
Risk Factors For Ischemic Stroke
Primary Risk Factors Differential Diagnosis of Risk Factors for Ischemic Stroke
Specific risk factors determine which form of vascular disease is most likely in a given clinical circumstance. Primary risk factors of age (accumulating atherosclerotic lesions), African
The nonmodifiable primary risk factors for ischemic stroke are male sex, age, African-American or Asian ethnicity and family history. The modifiable risk factors are hypertension, smoking, diabetes mellitus, hypercholesterolemia, hyperhomocystinemia, excessive alcohol and drug abuse.
Chapter 1. Ischemic Stroke Secondary Risk Factors for Stroke
Hypertension There is a positive linear relationship between both systolic and diastolic pressure and the incidence of stroke, at any age in both sexes. After one year of therapy, there is evidence for a reduction of stroke risk and coronary artery disease in hypertensive patients, treated with diuretics and betablockers but not with either ACE inhibitors or calcium channel blockers. If the diastolic blood pressure is reduced 5–6 mmHg there is a 42% reduction in the incidence of all strokes and a 45% reduction in the incidence of fatal strokes. In a large series of patients (Medical Research Council Study) 65–73 years of age who were treated with hydrochlorothiazide or atenolol there was a 31% reduction in strokes, a 44% reduction in coronary artery events and a 35% reduction in all cardiovascular events. In the Medical Research Council Study, every 5.8 mm drop in diastolic pressure over a 2–3 year period produced a 42% reduction of stroke rate. Isolated systolic hypertension (systolic blood pressure > 170 mHg) should be treated. An 11 mmHg decrease of systolic blood pressure (The systolic hypertension in the elderly study) and a 3.6 mmHg reduction of diastolic blood pressure produced a 36% reduction in stroke risk.
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Postmenopausal hormonal replacement Two recent studies have demonstrated protective effects of hormonal replacement. Patient estrogen compounds had a relative risk of stroke of 0.72 while combination estrogen progesterone compounds had a relative risk score of 0.61. Less potent estrogen compounds were ineffective in stroke prevention. Strokes associated with hyperhomocystinemia Hyperhomocystinemia is a risk factor for premature atherosclerotic peripheral vascular disease, myocardial infarction and stroke. Prevalence of HHC has been noted in approximately 20–42% of stroke cohorts. Physical activity Physical exercise correlates with a progressive decrease in stroke rate. There is no evidence that weight reduction without exercise is beneficial for decreasing the risk of stroke.
Hyperlipidemia Elevated total cholesterol and low-density lipoproteins are independent risk factors for stroke.
Cholesterol reduction with statin drugs, risk of stroke and total mortality A total of 16 trials were evaluated that investigated approximately 29,000 subjects who were followed for >3 years. In those taking statin drugs (3-hydroxy-3-methylglutaryl coenzyme) reductase inhibitors (HMG-COA) had an average reduction in total and low density lipoprotein cholesterol of 22% and 30% respectively. Those taking statin drugs had a robust decrease of stroke of 29% and of mortality from stroke of 22%. Lipoprotein (a) is a low density lipoprotein (LDL) covalently linked by a di-sulfide-bridge to a large glycoprotein called apo(a). Sequencing of apo(a) suggests a high degree of homology with plasminogen. Lp(a) competes with plasminogen for the plasminogen binding site and reduces its cellular binding which may reduce endothelial cell fibrinolysis and thus produce a procoagulant state. Lp(a) accumulates on the endothelium of atherosclerotic coronary arteries but not on normal blood vessels. Lp(a) may be increased in a significant number of patients with acute stroke but has no association with cardiovascular risk factors stroke severity, or ischemic events during follow up.
Oral contraceptives Studies conducted with high estrogen formulations in the past demonstrated an increased risk of stroke empirically in women older than 35. Lower estrogen formulations in women younger than 35 who do not smoke have the same risk as the general population. The Nurses Health Study revealed that the relative risk of stroke was 1.2 with estrogen formulations, which was directly related to dose. Patients utilizing 50 μg of estrogen had a relative risk of 2.9, while in those utilizing 30–40 μg the relative risk was 1.8. The relative risk of progesterone preparations was 0.9. The problem with the study was that it was done in older women and few patients utilized oral contraceptives.
Silent cerebral infarction associated with coronary artery disease Silent cerebral infarction is a predictor of symptomatic cerebrovascular disease. Silent cerebral infarction by definition is an infarct demonstrated by CT or MRI without a history of stroke. In the Framingham study, latent, primarily lacunar infarcts were detected in 10% of patients. Silent cerebral infarction occurs in about 80% of patients with significant coronary artery disease. Myocardial infarction and angina pectoris are both associated with a high incidence of lacunar infarction. Patients who present with their first stroke (symptomatic) may have had a preceding silent infarct 25% of the time.
Diabetes mellitus The risk of stroke is increased 2.5 to 3.5 times in diabetics compared to controls. Long standing prospective trials with both insulin and hypoglycemic agents to reduce the risk of stroke are not convincing. Smoking Cigarette smoking increases the risk of stroke two times from accelerated atherosclerosis as well as effects on α1 antitrypsin and platelet inhibitory factor. The increased risk is dose dependent. Cessation of smoking reduces the risk of stroke rapidly at any age, whereas it takes 1 year to effect a 50% reduction of coronary artery events and 10 years to decrease the risk of lung cancer compared to controls.
SECTION I. Vascular Disease
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These infarcts are usually small, deep and in the basal ganglia. They are usually less than 1 cm. The occipital lobes may be disproportionately involved. Demographic variables that may be important for silent cerebral infarct (SCI) are age, male gender and African-American ethnicity. Left atrial enlargement may also be a risk factor for SCI.
4. Diffuse vasculopathy 5. Irregular heart rhythm a. Atrial fibrillation b. Sick sinus syndrome 6. Left ventricular hypertrophy
Characteristics of Silent Cerebral Infarction at First Stroke Presentation
Modifiable Risk Factors
1. 2. 3. 4. 5. 6.
Advanced age Small <1 cm Lacunar infarcts of BG Higher than expected in the occipital lobe In association with significant coronary artery disease In association with enlarged left atrium
Alcohol Consumption and Risk of Ischemic Stroke
Systolic blood pressure and high density lipoproteins (HDL) are modified by alcohol. Alcohol increases insulin sensitivity and has an antithrombotic effect on the coagulation system. Beer, wine and spirits have different effects on the risk of cardiovascular disease, due possibly to other substances consumed with the alcohol. Present evidence suggests that there is a small beneficial effect of alcohol (wine particularly) on the risk of ischemic stroke. However, high alcohol consumption may be associated with an increased risk of stroke and intracranial hemorrhage. Wine contains flavonoids and tannins, which may be beneficial. Infectious Disease and Risk of Ischemic Stroke
A large prospective study of patients with either TIA or completed stroke in a large inner city hospital demonstrated a high seropositivity for syphilitic infection but a low rate of meningovascular syphilis (0.4% was detected by CSF analysis). The role of infectious agents and occlusive vascular disease has been noted in rapidly progressive coronary atherosclerosis, in cardiac transplant patients (cytomegalovirus infection) as well as chlamydia pneumoninae for CAD. Antibodies to chlamydia pneumoniae have been detected in chronic coronary artery disease and acute myocardial infarction. There seems to be an association between ischemic vascular disease and chlamydia pneumoniae infection in general and with recurrent infection and acute stroke. HIV infection also confers a significant risk for ischemic vascular disease.
Major Secondary Risk Factors
1. Previous TIA or stroke 2. Previous myocardial infarction or angina 3. Carotid artery stenosis
Previous stroke or TIA Hypertension Atrial fibrillation Carotid bruits Left ventricular hypertrophy Coronary artery disease Congestive heart failure Diabetes mellitus Smoking
Approximate median risk 10× 6× 5.6× 3.0× 2.2× 2.2× 1.7× 1.7× 1.5×
Medical Diseases and Risk of Stroke
Atrial Fibrillation (AF)
1. Framingham Heart Study Group – a twenty-two year prospective study a. New AF incidence of stroke is 2.5/1,000 males and 17.1/1,000 females 2. Stroke rate Age 25–34 Age 35–64 Males 2.6/1,000 37.9/1,000 Females 2.2/1,000 29.9/1,000 3. European Study – a 14 year prospective study Stroke rate a. Patients less than 60 years of age 3% year b. Patients >76 years of age – 5.4% year c. Inpatients – 5–9% incidence of stroke d. Outpatient – 1.9–4.8% incidence of stroke Atrial Fibrillation Alone (Framingham Study Group)
Patients with coronary artery disease, congestive heart failure, and rheumatic heart disease were excluded. Ninety percent of patients were greater than 60 years of age. Patients were included who had nonspecific EKG changes. Patients with AF alone had a four times higher risk of stroke (24%). Mayo Clinic Study Group – 15 year prospective study. This study had the same exclusion factors as the Framingham study but added hypertension and nonspecific EKG changes. The cumulative incidence of stroke was 1.5%. The Olmsted County Minnesota Study – This study had the same entrance and restrictions criteria as the Mayo Clinic Study and found a 17% incidence of stroke.
Chapter 1. Ischemic Stroke Acute Myocardial Infarction (6 studies)
The risk of stroke with anterior wall MI is 6% (4–12%). Inferior wall MI carries a risk of 10%. Most cardiac embolic events occur within 1–2 weeks after the infarction. Left Ventricular Thrombus After Myocardial Infarction
Forty percent of patients that suffered a stroke after MI had a left ventricular thrombus (LVT), which is usually absent the first 24 hours after a myocardial infarction. Most thrombi develop between 1–14 days after infarction. Transthoracic echocardiography cannot detect thrombi less than 5 mm. Nonischemic Cardiomyopathy
The incidence of stroke is 4%/year in three studies of cardiomyopathy (0–12%). Echocardiographic detection of LVT ranged from 0–37% in five studies. The risk of emboli is linear with the severity of the cardiomyopathy. It is difficult to determine the true rate of embolic ischemic stroke from these studies because many different causes of myopathy were included. Mitral Valve Prolapse (MVP)
The prevalence of MVP is approximately 5% in the general population. The most common cause of MVP is a variant of mitral leaflet excursion rather than myomatous degeneration of valve leaflet chordae or the annulus. Five studies revealed an incidence of 4% of stroke with MVP in young adults (2– 6%). There are two distinct populations of patients with MVP. It is most common in young women. The complications are most prevalent in older patients and men. Complication prone MVP is most likely with older age, male sex, redundant and thickened leaflets, associated mitral regurgitation, tricuspid valve prolapse and mitral annulus abnormality. Infective Endocarditis
The prevalence of stroke in infective endocarditis is 15–20%. The majority of strokes occur within 48 hours of diagnosis or at presentation. The risk of stroke after antibiotic treatment is 5%. Staphylococcus aureus, and mechanical valve SBE are positive predictors for stroke whereas valve site is not. Mycotic aneurysms amenable to surgery are seen in 2% of patients. Large and enlarging mycotic aneurysms can be healed by antibiotic therapy. The risk of late rupture of mycotic aneurysms is low. They are invariably found on peripheral vessels rather than at the Circle of Willis. Intracranial hemorrhage carries a high mortality. Left Ventricular Aneurysm (LVA) and Left Ventricular Thrombi (LVT) Remote from the Site of MI
LVT usually are noted within two weeks of an acute MI and spontaneously resolve or may persist indefinitely. LVT that
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overlie wall motion abnormalities may have a delay of many months before they are detected after the acute MI. Left ventricular aneurysm (LVA) after acute MI has a low incidence of associated LVT as determined by cardiac catheterization. Emboli occurred in 3% of patients that were anticoagulated with LVT and 13% of those not anticoagulated. Nonbacterial Thrombotic Endocarditis (NBTE)
NBTE is frequently unrecognized although it accounts for 27% of ischemic strokes in cancer patients and had a prevalence of 1–5% in one autopsy series. It is associated with the prothrombotic state seen with cancer and has its highest occurrence during chemotherapy.
Special Risk Factors for Ischemic Stroke
Asymptomatic Large Vessel Atherosclerosis
There is a clear-cut benefit for secondary prevention of stroke if the carotid artery is narrowed >70% (NASCET and ECST European Carotid Surgery Trial). The benefit of surgery for 30–69% stenosis of symptomatic arteries is being evaluated. Asymptomatic stenosis surgery in the best surgical centers carries a 1.5–2.7% risk of stroke. Risk of Stroke with Intra-aortic Atherosclerotic Debris
Atherosclerotic disease of the thoracic aorta is common in elderly patients with coronary artery disease. Emboli arise from thrombi, fibrinous material, and cholesterol crystals that dislodge from complex ulcerated plaques. Transesophageal echocardiography with the high frequency (5MHZ) transducer can resolve intraaortic atherosclerotic debris from a simple atherosclerotic plaque. Autopsy studies have demonstrated a prevalence of 38% of complex atherosclerotic aortic plaques greater than 8 nm in patients with clinical coronary artery disease. Pedunculated and highly mobile plaques have a higher embolic potential than layered and immobile atherosclerotic debris. Risk of Catheter Related Emboli in Patients with Atherosclerotic Debris in the Thoracic Aorta
Cardiac catheterization or intra-aortic balloon placement in patients with transesophageal echocardiographic evidence of atherosclerotic debris carries a significant risk of embolization (10% and 5% respectively). The strongest predictors of atherosclerotic aortic debris are advanced age and peripheral vascular disease. The classifications of degrees of aortic atherosclerosis are: (1) grade 1 – normal aorta; (2) grade 2 – simple atherosclerotic plaque (intimal calcification); (3) grade 3 – plaque protruding <5 mm into the aortic lumen; (4) grade 4 – plaque protruding >5 mm into the aortic lumen which is layered; (5) grade 5a – 5 mm plaque that is mobile.
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SECTION I. Vascular Disease
Embolic events occurred following femoral catheterization (17%) while none occur following brachial catheterization. Embolic events from insertion of intra-aortic balloons occur in 40–50% of patients with atherosclerotic aortic debris and are primarily peripheral. The generally accepted incidence of stroke or peripheral embolization from cardiac catheterization is approximately 0.07%. Patients at particularly high risk of catheter related emboli are older than 65 years and have had a prior history of stroke. The incidence of catheter related stroke is 30% in those patients with mobile aortic debris and approximately 6% in those with layered aortic debris. Stroke Risk with CABG (Coronary Artery Bypass Graft) Surgery
There is approximately a 20% mortality from stroke in the setting of a CABG 6.1% of patients undergoing this procedure suffer a serious adverse cerebral outcome. The high risk features for a type I outcome (fatal cerebral injury and nonfatal strokes) are: advanced age, proximal aortic atherosclerosis, pulmonary disease, neurologic disease and hypertension. The most significant of these risk factors is atherosclerotic emboli released into the circulation by surgical manipulation of the aorta. This condition is found in approximately 20% of patients older than 70 and in approximately 12% of all patients undergoing the procedure. A history of prior TIA or stroke is also a significant risk factor. Increased risk of stroke is also seen with DM, unstable angina, prothrombic state, left ventricular thrombus and use of an intra-aortic balloon pump. The Risk of Stroke Associated with Cardiac Surgery
In general, patients undergoing coronary artery bypass, valvular surgery or both have a risk of stroke between 2–6%. Patients who suffer stroke are older and have a high rate of prior TIA, congestive heart failure and peripheral vascular disease. Surgical aspects that predispose to stroke are a pump time of greater than 120 minutes. Most strokes occur (approximately 60%) by postoperative day 2, but a significant number of delayed strokes occur (post operative day 3 to 9). Hemispheric syndromes are seen in approximately 2/3 of patients, brainstem and cerebellar infarction in 10–15% and lacunar syndromes in a similar number. Delayed strokes may occur due to a disrupted embolic source (plaque in the arch of the aorta) or an ongoing hypercoagulable state. Many studies have noted other variables associated with an increased risk of stroke with heart surgery. These include: carotid artery stenosis greater than 50%; repeat heart surgery, valve surgery, prior stroke, and perioperative hypotension. Late stroke risk factors are possibly: (1) anemia; (2) embolism (calcified atheromatous platelet fibrin complicated plaques); (3) decreased platelet number and function are decreased following surgery which increases the risk of bleeding; (4) reactive thrombocytosis.
Risk of Stroke in Cardiac Surgical Patients with a History of Stroke
Patients with deficits from previous strokes have a higher chance of experiencing a new stroke and of suffering reappearance or worsening of old deficits. These patients have a higher mortality rate, take longer to awaken from anesthesia, and to extubate. They are more likely to sustain a depressed level of consciousness and confusion after operation and are more likely to aspirate and require reintubation. Patient age rather than the interval between stroke and surgery is most significant. In general, a recent stroke is associated with reappearance or worsening of the prior deficit and a remote stroke predisposes to a new focal postoperative deficit. Retrospective studies suggest a stroke rate of approximately 13% inpatients with a prior stroke while a large prospective study demonstrated a rate of 43%. The stroke rate of patients with no prior history of stroke undergoing cardiac surgery varies between 1.5% to 5%.
Special Cases of Stroke Risk in Carotid Endarterectomy
Preoperative Risk Factors for Endarterectomy for Asymptomatic Carotid Artery Stenosis
The benefit of carotid endarterectomy (CEA) for significant asymptomatic carotid stenosis (>70%) is dependent on surgical risk (<3%). In general, diabetes, contralateral carotid artery stenosis, and never having ingested alcoholic beverages were associated with a higher risk of perioperative complications. Females, age 75 years or older with a history of congestive heart failure are associated with a higher risk of postoperative stroke or death. Patients undergoing CEA and concomitant coronary artery surgery were also at greater risk. Intraoperative risks 1. Cross-clamp time 2. Use of a shunt 3. Use of glucose solutions Surgical complications 1. Carotid occlusion 2. Thrombus 3. Ligation 4. Tacking sutures 5. Patch angioplasty Preoperative Risks Predict Severity of Carotid Endarterectomy Related Stroke
Advanced age, angina, and myocardial infarction in the past 6 months, congestive heart failure, hypertension, obesity and chronic obstructive lung disease are medical risk factors. Neurological risk factors are crescendo TIAs (multiple TIAs/day), TIA while anticoagulated with heparin, multiple
Chapter 1. Ischemic Stroke
completed strokes and ischemic symptoms <24 hours prior to the surgical procedure. Angiographic risk factors are: occlusion of the contralateral internal carotid artery, siphon stenosis on the operative side, plaque extension more than 3 cm distal to the origin of the ICA, high bifurcation of the carotid artery, and thrombus extending from the operative lesion. The higher incidence of poor outcome following stroke occurred in patients with neurological risk factors with or without medical or angiographic risk factors. Patients sustaining a surgical complication are more likely to have a CVA (60%). Surgical complications did not predict poor stroke outcome. The most common surgical complication is carotid thrombus formation. Preventative measures include: (1) nonreversal of intraoperative heparin; (2) avoidance of hypotension; (3) administration of postoperative dextran. The presence of an intimal flap or vessel kinking after closure may lead to a nidus for vessel thrombus formation. Carotid Recurrent Stenosis and Risk of Ipsilateral Stroke
The risk of recurrent stenosis is highest in the first years after carotid endarterectomy and lower in later years. A crude post endarterectomy stroke incidence (including perioperative stroke) is 1.6–3% per year. The annual stroke rate for all persons 55 to 64 years is 0.29%. For those 65 to 74 it is 0.55%. For those 75 to 84 years, it is 1.2%/year. After patients have had CEA they are 1.3 to 10 times at higher risk of stroke than the general population. Recurrent stenoses occurring within the first 2 years after operation are due to pseudointimal hyperplasia. Those occurring later are due to recurrent atherosclerosis. Low incidence of stroke early may be due to smooth homogeneous fibrous plaques with minimal ulceration or hemorrhage. Early stenosis has an incidence of 0.45% of stroke whereas restenosis after 36 months is 2.1%. Annualized risk of stroke related to restenosis is 0.15% in the first 36 months period and 0.5%/year after 36 months. Patch angioplasty may be most effective for arteriotomy closure. Carotid Endarterectomy in Patients with Near Occlusion of the Carotid Artery
Near occlusion of the carotid artery also known as the “string sign”, “slim sign”, or atherosclerotic “pseudo-occlusion” does not increase the risk of CEA more than that noted for CEA of 70–94% stenosis. In general, patients with anatomically normal but collapsed distal internal carotid arteries do better than those with fibrosis or atherosclerosis of the distal and proximal artery. CEA reduces the risk of stroke in symptomatic near occlusion. Emergency CEA is not necessary. The Influence of Carotid Siphon Stenosis in Short and Long-Term Outcomes after Carotid Endarterectomy
Early studies suggested that the risk of perioperative stroke and recurrent symptoms was higher in those patients with
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ipsilateral carotid stenosis and that siphon stenosis increased the severity of cerebral ischemic symptoms. Recent studies demonstrate no change in the short and long term stroke morbidity rates after carotid endarterectomy. Late death (>5 years) was caused most frequently by concomitant heart disease and was slightly higher in patients with siphon stenosis. Moderate siphon stenosis is a 50–79% diameter-reducing lesion. The incidence of ipsilateral carotid siphon stenosis is about 21.4%. Hemodynamically significant ipsilateral carotid siphon stenosis is approximately 14%. In those series that utilized a criterion of carotid siphon stenosis of greater than 20%, than approximately 40% of the ipsilateral carotid (extraaxial) will have concomitant siphon stenosis. Some natural history studies have documented decreased long-term survival of patients with siphon stenosis. The major hypothesis is that intracranial stenosis is a marker of wide spread vascular disease. Siphon stenosis is found ipsilateral to 20% of stenotic arteries and is usually 20–40%. It may increase the rate of late death (5–7 years), and may slightly lower the stroke free survival rate (from 80% to 50%). Simultaneous Carotid Endarterectomy and Coronary Bypass Risk of Stroke and Long Term Survival
The association of coronary and carotid atherosclerotic disease is clear. Greater than 50% of patients with carotid endarterectomy have had a previous infarct, angina, or ischemic EKG abnormalities. In patients undergoing coronary bypass, duplex ultrasound studies reveal >50% carotid stenosis in 3.4% to 22% of patients. The incidence of >80% stenosis is approximately 6–12%. Stroke complicates 1% to 4% of all coronary artery bypass procedures. It is higher in patients with extracranial carotid disease. Coronary Bypass Related Stroke Causes
1. 2. 3. 4. 5. 6.
Emboli from the carotid and aortic arch Endocardium (emboli) Pump oxygenator (emboli) Hypoperfusion (occlusive arterial lesions or hypotension) Air embolization Extracranial hemorrhage Carotid lesions of at least 60% will occur in 3% to 15% of patients undergoing a CABG. Selection criteria for the combined CABG-CEA patients versus CEA alone are accounted for by differences in perioperative morbidity and mortality. Ultrasound Lesion Morphology in Retinal Ischemia
Carotid arterial disease is a significant factor in causing retinal ischemic symptoms. The retinal ischemic symptoms are related to the morphology of the plaque lesion as well as the degree of carotid stenosis. Approximately 10% of patients who present with retinal ischemic symptoms first will develop
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SECTION I. Vascular Disease
a stroke. Complex heterogeneous plaques have an uneven distribution of low level and high level ultrasound echoes within the lesion and have an irregular or pitted surface and have been associated with both cerebral and retinal ischemia. In patients who presented with retinal ischemia there is a low incidence of continuing retinal emboli but a 26% rate of cerebrovascular or cardiovascular events. Complex heterogeneous plaque morphology is a significant risk factor for cardiovascular events. The Risk of Stroke in Patients with First Ever Retinal Transient Ischemic Attacks and High-Grade of Carotid Stenosis
The risk of ipsilateral stroke at 2 years following first ever retinal TIA is approximately 15% whereas it is approximately 40% if the first event was a hemispheric TIA. Most of the 2 year risk for both groups occurred in the first 2 months after the initial event. Patients with hemispheric TIAs as their first ever event were approximately 3 times more likely to suffer an ipsilateral stroke at 2 years than those patients who suffered retinal TIA as their first ever event regardless of stenosis severity within the 70–79% range. Patients with amaurosis fugax from all sources have a yearly stroke rate of 2–4%.
Natural History of Stenosis from Intracranial Atherosclerosis
Atherosclerosis of the intracranial vessels occurs in the setting of widespread vascular disease but may develop selectively in Blacks and Asians. Risk factors for intracranial atherosclerosis are race, hypertension, diabetes, smoking, and hyperlipidemia. These patients have an increased risk of heart disease, stroke and death. In patients who have failed medical therapy (anticoagulation), angioplasty of intracranial vessels carries a risk of stroke of 20–33%, which is secondary to occlusion of small perforating vessels, selection bias, vessel dissection and thromboembolism. In general, intracranial petrous to supraclinoid carotid lesions were stable while ACA, MCA, PCA and distal vertebral and basilar artery vessels progressively stenosed. In general 40% of stenoses were stable, 20% regressed and 40% progressed. Pathological specimens demonstrate that narrowing is caused by atherosclerosis and at times concomitant thrombosis. Emboli may also cause vessel narrowing and then complete resolution due to clot lysis. Absence of carotid bifurcation disease is associated with lesion progression while duration of tobacco use, hypertension and diabetes were associated with ICA atherosclerosis. Intracranial atherosclerotic lesions like coronary artery atherosclerotic disease are dynamic and both progress and regress over time.
Special Risk Factors for Ischemic Stroke (Summary)
1. Asymptomatic stenosis of >70% 2. Intra-aortic atherosclerotic debris 3. Catheter related emboli with thoracic aorta debris or other material 4. Stroke risk of CABG 5. Stroke risk with cardiac surgery 6. Risk of stroke in cardiac surgery patients with a history of stroke 7. Preoperative risks factors for asymptomatic CEA 8. Preoperative risks predict severity of CEA related stroke 9. Carotid recurrent stenosis and risk of stoke 10. Risk of stroke in carotid near occlusion 11. Carotid siphon stenosis and risk of stroke 12. CEA and CABG stroke risk 13. Lesion morphology as risk of retinal stroke 14. Stroke risk in first ever retinal TIA vs hemispheric TIA 15. Natural history of intracranial stenosis
Ischemic Vascular Disease
The hallmarks of ischemic cerebrovascular disease are the suddenness of the ictal event, the preceding risk factors, the patterns of the deficits and the course of recovery. Transient ischemic attacks precede 70% of ischemic events in the anterior circulation and 50% of those that occur in the posterior circulation. They may be divided into short <1 hour or >1 hour ischemic deficits although most last between thirty seconds and 2 minutes. Transient ischemic attacks are overwhelmingly caused by intraarterial artery to artery emboli, primarily thrombus material or detritus from atherosclerotic plaques, or clots from the atrial appendices, the walls of dyskinetic heart segments or from heart valves. There are a great number of causes of emboli originating from the heart due to intrinsic heart disease, tumor of the valves and systemic disease. Larger TIAs in general are caused by cardiac clots or large vessel emboli whereas those that last <1 hour are more after associated with lacunar infarcts or small vessel disease. Lacunar infarction may have a stuttering course. Recent studies demonstrate that atherosclerotic lesions of the aortic arch are associated with 20–25% of emboli to both circulations. Transient ischemic attacks of the anterior circulation may cause painless loss of vision in one eye (amaurosis fugax). This is frequently described as a shade descending over the eye and may last for 30 seconds to 1 minute; occasionally they may last for 5 minutes to 30 minutes. Rarely, a yellow birefringent cholesterol embolus can be seen at a retinal artery bifurcation (Hollenhorst plaque) and frequently appears to be larger than the vessel wall. The emboli move peripherally as vision clears. Smaller white fibrin platelet emboli are seen at retinal artery bifurcations and originate from complex plaques in the carotid artery or a cardiac valve or annulus source. It is extremely rare for amaurosis fugax to be
Chapter 1. Ischemic Stroke
associated with contralateral weakness or sensory loss. Constriction of the visual field or a monocular visual loss is from marginal or failed perfusion of the retina. TIAs are transient neurologic deficits that frequently precede ischemic stroke.
Clinical Signs and Symptoms of Anterior TIA (Carotid, Anterior, Middle Cerebral Artery Circulation Territories)
1. Numbness or heaviness of the contralateral face, arm or leg 2. Slurred speech 3. Anterior or posterior aphasia 4. Weakness of face, arm or leg 5. Perioral numbness of one side of the mouth either alone or concomitant with the hand (cheiro-oral pattern) 6. Amaurosis fugax in the ipsilateral eye 7. Temporal or parietal headache 8. Dizziness or light headedness 9. Imbalance 10. Dominant and nondominant hemispheric parietal deficits 11. Unilateral orthostatic clonic tonic jerks (primarily carotid stenosis)
Posterior Circulation TIA (Vertebrobasilar Arteries, Posterior Cerebral Artery Branches)
Clinical Signs and Symptoms
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
13.
14. 15. 16. 17. 18.
Bilateral visual loss or blurriness Vertigo or dizziness Bilateral peri-oral numbness Ataxia, imbalance, clumsiness/disequilibrium not associated with vertigo Diplopia Dysarthria Dysphagia Bilateral weakness or shifting weakness Bilateral sensory loss; shifting numbness Dissociated sensory loss (face and contralateral body) Medial or lateral spinothalamic tract sensory loss (face) Drop attacks corticospinal, cerebral peduncle, pyramidal tracts in the medulla or medial reticular formation ischemia Dysgeusia; (nucleus tractus solitarius from posterior circulation; ischemia of the VIIth nerve peripherally (supplied by the inferolateral trunk of the external carotid) Numbness of 1/2 of the tongue (patient aware of the deficit) Hearing loss (unilateral AICA or bilateral pontine ischemia) Persistent vomiting out of proportion to dizziness Singultus (hiccoughs) Basioccipital headache
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Differential Diagnosis of Transient Ischemic Attacks
The differential diagnosis of TIA is best thought of by mechanism. As stated earlier, most TIAs are embolic with the source being artery to artery or clots or other material from the heart of the TIAs are widely separated in time they most likely are from a large artery that is undergoing gradual occlusion. The carotid bifurcation may gradually occlude and during this process cholesterol debris as well as platelet fibrin clots form and dislodge from the area of ulceration. As the artery reaches a critical flow limiting state greater than 95% occlusion the TIAs may come very rapidly and may be a combination of distal field ischemic as well as artery to artery emboli. These may be known as crescendo TIAs and most often present as multiple episodes of amaurosis fugax. Tight stenosis of intracranial proximal conducting vessels (stenosis M1 of the MCA and AI and P1 of the anterior and posterior circulation) and factors combined with lower systemic pressure and CBF flow are causative. MRI scans demonstrate high signal T2 weighted lesions in the affected side periventricularly (vascular stripe). Tandem lesion of the carotid bifurcation siphon and M1 segment also cause susceptibility to fluctuations in blood pressure. Specific stenotic lesions cause stereotypical neurological symptoms as opposed to emboli which are slightly different from attack to attack, but often may lodge in the same or adjacent vessels due to laminar flow characteristics. Embolic TIAs particularly from the heart occur in specific settings. Some are pathognomonic such as a pure receptive aphasia which is characteristic of obstruction of the temporoparietal branch of the inferior division of the MCA from atrial fibrillation. Patients with dilated cardiomyopathy invariably embolize over time. Emboli may not cause catastrophic symptoms. A sudden headache or dizziness rather than hemiparesis, hemisensory loss or aphasia may be the only symptoms. Visual field loss of the superior quadrants suggests emboli to the lower banks of the calcarine cortex in the setting of atrial fibrillation. Ten percent of cancer patients suffer non-bacterial thrombotic emboli. Cardiac valve lesions even in those patients that are perfectly anticoagulated may embolize. The mitral valve is the most commonly affected followed by the aortic valve. Subacute bacterial endocarditis frequently is announced by an embolus to the middle cerebral artery territory. Atrial myxomas are noted for small embolic strokes but the clinical picture may be clouded by fevers and a remittent course due to an immunological response to the myxomatous material. This diagnosis may be heralded as well by the presence of a peripheral aneurysm. A peripheral aneurysm that has ruptured suggests SBE. Emboli occur during wakefulness. Occasionally, they are seen as a patient gets up to urinate at night or during a Valsalva maneuver suggestive of patent foramen ovale. The characteristic feature is the maximum deficit at ictus with clearing rather than deterioration which is more
14
SECTION I. Vascular Disease
common with ischemic occlusion. Headache occurs if the dura is involved. There is a small amount of CSF blood (approximately 100 RBC/mm3 ) and a higher incidence of seizures. Mobile plaques of the arch of the aorta and associated atherosclerotic detritus account for 30% of emboli to the posterior circulation and can now be evaluated with TEE. Patent foramen ovale with or without atrial septal aneurysms or tunnel emboli account for a large number of formerly cryptogenic emboli in younger patients. Symptoms form extracranial arterial dissections are usually form emboli rather than limitation of flow. Rarer causes of emboli are myxomatous degeneration of valves noted in mitral valve prolapse, verrucous endocarditis of SLE and air, fat, and calcium. The only common condition that causes vasospasm and TIS is migraine. The differential points for migraine versus embolism or ischemia as a cause of neurological dysfunction are clear. Migraine is noted for positive visual symptoms of scintillating or fortification scotomata, a gradual evolution over 20 minutes, one somatosensory complaint gradually merging with the next (visual symptoms merging with parietal sensory loss) and a headache after the neurological symptoms. Embolic or ischemic events are characteristic for the association of all deficits simultaneously with primarily negative symptomatology (heaviness, visual loss and weakness). Family history and risk factors are different. However, CADASIL (cerebral AD arteriopathy with subcortical infarction and leukoencephalopathy) as well as mitochondrial disease are noted for concomitant migraine headaches. SLE and other connective tissues have a high incidence of associated migraine. Emboli may occlude deep penetrating blood vessels mimicking lacunar disease (10–12 penetrators from the lenticulostriate arteries) of the internal capsule or basal ganglia. Congophilic angiopathy patients may suffer repeated small bleeds (noted by gradient Echo MRI) that mimic emboli. Imaging studies are extremely helpful. CT scan may demonstrate older lesions in two circulations or a dense MCA sign. This is at the site of embolic occlusion. Diffusion weighted MRI demonstrates areas of acute ischemia and in tandem with perfusion studies demonstrates the ischemic penumbra. Occasionally, one see lesions not only in different circulation, but demonstrating different intensities suggesting earlier events. Transcranial Doppler studies, particularly during carotid surgery, have shown that most emboli are asymptomatic (similar to the lung). The frequency characteristics suggest size of the embolic material. Carotid Doppler characteristics suggest qualities and morphology of the ulcerated plaque or dissection. As Dr. Caplan has pointed out, it is most important to discover the type of bird that has left the nest.
Differential Diagnosis of TIA
1. Seizure (including inhibitory seizure) A shaking TIA from carotid stenosis and hemispheric ischemia (distal field ischaemia) occurs with decreased cerebral blood flow. There are no auras, no loss of consciousness or mental clouding and no post ictal clouding. Bilateral shaking of the upper extremities and lower extremities may occur with internal capsule or cerebral peduncle ischemia (top of the basilar distal field ischemia). Extremely rare, a seizure emanating from the suppressor strip of the motor cortex (area 6) may cause contralateral paralysis of the face and arm. This does not clear for hours. There is no associated loss of consciousness. Todd’s paralysis from a focal seizure usually lasts less than one hour, but may persist for one week to ten days. Recently, prolonged Todd’s paralysis have been noted in that affect speech areas. They denote focal brain disease. The underlying seizure history and length of the attack differentiate them from TIA. 2. Demyelinating disease The short symptoms of demyelinating disease, those that last for a few minutes are thought to occur from Utoff’s phenomena (failure of partially demyelinated axons to conduct with heat) or blocking antibodies. The blocking antibodies may affect the optic nerves or sensory pathways most frequently with scotomata or paresthesia (less than five minutes). Most demyelinating attacks take weeks to clear. Paroxysmal ataxia pain, sensory and motor loss do occur with demyelinating disease. The underlying hyperreflexia, ataxia intranuclear ophthalmoplegia and cortical deficits suggest demyelinating disease rather than TIA. 3. Migraine Bickerstaff migraine with bilateral visual loss, paresthesias of the hands, perioral numbness, bilateral visual disturbance (visual field deficits, scintillating scotomata, teichopsia), dysarthria and loss of consciousness may be confused with brain stem stroke. In general, migraine can be differentiated from ischemic stroke by risk factors, age and hereditary pattern. Most migraine symptoms are positive and the progression is one modality affected seriously. Thus, visual loss slowly melds with parietal sensory loss and other weaknesses. The symptoms frequently precede the headache. The patients with ischemia suffer deficits in several modalities simultaneously. In general, these are negative – loss of vision, numbness and weakness. The headache is usually concomitant. Surprisingly, headache is suffered more frequently in patients with posterior rather than anterior circulation ischemia. This phenomenon has been ascribed to V1 innervation of the dura and the tentorium. Several drug intoxications are notable for focal neurologic deficits. Most often distributed cortical or brainstem networks with multiple synapses are affected. Hypoglycemia, hepatic insufficiency and phenobarbital poisoning dose cause focal deficits. If a patient had a prior deficit and then has metabolic
Chapter 1. Ischemic Stroke
compromise, the prior compensated deficit may become manifest. Diseases that are exacerbated by temperature may demonstrate the onset of new focal symptoms. These include multiple sclerosis, myasthenia gravis, the Lambert–Eaton syndrome and Fabry’s Disease. The neuromuscular junction deficits have cranial nerve, fluctuating weakness and maintained reflexes. Lambert–Eaton may at times demonstrate hyporeflexia and myasthenia gravis hyperreflexia (spreading acetylcholine sensitivity of the sarcolemmical membrane). Fabry’s Disease patients may present in coma under thermal stress that mimics basilar artery occlusion. The cataracts, skin lesions (bathing suit distribution) family history and painful neuropathy are diagnostic. Stroke and renal disease also occur in Fabry’s disease. Mitochondrial disease particularly MELAS, presents with stroke like episodes. Migraine, fatigue with exercise, short statue, exercise intolerance and VIIIth nerve deficits are characteristics. The MRI demonstrates basal ganglia involvement (probably white matter) within the basal ganglia. Posterior leukoencephalopathy may be present. Subclavian steal is over diagnosed and rarely is clinically significant as demonstrated by arteriographic studies on young Japanese women with Takayasu’s Disease. In general, the patient is vigorously rising the right arm overhead (which further lowers the pressure in the arm by dilating muscle vessels) the subclavian artery is stenosed prior to the origin of the vertebral artery and blood then flows from the ipsilateral brainstem through the vertebral artery and into the exercising arm. Patient’s demonstrate brainstem signs and symptoms. Syncope whether vasovagal (drop of systemic pressure) or vago-vagal and increase of vagal tone from the dorsal vagal nucleus to the nucleus tractus solitarius and then the SA and AV node) non-focal and in less than 15 seconds.
15
sidious and has been accompanied by extensive collateralization. Patients have been described with slowly developing complete carotid and vertebral occlusion that are relatively asymptomatic. In the face of acute occlusion without sufficient collateralization patients suffer weakness or paralysis of the contralateral arm, face and leg, the head and eyes are deviated to the side of the lesion (may not be dolled across the midline to the opposite side for 12–24 hrs) and may have a contralateral hemisensory deficit to all modalities. Cerebral edema supervenes within the first 12–24 hours and is manifest by lethargy, Cheyne–Stokes respiration exacerbated (if cardiac or pulmonary disease is present) and slight downward deviation of the eyes (5◦ below the horizontal). The arm on the contralateral side is pronated and the leg externally rotated. If the infarction is in the dominant hemisphere (90% of dextral and sinistrals are dominant in the left hemispheres) expressive and receptive aphasia is evident. If the occluded carotid affects the nondominant hemisphere (NDH) hemineglect may be associated with episodes of weakness of the contralateral leg which is precipitated by walking or standing. Similarly contralateral coarse shaking or involuntary movements may be seen in the extremities opposite the stenotic carotid artery precipitated by standing, walking, or head hyperextension due to ischemia of the ipsilateral corticospinal pathways. Severe Preocclusive Carotid Disease
A. Clinical Symptoms and Signs of Major Vessel Stroke
Severe preocclusive carotid disease may present with recurrent TIA’s, a stepwise onset, or a pseudotumoral slowly progressive form. Ischemic orbital pain may awaken the patient from sleep and is described as severe, deep and boring. Ischemic oculopathy with a swollen disc, and neovascularization may occur in conjunction with engorgement of conjunctival and episcleral vessels. The intraocular pressure may be extremely low. Optic atrophy on the ischemic side is rare. High grade stenosis may be associated with a unilateral loss of vision in bright light which may persist for seconds to hours and is related to delayed regeneration of visual pigments in the retinal pigment epithelial layer. These phenomena may occur bilaterally if both carotids are severely stenotic. Monocular visual loss may also be described as dimming or blurring of vision or seeing through a fog. The attacks are short, from 1–2 minutes, but occasionally last for 20 to 30 minutes. They are not positionally related. Bruits are frequently associated with severe stenosis but frequently disappear when the occlusion reaches approximately 90% of the arterial diameter. A diastolic component to the bruit is very significant. A bruit may be heard contralaterally in a minimally affected carotid due to augmented blood flow through the less diseased artery.
Carotid Occlusion
Acute Carotid Occlusion
A patient that has suffered a complete carotid occlusion is not infrequently asymptomatic if the process has been in-
Carotid occlusion at or below the bifurcation may cause a complete Horner’s syndrome with ptosis meiosis, facial
Differential Diagnosis of TIA
1. 2. 3. 4. 5. 6.
7. 8. 9.
Seizure (including inhibitory seizure) Demyelinating disease Anterior or posterior migraine (Bickerstaff’s) Rare metabolic dysfunction (phenobarbital, hepatic failure, drugs) Hypoglycemia Temperature exacerbated disease (myasthenia gravis, Lambert–Eaton syndrome, Fabry’s disease, demyelinating disease) Mitochondrial disease (MELAS) Subclavian steal Syncope
16
SECTION I. Vascular Disease
anhidrosis and apparent enophthalmos. If only the internal carotid is occluded past the branching of the external carotid there, will be no facial anhidrosis. The sympathetics surround the internal carotid artery to innervate the iris whereas the external carotid carries sympathetic innervation to the face. In a few patients, the pupil on the affected side will be dilated (less than 10%) and unresponsive to light due to iris ischemia. Pupillary cortical representation may lie in the motor sensory cortex or the prefrontal eye fields so that unilateral infarction may cause unilateral or bilateral ptosis (cortical innervation to the central caudal nucleus which innervates the levator palpebrae) and ipsilateral meiosis. This constellation is known as a cortical baby Horner’s syndrome. If severe carotid stenosis has preceded acute occlusion, the arcus senilis may be less apparent on the affected side. A major motor seizure may occur in a small proportion of patients concomitant with the occlusion. Waxing and waning of consciousness occurs during the first few days and Cheyne–Stokes respiration is common. The anterior 2/3 of the hemisphere is most severely affected. Rarely the affected side demonstrates hyperhidrosis (involvement of the anterior hypothalamus supplied by the meningohypophyseal trunk of the cavernous carotid). The hemisphere may be more severely involved if it is isolated due to hypoplasia of the anterior or posterior communicating arteries or if there is a fetal origin of the posterior cerebral artery from the carotid (concomitant hypoplastic ipsilateral posterior communicating artery). The stenotic or emboli lesions may extend to occlude the origin of the anterior cerebral artery with its consequent occlusion or in the case of a fetal origin of the posterior cerebral artery it may be occluded along with the middle cerebral artery. The size of the ICA occlusion may be minimized by collateral circulation through the Circle of Willis, cortical leptomeningeal vessels and those from the external carotid (internal maxillary, superficial temporal artery to meningeal vessels, ophthalmic and external carotid vessels to middle cerebral artery branches). Clinical correlate of the acute carotid occlusion: 1. Lethargy, fluctuating level of consciousness, rare seizures 2. Horner’s syndrome (ipsilateral) 3. 10% dilated unresponsive pupil (iris ischemia) 4. Periodic respiratory breathing pattern 5. Head and eyes deviated ipsilaterally (frontal eye fields are 8 and 10) 6. Hemisensory deficit to all modalities (contralaterally); vibration spared 7. Broca’s aphasia > Wernicke’s (DH) 8. Hemineglect contralateral side (NDH) 9. Pronated arm, externally rotated leg (contralaterally) 10. Depressed reflexes (contralaterally) acutely 11. Babinski’s sign (contralaterally)
Features of Intracranial Internal Carotid Occlusive Disease
Atherosclerosis of the Carotid Siphon
Calcification of the siphon is common and is coexistent with extracranial disease. There is a high death rate from coronary artery disease and disease in this location is more common in Afro-American than Caucasians. There are frequent concordant lesions in the origins of the internal carotid and vertebral arteries. Tandem ICA and siphon disease is common. There is a higher ratio of stroke to TIA in carotid siphon disease than cervical carotid disease. The major clinical differential points of siphon versus internal carotid diseases are: 1. Few episodes of amaurosis fugax 2. No ocular retinal pathology 3. Retrograde extension of the siphon clot may cause delayed optic ischemia 4. Leg is more affected than the arm 5. Associated scattered ACA and MCA infarcts are noted. These may involve the foot and face, sparing the arm 6. Slowly progressive symptoms 7. Worse prognosis than ICA origin disease 8. There are no collaterals through the external carotid artery Occlusion of the Top of the Carotid (T Portion)
A block at the top of the carotid causes infarction of both the anterior cerebral and the internal carotid artery. It is most common with sickle cell disease and with circulating anticoagulants.
The Anterior Choroidal Artery (ACHA) Syndrome
The anterior choroidal artery is the second branch of the internal carotid artery. It partially supplies the caudal 2/3 of the posterior limb of the internal capsule, the posterior optic tract, the uncus of the temporal lobe, medial GP1 , cerebral peduncle, lateral geniculate body and portions of the thalamus. AchA does not supply the corona radiata or the ventricular wall. Its most consistent branches are to the optic tract, cerebral peduncle and choroid plexus. There are variable anastomosis with branches of the MCA, PCA and posterior communicating artery. This artery supplies territories in both anterior and posterior circulations. A. Most Consistent Clinical Presentation 1. Hemiparesis, hemisensory loss, hemianopsia a. Pure motor hemiplegia (face, arm and leg affected) b. Bilateral AchA infarcts: 1) pseudo bulbar palsy; 2) mutism; 3) quadriparesis c. Hemisensory symptoms: incomplete or temporary and comprise all modalities B. Unusual Sensory Manifestations 1. Hemisensory deficit with spared proprioception 2. Painful thalamic-type syndrome
Chapter 1. Ischemic Stroke
C.
D.
E.
F.
G.
H.
a. Formication (crawling paraesthesias) b. Feeling of limb swelling c. Pain in the arms and legs 3. Hemiataxia with the sensory symptoms 4. Temporary sensory loss Clinical Features of the Motor Deficit 1. Face, arm and leg affected 2. Ataxic hemiparesis (thalamic) 3. Hypesthetic ataxic hemiparesis Visual Field Deficits and Eye Movement Abnormalities 1. Congruent homonymous visual field deficit sparing the central sector a. Lateral geniculate body infarcted b. Known as a quadruple sectoranopic defect 2. Homonymous congruent superior quadrantanopia a. With or without macular sparing 3. Congruent homonymous hemianopia 4. Ipsilateral conjugate eye deviation Higher Cortical Deficits with AchA Infarction (Unusual) 1. Nondominant hemisphere a. Visual neglect b. Constructional apraxia c. Short term visual memory loss d. Anosognosia e. Motor impersistence 2. Dominant hemisphere infarction a. Decreased fluency b. Semantic paraphasia c. Perseveration d. Deficits in language processing e. Poor understanding of word associations f. Poor comprehension g. Short term verbal memory loss AchA Infarction of Lateral Thalamus and Posterior Limb of the Internal Capsule 1. Dysarthria 2. Language processing defects 3. Short term verbal memory loss Bilateral AchA Infarction 1. Urinary incontinence without dementia 2. Dysarthria 3. Dysphagia 4. Dysphonia 5. Palatal paralysis – (may occur with unilateral stroke) 6. Pseudobulbar affect 7. Depression 8. Blunted affect 9. Mutism 10. Lethargy Anatomic Variants of AchA 1. Anastomosis with: a. MCA b. Posterior communicating artery 2. Paraventricular areas
17
a. Watershed between the deep MCA perforators and lateral lenticulostriate arteries b. Watershed between the posterior choroidal arteries (near the superior portion of the internal capsule) 3. May supply the temporo-occipital lobe (PCA territory) I. Pathogenesis of AchA Occlusion 1. Surgical manipulation a. Aneurysm (spasm) b. Seizure surgery 2. Hyperviscosity states 3. Decreased perfusion 4. Embolism a. Cardiac b. Often with concomitant MCA embolism 5. Thrombosis a. Intracranial atherosclerosis
Anterior Cerebral Artery
The anterior cerebral artery arises from the internal carotid artery at the level of the anterior clinoid process to supply the medial surfaces of the frontal and parietal lobes as well as the anterior 4/5 of the corpus callosum, the ventrobasilar frontal cortex (substantia innominata, septal nuclei, and nuclei of the diagonal band) and the anterior thalamus. The A1 segment from the carotid joins the anterior communicating artery AcoA in the interhemispheric fissure. There are approximately 8 perforating branches from the A1 segment. Proximal A1 branches perfuse the genu, contiguous areas of the posterior limb of the internal capsule, the anterior hypothalamus, anteroventral putamen and pallidum. Distal A1 segment branches perfuse the optic nerve, chiasm and tract. The perforating branches of the AcoA perfuse the most anterior aspects of the hypothalamus, the basal forebrain, and the medial anterior commissure, fornix and lamina terminalis, corpus callosum and anterior cingulum. A2 branches, part of the ascending segment, perfuse the gyrus rectus, the inferior frontal cortex, the anterior thalamus and the rostrum of the corpus callosum. The recurrent artery of Heubner takes origin near the AcoA and travels backward along the A1 segment to penetrate the brain at the lateral anterior perforating substance, Sylvian fissure or orbitofrontal cortex to supply the head of the caudate and anterior limb of the internal capsule. The distal A2–A5 segments comprise the pericallosal and callosomarginal arteries. If the callosomarginal artery is absent, all cortical branches originate from the pericallosal artery (18–60%) of patients. The ascending orbitofrontal and the frontopolar arteries arise from the A2 segment and supply the inferior, medial and lateral surfaces of the frontal pole. The superior frontal gyrus is supplied rostrocaudally by A2–A4 segments of the pericallosal artery. The paracentral artery, the superior parietal artery may arise from either the callosal marginal or the A4–A5 segment of the pericallosal
18
SECTION I. Vascular Disease
artery to supply the superior precuneus while the posterior inferior cuneus is supplied by A5 branches of the inferior parietal artery from the pericallosal artery. There are a great number of normal variations of the anterior cerebral artery and anterior portion of the Circle of Willis. The usual etiology of ACA-territory infarction is a cardioembolic stroke particularly if there is increased blood flow through the artery due to a contralateral ICA occlusion or a congenital defect of the anterior Circle of Willis. In situ thrombosis of the artery is more common in Asian patients. Extension of thrombus from the ipsilateral carotid is the usual atherosclerotic mechanism. Occlusion by transtentorial herniation, vasospasm from ruptured ACOA aneurysm or embolisms from these aneurysms are particular causes of infarction peculiar to this artery. Bilateral occlusion is rare but has been reported. Approximately 25% of these patients have had an azygous or unilateral supply of both ACAs from one carotid artery, the others having suffered probable emboli from atrial fibrillation or recent myocardial infarction. Bilateral infarction of the ACA causes akinetic mutism with poor recovery. The artery may be infarcted by the angitis of collagen vascular disease, prothrombotic states, lacunar infarction, rare emboli (fat, air, and atrial myxoma), dissection or fibromuscular dysphasia.
Anterior Cerebral Artery (ACA) Stroke: Clinical Signs and Symptoms
The clinical signs and symptoms of ACA are distinct. The artery is involved primarily following vasospasm secondary to anterior communicating aneurysm rupture, damage from neurosurgical procedures, propagation from ICA occlusion and artery-to-artery embolism from more proximal atherosclerotic occlusive disease. Cortical branch occlusion causes severe weakness of the distal foot and leg, the proximal arm with sparing of the face and tongue. The patient can frequently perform fractional movement of the hand and thumb. Muscle tone is flaccid early and then becomes spastic. The paracentral lobule, upper motor cortex and subcortical fibers from these areas that project into the corona radiata are affected. A few patients may only suffer a crural monoplegia (contralateral weakness of the leg). The pattern of weakness may vary considerably with some patients suffering arm and leg weakness to the same degree, others with hemiparesis and brachial predominance. Distal occlusion of the ACA may also cause pure motor hemiparesis and homolateral ataxia and crural paresis.
Patterns of ACA Weakness
1. Paresis of foot and leg > arm; face and tongue spared 2. Crural monoplegia (contralateral paralysis of leg and foot) 3. Contralateral arm and leg involved equally
4. Contralateral hemiparesis with brachial facial predominance 5. Homolateral ataxia with crural paresis 6. Pure motor hemiparesis Infarction of the recurrent artery of Heubner from the A1 segments affects the head of the caudate, the putamen and the anterior limb of the internal capsule. This lesion may cause faciobrachial predominance in the observed hemiparesis. The proximal perforators from A1 may also supply the genu and anterior internal capsule. Right-sided > left-sided medial frontal infarction that includes the SMA may cause contralateral motor neglect. Sensory deficits are most severe in the foot and leg contralaterally. They are most often in discriminative touch but may be severe to all modalities.
Psychomotor Dysfunction
The anterior cerebral artery supplies regions of the limbic system and basal ganglia essential for integration of emotional aspects of movement and frontal lobe function. Transient loss of consciousness may occur with ACA infarction. Bilateral damage to the anterior cingulate gyrus or head of the caudate nucleus may cause akinetic mutism. These patients do not initiate speech or movement and have no emotional expression. They do not respond to sensory stimuli but may follow the examiner with their eyes. Transient abulia may be seen with a unilateral lesion of the caudate head and cingulate gyrus and is characterized by decreased spontaneous speech and delayed response to questions, minimal spontaneous activity and impersistence. These patients may speak almost normally on the telephone. Infarction of projections from the caudate nucleus to the orbital and dorsolateral prefrontal cortex causes agitation hyperactivity and delirium. If they occur on the dominant side and disrupt connections into the thalamus, aphasia may be noted. Medial frontal lobe infarction causes euphoria, lability of affect and pathological jocularity. Antegrade amnesia may occur from damage to the paramedian basal forebrain during aneurysm surgery that damages perforators from the ACOA. If concomitant mesial frontal damage occurs confabulation may occur with the amnesia.
Aphasia and Language Disorders
Damage to the left supplementary motor area (SMA) may cause decreased spontaneous speech, normal articulation, repetition and comprehension. Transcortical motor or mixed transcortical aphasia have been documented with SMA lesions. Mirror writing can develop with right SMA lesions. Acquired stuttering may occur with anterior callosal or bifrontal lesions. Occlusion of either the right or left anterior cerebral artery may cause muteness.
Chapter 1. Ischemic Stroke Anterior Cerebral Artery Speech Disorders
1. 2. 3. 4. 5. 6. 7. 8.
Muteness Transcortical motor aphasia Transcortical sensory aphasia Acquired stuttering Whispered speech Reduced spontaneous speech Normal comprehension Normal articulation
Urinary and Fecal Incontinence
Unilateral or bilateral ACA infarction may cause urinary and fecal incontinence by damaging the midportion of the superolateral and medial superior frontal gyrus and the anterior cingulate gyrus. Damage to the paracentral lobule may induce precipitate micturition that cause patients to urinate uninhibitedly when their bladder is partially full.
The Grasp Reaction of ACA Infarction
The grasp reflex is caused by a contralateral basal ganglia or frontal lesion. This response is flexion and adduction of the hand when an object is gently moved from the palmar hypothenar eminence through the palmar index finger and thumb. This is an involuntary response. The instinctive grasp reaction is elicited by a stationary touch in the same areas of the hand and consists of: (1) several grasping movements directed toward the object; (2) a true grasp is one grasp in response to an object; (3) the traction response follows stretching of the patient’s flexed fingers that he cannot release; (4) a magnetic response in which the patient shadows the movements of the examiner’s hand. A contralateral lesion of the mesial superior frontal and cingulate gyrus or rarely the basal ganglia cause a grasp reflex.
Callosal Disconnection Syndromes Following ACA Infarction
In right-handed patients, a left handed ideomotor apraxia may occur following ACA infarction. The patient is unable to perform a simple command with the left hand such as a military salute. This is due to disconnection of Wernicke’s area and the premotor cortex from the premotor and primary motor cortex of the right hemisphere. It may also occur after infarction of the left premotor area (8), the anterior corpus callosum or the right premotor cortex. The patient may have impaired ability to imitate the examiner’s movements with the left hand. Left-hand agraphia may be seen with ACA infarction. Patients are unable to write readable letters, utilize correct words and often demonstrate substitutions or perseverations both to
19
dictation and with spontaneous writing. No linguistic mistakes are made with the right hand. They are able to write or copy correctly but cannot type or use block letters. In general, ideomotor apraxia and agraphia occur concomitantly with callosal lesions but may be dissociated. The callosal fibers for praxis cross the midline in the rostral portion of the posterior body of the corpus callosum. Unilateral tactile anomia occurs in the left hand. The patient can manipulate the objects correctly with either hand. He has an associated unilateral left agraphia that is caused by a lesion of the posterior part of the body of the corpus callosum. Right handed constructional dysfunction and crossed pseudoneglect to both visual and tactile line dissection tasks have been noted with callosal posterior body infarction. A crossed visuomotor ataxia results from damage to the dorsal aspect of the posterior callosum. A crossed avoiding reaction (patient unable to move the left hand when an object is placed in the right hemispace) has been seen with a lesion of the genu and body of the corpus callosum. The alien hand syndrome denotes a patient who has a feeling that the left hand does not belong to them and notes that one hand works at cross purposes with the other. In general, these patients have suffered a mesial frontal lobe and corpus callosum lesion. The patient cannot voluntarily suppress motor perseveration in which the patient compulsively repeats stereotyped movements. These movements are usually associated with a grasp reflex and instinctive grasp reaction. Compulsive manipulation of tools placed in front of the patient is a release of praxis from damage of the left mesial frontal lobe, cingulate gyrus and genu of the corpus callosum. The syndrome occurs with a concomitant grasp reflex and instinctive grasp reaction but no disconnection syndrome. The utilization behavior of Lhermitte differs from compulsive manipulation of tools because it is bilateral and lacks the compulsive quality noted in the compulsive manipulation of tools. Diagnostic dyspraxia is a dissociative movement in which the left hand undoes the actions of the right. Usually the left hand works at cross-purposes to the right. Damage to the body of the corpus callosum is required for this behavior. Damage to the contralateral mesial frontal lobe and genu of the corpus callosum may cause purposeless movements of the contralateral hand such as an updrift, tucking the hand in the axilla or grasping the throat.
Alien Hand Phenomena and Variants
1. 2. 3. 4. 5. 6.
Le signe de la main étagère “strange hand” Intermanual conflict Motor perseveration Compulsive manipulation of tools Diagnostic dyspraxia Updrift, hand in the axilla, grasping the throat
20
SECTION I. Vascular Disease
Callosal Disconnection Syndromes
Bifurcation Pattern (Superior/Inferior Division)
1. Ideomotor apraxia – left hand 2. Agraphia – left hand 3. Tactile anomia – left hand
1. Superior division (pial branches): a. Ascending orbitofrontal branch b. Prefrontal branches c. Precentral branches d. Central or central sulcal branches e. 2–3 anterior parietal branches f. 1–3 angular branches 2. Inferior division (pial branches): a. Ascending temporopolar branch b. Anterior temporal branch c. Middle temporal branch d. Posterior temporal branch
Pathologic Grasp Phenomena
1. Grasp reflexes 2. Instinctive grasp reaction: a. True grasp c. Traction response b. Instinctive groping d. Magnetic response
The Middle Cerebral Artery
The middle cerebral artery is most commonly affected in ischemic cerebral vascular disease. African-American or Asian patients have a higher incidence of infarction of this artery than white patients. The TIAs of the MCA disease are less frequent than those stemming from carotid disease and occur over a shorter time period. White patients present with TIAs of the MCA more frequently than with stroke; cigarette smoking is a strong risk factor for all groups that suffer MCA infarction. Major differential points of MCA occlusive disease from that of the ICA are: (1) deficits on awakening; (2) fluctuation or progression of symptoms over the following 1–7 days; (3) probable low flow mechanism. Carotid disease is more suggestive of an embolic mechanism. There are no ocular symptoms with MCA disease. Approximately 2/3 of all first brain infarcts are in the MCA territory. Approximately 1/3 affect the deep MCA territory and 10% occlude both deep and superficial territories. Approximately 50% of MCA infarction are restricted to the superficial pial arteries.
Anatomy of the MCA and Its Patterns
1. Pial branches supply: a. Almost the entire convex surface of the brain b. Lateral frontal, parietal and temporal lobes c. Insula, claustrum and extreme capsule 2. MCA emerges from the ICA for 1.8–2.6 cm as a single trunk a. Proximal M1/M2 segments give rise to medial and lateral lenticulostriate arteries 3. The stem divides into three patterns: a. Bifurcation pattern 1) Superior and inferior division – 79% b. Trifurcation pattern: 1) Superior, middle, inferior division – 12% c. Four or more trunks – 10%
Trifurcation Pattern
1. Superior division: a. Ascending orbitofrontal branch b. Prefrontal branches c. Precentral branches 2. Middle division: a. Central/central sulcal branches b. Variable origin of: 1) Precentral/anterior and posterior parietal branches 2) Angular/temporo-occipital branches 3. Inferior division (pial branches): a. Ascending temporopolar b. Anterior temporal branches c. Middle temporal branches d. Posterior temporal branches e. Variable origin of (posterior parietal/angular/temporooccipital arteries): 1) In both bifurcation and trifurcation patterns superficial branches may come from the stem of the MCA prior to its division: a) Ascending temporopolar branches b) Anterior and middle temporal branches
Anomalies of the Middle Cerebral Artery
1. Rare: occur in 3% of individuals 2. Duplication of the MCA: a. A second vessel arises from the ICA which supplies the anterior and middle temporal territories 3. Variable patterns of ACA and PCA pial terminal anastomosis at hemispheric border zones 4. If the main MCA trunk is short the lenticulostriate arteries may arise from the superior division
Chapter 1. Ischemic Stroke General Features of Superficial Middle Cerebral Artery Territory Infarction
Patients frequently develop distal MCA trunk occlusions that spare the deep penetrators from the M1 and M2 segments of the proximal MCA. The pathogenesis is most often thrombosis in situ rather than embolic. Complete infarction of the superficial MCA territory of the dominant hemisphere causes head and eye deviation to the side of the lesion, lethargy, global aphasia (often early mutism) and perseveration. The hemiparesis and hemisensory loss is brachiocephalic predominant with an invariant contralateral homonymous hemianopia. Nondominant hemisphere infarction in addition to similar motor and eye signs demonstrate contralateral neglect, constructional apraxia, alloesthesia, anosognosia and multiple nondominant (ND) parietal lobe symptomatologies. Superior division dominant (D) hemisphere infarction causes brachiofacial predominant motor and sensory symptoms, no visual field deficits, but gaze preference or eye deviation (Brodmann’s 8 and 10) to the affected side. Broca’s aphasia, ipsilateral ideomotor or limb kinetic apraxia and oral buccal lingual apraxia may be seen. Nondominant infarcts have similar motor and sensory deficits with hemi spatial neglect and emotional aprosody. Inferior division territory infarction causes minimal weakness but usually an up drift can be appreciated acutely. Astereognosis, difficulty with dynamic and static parietal copy, point localization is noted after the ictus. The most common visual field deficit is a contralateral superior quadrantanopsia if Meyer’s loop is involved, although a contralateral noncongruent homonymous hemianopsia may also be seen (optic tract). Dominant hemisphere lesions cause a Wernicke’s aphasia with an occasional patient demonstrating acute agitation. Characteristics of nondominant lesions are a contralateral predominant sensory hemineglect, anosognosia, constructional apraxia and an agitated confusional state.
Superior Division of the Middle Cerebral Artery (Pial Branches)
Ascending Orbital Frontal Artery
This artery perfuses the orbital portion of the middle and inferior frontal gyrus and the inferior pars orbitalis. Its infarction (emboli or arteritis) causes behavioral disinhibition and a contralateral grasp sign. Prefrontal Arteries
The territory perfused by these arteries is the middle frontal gyrus, pars triangularis, anterior pars opercularis and superior pars orbitalis. The clinical symptomatology includes apathy, abulia, poor ability to change motor sets, perseveration (DH), impersistence (NDH), poor judgment and abstraction, imitation and utilization behavior, and poor retrieval of short
21
term semantic material. A transcortical motor aphasia may be noted with (DH) lesions and motor neglect with nondominant hemisphere infarction. Precentral Arteries
This group of arteries supplies the posterior middle frontal gyrus, the posterior pars opercularis and the anterior and midportion of the precentral gyrus. The clinical features of infarction of this branch or branches are proximal upper extremity weakness or distal brachiofacial weakness. Dominant hemisphere lesions may have a concomitant transcortical motor aphasia. Due to infarction of area 8, patients may have bilateral upper extremity ideomotor apraxia. If the infarction involves the posterior left middle frontal gyrus (Exner’s area) they may have agraphia out of proportion to hand weakness. Central Sulcal Artery
The central artery group supplies the posterior bank of the precentral gyrus and the anterior half of the post central gyrus. A pathognomic clinical sign of infarction of this territory is monoparesis of the upper extremity (pseudoradial palsy) although brachiofacial weakness is the most common pattern. Infarction of the motor knuckle anteriorly causes selective weakness of muscles innervated by C5 and C6. Posterior infarction causes C8–T1 innervated muscle weakness. Sensory loss is noted in the same distribution. Rarely a pure motor stroke affecting arm, face, and leg occurs. Infarction of the parietal operculum may cause a cheiro-oral sensory loss (corner of the mouth and hand). Dominant hemisphere infarctions cause Broca’s aphasia or dysarthria and dysprosody. Nondominant hemisphere infarction usually causes less severe dysarthria. Anterior Parietal Artery
This artery or group of arteries supplies the post central gyrus, parasagittal portion of the central sulcus, and the anterior inferior portions of both the inferior and superior parietal lobules. Anterior parietal branch occlusions may cause a contralateral updrift of the arm with abnormal proprioceptive finger movements (mini myoclonus). Loss of touch, pain and position sense is common in the arm and face distribution. Vibration is usually spared. The distal upper extremity may be most severely affected. Incoordination of the affected hand may be noted. Dominant hemisphere infarction may cause conduction aphasia while nondominant lesions are associated with visual-spatial deficit. Posterior Parietal Artery
Infarction of this territory involves the posterior portions of the superior and inferior parietal lobules and the supramarginal gyrus. Discriminative sensations such as two point localization, stereognosis and graphesthesia are predominantly
22
SECTION I. Vascular Disease
involved. Patients may demonstrate an inferior quadrantanopsia or noncongruent homonymous hemianopsia. Dominant hemisphere lesions may cause anomic aphasia (SMG), agraphia, and alexia (areas 39, 40, 41). Ideational and bilateral representational ideomotor apraxia as well as a posterior alien hand syndrome may occur. Left right confusion, finger agnosia, dyscalculia, inability to cross the midline and dysgraphia (Von Gerstmann syndrome) may be seen singularly or concurrently. Nondominant hemisphere infarction causes contralateral sensory spatial neglect, constructional apraxia and visuospatial deficits. Differential Diagnosis of Parietal Sensory Loss
In general, parietal sensory symptoms from infarction have a regional pattern. Dramatic involvement of 1/2 of the body is characteristic of thalamic disease. Other thalamic signs are the upper extremity is more severely affected and often the trunk is spared. The deficit may be limited to the finger tips (ventral posterior inferior nucleus) and primarily involves the discriminative aspects of sensation. Vibration loss is a thalamic or dorsal column nuclear deficit. Motor dysfunction with these sensory symptoms occurs in a large majority of patients. This motor deficit first described by Foerster as an afferent paresis or tactile paresis (loathness to move). Partial pseudosegmental, pseudoradicular, cheiro-oral (posterior parietal operculum) pseudospinal patterns may be seen with parietal lesions. The usual pseudoradicular pattern is C6 or C8–T1. A pseudothalamic pattern (SI area) consists of deficits of elementary modalities of sensation with faciobrachial predominance (syndrome of Roussy and Foix). Spinothalamic type of sensory loss (Brodmann’s area 43, part of SMG and the posterior insula) may be seen. Patients may demonstrate asymbolia for pain, if SII is infarcted (adjacent to the lower extent of SI). Portions of the cortical sensory syndrome with loss of discriminative touch, position sense, astereognosis, ability to copy posture, sensory hemineglect (NDH) with preserved vibration sense may be seen with both anterior and posterior parietal branch infarctions. Corona radiata and occasionally SI infarction may cause a feeling of heaviness in the contralateral extremities and are associated with difficulty initiating and sustaining movement (disconnection of deep SI, 3b and area 4) in the depths of the central fissure. Angular Artery Branch
This artery supplies the posterior portion of the superior temporal gyrus, parts of the supramarginal and angular gyri and the superior lateral occipital gyri. The major features of infarction of this branch are the angular gyrus syndrome (Von Gerstmann). Frequently associated is anomic or transcortical aphasia, alexia without agraphia, an inability to cross the midline and constructional apraxia. Nondominant lesions are associated with: (1) contralateral spatial neglect; (2) visuospatial and constructional deficit; (3) loss of opticokinetic nystagmus (eyes remain toward the ipsilateral side); (4) hemianopia or inferior quadrantanopsia; (5) anosognosia (denial
of illness); (6) asomatognosia (denial of a limb); and (7) alloesthesia (perception of sensation on the normal side when the affected side is stimulated are seen). If there is a short mainstem MCA, the lenticulostriate arteries may originate from the superior trunk. Infarction in this circumstance would involve the basal ganglia and the internal capsule. Inferior Division of Middle Cerebral Artery
The general characteristics of an inferior division MCA infarction are: (1) Wernicke’s aphasia (DH); (2) contralateral superior quadrantic VF deficit; (3) poor drawing and copying (NDH); (4) agitation (NDH). Ascending Temporopolar/Anterior Temporal/Middle Temporal Branch Occlusion
The anterior temporal artery supplies the anterior portion of the superior, middle, and inferior temporal gyri. The temporopolar artery complex supplies the anterior pole of the superior middle and inferior temporal gyri. The middle temporal group of arteries supplies the superior gyrus below the pars triangularis and pars opercularis as well as the middle portion of the middle temporal gyrus and posterior portion of the inferior temporal gyrus. The clinical features of infarction of the anterior temporal branches are a contralateral homonymous superior quadrantanopsia. If on the dominant side, the visual field deficit may be associated with an anomic aphasia with categorypredominant naming deficits. Nondominant infarction may cause hemispatial neglect and an acute confusional syndrome. Temporo-Occipital/Posterior Temporal Branch Occlusion
These arteries supply the posterior half of the superior temporal gyrus and the posterior portions of the middle and inferior temporal gyri and the inferior portion of the lateral occipital gyri. These occlusions cause a contralateral superior quadrantanopsia or hemianopsia. Dominant hemisphere infarction of the posterior superior temporal gyrus causes Wernicke’s aphasia. This infarction is frequently embolic and if pure (no other neurologic symptoms) is often caused by atrial fibrillation or another cardiac source. Nondominant hemisphere infarction produces an acute confusional state, contralateral hemispatial neglect and constructional apraxia.
Other Common MCA Occlusions of the Superficial Territory
Insular Branch Occlusion
The insula is supplied by the MCA trunk or proximal portions of its division and is rarely infarcted in isolation. Bilateral infarctions from seriatim strokes cause the Foix–Marie– Chavany syndrome which consists of severe apraxia for all of
Chapter 1. Ischemic Stroke
the muscles of branchial origin. Patients have difficulty swallowing, moving the face and tongue, buccal movements and initiating and articulating speech. This is a cause of aphemia which is a dramatic dysarthria that renders speech unintelligible. It may occasionally occur from unilateral insular branch occlusion. Long Penetrating Medullary Artery Occlusion
Infarction of a group of long-penetrating arteries cause large infarcts in the centrum semiovale. Their origin is in the MCA pial branches and they usually cause a contralateral motor and sensory deficit as well as a noncongruent hemianopsia. If in the dominant hemisphere, patients are dysphasic while NDH lesions are associated with hemineglect and visuospatial deficits. Infarcts of less than 1.5 cm in diameter cause pure motor or sensory strokes, ataxic hemiparesis without cognitive impairment or isolated involvement of face, arm or leg (fibers are widely separated). This fractionation is less common than with deep subcortical infarcts. Severe ipsilateral carotid disease produces the lesions by distal field ischemia or embolic disease.
Deep Territory MCA Infarction
The deep territory is composed of penetrating branches from the M1 and M2 proximal segments of the MCA which are known as the lenticulostriate arteries. If these arteries are infarcted, the process is usually embolic and occlusion of many perforators occurs simultaneously. This type of infarction is a striatocapsular infarction rather than a lacunar infarction in which only 1 lenticulostriate perforator is occluded. In general, striatocapsular infarction involves the head of the caudate, the putamen, and the lateral internal and external capsule and may extend into the corona radiata. The insular cortex and the thalamus is spared. Striatocapsular infarcts may involve the territory of Heubner’s artery (recurrent branch from A1) or the anterior choroidal artery. In general, the area infarcted is in the range of 2–7 cm, is wedge or comma shaped, and is not ovoid as are the smaller lacunar infarctions. Cortical symptoms are rare and if present resolve quickly. The cortex is not infarcted due to leptomeningeal anastomoses. In situ thrombosis or cranial arteritis involving a segment of M1 that occludes multiple perforators is rare. Acutely, patients present with predominantly motor or sensory motor hemiparesis with or without dysarthria. Hemiparesis results from damage to the posterior limb (mid 1/3) of the internal capsule (motor cortex corticospinal fibers) or if only the frontal part of the internal capsule is involved (the lateral premotor cortex corticospinal fibers or those from the SMA cortex in the genu) are involved. The differential diagnosis of striatocapsular infarcts are: (1) lacunar syndromes; (2) pure sensory stroke; (3) strokes in
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the basis pontis; (4) ICH of the striatum. If the leptomeningeal anastomosis fails patients may suffer cortical deficits which add to the underlying deficit and rule out lacunar stroke. In striatocapsular stroke, cortical deficits such as aphasia or neglect resolve in the face of persistent motor or sensory deficits. In a moderate or large territorial or MCA branch occlusion the cortical deficits are more severe and long lasting. Extended striatocapsular stroke is most often associated with Wernicke’s aphasia (involvement of insular or superior temporal gyrus). Rarely focal dystonia, contralateral choreoathetosis, or hemiballismus has been noted. Bilateral striatocapsular infarction may cause tetraplegia and akinetic mutism.
Striatocapsular Stroke
1. 2. 3. 4. 5.
Predominant motor or sensorimotor hemiparesis Minimal cortical signs and symptoms that resolve 2 to 7 cm in size Wedge or comma shaped Involves caudate, putamen, anterior or posterior limb of the internal capsule 6. Rare contralateral movement disorder 7. Rare tetraplegia with akinetic mutism (if bilateral) Distal field infarction (or low flow state in the periventricular white matter) between the penetrating cortical branches and the ascending lenticulostriate branches that does not infarct the basal ganglia or internal capsule may mimic some of these findings. If the head of the caudate nucleus, the putamen and the anterior portion of the internal capsule are infarcted the pattern represents that of occlusion of the recurrent artery of Heubner whose origin is the A1 segment of the ACA aberrant (medial lenticulostriate artery). The resultant hemiparesis has brachiocephalic predominance with tongue involvement. A similar infarction can occur from occlusion of the perforating branches of the most proximal portion of the A1 segment of the ACA artery. If the caudate head and the anterior limb of the internal capsule are involved, the eyes may be deviated ipsilaterally and the face and arm are more severely affected than the leg. Caudate infarction interrupts fibers that project to the frontal and dorsolateral prefrontal cortex and may be associated with an acute confusional, agitated or an abulic state. If the infarction extends anteriorly and destroys fibers that project to the medial dorsal and anteroventral thalamic nuclei, patients may have an expressive aphasia. Rarely with infarctions in this area patients demonstrate a hemisensory defect that affects the face and hand more severely than the leg. Dysarthria is more severe with left sided than right sided capsular lesions (corticobulbar projections to cranial nerves VII, X and XII). A noncongruent homonymous hemianopsias results from optic tract infarction. This may also be accompanied by a Behr’s pupil (larger, poorly reactive pupil on the ipsilateral side).
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SECTION I. Vascular Disease
The lateral lenticulostriate group of perforators takes origin from the M2 proximal middle cerebral artery segment and supplies the putamen, claustrum, external and extreme capsule and the insular cortex. Putaminal infarction causes brachiocephalic predominant weakness with increased tone and hyperreflexia but no sensory loss. Rarely putaminal infarction causes contralateral dystonia, choreoathetosis, and abnormal contralateral hand posture. Bilateral insular cortex infarction (insular branches of the MCA) produces the Foix–Chavany– Marie syndrome which causes apraxia of all branchial derived musculature and disrupts speech and swallowing. The dysarthria may be so severe that speech is unintelligible (usually requires bilateral infarction).
b. Posterior 1/3: 1) Pure sensory 2) Arm, face, and leg involved c. Arterial supply (lenciculostriate) 6. Rare behavioral signs and symptoms of striatocapsular stroke are: a. Fluctuating alertness b. Inattention c. Memory loss d. Apathy e. Frontal lobe deficits 7. These deficits are caused by infarction of: a. Inferior and anterior thalamic peduncles b. Anterior limb of internal capsule
The Capsular Warning Syndrome
The Differential Diagnosis of Striatocapsular Infarctions
These are TIA’s restricted to the face, arm and leg and are not often seen with severe carotid stenosis accompanied by a low flow state. The major clinical features are: 1. Simultaneous sensorimotor involvement of face, arm and leg 2. No neglect, dysphasia or dyspraxia 3. Three or more clinical events within 24 hours 4. Onset over seconds 5. Pure motor hemiparesis is most common 6. Sensory symptoms clear prior to motor signs 7. Capsular infarction follows in approximately 40% of patients As noted above, the capsule may be predominately involved in specific areas.
1. 2. 3. 4.
Capsular Genu Syndrome
1. Contralateral facial, lingual and brachial weakness 2. With or without ipsilateral horizontal conjugate eye deviation 3. Rare thalamic aphasia
Midpoint Infarction of the Upper Capsule with Lower Corona Radiata Extension (Anterior 1/3 of the Posterior Limb)
Clinical Signs and Symptoms
1. 2. 3. 4.
Dysarthria Contralateral clumsy hand Faciolingual weakness Blood supply is from the lenticulostriate arteries that concomitantly supply the upper ventricular wall (anastomosis with ependymal vessels) 5. Posterior 1/3 limb of internal capsule infarction: a. Middle third 1) Face < arm < leg weakness 2) Purely motor
Lacunar infarcts (1–2 perforating vessels) Pure sensory stroke (thalamic infarction) Infarction of the basis points (penetrating basilar branches) Small striatal or intracranial hemorrhage If leptomeningeal anastomoses fail, or there is a concomitant shower of emboli, patients may suffer cortical deficits. As noted earlier, lack of cortical dysfunction is characteristic of lacunar stroke.
Clinical Differential Diagnosis of Capsular Infarction
1. The first of frequent hemiplegic events is more likely capsular than pontine. 2. Premonitory events are characteristics of anterior choroidal artery ischemia. 3. Capsular ischemia: patients are aware of its onset; it resolves over seconds to minutes. 4. Incipient occlusion of the ICA often is accompanied by repetitive events with cortical dysfunction. 5. Hemodynamic events are posturally influenced and are shorter than embolic events. 6. Artery-to-artery embolic events are more widely separated in time.
Rare Patterns of Stroke in the MCA Territory
Central sulcal branch artery infarction may cause a right pseudothalamic sensory loss (primary sensory modality involvement), ideational apraxia and conduction aphasia. Wernicke’s aphasia and hemianopsia often follows embolic occlusion of the temporooccipital branch of the inferior MCA division particularly in the setting of atrial fibrillation. Precentral branch occlusion may cause transcortical motor aphasia, proximal weakness of the arm and ideomotor apraxia. The anatomical variants of the middle cerebral artery, specifically the origin of the angular artery may determine
Chapter 1. Ischemic Stroke
unusual stroke symptoms following infarction in the MCA territory. Stenosis of the M1 segment of the MCA in conjunction with hypertension may cause periventricular longitudinal infarction. Double infarcts are those that involve two components of one arterial territory. Aphasia without hemiparesis occurs when Broca’s and Wernicke’s area are infarcted leaving the motor strip intact. Hemiplegia with visual field deficits occur when the superior division (central sulcal branches) are occluded concomitantly with temporo/occipital branches (inferior division) thus sparing the primary sensory cortex. Conduction aphasia with hemiparesis has been noted with motor cortex and supramarginal gyrus lesions. Fragmentation of emboli at the MCA bifurcation or seriatim strokes are the most likely mechanisms.
Complete MCA Infarction (Superficial and Deep Territory)
Panhemispheric MCA occlusion is often embolic particularly if sudden. If it occurs with a slower or stuttering onset it is most likely due to carotid occlusion. These patients have cerebral swelling usually within 12 hours of infarction that impairs consciousness. Their head and eyes are deviated ipsilaterally, they demonstrate periodic or Cheyne–Stokes respiration, a flaccid contralateral hemiparesis and hemisensory deficit, homonymous hemianopsia and global aphasia (DH), or severe contralateral sensory neglect (NDH). The eyes are usually congruently deviated slightly below the horizontal due to pressure on the center for upgaze (the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)that is ventral to the superior colliculus. In stem MCA infarction, edema is most severe at 3 days. Prior to herniation, patients may demonstrate an ipsilateral sluggish and oval pupil (pressure on the III nerve) as well as ipsilateral or bilateral ptosis (frontal eye field compromise).
Clinical Summary of Complete Superficial Territory Infarction
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
Hemiparesis faciobrachial > leg Hemineglect for space and motor activity (NDH) Anosognosia (NDH) Asomatognosia (NDH) Spatial disorientation (internal/external/geographical) NDH Disorientation NDH > DH hemisphere Depressed reflexes contralaterally (acutely); rarely increased (cortical disinhibition) Babinski’s sign contralaterally (ipsi or bilaterally if there is increased ICP) Angular gyrus syndrome (DH) Supra marginal gyrus syndrome (DH) Wernicke’s aphasia (DH)
12. 13. 14. 15. 16. 17. 18. 19.
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Broca’s aphasia (DH) Conduction aphasia (motor DH) Conduction aphasia (sensory DH) Alexia without agraphia (DH) Ideomotor/limb-kinetic apraxia D > NDH Ideational apraxia (DH) Alien hand syndrome (DH > NDH) Sympathetic apraxia or callosal apraxia (DH)
Superior Division MCA Occlusion (Bifurcation Pattern)
1. Broca’s aphasia (DH) 2. Exner’s area (severe inability to write) DH; Brodmann’s area 45 3. Parietal hand (updraft; loathness to move) 4. Dysarthria 5. Motor conduction aphasia (DH) 6. Limb kinetic/ideomotor apraxia (DH) 7. Alien hand syndrome (area6/DH) 8. Brachiofacial pattern of weakness > leg weakness 9. Depressed reflexes contralaterally 10. Head and eye deviation (ipsilaterally) 11. Babinski’s sign contralaterally 12. Frontal behavioral syndrome 13. Apathy and abulia 14. Brachiofacial crural weakness (rare) 15. Phonemic paraphasia 16. Rare cheiro oral sensory loss Inferior Division MCA Occlusion (Bifurcation Pattern)
1. 2. 3. 4. 5. 6.
Wernicke’s aphasia (DH) Sensory conduction aphasia (DH) Supramarginal gyrus syndrome (DH) Angular gyrus syndrome (DH) Hemineglect for space (NDH) Depressed opticokinetic nystagmus (ipsilateral hemisphere) 7. Depressed optic scanning (contralateral space) 8. Constructional apraxia (NDH) Prosopagnosia (NDH) 1. Loss of higher cortical sensory function (contralateral) 2. Ideational apraxia 3. Posterior type alien hand Summary of MCA Infarctions
a. 2/3 of first brain infarcts involve the MCA b. 1/3 of MCA infarction involves the deep MCA territory c. 1/10 of MCA infarction involves both superficial and deep territory d. 50% are branch occlusions
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SECTION I. Vascular Disease
Sentinel Differential Diagnostic Feature of Large Vessel Stroke of the Anterior Circulation
The hallmark of carotid disease is retinal involvement either embolic from burst plaques or artery to artery. Hollenhorst plaque material at a bifurcation of a retinal artery is pathognomonic. Horner’s syndrome associated with a brachycephalic predominant lesion points to the internal carotid artery. Due to the circle of Willis collaterals may save a great deal of the hemisphere. Carotid siphon disease has no ocular pathology, but the anterior cerebral artery may be involved concomitantly with the middle cerebral artery. Emboli from the siphon may occlude the anterior cerebral artery and the inferior branch of the dominant middle cerebral artery sparing the major portions of the motor sensory cortex. This causes a Wernicke’s aphasia with shoulder and leg weakness. The anterior choroidal artery supplies aspects of both anterior and posterior circulations. The hallmark of its infarction is a quadruple sectoranopic defect that spares the central sector. The defect arises from infarction of the lateral geniculate body. Infarction of the uncus and components of its thalamic supply cause a deficit in short term memory and language processing. Hyperesthetic hemiparesis (thalamic) and hyperesthetic ataxic hemiparesis are patterns of infarction. The usual pattern of anterior cerebral artery infarction is severe weakness and sensory loss of the foot, minimal involvement of the shoulder and face with excellent preservation of hand movement. The patient may be able to wiggle the thumb, but not the arm if the Az section is involved. If the recurrent artery of Heubner is infarcted and the patient demonstrates facio brachial predominant weakness. Involvement of the supplementary motor area (distal ACA) causes transcortical motor aphasia, mirror writing acquired stuttering and muteness. Muteness is often seen as well with sudden occlusion of the stem of the MCA. Medial frontal lobe infarction often causes euphoria, lability and iocularity. Anterior callosal involvement causes sympathetic apraxia (inability to follow commands with the left hand) and the anterior alien hand syndrome (inter manual conflict). The major differential distinction of middle cerebral artery disease is that from internal carotid artery occlusion. TIAs in the middle cerebral artery distribution occur on awakening, are less frequent than carotid TIAs and once initiated occur over a shorter time period. They frequently fluctuate or progress over 1–7 days. The mechanism often is distal field ischemia so symptoms often vary with posture. There are no monocular symptoms. Characteristic of superficial territory involvement is hemiparesis and hemisensory deficit with brachycephalic predominance. The frontal eye fields are frequently involved (FEF) with no corresponding visual field deficit. Severe motor neglect and parietal visuospatial deficits are noted if the non-dominant parietal lobe is involved. The angular artery syndrome of Van Gerstmann localizes the lesion to posterior parietal territory if the DH is involved. The pre and frontal superficial branches of the superior division
supply Broca’s area (44). The DLPC (dorsolateral pre frontal cortex) is also frequently involved and causes memory retrieval difficulties. Characteristic of inferior division infarction of the superficial territory is Wernicke’s aphasia (pathognomonic of embolus if isolated and concomitant with atrial fibrillation) and agitation. Deep territory middle cerebral artery territory infarction is characterized by internal capsule and basal ganglia infarction. The important differential point from superficial territory and carotid infarction is involvement of the leg, absence of eye deviation and the transient nature of any cortical deficits. This infarction causes a striatocapsular stroke with persistent motor sensory signs. The medial and lateral lenticulostriate group of arteries from the M1 and M2 segments of the MCA of the lateral group is involved. The putamen may be affected causing motor weakness, increased tone and reflexes without sensory loss. The capsular warning and genu syndromes may be seen prior to stroke.
Differential Diagnosis of Posterior Circulation Stroke
General Features
The posterior circulation can be considered the arch of the aorta, the innominate and subclavian arteries and vertebral, basilar posterior cerebral and their derivative arteries. The arch of the aorta is a rich source of embolic material to the posterior circulation. Its prominence in this regard has recently been accentuated by transesophageal echo cardiography. A mobile grade V plaque is extremely dangerous as a source of embolus. Approximately 30% of emboli to the posterior circulations arise from this source. Emboli to both anterior and posterior circulations arise from the heart or the arch of the aorta in the great majority of cases. The embryologic connections from the carotid to the basilar artery are rare source of emboli. These include the persistent trigeminal artery, the otic, hypoglossal and pro-at canthal arteries. The most significant of these arteries is the persistent trigeminal which connects this top of the basilar to the carotid artery just below the siphon. The vertebrobasilar system can be divided into diagnostic thirds. Each major artery has sentinel features that can guide diagnosis. Characteristic of a subclavian stenosis proximal to the origin of the vertebral artery is the subclavian steal syndrome. The patient uses the affected arm (left greater than right) which further lowers pressure in the arm (lower than that in the vertebrobasilar system) and blood flows to the arm from the vertebral supply. Most patients have a clear difference in blood pressure between the two arms and a significant decrease of pulse volume and clear lag of the pulse in the affected side. The syndrome usually causes more claudication in the arm than brainstem symptoms. It is rarely significant clinically. A rare syndrome of ischemia of the brachial plexus and posterior circulation can occur from ischemia of the vertebral and axillary artery (feeds the plexus) that occurs simul-
Chapter 1. Ischemic Stroke
taneously. Patients may complain of arm pain in the lateral or medial cord distribution, hand weakness concomitantly with lower brainstem, and cranial nerve symptoms. Atheromatous occlusion with or without emboli may cause simultaneous carotid and vertebral artery symptoms on the right side. In general, the left carotid takes origin from the aorta and this will not occur on this side. The common congential anomaly of the posterior cerebral artery taking origin from the carotid may cause complete hemispheric infarction if that carotid is occluded. The patency of the posterior communicating arteries may determine upper basilar perfusion if there is occlusion of the mid basilar or vertebral arteries. Proximal vertebral artery disease is most common at the origin from the subclavian artery which is accessible to stenting and angioplasty. The most prominent clinical symptoms are dizziness, diplopia (VIth nerve), dysphagia, oscillopsia, bilateral leg weakness and sensory loss on the trunk. Isolated dizziness especially points to the labyrinth rather than the brainstem. The origin of the posterior inferior cerebellar artery is from the vertebral. It is most commonly involved due to occlusion of the parent artery. The sentinel features of its involvement are dysphagia, nausea and vomiting (out of proportion to dizziness), hoarseness, lateral pulsion to the side of the lesion). These patients have a great deal of difficulty walking which is out of proportion to their ipsilateral ataxia. Seventh nerve weakness (ipsilateral) may occur due to recurrent medullary fibers. Ipsilateral facial pain “salt and pepper” in Vth nerve distribution is characteristic. Medial medullary infarction is suggested by contralateral flaccid paralysis of arm and leg (infarction above C2) or ipsilateral flaccid hemiparesis if ischemia involves the cervical medullary junction. Spasticity evolves within days to weeks and causes flexion of the upper extremity and extension of the lower extremities. The motor deficit is more severe distally in the upper extremity which is also typical for pontine infarction. Infarction of the pyramidal decussation may cause a crural paresis. The sensory loss is lemniscal, the face may be involved alone and rarely there is dissociation of position severe and vibratory loss. Upbeat nystagmus implies pontomedullary junction infarction. Respiratory dysfunction (Ondine’s curse), mild ptosis with hypohidrosis and XIIth nerve involvement may occur. Bilateral medial medullary infarction is manifest by flaccid quadriplegia, paralysis of the tongue, loss of lemniscal sensation, and cardiorespiratory failure. Combined medial and lateral medullary infarction is suggest by ipsilateral involvement of IX, X, XI, XII a Horner’s syndrome, contralateral lemniscal and spinothalamic sensory loss and hemiparesis. Ipsilateral ataxia is apparent if the patient is hemiparetic. The most common infarction of the pons is ventral and occurs due to occlusion of the anteromedial or anterolateral branches from the basilar artery. These infarctions are suggested by the constellation of facio-branchial crural
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hemiparesis, brachiocrural ataxia (homo-lateral to the motor deficit), ataxic hemiparesis and the dysarthria clumsy hand syndrome. Ataxic hemiparesis and dysarthria clumsy hand occur more often in the middle and upper pons or at the ventrotegmental junction. Pontine hemiparesis is greater in the distal upper extremity than the lower extremity. Pontine tegmental involvement is suggested by cranial nerve involvement (V, VIth) a depressed level of consciousness and an intranuclear ophthalmoplegia or 1½ syndrome. Tegmental pontine syndrome from occlusion of short circumferential vessels is headed by mild motor deficit, cranial nerve involvement V–VII, and lemniscal (medial) or spinothalamic sensory loss. The major circumferential artery of the lower pons is the anterior inferior cerebellar artery. Infarction of this artery characteristically causes sudden ipsilateral hearing loss, ipsilateral ataxia arm greater than leg (the reverse of PICA), dizziness, ipsilateral VIIth nerve palsy (small artery to the facial nerve peripherally in the CPA angle) and contra lateral loss of pain and temperature of the limbs and trunk. Mid basilar branch disease is suggested by the motor deficits with a fluctuating and progressive course, the ocular signs of horizontal gaze dysfunction, ataxic hemiparesis (level of the MCP) the clumsy hand dysarthria syndrome and classic lacunar syndromes. Basilar artery thrombosis may have dizziness as the most frequent early symptom, a herald hemiparesis, alternating levels of consciousness to stupor or coma. Dysarthria, pseudobulbar symptoms, tongue paralysis are common. Pin point pupils and ocular bobbing are diagnostic. The locked in syndrome with maintained consciousness is pathognomonic of ventral pontine infarction. The top of the basilar (distal 1/3) is commonly involved from embolic disease. The superior cerebellar artery and specific components of the posterior cerebral artery are involved and determine the specific symptoms and signs of the infarction. The superior cerebellar artery brainstem territory is most often infracted in conjunction with the posterior cerebral artery. Severe dysarthria with various degrees of appendicular ataxia are characteristic. The associated components of the posterior cerebral artery often suggest the diagnosis. The posterior cerebral artery supplies the medial temporal lobe, the midbrain (paramedian branches), the medial and lateral motor sensory thalamus, medial parietal lobe and the occipital cortex. Hippocampal formation ischemia from proximal PCA branch occlusion causes transient global amnesia. A similar amnestic syndrome, much longer lasting may also occur from dorsal medial thalamic ischemia from occlusion of the paramedian top of the basilar branch occlusion. Midbrain involvement from paramedian ischemia causes clonic syndromes involving the third nerve. Crossed hemiparesis is webers syndrome, crossed movement disorder is Benedict’s, and Claude’s is cerebellar ataxia. Disorders of vertical gaze such as 1½ syndrome, dissociation of vertical and horizontal
28
SECTION I. Vascular Disease
opticokinetic nystagmus and pupillary abnormalities are characteristic. A peduncular hemiparesis from cerebral peduncle infarction may simulate MCA infarction. The IIIrd nerve is not involved and the face may be spared. Rarely a nuclear IIIrd nerve syndrome is noted with bilateral ptosis, pupillary dilatation and failure of upgaze. Nystagmus retractorius may occur from vascular lesions of the periaquaductal ava but is more characteristic of dorsal midbrain pressure. Posterior cerebral artery thalamic involvement is characterized by stricking sensory involvement. The patient is aware of a midline split of sensory deficit. The leg may be involved first (VPL). The finger tip involvement of one hand is diagnostic of thalamic VPI nuclear involvement. Bilateral involvement of intraoral sensation is characteristic of VPM ischemia. Thalamic sensory loss includes vibration. This modality is never lost with a cortical lesion, but may be seen with dorsal column nuclear lesions. Thalamic motor involvement may be suspected from a characteristic thumb in the palm drift. Proprioceptive deficits combine with weakness. Ataxia of stance is characteristic of thalamic lesions that affect zones of proprioceptive and cerebellar input that converges in VL. Rarely dystonic postures are seen after UA/VL thalamic motor lesions. Occipital lobe posterior cerebral artery involvement should always be suspected in the face of a dense congruent VF deficit of which the patient is aware. If there is visual neglect the patient has parietal lobe involvement. Deficits in optic scanning and visio-coordinative hand function and fixation gaze comprise Balint’s syndrome that overlaps parietal and occipital posterior cerebral artery territories. Anton’s syndrome of cortical blindness is manifest by visual confabulation euphoria and normal pupillary function. Specific field deficits such as a checkerboard field, quadrantic altitudinal deficits, macular sparing and temporal crescent of spared vision all point to PCA occipital lobe branch occlusions. Lateral posterior choroidal artery infarction is suggested clinically by a homonymous quadrantanopsia. If the lateral geniculate body is involved, patients demonstrate a homonymous horizontal sectoranopia. There may be a concomitant transcortical aphasia and hemisensory deficit. This infarction is suggested by pulvinar involvement on MRI or CT. Medial posterior choroidal artery infarction is less common than lateral PchA infarction and is suggested by nystagmus retractorius and a central Horner’s syndrome. A mild hemiparesis and lemniscal sensory deficit may occur. CT or MRI of medial pulvinar involvement suggest this atrial territory. The following is a detailed differential analysis of posterior circulation vascular infarctions.
a. Arise from the proximal subclavian arteries b. Subclavian steal syndrome: 1) Obstruction of proximal subclavian artery (prior to the origin of the vertebral artery): a) Low pressure system within the ipsilateral vertebral artery b) Blood supply of the ipsilateral arm is deficient. During exercise these blood vessels dilate which further lowers vascular resistance in the exercised arm c) Higher pressure system: (1) Contralateral vertebral artery (2) Blood flows retrogradely down the ipsilateral VA into the arm (brainstem becomes ischemic) 2. Clinical symptoms: a. Most patients are asymptomatic in the face of arterial demonstration of a steal b. Complaints relate primarily to arm ischemia: 1) Fatigue, achiness with exercise, autonomic dysregulation (coolness) c. Neurologic symptoms are more common with concomitant carotid disease d. 75% of patients are asymptomatic (demonstrated in Takayasu’s disease) e. Rare neurologic symptoms (usually brief) occur: 1) Arm is used repetitively and often overhead 2) Blurred vision 3) Oscillopsia 4) Diplopia 5) Vertigo/spinning 6) Incoordination and imbalance 3. Clinical signs: a. Delayed antecubital and wrist pulse on the stenotic ride b. Smaller pulse volume c. Supraclavicular bruit (rare) d. Inflation of blood pressure cuff on the ipsilateral side: 1) If the bruit is generated from ECVA the bruit increases as more blood flows through the stenosis (less reversal) 2) If the bruit is generated from the subclavian stenosis the bruit decreases (increased pressure of ipsilateral system because there is no arm “run-off”) e. Clinical sequelae: 1) Stroke is rare with subclavian steal 2) Clots can form in a subclavian occlusion a) Embolization to vertebral artery territory 3) Raynaud’s phenomenon and autonomic dysregulation of the affected extremity may occur
Posterior Circulation
Occlusion or Severe Stenosis of the Subclavian and Innominate Arteries
1. Extracranial vertebral arteries (ECVA):
Innominate Stenosis on the Right Side
1. Decrease of carotid flow 2. Exacerbated by cigarette smoking
Chapter 1. Ischemic Stroke
3. 4. 5. 6.
Women > men Associated with other large vessel occlusive disease Right subclavian steal < frequent than left Clot may spread from the innominate into the carotid arteries a. Recurrent arm and brain ischemia b. Floating thrombi within the innominate artery 4. Differential Diagnosis of Subclavian Artery Disease a. Takayasu’s disease b. Severe atherosclerosis c. Aortic arch syndrome d. Syphilis (chronic aortitis) e. Cervical rib f. Giant cell arteritis g. Athletics that utilize a constant throwing motion In Takayasu’s disease, there is major inflammation and occlusion of the aortic arch vessels. Intermittent claudication of the arm is the most common symptom. Loss of vision with head position (precarious arterial supply to optic nerve head from posterior ciliary artery and central retinal artery compromise). Trophic loss of integument of the face and cataracts are common. Most patients with Takayasu’s disease are asymptomatic in the face of an arteriographic steal. Giant cell arteritis may compromise the great vessels at the arch with occlusion and stroke of the carotid artery. A cervical rib most frequently compresses the lower trunk of the brachial plexus with atrophy and weakness of the intrinsic hand muscles.
Vertebrobasilar Infarction
General Features of Lateral Medullary Territory Infarction
A. Proximal Vertebral Artery Disease 1. General Characteristics: a. Most frequent location of extra axial vertebral artery disease (ECVA) is at the origin from the subclavian artery (accessible to stenting and angioplasty) b. ICA and ECVA stenosis frequently are affected concomitantly c. Occurs in Caucasians > Asian and African Americans 2. Clinical Features a. Most common symptom is dizziness 1) Extremely rare for this symptom to be solitary 2) TIAs are not precipitated by arm movement as is the case with subclavian-steal syndrome (on rare occasions) b. Diplopia c. Dysphagia d. Oscillopsia (environment moving) e. Hemiparesis f. Bilateral leg weakness g. Sensory loss on the trunk
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3. Hypoplastic congenital vertebral and basilar arteries coexist: a. Patient suffers posterior circulation ischemia b. L-vertebral artery 80% of the time dominant over right c. Complete atresia of a vertebral artery is rare B. Lateral Medullary Territory (Posterior Inferior Cerebellar Artery) 1. Direct penetrators from the distal vertebral supply the lateral medulla and cerebellum 2. Posterior inferior cerebellar artery (PICA) supplies the lateral medulla and inferior cerebellum including the floccular nodular lobe 3. Posterior inferior cerebellar artery (PICA) frequently overlaps AICA territory or forms an AICA/PICA artery that supplies both territories 4. Variable: PICA/AICA supply to the lateral medulla or portions of the pons 5. Lateral medullary syndrome: most often occurs from occlusion of the distal perforators of the vertebral artery (VA) 6. If coexisting, AICA involved: middle cerebellar peduncle involved (core territory) 7. If coexisting, PCIA involved: lower cerebellum infarcted 8. Dorsal medulla supplied by branches of PICA (two posterior medullary arteries) C. Clinical Signs and Symptoms of Lateral Medullary Infarction 1. General: a. 40% are sudden (ictal) b. 60% a gradual or stepwise pattern over 24–48 hours c. 25% of patients have had a preceding TIA in the same arterial territory 2. Cranial Nerve Abnormalities: a. Dysphagia (rostral nucleus ambiguous) b. Hoarseness (caudal N. ambiguous) c. Crowing cough (N. ambiguous) d. Nausea and vomiting: 1) Vestibular nuclei 2) N. tractus solitarius (NTS) 3) Vomiting out of proportion to dizziness e. Ipsilateral Horner’s Syndrome 1) Descending central sympathetic fibers f. Hiccoughing (singultus; NTS) g. Ipsilateral VII nerve dysfunction 1) Occurs in 33–50% of patients. This is due to two groups of recurrent VII nerve fibers 2) In the upper medulla an origin that recurs through the lateral medulla 3) Fibers that leave the pyramidal tract (at the decussation in the medial medulla and course rostrally to the contralateral tegmentum h. Lateral medullary infarction lateral recurrent fibers of VII are infarcted
30
SECTION I. Vascular Disease
i. dysarthria caused by faciopalatal-glossal dysfunction and cerebellopetal pathways 3. Visual Signs and Symptoms a. Blurred vision b. Oscillopsia (with acute infarction) 1) Environment appears to move with patient’s nystagmus (usually horizontal) c. Vertical, horizontal or oblique diplopia 1) Disruption of the ocular tilt reaction (OTR) d. Incyclotropia 1) Cyclorotation abnormalities (clockwise or counterclockwise eye rotation) 2) Disruption of the vestibulo-ocular response (VOR) e. Horizontal and rotary nystagmus is most prominent to the ipsilateral side f. Skew deviation-ipsilateral eye down (otic-oculomotor pathways) g. Hypermetric saccades to the ipsilateral side (flocculo-nodular lobe of the cerebellum); hypoactive saccades to the contralateral side h. Deviation of the subjective visual vertical (SVV) to the ipsilateral side (internal concept of the body’s vertical position) 4. Motor Signs a. Ipsilateral hemiparesis (Opal ski’s Syndrome) 1) If the pyramidal fibers below the decussation at C2 are involved b. Contralateral hemiplegia occurs with the combined lateral and medial medullary syndrome; no weakness with pure PICA infarction c. Most often there is ataxia without weakness 5. Sensory Signs and Symptoms a. Ipsilateral facial pain and sensory loss 1) Touch, temperature, pain, cold decreased (ipsilateral V) 2) Loss of ipsilateral corneal reflex (V) 3) “Salt and pepper” facial paresthesia and pain b. Far lateral medullary infarction of the spinothalamic tract (STT) 1) Crossed hemisensory loss to pinprick and temperature on the contralateral body below the clavicle c. More medial infarction of the lateral medullary STT 1) Contralateral loss of pinprick and temperature of the face, trunk, and upper limb (the ipsilateral STT from the arm, trunk and leg) and the crossed ventrotegmental ascending fibers that cross medially in the medulla that subserve the contralateral face d. Medial medullary infarction 1) Bilateral facial hypalgesia with variable contralateral sensory loss (dog’s nose pattern) 2) “Onion skin” facial sensory loss
a) Nose involved b) Preauricular area spared c) Maybe seen as well with V nerve entry zone lesions 6. Headache a. Occipital b. Unilateral c. Non-throbbing d. Vth nerve origin of trigeminal pain afferents to the dura, proximal blood vessels and sinuses (somatic visceral convergence) 7. Brainstem Dysfunction a. Autonomic dysregulation 1) Cardiac arrhythmia 2) Blood pressure variability a) Lateral medullary vasomotor center b) Most often postural hypotension b. Respiration 1) Sleep apnea 2) Failure of automatic breathing Ondine’s curse a) Disruption of oscillations of lateral and medial respiratory neurons b) Afferent disruption of IX and X pulmonary afferents (Herring-Breuer reflex) may be carried centrally in STT 8. Cerebellar Syndrome a. Gait and ipsilateral limb ataxia b. Axial lateropulsion (if restiform body involved from concomitant medial branch infarction); patient is pushed to the side of the lesion
Unilateral Medial Medullary Infarction (Dejerine’s Syndrome)
Less than 1% of posterior circulation strokes Branch occlusion from the VA A. Motor Signs and Symptoms 1. Flaccid hemiparesis a. Contralateral if above C2 b. Ipsilateral if the infarction spreads to the cervical medullary junction 2. Spasticity within days to weeks a. Flexion of upper extremities b. Extension of the lower extremities 3. Rarely weakness can be minimal or absent 4. Rarely upper limb monoparesis a. Fibers after decussation may be lateral 5. Motor deficit is more severe distally in the upper extremity (also typical for pontine infarction) 6. Patterns of weakness at the level of the pyramidal decussation a. Leg fibers may cross anteriorly and then remain lateral to arm fibers
Chapter 1. Ischemic Stroke
b. Some studies – arm fibers decussate anteriorly to leg fibers c. Crural paresis: 1) Proximal portion of the limbs affected with finger and toe movements preserved 2) Hemiplegia cruciatas a) Arm involved ipsilaterally with contralateral leg weakness d. Pontine recurrent pathway may be infarcted with facial weakness B. Sensory Signs and Symptoms 1. Contralateral lemniscal type sensory loss of the hemibody with or without the face 2. More marked distally 3. May involve the face only 4. Pseudospinal dropped sensory level on the trunk 5. Dissociation between vibration and position loss a. Vibration may be involved with more lateral extension 6. Pain sensation a. Occasionally decreased with preserved temperature, sensation, and mild hypesthesia C. Cognitive Dysfunction 1. Medial reticular formation involvement: a. Apathy b. Somnolence c. Hallucinations d. Delirium 2. Pathologic laughing and crying with infarction of: a. Internal capsule b. Pons c. Pyramidal tract (usually bilateral) d. Bilateral temporal lobe (usually trauma) e. Medial frontal lobe (laughing) D. Ophthalmologic Signs 1. Upbeat nystagmus: a. Dorsolateral medulla or pontomedullary junction infarction that spares the medial medulla b. Ipsilateral MLF or perihypoglossal nuclei are involved in upgaze c. Horizontal nystagmus (ipsilateral) or multiple directional nystagmus related to vestibular nuclear involvement or their connections to the cerebellum in the lateral medulla d. Rare – ocular bobbing (usually a pontine lesion) E. Lateral Pulsion 1. Contralateral lateral pulsion a. Dorsolateral medulla and cerebellum are not involved b. Patient feels as if he is pushed to the side c. Lesion at the level of the restiform body F. Respiratory Dysfunction 1. Ataxic breathing 2. Decrease of voluntary control of breathing secondary to corticospinal destruction and lack of intercostal muscle control
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3. Loss of automatic breathing (Ondine’s curse) G. Autonomic Dysregulation 1. Mild ptosis with hypohidrosis a. Severe miosis (0.5 mm pupil) with pontine infarction b. Dissociation of ptosis and pupillary sympathetic fibers is due to a somatotopic arrangement of sympathetic fibers around the N. ambiguus 2. Bladder retention or inhibited contractions only occur with bilateral MMI H. Cranial Nerve XII 1. Isolated contralateral XII nerve 2. More common with hemorrhage than infarction I. Isolated Drop Attacks 1. May progress to stroke over several days 2. Ischemia of: a. Medullary or pontine corticospinal fibers b. Medial reticular formation involvement (loss of tone)
Differential Diagnosis of Vascular Etiologies of Unilateral Medial Medullary Infarction
a. b. c. d. e.
Branch occlusion from VA (upper medulla) Dolichoectasia of vertebrobasilar system Embolus Syphilis Branch occlusion from the anterior spinal artery (lower medulla) secondary to atheroma f. of the VA or anterior spinal artery
Underlying Associated Conditions
a. b. c. d. e.
Diabetes mellitus Birth control pills Dissection of VA in 3/4 of patients Thrombosis of VA in 3/4 of patients Embolus in 1/4
Bilateral MMI Infarction
A. Clinical Features: 1. Quadriplegia (flaccid) 2. Associated loss of lemniscal sensation 3. Paralysis of the tongue 4. May have step wise progression 5. Bladder retention or uninhibited contractions 6. Death by cardiorespiratory failure B. Differential diagnosis: 1. Anomalous anterior spinal from one vertebral artery 2. Occlusion of the ASA after it forms a single vessel
32
SECTION I. Vascular Disease
Medial and Lateral Syndrome (Babinski–Nageotte)
1. Clinical features of combined LMI and MMI: a. IX, X, XI, XII ipsilaterally b. Horner’s ipsilaterally c. V ipsilateral (most often STT modalities) d. Ocular findings (LMI and MMI) e. Contralateral hemiparesis; may be ipsilateral (depending on infarction below decubation be C2) f. Lemniscal and STT sensory loss (contralateral) g. Ipsilateral ataxia
Pontine Infarction
1. General Features a. Isolated pontine infarction occurs in 15% of acute vertebrobasilar strokes b. The territory supplied by intrinsic pontine vessels is constant c. In 1/3 of patients TIAs precede stroke onset: 1) Spontaneous laughing and crying spells – “Fourier prodromique” 2) Herald hemiparesis 3) Pseudoseizure – tonic limb spasms with consequent paresis
d. Dysarthria clumsy hand (DCH) syndrome e. AH and DCH occur in the middle upper pons; in the ventrolateral pons, or at the ventrotegmental junction f. Dysarthria (posterior 1/3 of ventral pons; medial)
Patterns of Weakness in Pontine Hemiparesis
a. Greater in the distal upper extremity than lower extremity b. Less commonly the leg has distal weakness greater than the arm c. Crural or brachiocrural paresis with preservation of finger and toe movement d. Arm fibers – disrupted by more dorsal lateral lesions e. Leg fibers – disrupted by more lateral lesions f. Facial palsy associated with palato-glossal weakness – involvement of pontomedullary bundle g. Dysarthria more common in left pontine infarction h. Isolated dysarthria and facial weakness are rare i. Correlation of severity of motor deficits and contralateral ataxia j. Ataxia – involvement of corticopontocerebellar fibers (Türck’s tract); make up the MCP
Ventral Pontine Infarcts and Tegmental Involvement Ventral Infarction of the Pons
a. Most common type; approximately 55% of pontine infarcts b. Occlusion of anteromedial or anterolateral arteries (from the basilar artery) c. Localized to the middle or lower pons d. May involve the medial tegmentum e. Rarely reaches the floor of the IVth ventricle
Ventromedial Pontine Syndrome
a. Large infarcts: anteromedial or anteromedial and anterolateral territories b. Facio-brachial crural hemiparesis with dysarthria c. Homolateral (to the motor deficit) brachiocrural ataxia; occasionally contralateral curral ataxia d. Dysarthria with medial infarction at the level of the MCP
Ventrolateral Pontine Syndrome
a. Smaller infarction in anterolateral territory b. Pure motor hemiparesis (PMH); leg representation is dorsolateral c. Ataxic hemiparesis (AH)
1. 3/4 of patients – associated medial tegmental dysfunction, usually mild and transient a. Lemniscal sensory deficit b. Vth nerve weakness c. Decreased level of consciousness d. Fascicular VIth nerve palsy e. Intranuclear ophthalmoplegia f. One and a half syndrome (abduction alone of the contralateral eye) 2. Collateral vascularization of short and long circumferential vessels is the explanation for transient nature of tegmental signs 3. isolated dorsal pontine syndrome is rare, suggests nonischemic etiology
Tegmental Pontine Syndrome
1. Represent approximately 30% of pontine infarctions 2. Small lacunar infarcts 3. Mediolateral tegmental area of the middle upper pons; occlusion of short circumferential vessels 4. Mild motor deficit 5. Eye movement disturbance 6. Lemniscal or spinothalamic sensory loss 7. Cranial nerve palsy V to VII
Chapter 1. Ischemic Stroke Ventrotegmental Pontine Syndrome
Bilateral Ventrotegmental Infarcts
1. Combination of lateral and medial tegmental signs 2. Intranuclear ophthalmoplegia with severe motor deficit
1. 2. 3. 4. 5. 6. 7.
Lateral Pontine Syndrome (Long Circumferential Cerebellar Arteries)
1. AICA or superior cerebellar artery infarction 2. Lateral pontine syndrome of Marie-Foix is rare a. Homolateral cranial nerve palsies are rarely seen
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Least common of isolated pontine infarcts (11%) Associated with extension or multiple brainstem infarction Acute pseudobulbar palsy Bilateral motor deficits with tegmental signs Para and tetraplegia Ataxic tetraparesis Locked in syndrome: a. Awake b. Unable to move c. Upgaze and eye closure maintained
Pontine Pure Motor Hemiparesis (PMH)
Clinical features of pontine hemiparesis: 1. Dysarthria, vertigo, gait abnormality 2. Lacunar process (spares the basal surface); if the basal surface is involved this suggests a branch artery occlusion 3. Approximately 60% have transient symptoms 4. Midpontine – primarily upper limb involvement 5. Mild dysarthria-corticobulbar fibers are affected 6. Contralateral cerebellar ataxia (25% of patients)
Basilar Branch Disease
a. Nonlacunar (maximal diameter > 1.5 cm) b. Unilateral ventral infarct extending to pontine surface c. Bilateral infarcts: atheroma of the basilar artery wall occludes one or more perforators d. Motor deficits with fluctuating and progressive course e. Small artery disease: tegmental or small ventral infarcts do not extend to the surface of the pons; 1) Classic lacunar syndrome
Pontine Ischemic Rarefaction (MRI Evaluation)
1. 2. 3. 4. 5.
Hypertensive vascular changes Increased perivascular changes Perivascular demyelination Gait instability MRI increased T2 pontine signal
Pontine Signs
1. 2. 3. 4.
Horner’s syndrome (lateral involvement) Hypogeusia (ipsilateral taste loss) Hemiataxia (MCP) Oculopalatal pharyngeal myoclonus a. Mollaret’s triangle b. Disruption of fibers between the inferior olive, dentate nucleus and the VL nucleus of the thalamus 5. Contralateral STT sensory loss
Isolated Tegmental Pontine Infarcts
1. Supranuclear eye movement disturbance 2. Sensory deficit: one limb; cheiro-oral pattern a. Abducens palsy (isolated) b. Facial palsy (isolated)
Clinical Signs and Symptoms of Basilar Artery TIA Prior to Infarction
1. Increasing TIA frequency 2. Diplopia, vertigo, blurred vision, ataxia, gait disturbances, hemiparesis 3. Confusion and somnolence; to stupor and coma 4. Motor abnormalities, pupillary abnormalities, hyperreflexia, bilateral Babinski signs
Clinical Signs and Symptoms of Basilar Artery Thrombosis
1. 2. 3. 4. 5.
Herald hemiparesis Dizziness most frequent early symptom Dull, non-throbbing headache (basiocciput) Alternating levels of consciousness (confusion to stupor) Dysarthria, pseudobulbar symptoms, paralysis of the tongue, emotional lability 6. VI and VII cranial nerve palsies with contralateral hemiplegia and paraesthesias 7. Bilateral pontine infarction symptomatology 8. Ocular bobbing, ocular dipping, <0.5 mm pupils
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SECTION I. Vascular Disease
Midbrain Infarction
Neurophthalmological Deficits
1. Paramedian arteries a. Isolated third nerve palsy b. Nuclear third nerve: bilateral ptosis; bilateral pupillary dysfunction (large): bilateral failure of upgaze (superior rectus palsy) 2. IIIrd nerve and contralateral hemiplegia (Weber’s Syndrome) a. Supranuclear gaze palsy; mydriatic or miotic pupil depending on sympathetic involvement; occasional sensory dysfunction: P1 segment of the PCA is infarcted (medial 3/5 of the cerebral peduncle infarcted); patients are awake; hemiparesis may spare the face b. Concomitant thalamic and occipital lobe involvement may occur 3. IIIrd nerve plus cerebellar signs a. IIIrd nerve palsy and contralateral cerebellar dysfunction is Claude’s Syndrome. Basilar paramedian artery (dentatothalamic projections are involved) b. IIIrd nerve palsy plus contralateral abnormal movements (Benedict’s Syndrome). Tremor (rubral, large amplitude at right angle to the line of movement); chorea (paramedian artery; infarction of the red nucleus, dentatothalamic fibers often with third nerve paralysis) c. The closer the infarction is to the red nucleus, the greater the tremor and failure of extremity postural fixation 4. Supranuclear conjugate vertical gaze palsy a. Median or paramedian infarction of the upper midbrain b. Superior cerebellar artery: infarction; destruction of: 1) Periaqueductal grey matter 2) Posterior commissure c. Single trunk (paramedian thalamic mesencephalic artery of Percheron) infarcts involves the medial and subthalamic (STN) areas bilaterally as well as the upper midbrain d. Upgaze paralysis: 1) Posterior commissure, riMLF (rostral interstitial nucleus of the MLF); PAG e. Down-gaze palsy: 1) Bilateral upper midbrain infarction; more caudal than upgaze palsy (above the red nucleus; Pasik’s syndrome) f. Combined up and down gaze palsy: 1) Bilateral or unilateral midbrain infarcts 2) Unilateral lesion of the riMLF may decrease conjugate vertical gaze g. Supranuclear disconjugate vertical gaze palsies: 1) Monocular elevation palsy 2) Vertical one and a half syndrome 3) Infarction of paramedian upper midbrain
1. Skew deviation (lesion is on the side of the down eye) 2. Tonic ocular-tilt reaction (incyclotropia or excyclotropia) dysfunction 3. Intermittent corectopia (pupillary size changes) 4. Upper lid retraction (Collier signs; increased upper lid retraction on down gaze; central caudal nucleus of the IIIrd nerve involved) 5. Ptosis with intranuclear ophthalmoplegia 6. Convergence retraction nystagmus (PAG; and involvement of the periaqueductal grey area) 7. Dissociated vertical gaze palsies
Associated Clinical Midbrain Signs
Gaze palsies with: a. Coma and hypersomnia b. Akinetic mutism c. Disorientation to time and place d. Antegrade amnesia e. Motor and multimodal neglect f. Faciobrachial hypesthesia g. Transcortical motor aphasia h. Delayed athetoid or clonic movements
Specific Stroke Syndromes
1. Classic lacunar syndromes from midbrain infarcts (Weber’s; Claude’s, Benedict’s, Masugi’s) 2. Lateral midbrain involvement of the cerebral peduncle (P1-PCA) pure motor stroke 3. Dorsolateral midbrain: hemiparesis, hypesthesia, ataxia
Midbrain Locked-in-Syndrome
1. Bilateral lateral midbrain infarction 2. Midbrain hematoma-pure sensory stroke (rare)
Hemiplegia with Posterior Cerebral Artery Occlusion
1. Proximal P2 infarction a. Hemiplegia b. Visual disturbance c. Neuropsychological abnormalities d. Mimics MCA occlusion
Chapter 1. Ischemic Stroke Rare Stroke Syndromes from Midbrain Infarction
1. Subthalamic small deep infarcts a. Abnormal movements and asterixis b. Unilateral or bilateral ballistic movements c. Blepharospasm 2. Cerebellar syndromes a. Rostral and lateral red nucleus infarcts with cerebellar syndromes b. Unilateral ataxia with superior cerebellar infarct (SCA) with rostral midbrain signs c. Superior cerebellar decussation syndrome (ataxia of all extremities); infarction of the decussation of the brachium conjunctivum (Windekink’s commissure; level of the IVth nerve at the inferior colliculus) 3. Masugi’s syndrome a. Ipsilateral IIIrd, IVth nerve b. Ipsilateral ataxia (SCP) c. Contralateral hemiparesis d. Contralateral hemisensory defect e. Infarction of the superior cerebella artery or branches of lateral and medial posterior choroidal arteries 4. Peduncular Hallucinosis a. Vivid visual hallucinations; objects moving (kaleidoscopic); peculiar dress b. Rarely auditory hallucinations c. Often occurs at sundown
Posterior Circulation Major Artery Strokes (Long Circumferential Arteries)
Superior Cerebellar Artery Infarcts
A. General Features: 1. Rarely involve the brainstem territory of the SCA; usually partial; good outcome 2. Early and delayed edema (one week); brainstem compression with tonsillar herniation if edema is severe (4–7 days; pseudotumoral presentation) 3. Associated infarction in other territories with complete SCA infarction (usually that of PCA) a. Rostral territory of the basilar artery b. Unilateral or bilateral occipitotemporal lobe infarction c. Thalamic; subthalamic and mesencephalic infarcts d. Rare upper ventral pontine infarction e. 1/3 occur with PICA and AICA infarction f. Partial SCA infarcts most frequently involve the rostral superior cerebellar artery territory g. Some SCA infarcts occur with MCA infarcts due to emboli
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Clinical Features of SCA: 6 Clinical Patterns
1. Classic SCA a. Occur in 3% b. Involves the brainstem territory of SCA c. Ipsilateral limb dysmetria d. Ipsilateral Horner’s syndrome e. Contralateral IV nerve involvement f. Contralateral loss of pain and temperature Unusual signs and symptoms of classic SCA infarction a. Ipsilateral loss of mimetic facial b. Unilateral or bilateral hearing loss (nucleus of lateral lemniscus) c. Sleep disorder (locus ceruleus) d. Ipsilateral choreiform, athetotic or coarse tremor e. Head tremor or unsteadiness of the head f. Palatal myoclonus; may be associated with myoclonus of the tongue, vocal cord, jaw and face 2. SCA infarction with top of the basilar artery involvement a. Vomiting, dizziness, visual field deficits, diplopia, paraesthesia, ataxia, weakness and drowsiness b. Occipitotemporal lobe concomitant involvement: 1) Cortical blindness and hemianopsia (Anton’s syndrome) 2) Balint’s syndrome 3) Memory loss or confusion c. Thalami-mesencephalic infarction 1) Thalamic multimodal sensory loss; latter possibly Dejerine Roussy syndrome (VPL) 2) Contralateral Horner’s syndrome 3) Appendicular ataxia (ataxia of stance); involvement of cerebellar thalamic projections 4) Behavioral abnormalities: abulia, contralateral spatial neglect, memory loss, transcortical motor aphasia d. Midbrain infarction (concomitant) 1) Claude’s, Benedict’s, Weber’s, Nothnagel’s Syndromes, Masugi’s 2) Parinaud’s Syndrome 3) Pseudo VIth nerve, gaze paresis or deviation, Collier’s sign, pupillary abnormalities (light near dissociation, inverse Argyll–Robertson pupil, miosis or mydriasis, corectopia) 4) Drowsiness, peduncular hallucinosis, confusion 5) Hemiballismus (subthalamic involvement) 3. Coma at initial presentation a. Tetraplegia and III nerve palsy b. Embolic occlusion of basilar tip 4. SCA involvement with ICA infarction a. Aphasia b. Brachiofacial sensorimotor hemiplegia c. Cardiac embolism; occlusion of innominate artery with embolism to right MCA and vertebral artery with propagation to SCA 5. Cerebellar vestibular syndrome
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SECTION I. Vascular Disease
a. Occipital headache and gait ataxia b. Dizziness and vomiting c. Nystagmus (most often horizontal to affected side) or contralaterally; rarely vertical d. Dysarthria-cardinal symptom of SCA infarct e. Hemiparesis in 25% 6. Lateral SCA Syndrome (anterior rostral territory) a. Arm and leg dysmetria b. Ipsilateral axial lateropulsion c. Dysarthria d. Nystagmus; saccadic overshoot (ipsilaterally) 1. Medial SCA syndrome a. Most medial branch: unsteadiness of gait b. Lingula, culmen, centralis lobules (anterior cerebellar lobe) appendicular ataxia (legs affected > arm), head tilt (ipsilateral) c. Paraverbal involvement: dysarthria; left sided paravermal zone of rostral cerebellum causes consistent dysarthria
Clinical Signs and Symptoms
1. Prodromal vertigo (minutes); dizziness, dysarthria a. Ipsilateral peripheral VIInd nerve (small artery to facial nerve in CPA angle) b. Hearing loss (sudden) ipsilaterally c. Ipsilateral Vth nerve involvement d. Horner’s syndrome (ipsilaterally) e. Ipsilateral appendicular dysmetria (arm > leg) f. Contralateral loss of pain and temperature of the limbs and trunk g. Delayed facial paralysis Unusual Signs
a. Ipsilateral conjugate or lateral gaze palsy (floccular involvement) b. Dysphagia (superior part of the lateral medulla) c. Ipsilateral motor weakness (involvement of the corticospinal tract in the pons or mesencephalon contralaterally) d. Periodic alternating nystagmus
Differential Diagnosis of Causes of SCA Infarction
Coma
1. Cardiac embolic source 2. Artery-to-artery embolus a. Vertebral artery b. Aortic arch 3. Vertebral dissection 4. In young patients a. SCA dissection b. Fibromuscular dysplasia (FMD) c. Patent foramen ovale (PFO)
Anterior Inferior Cerebellar Artery Infarction
1. Origin: first 1/3 of the basilar artery 2. Brainstem signs at presentation 3. Involved territory: lateral caudal pons; middle cerebellar peduncle (always involved) 4. Supplies the inner ear: internal auditory artery from which derive the anterior vestibular artery; common cochlear artery 5. 70% involve the anterior inferior flocculus 6. AICA and PICA may arise from a common trunk from the vertebral or basilar artery 7. Anastomosis between the AICA and PICA – constant when both arteries have equal dominance 8. AICA dominance on one side; then consequent ipsilateral vertebral PICA hypoplasia 9. Infarction of the inferolateral pons; may extend up to the middle third of the lateral pons or down to the superior part of the lateral medulla 10. AICA infarction: may be associated with PICA and SCA infarction with consequent ventromedial pontine infarction
a. Tetraplegia (massive ventromedial infarction of the basis pontis) b. Cerebellar infarction PICA/AICA/SCA distribution c. Isolated vertigo mimicking labyrinthitis; infarction of the internal auditory artery or its superior vestibular division d. Isolated cerebellar signs Differential Diagnosis of SCA and AICA Infarction
1. Atherosclerotic lower basilar artery occlusion 2. Occlusion of the vertebral artery above PICA 3. Vascular anomalies of the vertebrobasilar system: a. Persistent trigeminal artery with embolus from carotid system b. Dolichoectasia of the basilar artery c. Hypoplastic vertebral artery 4. Pure AICA: a basilar branch occlusion; plaque in the basilar extends to occlude its origin; micro atheromata block the origin of the artery 5. Migraine (Bickerstaff variant) 6. Extracranial and intracranial vertebrobasilar dissection: a. Intradural dissection: 1) Subadventitial hematoma of the basilar artery causes: a) Subarachnoid hemorrhage b) Brainstem stroke c) Pseudoaneurysm d) May occur silently b. Extracranial dissection 1) Hematoma within the media or intima 2) Emboli at the site rather than a blood flow limiting process cause symptoms
Chapter 1. Ischemic Stroke
7. Post operative cerebellar and brainstem stroke: Signs and symptoms: a. Altered consciousness; stupor, restless agitation b. Vestibulocerebellar syndrome Differential diagnosis: a. Neck positioning during or after surgery b. Thrombus that embolized from compressed arteries 8. Hypercoagulability after surgery a. Increased thrombin activity b. Increased fibrinogen c. Increased factor VIII d. Decreased fibrinolytic activity e. altered platelet function
Posterior Cerebral Artery (PCA) Infarction
Vascular Territory Supplied by the PCA
General 1. Major blood supply of: midbrain, thalamus, occipital lobes, part of the posterior inferior parietal lobe 2. The arterial segment prior to the posterior communicating artery fusion with the basilar artery is the P1 segment a. 10% of PCAs take origin from the carotid artery (fetal origin). If this occurs, there is a concomitant hypoplastic P1 from the basilar artery 3. 29% of patients have large or (24%) unusually small PCA arteries Vascular Supply 1. Vascular supply of the P1 segment (peduncular or pre communal segment; between the tip of the basilar artery and the posterior communicating artery) is: a. Medial midbrain; posteromedial thalamus b. Origin of the paramedian mesencephalic arteries (take off is the top of the basilar) 2. Tuberothalamic (polar arteries) a. Origin is the posterior communicating artery b. Anterior and anterolateral thalamus c. Tuber thalamic artery may be absent. Its territory is then supplied by the thalamic subthalamic artery (thalamoperforating arteries) 3. P2 segment is the origin of the peduncular perforating (PPA); thalamogeniculate arteries (TGA) a. Thalamoperforate artery supplies: 1) Lateral midbrain 2) VA and VL of the motor thalamus 3) Part of the internal capsule 4) VPL, VPM of the thalamus b. Thalamogeniculate artery supplies the ventrolateral thalamus: arteries arise form the ambient portion of the PCA c. Anterior temporal artery arises form the ambient portion of the PCA and supplies the medial temporal lobe
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d. Posterior temporal artery (origin between the tentorium and the medial temporal lobe) e. Parietooccipital artery: originates form the ambient segment; supplies the occipital and medial inferior parietal lobe); this branch is the origin of the posterior pericallosal artery f. Calcarine artery 1) Usually arises as a single branch of the PCA 2) In 16% of patients the calcarine artery arises from the parietooccipital artery
Clinical Symptoms and Signs of Unilateral PCA Ischemia and Infarction
1. PCA stenosis: a. TIA’s precede infarction b. Usually atherosclerotic narrowing 2. General Features of PCA Infarction: a. Ambient section is affected most frequently which causes a hemispheric branch occlusion b. P1 segment – 13% of PCA occlusions c. PCA with thalamic involvement – 37% of infarctions d. Occipital, parietal and posterior temporal branch arteries are frequently involved concomitantly e. Anatomic areas involved: medial midbrain, posteromedial thalamus, lateral thalamus, and posterior hemisphere f. Penetrating arteries from the top of the basilar artery may arise from one PCA (artery of Percheron) and therefore the thalamic infarction may be bilateral and paramedian: 1) Infarctions are usually embolic from the heart, proximal aorta and the proximal vertebral arteries (to the top of the basilar artery) 2) Patients that have suffered rostral paramedian tegmental mesencephalic and posteromedial thalamic infarcts are comatose, hyper somnolent and may demonstrate vertical gaze palsies and an amnestic state The distinguishing features of proximal PCA infarction (P1 precommissural branch) are: a. Hemiplegia, infarction of the cerebral peduncle (medial 3/5); may spare the face b. Paramedian mesencephalic and PPA arteries are involved c. Partial or complete III nerve palsy d. Nuclear III rd nerve signs include: 1) Bilateral ptosis (central caudal nucleus) 2) Failure of upgaze bilaterally (superior rectus is bilaterally innervated) 3) Dilated pupils 4) Rare a. Midline infarctions: patients are lethargic and abulic
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SECTION I. Vascular Disease
Ambient Segment (P2) Infarction (Thalami Perforating Artery)
Occlusion is proximal to the origin of the thalamogeniculate artery: 1. Vascular supple to the motor thalamus a. Ventroanterior, ventrolateral nuclei b. VOA, VIM, VOP (stereotactic nomenclature, part of VL) 1) VIM is the target for stereotactic surgery to relieve tremor) 2. Motor symptoms: a. Contralateral 4–6 HZ tremor b. Usually sudden onset of choreoathetosis: 1) Frequent arterial involvement of diabetic patients c. Rare contralateral dystonia d. Thalamic hand e. More medial lesions in this territory cause thalamic ataxia 1) Interrupt cerebellar projections (dentatorubral loop) 2) “ataxia of stance”
Thalamogeniculate Artery Infarction (TGA)
a. Infarction of the lateral thalamus and posterior temporal lobe is known as the syndrome of Foix–Hillman a. Pathogenesis: trunk PCA occlusion (multiple penetrating branches involved) or single atheromatous branch occlusion
Symptoms of Ventrolateral Thalamic Infarction (thalamogeniculate artery, TGA)
1. Sensory symptoms a. Leg may be involved most severely; pattern of face, arm and leg b. Conscious perception that the symptoms bisect the body (face, trunk, penis) c. Intraoral involvement (may be bilateral) d. Quality of sensation: tingling, pricking, crawling, burning (active dysesthesias and paraesthesias) e. Loss of pinprick, touch, or thermal sensation. May lose vibration sensibility which is rarely lost with cortical infarction. The other location for vibratory loss is the dorsal column nuclei. f. If medial, ventrolateral or thalamoparietal projections are involved: a. Proprioceptive, thermal sensory loss, decreased pain g. Tips of the fingers of the contralateral hand (VPI nucleus) 2. Slight hemiparesis 3. Clumsiness and ataxia (dentate thalamic projections) 4. Choreiform and ataxic limb movements (contralateral)
5. Thalamic hand posture 6. Clinical symptomatology of thalamic pain: a. Delayed onset (months after VPM/VPL infraction) b. Hyperpathic c. Mechanical and thermal hyperalgesia and allodynia of the affected area d. Spontaneous e. If provoked-not stimulus bound 7. Associated infarcts in the temporal and occipital lobes if midbrain and thalamus are involved
PCA – Hemispheral Infarction
1. Visual field loss: a. Most common defect – contralateral homonymous dense VF loss b. Infarction may occur in: lateral geniculate body, optic radiations, or the striate cortex c. 50% of patients are aware of the deficit d. If unaware of the deficit there is parietal lobe involvement 2. Acute or with resolution of VF defect: a. Photopsias, colors, and hallucinations in the affected field 3. Usual VF deficits: congruent contralateral hemianopia, inferior or superior quadrantanopsia a. Macular sparing often noted (middle cerebral artery supply) b. Involvement or sparing of the contralateral visual temporal crescent (anterior most portion of the calcarine fissure subserves the most peripheral temporal field) c. Homonymous central scotomata (occipital pole infarct) d. “Checker board” deficit (one inferior quadrant with contralateral superior quadrant) 4. Complex visual phenomena Visual Perseveration a. Object seen in sighted field-then noted in the defective hemifield although gaze fixation maintained b. Object in sighted field appears in the defective hemifield after gaze is shifted to defective field c. Palinopsia (perseveration of an object) d. Motion detection in blind field but no ability to discriminate (Riddoch’s object phenomena) e. Defects in distance, depth and localization in the defective hemifield 5. Sensory symptoms of PCA hemispheric infarction a. Paraesthesia, numbness or loss of pain; thermal or positional sense loss
Higher Cortical Deficits from Hemispheric Infarction
1. Dominant Hemisphere: parieto-occipital and or temporal branch occlusion:
Chapter 1. Ischemic Stroke
2.
3.
4.
5.
a. Alexia without agraphia patients; write, speak, and spell normally. They cannot read words or name colors (damage must include left occipital cortex and splenium of the corpus callosum). Can read letters and numbers. Cannot access Wernicke’s area b. Alexia with agraphia 1) Angular gyrus or white matter of the inferior parietal lobule involved 2) Abnormalities of reading, writing, and spelling Inferior parietal lobule infarction a. Decreased ability to read letters and paragraphs b. Decreased spelling and writing c. Components of Gerstmann syndrome are noted: dyscalculia, finger agnosia, right left confusion, and dysgraphia and conduction aphasia. The latter may be accompanied by paraphasia Paralexia a. DH: reading errors to the right side of words b. NDH: reading errors at beginning of words Visual agnosia a. Dominant hemisphere b. Concomitantly with alexia and agraphia and decreased color naming Amnesia a. Involvement of left hippocampus and adjacent white matter
ND Hemisphere – PCA Infarction
a. Neglect of contralateral visual field b. Constructional apraxia (parietal and temporal lesions) c. Right posterior parietal lesion-disorientation for geographical space d. Reduplicative paramnesia (two versions of a geographic location)
Mechanisms of Unilateral PCA Infarction
1. Embolism: cardiac, proximal vertebral artery, arch of aorta, fetal origin of PCA 2. Emboli arise from the end of atheromatous plaques of recently occluded proximal vertebral artery 3. African Americans and Asians patients: infarction is more frequent in context of stenosis with in situ thrombosis 4. Migraine 5. Coagulopathy 6. Transtentorial herniation – temporal and calcarine branches compressed against the tentorium
Bilateral PCA Infarction
1. Infarcts often restricted to bilateral inferior or superior calcarine branches
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Clinical Syndromes
A. Cortical blindness (Anton’s syndrome) 1. Bilateral infarction of the striate cortex a. Anton’s syndrome 1) Denial of blindness 2) Maneuver around objects (visual crescent remains, bilateral hemianopsias or scotomata) 3) Visual confabulation 4) Normal pupillary reaction to light 5) Euphoria B. Balint’s Syndrome (Superior Parietal and Occipital Lobe) 1. Simultagnosia (patients see objects piecemeal); cannot describe the entire object) 2. Optic ataxia (lack of coordination of hand eye movements; usually under reaching the object) 3. Apraxia of gaze (inability to look at an object on command) 4. Difficulty in breaking fixation of gaze 5. Poor visual scanning of areas of interest 6. May be limited to one visual field C. Amnesia 1. Bilateral infarction of the temporal lobe 2. Amnesia occurs concomitantly with visual sensory loss and acute depression of level of consciousness D. Emboli and infarction (below calcarine fissure) 1. Upper quadrant altitudinal defect 2. Abnormal color perception 3. Difficulty in recognizing faces (prosopagnosia) 4. Inability to re visualize the form of an object; able to re visualize direction and place relationships of objects 5. Agitated delirium (involvement of the lingual and fusiform gyri, inferior temporal lobe) 6. Central achromatopsia (may perform adequately on Ishihara plates) unable to match hues or colors 7. Agitated delirium (left posterior inferior temporal lobe) 8. Emboli to tip of the basilar artery have predilection for inferior calcarine branches Bilateral Superior Bank Infarction a. Severe hypotension (MCA/PCA border zone) is the usual mechanism b. Less common than lower bank infarcts c. Disorientation to place, difficulty in revisualization of locations (where people and places are topographically) E. Pathogenesis of Bilateral PCA Infarction 1. Seriatim infarction; stenosis of arteries from atherosclerosis 2. Simultaneous; embolus to top of the basilar artery or from thrombus in the basilar artery 3. Capillary-leak syndrome (primarily white matter) of the occipital lobe a. Hypertensive encephalopathy
SECTION I. Vascular Disease
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b. c. d. e.
Cyclosporine and FK 506 (tacrolimus) Uremia Eclampsia Dissection of distal basilar artery
a. Homonymous horizontal sectoranopia 2. AchA a. AchA-middle horizontal sector is spared
Ocular Motility Deficits with PchA Infarction Infarction of the Lateral Posterior Choroidal Artery (L PchA)
PchA territory involved: 1. Lateral geniculate body (LGD) 2. Pulvinar and posterior thalamus 3. Hippocampus and parahippocampal gyrus Clinical syndromes of lateral PchA infarction 1. Homonymous quadrantanopsia 2. With or without hemisensory loss 3. Homonymous horizontal sectoranopia (lateral LGD) 4. Memory loss 5. Delayed movement disorder 6. Transcortical aphasia Specific visual field deficits 1. Wedge or tubular homonymous sectoranopia with delayed sectorial optic atrophy 2. Lower or upper quadrantanopsia more common but less specific with LGD infarction 3. Wedge or tubular sectoranopia also possible with AchA, MCA, PCA infarction 4. Visual field deficits with concomitant anatomical lesions of the LGD Correlative anatomy of the lateral geniculate body 1. Anterolateral LGD subserve lower quadrants 2. Anteromedial LGD subserve medial quadrants 3. Posterior LGD subserve the macula 4. Central LGD: supplied by lateral posterior choroidal artery a. VF defect: homonymous horizontal sectoranopia b. Supplied by PchA 5. AchA also supplies the LGD Visual field deficits 1. Quadruple sectoranopia is characteristic 2. Complete homonymous hemianopia 3. Superior quadrantanopsia-may have macular sparing 4. Homonymous hemianopia a. Sparing of the horizontal sector b. Inferior lateral LGD infarction 5. Homonymous superior-quadrantanopsia a. Lateral geniculate infarction b. Infarction of: 1) Optic tract 2) Origin of the geniculocalcarine tract
Differential Point Between AchA vs PchA Infarction by VF
1. PchA
1. Impairment of ipsilateral pursuit 2. Poor contralateral saccades
Sensory Symptoms with PchA Infarction
1. Involvement of thalamic radiations of the internal capsule or damage to ventroposterior nucleus (caudal part)
Motor Symptoms of PchA Infarction
1. Damage to corticospinal or corticobulbar fibers in the internal capsule (PchA) 2. AchA more severe hemiparesis than PchA
Aphasia and Higher Cortical Deficits (PchA)
1. Transcortical motor aphasia – pulvinar damage 2. Transient visual and verbal memory disturbance 3. Disorientation for time without confusion or confabulation a. May also be seen following thalamic stereotactic surgery 4. Abulia 5. NDH lesion: a. Visual spatial processing deficit with dorsal lesions
Thalamic Stroke with PchA Infarction
1. Neuropsychologic deficits 2. Pulvinar infarction on CT/MRI 3. Paramedian infarction; tuber thalamic artery involvement (concomitant)
Visual Hallucinations (PchA)
1. Paramedian thalamic infarction
Medial Posterior Choroidal Artery (M PchA)
General Features: 1. Territory supplied: medial pulvinar; dorsomedial thalamus; anterior thalamic nuclei 2. Less common than lateral PchA infarcts
Chapter 1. Ischemic Stroke Clinical Signs and Symptoms
Ocular Signs (Midbrain)
1. 2. 3. 4.
Nystagmus retractorius Up gaze or horizontal gaze paralysis Meiosis Central Horner’s syndrome
Sensory Loss (MpchA)
a. Lemniscal or spinothalamic Motor Symptoms
a. Mild hemiparesis Pathogenesis (MpchA)
1. HCVD and DM 2. Cardiac embolism, large artery disease, migrainous stroke, catheter induced thrombosis
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patients tend to infarct the border zones of the posterior circulation. Specific syndromes have been described for many of these infarctions. The “man in the barrel” suggests an anterior cerebral/middle or cerebral artery border zone infarction. The shoulder on upper arm components of the homunculus are involved. These patients have preserved intrinsic hand muscle function. Posterior MCA/PCA infarction may cause Balint’s syndrome of infarction of the superior parietal lobule. These patients have a simultagnosia, poor optic scanning, failure to break fixation and optic ataxia. Ascending lenticulostriate and penetrating medullary vessels from pial conducting vessels cause the periventricular vascular stripe. Leg fibers may be preferentially affected. Isolation of the speech area suggests serve cortical hypoxia, carbon monoxide poisoning or hypotension. Ischemia of the optic nerve head from poor perfusion of the central retinal artery and posterior ciliary artery with giant cell arteritis and prolonged hypotension. Border zone infarcts of the brainstem do not demonstrate clear patterns of anatomical localization as those of the anterior circulation. The following discussion is of the differential diagnosis and characterization of border zone infarcts.
Differential Diagnosis of M PchA vs Pch A vs Ach A
1. M PchA: a. sensory loss is noted acutely with later onset of pain and abnormal movements 2. Movement disorder: a. Choreoathetotic myoclonic syndrome b. Pseudobulbar tremor c. Dystonic posture of the fingers d. Dystonic thalamic hand worsened by voluntary activity e. Akathisia 3. L PchA infarct a. Sectoranopia VF deficit 4. AchA infarct: a. Quadruple sectoranopia VF deficit b. Greater hemiparesis than L PchA stroke
Border Zone Infarction
Border zone infarctions occur between two or three arterial territories during prolonged periods of hypotension or cardiac arrest. The infraction may occur between pial conducting vessels or internally between ascending vessels that are feeding deep nuclear structures and descending penetrating vessels. They tend to be symmetric and occur in characteristic areas. There are internal laminar infarctions between the capillaries that are the functional metabolic columns of the brain. An O2 molecule diffuses approximately 10μ from the hemoglobin of its 7μ RBC. These 10μ constitute the functional intercapillary metabolic zones of the brain. Patients less than 40 years of age have infarctions in the anterior circulation while older
Border Zone Infarcts
1. Infarctions at the junction between two or three arterial territories a. watershed infarcts 1) Between two arterial territories with a reciprocal arteriolar collateral network: a) In the hemisphere between two pial networks 2) End artery border zone infarcts a) Terminoterminal infarcts
Differential Diagnosis
1. Stenosis or occlusion of extracranial arteries Initiating factors: bradycardia, high hematocrit, systemic hypotension, drop in cerebral perfusion pressure 2. Systemic hypotension due to: a. Cardiac surgery b. Bilateral symmetrical distributions c. More common in posterior watershed zones (MCA/ PCA) 3. Systemic disease a. Artery-to-artery cholesterol microemboli b. Sickle cell anemia c. Polycythemia vera 4. Clinical features of border zone infarcts a. Rare headache b. Syncope at onset c. Dizziness in brainstem zones
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SECTION I. Vascular Disease
Anterior Border-Zone Infarction (MCA Territory)
Posterior Border-Zone Infarction (MCA/PCA Territory)
1. Clinical patterns a. Motor weakness of the contralateral leg > arm with spared face; shoulder weakness 2. DH infarcts: a. Transcortical motor aphasia b. No initial mutism (more for stem or SMA occlusion) 3. NDH: mood disturbance usually mild or absent 4. Proximal arm weakness with preserved distal movement and strength if limited to the cortex “Man in the Barrel” if bilateral: a. Severe shoulder proximal weakness b. Preserved strength and fine movement of the hand c. Preserved movement of the thumb; extremely rare in core MCA territory. Thumb may be spared in posterior motor knuckle syndrome d. Similar pattern may occur with multiple emboli from MI stenosis
1. Lateral homonymous hemianopsia or lower quadrantanopsia 2. Transcortical sensory or Wernicke’s aphasia 3. No pure alexia 4. NDH: hemineglect and anosognosia 5. Brachiofacial hemiparesis or no motor deficit 6. Hemihypesthesia and cortical sensory loss
Internal Watershed
1. Homolateral carotid stenosis with M1 in situ stenosis: a. Ischemia of periventricular white matter b. Sensorimotor stroke c. Occurs in a setting of severe systemic hypotension 2. Patients with ICA occlusion have no border zone infarction in this distribution if there is collateral flow through the posterior communicating artery
Deep Cerebral Infarcts Extending to the Subinsular Region
1. Extend between the lateral ventricle and subinsular region 2. Paraventricular region extends for 7.5 cm 3. Subinsular extent of 1/3 of the anterior posterior extent of the insula 4. Clinical features a. Hemiparesis b. Aphasia (transcortical conduction type) c. Dysphasia d. Dysarthria 5. Clinical features overlap with paraventricular infarcts 6. Deep cerebral infarcts (DCI) > paraventricular infarcts a. Risk factors: 1) Cigarette smoking 2) HCVD 3) Large artery occlusion (ICA; MCA) 7. Larger size of DCI a. Poorer collateral blood supply
Capsular-Thalamic Border Zone Infarction
1. Deep border zone between the carotid and vertebrobasilar circulation 2. Ischemic area is between the internal capsule and lateral thalamus a. Also territory between the ascending lenticulostriate arteries from the MI segment of the MCA and the descending pial MCA arteries (medullary arteries) 3. Clinical signs and symptoms a. Brachiofacial paresis b. Corresponding sensory loss (cortical type) c. DH: subcortical aphasia 4. Vascular stripe on MRI a. T2 weighted signals periventricularly
Bilateral Hemispheric Border Zone Infarction
1. 2. 3. 4.
Transient loss of consciousness (global hypoperfusion) Bilateral motor and sensory loss No dysconjugate eye movements (I & O or 1½ syndrome) Bilateral cortical anterior border zone: “man in the barrel” syndrome (proximal arm muscles weakness) 5. Deep subcortical white matter: paraparesis or plegia (spinal stroke pattern); motor cortical fibers to lower extremities (infarction of the centrum semiovale) 6. Bilateral posterior border zone infarction a. Balint’s syndrome (optic ataxia) b. Anton’s syndrome (cortical blindness) c. Visual disorientation and hallucinations
Border-Zone Cerebellar Infarction
A. General Features: 1. Less than 2 cm in diameter 2. Between SCA and PICA boundary zones 3. Between left and right SCAs on the cortex 4. Between SCA and PICA branches in the deep cerebellar white matter B. Involved Territories 1. Cortical border zone infarcts a. Perpendicular to the cortex
Chapter 1. Ischemic Stroke
b. At boundary zones between 1) SCA and PICA territories 2) AICA-PICA 3) Medial PICA–lateral PICA 4) Medial PICA-SCA 5) Medial SCA–lateral SCA c. Between the medial rostral territories of the right and left SCA territories 2. Deep watershed territory: a. Caudal cerebellum b. Deep boundary zones of AICA–lateral PICA, medial PICA–lateral SCA and medial SCA territories c. Appear as round holes above the dentate nucleus; d. Rare cortical dorsal border zone infarcts between PICA and SCA territories C. Clinical Features 1. Similar to territorial infarcts 2. Rarely: transient loss of consciousness; pitching sensation; dysequilibrium 3. May represent low flow state of the posterior circulation D. Differential Diagnosis of Pathogenesis (BZI) 1. Focal hypoperfusion from severe occlusive disease of the vertebral or basilar artery secondary to atherosclerosis 2. Rarely generalized hypotension
Border-Zone Brainstem Infarction
1. Hypotensive setting 2. Symmetrical necrosis of the tegmentum a. Between pontine penetrating vessels and short and long circumflex arteries 3. Clinical picture a. Cranial nerve/brainstem dysfunction b. Coma
Granular Cortical Atrophy
1. Multiple small foci of cortical infarction in all borderzones
Lacunar Stroke
Lacunes are small ovoid lesions 1–2 mm in size noted in deep nuclear grey matter of the basal ganglia and thalamus as well as the internal capsules, centrum semiovale and pons. They are found in the setting of poorly controlled diabetes and hypertension. They are caused by fibrinoid necrosis of the endothelium and adventia of the single perforating arterioles. The infarct is limited to the territory of deep perforators and is caused by in situ infarction. The process may also be caused
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by atheromatous occlusion of the mouth of these blood vessels. If a series or group of perforators are involved simultaneously emboli are suspected as causal (thus most often occurs in the lenticulostriate territory). Discrete clinical syndrome are noted with infarctions of these perforators which outline their territory and allow anatomic localization. Involvement of arm, face, and leg suggests lacunar infarction of the middle 1/3 of the posterior limb of the intend capsule. Genu involvement is suggested by more face than arm involvement and severe dysarthria. The posterior 1/3 of the capsule may be selectively involved with hemisensory numbness. Occasionally, a single extremity may become weak from involvement of the medullary strica arteries is then perfuse the centrum semiovale. The motor and sensory fibers are separated in the fiber deep into the brain. The dysarthria clumsy hand syndrome occurs from posterior ventral 1/3 pontine infarction in which the corticobulbar fibers, speech and arm fibers are closely opposed. Ataxic hemiparesis suggests pontine lacunar involvement at the midpontine level. Lacunar infarctions rarely ever are associated with headache VF cut or aphasia. Pine motor, pure sensory and mixed deficits are common. There is no cortical sensory, behavior manifestations which differentiates this from pial artery stroke. Puremotor hemiparesis with III nerve pattern (Weber, Benedict; Claude’s and Nothnagel’s) places the lesion in the midbrain. Rarely hemiballisms occurs from lacunar infarction of the subthalamic nucleus due to paramedian thalamic involvement. Lacunes of basilar artery territories are suggested by dizziness, diplopia, and intranuclear ophthalmoplegic without weakness.
Lacunar Disease
1. General Features: a. Involvement of the territory of one single perforating arteriole b. <1.5 cm lesion on CT or MRI; (ovoid in shape) c. Infarct is limited to the territory of the deep perforators d. Caused by in situ small vessel disease 2. Infarcts limited to the territory of deep perforators may occur with: a. Cardiac emboli b. Ipsilateral internal carotid artery stenosis or occlusion 3. Diabetes is a major risk factor for lacunes 4. The most suggestive clinical syndrome for lacunar infarction: a. Pure motor hemiparesis with face, arm and leg involvement 5. Arterial networks that supply subcortical territories: a. Deep perforating branches form the ACA 1) Recurrent artery of Huebner (A2) 2) Direct anterior lenticulostriate branches
44
SECTION I. Vascular Disease
b. Deep perforating branches from the anterior choroidal artery c. Thalamic arteries from P1 and P2 segments 1) Interpeduncular (top of the basilar) 2) Thalamoperforate 3) Thalamogeniculate 4) Posterior choroidal artery 5) Tuberothalamic artery (from the posterior communicating artery) These arteries are perforators, but have collateral branches and are not terminal branches d. White matter medullary arteries 1) Originate from the superficial (pial) branches of the MCA > ACA > PCA 2) 2–5 cm long 3) Selective territories 4) No collaterals 5) Subserves the centrum semiovale 6) Do not anastomose with the deep perforators (lenticulostriate arteries) e. Cortical arteries with subcortical territories that supply: 1) U fibers 2) Extreme capsule 3) External capsule 4) Claustrum f. Most commonly found: 1) Centrum semiovale 2) Basal ganglia 3) Thalamus 4) Midbrain 5) Pons 6) Medulla Infarction in these territories are often not lacunar (i.e., from one perforator) but may be secondary to distal field ischemia (carotid stenosis) or cardiac thromboembolism.
Epidemiology of Lacunar Stroke
1. Lacunes – 20–30% of ischemic strokes 2. Blacks and Hispanics 2x incidence of whites 3. No increase in HCVD, DM, cigarette smoking, hypercholesterolemia or TIA compared to other ischemic strokes 4. Some series a 40–50% incidence of ischemic heart disease 5. If a specific lacunar syndrome is present: there is an 87% chance the patient has suffered a lacunar stroke 6. Predictive value for lacunar stroke a. Pure sensory stroke 100% b. Highly correlated 1) Ataxia, hemiparesis 2) Sensorimotor stroke 7. Ataxic hemiparesis can occur from: corona radiata, pons, basal ganglia or thalamus infarction a. Pontine site is the most frequent
8. 25% of lacunes are due to a non-lacunar mechanism a. Atherosclerosis b. Cardiac source of emboli 1) 10–15 perforators are affected simultaneously 2) Larger size
Clinical Presentation of Lacunar Infarction
General Features: 1. Occur more commonly during sleep 2. Arm, face, leg may be affected separately (corona radiata and pons most common areas of infarction) 3. Pure motor, pure sensory or mixed clinical patterns 4. Rare aphasia (a differential point against lacunar stroke) 5. No headache 6. No visual field deficit 7. May have stuttering course over 2–3 days 8. No cortical sensory or behavioral manifestations (strong differential point for lacunar stroke) 9. Cause of multi-infarct dementia (état spongiosis)
Clinical Patterns of Lacunar Stroke
1. Pure sensory stroke (PSS) (primarily thalamus) 2. Pure motor hemiparesis a. Corona radiata b. Middle internal capsule c. Cerebral peduncle (medial 3/5) d. Ventral pons e. Medullary pyramidal 1) At decussation with cruciate pattern (ipsilateral arm; contralateral leg) 3. Ataxic hemiparesis (AH) (pontine grey – MCP and descending CST) 4. Dysarthria clumsy hand syndrome (pons) 5. Pure motor hemiparesis sparing the face (farther posterior in the middle 1/3 of the posterior limb of the internal capsule) 6. Mesencephalic; decreased upgaze (Nothnagel’s syndrome) 7. Thalamic dementia (DM, AV nuclei) 8. PMH with horizontal gaze palsy – lower 1/3 of pons, PPRF (para pontine reticular formation) 9. PMH with III nerve (Weber’s syndrome) 10. PMH with III nerve and ataxia – Claude’s syndrome (midbrain) 11. PMH with III and movement disorder (Benedict’s) (midbrain) 12. PMH with VI nerve palsy (Ramon’s syndrome); pons 13. PMH with confusion (brainstem RF; thalamus AV/DM) 14. Sensorimotor stroke (thalami-capsular) 15. Hemiballism – (STN; paramedian mesencephalic vessels)
Chapter 1. Ischemic Stroke
16. Lacune of basilar territory (dizzy, diplopia, gaze dysfunction) 17. Lateral medullary partial infarction (penetrators from the vertebral artery) 18. Lateral pontomedullary territory (partial AICA) 19. Loss of memory (DM nuclei of thalamus); paramedian perforator 20. Locked in syndrome (infarction of ventral pons; bilateral cerebral peduncles) 21. Unusual lacunar syndromes a. Weakness in one leg with falling (corona radiata; ventral portion of ventral pons) b. Pure dysarthria – posterior 1/3 of ventral pons c. Acute dystonia (thalamoperforate to basal ganglia)
Differential Diagnosis by Arterial Territory and Anatomical Structure of Pontine Stroke with Lacunar Infarction
1. Paramedian arteries a. Medial basis pontis b. Ventral tegmentum 1) Corticospinal tract 2) VIth cranial nerve fibers as they exit 3) Facial nerve fibers as they exit 4) Rare PPRF (para pontine reticular formation by extension) 2. Short circumferential arteries a. Lateral 3/5 of the pons involved 3. Long circumferential arteries a. Lateral tegmentum b. Tectum 1) Cerebellar projections 2) Vth and VIIIth cranial nerves 3) Part of sensory lemniscus infarcted 4. Large bilateral pontine infarcts a. Basilar artery lesions 1) PPRF, 1½ syndrome 2) Ocular bobbing and dipping 3) <0.5 mm pupils 4) Decreased consciousness 5) Decerebration 6) Hyperactive reflexes 7) Babinski signs
Differential Diagnosis Between Pontine Hemorrhages vs. Infarction
1. Ischemic: a. Prior TIA b. Stuttering clinical course 2. Hemorrhage: a. Abrupt headache b. Nausea and vomiting
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c. Meningeal imitation d. Rapid decrease of consciousness 3. Lacunar syndrome may be due to hemorrhage or infarction; isolated small hemorrhage may be associated with: a. Dysarthria clumsy hand syndrome b. Pure sensory stroke c. Ataxic hemiparesis
Clinical Presentation and Patterns of Pure Motor Hemiparesis
1. Motor Cortex a. Hand and arm representation is in the precentral gyrus “motor knuckle” 1. C5–C6 roots are represented medially 2. C8–T1 are more lateral b. Infarction frequently appears as a pseudo radial palsy (wrist drop) c. Embolic pathogenesis from the internal carotid artery d. Rare that face is involved in isolation e. Cranial nerve III or VI involved with pure hemiparesis, ataxia or movement disorder f. Medullary pyramid-flaccid hemiparesis that spares the face 2. Ataxic Hemiparesis or Corticobulbar Dysfunction a. Ataxic hemiparesis 1) Infarction of the descending corticospinal tracts and pontine crossing fibers (comprises the middle cerebellar peduncle) 2) Leg more severely affected than the arm b. dysarthria – clumsy hand syndrome 1. Corticobulbar fibers to the X and XII nerve with contralateral ataxia of the hand and arm 2. III nerve palsy with contralateral ataxia (Claude’s syndrome); contralateral movement disorder (Benedict’s); failure on up gaze Nothnagel’s) 3. Pure Sensory Stroke a. Lacune in the centrum semiovale (deep penetrating medullary arteres) 1) Usual feeling of numbness or heaviness. b. Infarction of ventrobasilar thalamic complex (VPM or VPL): 1) Patients may describe numbness, paraesthesias, formication or pain 2) Bilateral intraoral loss of sensation (VPM). This is to be differentiated from a vascular brainstem stroke in which patients may feel numbness on one side of the tongue. VPL involvement may present as numbness of the trunk and extremities in 20% of patients. Dysesthetic, paraesthetic and burning occurs more often in the involved territory. Later this territory may be associated with the hyperpathia of Dejerine-Roussy syndrome (thalamic pain). Associated thermal and mechanical allodynia and hyperalgesia are frequently present concomitantly with this
46
SECTION I. Vascular Disease
syndrome. Thalamic lesions respect the midline and may involve vibration sensibility. Exception is bilateral decreased periumbilical sensation c. Thalamic-capsular lacunar infarction most often causes sensorimotor stroke. Feeling loss is perceived as numbness and heaviness d. Involvement of the ventral medial spinothalamic tract (quintothalamic tract) by lacunar infarction at medullary levels causes unilateral or bilateral facial pain or numbness (onion skin distribution) 4. Hemiballism – infarction of at least 2/3 of the corpus Luysi (subthalamic nucleus. Usually thalamoperforate or paramedian thalamic penetrating artery is occluded.) 5. Tetraplegia (locked in syndrome) a. Patients are fully awake b. Quadriplegic c. Able to blink and look up and down on command d. Unable to perform lateral eye movements e. Involvement of the basis pontis (basilar artery) or the cerebral peduncles (bilaterally) 1) P1 segment of the PCA’s 6. Patterns of lacunar weakness a. Weakness in one leg with falling 1) Basis pontis (ventral portion of ventral pons) 2) Posterior corona radiata fibers b. Pure dysarthria: corona radiata, internal capsule, cerebral peduncle; basis pontis 1) No difference in dysarthria 2) Imprecise articulation of labials and glottals 3) Monotonous voice 4) Slowed rate 5) Pontine or medullary areas more severe 6) Left paraverbal cerebellar lesions a) Coordination of articulation and respiration is disrupted c. Acute dystonia 1) Thalamus (VA, VL, or VIM) 2) Putamen
Rarer Lacunar States
1. Loss of memory a. Anterior thalamic nuclei b. Anterior limb of internal capsule that involves anterior thalamic efferent fibers 2. Thalamic dementia (dorsal medial nucleus from paramedian infarction) 3. Pure motor hemiparesis sparing the face 4. Multiple lacunar infarctions: a. Primarily in the basal ganglia b. “État” Lacunaire 5. Dysarthria, facial, lingual paresis a. Genu capsular syndrome 6. Cerebellar lacunes
a. Unusual small round lesions in the watershed between SCA, PICA, AICA b. One case of giant lacune in the cerebellum c. SCA greater deep territory supply from AICA or PICA d. Large artery occlusion, cardiac embolic, end artery lesion
Multiple Infarctions
The differential diagnosis of multiple infarctions is usually suggested by the clinical setting. Not surprisingly many patients in the course of their evaluation for their first clinical stroke are found to have had either asymptomatic prior strokes or concomitant strokes in territories other than that suspected by their clinical presentation. The major categories of illness that cause multiple infarctions are: 1) Atherosclerosis 2) Cardiac emboli 3) Angiopathies 4) Hematologic disorders 5) Hypoperfusion and venous infarction Patients with poorly controlled diabetes, hypertension and similar history have an overwhelming probability of suffering both large and small vessel disease. Lacunes are expected in the basal ganglia, pons, internal capsule, thalamus and centrum semiovale. Accelerated and disseminated large vessel atheroma will be seen at the carotid bifurcation, siphon, and at M1 and M2. Calcified and thick, vertebral carotid and basilar arteries are expected on CT. Severe hypertension will produce dolicoectasia. In situ thrombosis, flow limiting ischemic stenosis greater than 70% and cholesterol laden plaques will be seen asymmetrically in both anterior and posterior circulations. Accelerated atherosclerosis will be seen beyond bifurcations of the great vessels and intracranially in the fields of X-ray therapy. Cardiac emboli from clots formed over ischemic myocardium, arrhythmias dilated myocardial failure valve disease embolize primarily to the MCA circulation that receives the most CBF. Emboli tend to go to the same territory due to flow and viscosity characteristics. They often occur in showers in which two circulations are involved simultaneously. Emboli from atrial fibrillating often occlude the temporoparietal occipital branch of the inferior division of the MCA. Carotid distribution and superior cerebellar artery concomitant stroke suggest an embolic cardiac origin. Occlusion of the top of the basilar artery is most often embolic often from a cardiac source is which the midbrain, thalamus and posterior cerebral arteries are involved. An embolic event in younger patients in two distinct circulations over a long time course suggest a patent ovale with or without an atrial septal aneurysm. Peripheral aneurysms in two distal circulations suggest atrial myxoma. Rhabdomyosarcoma is to be expected
Chapter 1. Ischemic Stroke
with tuberous sclerosis. A shower of emboli in a cancer patient suggests non-bacterial thrombolic emboli. Severe migraine with visual aura and stroke in two circulations is strong evidence for the anticardiolipin syndrome. Small strokes in pial conducting vessels of all territories of the cerebral cortex occur with active and severe collagen vascular disease. SLE is the most prominent of these illnesses. Hematologic illness such as leukemia and lymphoma, particularly when the white cell could approach 250,000/mm3 is attended by strokes in multiple territories. Polycythemia most frequently occlude the posterior circulation. Disseminated intravascular coagulation may strike large extracranial vessels as well as conducting intracranial vessels. Sickle cell disease affects large and small vessels of both anterior and posterior inculpations. Hypoperfusion causes strokes by distal perfusion failure in affected arteries as well as by circulatory compromise between vascular territories. This complication is to be expected and is routine with cardiac pump surgery and following cardiac arrest. Venous infarction is immediately suggested in the setting of pregnancy and delivery, dehydration and a hypercoagulable state. Bilateral thalamic infarction easily seen on CT or MRI is characteristic as is superficial vascular cortical infarction. Multiple infarctions other than that from atherosclerosis suggests internal medical and cardiac disease as the source. The younger the patient the more this is true.
Multiple Infarctions
Concomitant Infarction
1. 33% of patients when diagnosed with first stroke have multiple infarcts in the carotid territory 2. 2% of multiple infarcts are in vertebrobasilar territory 3. 2% of patients at first infarct have had prior strokes in both territories (carotid and vertebrobasilar territories) Asymptomatic Infarction
1. Occurs in 10–38% of stroke patients 2. Often occurs in non-critical areas and are small 3. Right sided deep hemisphere and basal ganglia lesions more common than left sided if nonlacunar 4. Risk the same in multiple and single lesions
Differential Diagnosis of Multiple Infarctions
A. Atherosclerosis 1. Atherosclerosis: large and medium sized arteries 2. Small vessel disease a. Lipohyalinosis (penetrating vessels); HCVD
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b. Spread of atheromatous plaque to occlude adjacent origins of major vessels c. Atheroma at origin of penetrating vessels d. Emboli: artery to artery; cardiac or arch of aorta sources e. recurrent stroke in patients with first lacunar infarct is 1.8% B. Cardiac Embolism 1. Nonrheumatic atrial fibrillation (AF) most common source of cardiac embolism 2. AF with emboli 10% per year: a. Multiple pial territory infarction suggests cardiac emboli source b. Bilateral anterior circulation infarcts are more common in patients with emboligenic heart disease C. Angiopathies 1. Isolated angiitis of the CNS (cerebrum, cerebellum) 2. Granulomatous vasculitis 3. Herpes Zoster a. Affects small and medium sized vessels b. Infarction more common than hemorrhage c. Localized lesions: cerebrum, cerebellum, brainstem in >75% of patients d. May occur in carotid MCA territory if V1 involved. Occurs 2 weeks after onset of skin lesions or may be delayed 4. SLE a. Vasculitis (inflammation of blood vessels) less common than vasculopathy (abnormalities of blood vessel intima and media) b. Embolic infarcts most common cause of infarction: 1) Libman Sachs endocarditis 2) Chronic valvulitis 3) Mural thrombus c. Antiphospholipid antibodies d. Lupus anticoagulant e. Seizures f. Psychosis g. Recurrent and multiple small strokes 5. Differential diagnosis of noninflammatory angiopathies with multiple strokes: a. Eales Disease (arterioles and venules involved) b. Sneddon’s syndrome (livedo reticularis) c. Moyamoya syndrome (carotid occlusion at siphon with collaterals) d. MELAS (mt DNA) mitochondrial encephalopathy with lactic acidosis and stroke e. Cerebral amyloid angiopathy (associated dementia) f. Intravascular lymphoma (angiotrophic endovascular lymphomatosis); dural involvement g. Arterial dissection of intracranial and cervical arteries (diseases of collagen) D. Hematological Disorders 1. Thrombotic thrombocytopenic purpura (TTP) a. Multiple occlusions of small vessels
SECTION I. Vascular Disease
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2.
3.
4.
5.
b. Large artery occlusion c. Hallucinations d. Renal failure e. Focal cortical deficits f. Seizures Polycythemia vera a. Posterior > anterior circulation stroke b. Megakaryocyte proliferation greater than one million has a high incidence of stroke c. Hemoglobins of 18–22 g/dl d. Rheological abnormalities (dysfunction of laminar flow) Sickle Cell Disease (HbSS) a. Stroke occurs in 3–17% of patients b. Ischemic stroke 15% c. Large and small vessels involved d. Strokes <15 years of age; border zone, and subcortical areas e. Hemoglobin C: strokes in pregnancy; aseptic necrosis of the hip f. Severe abdominal and joint pain Disseminated intravascular coagulations (DIC) a. Small and large vessel strokes (often concomitantly) b. Encephalopathy c. Nonbacterial thrombotic emboli (NBTE) frequently associated d. SAH Systemic lupus erythematosus a. Vasculopathy affecting: 1) Small arteries 2) Arterioles 3) Capillaries 4) Pathology is fibrinoid neurosis b. Vasculitis 1) Pathologically similar to hypersensitivity 2) Approximately 10% of patients c. Microangiopathy: 1) 50% of SLE patients 2) Circulating antiphospholipid antibodies (APA’s) 3) 2 mm to 3 cm infarction size d. Clinical manifestation of stroke: 1) May occur at any time during course of the disease 2) Caused by APA’s (antiphospholipid) a) Titer may fluctuate and is not tightly correlated with systemic disease activity b) Circulating IgG and IgM antibodies associated with the thrombotic events c) APA’s that bind to the phospholipid on factor V and X (1) Inhibits conversion of prothrombin to thrombin: (a) Anticoagulant properties in vitro (lupus anticoagulant) LAC (b) Some LAC are procoagulant
3) High titers of anticardiolipin antibodies (ACL) a) Greater specificity for thrombotic events b) IgG > association with thrombosis than IgM c) Stroke risk with secondary APA’s in SLE is increased with: (1) Oral contraceptives (2) Smoking (3) Hypertension 4) Stroke types a) Branch occlusion most common b) Multiple infarcts c) Centrum semiovale strokes d) Cardioembolic from Libman–Sachs endocarditis 5) Vasculitis in SLE a. Ischemic and hemorrhagic stroke b) Intracranial hemorrhage (1) Parenchymal (2) SAH (3) Most associated with vasculitis c) Most likely cause of stroke if: (1) Active systemic disease (2) Normal TEE 6) Associated collagen vascular disease 7) Hyperviscosity syndromes a) Bing–Neel syndrome (poor cerebral perfusion from high viscosity) b) Bleeding gums c) Myeloproliferative and dysglobulinemia states (IgM particularly severe) d) Multiple occlusions of small blood vessels e) Petechial hemorrhage f) Waldenström’s macroglobulinemia (1) Petechia below the knee (2) Acrocyanosis E. Hypoperfusion 1. Severe hypotension (cerebral perfusion pressure of less than 70 mm systolic) 2. Prolonged hypoxemia 3. Cardiac circulatory failure (no reflow phenomena of specific microcirculations) 4. Symmetrical and asymmetrical watershed infarcts 5. Infarcts in deep and superficial MCA territories 6. Cerebellar watershed infarcts 7. Multiple clinical syndromes depending on involved circulations F. Venous infarction 1. Hemorrhagic 2. Specific circumstance: pregnancy, prothrombotic state, cancer, Behçet’s disease 3. Grey matter (basal/thalamus); subcortical white matter Differential Diagnosis of Stroke in Young Patients
Approximately forty percent of cerebral thrombosis in young patients will be caused by HCVD 23%, diabetes mellitus
Chapter 1. Ischemic Stroke
11%, and migraine in 6%. Dissection certainly must be considered in patient with neck or face pain. Carotid dissection will often be announced by oculosympathetic paresis. Posterior neck pain, occasionally accompanied by lateral eye brow pain occurs with vertebral obstruction and dissection. Migraine headaches are characteristic of mitochondrial disease, collagen vascular disease and CADASIL. Sporadic hemiplegic migraine has a greater chance of permanent stroke than familial migraine. Migraine with multiple visual auras is suggestive of anticardiolipin antibody syndrome. Prothrombotic states should always be sought in the context of a family history of thrombophlebitis or venous clotting in the upper extremity or chest wall. Vasospastic occlusion as well as hemorrhage from underlying vascular malformation or aneurysms are characteristics of strokes from cocaine or other sympathomimetic drugs. Oral contraceptives, hypertension and diabetes cause strokes of PICA and the thalamoperforate and thalamogeniculate arteries. Cigarette smoking in this context exacerbates this risk in young patients. Sickle cell disease, leukemia and lymphoma cause approximately 5–10% of thrombotic strokes in young patients. Sickle cell disease is particularly dangerous during pregnancy. Stroke is frequent during chemotherapy for leukemia and lymphoma possibly due to the release of thromboplastin from lysed neoplastic cells. Cardiac causes of stroke in young patients are similar to those in adults except that congenital anomalies, infective endocarditis (drug use), mitral valve prolapse and PFO are more common.
Stroke in Young Patients
1. Approximately 3% of cerebral infarctions occur in patients <40 years of age) 2. Specific age related vascular disease: a. 70% of subarachnoid hemorrhage <40 years of age b. 97% of cerebral infarction >40 years of age c. 60% of cerebral infarctions occur between 65 to 84 years of age 3. Differential diagnosis of cerebral thrombosis in young patients: a. HCVD (23%) b. Diabetes mellitus (11%) c. Migraine (6%) d. Collagen vascular disease (5%) e. Cryptogenic (10–30%) f. Dissection of carotid or vertebral artery (10%) g. Prothrombic states (5%) h. Hematologic diseases (5%) 4. Stroke in women (15–45 years old) a. Aneurysm or AVM without hemorrhage in 3.4% b. Hemorrhage – 42% c. SAH – berry aneurysm > AVM d. Intracranial hemorrhage
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1) Leukemia 2) Thrombotic thrombocytopenia 3) Aplastic anemia e. Infarction – 18% f. Embolism – 56% cardiac (33% from cardiovascular surgery) g. Thrombosis 1) Carotid 30% 2) Vertebrobasilar 7% 5. Early onset atherosclerosis with or without HCVD associated with: a. Evidence of: coronary artery disease, peripheral vascular disease or arterial occlusive disease 6. Oral contraceptive risk (general) a. 1/10,000 women b. Death from stroke
Migraine
1. 5% of stroke in young women 2. No relation to specific attack 3. Vasospasms, vessel occlusion, platelet hyper agreeability (subset of migrainous)
Pregnancy
1. Pregnancy and the puerperium a. 3% of cerebral thrombosis in young women b. 4% within 30 days
Differential Diagnosis of Stroke from Cross Section of Community or Referral Hospitals
1. Stroke in patients (15 to 44); heterogeneous population a. 50% probable cause b. 20% possible cause c. 30% (cryptogenic); arch of aorta source, PFO and atrial septal aneurysm discovery are decreasing this percentage 2. First Stroke a. 50% women b. 60% black patients (38% of population studies); 35% Caucasian patients (60% of population studied) 3. Patients with recurrent stroke: a. 60%women b. 70% black patients c. 16% <30 years old d. <2% more than one probable cause 4. Probable cause (approximately percentage) a. Cardiac embolism – 16% b. Lacunar stroke – 10% c. Hematologic – 10% d. Non atherosclerotic vasculopathy – 6% e. Elicit drug use 5% (probably much higher)
SECTION I. Vascular Disease
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f. Oral contraceptive 5% g. Large artery atherosclerosis <2% h. Migrainous <1% (probably higher) Cardiac Causes of Stroke in Young Patients
High risk cardiac source: 1. Ischemic heart disease and dyskinetic left ventricular segment 2. Atrial Fibrillation (AF) 3. AF with dilated left atrium 4. Mechanical prostatic valve with AF 5. Rheumatic mitral stenosis, atrial fibrillation, dilated left atrium 6. Left ventricular thrombus 7. Dilated cardiomyopathy with left ventricular clot 8. Atrial myxoma 9. Infective endocarditis 10. Congenital heart disease – atrial septal defect perioperative 11. Congenital heart disease – Ebstein’s anomaly 12. Congenital heart disease – Tetralogy of Fallot Medium risk cardiac source: 1. Patient foramen ovale (PFO) 2. Atrial septal aneurysm and PFO 3. Mitral valve prolapse (MVP) 4. Hypertensive heart disease and hypokinetic left ventricular segment
Differential Diagnosis of Stroke in the Young
Age 15–29 Atherosclerosis Lacunar infarction Cardiac embolism Other determined causes Dissection Sickle cell disease Arteritis Infection Undetermined
Approximate percentages 3% 3% 30% 25%
17%
Determined Causes of Stroke (15–40)
Hematologic disorder Arterial dissection Vasculitides SLE Primary antiphospholipid antibody syndrome Migraine Neurocysticercosis (specific populations) Eclampsia Oral contraceptives Extracranial carotid aneurysm Central venous thrombosis Vasospasm after subarachnoid hemorrhage Complication of angiography Moyamoya disease
Cardiac Valve Tumors
A. Have risk of cardiac emboli: 1. Aortic > mitral > pulmonary > tricuspid 2. Mean age 52 (2–88 years) 3. Male patients more than female 4. Less aggressive than non valve tumors 5. Less than 10% of cardiac tumors are on the valve B. Clinical presentation 1. Most are asymptomatic 2. Cardiopulmonary symptoms a. Coronary artery occlusion b. Congestive heart failure 3. Embolic stroke (usually pial vessels) 4. Rare occurrence of sudden death 5. Left sided more symptomatic than right sided lesions 6. A few patients have multiple tumors Valvular Cardiac Tumors
1. 2. 3. 4. 5. 6. 7.
Papillary fibroelastoma (most common) Myxoma (medium stroke risk) Fibroma Sarcoma (rhabdomyosarcoma; tuberous sclerosis) Hemangioma Histiocytoma Undifferentiated
Cerebral Embolism (15–40 Order of Frequency)
Synthetic valve Mitral valve prolapse Cardiomyopathy
Apical aneurysm Segmental hypokinesia Acute myocardial infarction Aseptic endocarditis (NBTE)
Ischemic Stroke Due to Deficiency of Coagulation Inhibitors (young patients)
1. Thromboses secondary to hematologic or clotting disorders occurs in approximately 4% of young patients 2. Hematologic disturbances young stroke patients a. Abnormalities of platelet function b. Coagulation inhibitors c. Fibrinolysis defects 3. Free protein S enhances inhibition of V and VIII by activated Protein C; oral contraceptives and inflammatory conditions may decrease its concentration 4. Antithrombin III; inhibits thrombin (factor Xa, IXa, XIa, XIIa – minor effect) deficits may be AD; acquired deficits a. Inhibits thrombin b. Minor effect inhibits clotting factors c. AD form
Chapter 2. Venous Strokes
d. Acquired deficits 1) Failure to synthesize due to cirrhosis 2) Diabetes 3) Age 4) Protein malnutrition 5) Low serum albumin 5. Acquired deficiencies of coagulation inhibitory proteins occur with: a. Malignancies d. Nephrotic syndrome b. Plasmapheresis e. Hepatic failure c. Hemolysis f. Oral contraceptives 6. Factor V Leiden defect (effects on protein C) 7. Prothrombin gene defect 8. Increased fibrinogen and factor VIII levels and acquired hyperfibrinolysis occur in young adults with ischemic stroke 9. Strong predictors of myocardial infarction and stroke a. Plasma levels of fibrinogen (increased) b. Tissue plasminogen activator concentration (decreased) c. Plasminogen activator inhibitor type I (PAI-1) concentrations (decreased) 10. Decreased fibrinolytic factors: a. Obesity b. Hyperlipidemia Young stroke patients (subgroup) have: a. Generalized defect in fibrinolytic system b. Diurnal circadian rhythm of tPA and PA1-1 tPA 1) PA I-1 activity doubles from early morning until afternoon c. Genetic control of circulating PAI-1 (plasminogen activator inhibitor type I)
Chapter 2 Venous Strokes
Venous strokes should be suspected in the setting of the last trimester of pregnancy and the first month of the perineurium, any prothrombotic state and dehydration. Clinically, there is a depressed mental status early in the course of the process as well as a step wise and progressive onset rather than an apoplectic initial event, which characterizes embolus, hemorrhage and ischemic stroke. Repeated seizures and vomiting are common associated with severe headache. Papilledema is more common than with ischemic or hemorrhagic events. The sinuses are commonly occluded. Lateral sinus involvement should be suspected with mastoid pain that may radiate to the sternocleidomastoid muscle associated with Vth and VIth nerve involvement. The temporal lobe and cerebellum may be involved concomitantly. The sagittal sinus frequently presents with focal seizures of the leg or bilateral signs and symptoms.
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Severe headache, papilledema and rapid loss of consciousness strengthen the diagnosis. Cavernous sinus involvement is frequently heralded by periorbital headache, fever, stiff neck. There is progressive orbital and retinal congestion culminating in paresis of III, IV, VI, V. Often there is complete ophthalmoplegia and frequent spread to the contralateral eye. Occlusion of the internal cerebral veins, veins of Galen and straight sinus present in stupor or coma. They often have had a severe headache and hemiparesis prior to depression of mental status. Cortical cerebral venous occlusion presents with focal neurological signs, seizures at presentation, headache but minimal depression of consciousness. Cerebellar venous occlusions often pursue a pseudotumoral course with brainstem compression. MRI evaluation that demonstrates a delta sign at the confluences of sinuses, bilateral thalamic and basal ganglia hemorrhage, small compressed ventricles and vascular lesions out of a typical arterial distribution suggest venous stroke and sinus occlusion. The following is a detailed discussion of the major differential points of venous stroke and specific sinus occlusion.
Venous Strokes
Specific territories of venous drainage: 1. Superior sagittal sinus (SSS) and its draining veins a. Major part of the cerebral hemispheres 2. Inferior sagittal sinus, straight sinus and tributaries a. Deep white matter of the cerebral hemispheres b. Basal ganglia 3. At the torcular of Herophilus (confluens of sinuses) a. SSS continuous with the right lateral sinus b. Straight sinus continuous with the left 4. Lateral sinus (two segments) a. Transverse (attached border of tentorium) b. Sigmoid (inner aspect of the mastoid bone) 5. Cavernous sinus a. Drains periorbital and facial territories b. Joins the internal jugular vein and transverse sinus through the petrosal sinus c. Drains Sylvian fissure through the sphenoparietal sinus C. Pattern of Pathology 1. Superior sagittal sinus thrombosis with cortical vein thrombosis a. Involves the superficial cerebral hemispheres 2. Thrombosis of the straight sinus involves the basal ganglia 3. Isolated cortical vein thrombosis is rare 4. Usual pathology: venous thrombosis with or without cerebral infarction, basal ganglia or thalamic hemorrhage 5. Venous obstruction causes: a. Cerebral edema b. Infarction or hemorrhagic infarction of the cortex c. Petechial hemorrhage
SECTION I. Vascular Disease
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d. Superior sagittal sinus thrombosis may cause: 1) Bilateral basal ganglia hemorrhage 2) Unilateral or bilateral thalamic hemorrhage e. Hemorrhagic infarction circumscribed or wide spread that may involve cortical and deep structures f. Multiple or single intracerebral hemorrhage
Venous Sinus Thrombosis
General Signs and Symptoms
A. General Features: 1. Seizures with severe headaches 2. Depressed mental status early in the course of illness with papilledema (40%) 3. Stepwise and progressive onset 4. Vomiting common 5. Repeated seizures 6. Hemiparesis commonest focal deficit 7. Hemisensory symptoms approximately 10% 8. Neurologic signs are cumulative 9. Alternating or ascending hemiparesis is rare 10. Bloody cerebral spinal fluid B. Causes of venous thrombosis Clotting disorders: 1. Antithrombin III 2. Protein C and S deficiency 3. Factor V Leiden mutation 4. Prothrombin gene mutation 5. SLE anticoagulant 6. Activated Protein C resistance 7. Methylene tetrahydrofolate reductase deficiency 8. Anticardiolipin antibody 9. Increased factor VIII 10. Oral contraceptives 11. Ulcerative colitis 12. Regional enteritis 13. Polycythemia vera 14. Hemolytic anemia 15. Pregnancy and the puerperium 16. Leukemia 17. Paroxysmal nocturnal hemo globulinuria (decreased membrane glyco protein) 18. Carcinoma (thrombin like material) 19. Idiopathic thrombocytosis 20. Nephrotic syndrome 21. Ménétrièr’s syndrome (protein losing enteropathy) 22. Androgen therapy 23. Asparaginase therapy (blocks antithrombin III) 24. Cryofibrinogenemia 25. Disseminated intravascular dissemination 26. Behçet’s disease C. Changes in the Venous Sinus Wall 1. Metastatic disease (invasion)
a. lung; breast, choriocarcinoma, prostate 2. Lymphoma (invasion) 3. Non-Hodgkin’s lymphoma 4. Behçet’s disease 5. Arteriovenous malformation 6. Sarcoidosis 7. Leukemia (invasion of wall) 8. Meningitis 9. Chronic otitis media 10. Wegener’s granulomatosis 11. Aspergillosis 12. Mastoiditis (lateral sinus) D. Blood Flow, Rheology, Systemic Causes of Venous Occlusion 1. Congestive heart failure 2. Cachexia and marasmus 3. Trauma 4. Cerebral artery thrombosis 5. Chronic obstructive airway disease 6. Trichinosis 7. Transvenous pacemaker placement 8. Dehydration 9. Hyperpyrexia (release of thromboplastin from platelets) 10. Congential heart disease 11. Budd–Chiari syndrome 12. Diabetes mellitus 13. Vasculitis 14. Homocystinuria 15. SS disease
Clinical Signs and Symptoms of Specific Sinus Thrombosis
1. General epidemiology a. The SSS is the most commonly involved 1) Involved alone approximately 30–40% of the time b. Unilateral lateral sinus thrombosis, 10–15% of patients 2. Rarer involvement a. Deep venous system c. Isolated cortical veins b. Cerebellar veins I. Lateral Sinus Thrombosis 1. Etiology a. Coagulopathy and systemic illness b. Spread of infection from middle ear and mastoid 1) Infection spreads through emissary veins 2) Spread of infection from the lateral sinus through jugular veins c. Infection from central venous lines 2. Lateral sinus thrombosis from otic causes: a. Draining ears and perforated ear drums b. Pain occurs: 1) Mastoid area 2) Sternocleidomastoid muscle
Chapter 2. Venous Strokes
3) Headaches in frontotemporal and occipital areas c. Vertigo, nausea and vomiting d. Diplopia VIth nerve involvement (Dorello’s canal at the petrous apex under the petroclinoid ligament) e. Vth nerve involvement (Meckel’s cave) f. Vth/VIth nerve involvement (Gradenigo’s Syndrome) 1) Nerves are affected at the petrous apex 2) Requires pneumatized temporal bone g. Lethargy (increased ICP) h. Temporal lobe and cerebellum involved concomitantly 3. Approximately 2/3 of patients have involvement of more than one sinus 4. SSS involved more commonly than expected during the puerperium 5. Septic processes frequently involve the cavernous and lateral sinus Sagittal Sinus
1. Etiology: a. Puerperium b. Parasagittal meningioma c. Carcinomatosis of the meninges 1) Breast and prostate carcinoma d. Head trauma e. Behçet’s disease f. Prothrombotic states g. Paranasal sinus involvement 2. Clinical signs and symptoms a. Depends on concomitant involvement of cortical veins 1) Focal motor or sensory deficits 2) Seizures (leg > arm) 3) Bilateral signs and symptoms 4) May have transient signs and symptoms b. Pseudotumor cerebri if SSS is involved alone: 1) Severe headache 2) Papilledema 3) VIth nerve palsy 4) Decreased level of consciousness 5) Edema and hemorrhage of the medial dorsal cerebral hemisphere 3. Temporal lobe involvement a. Posterior aphasia b. Superior quadrantanopia c. Agitation 4. Cerebellar involvement a. Gait ataxia b. Ipsilateral rotary nystagmus 5. Spread of thrombus: a. Into jugular vein (if an axillary or jugular line is infected the spread is to the lateral sinus) b. Adjacent dural sinuses c. Rare concomitant pulmonary emboli 6. Imaging studies: a. Lytic lesions, opacification of mastoid air cells, eburnation and bone sclerosis b. Secondary cholesteatoma
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Cavernous Sinus Thrombosis
1. Etiology a. Infection of veins draining the medial face, orbit, nose and nasal sinuses b. Infectious etiologies 1) Staphylococcus aureus 4) Gram negative bacteria 2) Pneumococci 5) Mucormycosis (3) Streptococci 6) Aspergillus c. Noninfectious etiologies 1) Surgery of sinuses/facial structures 2) Prothrombotic states 3) Thrombosis of dural A-V fistula 2. Clinical Features: a. Fever; often with stiff neck b. Headache (particularly periorbital) c. Facial pain d. Conjunctival edema and erythema e. Orbital and retinal congestion f. Dysfunction of: 1) III, IV, V nerves 2) V1 and occasionally V2 3) Complete ophthalmoplegia 4) Occlusion of ophthalmic artery (blindness) 5) Bilateral eye findings 6) Involvement of ICA with hemiparesis (rare) 7) Cavernous sinus thrombosis with spread to superior petrosal sinus a) Vth nerve is involved g. Noninfectious etiologies 1) Indolent course 2) Proptosis 3) Conjunctival edema 4) No or minimal occulomotor involvement 3. Cavernous sinus anatomy a. Anterior and posterior intercavernous sinus (connects the two sides) b. Inferior petrosal sinus drains into the sigmoid sinus c. Superior petrosal sinus drains into the transverse or sigmoid sinus
Internal Cerebral Veins; Vein of Galen and Straight Sinus
1. Deep system drains: a. Thalamus d. Geniculate bodies b. Basal ganglia e. Cerebellum c. Midbrain 2. Etiology: a. Dehydration d. Ulcerative colitis b. Sickle cell disease e. Oral contraceptives c. Infection 3. Internal cerebral vein and vein of Galen occlusion: a. Clinical features 1) Patients present stuporous or in coma
SECTION I. Vascular Disease
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2) Severe headache may precede decreased level of consciousness 3) Hemiparesis b. Thalamic and basal ganglemic hemorrhage 1) Coma 2) Decerebrate posture 3) Vertical gaze palsy 4) Apathy and abulia in some patients as a presenting sign
Jugular Vein Thrombosis
1. Clinical features: a. Headache c. Vomiting b. Fever d. Involvement of IX, X, XI cranial nerves
Cortical Cerebral Venous Thrombosis
1. Clinical features: a. Seizures at presentation b. Focal neurological signs 1) Aphasia 2) Hemiparesis c. Headache d. Less commonly a decreased level of consciousness 2. MRI evaluation: a. Brain edema with hemorrhage b. Pial surface of the hemisphere is involved
Cerebellar Venous Occlusion
1. Clinical features: a. Severe headache b. Incoordination c. Cranial nerve palsies d. Pseudotumoral course with brainstem compression 2. Clinical Features of Venous Sinus Compression from Tumor Metastasis Usual Tumors: a. Ewing’s sarcoma (occipital region of skull) b. Plasmacytoma c. Metastatic lung cancer d. Neuroblastoma e. Choriocarcinoma f. Metastatic breast carcinoma Differential rests between mass beneath the inner table of skull versus tumor invasion of the dura and sinus. Isolated dural sinus thrombosis may be benign. 3. Diagnostic Features of Venous Occlusive Disease: a. Specific circumstances as noted b. Headaches is often the presenting symptom c. Seizure and lethargy more common than in arterial disease
d. Increased intracranial pressure in the absence of focal deficits e. Slower and more indolent progression than arterial disease 4. Imaging evaluation: a. CT: 1) Evidence of sinus and middle ear disease 2) Cord sign a) Cerebral vein imaged as high density linear, thin tubular structure 3) Delta sign at the confluens of sinuses a) Hyperdense triangular mass within the sinus on contrast CT; which does not enhance 4) Bilateral thalamic and basal ganglia hemorrhage 5) Small compressed ventricles 6) Lesions out of a typical arterial distribution b. Contrast enhanced CT: 1) Dilated cortical and medullary veins 2) Gyral enhancement c. Deep Venous Occlusion demonstration by CT 1) Bilateral hypodensity of thalamus and basal ganglia 2) Edema and compression of the IIIrd ventricle 3) Retention of contrast in thalamostriate veins, basilar vein of Rosenthal, non- opacification of vein of Galen d. MRI/MRV: 1) May directly image the occluded venous sinus 2) Demonstrates collaterals e. Arteriography 1) Delineates all venous and arterial structures a) Now necessary as angioplasty and intravenous thrombotics may be options b) Better visualization of congenital variants 2) Multifocal and bilateral 3) Seizures and increased intracranial pressure 4) Cortical surface causes focal leg seizure (superior sagittal sinus) or arm (cortical vein)
Chapter 3 Medical Causes of Stroke
The medical cause of stroke occur in younger patients associated with cardiac disease, autoimmune vasculitis, infection, mitochondrial deficits or clotting factor dysfunction. Dissection from trauma or in association with collage vascular disease and migraine is also common. Specific symptoms such as cerebral autosomal dominant arteriopathy with subcortical infarction and stroke (CADASIL), hereditary endoheliopathy, neuropathy, renal disease and stroke as well as mitochondrial disease and named syndromes such as Susac, Eales, Sneddon’s, Cogan’s and Grönblad–Strandberg Disease, all test the
Chapter 3. Medical Causes of Stroke
diagnostic acumen of the examiner. Clotting disorders of deficiency, inhibition of activated coagulation factors or hereditary fibrinolytic defects are AD, AR or acquired. The examiner needs to elicit the sentinel characteristic of each entity to diagnose the category of medical illness and then the specific disease. Genetic cause of embolic stroke are: 1. AD, MVP 2. Tuberous sclerosis 3. Familial atrial myxoma (AD; AR); 4. Hereditary cardiac conduction defects (long QT) 5. Hereditary cardiomyopathies 6. Mitochondrial disease Mitral valve prolapse has a prevalence rate of 5–21% in the population. It occurs occasionally in an AD form and rarely causes a cerebral embolus. Auscultation reveals a mid systolic click-systolic murmur and 2D-ECHO cardiography determines greater than 2 mm or more abnormal movement of the anterior or posterior leaflets. Tuberous sclerosis patients are easily diagnosed by their characteristic skin manifestations, seizures and mental retardation. Rhabdomyosarcoma may be the cause of cerebral emboli. Heredity is AD. Hereditary long QT defects most frequently presents with syncope especially provoked by drugs that decrease cardiac conduction or with rare sudden death during strenuous athletics. Hereditary cardiomyopathies with a dilated myocardium occur in mitochondrial disease, limb-girdle muscular dystrophy, congenital myopathies, DMD, BMD, and myotonia type; all of these entities have characteristic physical findings such as proximal weakness, calf hypertrophy contracture of elbows, arms and ankles (Emery–Dreifuss muscular dystrophy); rigid spine syndrome. Mitochondrial disease should be suspected in short patients with undue fatigue with exercise, sensorineural hearing loss, diabetes and dilated cardiomyopathy. Atrial myxomas with emboli may present with fevers of unknown origin, petechiae across the chest wall, pial vessel emboli and peripheral cerebral aneurysm that bleed (myxomatous material grows through the walls of the affected arteries). Genetic cause of thrombotic stroke are: 1. Homocystinuria (marfanoid habitus) and dislocated arm 2. Dyslipoproteinemias such as Tangier disease with orange tonsils, alpha hypolipoproteinemia and intermittent neuropathy 3. Hemoglobinopathies particularly SS disease have relevant telangiectasis and arachnodactyl; while neurofibromatosis type I with characteristic coast of Maine spots and abnormalities of renal vasculature Clotting disorders secondary to polycythemia vera occur primarily in the posterior greater than anterior circulation and tend to thrombose large cerebral vessels. Retinal venous occlusion in coagulopathies from clotting factor deficiency are
55
characteristically seen in young patients whose parents have had a fetal wastage, protein losing enteropathy, nephrotic syndrome or migraine with aura. Protein S deficiency and stroke occurs in middle aged women. Protein C deficiency often occurs concomitantly with the Factor V Leiden mutation. Antithrombin III deficiency should be suspected in the setting of severe resistance to heparin anticoagulation. Anticardiolipin antigen and lupus anticoagulant often are associated with migraine with visual aura. Cerebral sinus thrombosis is common in all defects of inhibitors of clotting. Platelet abnormalities and stroke should be suspected in a setting of petechiae particularly of the lower extremities. The primary anti-phospholipid antibody syndrome is associated with spontaneous abortion and fetal wastage. Valve cusps are affected and the syndrome may be associated with cerebral emboli. The lupus anticoagulant is an antibody to phospholipids (on platelets) which blocks the formation of the prothrombin activator and is associated with clotting and not hemorrhage. There is usually evidence of systemic venous clotting. In general platelet counts greater than one million/mm3 are associated with hypercoagulability. Functional platelet abnormalities rather than absolute number may be the important parameter. This may occur in a small group of migraine patients and in essential thrombocythemia. Heparin induced thrombocytopenia and thrombosis occurs as a transitory and asymptomatic reduction in platelet count or as an immunopathologic condition. The later (Type II) usually occurs after the 5th day of treatment and causes both arterial and venous thrombosis. Gangrene of a limb, thrombosis and stroke is the usual triad. White clots are noted in blood vessels. Disseminated intravascular coagulation occurs in a setting of gram negative sepsis, cancer and obstetrical emergency. It is announced by oozing from all venipuncture sites and acrocyanosis. Arterial and venous clotting as well as hemorrhage dominate the clinical profile. The following discussion highlights the major characteristics and differential features of the genetic causes of embolic and thrombotic stroke, coagulopathies and rheological abnormalities that are seen in clinical practices.
Genetic Causes of Embolic Stroke
1. Mitral valve prolapse (MVP) – AD 2. Tuberous sclerosis – AD 3. Familial atrial myxoma (AD, AR) 4. Hereditary cardiac conduction defects (long QT) AD 5. Hereditary cardiomyopathy AD, AR, X-linked 6. Mitochondrial disease (maternal inheritance) A. MVP 1. Associated with:
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SECTION I. Vascular Disease
a. Osteogenesis imperfecta e. Becker MD b. Ehlers Danlos syndrome f. Van Willebrand’s c. Marfan’s Syndrome disease d. Duchenne MD g. Fragile X syndrome B. Tuberous Sclerosis 1. Cardiac rhabdomyomas that cause emboli 2. 80% are new mutations 3. Abnormalities of cerebral arteries and aorta also occur C. Atrial Myxoma 1. AD/AR forms; most atrial myxomas are sporadic 2. 20% of familial atrial myxoma are associated with an AD heredity 3. Associated with: a. Myxoid fibroadenoma b. Lentiginous blue nevi c. Large cell calcifying Sertoli cell tumors d. Primary adrenocortical nodular dysplasia e. Pituitary growth hormone tumors
Cardiac Dysrhythmia with Emboli
A. Idiopathic Hypertrophic Subaortic Stenosis (IHSS) 1. Syncope after exercise a. Muscle constricts subaortic outlet; epinephrine dilates blood vessels in muscle. Severe hypotension results after strenuous exercise 2. Atrial fibrillation late in the course of the illness a. Emboli during the arrhythmia 3. Female > male at risk for stroke 4. Hypertension a cause of stroke 5. Other stroke mechanisms: a. Associated mitral annulus calcification b. AV conduction defect B. mt DNA Cardiomyopathy 1. Kearns–Sayre syndrome a. Heart/block (bundle branch block; AV node block) b. Ophthalmoplegia c. Hearing loss (VIIIth nerve) d. Diabetes mellitus e. Dilated cardiomyopathy with emboli (poor flow; clot formation) f. Decreased ventricular ejection fraction g. Endocardial thickening h. Intellectual decline i. Cerebellar ataxia j. Stroke like episodes after seizure C. Dilated cardiomyopathy (DCM) 1. DCM with and without conduction-system disease 2. Familial DCM with CSD (conduction syndrome) chromosome 1 p1-q21 3. X-linked dystrophinopathy (Becker’s; Duchenne) 4. Female carrier of BMD and DMD 5. Sporadic and AR limb-girdle muscular dystrophy 6. Emery Dreyfus Muscular Dystrophy
7. 8. 9. 10. 11. 12.
Adhalinopathies Barth Syndrome Rigid Spine Syndrome Welander’s distal myopathy Distal vacuolar myopathy Systemic carnitine deficiency
Genetic Causes of Thrombotic Stroke
A. Homocystinuria (AR) 1. Homocysteine to cystathionine; deficient enzyme is cystathionine beta synthase (most common defect) 2. Homocystinuria a. Severe atherosclerotic changes b. Increased levels of homocysteine injuries endothelium 3. Clinical Features: a. Marfanoid habitus b. Osteoporosis c. Mental retardation d. Premature atherosclerosis e. Venous and arterial occlusions f. High myopia g. Dislocated lens 4. Heterozygosity a. Incidence 1 : 200 persons b. Increased stroke risk c. Oral methionine load causes increased homocysteine level in the serum B. Dyslipoproteinemias 1. Familial hypoalphalipoproteinemia (Tangier Disease) a. Tangier Disease: 1. AR 2. Low HDL 3. Increased triglycerides 4. Orange tonsils 5. Intermittent neuropathy 6. Premature atherosclerosis with stroke 7. Increased carotid artery intima-media thickness in subjects with primary hypoalphalipoproteinemia 8. ABCA1 Gene Mutation a. Cell membrane protein is deficient
Hemoglobinopathies
A. General Vascular Features 1. Small and large vessel thrombosis 2. Sickling in the vaso-vasorum (blood supply of the vessel wall) 3. SAH 4. ICH 5. Embolic disease
Chapter 3. Medical Causes of Stroke Hemoglobinopathies
SS Disease 1. General Characteristics a. Scleral telangiectasia b. Arachnodactyly c. Auto splenectomy d. Pneumococcal peritonitis e. Meningitis f. Bone marrow infarction g. Severe joint and abdominal pain A. Occlusive disease: 1. Large intracranial arteries 2. Small penetrating vessels 3. Dilated and ectatic arteries 4. Moya-Moya collateral pattern 5. SAH B. MRI/CT Evaluation 1. Subcortical infarction 2. Cortical infarction 3. Border-zone infarction C. Pathology 1. Thickened arterial walls from intimal and subintimal proliferation 2. Rare thrombosis of veins and cerebral sinuses D. Sickled Cells 1. Adhere to the endothelium 2. Activate inflammatory cells and clotting factors that form the nidus for thrombosis 3. Small vessel sludging 4. Deficiency of nitric oxide decreases compensatory vasodilatation E. TCD 1. Velocities above 200 cm/second may occur in large vessels SSA Disease 1. Stroke propensity SC Disease 1. “Sea fan” macular sign (abnormal collection of blood vessels) 2. Propensity of strokes during pregnancy 3. Aseptic necrosis of the hip
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b. Moya-Moya like syndrome occurs with carotid occlusion c. Hypertensive vascular disease secondary to renal artery stenosis 1. Rarely secondary to associated pheochromocytoma
Polycythemia Vera
A. General Characteristics 1. AD form 2. Variants: a. High oxygen affinity variant b. Mutant hemoglobin c. Mutant receptor for erythropoietin d. Increased erythropoietins (E) e. Abnormal metabolism of 2,3-diphosphoglyceride B. Neurologic Features 1. Thrombotic events occur in 20–50% of patients 2. Thrombosis of large cerebral vessels a. Posterior greater than anterior circulation thrombotic stroke b. Scattered lesion pattern: 1. Suggestive of embolic microcirculation strokes c. Retinal venous occlusions d. Risk factors for thrombosis: (1) Age (2) Use of phlebotomies (3) Rate of phlebotomies (4) Prior history of thrombosis (5) Platelet counts not definitively linked to increased risk of thrombosis (6) Risk of stroke occurs with > 1.5 million platelets/mm3 e. Thrombotic events: 1) Most frequently occur 2 years preceding diagnosis 2) Thrombosis 3.4% per year 3) Overall mortality of 2.9/100 patients/year 4) patients receiving chemotherapy have higher mortality
Coagulopathies Neurofibromatosis I
A. General Characteristics 1. Associated with abnormalities of the renal and cerebral circulation B. Abnormalities of the Intracranial Vasculature 1. Beading of blood vessels 2. Aneurysms and arterial stenosis a. Intracerebral carotid artery 1. at the level of the ophthalmic artery
A. General Categories: 1. Decreased inhibitors of activated coagulation factors 2. Hereditary fibrinolytic deficits 3. Clotting factor deficiencies B. Autosomal Dominant Defects 1. Heparin co-factor II 2. Protein C deficiency 3. Decreased release of plasminogen activator 4. Homozygote XII deficits (thrombotic tendency)
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SECTION I. Vascular Disease
5. Prothrombin gene defect C. AR Defects: 1. Prekallikrein deficiency (Fletcher factor) D. Propensity for Thrombosis 1. Antithrombin III defects 2. Protein S deficiency 3. Plasminogen defects 4. Factor V Leiden defect E. Acquired Causes of Hypercoagulability 1. Diabetes mellitus 2. Hyperlipidemic states 3. DIC (consumption with fibrinolysis) 4. Platelet disorders 5. Vasculitis 6. Malignancy (thromboplastin-like substances released into circulation) 7. Hyperagreeable (sticky) platelets 8. Endothelial damage 9. Cardiopulmonary bypass: a. Increased fibrinolytic activity b. Decreased coagulant activity c. Increased plasminogen activator inhibitor level d. Platelets >1,000,000 – 7× risk of bleeding 10. Antiphospholipid antibody 11. Anticardiolipin antibody 12. Lupus anticoagulant 13. Heparin induced thrombosis 14. Rheological Abnormalities a. Hyperviscosity b. Deficits in laminar and pulsatile flow
Hereditary Cause of Hemorrhagic Stroke
1. X-linked VIII and IX deficiency 2. AR-afibrinogenemia 3. Factor VII, X, XI, XIII deficiency A. Clinical Features: 1. Rare bleeding in factor XI deficiency 2. VIII deficiency less than 10% of normal values are necessary to bleed 3. Latent period of deficits prior to stroke
Coagulopathies: General Categories
A. Comprehensive Procoagulant Screen 1. Common gene mutations a. Factor V (R1691A) mutation b. Prothrombin (G20210A) mutation c. MTHFR (C677T); methyl tetrahydrofolate reductase mutation 2. Rare Genetic Deficiencies a. Protein C c. Antithrombin III b. Protein S d. Plasminogen
3. Putative candidates for genetic thrombophilia a. Elevated lipoprotein b. Homocysteine Probable genetic risk factors 1. Increased: a. Fibrinogen c. Factor VIII b. Factor IX d. Decreased factor XII
Platelet Dysfunction
A. General Features 1. Increased platelet counts – above 1 million a. Associated with hypercoagulability 2. Increased coagulability may occur with increased adhesion and aggregation a. Functional platelet abnormality > than absolute number may be the important parameter 1) Sticky platelets B. Essential Thrombocythemia 1. Associated with stroke and digital artery infarction 2. Transient ischemic attacks 3. Major ICH
Leukemia
A. General Characteristics 1. Rheological abnormalities occur with WBC > 250,000/mm3 a. Capillary sludge 1) Infarction 2) Small brain hemorrhages 2. SAH a. Vaginal bleed prior to cerebral bleed at approximately 30,000 platelets Decreased Natural Inhibitors of Coagulation (a) Antithrombin III (b) Low levels of heparin releasable tissue factor inhibitor in young patients with thrombosis 1) Coincidence of defect with thrombosis is putative (c) Pre-Kallikrein deficiency 1) Severely prolonged activated partial thromboplastin time (a PTT) 2) Due to Factor XII activation 3) No increased bleeding risk 4) Bleeding risks occur in association with hereditary defects of: a) VIII, IX, XI
Most Common Deficiencies of Inhibitors of Clotting
1. Antithrombin III 3. Protein S 2. Protein C 4. Factor V Leiden Antithrombin III Deficiency:
Chapter 3. Medical Causes of Stroke
1. General Characteristics a. Usually AD inheritance b. Defect may be qualitative as well as quantitative c. Reduced synthesis in the liver d. May be lost in the nephrotic syndrome or by protein losing enteropathy Clinical Features: 1. Strong family history of venous thrombosis 2. Approximately 50% of patients with deficiency suffer: a. Venous thrombosis b. Pulmonary embolism c. Rarely myocardial infarction d. Rarely peripheral arterial disease e. Occasional stroke f. Other thrombolic risk factors potentiated in this setting
Protein C
1. General characteristics: a. AD b. Most common functional defect occurs with concomitant Factor V Leiden mutation: 1) Causes resistance to activated protein C which prevents degradation of factor V c. Hereditary protein C deficiency: 1) Lowered plasma levels in the patient and one first degree relative 2) Protein C to S ratio is a better determinant of protein C gene mutation or carrier status d. Clinical Features 1) Cerebral venous thrombosis 2) Occasional arterial thrombosis 3) Rare cerebral emboli from the heart
Protein S
1. General Characteristics a. Increases affinity of protein C for phospholipid b. Protein C inhibits procoagulant activity of Factor V and VIII c. 65% of plasma protein S is bound to c4b-binding protein which increases during infection d. Levels of protein S are low with: 1) Nephrotic syndrome 2) Protein losing enteropathy 3) Failure of synthesis with liver disease 4) Antibodies to protein S occur with post varicella purpura fulminans 5) Lower levels in women than men e. A particularly important risk factor for stroke in middle aged women 2. Clinical Features a. Dural venous thrombosis
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b. Arterial stroke c. Stroke in young patients with the concomitant risk factor of smoking
Factor V Leiden
1. Most common cause of decreased protein C function 2. Mutation of the gene that codes coagulation factor V (factor V G1691A) 3. Factor V Leiden prevalence in population: a) heterozygotes 7.7% b) hemo zygotes 0.2% 4. Risk for ischemic stroke a) heterozygotes + hemo zygotes – 0.92% b) control population – 0.68% 5. Clinically correlated with: a) thromboembolism in pregnancy b) venous thromboembolism of lower extremity c) cerebral venous and dural sinus thrombosis
Prothrombin Gene Defect
1. Second most common gene mutation causing prothrombotic state a) AR (G20210A mutation) b) Substitution, deletion or insertion of single nucleotides in the prothrombin gene 2. Two phenotypes: a) hypoprothrombinemia 1) low levels of coagulant activity 2) antigen type 1 b) dysprothrombinemia 1) low coagulant activity 2) borderline or normal antigen levels A. Clinical Manifestation 1. Cerebral venous thrombosis 2. Recurrent peripheral venous thromboembolism 3. Rare arterial clotting B. Factor VIII Alteration 1. Deficiency causes bleeding into: a) joints c) abdomen b) skin d) cranium 1) SDH 2) ICH 2. Increased Factor VIII in patients associated with: a) Thrombophlebitis b) Spontaneous abortion c) Increased incidence of stroke d) May be associated with: 1) Infections (preceding occlusive disease) 2) Crone’s disease and ulcerative colitis
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SECTION I. Vascular Disease
Chrone’s Disease and Ulcerative Colitis
Circulating Lupus Anticoagulant
General Characteristics 1. Associated with: a) Increased factor VIII b) Elevated factor V c) Reduced levels of antithrombin III d) Platelet dysfunction 2. Clinical associations: a) Venous dural sinus occlusion b) Ischemic arterial stroke c) Thrombophlebitis d) Putative mechanism for increased coagulability: 1) concomitant endothelial and valve injury e) patients with high IgG antibody titers in the presence of APLA syndrome 1) higher probability of stroke
General Characteristics: 1) High levels with the appropriate clinical symptomatology constitutes the antiphospholipid antibody syndrome 2) Lupus anticoagulant: a) Is an antibody to phospholipids b) Blocks the formation of the prothrombin activator (1) Causes a prolonged activated partial thromboplastin time (APPT) that is not corrected by added plasmin c) Most patients with the antibody do not have SLE d) Associated with increased clotting and not bleeding e) Anti IgA, IgG or IgM anticardiolipin (antiphospholipid antibodies) are found without concomitant autoimmune disease-the process is a primary APLA syndrome. 3) Clinical manifestations: a. evidence of systemic venous clotting b. large and small artery occlusions c. mitral and aortic valve lesions
Primary Antiphospholipid Antibody Syndrome
1. General Characteristics a. IgG, IgA, IgM are formed against phospholipids. Those on platelets include: 1) Phosphatidylethanolamine 2) Phosphatidylserine b. No identified autoimmune disease is present 2. Clinical features: a. Thrombophlebitis b. Small and large vessel arterial stroke c. Spontaneous abortions and fetal wastage d. Thrombotic endocarditis 1) Organized thrombus with marked fibrosis of the valves a) Valve cusps are involved b) Lesions embolize
Neurologic Manifestations
1. 2. 3. 4. 5. 6. 7. 8. 9.
Amaurosis fugax Chorea Migraine Transverse myelitis Stroke may be the initial presentation Intracranial occlusive disease Venous and dural thrombosis Atypical extracranial occlusions Binswanger’s leukoencephalopathy
APLA Syndrome Associations
Heparin Induced Thrombocytopenia and Thrombosis
1. SLE found in 1/3 of patients 2. SLE like syndrome in 5% of patients 3. Most patients have a higher frequency of: a. Myocardial infarction b. Arterial thrombosis of the lower extremities c. After age 50 males > females
A. General Characteristics Two types of heparin-induced thrombocytopenia (HIT) 1. Type I a. Transitory and asymptomatic reduction in platelet count b. Rarely < 100,000 platelets c. Resolves spontaneously d. Does not require cessation of the drug e. Putative mechanism: heparin induced platelet clumping f. Rare clinical manifestations 2. Type II a. Immunologic pathophysiology b. Occurs after the 5th day c. <30,000 platelets mm3 d. Resolves 5–15 days after cessation of heparin (1) May take months to resolve
Infections Preceding Stroke and Relationship to Clotting
1. General Characteristics a. May occur days to weeks prior to the stroke b. Evidence most convincing for chlamydia infection c. Putative mechanisms are increased levels of: 1) Acute phase reactants 4) Factor V 2) WBC 5) Factor VII, VIII 3) Fibrinogen d. May require prior endothelial injury
Chapter 3. Medical Causes of Stroke
B. Epidemiology 1. <5% from bovine heparin 2. 1% porcine heparin 3. <1% due to heparin prophylaxis C. Pathophysiology 1. Antibody to PF4 complex of the platelet 2. Ab binds to FC receptor D. Clinical Manifestation of HIT II 1. Thrombocytopenia independent of: a. Type of heparin b. Dosage c. Route of administration d. Higher risk: (1) Elderly patients (2) Post surgical prophylaxis for deep vein thrombosis (orthopedic and cardiovascular surgery) (3) Prothrombotic concomitant risks associated in 60% 2. Associated cutaneous allergic and skin necrosis 3. Major clinical neurological complications: (a) Arterial and venous thrombosis (b) May occur in the absence of thrombocytopenia and arterial thrombosis (c) Greater occurrence in cardiovascular disease (d) Arterial complications most common in large vessels (1) Gangrene of limb (2) Cardiac thrombosis (3) Stroke (4) Myocardial infarction (e) Venous complications (1) Deep vein thrombosis (2) Pulmonary embolism (3) Clotting of dialysis shunts (4) Cerebral sinus thrombosis (5) Rare complications (1) Hemorrhagic adrenal necrosis (2) DIC (6) “white” clots in blood vessels E. Laboratory Diagnosis (1) SRA Test (a) Heparin-dependent HIT antibodies release 14eserotonin from platelets (2) Heparin-induced platelet aggregation test
Disseminated Intravascular Coagulation
A. General Characteristics 1. Simultaneous clotting and activation of the fibrinolytic system 2. Causative disease entities: (a) Sepsis (b) Obstetrical emergencies (amniotic fluid emboli) (c) Cancer (release of thromboplastic-like substances)
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(d) (e) (f) (g)
Damage to blood vessel endothelium Severe brain injury or surgery Heat stroke (platelet activation) Treatment of leukemia and lymphoma (after IV chemotherapy) (h) SAH (i) Vascular malformations (Kasabach–Merritt Syndrome) 3. Abnormal activation of intravascular thrombin a. Deposition of thrombin throughout systemic and intracranial vasculature B. Neurological Manifestations (1) Large and small vessel arterial thrombosis (2) SAH (3) SDH (subdural hematoma) (4) NBTE (emboli) in cancer patients (5) Intracranial hemorrhage in non hypertensive areas (6) Multifocal encephalopathy (7) Severe acrocyanosis (8) Bleeding from prior venipuncture sites C. Laboratory Diagnosis 1. Low Platelets (thrombocytopenia) a) <30–50,000/mm3 b) Decreased factors V and VIII c) Decreased fibrinogen levels d) Prolonged PT and partial thromboplastin time e) d-dimer (new antigen) appears in the blood
Rheology
A. General Characteristics 1. Cerebral blood flow (CBF) dependent upon: a. Viscosity of the blood 1) Erythrocyte quantity and quality 2) Fibrinogen level 3) Immunoglobulins (particularly IgM) b. Perfusion pressure c. Cerebral vascular resistance B. Pathologic Increases in Blood Viscosity and Stroke occur with: 1. Polycythemia vera 2. Leukemia and lymphoma >250,000 WBC/mm3 3. Hyperfibrinogenemia 4. Waldenstrom macroglobulinemia 5. Myoglobulinemia 6. Multiple myeloma 7. High concentrations of serum lipids C. Clinical Manifestations of Hyperviscosity Syndromes 1. Lower leg petechia (Waldenström’s) 2. Poor perfusion of distal extremities; acrocyanosis 3. Bleeding gums 4. Dilated and tortuous retinal veins 5. “Box car” formation of RBC’s in retinal veins (abnormal clumping)
SECTION I. Vascular Disease
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D. Neurological Manifestations of Hyperviscosity 1. Encephalopathy 2. Headache 3. Seizures 4. Ataxia 5. Decreased vision 6. Stupor 7. Bing Neel Syndrome 8. Encephalopathy with slow processing E. Laboratory Evaluation 1. Serum viscosity compared to water is normally 1.8 2. Serum viscosity of 5–6: a) Associated with encephalopathy 3. Hematocrit > 60–65 associated with poor cerebral perfusion a) Tetrad attacks in tetralogy of Fallot (Hct > 67) 4. Sickled cells a) Poor laminar flow through capillaries 5. Endothelial factors putative cause of poor microcirculatory flow
Autoimmune Disease and Stroke
Almost all autoimmune diseases are associated with stroke, especially during exacerbations of the dysimmune process. The patient’s symptoms and signs may be dominated by organ system failure or by the other aspects of cerebral involvement such as seizures, dementia or movement disorder. The specific pattern of organ, central and peripheral nervous system involvement are the clinical clues that differentiate the entities. Neurologic manifestations and stroke frequently occur in the setting of: SLE Periarteritis nodosa Microscopic polyangiitis Sjögren’s Disease Sarcoid Rheumatoid arthritis Scleroderma Churg–Strauss Henoch–Schönlein
Wegener’s granulomatosis Allergic arteritis Thrombotic thrombocytopenia purpura Mixed collagen vascular disease Reiter’s Syndrome Relapsing polychondritis Ulcerative colitis and regional enteritis Celiac disease
Systemic Lupus Erythematosus (SLE) is generally dominated by renal, cardiac and serosal surface involvement. If there is a rash in the hand it is between the interphalangeal joints as opposed to dermatomyositis where the rash is over the joint (Groton’s sign). The malar rash is characteristic. Periungual telangiectasia and finger tip pain occur with disease activity. Pial vessel strokes occur although seizures, psychosis and proximal myopathy are the most common neurologic features. A vasculopathy rather than a vasculitis is the predominant pathology of cerebral blood vessels.
Periarteritis nodosa usually affects the peripheral nervous system with mononeuritis multiple or a multiradicular pattern of involvement. Renal medullary artery involvement with severe hypertension dominates the active phase of the disease. Late onset asthma, testicular and hepatic artery infarction occur. Eosinophilia is common. Stroke is rare. Microscopic polyangiitis is a variant of periarteritis nodosa that affects venules, arterioles and small arteries. It is the most common pulmonary-renal vasculitic syndrome. It, like periarteritis nodosa, most commonly affects the peripheral nervous system, but ischemic and hemorrhagic infarction may be seen secondary to hypertension. Sarcoid affects both the PNS and CNS. It usually comes to medical attention from its diffuse infiltrative or periaortic node involvement, Ankle pain is characteristic as are cardiac conduction abnormalities. MRI evaluation demonstrates posterior hypothalamic, chiasmatic and parenchymous granulomata. Characteristically, the dura is involved. It is associated with a cerebral vasculitis and retinal inflammation (a periphlebitis). A VII nerve palsy in association with uveitis (Heerfordt’s Syndrome) is diagnostic. Sjögren’s Syndrome is very prevalent in the population and is most often associated with rheumatoid arthritis. Its cardinal diagnostic feature is keratoconjunctivitis sicca and xerostomia (dry mouth). Peripherally there is a large fiber sensory loss with dorsal column spinal cord involvement. Both conducting and pial vessels may be involved in the CNS. Rheumatoid arteritis is most often associated with a severe motor neuropathy of the hands that causes intrinsic muscle wasting in association with CTS. Subluxation (atlantoaxial) at C2–C3 is a feared complication. Localized vasculitis is rare. Scleroderma produces a microvascular pathology that produces characteristic fibrosis of multiple organ systems. Gastrointestinal tract and renal involvement as well as its skin manifestations are characteristic. It frequently affects the Vth cranial nerve (as does Sjögren’s syndrome). A disseminated cerebral vasculitis has been noted. Churg–Strauss Syndrome should be considered in a patient presenting with asthma, eosinophilia and pituitary infarction. A CNS small vessel necrotizing arteritis may accompany the medical triad. Henoch–Schönlein is usually a disease of childhood and presents with abdominal pain, arthritis and prominent purpura. Allergies to drugs may be a precipitant. Rare small vessel stroke has been reported. Wegener’s granulomatosis should always be borne in mind in the setting of refractory chronic sinus disease. The usual medical evaluation reveals upper respiratory tract necrotizing vascular lesions. Orbital involvement is common with extraocular muscle paresthesia. A cerebral arteritis with pial vessel infection occurs. Hypersensitivity vasculitis primarily affects the skin in the form of a purpuric skin rash. Specific allergies trigger the process (particularly sulfa). The extremities are symmetrically swollen, erythematous and painful. Stroke is rare.
Chapter 3. Medical Causes of Stroke
Mixed collagen vascular disease is an overlap of SLE, scleroderma and polymyositis. Encephalopathy, seizure and aseptic meningitis are much more common CNS manifestations than stroke from vasculitis. Peripheral nerve involvement is more common than are CNS manifestations. Thrombotic thrombocytopenic purpura often has a dramatic explosive onset manifested by seizures, hallucinations, fever and renal failure. Transient focal neurologic deficits dominate its course. Multifocal microinfarctions of the cortex is seen pathologically. Reiter’s syndrome should be suspected in a patient with diarrhea and heel pain associated with optic neuritis, encephalitis and pial artery stroke. Relapsing polychondritis is an autoimmune disease of cartilage. It may present with inflamed sore ear lobes (also occurs in ochronosis) conjunctivitis, lip scleritis and laryngotracheal involvement. Stroke is rare. Ulcerative colitis and regional enteritis are associated with both venous and cerebral sinus thrombosis as well as large vessel stroke. Celiac disease presents most commonly with severe diarrhea. Its neurologic manifestations are proximal myopathy and ataxia. Occasionally, patients suffer conducting vessel and pial strokes. The following is a detailed description of the major neurologic and general medical features that differentiate the autoimmunize entities that cause stroke.
Systemic Lupus Erythematosus
A. General neurologic manifestations 1. Psychosis 2. Proximal myopathy 3. Sensorimotor neuropathy 4. Mononeuritis multiplex 5. Migraine headaches 6. Chorea 7. Seizures 8. Stroke (pial arteries; multifocal) 9. Retinal findings: (a) Cytoid bodies (b) Increased nicking of arterioles B. Arteritis: 1. Vasculopathy more common than arteritis. Change in the vascular wall rather than WBC invasion C. Hematologic Abnormalities in SLE 1. Clinical signs and symptoms of Lupus anticoagulant: a. Miscarriage b. Recurrent thrombophlebitis c. Small vessel ischemic stroke 2. Thrombocytopenia 3. Platelet abnormalities 4. Thrombotic thrombocytopenic like syndrome a. Platelet thrombi in arteries and capillaries
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b. Subendothelial hyaline deposits c. Arterial microaneurysms D. Source of Cardiac Emboli in SLE: 1. Libman Sachs (verrucous) endocarditis 2. Marantic endocarditis 3. Mural thrombi 4. Endocarditis (infectious) E. Prognosis 1. Approximately 30% of patients die from cerebral thrombosis 2. Anti-ds double stranded DNA and antiphospholipid antibodies have predictive value for development of SLE Stroke Mechanisms
A. Libman Sachs endocarditis with emboli B. Coagulopathy (1) lupus anticoagulant (2) anticardiolipin antibody C. Noninflammatory vasculopathy D. Small deep infarcts (1) associated HCVD E. Intracranial branch artery occlusion F. Cortical and subcortical infarcts (arteritis) G. Large Vessel Stroke (1) in approximately 86% of patients the disease is active at stroke occurrence (2) stroke occurs after 4–5 years of disease (3) headache is common at onset (4) often associated with low protein S activity (5) antiphospholipid antibody associated with Libman– Sachs endocarditis (6) global depression of left ventricular function (a) cardiac small vessel arteritis (b) poor ejection fraction and embolus H. Unusual Vascular Manifestations: (1) vertebrobasilar territory infarction at presentation (2) vascular monocular or binocular optic neuropathy (3) posterior ischemic optic neuritis
Periarteritis Nodosa
A. General Characteristics 1. Multisystem involvement: (a) Late onset asthma (b) Testicular infarction (c) Lobar hepatic infarction (d) Eosinophilia (e) Severe hypertension from renal involvement (f) Palpable arteriolar enlargement in the skin (g) May occur with hepatitis B and C B. Neurological Manifestations: 1. Peripheral nerve involvement
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C.
D.
E.
F.
SECTION I. Vascular Disease
(a) Mononeuritis multiplex (b) Guillain Barré-like syndrome CNS involvement (a) Occurs in 20–40% of patients late after onset of systemic and PNS disease Stroke (1) Occurs late in the illness (2) Often secondary to renal induced hypertension (3) Illness never presents with stroke Ocular manifestations 1. Any orbital structure may be involved 2. Conjunctivitis 3. Episcleritis 4. Extraocular muscle palsy 5. Optic neuritis 6. Orbital pseudotumor Pathology 1. Involvement of medium sized arteries a. Disease occurs at branch points b. Necrotizing arteritis: 1) Increased levels of adhesion molecules 2) Invasion of arterial wall by leukocytes and monocytes 3) Fibrinoid necrosis 4) Endothelial proliferation with thrombosis c. Rare ANCA antibodies (pANCA); antinuclear cytoplasmic antibodies d. Multiple microaneurysms and stenosis of medullary renal arteries
Microscopic Polyangiitis (Periarteritis nodosa variant)
A. General Features 1. A form of necrotizing small vessel vasculitis a. Affects venules, arterioles and small arteries b. Rarely medium-sized arteries are affected 2. Absence of or minimal immunoglobulin location in vessel walls distinguishes it from: a. Henoch–Schönlein purpura b. Cryoglobulinemic vasculitis 3. Associated medical conditions: a. Immune necrotizing and crescentic glomerulonephritis b. Hemorrhagic, pulmonary capillaritis c. Most common cause of pulmonary-renal vasculitic syndrome 4. Pathologically vasculitis similar to: a. Wegener’s b. Churg–Strauss 5. Associated with circulating pANCA antibodies 6. Putative role for neutrophiles/monocytes in vascular injury B. Systemic Features 1. Fever, weight loss and fatigue in majority of patients 2. pANCA is antibody seen
(a) Myeloperoxidase is in the epitope that pANCA binds 3. Elevated C-reactive protein and sedimentation rate prominent at diagnosis C. Neurological Signs 1. Optic neuritis 2. Peripheral nervous system involvement a. GBS b. Mononeuritis multiplex c. Vasculitic induced sensorimotor neuropathy 3. Ischemic and hemorrhagic infarction from hypertension
Sarcoid
A. General Characteristics: 1. Pulmonary periaortic node involvement 2. Diffuse infiltrative lung pattern 3. Cardiac conduction abnormalities 4. Rheumatologic manifestations (ankle involvement prominent) 5. Skin manifestations (neck and nose) B. PNS Involvement: 1. Cranial nerve VII (with uveitis is Heerfordt’s syndrome) 2. Optic nerve (compression by meningeal infiltration) 3. Sensorimotor neuropathy 4. Myopathy 5. Chiasmatic involvement C. CNS Involvement 1. Chiasm 2. Parenchymatous granuloma occur in the: a. Posterior hypothalamus b. Pituitary c. Hemisphere 3. Meningeal involvement; may compress optic nerves 4. Compressive myelopathy 5. Meningitis: a. Glucose 30–40 mg% b. Slightly elevated protein 60–80 mg% c. Lymphocytic pleocytosis (30 cells mm3 ) 6. Stroke: a. Cerebral vasculitis b. Associated with pleocytosis c. Retinal inflammation (periphlebitis) d. Spread of inflammatory cells from the meninges through the Virchow–Robin spaces to pial vessels e. Predilection for veins (phlebitis) 7. Stroke pattern a. TIA b. Superficial pial artery stroke 8. Retinal changes: a. Periphlebitis (diffuse sheathing of retinal veins) b. Hard exudates (“taches de bougie”; candle wax dripping) c. Chorioretinal scars
Chapter 3. Medical Causes of Stroke Sjögren’s Syndrome
General Characteristics: 1. May affect 3% of population; women > men 2. 50% of patients it is secondary (occurring with other processes) a. Most often associated with rheumatoid arthritis 3. characterized by: a. Keratoconjunctivitis sicca b. Xerostomia c. Associated with other connective tissue diseases 4. Lymphoid invasion of exocrine tissues of the body: a. Otitis (eustachian tube dysfunction) b. Recurrent bronchial infection c. Dryness of genital mucosa d. Atrophic gastritis e. Atrophy of the oral mucosa 5. Raynaud’s phenomena 6. 50% of patients have arthralgias 7. Renal interstitium involved 8. Muscle, skin, nerve, vasculitis a. Usually involved with RA (rheumatoid arthritis) 9. Neurological manifestations 10. peripheral nervous system: a. Large fiber sensory loss b. Dorsal column involvement c. Autonomic impairment 1) Adies pupil (tonic pupil) 2) Anhidrosis 3) Orthostatic hypotension d. Vth nerve involvement 1) Gasserian ganglionitis e. Central nervous system involvement: 1) Myelitis 4) Meningoencephalitis 2) Seizure 5) Focal brain infiltrates 3) Dementia 6) f. Stroke: 1) Pial vessels 3) Hemiparesis, aphasia, ataxia 2) Large vessels 4) Cognitive and behavioral deficits g. Associated with primary progressive multiple sclerosis h. CSF: 1) Lymphocytic pleocytosis < 30 cells mm3 2) Mildly elevated protein 60–80 mg% i. MRI evaluation 1) Lesions resemble those of MS 2) Dorsal column spinal cord lesions 3) Discrete cortical lesions that resemble infarcts
Rheumatoid Arthritis
General features: 1. Crippling arthritis associated with: a. Ocular manifestations (keratoconjuctivitis) b. Cardiac involvement
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c. Vasculitis of the bowel 2. Possibly affects 1% of the population 3. Associated neurological manifestations: a. Myopathy (proximal) b. Neuropathy (severe atrophy of intrinsic hand muscles) c. Atlantoaxial subluxation (C2–C3; spinal cord compression) d. Rheumatoid pachymeningitis e. Rheumatoid dural nodules (seizures) f. Encephalopathy g. Generalized sensorimotor neuropathy h. Rare mononeuritis multiplex i. C2 pannus with spinal cord compression j. CTS 4. Cerebral rheumatoid vasculitis occurs: a. Concomitantly with aggressive systemic rheumatoid vasculitis b. Rarely in isolation c. Ischemic stroke associated with: 1) Localized vasculitis (rare) 2) Rheumatoid pachymeningitis 3) Cardiac emboli 4) Multifocal small infarcts d. Cerebral hyperviscosity syndrome due to: 1) High titers of circulating rheumatoid factor 2) Increased levels of fibrinogen, and fibrinogen depredation products
Scleroderma
A. General Features: 1. Microvascular pathology and diffuse tissue fibrosis that affects: a. Skin d. Heart b. Gastrointestinal tract e. Kidneys c. Lungs 2. Neurological Manifestation Peripheral nervous systems: a. Myopathy in 17% of patients b. Cranial nerve involvement 1) Vth nerve most often involved 2) Possibly at the ganglion level c. Sensorimotor neuropathy d. Mononeuritis multiplex e. Carpal tunnel syndrome f. Cranial neuropathies (Vth nerve) g. Autonomic neuropathy h. Myelopathy (rare) 3. CNS Features: stroke a. Disseminated cerebral arteritis b. Hemorrhage from renal hypertension c. SAH (rare) d. Cardiac emboli (rare)
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SECTION I. Vascular Disease
Churg–Strauss Syndrome
A. General Characteristics 1. Asthma 2. Eosinophilia 3. Previous allergic disorder 4. Lung involvement 5. Pituitary infarction 6. >60% of patients have CNS involvement 7. May be relapsing B. Primary Vascular Involvement 1. venules 3. arterioles 2. capillaries 4. small vessel necrotizing vasculitis C. Neurological Manifestations 1. Encephalopathy 2. Peripheral neuropathy a. Distal motor sensorimotor 3. Rare small vessel stroke 4. Pachymeningitis
Henoch–Schönlein
1. General characteristics: a. Predominant IgA meningeal deposits (1) Small vessel necrotizing arteritis b. Clinical associations: (1) Purpura (2) Abdominal pain (3) Arthritis (4) Renal involvement (5) Carcinoma of respiratory and GI tract (6) Adult involvement (a) Preceded by mucosal infection of the upper respiratory tract 2. Neurological complications a. Occasional small vessel stroke (1) Primarily in children (2) ICH (children) (a) Factor XIII deficiency b. Allergic reactions to drugs are a precipitant
3. 4. 5. 6.
Eosinophilic fasciitis (rarely associated) Jaw claudication (rare) Rarely associated with temporal arteritis Stroke a. Cerebral arteritis b. Pial vessel infarcts 7. Laboratory evaluation a. Sed rate a good measure of disease activity b. pANCA elevated c. Overlap with other serum markers of hypersensitivity disease
Hypersensitivity Vasculitis 1. General characteristics: a. Rash b. Palpable purpuric skin lesions c. Legs more commonly affected than arms d. Extremities may be symmetrically swollen and erythematous 2. Etiology a. Specific allergens c. Post infectious b. Penicillin and sulfa drugs 3. Henoch–Schönlein: General manifestations: a. Joint pain may be prominent 4. Mixed cryoglobulinemia a. Acrocyanosis b. Cold induced acroparesthesias c. Sensorimotor neuropathy d. Increased IgM
Peripheral Nervous System Manifestation
1. Sensorimotor neuropathy 2. Plexopathy 3. More common than CNS manifestations
Stroke 1. Diffuse petechiae in centrum semiovale a. Secondary to low platelets
Wegener’s Granulomatosis
A. General characteristics 1. Necrotizing vasculitis of: a. Sinuses c. Upper respiratory tract b. Lungs d. Kidneys 2. Neurological manifestation a. Optic nerve ischemia b. Orbital involvement c. Extraocular muscle palsies d. Retinal involvement e. Posterior ischemic optic neuropathy
Mixed Collagen Vascular Disease
1. General characteristics a. Features of: 1) SLE 2) Scleroderma 3) Polymyositis b. Concomitant high titers of antibody to: 1) RNase-sensitive ribonucleic complex a) small RNPC (ribonucleic protein)
Chapter 3. Medical Causes of Stroke
2. Neurological manifestations: a. Headache g. Aseptic meningitis b. Seizure h. Monocular blindness c. Psychosis i. Vth nerve involvement d. Encephalopathy j. Sensorimotor neuropathy e. Transverse myelitis k. Entrapment neuropathy f. Ataxia 3. Stroke a. Rare b. Secondary to cerebral vasculitis 4. Neurologic features are dependent on the dominant clinical syndrome, i.e., SLE vs scleroderma vs polymyositis
Thrombotic Thrombocytopenic Purpura (Moschowitz Syndrome)
1. General characteristics a. Female 2 : 1 > male b. Fever (interleukin I) c. Renal failure d. Thrombocytopenia e. Microangiopathic hemolytic anemia 2. Associated with: a. Pregnancy b. Bone marrow transplantation c. HIV d. SLE e. Ticlopidine f. Sjögren’s Syndrome g. Rheumatoid arthritis h. Influenza vaccination i. D-penicillamine j. Cyclosporine k. Citomycin 3. Neurological manifestations a. Diffuse encephalopathy 1) Visual hallucinations 3) Seizures 2) Headache 4) Visual loss b. Transient focal deficits c. Aphasia d. Papilledema e. Relapsing course f. Posterior leukoencephalopathy 4. Pathology a. Arteriolar and capillary involvement b. Platelet rich thrombi c. Multifocal microinfarctions 5. Pathogenesis a. Non-familial form 1) Inhibitor of Von Willebrand factor cleaving protease b. Familial form (constitutive deficiency of the protease) c. Large multimeres of Von Willebrand Factor adhere to and aggregate platelets
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Reiter’s Disease
1. General characteristics: a. May follow G.I. illness b. Severe heel pain 2. Neurologic complications: a. Optic neuritis b. Encephalitis c. Ascending motor paralysis (GBS like syndrome) d. Seizures e. Brainstem dysfunction f. Acute transverse myelitis g. Neuralgic amyotrophy h. Superficial pial stroke
Relapsing Polychondritis
1. General characteristics a. Episodic inflammation of cartilage throughout the body 2. Clinical characteristics a. Pain and tenderness of cartilaginous portions of the ear in 85% of patients b. 40% suffer inner ear disease with: 1) Hearing loss 3) Vertigo 2) Tinnitus 4) Rarely deafness c. Ocular involvement: 1) Conjunctivitis, episcleritis, scleritis 2) Iritis and iridocyclitis 3) Keratoconjunctivitis sicca 4) Choroiditis 5) Orbital pseudotumor (proptosis) 6) Optic neuritis 7) Retinal vasculitis d. Nasal cartilage inflammation 1) 70% of patients 2) Saddle nose deformity e. Aortic insufficiency f. Laryngotracheal involvement in 50% g. 10% of patients develop PAN 3. Associated Diseases: a. Rheumatoid Arthritis b. Systemic lupus erythematosus c. Reiter’s syndrome d. Ankylosing spondylitis e. Ulcerative colitis f. Hashimoto’s thyroiditis g. 25% have myelodysplastic syndrome 4. Neurologic Signs and Symptoms: a. Occur in 3% of patients b. Extraocular muscle palsy c. Optic neuritis d. Bilateral VIIth nerve 1) Associated with inner ear disease e. Mononeuritis multiplex 1) Associated with PAN
SECTION I. Vascular Disease
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f. CNS manifestations: 1) Meningoencephalitis 2) Headache 3) Altered consciousness 4) Papilledema 5) Meningeal signs 6) Seizure 7) Ischemic stroke
Ulcerative Colitis and Regional Enteritis
A. General characteristics 1. Dominant bowel symptoms 2. Large joint arthritis 3. Keratoconus B. Neurological Manifestations 1. Cerebral venous and sinus thrombosis 2. Large vessel strokes 3. Loss of protein C and S (protein losing enteropathy)
Celiac Disease
1. General characteristics: a. Severe diarrhea c. Antibodies to gliadin b. Gluten sensitivity 2. Neurologic manifestations: a. Proximal myopathy b. Sensorimotor peripheral neuropathy c. Spinal cord dysfunction d. Cerebellar degeneration with ataxia 3. Stroke a. Large conducting and pial vessel stroke
Giant Cell Arteritis
1. General characteristics a. Incidence of 17.4/100,000 people b. Superficial temporal and occipital arteries are most frequently involved c. Internal carotid, extracranial vertebral arteries, coronary, femoral and rarely intracranial arteries may be affected d. Extracranial vessels most commonly involved in giant cell arteritis are: 1) Aortic arch (dissection) 2) Rupture of an aortic aneurysm 3) Annuloaortic ectasia 2. Presents as a systemic illness: a. Low grade fever b. Iching of proximal muscles c. Weight loss d. Onset of headache
1) Painful burning scalp 2) Not pulsatile e. Jaw claudication f. Perforated nasal septum g. Ischemic tongue lesions (similar appearance to carcinoma) h. Painful cord like superficial temporal arteries (only 30– 40% positive by biopsy) 1) ESR is increased in greater than 90% of patients’; biopsy negative in at least 50% of patients i. Sites of arterial involvement causing stroke: 1) Distal extracranial ICA at the carotid siphon 3. Rare sites of involvement: a. Pial and brainstem arteries 4. Extracranial giant cell arteritis: a. Occurs in 10–15% of patients with polymyalgia rheumatica 5. Relapses may occur after successful treatments
Neurological Manifestations
1. Blindness from: a. Occlusion of the posterior ciliary arteries (derived from the internal carotid) or their collaterals (from the external carotid) b. Central retinal artery occlusion c. Ischemic optic neuropathy from infarction at the optic disc d. Visual loss occurs suddenly 1) may occur in the second eye within minutes or at approximately 2 months 2) men > women with severe ocular problems 3) visual loss is permanent due to infarction of the optic nerve head and retina 2. Visual field deficits a. Altitudinal rather than central 3. Anterior optic nerve involvement: a. Mild papilledema b. Infrequent disk hemorrhage c. Resolves over 10 days 4. Retrobulbar ischemic optic neuropathy: a. Gradual optic pallor and atrophy 5. Diplopia: a. 2–14% of patients b. Vasculitis of extraocular muscles with total ophthalmoplegia (rare) 6. Cranial nerve palsies: a. Rare that VIII th nerve is involved b. Infarction of the internal auditory artery (origin is AICA) 7. Tongue: a. Hemianesthesia of the tongue b. Lingual paralysis c. Ischemic tongue lesion 1) Similar to squamous cell carcinoma in appearance
Chapter 3. Medical Causes of Stroke
8. Facial pain: a. Arteritis of the facial branch of the external carotid artery 9. Myelopathy: a. Vasculitis of the vertebral and anterior spinal artery with cervical cord infarction 10. Peripheral neuropathy: a. Distal symmetrical sensorimotor neuropathy b. Mononeuritis multiplex c. One month after onset 11. Myopathy: a. Steroid related proximal myopathy
Cerebrovascular Disease
1. TIA of anterior and posterior arterial systems 2. Encephalopathy a. Arteritis of pial and superficial arteries 3. Multiinfarct dementia 4. Infarction of major branches of both anterior and posterior circulations 5. arotid bruits noted in 10–20% of patients: a. Bilateral bruits: 1) 60% of these patients have associated involvement of the aortic arch 6. Vertebrobasilar arterial involvement may present with: a. Acute confusional state b. Coma
Laboratory Evaluation
(1) Elevated sedimentation rate (2) Mild normocytic anemia (3) Mild peripheral leukocytosis
Isolated Angitis of the CNS
A. General features: 1. This is putatively and immune mediated arteritis of strictly cerebral blood vessel 2. Other names for the process: a. Isolated granulomatous angiitis b. Giant cell granulomatous angiitis of the CNS 3. Mean age of onset 49; any age can be affected 4. Male predominance 2 : 1 5. Vasculitis isolated to the CNS: a. Exclusion of systemic inflammation, infection or other causes of CNS vasculitis; rarely associated with angioid angiopathy 6. Segmental necrotizing granulomatous vasculitis that involves: a. Cortical arteries b. Spinal arteries
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c. Leptomeningeal arteries d. Usual vessel size involved is 200–500 μm (microns) 1) Any size vein or artery may be involved 2) Precapillary arterioles < 200 μm are involved e. Intima and adventitia of arteries are infiltrated with: 1) Lymphocytes, giant cells, and granulomas 2) Granulomas may invade the cortex f. Veins may be affected in 50% of patients B. Neurologic Manifestations 1. Earliest symptoms: a. Headache b. Phonophobia c. Photophobia d. Unusual stroke-like presentation e. Diffuse encephalopathy (usual presentation) f. Gradual onset 2. Later signs and symptoms: a. Altered mental status b. Dementia c. Myelopathy d. Hemiparesis e. Diffuse encephalopathy f. Rare territorial stroke g. Pathology of intracranial vessels 1) Thrombosis 2) Small aneurysms develop on arteries h. Myelopathy may precede encephalopathy i. Seizures occur j. Usual progression 1) Step-like deterioration of a progressive encephalopathy k. Rare SAH C. Imaging Evaluation 1. MRI a. Positive 68% of the cases b. Infarcts demonstrated (ischemic) c. Rarely hemorrhagic infarction d. Small hematoma (rare) e. Rare intracerebral aneurysm 2. Arteriogram a. Positive in approximately 50% of patients; involved vessels <500 μm b. Segmental narrowing, dilatation and beading 3. Laboratory Evaluation a. Elevated sed rate in 2/3 of patients b. CSF 1) Mononuclear and lymphocytic pleocytosis a) CD4+ lymphocytes involved b) Protein elevated in 80%of patients > 100 mg/dl
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SECTION I. Vascular Disease
Nongranulomatous Angiitis of the CNS
A. General characteristics: 1. Segmental necrotizing angiitis without granulomata 2. Male: female 1.8 to 1 3. Multiple small but occasionally large foci of infarction throughout the CNS 4. Mean age at onset 49 B. Neurological Manifestations: 1. Acute presentation a. Stupor or coma within days to weeks 2. Classic presentation: a. Fever and weight loss uncommon b. Mental status change c. Headache d. Hemiparesis e. Impairment of consciousness f. Focal, multifocal or diffuse encephalopathy 3. Rare vascular presentation: a. TIA c. SAH b. large vessel stroke d. Multiinfarct stroke 4. Rare neurologic presentation a. Increased ICP b. Chronic meningitis or arachnoiditis c. Cerebral hemorrhage d. Radiculopathy C. Evolution of the Disease 1. Stepwise occurrence of focal neurologic deficits D. Laboratory Evaluation 1. Mild elevation of ESR in 2/3 of patients 2. CSF mononuclear pleocytosis (mean of 70 monocytes/ mm3 ) E. Imaging Evaluation: 1. MRI: a. White and grey matter involvement b. Occasional hemorrhage c. Bilateral subcortical lesions d. Enhanced meninges 2. Arteriography a. Abnormal in approximately 60% 1) Segmental narrowing and sausage shaped dilatation (beading) 2) Rarely: avascular mass or intracerebral aneurysm 3) Affected vessels < 500 μm 3. Leptomeningeal biopsy more often positive than brain biopsy
Benign Angiitis of the CNS
A. General Characteristics 1. Affects young women 2. Setting of intermittent hypertension B. Neurologic Manifestations
1. Transient reversible neurologic deficits 2. Multi-segmental arterial narrowing 3. Self limited course C. Course, setting and favorable prognosis differentiate this entity from isolated angiitis of the CNS
Post Partum Cerebral Angiopathy
General Characteristics: 1. May occur up to two days after delivery 2. Associated with a. Bromocriptine c. Ergotamines b. Sympathomimetic drugs 3. May be recurrent Neurological Manifestations 1. Transient bilateral parieto-occipital high signal intensity lesions on MRI (T2) 2. Frontal intracranial hemorrhage 3. Primary angiitis of the central nervous system associated with cerebral amyloid angiopathy General Characteristics 1. Mean age of onset: a. PACNS with amyloid angiopathy (65 years) b. PACNS (44.8 years) c. Cerebral angioid angiopathy (CAA) (76 years) Neurological Manifestations 1. Multifocal neurological signs and symptoms 2. Headache 3. Hallucinations 4. Subacute cognitive deficits CSF 1. Eosinophilic pleocytosis 2. Xanthochromia >40% of patients The following are different conditions that mimic vasculitis of an immune basis and vasculitis differentiated by pathologic process, association with neoplastic disease, site of involvement, topography, vessel size and segmental narrowing on arteriogram.
Differential Diagnosis of Conditions Mimicking Vasculitis
1. Dissecting aneurysm 2. Antiphospholipid syndrome 3. Drugs a) Methamphetamine d) Ephedrine b) Sympathomimetic drugs e) Propyl ethanolamine c) Ginseng f) Cocaine 4. Cholesterol emboli 5. Intravascular lymphomatosis 6. Coll.’s syndrome
Chapter 3. Medical Causes of Stroke Differential Diagnosis of Arteritis Associated with Autoimmune Diseases
1. SLE 2. PAN 3. Sarcoid 4. Sjögren’s 5. Rheumatoid arthritis 6. Scleroderma 7. Churg–Strauss 8. Wegener’s granulomatosis 9. Hypersensitivity arteritis 10. Mixed collagen vascular disease
11. Giant cell arteritis 12. Reiter’s Syndrome 13. Relapsing polychondritis 14. Ulcerative colitis 15. Regional enteritis 16. Celiac Disease 17. Serum sickness 18. Henoch–Schönlein purpura 19. Cryoglobulinemia
Differential Diagnosis of Systemic Necrotizing Arteritis
1. 2. 3. 4.
Wegener’s granulomatosis Lymphomatoid granulomatosis Sarcoid Hairy cell leukemia
Differential Diagnosis of Arteritis with Neoplasia
1. 2. 3. 4. 5.
Hodgkin’s disease Non-Hodgkin’s lymphoma Neoplastic angioendotheliosis Hairy cell leukemia Angiocentric endothelial lymphomatosis
Differential Diagnosis of Isolated Angiitis of the CNS
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
Necrotizing vasculitis HZ Hodgkin’s disease HIV Sarcoid Hypersensitivity arteritis PAN Lymphomatoid granulomatosis Methamphetamine Sympathomimetic drugs Coll.’s Disease Wegener’s granulomatosis
Differential Diagnosis of Systemic Vasculitis Resembling Isolated Angiitis of the CNS
1. Vasculitis with connective tissue disease 2. PAN
3. 4. 5. 6.
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Wegener’s granulomatosis Giant cell arteritis Takayasu’s Disease Behçet’s Disease
Differential Diagnosis of Vasculitis Associated with Granulomatous Parenchymal Lesions
1. Wegener’s granulomatosis 2. Sarcoid 3. Lymphomatoid granulomatosis 4. Granulomatous angiitis Differential Diagnosis of Granulomatous Angiitis of the CNS 1. Hodgkin’s Disease 2. Sarcoid 3. HZ 4. Methamphetamine 5. Sympathomimetic drugs 6. Coll.’s Disease Differential Diagnosis of Vasculitis By Characteristic Sites of Involvement 1. Takayasu’s Disease: a) Arch of the aorta b) Mid common carotid artery c) Mid descending aorta 2. Sneddon’s Syndrome a) Skin (livedo reticularis) 3. Köhlmeier–Degos Syndrome a) Atrophic skin lesions 4. Giant cell arteritis a) Primarily external carotid system b) May affect the ICA, and arch of the aorta
Differential Diagnosis of Vasculitis by Topography
1. Focal a. Herpes Zoster 1) Proximal MCA; ACA (side of the skin lesions) 2. Multifocal a. SLE b. Primarily separate areas of the cortex 3. Disseminated a. Isolated or primary angiitis of the CNS
Differential Diagnosis of Vasculitis of Medium Sized Arteries
1. PAN 4. Sjögren’s Syndrome 2. SLE 5. Buerger’s Disease 3. RHA
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SECTION I. Vascular Disease
Differential Diagnosis of Vasculitis of Small Sized Arteries
1. 2. 3. 4.
Churg–Strauss Polyarteritis nodosa (microangiopathic variant) Wegener’s granulomatosis Hypersensitivity arteritis
Differential Diagnosis of Segmental Narrowing of Cerebral Arteries on Arteriogram
1. Arteritis (infective; inflammatory; necrotizing) 2. Leptomeningitis (infective, chemical, carcinomatous) 3. Vasospasm (SAH, migraine, hypertensive encephalopathy) 4. Atherosclerosis 5. Fibromuscular dysplasia 6. Recanalization of emboli 7. Sickle cell disease 8. Sympathomimetic drug abuse 9. Neoplasms (angioendotheliosis, glial and meningeal tumors, atrial myxoma) 10. Closed head injury 11. Radiation therapy (X-RT) 12. Neuroectodermal dysplasia (neurofibromatosis; tuberous sclerosis)
Differential Diagnosis of Infectious that Cause Stroke
The differential diagnosis of the infections that cause stroke rests on the specific pathologic mechanisms induced or associated with each infection. The neurology of each infection is different and often the extracranial manifestation of the infection provides the clue to the specific diagnosis. Bacteria viruses and fungi cause stroke as due spirochetes and protozoa. Stroke may occur in the setting of bacterial meningitis. Pus may directly involve the pial vessels that encases them on the cortex. Pneumococcus may concomitantly infect heart valves and mycotic aneurysm with hemorrhage and stroke may occur 6–8 weeks after the primary infection. Meningococcal infection occurs frequently in settings in which young healthy adults are living in close quarters. The speed of the infection (headache to coma) within hours is characteristic. The course is dominated by the meningitis. Stroke is rare. Listeria infections occur following head and neck surgery and during pregnancy and delivery. The seminal feature is brainstem infarct with dorsal pontine involvement. Bartonella henselae infection follows exposure or inoculation from cats. Seizures and retinitis are the seminal features following extremity lymphadenitis.
Syphilis has made a comeback as a serious cause of infection due to HIV. It may be telescoped where all three stages are seen within a short period of time. In the past, brainstem strokes were noted in the meningovascular stage. This pattern persists, but may be more associated with gumma formation and less with clonic syphilitic optic nerve and pretectal involvement (Argyl Robertson pupils). If meningitis is seen concomitantly the CSF sugar is usually normal. Lyme disease is the most common vector borne infection in the United States and has protein manifestations. If VIIth nerve palsy and characteristic rash and large joint arthritis is present diagnosis is straight forward. Unfortunately, many patients present in later stages with asthenia and low grade encephalopathy weeks or months after the infection. Strokes are rare, but are described. Tuberculosis causes strokes because of cortical and basilar exudates. It is a more chronic illness in Western countries and is often seen as a low grade dementing illness. It should always be suspected in HIV infected patients with lower cranial nerve abnormalities (particularly the VIIIth nerve). Fungal infections occur most frequently in the immunocompromised host. Disorders of B-lymphocyte function are associated with encapsulated bacterial pathogens. Impaired T-lymphocyte or macrophage function causes infection by intracellular pathogens such as aspergillus and fungi, nocardia (bacterial) viruses and parasites (toxoplasmosis gondii). Extra CNS sites of infection suggest aspergillus and nocardia that may present subacutely or chronically. T-lymphocyte dysfunction with meningitis is Listeria or cryptococcus. Aspergillus can present as a CNS mass lesion or stroke but most often as meningitis. Mucormycosis is associated with all forms of immunosuppression, but particularly with diabetic ketoacidosis and renal failure. The fungus is associated with sinus infection and venous infarction. It should be suspected in this circumstance in a patient with ophthalmoplegia. Aspergillosis infects isolated lung abcesses and is associated with osteomyelitis of the base of the skull. It is notorious for fungal hyphae occluding cerebral conducting vessels. Fungal balls from valve leaflets are large enough to occlude peripheral extremity arteries. Cryptococcus usually presents as a chronic dementia in the setting of immunocompromise. It spreads through the Virchow–Robin spaces to involve the basal ganglia. This is most helpful in setting of stroke and T2 enhancement of the caudate and putamen. Proximal MCA branches and vessels in the posterior perforated substance are most frequently involved. Coccidiomycosis is common in the American SW. Extracranially it affects lungs and joints. Sacral involvement is frequent as is involvement of the jaw. Proximal MCA and the arteries of the perforated posterior substance are most often involved. Histoplasmosis is most often encountered in the Mississippi Valley. It may be associated with adrenal failure with
Chapter 3. Medical Causes of Stroke
concomitant splenic calcification. Arteries are inflamed in the chronic basilar exudate. Viral infectious cause stroke by direct invasion of the vessel wall or its endothelium, an immune response triggered by vessel epitopes or immune complex deposition. Herpes Zoster causes a middle cerebral artery stroke of the ipsilateral MCA on the side of the Vth nerve involvement. This characteristically occurs 6–8 weeks following the rash, but has been seen within two weeks. Both anterior and posterior circulation large vessels may be involved. Immune compromised HIV patients may suffer small vessel disease. One mechanism is involvement of vessel wall endothelial antithrombotic systems. HIV itself is associated with stroke from various mechanisms: 1. Immune complex formation 2. Cell mediated vasculitis 3. Inflammation from direct viral invasion 4. Associated infections that cause stroke Most often the pathology is in medium sized arteries. The clinical manifestations of severe HIV infection suggest the diagnosis. Cerebral malaria may be the most widespread CNS infection with stroke as a consequence. It most often occurs with plasmodia falciparum and occurs due to obstruction of main capillaries by parasitized RBC. The following is a more detailed description of the various infections that cause stroke.
Infections that cause stroke
1. Bacterial meningitis a. Pneumococcus: 1) Early hematogenous spread from the lung 2) Simultaneous infection of the heart valve (may occur); later SBE 3) Stroke of superficial pial vessels 4) Course clinically dominated by meningitis b. Meningococcal infection: 1) Early headache, nausea and vomiting; “flu-like” 2) Rapid progression to lethargy in 6–12 hours 3) Pial artery strokes 4) Adrenal failure (Waterhouse–Frederickson Syndrome) 5) Clustered infection a) Close living quarters (army barracks’ camp, college dormitories) 6) Bacteria may be seen in cerebral spinal fluid prior to neutrophils c. Listeria monocytogenes 1) Head and neck cancer patients 2) Abrupt onset of symptoms 3) Clinical involvement of: a) Medulla
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b) Pontine tegmentum (seminal feature) c) Lower cranial nerve palsies d) Arteritis of the brainstem with multiple infarcts e) Focal encephalitis f) Monocytic cerebral spinal fluid pleocytosis d. Bartonella henselae (cat-scratch fever) 1) Lymphadenopathy in drainage area of the scratch 2) Seizures (generalized) 3) Retinitis 4) Intracranial stenosis and arteritis
Syphilis
1. Arteritic attacks occur in stage II disease (meningovascular syphilis) a. Many brainstem syndromes were originally described in patients with syphilis b. “Heubner’s arteritis” 2. A proliferative endarteritis 3. Primarily occurs in small penetrating vessels of the brainstem 4. Pupillary abnormalities: a. Oval pupil b. Argyle–Robertson pupil c. Paralytic tabetic pupil 5. Associated retinitis pigmentosa a. Pigmentary migration around choroidal blood vessels 6. Concomitant neurologic manifestations: a. Progressive encephalomyelitis b. Meningovasculitis (syphilitic) c. Peripheral unilateral > bilateral VII nerve palsies (Bernhardt’s disease) d. Peripheral neuropathy e. Headache with meningitis 1) Skin rash involving the palms and soles f. VDRL in cerebral spinal fluid is positive 1) Sugar is normal 2) Acute meningitis with neutrophiles 3) Protein moderately elevated g. Spinal cord strokes occur h. Infection more virulent in HIV patients: 1) Telescoped spinal fluid (3rd stage CSF, lymphocytes, may be seen early in infection)
Lyme Disease
General Features 1. The most common vector borne infection in the United States: a. 15,000 cases/year b. Three distinct foci 1) Maine to Maryland 2) Wisconsin and Minnesota
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SECTION I. Vascular Disease
3) Northern California and Oregon 2. Borrelia burgdorferi: a. Tick borne spirochete 1) Ixodes ricinus complex b. Vectors are: 1) Deer; white footed mice; dusky footed wood rats 3. Medical Complications: a. Early infection 1) Localized erythema migrans (stage 1) 2) Disseminated infection (stage 2) a) Nervous system b) Heart c) Joints d) Occurs within days or weeks of infection 3) Late or persistent (stage 3) a) Weeks or months after infection 4. Medical system involvement: a. Skin 1) Erythema migraines b. Cardiac 1) AV block; subtle myocarditis c. Joints 1) Oligoarticular arthritis 2) Treatment resistant arthritis in 10% of patients d. Asymptomatic infection about 10% of patients 5. Neurological complications: a. Acute phase: 1) Severe headaches 2) Meningitis (lymphocytic) 3) Neck stiffness 4) Radiculoneuritis 5) Mononeuritis multiplex 6) Cerebellar ataxia 7) Myelitis b. Chronic phase: 1) Uni or bilateral VII nerve palsy 2) Encephalopathy 3) Cognitive dysfunction 4) Sensory polyneuropathy a) No acrodermatosis Laboratory evaluation: 1. An antibody response to B. burgdorferi by enzyme-linked immunosorbent assay (ELISA) 2. Western blotting of CSF (positive) 3. Intrathecal production of IgM, IgG or IgA antibody 4. After antibody treatment: a. Antibody titers fall slowly and may persist for years
Tuberculosis
1. Infarction of arteries within cortical and basilar exudates a. Superficial pial arteries most often affected 2. Exudates at the base of the brain 3. Seizures (focal or generalized)
4. Cranial nerve VIII and lower cranial nerves most frequent affected 5. Frequently associated with HIV 6. Chronic dementia
Cerebral Nervous System (CNS) Infections in the Immunologically Compromised Host
1. General neurological manifestations: a. Meningeal signs d. Seizures b. Mass lesions e. Stroke-like presentation c. Encephalopathy 2. Presentation depends on specific characteristics of the organism 3. CNS mass lesions a. Subacute or chronic presentation 4. Meningitis and encephalitis a. Acute presentation 5. Disorders affecting B-lymphocyte function: a. Meningitis caused by encapsulated bacterial pathogens b. Bacterial meningitis similar presentation in normal and compromised hosts 6. Impaired T-lymphocyte or macrophage function: a. Infection caused by intracellular pathogens 1) Aspergillus and fungi 2) Nocardia (bacteria) 3) Viruses a) HSV b) JC c) CMV d) HH-6 4) Parasites a) Toxoplasmosis gondii 7. Extra-CNS sites of infection a. Lung and brain infection 1) Aspergillus 2) Nocardia 3) Subacute or chronic presentation 8. T-lymphocyte dysfunction with meningitis: a. Listeria b. Cryptococcus 9. Failure of anti-toxoplasmosis on the therapy for a mass lesion: a. Probable central nervous system lymphoma 10. Aspergillus presentation: a. Mass lesion c. Rare as meningitis b. Stroke
Fungus Infections
A. Mucormycosis
Chapter 3. Medical Causes of Stroke
1. Associated with ethmoid, sphenoid, maxillary sinus infection 2. Ophthalmoplegia (cavernous sinus involvement) 3. Black palate (associated with lateral sinus thrombosis with cyanotic congested palate) 4. Occurs in immunocompromised patients: a. Diabetic ketoacidosis b. Renal failure c. HIV 5. May have indolent cause with ophthalmoplegia 6. Basilar arteritis a. Pontine infarction b. Skull base involvement 7. Intracranial hemorrhage 8. Large vessel stroke 9. Involvement of intracranial vessels B. Aspergillosis 1. Immunocompromised patients a. Inhalation of spores b. Aspergillomas in lung cavities c. Disseminated after bone marrow transplantation d. Common after ENT surgery (paranasal sinus) e. Involves blood vessels f. Associated mycotic aneurysms g. Intraluminal extension of fungal hyphae with ischemic stroke h. Aspergillomas occur in sphenoid sinus 1) Associated skull base osteomyelitis 2) Cranial nerve involvement 3) Cavernous sinus thrombosis 4) Rare spinal cord involvement C. Cryptococcus 1. Meningitis a. Sugar 30–40 mg% b. Lymphocytic pleocytosis c. PCR positive d. Moderate protein elevation of 50–80% 2. Chronic dementia with headache 3. Common in all immunocompromised patients (especially those with HIV) 4. Affects cranial nerve II accumulate (under optic nerve dura) 5. Basal ganglia and midbrain involvement (spreads through Virchow Robin space) 6. Proximal MCA and arteries in the posterior perforated substance most frequently involved 7. Occasional pial artery stroke D. Coccidia mycosis (coccoides immitis) 1. Spores inhaled from the soil 2. Endemic in deserts of SW USA 3. Pulmonary route of infection a. “flu-like” illness 4. Propensity to invade bone a. Jaw b. Lumbosacral area
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5. Chronic basilar meningitis a. Inflammation of arteries within the inflammatory exudate b. Proximal MCA and arteries of the posterior perforated substance involved
Histoplasmosis
1. 2. 3. 4. 5.
Endemic in the Mississippi Valley Pulmonary route of infection Adrenal failure (rare) Skin manifestations Central Nervous System: a. Basilar meningitis b. Proximal great vessel involvement
Fungal Aneurysms
1. Fusiform in shape 2. Involve longer and more proximal segments of intracranial vessels 3. Intradural portion of the carotid artery most common site of fungal neurysm 4. Vessel invasion occurs from extension of the hyphae into the lumen which cause: a. In situ thrombosis b. Embolization of hyphal masses c. Major portions of vessels involved 1) Large infarctions CT Signs of Fungal Infection of a Sinus
1. Sclerotic thickening 2. Erosion 3. Remodeling a. All rare in bacterial infections 4. Central area of high density within the sinus cavity 5. Low signal on MRI in all sequences a. paramagnetic substances within fungal mycetomas 6. Aggressive extension of fungus form the sinus to: a. Orbit c. Intracranial cavity b. Facial tissues 7. Vascular invasion
Viral Infections and Stroke
1. General features: a. Vasculitis from a viral infection effected by: 1) Direct invasions of central nervous system vessels 2) Triggering an immune response to epitopes of the vessel wall 3) Immune complex deposition
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SECTION I. Vascular Disease
Herpes Zoster
1. General vascular manifestations a. Delayed brain infarction following infection 1) Contralateral hemiplegia form ipsilateral MCA involvement 2) Days to 6–8 weeks following onset of the rash 3) Occlusion or stenosis of the carotid siphon, ACA or MCA a) May be preceded by a TIA b) Usual clinical onset in that of an abrupt stroke 4) Concomitant encephalitis 5) Recurrent and multiple infarcts 6) rash may occur in V2, V3 or vertebrobasilar territory 7) Rare involvement of PCA or vertebrobasilar territory 8) Infarct and stenosis may occur in young adults b. Arteriographic evaluation 1) Stenosis of proximal MCA and basilar artery a) Induce large infarction 2) Occlusion of the supraclinoid ICA 3) Stenosis of intracranial large conducting vessels
2.
3.
4.
5.
6.
HZ Cerebral Infarctions in HIV-Infected Patients
7. 1. HZ ophthalmicus: a. Delayed contralateral hemisphere stroke 1) Granulomatous arteritis 2) Patient’s may have no preceding rash prior to stroke 3) Similar pathology to non-infected patients a) Segmental arteritis of the carotid siphon 4) Concomitant acute retinal necrosis 2. Immune competent HZ patients a. Large vessel disease 3. HIV patients a. Small vessel diseases b. Leukoencephalitis c. Ventriculitis 4. Children with concomitant HIV and HZ a. Dilatation arteriopathy with fusiform aneurysms of intracranial arteries b. Subarachnoid hemorrhage 5. Children with non-HIV, VZV stroke a. Typical delayed proximal intracranial arteritis
HIV
1. General features: a. Approximately 25% of HIV infected patients have cerebrovascular involvement 1) Concomitant infections that cause vasculitic syndromes are:
a) Ebstein–Barr virus c) Hepatitis B b) CMV d) HZ Vasculitis due to: a. Infections (viral, bacterial, fungal, parasitic) b. Lymphoma c. Lymphomatoid granulomatosis 1) Primarily affects the lungs 2) Angiocentric mixed inflammatory infiltration of central nervous system vessels 3) May involve into non-Hodgkin’s lymphoma Mechanism of vasculitis in HIV: a. Immune complex formation b. Cell mediated vasculitis c. Inflammation due to direct injury Clinical associations with HIV vasculitis a. Encephalitis c. Peripheral neuropathy b. Myelopathy d. Myopathy Types of vasculitis with HIV infection a. Necrotizing c. Granulomatous b. Eosinophilic MRA evaluation of HIV arteritis: a. Vascular abnormalities seen in medium sized blood vessels 1) Aneurysmal dilatation 2) Thickening and contrast enhancement of vessel walls Primary angiitis of the central nervous system in an HIV infected patient: a. All other etiologies ruled out b. Clinical features: 1) Acute or subacute recurrent focal deficits 2) Background of global central nervous system dysfunction
Parasitic Infections
Cysticercosis
1. General features: a. Infection with the larvae (cysticerci) of Taenia solium (pork tapeworm) 2. Types of infection a. Ventricular cysts (racemose form) b. Parenchymal involvement c. Subarachnoid space 3. Vascular manifestations a. Occurs primarily in the subarachnoid form of the disease 1) Meningitic spread to basal intracranial blood vessels a) Endarteritis of small vessels in the vicinity of the parasite 4. Patterns of infarction a. MCA > PCA > ACA infarcted
Chapter 3. Medical Causes of Stroke
b. Rarely involves the basilar territory c. Subcortical small infarcts d. Large cortical-subcortical strokes e. Intracranial hemorrhage (rare) 5. Clinical features: a. Stenosis of arteries may spontaneously improve b. Stroke may be precipitated by treatment with praziquantel c. Treatment may precipitate an inflammatory response that exacerbates the endarteritis Cerebral Malaria
1. General manifestations: a. Plasmodium falciparum b. Neurologic manifestations occur in 2% of all malarial infections c. RBC’s parasitized by P1 falciparum 1) Occurs maximally in brain capillaries 2) Clinical manifestations a) Prodrome of fever and headache b) Intracranial hypertension 1) Distention of capillaries and vessels 2) Cerebral edema c) Generalized petechial brain hemorrhages d) Hemiparesis and seizures most common neurological focal complications 3) Focal infarctions more common in children than adults 2. CT findings a. Severely ill patients demonstrate: 1) Thalamic and cerebellar attenuation 2) Cerebral edema b. Mildly affected patients may have normal initial CT scans c. Angiography and TCD in children 1) Demonstrate focal stenosis of the basal intracranial arteries d. Areas of petechial hemorrhage 1) Hallmark of cerebral malaria pathologically 2) Not demonstrated by CT e. Focal infarcts of the ophthalmic and major cerebral arteries are rare in adults MRI Evaluation of Cerebral Malaria
1. Cortical infarcts 2. T2-weighted and FALIR hyperintense lesions a. Diffuse or symmetrical
Stroke in Association with Named Syndromes
It is surprising how many named stroke syndrome have seminal skin manifestations. Köhlmeier Degos syndrome is associated with characteristic whitish or erythematous papules
77
with a porcelain white center. Associated severe gastrointestinal symptoms are diagnostic. Mencke’s syndrome has diagnostic course, stiff hair associated with severe hypotonia, seizures, and branch artery occlusion. There is often survival to early adulthood. Vogt–Koyanagi disease is distinguished by a white forelock, eye lashes and eyebrows. The skin manifestations are noted with a uveal meningeal presentation, ocular and brainstem signs and symptoms of the VIIIth nerve is involved the syndrome becomes Voigt–Koyanagi–Harada. Sneddon’s syndrome is characterized by severe livedo reticularis in the extremities and is associated with stroke in young adults. Divry Von Bogaert disease is seen in older patients has livedo reticularis and is associated with seizures and dementia. The skin is clearly hyperelastic in pseudoxanthoma elastica (Grönblad–Strandberg disease) and has a characteristic cigarette paper thinness in the posterior neck area. Hyperelastic skin may also be noted in Ehlers Danlos Type I and IV as well as Marfan’s Syndrome. Characteristic dissections of extracranial arteries (often bilateral), aortic disease and aneurysms distinguish these entities. Fabry’s disease has characteristic angioma in the bathing suit distribution and other seminal feature of heat sensitivity, renal failure, premature coronary artery disease and painful neuropathy. Hemorrhage rather than stroke syndrome are characteristic of Van Hippel Lindau disease, Sturge Weber, Cobb’s disease and Klippel–Ternary–Weber Syndrome. The strawberry hemangioma must cover the upper eyelid (V1) distribution in Sturge–Weber Syndrome. Its most characteristic features are intractable seizures, mental retardation and trans-track calcification of the parieto occipital cortex. Von-Hippel Lindau has characteristic retinal artery venous malformations with lesions also noted in the cerebellum and spinal cord. Associated renal carcinoma is expected. Wyborn–Mason is characterized by strawberry hemangioma on the face or trunk with a midbrain hemangioma Cobb’s Syndrome presents with massive truncal hemangioma and hemispheric AVM. Osler Weber Rendu often presents with telangiectasia of the lower lip, conjunctiva and nasal mucous membrane. Stroke may be emboli from pulmonary shunts. Thrombophlebitis with dilated veins in the upper extremity or chest wall (Mondor’s syndrome) suggests nonbacterial thrombophlebitis from an underlying malignancy. Well known in this regard is pancreatic cancer. Petechiae and purpura are frequently associated with syndromic stroke. Thrombotic thrombocytopenic purpura (Moschowitz’s syndrome) presents with generalized purpura, seizures, hallucinations, focal neurologic signs and renal failure. Waldenström’s macroglobulinemia may be associated with rheological causes of stroke difficulty with perfusion of capillaries, due to high concentrations of IgM. The petechiae are characteristically noted below the knee. Cryoglobulinemia may present similarly, but often with acrocyanosis. The Bing Neel Syndrome is inclusive of all disease processes that interfere with cerebral perfusion. Bleeding from the gums,
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SECTION I. Vascular Disease
petechiae and depressed consciousness are diagnostic. Small cortical strokes may occur. Kawasaki’s disease frequently presents with an explosive course and mucous membrane involvement. Unusual coronary artery occlusion and stroke occur. Behçet’s Syndrome may present with painful erythematous, well demarcated skin lesions and stroke. Most frequently mouth and genital ulcers are seen concomitantly. Eye findings and named stroke syndromes are common. Susac disease is a combination of retinitis and VIIIth nerve involvement with stroke. It is a microangiopathy of the main vestibulocochlear complex and retina. There is striking obliteration and amputation of retinal vessels. Acute posterior multifocal placoid pigment epitheliopathy affects young adults and is a putative autoimmune process. The patients may suffer arteritic strokes. The major pathology is in the retinal pigment epithelium although the optic nerve may be involved concomitantly. Cogan’s syndrome and its variants affect young adults and cause an acute interstitial keratitis as well as vestibular and auditory dysfunction. Central retinal artery or vein occlusion occurs in association with pial artery stroke. Atypical variants have vasculitis and systemic manifestations. Eales disease occurs in young men and is prevalent in the Middle East and India. Retinal periphlebitis and vitreous hemorrhage are common with occasional large vessel stroke. The ophthalmologic symptoms predominate. Eye findings in association with stroke occur in osteogenesis imperfecta (robin’s egg blue sclera); PXE (angioid streaksdisruption of Bruch’s membrane), homocystinuria and Marfan’s syndrome (lens dislocation), cat scratch fever (infectious retinitis) syphilis (retinitis pigmentosa, argyle Robertson pupil, optic atrophy). The defects in Ehler Danlos disease causes arterial dissection, intracerebral an extracranial aneurysm and cavernous sinus fistula. Gastric hemorrhage, skin manifestations, mitral valve prolapse due to elongated chordae tendinea and aortic root ectasia occur. Marfan’s osteogenesis imperfecta, Ehlers Danlos type I and IV are the primary named entities. Strokes and bowel defects are related most often due to protein losing enteropathy known as Ménétrièr’s syndrome. Ulcerative colitis and regional enteritis are associated with large vessel stroke due to loss of protein C and S. Behçet’s may affect the gastrointestinal tract with mucosal ulcers. Köhlmeier–Degos disease frequently is initiated by abdominal pain and diarrhea. Henoch–Schönlein purpura may be attended by early and severe joint and abdominal pain. Loeffler’s syndrome and Churg–Strauss disease are associated with pulmonary intersitial disease, eosinophilia and stroke. Pituitary infarction is peculiarly common with Churg– Strauss disease. Vasculitic sarcoid affects the lung and cerebral vessels as does the hyper eosinophil syndrome (20,000 eosinophil/mm3 ). Arterial involvement as the primary disease process occurs in both Moya-Moya syndrome and Buerger’s syndrome.
In Moya-Moya disease there is progressive relentless occlusion of the origin of the carotid arteries. The resulting collateral circulation and exuberance of lenticulostriate arteries produce the characteristic “puff of smoke” on arteriograms. In the United States it is seen with sickle cell disease, tuberculosis that affects the origin of the great vessels as well as X-ray therapy. Frequently it is idiopathic. Surprisingly, it may present in elderly patients and as a primary subarachnoid hemorrhage rather than occlusive ischemic stroke. Buerger’s disease often presents with severe occlusive disease below the knee rather than the distal 1/3 of aorta or iliac arteries that is characteristic of atherosclerosis. A dementia secondary to a generalized granular cortical atrophy is more common than conducting vessel stroke. Erdheim–Gesell syndrome is medial cystic necrosis. Dissection of the great vessel is common. Arterial thickening of the radial artery at the wrist and aortic insufficiency bolster the diagnosis. As noted above, osteogenesis imperfecta, Marfan’s syndrome and homocystinuria (accelerated atherosclerosis) all present as primary disease of blood vessels. May Turner Disease is iliofemoral deep vein thrombosis that is associated with embolus to the top of the basilar artery. Takayasu’s disease dramatically affects the blood vessels emanating from the aortic arch and the aorta itself. Subclavian steal is prominent arteriographically, but rarely clinically significant. Cataracts and facial atrophy are prominent due to loss of nutritive blood supply to the face. The strokes are primarily in the anterior circulation. Claudication of vision occurs with head position and walking due to the tenuous blood supply to the retina. It occurs with rheumatic diseases as reported from Scandinavia. HERNS disease is a hereditary stroke syndrome associated with endotheliopathy, renal disease neuropathy and stroke. Polyarteritis and polyangiitis are the other vascular arteritides which is associated with renal disease. Cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy is a named disease associated with dementia. Severe migraines are common. Binswanger small vessel microangiography also is associated with dementia. Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes are also associated with dementia and migraine. Posterior leukoencephalopathy is characteristic in parietal occipital areas. In a similar syndrome reported in French Canadians Saquenay Lac St. John Syndrome, the leukoencephalopathy is frontal rather than parieto occipital. Divry Von Bogaert’s disease is also associated with dementia. Stroke in Association with Named Syndromes 1. Eales disease 2. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) 3. Buerger’s disease (thromboangiitis obliterans) 4. Ehlers–Danlos syndrome (type IV) 5. Homocystinuria
Chapter 3. Medical Causes of Stroke
6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31.
Moyamoya disease Antiphospholipid antibody syndrome (aPL) Sneddon’s syndrome Susac syndrome (microangiopathy of the retina, inner ear, and brain) Takayasu’s disease Divry von Bogaert syndrome Grönblad–Strandberg Disease (pseudoxanthoma elasticum) PXE Kohlmeier–Degos disease (malignant atrophic papulosis) Behçet’s Disease Moschowitz syndrome (thrombotic thrombocytopenic purpura) TTP Disseminated intravascular coagulation (DIC) Sturge–Weber Disease Osler Weber Rendu Bing Neel syndrome Kawasaki syndrome Loeffler’s syndrome Ménétrièr’s syndrome Acute posterior multifocal placoid pigment epitheliopathy Voigt Koyanagi disease Hereditary endotheliopathy renal neuropathy syndrome (HERNS) Fabry’s disease Sanguinary Lac St. John Syndrome Erdheim–Gesell Syndrome (medial cystic necrosis) May Turner Syndrome Cogan’s Syndrome Churg–Strauss
Eales Disease
A. General characteristics 1. Disease of young men 2. Prevalent in the Middle East and India 3. No systemic symptoms 4. Eye symptomatology is dominant B. Ophthalmological Manifestations 1. Retinal periphlebitis 2. Vitreous hemorrhage 3. Retinal capillary ischemia 4. Retinal revascularization 5. Perivenous and periarterial sheathing 6. Macular arteries are less severely affected a. relative sparing of central vision 7. Uveitis C. CNS Manifestation 1. Meningitis 2. Stroke (a) Focal infarcts (b) Occasional large vessel involvement
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CADASIL
General characteristics 1. AD inheritance chromosome: 19q12 2. Onset 30–50 years of age; notch 3 gene mutation 3. Migraine like headaches 4. Depression 5. Diffuse leukoencephalopathy (MRI) 6. Recurrent stroke-like episodes 7. Basophilic granular material replaces the smooth muscle cells of the media a. Small medium sized vessels 8. Strokes in basal ganglia; thalamus, brainstem, meninges and cerebellum 9. Blood vessel changes: myocardium, spinal cord, muscle 10. Unusual neurologic features: a. Seizures b. Small cortical infarcts 11. Gradient ECHO sequence demonstrates the hemosiderin of old infarcts 12. APOE e2 allele a. More hemorrhage b. Vasculopathy 13. May involve external capsule a. Longest penetrating blood vessels 14. A3243G mutation a. Occipital infarcts are prominent Neurologic manifestations: a. Small lacunar infarcts; brainstem, thalamus, basal ganglia, meninges and spinal cord b. Ischemic atherosclerotic white matter changes with posterior predominance c. Strokes may involve the external capsule (longest penetrating arteries) d. Recurrent stroke-like episodes e. Most frequent presentation is hemorrhage 1) Lobar (superficial) 3) Recurrent 2) White matter f. Progressive 1) Gradual 2) Step-wise g. Gait disturbances h. Seizures and small cortical infarcts are rare Japanese variant a. Occurs in young men b. Alopecia c. Back pain d. Affects small arteries 1) Hyalinosis 2) Deterioration of internal elastic membrane MRI evaluation a. Diffuse leukoencephalopathy (posterior predominance) b. T2 weighted lesions may be seen prior to symptoms c. Gradient ECHO sequences demonstrate hemosiderin from prior bleeds
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SECTION I. Vascular Disease
Differential diagnosis 1. Binswanger 5. Vasculitis 2. MS 6. Hexosaminidase A deficiency 3. HIV 7. Adrenomyeloneuropathy (AMN) 4. Neurosyphilis 8. Adrenoleukodystrophy (ALD) Mitochondrial Encephalomyelopathy with Lactic Acidosis Stroke-Like Episodes (MELAS) 1. General features: a. Ischemic brain lesions 1) Metabolic dysfunction of mitochondria 2) Decreased COX activity (mitochondrial complex III) 3) Arteries supplying (ischemic areas) are open 2. Maternal mutation of mtDNA 3. Clinical features: a. Short stature f. Hemiparesis b. High incidence of diabetes g. Seizures c. Migraine – like headaches h. Ataxia d. Sensorineural hearing loss i. Fatigue with exercise e. Visual dysfunction 4. Point mutation A3243G a. Severe occipital infarcts 5. Laboratory evaluation: a. Elevated resting pyruvate/lactate levels b. Ragged red fibers; COX deficiency on muscle biopsy 6. MRI evaluation: a. Multifocal lesions b. Parieto-occipital predominance c. Cortex and underlying white matter affected d. High incidence of basal ganglia calcification 7. Other MtDNA diseases such as MERFF and KSS a. Demonstrate leukoencephalopathy
Buerger’s Disease (Thromboangiitis Obliterans)
A. General Manifestations: 1. Severe peripheral vascular disease. Extremity lesions are typically below the knee in the posterior and anterior arteries rather than the distal 1/3 of the aorta or the iliac arteries 2. Intermittent claudication often presenting in the medial foot (in step) 3. Coronary and renal arteries may be affected B. Neurological Manifestations 1. Large vessel stroke 2. Granular cortical atrophy a. Dementia
b. Affects young women c. Most prevalent in second to fourth decade 2. Clinical manifestations: a. Retina 1) Large retinal arteries are involved: a) Obliteration and amputation of vessels b) Increased light reflex c) Narrow attenuated arteries b. Bilateral visual loss c. Tinnitus and hearing loss d. Bilateral pyramidal tract dysfunction e. Cerebellar ataxia f. Dementia g. Gradual or step wise progression 3. Laboratory evaluation a. CSF 1) Minor lymphocytic pleocytosis 2) High protein 1g/dl 4. Pathology a. Obliteration of small intracranial arteries b. No inflammation or granuloma formation
Acute Posterior Multifocal Placoid Pigment Epitheliopathy
1. General characteristics: a. Affects young adults b. Precedent flu-like febrile illness 2. Clinical features: a. Both eyes are affected simultaneously; ocular involvement may occur seriatim b. Visual blurring; scotoma and distortion of vision c. Vision recovers after several weeks; deficits may be permanent d. Funduscopic examination 1) Pathology in the retinal pigment epithelium 2) Well circumscribed grey-white flat lesions 3. Neurologic features: a. Optic neuritis b. Headache c. Stroke 1) May have arteritis pattern 4. Pathology a. Focal granulomatous inflammation of medium sized blood vessel (one patient)
Takayasu’s Disease Susac Syndrome
1. General Characteristics a. Microangiopathy of the brain, vestibulo-cochlear complex and retina
A. General characteristics 1. Most common in Asia; may be seen sporadically in the West 2. Prodrome of fever and night sweats 3. High sedimentation rate; anemia
Chapter 3. Medical Causes of Stroke
4. Gradual obliteration of: a. Major arterial branches of the arch of the aorta b. Vertebral arteries are relatively spared B. Neurological manifestations 1. Loss of extremity and neck pulses 2. Asymptomatic subclavian steal 3. Intermittent claudication of vision a. Tenuous blood supply to the optic nerve and retina 4. Early onset of cataracts 5. Facial atrophy 6. Headache 7. Dizziness 8. Hypothyroidism a. Increase thyrocervical trunk collaterals destroy the gland 9. Arm and leg claudication C. Stroke 1. Ischemic stroke a. Less frequent than expected from the radiologic evaluation b. Media and adventitia of blood vessels involved in an inflammatory response c. Late stage fibrosis d. Etensive collateral circulation associated with 1) SAH 2) ICH D. Arteriographic evaluation: 1. Occlusion, stenosis, ectasia, aneurysm formation at vessel origins of the aortic arch 2. Most common sites of involvement: a. Mid portion of the left common carotid artery b. Left and right subclavian arteries c. Mid portion of the innominate artery
Behçet’s Disease
A. General Characteristics 1. Relapsing remitting course 2. Major features a. Oral ulcers c. Uveitis b. Genital ulcers 3. High incidence in Turkey and Japan a. World-wide distribution 4. Systemic involvement: a. Skin: 1) Aphthous mouth ulcers 2) Folliculitis 3) Erythema nodosum 5. Ulcerative lesions of bowel/bowel mucosa 6. Stomach ulcers 7. Synovitis 8. Large joint arthritis 9. Thrombophlebitis 10. Affects young adults 11. Male > female 2 : 1
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12. Neurologic involvement <10% B. Neurological manifestations include: 1. Retinal vasculitis 2. Demyelinative and/or ischemic foci in: a. Midbrain (most extensive) e. Globus pallidus b. Basis pontis f. Spinal cord c. Medulla g. Hypothalamus d. Optic nerve C. Pattern of involvement 1. Ocular a) Uveitis b) Optic nerve inflammation 2. Brainstem a) Cranial nerve inflammation 3. Cortical: a) Subcortical dementia 4. Stroke: a) Large artery stroke b) Vasculitis c) Cerebral venous thrombosis in 10% 1) Hetero or homozygous for Factor V Leiden defect 5. Dementia: a. Frontal lobe type b. Subcortical c. Rarely accompanied by: 1) Seizures 2) Aphasia 6. Late stage disease a. Quadriparesis b. Pseudo bulbar palsy D. Cerebral infarction: 1. Branch occlusion > large vessel 2. Dural venous sinus thrombosis 3. Primarily ocular manifestations 4. Brainstem syndrome (rhombencephalitis) 5. Neurologic signs and symptoms are frequently relapsing and remitting 6. Spinal cord may be involved E. MRI Evaluation: 1. Topography of involvement a. Pons > midbrain > basal ganglia > thalamus 2. Small well delineated T2 weighted lesions a. Brainstem lesions 1) Not in arterial territories b. Grey and white matter lesions c. 10 mm sharply marginated irregular and confluent lesions in affected areas
Cogan’s Syndrome
A. General Characteristics 1. Occurs in young adults 2. Clinical features: a. Acute interstitial keratitis b. Vestibular auditory dysfunction 1) Inflammation of the labyrinths
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SECTION I. Vascular Disease
c. Stroke (pial arteries) B. Typical Cogan’s 1. Photophobia, lacrimination, eye pain 2. Blurred vision 3. Intermittent symptoms for years 4. Ménière’s like attacks may precede eye pain 5. Total deafness and absence of vestibular function C. Atypical Cogan’s Syndrome 1. Vasculitis and systemic manifestations 2. Eye pathology includes: a. Retinal hemorrhage b. Papilledema c. Orbital pseudotumor d. Central artery or vein occlusion 3. Vestibula auditory dysfunction may occur >2 years after onset of eye symptoms 4. Vasculitis a. Occurs in atypical disease b. Aortitis and aortic insufficiency in the classic syndrome c. Neurologic symptoms 1) Stroke 2) Encephalopathy 3) Seizure 4) Myelopathy 5) Mononeuritis multiplex 6) Cavernous sinus thrombosis d. Differential diagnosis includes syphilis
Ehlers Danlos Syndrome
A. General features 1. Hyperelastic skin 2. Hyperextensible joints 3. Increased scarring after injury 4. Platelet dysfunction 5. Cardiac defects B. Nine subtypes of the syndrome 1. Major types are I, II, or III (approximately 50% of patients) C. Subtype IV most important for cerebrovascular lesions: 1. Decreased synthesis of type III collagen a. All of these patients demonstrate AD inheritance b. COL 3A1 gene (mutations); chromosome 2 1) Codes for alpha-1 chain of type III collagen D. Neurological features: 1. Aneurysms (IV; rarely type I) a. Intra and extracranial aneurysms b. Multiple aneurysms c. Most common aneurysm is of the ICA 1) In the cavernous sinus 2) At the site of emergence from the sinus d. Presentation of aneurysms: 1) SAH 2) Carotid cavernous fistula (rupture of the cavernous sinus aneurysm)
Differential Diagnosis between Marfan’s Syndrome and Ehlers Danlos Buerger’s Disease (Thromboangiitis Obliterans)
1. General Characteristics a. Vasculitis of medium and small vessels b. Primary involvement in distal extremity vessels c. Rarely affects veins d. Onset prior to age 45 2. Brain vessel topography: a. Watershed zones between ACA/MCA and MCA/PCA territories b. Possibly two vessel size involved: 1) Arteries <1 mm 2) Large proximal arteries 3. Systemic characteristics a. Intermittent claudication of the legs 1) Involvement of the in-step rather than the calf b. Upper extremity claudication of the arms as the disease progresses c. Claudication particularly prevalent in smokers 1) Regresses with cessation of tobacco use 4. Neurological features: a. Monoparesis c. Visual field deficits b. Hemiparesis
1. Marfan’s syndrome fewer cerebrovascular aneurysms 2. Aortic arch and pulmonary arteries affected more in Marfan’s syndrome 3. Carotid-cavernous fistula (both) a. May follow minor head trauma b. Spontaneous occurrence c. May occur concomitantly with intracranial aneurysms 4. Arterial Dissections (both) a. Arteries fail to hold sutures b. Dissection of both intra and external arteries c. Carotid and basilar arteries are thin walled, enlarged and tortuous d. Arteriograms are dangerous
Moyamoya Syndrome
A. General Characteristics 1. Defined by the angiographic appearance of the collateral circulation following carotid occlusion 2. Obstruction of the carotid arteries occurs at the siphon (T Portion). Proximal portion of the MCA and ACA
Chapter 3. Medical Causes of Stroke
3. Enlargement and tortuosity of basal penetrating collaterals of the ICA, MCA, and ACA cause: a. Hazy appearance of the area like “cigarette smoke” on angiograms b. Exuberant basilar collateral networks 1) Ethmoidal moyamoya if collaterals are restricted to frontobasal territory 2) Vault moyamoya if there are generalized collaterals c. Rare involvement of branches of the external carotid artery 4. Epidemiology a. Prominent genetic predominance in Japan b. Sporadic cases are noted world wide 5. Differential diagnosis: a. Sickle-cell disease b. Basal meningitis (particularly tbc) 6. Usually present in children >15 years a. Late neurological presentations occur b. Girls > boys 50 : 1 c. Adult present 3–5th decade B. Pathology 1. Endothelial fibrosis and hyperplasia 2. Abnormalities of the internal elastic membrane 3. No inflammatory changes C. Neurological features: 1. Childhood presentation: a. Transient hemiparesis precipitated by exercise or hyperventilation b. Cognitive decline c. Rare intermittent choreoathetosis d. Headaches e. Seizures 2. Adult presentation: a. Brain hemorrhages 1) Thalamus, basal ganglion, deep white matter 2) Aneurysmal dilations of the collateral vessels with rupture b. SAH and intraventricular hemorrhage c. Aneurysms of the circle of Willis develop. Predilection for: 1) Anterior communicating artery 2) Basilar artery d. Unusual prominent collaterals: 1) Ethmoidal arteries (from carotid) 2) Superficial temporal and middle meningeal arteries to transdural arteries e. Process may stabilize with age MRI/MRA Evaluation
1. Collateral flow voids are prominent 2. Multiple bilateral infarctions of: a. Basal ganglia 3. Subcortical white matter infarctions
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4. Cortical atrophy and hydrocephalus ex vacuo 5. Conventional arteriography a. Demonstrates typical lenticulostriate collaterals (“puff of smoke”) b. Terminal carotid proximal ACA and MCA occlusions c. Dilated collateral vessels Antiphospholipid Antibody Syndrome (APL)
Sneddon’s Syndrome
A. General Characteristics 1. Young patients; pial artery strokes 2. Livedo reticularis of the skin a. Reticulated skin pattern b. Involves trunk and all extremities 3. Cold extremities 4. Diminished pulses 5. Differential diagnosis a. Sympathically maintained pain patients: 1) Usually have concomitant allodynia, hyperalgesia, autonomic dysregulation
Differential Diagnosis between Sneddon’s Syndrome and APL (antiphospholipid syndrome)
1. Antiphospholipid antibody titers (APL) approximately equal in both 2. APL Sneddon’s patients are older than APL patients 3. Miscarriages more frequent in APL patients 4. Cardiac valve abnormalities APL > APL patients (marantic endocarditis) 5. Venous thrombosis more common in APL than APL patients
Differential Diagnostic Points between Sneddon’s vs. APL Patients
1. Digital artery narrowing and dilation demonstrated angiographically; acrocyanosis (Sneddon’s) 2. Early inflammatory skin lesions (Sneddon’s) a. Medium-sized arteries between the dermis and subcutis affected 3. May be familial (Sneddon’s) 4. May have antiphospholipid antibodies (Sneddon’s) 5. Valvular cardiac defects less common than APL+ 6. Neurological manifestations of Sneddon’s a. Multifocal cortical infarcts b. Lesions in the cerebral white matter c. Intranuclear ophthalmoplegia 7. Arteriography a. Branch occlusions of intracranial arteries
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SECTION I. Vascular Disease
Differential Diagnosis of Livedo Reticularis
1. Collagen vascular disease a. SLE b. Rheumatoid arthritis c. PAN 2. Tuberculosis 3. Syphilis 4. RSD (usually allodynia/hyperalgesia associated) 5. APL syndrome 6. TTP 7. Thrombocythemia 8. DIC 9. Oral contraceptives 10. Neoplasm 11. Cryoglobulinemia (legs) 12. Cholesterol emboli syndrome (legs and toes are blue) 13. Divry Von Bogaert Syndrome
Susac’s Syndrome (Retinocochleocerebral Syndrome)
A. General characteristics 1. Obliteration of large retinal arteries 2. Gradual bilateral visual loss 3. Effects young women in second to fourth decade B. Neurological manifestations 1. Tinnitus and hearing loss 2. Bilateral pyramidal tracts signs 3. Cerebellar dysfunction 4. Dementia (paranoid, bizarre behavior) 5. Stepwise or gradual progression 6. Self-limiting 1–2 years C. CSF Evaluation 1. High protein; rarely >1 gram/dl 2. Minimal pleocytosis D. Pathology 1. Obliteration of small arteries E. Forme Frustes: 1. Branch retinal occlusions 2. Multifocal small infarctions 3. No VIIIth nerve deficits 4. Retinal and VIIIth nerve involvement a. no other neurological deficit
Acute Posterior Multifocal Placoid Endoheliopathy
A. General characteristics 1. Preceding “flu-like” illness 2. Disease of young adults 3. Eyes may be affected singularly or sequentially 4. Ophthalmological findings a. Scotomata b. Lesions of the retinal pigment epithelium
c. Vision recovers within weeks. An occasional patient has permanent visual loss d. Choroidal vasculitis B. Neurological manifestations 1. Headache 2. Optic neuritis 3. Stroke 4. Visual blurring, distortion and scotomata C. Arteriogram 1. Endarteritis
Mencke’s Disease
A. General characteristics: 1. X-linked recessive 2. Mitochondrial dysfunction (lack of copper) a. Impaired intestinal copper absorption 1) Low copper in serum; high excretion in feces b. Mutation in gene encoding metal transporter (MNK ATP 7Ap ) 3. Occipital horn syndrome (OHS) a. Milder phenotype b. Caused by ATP7A P-type gene mutation B. General Clinical Features 1. Coarse, stiff hair (triangular) 2. Hypothermia 3. Onset and death usually early childhood C. Neurologic Features 1. Hypotonia 3. Failure to thrive 2. Seizures D. Diagnostic Features 1. Muscle COX deficit; RRF (ragged red fibers) 2. EM: abnormal mitochondria E. Pathology 1. Microinfarcts 2. Occlusion of branch arteries 3. Cerebral atrophy
Vogt–Koyanagi Harada Syndrome
A. General characteristics: 1. Uveomeningeal process 2. White forelock and eyelashes 3. Alopecia 4. Iridocyclitis 5. Choroiditis B. Neurological manifestations 1. Meningeal signs (cause of recurrent meningitis) 2. Adhesive arachnoiditis 3. Papilledema 4. Increased intracranial pressure 5. Dementia 6. Cerebellar signs
Chapter 3. Medical Causes of Stroke
7. May remit after 6–12 months C. Laboratory Evaluation 1. CSF lymphocytic pleocytosis
Divry Von Bogaert Syndrome (DVBS)
A. General characteristics: 1. Presents in adults between 18–40 2. May be familial or sporadic in the adult form 3. Affects males in the adult form 4. Juvenile form may follow vaccination or viral illness 5. Livedo reticularis is present 6. Death usually occurs in 20 years B. Neurological manifestations 1. Presenting symptoms: a. Seizure b. Dementia c. Rigidity d. Hyperreflexia e. Ataxia f. Multiple deep and superficial infarction that leads to: 1) Pseudo bulbar palsy 2) Corticomeningeal non-calcifying angiomatosis of vessels; arteries develop fibrous thickening
Sanguinay Lac St. Jean
A. General characteristics 1. AR 2. Decreased COX (cytochrome oxidase) in tissues B. Neurological manifestations 1. Frontal cortical lesions 2. Stroke-like episodes C. Differential point: 1. MELAS affects parietoccipital areas primarily
Disseminated Intravascular Coagulation (DIC)
A. General characteristics 1. Occurs in a setting of: a. Septicemia b. Cancer c. Obstetrical procedures with release of amniotic fluid into the circulation d. Neurosurgical procedures (release thromboplastin) e. Chemotherapy f. Viremia: 1) HIV 3) Varicella 2) Hepatitis g. Intravascular hemolysis h. Heat stroke
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i. Burn patients j. Liver disease k. Prosthetic devices l. Collagen vascular disease 2. Clotting and fibrinolytic system are activated simultaneously 3. Usually systemic hemorrhage and thrombosis: a. Hypotension b. Fever c. Hypoxia d. Acidosis e. Shock f. Acrocyanosis g. Bleeding from all punctures sites B. Neurological manifestations 1. May present in coma with a nonfocal neurological exam 2. Large vessel occlusion 3. Lethargy; stupor 4. Cranial nerve palsies 5. Seizure 6. SAH 7. Emboli from NBTE 8. Multifocal hemorrhage and infarction C. Laboratory evaluation 1. Peripheral blood smear: a. Schistocytes (fragmented RBC’s) in 50% of patients b. Thrombocytopenia <50,000 platelets mm3 c. Reticulocytosis d. Slight shift to immature leukocytes 2. Clotting abnormalities: a. Prothrombin time decreased b. Activated partial thromboplastin time (aPTT) decreased c. Exception: 1) 25% of DIC patients have a normal PT or fast time due to circulating activated clotting factors or early degradation products 2) 40–50% of patients may have normal or fast aPTT for similar reasons d. Decreased factors II, V, VIII e. Decreased antithrombin III f. Elevated levels of B-peptides 15–42 g. D-dimer neoantigen DD-3B6/22 is noted h. Elevated levels of platelet factor IV 3. Differential diagnosis of DIC from multiorgan thrombotic illness: a. SLE with or without antiphospholipid syndrome b. Thrombotic thrombocytopenic purpura hemolytic uremia syndrome (TTP-HUS)
Sturge Weber
A. General characteristics
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SECTION I. Vascular Disease
1. Port wine nevus that covers the upper eyelid (V1 ) 2. Probable dural malformation of the parietal and occipital lobes 3. Hemiatrophy of the side opposite the malformation 4. Tram track cortical calcifications of the malformation 5. Malformation may be bihemispheric B. Neurological manifestations 1. Mental retardation 2. Intractable focal seizures 3. Stroke (ischemic) 4. Seizures and hemiparesis a. Onset 2–3 years of life b. During febrile illnesses c. Focal motor tonic clonic or partial complex in adult 5. Intracranial hemorrhage a. Rare 6. Repeated venous occlusions occur a. Cause of stepwise deterioration 7. Ophthalmological manifestation a. Buphthalmos b. Amblyopia c. Anomalous angle of the anterior chamber 1) Glaucoma
Osler Weber Rendu
A. General characteristics 1. AD 2. Telangiectasias are found: a. Face b. Nasal mucosa (nose bleeds) c. Conjunctiva (30%) d. Hands > legs and trunk e. Anterior tongue f. Retina (10%) 3. Telangiectasia a. Enlarge and multiply 4. Telangiectasia occur in internal organs a. Lungs c. Genitourinary tract b. GI tract B. Neurological manifestations: 1. CNS affected in 8–12% of patients 2. Increased incidence of migraine 3. <1% develop cerebral abscess a. Septic emboli access the brain through pulmonary A-V shunt 4. Large pulmonary AV shunts produce: a. Polycythemia b. Paradoxical embolus 1) MCA most affected 2) Transient neurologic symptoms in conjunction with: a) Hemoptysis
b) Air in the arterial circulation through bleeding arteriovenous fistula C. Associated Intracranial Vascular Anomalies: 1. Angioma 2. Arteriovenous malformation 3. Carotid cavernous fistula D. Telangiectasias located: 1. Brain 2. Meninges 3. Spinal cord lesions: a. Occur most commonly in the lumbar and lower thoracic areas b. Posteriorly within the cord c. Neurologic consequence: 1) SAH 2) Cord compression 3) Lesions within the cord
Bing Neel Syndrome
A. General characteristics 1. Increased blood viscosity with decreased or slowed cerebral laminar flow 2. Hematocrit >67 3. Hemoglobin at 18–22 grams/ml 4. Bleeding from the gums 5. Dilated tortuous retinal veins a. Box car phenomena (pressure on the globe with clumping of RBC’s in the central retinal veins) 6. Petechiae of the lower extremities 7. Associated with: a. IgM > IgG monoclonal gammopathy b. Waldenström’s macroglobulinemia B. Neurological manifestations 1. Encephalopathy a. Poor cerebral perfusion b. Cerebral small vessel ischemia
Grönblad–Strandberg Disease (Pseudoxanthoma Elasticum) PXE
A. General characteristics 1. Angioid streaks in the retina a. Grey streaks radiating from the disk b. Break in Bruch’s membrane 2. Thickened soft skin in general and particularly in the lower abdominal area 3. Angioid streaks are present in 85% of patients 4. Chorioretinal scarring 5. Macular degeneration 6. Leukoencephalopathy 7. Genetics a. AR most common
Chapter 3. Medical Causes of Stroke
b. AD c. Sporadic forms 8. Female > male predominance 9. Progressive disease 10. Systems involved prematurely: a. Cardiovascular c. Skin b. Ocular 11. Arterial disease: a. Accelerated atherosclerosis b. Calcification c. Large and medium size vessels affected 12. Hypertension 13. Gastrointestinal hemorrhage a. Intestinal and gastric mucosal vessel involvement B. Neurological manifestations 1. Stroke a. Large artery infarction 2. Hemorrhage a. Hypertension c. Saccular aneurysm b. Microaneurysm d. SAH 3. Cavernous artery aneurysm.
Köhlmeier Degos Disease (Malignant Atrophic Papulosis)
A. General characteristics 1. An occlusive endarteropathy a. Involves small and middle size arteries and veins b. Proliferative vasculopathy 2. Affects young adults a. May be a more benign childhood form 3. Skin manifestations are pathognomic a. May be absent early b. Whitish or erythematous papules c. Involve the trunk and limbs d. Central part of the lesion is atrophic 1) Porcelain white 4. Gastrointestinal lesions a. Early stages associated with abdominal pain and diarrhea b. Intestinal obstruction c. Perforation (often the cause of death) 5. May affect all organ systems B. Neurological manifestations 1. Stroke may precede other systemic manifestations 2. CNS dysfunction a. Cranial nerve involvement b. Cognitive decline c. Ophthalmoplegia d. Focal motor or sensory deficit e. Multifocal infarction and hemorrhage f. SAH (rare) g. Dural sinus thrombosis 3. Peripheral nerve involvement a. Demyelinative peripheral neuropathy
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b. Rare polyradiculopathy C. Ophthalmological involvement of: 1. Conjunctiva 5. Urea 2. Sclera 6. Pupils 3. Retina 7. Optic nerve 4. Choroid 8. Optic tracts D. Angiography 1. Occlusions and beading a. Distal branches of intracranial vessels Cogan’s Syndrome
A. General characteristics 1. Affects young adults 2. Autoimmune vasculitis (putative) 3. Presents with visual symptoms: a. Red eyes d. Interstitial keratitis b. Photophobia e. Uveitis (rare) c. Reduced vision 4. Vasculitis of small and medium sized blood vessels 5. Fever 6. Aortitis and bowel disease 7. Aortic aneurysm B. Neurological manifestations 1. Blindness (corneal opacification) 3. Vertigo 2. Hearing loss 4. Ataxia Erdheim–Gesell Disease (medial cystic necrosis)
A. General characteristics 1. Medial cystic necrosis B. Neurological manifestations 1. Spontaneous arterial dissection 2. Pathology a. Necrosis of smooth muscle of the lamina media May Turner Disease
A. General characteristics 1. Iliac vein/artery compression 2. Iliofemoral deep vein thrombosis B. Neurological manifestations 1. Embolus to basilar apex Vasculopathy
The term vasculopathy as used for this section denotes an abnormality of the vascular wall that predisposes to occlusion, emboli, hemorrhage or compression of neighboring structures. They most frequently occur in younger patients and are a significant component of the differential diagnosis of stroke in the young. The following is a description of the major vasculopathies and their differential diagnosis.
SECTION I. Vascular Disease
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Differential Diagnosis of Vasculopathy
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.
Antiphospholipid syndrome Recanalization of atherosclerotic emboli Fibromuscular dysplasia Thrombotic thrombocytopenia purpura Sarcoid Neurofibromatosis 1 Tuberous sclerosis SLE X-RT (irradiation treatment) Pseudoxanthomata elastica (PXE) Marfan’s Disease Medial cystic necrosis – Cerebral arterial ectasia and dolichoectasia Congophilic amyloid angiography –
Neurological manifestations of FMD
1. 2. 3. 4. 5. 6. 7.
TIA Stroke Dissection Horner’s syndrome Headache Syncope Intracranial hemorrhage a. Renal hypertension 8. Neurological complications of dissection 9. Stroke recurrence is rare 10. Internal carotid involvement a. Periorbital pain
Neurofibromatosis Type I Recanalization of Embolus with Thrombus
1. Embolus: a) Fragments and moves distally b) Movement occurs most often in the first 48 hours 2. recanalization of a thrombosed intracranial artery: a) Evident by 14–21 days b) Irregular vascular wall of the affected vessel
1. General characteristics: a. vasculopathy in the setting of other general manifestations of the disease b. may also overlap with tuberous sclerosis that also demonstrates arteriopathy 2. dilated vascular wall 3. rarely causes stroke
Fibromuscular Dysplasia (FMD) X-RT
1. General characteristics: a) Affects systemic arteries: 1) Renal arteries with consequent hypertension b) May involve the entire arterial wall c) Incidence of 6% in selected arteriogram d) Most common in middle aged women e) Bilateral ICA involved in 86% of patients f) Spares the carotid bifurcation: 1) Most common in the pharyngeal carotid artery 2) Spares the in the intracranial carotid artery g) 20% of patients have concomitant extracranial vertebral artery involvement (ECVA) h) The media most often involved 1) Constricting bands (MRA; arteriogram) 2) Proliferation of smooth muscle cells that alternate with media thinning and disruption of the elastic membrane 3) Hypertrophy of fibrous tissue leads to focal stenosis 4) Band-like diaphragms within enlarged carotid bulbs (mega bulbs) (a) Embolic source 5) Affects medium sized muscular intracranial arteries 2. Associations: a) Aneurysms of intracranial arteries b) Arterial dissections
1. General Characteristics: a. Occurs following >3000 rads delivered to the arterial wall b. Carotid artery involvement most frequent after the irradiation of: 1) Pharyngeal tumors 2) Hodgkin’s and other lymphomas 3) Little soft tissue mass to protect the artery in the neck c. Characteristics of bifurcation atherosclerosis d. Arterial calcification 2. Neurological manifestations: a. TIA in the carotid and MCA territory b. Stroke in similar distributions 1) Embolic 2) Thrombotic 3) Distal field ischemia
Tuberous Sclerosis
a. Overlaps syndromically with NF-I b. Arteriopathy is usually asymptomatic
Chapter 3. Medical Causes of Stroke Cerebral Arterial Ectasia
1. General Characteristics a. May be seen in children b. Often involves several arteries c. Familial tendencies noted: 1) One family with alpha-glucosidase deficiency d. If severe the condition is known as dolichoectasia 2. Most frequent location: a. Posterior fossa b. Basilar and vertebral artery c. Middle cerebral artery d. Both anterior and posterior circulations may be involved concomitantly 3. Pathology: a. Gaps in the internal elastic lamina b. Decrease in the muscularis layer c. Fibrotic arterial segments d. Elastic tissue degeneration and increase in the vasa vasorum 4. Neurological manifestations: a. Spasticity (ventral pontine compression) b. Dysarthria (XIIth nerve compression) c. Hydrocephalus (pressure on the IIIrd ventricle); obliterates the prepontine cistern d. Ischemia in the distribution of the affected arteries: 1) Emboli from thrombi in ectatic aneurysms 2) Plaque or clot obstruction in penetrating arteries 3) Rare rupture of aneurysms with SAH 4) Distortion and elongation of arteries cause reduced blood flow 5. Transcranial Doppler Evaluation: 1) Reduced mean-flow velocities 2) Preserved peak-flow velocities 3) Reduced antegrade flow a) To and fro movement within the dilated vessel 6. Imaging Evaluation 1) CT, MRA > MRI are diagnostic a) Reveal dilated, enlarged tortuous vessels
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c. Younger at first hemorrhage d. Rare association with isolated cerebral angiitis 2. Genetic Groups Affected: a. Hereditary cerebral amyloidosis (Dutch); Icelandic b. chromosome 21 p11 c. APP gene (amyloid precursor protein) gene d. Clinical manifestations: a) Ocular vessels involved b) Leptomeningeal deposits of amyloid c) Lobar hemorrhages e. Icelandic 1. Cystatin C gene (chromosome 21 p11) 3. Clinical manifestations: a. Cerebral hemorrhages 1) Multiple 2) Superficial 3) Subcortical lobar 4) Recurrent b. Rare TIA c. Multiple infarcts d. SAH e. Leukoencephalopathy 1) Concomitant multiple infarcts 2) Clinically similar to Binswanger microangiopathy f. Dementing illness from: 1) Concomitant multiple infarcts 2) Alzheimer’s pathology 4. Imaging studies a. Gradient ECHO MRI 1) Demonstrates old hemorrhages (residual hemosiderin)
Rare Causes of Vasculopathy
1. Familial occipital calcification: a. Optic atrophy c. VIII nerve involvement b. Dementia by age 33 d. Hemorrhagic stroke
Vasoconstriction and Stroke Occulo Meningeal Amyloid
1. 2. 3. 4.
Primary uveal veil (vitreous) SAH with secondary vasospasm and stroke Thickened dura Acquired factor V deficiency
Cerebral Amyloid Angiopathy (congophilic angiopathy)
1. General characteristics: a. Increase of E2/E4 alleles b. Amyloid AB 39–43 amino acids 1) Usual vascular amyloid 39–40 aa
Migraine headache and vasoconstriction following subarachnoid hemorrhage are the two most common causes of cerebral artery vasoconstriction and consequent stroke. During migraine headache there is frequently demonstrated arteriographic vasoconstriction; a reduced cerebral blood flow and increase velocity measurement by TCD. F18-2DG PET studies have also demonstrated a spreading posterior to anterior Oligemia often preceding change in blood vessel diameter. This spreading cortical depression of metabolic activity with consequent lessened production of H+ from decreased production of lactic acid may also cause vasoconstriction. The DRASC receptor on cerebral blood vessels interacts with H+ to dilate the vessel. This autoregulation with a match between
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SECTION I. Vascular Disease
lCMR glu (and production of H+ ) and ICBF may determine the caliber of cerebral blood vessels during migraine attacks. The locus ceruleus (norepinephrine) may contract proximal cerebral blood vessels whereas out flow from the superior nucleus salivatorius may dilate cerebral blood vessels during a migrainous attack. The relationship between spreading depression and cerebral blood flow has not been fully elucidated. Migraine has been associated with severe intense vasoconstriction with infarction. Vasoconstriction in migraine may cause ICH and arterial dissection. Reversible cerebral segmental vasoconstriction usually affects young women following delivery, but may occur during their menopause. It may occur after carotid endarterectomy and involves large, medium and small vessels. There are focal regions of vasodilation and vasoconstriction. Vasoconstriction following subarachnoid hemorrhage is a major cause of death and morbidity from this event. It is most often seen at 4–7 days following the bleed and is correlated with the amount of blood surrounding the affected vessels. Mechanisms and characteristics will be discussed in the section on subarachnoid hemorrhage from aneurysms.
Migraine
1. General characteristics: a. Affects all age groups b. During attacks: 1) Vasoconstriction of intracranial blood vessels does occur 2) Spreading depression a) Occipital to frontal b) More important as basic mechanism than vasoconstriction for auras 2. Clinical manifestations 1. Ischemic symptoms a. Precede, are concomitant with or follow attacks b. Usually occur 10–20 minutes prior to the headache 2. Small vessel infarction a. Intense vasoconstriction with thrombosis b. Activation of platelets c. Vasoconstriction per se: 1) Stimulates endothelium to promote thrombosis 3. Migraine and possible association with reversible cerebral segmental vasoconstrictions 4. intracranial hemorrhage a. Reported during migraine attack b. Possible reperfusion etiology 5. Associated with carotid dissection
Differential Points of Migraine Versus Ischemia Stroke
1. Sensory modalities involved sequentially a. Vision, sensory, speech
2.
3.
4.
5. 6. 7.
8.
1) Several modalities involved concomitantly in stroke 2) Negative symptoms predominate in stroke Symptoms are positive in migraine: a. Scintillating scotomata c. Teichopsia b. Paresthesia d. Brightness in a VF Positive symptoms followed by negative symptoms in migraine a. Brightness followed by scotomata Headache follows neuralgic symptoms by 10–15 minutes in migraine a. Sometimes headaches precede symptoms b. Rarely headache and symptoms are concomitant Average attack lasts 20 minutes in migraine Women > men in migraine Attacks lasts over life time of the patient a. Acephalgic form of migraine occurs more frequently in older patients No atheromatous risk factors in migraine
Ischemic Symptoms in Stroke
1. 2. 3. 4. 5. 6. 7. 8. 9.
Several modalities involved concomitantly Negative symptoms predominate Deficits in two modalities occur simultaneously Headache often concomitant with deficits Small white platelet fibrin emboli cause deficits of <2 minutes; clots (red emboli) >5 minutes Distal field ischemia-same territory involved with each attack men > women Attacks <1 year duration Clear risk factors
Reversible Cerebral Segmental Vasoconstriction
1. General characteristics: a. Affects young women; during puerperium b. May occur at menopause c. Occurs at all ages d. Rarely after carotid endarterectomy e. Brain and coronary circulation after subarachnoid hemorrhage f. Involves large, medium, and small cerebral arteries 2. Neurological manifestations a. Severe headache b. Seizures c. Spectrum of altered mental status to coma d. Multifocal neurologic signs e. Edema 3. Laboratory evaluation a. Angiography 1) Multifocal vasodilatation and narrowing b. MRI/CT 1) Brain edema 2) Areas of infarction and hemorrhage
Chapter 3. Medical Causes of Stroke Differential Diagnosis of Reversible Vasculopathy
1. 2. 3. 4. 5. 6. 7. 8.
Cocaine Sympathomimetic drugs Pheochromocytoma Benign cerebral vasculitis Migraine Birth control pills with angiopathy Post partum angiopathy Subarachnoid hemorrhage from aneurysmal rupture
Collagen Defects and Stroke
Hereditary diseases of connective tissue involve the skin, all aspects of the vascular system, the eye and the gastrointestinal tract. PXE is characterized by tortuosity of cerebral vessels, vascular calcification, microaneurysms, fusiform aneurysms and initial hemorrhage. Gastrointestinal hemorrhage and retinal angioid streaks are seminal differential features. Ehlers–Danlos syndrome, primarily type I and IV affect the cerebral circulation. Elongation and degeneration of the chordae tendinea lead to mitral and tricuspid valve prolapse, septal defects and pulmonary and aortic dilatation. Carotid cavernous fistulae as well as rupture of cerebral vessels are seminal features. Marfan’s syndrome is recognized by clinical dysmorphisms. There is a defect of collagen and elastin. Subluxation of the lens, aortic insufficiency and aneurysms are seminal. Erdheim–Gesell Disease (Cystic medial necrosis) is caused by focal fragmentation of elastic fibers and loss of smooth muscle cells of the media. Deposition of mucopolysaccharides leads to thickening of the vessel wall which may be appreciated in the radial artery at the wrist. Huge dilated aortic arch aneurysm is a seminal feature.
Pseudoxanthoma elasticum
A. General characteristics 1. Prevalence of 1/160,000 people 2. AD and AR inheritance 3. Mutation of the ABC 6 (MRP6) gene a) Transporter for organic ions 4. Concomitant rheumatoid arteritis B. Eye and systemic manifestation 1. Retinal signs: a) Angioid retinal streaks occur in 85% of patients b) Grey in color c) Radiate outwardly from the optic disc d) Associated chorioretinitis e) Macular scarring; retinal hemorrhages f) Decreased visual acuity g) Due to a disruption of Bruch’s membrane 2. Gastrointestinal bleeding
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3. HCVD (renal artery involvement) 4. Arterial calcification 5. Premature atherosclerosis of vessels: a) Coronary b) Peripheral c) Retinal d) Cerebral 6. Blood vessel pathology (1) Fragmentation and calcification of the internal elastic lamina (2) Internal and medial vessel wall calcification (3) Topography of lesions: a) Aortic arch b) Intracranial arteries 7. Skin manifestation a) Skin of the neck and axilla prominently involved 1) Tan-yellow papules 2) Thickened and redundant skin particularly of the axilla, groin and flexor surfaces
Neurologic Manifestation
1) Rare aneurysms with SAH 2) Thrombosis of cerebral vessels: a) Rarely pial vessels b) Lacunar strokes c) Binswanger’s microangiopathy
Ehlers Danlos Syndrome
a. Type I (gravis): hyperextensibility of joints, fragile skin; prematurity, AD b. Type II (mitis): joint hyperextensibility limited to hands and feet; AD c. Type III (benign hypermobile): AD; hypermobility of joints d. 80% of patients have type I–III 1. Diminished collagen fiber diameters 2. Type IV decreased type III collagen which is most prevalent in blood vessels and GI tract 3. Type V; absence of Lysol oxidase (necessary for collagen and elastin cross-linking; x-linked) 4. Type VI (Kyphoscoliotic form) a) Hydroxylysine deficient collagen b) AR c) Mutation in Lysol hydroxylase 1 gene (PLOD 1) 5. Type VII: procollagen peptidase; enlarged form of collagen accumulates 6. Stroke syndromes a) Carotid cavernous fistula b) Intracranial aneurysm c) Arterial dissection 7. Patients with cerebrovascular lesions have type IV
SECTION I. Vascular Disease
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a) Decreased synthesis of type III collagen b) Major collagen of blood vessels Clinical Features a. Skin unusually soft; poor wound healing: molluscoid pseudotumors; freely moveable calcified areas; easy bruisability; excessive scarring b. Hyperextensible joints; dislocations of patella; shoulder c. Kyphoscoliosis; carious teeth d. Blue sclerae, microcornea myopia, keratoconus, dislocated lens; retinal detachment e. Cardiac lesions 1) MVP, tricuspid valve prolapse, septal defects (rare cause of emboli) 2) Dilatation of the aortic and pulmonary roots
4) Painless monocular blindness 5) Carotid occlusion is rare 6) Neck pain 7) Carotid territory stroke b. Vertebral artery 1) Pulsatile lateral neck mass 2) Pain in the neck 3) Embolic signs and symptoms 2. Enlarged and tortuous carotid and basilar arteries 3. Mortality for any type of vascular surgery is 40% 4. Post operative complication a. Vertebral artery dissection b. Pneumothorax
Marfan’s Syndrome Aneurysms with Ehlers Danlos Syndrome
1. Clinical features: a. May involve both intra and extracranial blood vessels b. Multiple intracranial aneurysms occur 1. Most common vessel is the internal carotid a. In the cavernous sinus b. As it emerges from the sinus 2. SAH from aneurysmal rupture a. Spontaneously b. During exercise
Carotid Cavernous Fistula with Ehlers Danlos
1. May occur with minor head trauma 2. Clinical manifestations: a. Proptosis b. Chemosis (conjunctival edema) c. Conjunctival arterialized venous blood 1) Small vessels reach the iris; with infection they don’t d. Proptosis e. Visual loss f. Diplopias g. Pulsatile tinnitus h. CCF may occur concomitantly with intracranial aneurysms of ICA
Arterial Dissection with Ehlers–Danlos
1. Clinical signs and symptoms depend on the artery affected a. Carotid artery 1) Oculosympathetic paralysis 2) Emboli rather than flow limiting signs and symptoms 3) Lateral face pain
1. General characteristics: a. AD b. Pevalence 4–6/100,000 individuals c. Fbrillin gene defect d. Cromosome 15 2. General features: 1) Arachnodactyly 2) Am spread > height 3) Lateral lens dislocation (50% of patients) 4) Pectus incurvatum 5) Hyperextensible joints b. Enlarged aortic root c. MVP associated d. Aortic insufficiency 3. Neurological manifestations a. Giant intracranial aneurysm (internal carotid) b. bBerry aneurysms occur with higher frequency than expected c. Rare vascular thrombotic or embolic stroke (MVP); emboli also from giant aneurysms d. Increased incidence of dissection
Cystic Medial Necrosis (Erdheim–Gesell Disease)
1. General Characteristics a. Focal fragmentation of elastic fibers b. Loss of smooth muscle cells of the media c. Deposits of mucopolysaccharides d. Similar lesions also noted in: 1) Ascending aorta of Marfan’s patients 2) Advancing age 3) Possible relationship to hypertension 2. Clinical Features: a. Coronary artery dissection b. Carotid artery aneurysm c. Giant aneurysm of the ascending aorta
Chapter 3. Medical Causes of Stroke
Fibromuscular dysplasia affects the media of the vessel wall with constricting bands that are composed of virous dysplastic tissue and proliferating smooth muscle cells. There are alternating areas of vessel wall dilatation related to medial thinning and disruption of the internal elastic membrane. The process affects renal vessels with consequent arterial hypertension. The entity will be discussed more completely under arterial dissection. Enzyme Deficiencies and Stroke
Enzyme deficiencies cause stroke by: 1. All acclerating atherosclerosis 2. Deposition subendothelial or the surface of vascular tissue 3. Clotting factor and platelet abnormalities Rarely, defects that cause hypertension (adrenal steroid enzymes) cause stroke by the induction of hypertension. The major enzyme deficiencies that cause stroke are: 1. Fabry’s disease 2. Homocystinuria 3. Paroxysmal nocturnal hemoglobinuria 4. Ehlers–Danlos syndrome
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Homocystinuria
1. General Characteristics: a. Definition: homocysteine is found in the urine b. Seven biochemically different entities have been identified c. Major categories of entities causing deficit: 1) Enzymopathies 2) Deficiencies of: a) B6 b) Tetrahydrofolic acid 2. Pathology of Elevated Homocysteine Levels 1. Related to: a. Stroke b. Premature atherosclerosis c. Myocardial infarction d. Venous thromboembolism e. More severe carotid disease 2. Injury to the vascular endothelium a. Platelet activation b. Formation of thrombi 3. Vascular smooth muscle proliferation
Fabry’s Disease
A. General Characteristics 1. X-linked 2. Deficiency of alpha-galactosidase A a. Deficiency of alpha activator protein 3. Primarily a small vessel disease 4. Larger vessel ectasia in posterior vessels of the posterior circulation a. TCD demonstrates elevated CBF velocities 5. Ceramide trihexoside accumulates in cerebral and somatic arteries B. Systemic Clinical Features 1. Decreased ability to sweat 2. Severe acroparesthesias 3. Cutaneous angiokeratomas a. Predilection for perineal areas 4. Renal failure 5. Severe heat intolerance (failure to sweat normally) a. Coma with increased temperature 6. Facial swelling (during heat stress) 7. Lumbosacral bone and disc disease in carriers 8. Exercise intolerance 9. Cardiomyopathy (percentage of patients) C. Neurologic Features 1. Large vessel strokes 2. Vertebrobasilar insufficiency (rare) 3. Autonomic nerve dysfunction (small fiber neuropathy a. Decreased sweating (hypotension) b. Syncope 4. Retinal angioid streaks 5. Aneurysmal dilatation of posterior circulation
Cystathionine Beta-Synthetase Deficiency
1. General Characteristics a. Common in Ireland b. AR; chromosome 21q c. Homocysteine interferes with the cross-linking of collagen 2. Systemic manifestations a. Mental retardation b. Osteoporosis c. Dislocation of the lens d. Occlusion of coronary and renal arteries e. Marfan habitus f. Premature atherosclerosis 3. Neurological manifestations: a. Thrombotic strokes may occur in the first decade; usually <30 years of age
Methylene Tetrahydrofolate Reductase Deficiency
1. General Characteristics a. Affects: 1) Methionine synthesis 2) Tetrahydrofolate generation a) RNA/DNA synthesis b. AR (very rare)
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SECTION I. Vascular Disease
Deficiency of Vitamin B12 Coenzyme Synthesis
1. General Characteristics a. 5 different defects in the activation of the vitamin precursor have been described 1) Cobalamine C,D,E,F,G b. AR
Methylmalonic Aciduria
1. General Characteristics a. Effect of activated B12 deficiency b. Megaloblastic anemia c. Clinical picture of homocystinuric d. Childhood onset
f. Intermittent paroxysms of hemolysis 1) Rare spontaneous remission g. Rare leukemic transformation <5% h. Hemolysis is cardinal feature i. Thrombosis 1) Hepatic vein propensity j. Dark urine upon arising k. Neutropenia and thrombocytopenic 2. Neurological features a. Thrombosis of large vessels b. Patients with aplastic anemia and only lab evidence of PNH 1) Less likely to suffer thrombosis c. Patients with active thrombosis and large proportion of PNH cells in the blood 1) Thrombosis in 50% 2) Death in 33 1/3% d. Cerebral venous and dural sinus thrombosis e. ICH secondary to thrombocytopenia
Pernicious Anemia
1. General Characteristics a. Adult onset b. Hemocystinuria secondary to PA has been associated with recurrent stroke 2. Low B12 levels in PA
Enzyme Defects causing Mineral Corticoid Excess with Hypertension (Possible Stroke)
1) I7 – alpha-hydroxylase deficiency 2) II – beta-hydroxylase deficiency 3) II – beta-ketoreductase deficiency
Paroxysmal Nocturnal Hemoglobinuria
1. General Characteristics a. Requires two coincident factors 1) Somatic mutation of the PIG-A gene (short arm of X-chromosome) 2) Hypoplastic bone marrow b. Failure of synthesis of glycosyl phosphatidyl inositol (GPI) anchor 1) Causes inability of proteins to attach to cell surfaces 2) RBC’s lose complement defense proteins a) Causes intravascular complement mediated hemolysis 3) Platelet activation by similar mechanism c. Associated with marrow aplasia and myelodysplasia d. Hemolytic and thrombotic features of PNH 1) Mediated by complement sensitivity a) CD59 (inhibitor of the membrane attack complex) is deficient e. Incidence 4/1 million people
Dissection of Intra and External Cranial Arteries
Dissection is a major cause of stroke in young patients. Most often the dissection itself is not flow limiting but causes stroke by embolization that forms at the site of the tear. Carotid disease has the seminal features of oculosympathetic paresis and ipsilateral facial pain. It is seen in the context of trauma, migraine headache, fibromuscular dysplasia and hereditary disease of collagen all of which predispose to the disease. Bilateral dissection, and intracranial dissection of the middle cerebral artery all suggest an underlying disease of connective tissue. Intracranial dissections cause infarction, subarachnoid hemorrhage or mass effect. Dissection between the media and intima are often flow limiting and cause infarction. The supraclinoid ICA and the stem MCA are often affected. Vertebral artery dissection is characterized by neck pain. Most symptoms are related to lateral medullary distribution ischemia and include dizziness, dysarthria, and lateral pulsion. Rarely patients suffer diplopia and cortical spinal tract involvement if the pons is involved by embolus or extension of the dissection. Extracranial vertebral artery dissection may be associated with cervical root pain. In general, TIA symptoms are less common with vertebral than carotid dissection. Rarely, vertebral artery dissection begins intracranially; patients may suffer chronic dissections with arteriographic evidence of recanalization. Patients with vertebral dissections may have only neck pain. Chiropractic manipulation in this setting may cause further dissection particularly of the C2 horizontal portion of the artery. Intracranial dissections may also present as mass lesions from aneurysmal dilation and compress adjacent cranial nerves and long tracts. A. Carotid artery 1. General features a. Location 1) Pharyngeal portion 2) Above the bifurcation
Chapter 3. Medical Causes of Stroke
b. Artery is mobile in this section c. Involves redundant portions of the artery d. Often associated with: 1) Minor trauma 2) Congential abnormalities of connective tissue as exemplified by: a) Cystic medial sclerosis b) Marfan’s Syndrome c) COLIA defects d) Fibromuscular dysplasia 3) Migraine a) edema of the vessel wall e. Pathogenesis of clinical phenomena: 1) Arterial wall tear a) Dissection of blood within the media longitudinally 2) Dissection of blood between the media and adenia a) Aneurysmal pouching of the artery demonstrated by arteriography 3) Intimal tear a) Reentry of blood into the intima at a distal site 4) Occlusion caused by: a) Compression of the lumen from blood in the arterial wall b) local thrombosis (endothelial procoagulant factors) 5) Emboli: a) From luminal clot b) Most common cause of clinical symptomatology f. Clinical manifestation: 1) Ipsilateral throbbing headache 2) Face, jaw, neck, pharyngeal pain 3) Ipsilateral partial Horner’s syndrome a) Ischemia of the vasonervorum of the oculosympathetic fibers that course with the internal carotid: (1) Ptosis (2) Meiosis (3) Apparent enophthalmos (4) Facial sweating intact (a) Course with the external carotid artery 4) Pharyngeal carotid segment aneurysm: a) Horner’s syndrome (complete) b) Dysgeusia c) Tongue atrophy (1) Compression of the hypoglossal nerve by the carotid sheath 5) TIA affecting the ipsilateral eye and hemisphere a) If extremely frequent, they may be termed carotid allegro 6) Scintillating scotomata 7) Pulsatile tinnitus
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8) Ischemic optic neuropathy: a) Dissection reaches the carotid sinus b) Often followed by stroke; may be delayed for days to weeks 9) Persistent neck pain: a) Suggests extension of dissection 10) Vertebral and carotid dissections may occur concomitantly a) Suggests collagen defect g. Patterns of dissection: 1) String sign (long dissection) a) Distal to the carotid bifurcation with extensions to the skull base 2) Radiographic signs of occlusion: a) >2 cm distal to ICA origin b) Spares the siphon c) Gradually tapering segment to area of occlusion d) Localized aneurysmal out pouching e) MRI/MRA demonstrate intramural bleeding and mural thickening
Extracranial Vertebral Dissection
General Features: 1. Precipitating factors: a. Neck trauma b. Sustained posture c. Chiropractic manipulation 1) Patients frequently go to the chiropractor because of neck pain 2) Further manipulation extends the dissection d. Collagen defects e. Maintenance of the neck in fixed posture 1) Prolonged surgical procedure 2) Following resuscitation 3) Involve the distal 1/3 of the vertebral artery Clinical Manifestation 1. Lateral neck pain a. May precede neurological symptoms b. May be the only symptom 2. Posterior circulation TIA a. Less common than from ICA dissection 3. Infarcts a. Most common in PICA territory b. Embolic pathogenesis c. Dissection may extend intracranially d. Rarely infarctions of SCA, basilar artery, PCA 4. Cervical root pain a. Aneurysmal dilation of the artery compresses the root 1) Motor, sensory, reflux signs 5. Hypoperfusion of the cervical spinal cord a. May cause infarction
SECTION I. Vascular Disease
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Intracranial dissection causes: 1. Infarctions 2. SAH 3. Mass effect Anterior circulation: 1. Supraclinoid carotid and may dissect into the intracranial MCA Posterior Intracranial Extension Affects: 1. Intracranial vertebral artery 2. Basilar artery Media and adenia dissection are associated with: 1. SAH (may be recurrent) Aneurysmal mass from dissection may cause: 1. Compression of cranial nerves and brain substance Chronic dissections: 1. Lesions are of different ages 2. Multifocal sites 3. Abnormal arterial media and internal elastic membrane 4. Most frequent with fibromuscular dysplasia Recanalization: 1. Occurs if some lumina is patent
Chapter 4 Cerebral Emboli
the night is often a common time for the occurrence of emboli. Cardiac emboli (red-fibrin dependent) are larger than cholesterol or platelet fibrin aggregates and the deficits last >30 minutes to hours. Deficits from the smaller cholesterol platelet-fibrin emboli in general last from 30 seconds to five minutes. Fluctuations and deterioration within specific territorial involvement occurs with distal migration of embolic material. Approximately 90% of emboli migrate in 2–3 weeks or recanalize. Emboli from the heart or venous system have no prior TIA in the affected arterial territory but may have caused TIA’s in another arterial territory. The most common symptoms of emboli are non-specific headaches or dizziness which are hard to document. Seizures occur in 10–15% of patients, 25% of patients have focal symptoms. The sudden onset of a pure Wernicke’s aphasia in the setting of AF suggests an embolus to the inferior division of the left MCA. Muteness may be caused by an embolus to the stem of the MCA or an ACA embolus that affects the supplementary motor area. Thalamic aphasia may occur with a top of the basilar embolus. Ten percent of patients suffer loss of consciousness at ictal onset. Many cerebral emboli are asymptomatic which has been clearly demonstrated by evidence of old lesions at presentation during the first ictus and by multiple emboli detected by TCD during carotid endarterectomy. Simultaneous involvement of ACA and MCA territories suggest a top of the carotid siphon localization. In approximately 50% of patients there are RBC’s in the CSF (80–100/mm3 ) at presentation.
Cardiogenic Embolic
The general clinical features of cerebral emboli are a sudden neurological deficit maximum at onset. There is usually some degree of recovery within 24 hours. Carotid crescendo TIA’s are caused by emboli from an area of critical stenosis associated with a burst plaque. The lipid core of the burst plaque activates platelets and the coagulation cascade with consequent detachment of platelet plugs and red cell fibrin material into the carotid territory. Frequently, the crescendo carotid TIA from emboli results in repeated monocular blindness described as blurry vision or dimness which is different from a patient with severe carotid stenosis. Sudden exposure to light in these patients may cause scotomata due to failure of replenishment of retinal pigments. Distal field ischemia with blindness, contralateral sensory loss or weakness may occur with postural lowering of perfusion pressure. These attacks are more frequent than those that occur following a burst plaque. Distal field ischemia may be manifest by shaking of the contralateral area with decreased perfusion. Similar attacks occur in the posterior circulation. These are rapid and clear quickly without a clinical deficit. Emboli most often occur during the usual activities of daily living. Often an embolus occurs during a Valsalva maneuver which suggests a PFO, atrial septal defect or ventricular septal defect. Getting up to urinate in the middle of
The majority of patients that suffer cerebral cardiogenic emboli have ischemic heart disease, non-valvular atrial fibrillation, prosthetic heart valves and various forms of dilated cardiomyopathy. The rarer causes of cerebral cardiogenic emboli are heart tumors, congenital right to left shunts, subacute bacterial endocarditis, mitral annulus calcification, mitral valve prolapse, venous clots that pass through a patent foramen ovale (PFO), atrial septal aneurysm, fat, air, septic material and fibromyxomatous degeneration of heart valves. Clinical Features of Cardiac Emboli 1. An abrupt onset of hemiparesis, aphasia (particularly Wernicke’s in a setting of AF), sensory deficit or hemianopic visual field loss. 2. MCA > PCA > ACA are the most frequent territories affected a. Some lacunar strokes may be embolic (several vessels affected that produce large lacunes) Preceding Symptoms and Signs 1. 10% may have prodromal symptoms prior to the presenting ictus: a. Stuttering focal deficits occur due to: 1. Distal movement of prior embolus 2. Collateral circulation
Chapter 4. Cerebral Emboli
3. Recanalization b. Cerebral infarction from cardiac emboli may be preceded by TIA’s that are longer with a more severe neurologic deficit than artery to artery emboli. 1. Cardiogenic emboli cause minutes to hours of deficit 2. Artery to artery <2 minutes of deficit 2. Anterior Circulation Clinical Pattern: a. Focal motor, sensory deficits with or without aphasia b. Muteness 1. Stem MCA 2. ACA (supplementary motor area) c. Seizures in approximately 10% d. <10% loss of consciousness at ictus e. Several vascular territories may be involved simultaneously 1. Multifocal neurologic deficits f. Evidence by imaging of prior embolic events Vertebrobasilar Signs and Symptoms of Cardiac Emboli 1. Most often the embolus lodges at the top of the basilar artery with midbrain, thalamic, parietal and occipital lobe symptomatology a. Diplopia b. Ataxia c. Vertigo d. Crossed or bilateral sensory or motor deficits e. Rarely coma at onset
Myocardial Infarction and Ischemic Heart Disease as a Source of Emboli
1. Arterial emboli occur in 2–4% of patients after myocardial infarction 2. Time of occurrence a. 10% in the first week b. 35% in the second week c. 15% in the third week d. 5% in the 3rd month e. Newer studies suggest the first 5 days are the major time of risk 3. Mural thrombi occur with higher incidence in: a. Large infarctions b. Transmural infarction involving the intraventricular septum c. Associated congestive failure d. Anterior > posterior wall e. Severe apical wall dyskinesia f. 75% of major anterior transmural infarctions have dyskinesias g. Most mural thrombi identified by TEE (transthoracic echocardiography) can be seen in 3–5 days 1. Embolize at 4 days 2. Rare after 4–6 weeks to embolize 4. Thrombi within cardiac chambers are due to:
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a. Stasis of blood that initiates: 1. Activation of factor XII and endothelin from the cardiac surface b. Endothelial cardiac wall injury 1. Loss of endothelium 2. Change of negative to positive charge on the cardiac endothelial surface and exposed collagen 3. Platelet aggregation at the site of charge change c. Prothrombotic State is initiated: 1. Low shear rate of circulating RBC within the cardiac chambers d. Echocardiographic correlates of ventricular dysfunction 1. Spontaneous ECHO contrast (“smoke”) a. Swirling haze within cardiac chambers b. Interaction of plasma protein, erythrocytes and shear rate 2. Determinants of “smoke” a. Slow intracardiac flow b. Hematocrit c. Fibrinogen level
Left Ventricular Thrombi
a. Occur in 20–40% of patients with anterior wall myocardial infarction b. Form in the apical wall of the left ventricle c. Mechanisms 1. Low ejection fraction 2. Left ventricular aneurysm 3. Dyskinesia from decreased contractibility
Mural Thrombi in Ventricular Aneurysms
a. 7.6% of patients develop intraventricular aneurysms after an MI b. Mural thrombi occur in 50% of ventricular aneurysms c. Clinical emboli occur in 1–3% of patients per year d. Usually occur within 4–6 weeks after MI
Impaired Left Ventricular Contraction
1. Risk of stroke is 4.6% 2. Ejection fraction of less than 28% is the highest risk 3. Asymptomatic or unexpected cardiac ventricular thrombi a. Patient with stroke is noted to have cardiac thrombi without known coronary artery disease b. Known cardiac thrombi may regress
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SECTION I. Vascular Disease
Arrhythmia and Cerebral Emboli
Clinical Features of AF
1. Most common arrhythmias associated with stroke: a. Chronic atrial fibrillation b. Intermittent atrial fibrillation c. Sick sinus syndrome 2. The majority of cardiogenic emboli are cerebral
1. Acute Wernicke’s aphasia as sole clinical finding: a. Embolus to the temporal-parietal occipital branch of the inferior division of the MCA 2. Highest risk for embolization: 1. Evidence of rheumatic heart disease 2. Onset of AF within the preceding 3 months 3. An enlarged left atrium
Cardiac Arrthymia
Atrial Fibrillation (AF)
1. General characteristics: a. 2–5% of the population > 60 have AF b. 35% of patients with AF will have an ischemic stroke over their life time c. Approximately 4% of AF patients suffer a stroke each year d. AF with no associated risk factors <2% of stroke per year 2. AF with known risk factors: a. Approximately 6% strokes per year b. AF and stroke; 75% have had an ischemic event secondary to AF c. AF plus RHD 1. 17 fold increase of stroke risk d. AF without RHD 1. 5.6 fold increase of stroke risk e. AF increases risk of stroke with age f. AF increases the risk of silent infarction g. 25% of stroke patients >70 years of age have nonvalvular AF h. NVAF – 3× greater risk of stroke related death i. Left atrial enlargement and decreased function causes increased risk of cardiac emboli j. Embolus rate highest after the onset of dysrhythmia k. 12% of patients’ cardioverter for AF suffer an embolus within the first few days of the procedure. 3. Causes of AF: a. 10–30% of AF no identifiable cardiovascular disease b. Identified causes 1. Dilated left atrium in mitral stenosis 2. Thyrotoxicosis 3. Pericarditis 4. Ischemic cardiac disease 4. Origin of embolic material: a. Left atrium or the left atrial appendage 1. 15–50% of valvular atrial fibrillation (VAF) have thrombi in the left atrium 2. Autopsy evidence of arterial emboli in 40% of nonvalvular atrial fibrillation (NVAF) b. Valvular disease with AF 1. 9–29% have left atrial thrombi
Recurrent Embolism in Non-Valvular AF (NVAF)
1. 50% of patients with cerebral embolism from AF suffer a second embolic stroke 2. Recurrence is greatest the first days to weeks (15–20% of patients); some evidence that the greatest risk is at 12–24 hours Paroxysmal Atrial Fibrillation
1. 2. 3. 4.
Cerebral emboli occur during a paroxysm of AF Thrombi form during the arrhythmia Cerebral rather than peripheral arteries are affected 2% may occur at the time of cardioversion
Sick Sinus Syndrome
1. Chaotic atrial activity 2. Changing p wave contour 3. Bradycardia with: a. Multiple recurrent ectopic beats b. Runs of atrial and nodal tachycardia 4. Associated arrhythmias: a. AF or atrial flutter with slow rate of response (70 beats per minute) b. Sinoatrial arrest c. Atrial tachycardia d. Sinus bradycardia 5. 29.9% of men and 1.5% of women >75 years may suffer the syndrome a. 14–18% of patients suffer cerebral emboli 6. The sinoatrial disease at greatest risk for embolism is the brady-tachy syndrome. A greater risk than sinoatrial disease without tachycardia or atrioventricular block a. Emboli are more common with prolonged atrial asystole b. Tachyarrhythmias > bradyarrhythmias are more likely to embolize Rare Causes of Emboli with Arrhythmia
1. Romano Ward Syndrome (AD) 2. Long QT Syndrome a. Jervell b. Lang–Nielsen
Chapter 4. Cerebral Emboli
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Rheumatic Heart Disease
Cardiogenic Site of Origin
1. Majority of RHD patients with cerebral emboli have mitral stenosis (10–20%) 2. Mitral insufficiency (MI) and aortic valve disease are the second most common cause of cerebral emboli in RHD 3. Mitral stenosis: a. Thrombi form in the left atrium b. Rarely on the valve 4. 50–75% of RHD patients have AF or other arrhythmias at the time of an embolus 5. Majority of RHD patients with mitral stenosis have a normal sinus rhythm a. AF greatly increase stroke risk 6. Systemic emboli occur in 10–49% of patients with RHD
General Features 1. Ejection fraction less than 40%: a. Contact factors of clotting mechanisms are activated (slow blood flow) b. Large atria c. Areas of muscle hypokinesia in the ventricles 2. Valve leaflets: a. Activation of platelets by shear forces b. Consequent dilatation of left atrium with arrhythmia c. Nidus for infection d. Platelet fibrin deposition from prothrombotic conditions 1. Non-bacterial thrombotic emboli e. Myxomatous valve and chordae tendinea degeneration f. Calcific aortic valve degeneration 3. Patent foramen ovale (PFO) 4. Atrial septal aneurysm (ASA) 5. Combination of PFO + ASA 6. Cardiac tumors: 1. Primary 2. Metastatic 7. Less common types and sources of emboli: a. Lodge in the carotid artery (Calcium; cartilage) b. Vertebrobasilar arteries at sites of narrowing
Sites of Origin of Artery-to-Artery Emboli
A. Site of Origin a. Artery-to-artery embolism 1. Carotid System a. Bifurcation of common and external carotid arteries b. T-portion (ACA and MCA) at the siphon c. From giant distal aneurysms (carotid; MCA) d. Embryologic connections from the basilar artery to the carotid (rare cause of posterior circulation embolus to reach the anterior circulation) 1) Trigeminal 3) Hypoglossal 2) Otic 4) Proatlantal 2. Intimal tears from dissection of the carotid are a source of emboli a. repair of carotid ulcers or stenosis b. Vertebrobasilar system sources: a. Arch of the aorta (mobile plaques) b. Vertebral artery c. Basilar artery d. Dolichoectatic vertebral basilar artery e. Giant aneurysms 1. Tip of the basilar c. Predilection for specific sites of embolic termination a. Arterial bifurcations b. Pial superficial MCA branches c. Upper and lower trunks of the MCA d. Distal basilar artery (top of the basilar) e. Posterior cerebral arteries f. Areas of greatest CBF: 1. 40% of anterior circulations emboli go to MCA territory g. Tendency to affect same location within an arterial territory 1. Laminar flow h. Aortic arch is the source of 25% of posterior circulation emboli i. 25% of emboli go to VB system (less than 20% of blood flow goes to this circulation)
Valvular Heart Disease as a Source of Emboli
General Characteristics: 1. Approximately 10–20% of patients with valvular heart disease embolize 2. Valvular outlet obstruction is caused by: a. Commisural adhesions b. Leaflet dystrophic calcification 3. Functional properties of stenotic valves: a. Decreased pliability b. Irregular surfaces c. Turbulent blood flow 4. Platelets are activated by turbulence 5. Thrombus formation is related to valve device turbulence 6. Abnormalities of blood flow distal to stenotic or incompetent valves cause: a. Prolonged contact of blood and platelets b. Formation of platelet and red cell fibrin thrombi 7. Atrial and ventricular enlargement from stenotic or incompetent valves: a. Enlarged left atria (mitral stenosis or incompetence) b. Prolonged contact of blood and platelets with cardiac and valve surfaces induces thrombus formation
Cause of Valvular Heart Disease Associated with Emboli
1. Rheumatic mitral and aortic valve stenosis and incompetence
SECTION I. Vascular Disease
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2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
Bicuspid aortic valve (congenital) Mitral annulus calcification Calcific aortic stenosis Mitral valve prolapse Bacterial endocarditis Non-bacterial thrombotic endocarditis Prosthetic heart valves Left ventricular assist devices (LVAD) Anti-phospholipid syndrome Fibrin valvular excressences
Aortic Valve Disease
a. General Characteristics 1. Progressive calcific aortic stenosis: a. Develops in patient’s with congential bicuspid valves; becomes symptomatic in the 4–5th decade b. Rheumatic valvulitis c. Idiopathic 1. Develops in 6–8th decade 2. An atherosclerotic degenerative process 2. Microthrombi in 53% of stenotic valves at necropsy 3. Neurologic complications a. Emboli possibly as high as 33% of patient’s with calcific stenosis b. Associated emboli to: 1. Retina (white and irregular, calcium deposits) 2. Coronary arteries 3. Renal arteries c. Embolization more common after cardiac catheterization or surgery than spontaneously d. Mitral valve > aortic valve embolization e. Incidence and clinical features of aortic insufficiency are unknown
a. Variable obstruction of left ventricular outflow from systolic anterior displacement of the mitral valve b. Concomitant structural abnormality of the mitral valve 2. Clinical Features a. Syncope with prolonged exercise: 1. Release of norepinephrine that constricts the myocardial septum 2. Epinephrine release from the adrenal that dilates skeletal muscle arteries; norepinephrine constricts the hypertrophied segment 3. Combination of peripheral vasodilation and ventricular outflow obstruction that induces hypotension after exercise b. Atrial fibrillation associated with left atrial enlargement occurs late in the course of the disease with a low rate of cerebral embolization c. Rare concomitant SBE of mitral valve or of the annulus calcification or may be causative
Mitral Annulus Calcification (MAC)
1. General characteristics a. Degeneration of the fibrous support of the valve b. Common in the elderly c. Women > men 2. Clinical symptomatology: a. Increased risk of stroke 1) Each millimeter of thickening on the echocardiogram increases the relative risk of stroke (RR) by 1.24 b. Calcification occurs 1. Posterior portion of the mitral annulus ring 2. May project into the cavity of the left ventricle c. Often MAC is accompanied by MI and AF d. May develop superimposed SBE
Mitral Valve Disease
Mitral Valve Prolapse
1. Valve most often involved in rheumatic fever a. Often concomitant aortic valve disease 2. Embolism in mitral stenosis: a. Occurs in 10–20% of patient’s; approximately 50–75% of these are to the brain b. Atrial fibrillation greatly increases the risk of embolism c. Incidence of embolization possibly 1.5% per year 3. Mitral insufficiency is a rare cause of cerebral embolism: a. Increased risk occurs with atrial enlargement and AF
1. Mid Systolic murmur a. Failure of mitral valve leaflet to coapt b. Some patients have abnormal left ventricular contractions 2. Most commonly diagnosed cardiac valve lesion: a. Prevalence of 5–20% in the general population b. Women > men 3. Pathology a. Disruption of valve collagen by infiltration of myxomatous material b. Thickened and elongated chordae tendinea c. Infiltration of the mitral valve annulus d. Fibrosis and thickening of the endocardial surface of the valve leaflets 4. Clinical symptomatology:
Idiopathic Hypertrophic Subaortic Stenosis
1. Asymmetric hypertrophy of the left ventricular septum that causes:
Chapter 4. Cerebral Emboli
a. Small percentage of patients develop severe mitral insufficiency with CHF b. AF may develop in elderly patients with MI and enlarged left atria c. Associated with Marfan’s syndrome, osteogenesis imperfecta and Ehlers–Danlos syndrome d. Rare endocarditis on myxomatous valves e. Low rate of cerebral embolization 5. Echocardiographic evaluation a. 2 mm or greater movement of the coapted anterior or posterior valve leaflets b. Valve leaflets are displaced into the left atrium during systole c. Mitral valve thickening or redundancy d. Regurgitation Neurologic Features 1. Emboli occur in young patients often without other associated risk factors 2. Strokes and TIA occur 3. Approximately 10% of patients have AF concomitantly with the stroke 4. Platelet dysfunction is reported in some patients with MVP: a. Shortened survival time b. Increased levels of beta-thromboglobulin and platelet factor IV 5. Recurrent embolic stroke is rare
Prosthetic Heart Valves
1. General Characteristics a. Dacron rings are a nidus for platelet activation and adhesion b. Prosthetic material activates intrinsic clotting cascade; erythrocyte-fibrin thrombi form c. Degeneration of bioprosthetic valves: 1. Deposition of white platelet fibrin thrombi 2. Cusp sinuses of bioprosthetic mitral valves: a. Undergo fibrosis and calcification b. Nidus for thrombi 2. Mechanical valves are: a. Metal and carbon alloys b. Bioprosthetic valves: 1. Heterography from pig and cow pericardium or valves 3. Non-tissue valves: 1. Thrombus forms at the component tissue interface or in areas of stenosis 4. Incidence of embolization is related to the degree of thrombogenicity: a. Non cloth covered prosthetic valves > cloth covered prosthetic valves > tissue valves 5. Increased risk for embolization:
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a. Caged ball valve prosthesis b. Mitral valve (associated with AF) c. Multiple prosthetic valves d. Age > 70b years e. AF f. Decreased left ventricular ejection fraction g. SBE h. Pregnancy and the puerperium 6. Mitral valve embolize > aortic valves 7. Risk of bioprosthetic valve embolization equals that of mechanical valves that are adequately anti-coagulated 8. Size of the cerebral infarction is due to: a. Size of the embolus b. Stability of the embolus c. Adequacy of the collateral circulation
Subacute Bacterial Endocarditis
1. General Characteristics: a. Natural valves: staph aureus and group D streptococcus are the most common organisms b. Prosthetic valves: aspergillus most common for early emboli; strep viridans for late emboli 2. New epidemiology: a. Older patients b. Intravenous drug abuse patients c. Tricuspid valve is more frequently involved 3. 20% of patients with endocarditis suffer cerebral emboli: a. Small cortical or subcortical bland infarcts b. Large infarcts are secondary often to staph aureus 4. Valve pathology: a. Calcified valves d. Mitral valve prolapse b. Prosthetic valves e. Myxomatous mitral valves c. Rheumatic valves 5. 30–40% of emboli may occur from normal valves a. Aortic > mitral 6. 50% of infected prosthetic valves cause cerebral emboli 7. Neurologic complications are similar for native and prosthetic valves Clinical Characteristics 1. Systemic symptoms: a. Intermittent fever and fatigue b. Backache is common, early c. Embolization to other organs; large artery occlusion suggests fungus d. Sterile vegetations may embolize Systemic Symptoms 1. Intermittent fever and fatigue 2. Backache 3. Loss of weight and appetite Neurologic Signs and Symptoms 1. Cerebral and retinal TIA a. Most common early in the course of the infection 2. Brain ischemia
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SECTION I. Vascular Disease
a. 15–19% of patients 3. Ischemic stroke may occur after treatment has started 4. Intracranial Hemorrhage a. 2.8–7% of patients b. Hemorrhagic transformation of bland infracts c. Large hemorrhages occur: 1. Concomitant use of anticoagulants d. Rupture of septic arteritis e. Rupture of mycotic aneurysms 1. Occur in peripheral subpial vessels f. ICH occurs at or near time of presentation 1. May have had a preceding TIA g. Mycotic aneurysms may rupture after bacterial treatment
5. Early endocarditis: rapid hemodynamic deterioration, conduction defects, poor peripheral perfusion 6. Mortality for prosthetic valve endocarditis is 30–80% for the early form and 20–40% for the late form. 7. Infection with organisms other than streptococcus usually results in valve replacement.
CSF
1. Pleocytosis < 300 cells/mm3 ; neutrophilic early and lymphocytic late 2. Slight increase of protein 3. Normal sugar 4. May have normal CSF
Encephalopathy Non-Infective Endocardial Lesions
1. Most common with staph aureus: 1. Toxic metabolic factors 2. Secretion of interleukins (IL-6) with subsequent cerebral edema 3. Associated brain infarcts and microabscesses
Meningitis
a. Embolization of bacteria to meningeal arteries: 1. Presentation with neck and back pain prior to neurologic symptoms 2. 1.1–6.4% of patients with endocarditis have meningitis Vegetations 1. Millimeters to centimeters in size a. fungi are the largest 2. Potential for embolization is related to: a. Size b. Friability 3. Valve most like to embolize 1. Mitral > aortic > tricuspid
Endocarditis on Prosthetic Valve
a. Occurs in 3–6% of patients: 1. Early endocarditis <60 days; from perioperative bacteremia: skin, wound or contaminated valves; organisms: staph epidermidis or aureus, gram negative bacteria, diphtheroids, fungi, mycobacteria, legionella. 2. Late prosthetic valve endocarditis >60 days post operatively; streptococci, staph epidermidis. 3. The risk of endocarditis is similar for mechanical and bioprosthetic valves. 4. Most common symptoms and signs; fever, new or changing murmur, systemic embolization or congestive heart failure.
1. General Characteristics a. Occur primarily in SLE, the APLA syndrome and NBTE b. Probable similar pathogenesis c. All three entities are associated with: 1. Hypercoagulability 2. Thrombocytopenia 3. Embolic stroke 4. Platelet thrombi on valve and endocardial tissues 2. Noninfective valve lesions are associated with: a. Ergotamine b. Methysergide c. Dexfenfluramine d. Phentermine e. Carcinoid (high serotonin levels) f. Leukemia 3. Strands a. Trans esophageal echo cardiography may demonstrate: 1. Strands of mobile tissue attached to valve and endocardial surfaces b. Filamentous strands are known as Lambl excrescences: 1. Located on the atrial surfaces of mitral valves or the ventricular surfaces of aortic valves 2. Strands are composed of: a. Cellular connective tissue core covered by epithelium b. 1–10 mm in length c. May be related to fibrinous deposits on valve surfaces d. May spread to the endocardium and papillary muscles 3. Prevalence by TEE (transesophageal echocardiography) a. Approximately 4% on mitral valves
Chapter 4. Cerebral Emboli
b. 1.7% on aortic valves c. Incidence possibly 10% in patients who have suffered embolization 4. Association of stroke and strands: a. Young patients b. Mitral and aortic strands c. Low recurrent stroke risk d. Patients with SLE, APLAS and NBTE
Antiphospholipid Antibody Syndrome
1. General Characteristics a. Associated with: 1. Recurrent abortion 2. Phlebothrombosis (including the upper extremities) 3. Myocardial infarction 4. Thrombocytopenia 5. Pulmonary emboli b. Cardiac valvular lesions: 1. High frequency 2. Similar to the verrucous lesion of SLE 3. Mitral > aortic valves 2. Phospholipids are important constituents of: a. Platelets c. Coagulation factors b. Cardiac valve endothelium 3. Laboratory evaluation: a. Patients demonstrate lupus anticoagulant b. Anticardiolipin antibody (IgG or IgM) c. Patients with clinical features of APLAS may have embolic stroke and a negative screen for antibodies
Non-Bacterial Thrombotic Endocarditis
1. Associated most often with cancer (particularly mucinous adenocarcinoma, prostate, lung, or melanoma) 2. Other Associations: a. SLE b. APLAS c. Pneumonia d. Perforated ulcer e. Wasted, immunosuppressed patients f. Severe gram negative infection g. Pheochromocytoma 3. Order of valve involvement: a. Mitral > aortic > tricuspid > pulmonary b. Deposits are along lines of valve coaptation and consist of degenerating platelets, fibrin and leukocytes c. Bivalvular lesions occur d. Vegetations are bland and less than 5 mm in size 4. Both small and large vessel occlusions occur in the cerebral or systemic circulation a. Cerebral emboli with stroke occur in 50% of patients with valve lesions
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5. Often associated with DIC but also occur concomitantly with SAH, ICH and thrombotic stroke a. Elevated D-dimer seen in this context
Lupus Verrucous Endocarditis
1. Fibrous thickening of valves 2. Vegetations prominent along valvular closure lines and leaflets 3. Spread to the papillary muscles and endocardium 4. Associated with cerebral embolism
Cardiomyopathy
1. General Characteristics a. Embolism most common in dilated cardiomyopathies; ejection fraction less than 50% b. Loss of normal subendocardial trabeculations c. Stasis of blood; prolonged contact of platelets and contact factor XIII d. Mural thrombi form within the trabeculae carnea of the cardiac apex e. Embolism less frequent in hypertrophic cardiomyopathy unless there is concomitant AF f. Associated with the stasis of CHF 2. Cardiomyopathies associated with emboli: a. Idiopathic b. Post partum c. Viral d. Myocarditis (idiopathic) e. Ischemic cardiomyopathy f. Sarcoidosis g. Amyloidosis h. Endocardial fibroelastosis i. Mitochondrial myopathies j. Dystrophinopathy (DMD; Becker’s) k. Inflammatory muscle disease (IBM; DM/PM) l. Nemaline myopathy m. Glycogen: storage disease (debrancher) n. scapuloperoneal dystrophy with mental retardation o. Desmin myopathy p. Myofibrillar lysis q. Fabry’s disease r. Cocaine s. Endocrinopathies (acromegaly, hypothyroidism, adrenal insufficiency) t. Congenital myopathy
Hereditary Cardiomyopathies
I. General Characteristics:
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SECTION I. Vascular Disease
1. Categories of familial dilated cardiomyopathies (FDCM) a. Mutations in contractile protein genes b. Dystrophinopathy 1) Affected boys and men 2) Women carriers of Becker or Duchenne mutations 3) Mitochondrial disorders 4) Sarcoglycanopathies a) Limb girdle myopathies 5) Rare disorders 2. Genetics of FDCM a. Allelic and locus heterogeneity 3. Usual clinical features: a. Syncope b. Palpitations c. Dyspnea d. Heart failure e. Exertion induced sudden death f. Angina 4. Neurologic features: a. Cerebral emboli occur in patients with: 1) Ejection fractions of <30% 2) Trans echo cardiogram that demonstrate: a) “smoke” (echoic signals that signal altered intracardiac blood flow)
Familial Hypertrophic Cardiomyopathy (IHCM)
1. General Characteristics: a. Clinical onset from fetal life to adulthood b. Mutations in genes that encode cardiac contractile proteins 1) Most frequent mutations: a) B-myosin heavy chain b) High penetrance c) High incidence of sudden death 2) Less common mutations in genes for: a) Essential light chain protein b) Regulatory light chain protein c) Myosin binding protein 2. Clinical Manifestations by Mutation Characteristics a. Penetrance 1) B-myosin high penetrance a) High incidence of sudden death 2) B-myosin low penetrance a) Benign course b. Mutation specific cause of sudden death: 1) Myocardial ischemia that cause: a. Syncope c. Sudden death b. Pre-syncope 2) Heart block 3) Preexcitation syndrome c. Mutations causing functional deficits:
a) B-myosin heavy chain 1) Affects head-rod junction b) Expression of mutations in skeletal muscle with: 1) Decreased isometric force d. Mutations expressed in skeletal muscle 1) Heart and skeletal muscle affected concomitantly 2) B-myosin heavy chain; myosin light chains, tropomyosin affected Clinical Syndromes of ICHM 1. Variance in degree of heart muscle pathology a. Focal heart muscle pathology vs generalized heart muscle involvement 2. AD in some families 3. Penetrance is age dependent 4. Clinical heterogeneity within families
Dystrophinopathy
1. General Characteristics a. More limited the patients exercise tolerance the less symptomatic cardiomyopathy b. EKG abnormalities in BMD and DMD increase dramatically with age c. DMD carrier women 1) 38% abnormal cardiograms d. BMD carrier women 1) 34% abnormal cardiograms e. 8% of DMD carries suffer dilated cardiomyopathy f. X-linked cardiomyopathy 1) Similar dystrophin gene type gene mutation in some; others are new mutations a) High CPK b) Dystrophic myopathy by skeletal muscle biopsy g. Sarcoglycanopathy 1) Patients with dilated cardiomyopathy: a) Point mutation in gene for alpha sarcoglia
Mitochondrial Cardiomyopathy
1. General Characteristics: a. Dilated cardiomyopathy 1) More common in patients with maternally inherited point mutations 2) Mutations most common in: a) mt DNA-encoded t RNA’s 2. MELAS-3243 mutation a. Dilated cardiomyopathy 3. Progressive external ophthalmoplegia (PEO) a. Dilated cardiomyopathy b. Multiple mt DNA deletions c. Eastern Arabian Peninsula (most common) 4. Kearns–Sayre Syndrome: a. Dilated cardiomyopathy
Chapter 4. Cerebral Emboli
b. Adolescents with stroke c. Predominant cardiac feature is heart-block 5. Patients with dilated cardiomyopathy identified with: a. Complex I, III, and IV mitochondrial complex deficits Rare Myopathies with Emboligenic Cardiomyopathy
a. b. c. d. e.
Myofibrillar lysis Scapuloperoneal dystrophy with mental retardation Glycogen debrancher deficiency Nemaline myopathy Desmin myopathy
Hereditary Dysrhythmias with Embolic Stroke
Prolonged QT Syndromes 1. General Characteristics: a. Prolongation of the QT interval 1) Corrected for heart rate b. T-wave abnormalities c. Brachycardia d. Ventricular tachyarrhythmias e. Polymorphic ventricular tachycardiac f. Torsades de pointes g. Defects of cardiac repolarization 2. Usual Clinical Presentation a. Syncope c. Sudden death b. Seizure 3. Triggers: a. Exercise c. Noise b. Emotion d. Rarely sleep A. Romano Ward Syndrome 1. AD 2. Most common form B. Jervell 1. Rare 3. Sensorineural deafness 2. AR C. Lang Nielsen 1. Cardiac defect is AD 2. Deafness is recessive Mechanism
1. Heterogeneous genetic defects a. Mutation in the cardiac potassium channel HERG (KCNH2) b. Reduces the delayed rectifier KCN currents c. A trafficking defect that cause failure of delivery of the mutant protein to the plasma membrane
Cardiac Tumor and Cerebral Emboli
1. Atrial myxoma: a. Arise from either side of the atrial septum in the region of the fossa ovalis
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b. Left atrium > left ventricle: may have simultaneous origin from both atria c. Attached to atrial wall or are pedunculated and cause valve obstruction d. Gelatinous round, polypoid masses covered with platelet fibrin clots e. Emboli: Tumor fragments or thrombi f. Cardiac symptoms: 1. Syncope (change of cardiac output) 2. Tripopnea a. Right atrial myxoma b. Shortness of breath with position change (blockage of right ventricle outflow) 3. Heart murmur usually MI > MS (with mitral valve disease) 4. Occasionally a cardiac “plop” can be auscultated. Tumor falls into the valve and obstructs it g. Rare bilateral myxomas 1. Project from right atrium to left and through a PFO h. Less than 10% are in the ventricles
Neurological Signs and Symptoms of Myxoma
1. Superficial pial MCA territory most commonly affected 2. Peripheral aneurysm of superficial blood vessels: a. Small b. Multiple c. Rupture with SAH or hemorrhagic infarctions 1. Myomatous tissue grows through the vessel wall d. Rarely large peripheral aneurysms are seen 3. Delayed progressive neurologic signs are seen (rare) 4. 30–50% of cardiac myxomas embolize 5. Rare embolization to the spinal cord 6. Sudden death (possible coronary artery embolus)
Constitutional Symptoms and Signs of Myxoma
1. CHF 4. Weight loss 2. Polyarthralgia 5. Anterior chest wall petechiae 3. Fever
Papillary Fibroelastoma
1. General characteristics a. Multiple papillary bands that are attached to an avascular fibrocartilaginous core b. Arise from the aortic valve 2. Clinical symptomatology a. Angina due to embolization of the coronary arteries b. Multiple brain infarcts
SECTION I. Vascular Disease
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1. General characteristics a. Often are multiple b. Arise from the ventricular myocardium with projection into the ventricular chamber c. Associated with tuberous sclerosis and neurofibromatosis (NFI) 2. Emboli consist of tumor fragments
l. Valsalva maneuvers 3. Less than 1% of cerebral emboli are paradoxical 4. The clinical setting: a. Thrombosis of leg or pelvic veins b. Prothrombotic state c. Valsalva maneuvers d. Associated pulmonary embolism 5. Neurological signs and symptoms a. Most common stroke territory is that of the MCA b. Higher than expected vertebrobasilar embolization
Differential Diagnosis of Cardiac Tumors Patent Foramen Ovale
1. Rhabdomyoma 2. Atrial and ventricular myxomas 3. Fibroelastoma 4. Histiocytoma 5. Hemangioma
6. Hamartoma 7. Undifferentiated 8. Fibroma 9. Metastatic tumors
Differential Diagnosis of Intracardiac Lesions
1. Cardiac tumors 2. Metastatic tumors to the heart a. Hypernephroma (through the inferior vena cava) b. Squamous cell lung carcinoma (through the pericardium) c. Malignant melanoma (able to attach to the endocardium) 3. Ball valve thrombus 4. Mural thrombus a. Following myocardial ischemia b. Within ventricular aneurysm 5. Thrombi within septal aneurysms
Paradoxical Cerebral Embolus
1. General characteristics 1. Definition: embolus entering the arterial circulation from the venous side through a right to left shunt 2. Predisposition: a. Patent foramen ovale (20–25% of the population) b. Atrial septal defect’s, VSD, pulmonary AV fistulas c. Anovulatory drugs d. Lower extremity injury e. Prothrombotic states f. Jugular vein catheterization g. Cancer h. Obesity i. Prolonged bed rest j. Any increased source of right heart pressure k. Occurs in some patients with no evidence of right heart disease, thrombophlebitis or increased pulmonary pressure
1. General characteristics: a. Present to some degree in approximately 30% of patients b. Declines approximately 10% with age c. Average size is 4–5 mm; gradually increases with age 2. Neurologic signs and symptoms: a. MCA territory most frequently involved b. Approximately 1/3 involve the VB system which receives approximately 20% of CBF. MCA territory receives approximately 40% of CBF c. Predisposition for paradoxical embolus is the setting 3. Increased risk of paradoxical embolus with PFO by TEE a. Concomitant atrial septal aneurysm b. Larger PFO c. More microbubbles insonated in MCA territory
Atrial Septal Aneurysm
1. General characteristics a. Bulging of septum primum tissue of the atrial septum through the fossa ovalis 1. Into the right or left atria b. Association of atrial septal aneurysms and interatrial shunts c. High incidence of PFO with atrial septal aneurysms d. Atrial septal aneurysm with 10 mm excursion greater chance of embolization e. Thrombi may form within the aneurysm 2. Recurrence rate of stroke for PFO and atrial septal aneurysm when combined is approximately 2% per year; may have severe stroke at onset
Differential Diagnosis of Cardiac Sources of Emboli
A. Ischemic Heart Disease 1. Mural thrombus 2. Congestive heart failure 3. Ejection fraction of less than 30% 4. Ventricular aneurysm
Chapter 4. Cerebral Emboli
5. Akinetic or hypokinetic segments B. Cardiac Arrhythmia 1. Chronic or paroxysmal atrial fibrillation 2. Sick sinus syndrome 3. Brady-tachyarrhythmia 4. Long QT interval syndrome 5. Ward Romano Syndrome (AD) 6. Jervell Syndrome (AD) 7. Lang–Nielsen Syndrome (AR) C. Valvular heart disease 1. Rheumatic mitral stenosis 2. Rheumatic mitral insufficiency (rare) 3. Rheumatic aortic stenosis 4. Bicuspid aortic valve (congenital) 5. Calcific aortic stenosis 6. Mitral annulus calcification 7. Bacterial endocarditis 8. NBTE (marantic endocarditis) 9. SLE (verrucous endocarditis) 10. Antiphospholipid syndrome (APLS) 11. Left ventricular assist devices 12. Prosthetic heart valves 13. Fibrous and fibrinous endocardial lesions D. Cardiomyopathy 1. All dilated cardiomyopathies 2. Idiopathic 3. Post partum 4. Viral 5. Idiopathic myocarditis 6. Ischemic cardiomyopathy 7. Sarcoidosis 8. Amyloidosis 9. Endocardial fibroelastosis 10. Multiple mitochondrial myopathies 11. Duchenne muscular dystrophy 12. Becker’s muscular dystrophy 13. Idiopathic dilated cardiomyopathy 14. Variants of dystrophinopathy 15. Inclusion body myositis 16. Dermatomyositis/polymyositis complex 17. Nemaline myopathy 18. Debrancher glycogen storage disease 19. Scapuloperoneal dystrophy with mental retardation 20. Desmin myopathy 21. Myofibrillar lysis E. Intracardiac Lesions 1. Cardiac tumors (primary) a. Myxoma b. Fibroma c. Fibroelastoma d. Hamartoma e. Hemangioma f. Histiocytoma g. Rhabdomyoma (sarcoma) h. Undifferentiated
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2. Metastatic tumors a. Hypernephroma b. Melanoma c. Squamous cell carcinoma of the lung 3. Ball valve thrombus 4. Mural thrombus 5. Ventricular aneurysm with thrombus 6. Septal aneurysm with thrombus F. Intracardiac defects with paradoxical embolus 1. Atrial septal defects 2. Ventricular septal defects 3. Patent foramen ovale (PFO) 4. Atrial septal aneurysms 5. PFO plus atrial septal aneurysm
The Aorta as a Source of Emboli
General characteristics 1. Average diameter of an aortic plaque is 19 mm 2. Plaques are frequently on the anterior or posterior right side of the ascending aorta 3. The upper and lower half of the ascending aorta are equally involved 4. Aortic arch plaques a. At the edifice of the innominate artery 5. Plaque grading system a. 0 mm – 0 b. 1 mm – grade 1 c. 2 mm – grade 2 d. 3 mm – grade 3 e. 4 mm – grade 4 f. 5 mm – grade 5; mobile complex 6. Complex thick or mobile plaques are most likely to embolize 7. Plaques have disappeared after anti-coagulant therapy 8. Anticoagulants theoretically could potentiate cholesterol emboli by: a. Blocking protective clot thrombi that cover plaque ulceration Neurologic Signs and Symptoms 1. Protruding atheroma a. Related to emboli 2. Ulcerated plaque in the aortic arch may not correlate with atheromatous carotid disease 3. Ascending aorta and arch junction a. Important site for plaque that embolize as is the origin of the innominate artery 4. Frequency of brain infarction correlated with thickness of the aortic wall 5. Complex, thick or mobile plaques > 5 mm have 3× greater incidence of stroke than patients with plaques <5 mm
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SECTION I. Vascular Disease
Differential Diagnosis of Artery-to-Artery Embolism
1. Proximal extracranial and intracranial arteries a. Ulcerated and stenotic lesions 2. Dissection of arteries a. Thrombus at the site of the intimal tear 3. Post surgical sites (flaps, sutures) 4. Inflammatory arterial disease a. Giant cell arteritis c. Infectious arteritis b. Takayasu’s Disease d. Autoimmune arteritis 5. Thrombi within aneurysms a. Dolichoectatic arteries c. Fusiform aneurysms b. Saccular (giant aneurysms) 6. Fibromuscular dysplasia 7. Cancer: a. Direct invasion of arteries b. Promotion of clots within arteries encased by tumor 8. Hypercoagulable states 9. Aortic arch atherosclerosis with embolus: a. Infarcts MCA territory and brachial plexus b. Supraclavicular portions of the plexus supplied by ascending deep and transverse arteries c. Infraclavicular portions of the plexus supplied by 3–4 branches of the axillary arteries 10. Multiple brain gas embolisms: a. Ingestion of H2 O2 1. O2 embolism 2. Predominantly to grey matter b. Air embolism 1. Vascular surgical procedures: a. Open heart surgery b. Head and neck surgery in the sitting position. Air enters the jugular vein c. Pelvic vein insufflation (air) during pregnancy 11. Spectacular shrinking deficit a. Profound hemispheric ischemia b. Resolves over hours to days c. Minimal residual deficits d. Rapid embolic lysis and fragmentation e. 90% of emboli migrate or are recanalized within 2–3 weeks 12. Fat embolism a. Broken long bones in young patients b. Hip replacement surgery (even in elderly patients) c. Acute syndrome: 1. Interstitial lung involvement with low pO2 2. Petechiae across the anterior chest wall 3. Predilection for emboli a. Retina (fat globules visible) b. Corpus callosum c. Centrum semiovale d. Superficial pial vessels 4. Fat globules noted in the urine 5. Mechanism
a. Emboli pass through the lungs into the arterial circulation b. Precipitation of fat from chylomicra d. Late syndrome 1. 4–7 days following the event 2. Acute confusion
Differential Diagnosis of Unusual Emboli
1. Air (cardiac and neck surgery, diving accidents) 2. Fat emboli (diabetic ketoacidosis, trauma, pancreatitis) 3. N2 O (bends) diving, pressure from underwater construction (Caisson’s Disease) 4. Calcium (calcific aortic valves, calcified mitral valve annulus) 5. Fungus balls (SBE: aspergillus) 6. Bullets (shot gun pellets; rare bullet fragments) 7. Ectatic arteries 8. Aneurysms (giant > 1 cm; tip of the basilar, carotid, middle cerebral artery) 9. Tumor material 10. Thrombolytic therapy (lysis of clots that then expose underlying collagen which then forms new less adherent clots) 11. Iatrogenic occlusive therapy (embolization of AVM’s; Gelfoam) 12. Catheters 13. Defoaming agents 14. MAC attack (esophageal fistula to veins-McDonald hamburger fragments to veins) 15. Talc (addicts; increased right heart pressure from pulmonary fibrosis; paradoxical embolus) 16. Fibrocartilage (following orthopedic procedures)
Chapter 5 Hypoxic-Ischemic Encephalopathy General Characteristics
a. Decreased brain perfusion, oxygenation or both b. Decreased perfusion 1. Cardiac arrhythmia or arrest 2. Pump failure The brain is differentially susceptible to hypoxia, hypoglycemia and hypoperfusion. In general, areas most susceptible to hypoxia have the greatest required metabolic rate for glucose utilization and ATP requirement. In the case of cardiac arrest, pump failure, ventilatory failure they suffer first and most severely. In general, respiratory arrest without circulatory compromise carries a better prognosis. Complete circulatory arrest induces rheological changes that include endothelial cell
Chapter 5. Hypoxic-Ischemic Encephalopathy
swelling and viscosity changes that preclude reperfusion of cortical, basal ganglia and thalamic capillary net works. This constitutes the no-reflow phenomena. Hyperglycemia and acidosis at the time of arrest increase neuronal death. Pre arrest vascular compromise leads to distal field ischemia and stroke primarily in the anterior circulation in those under 40 and in the vertebral basilar system in elderly patients. Prolonged hypoperfusion and anoxia lead to border zone infarction (posterior zone between MCA/PCA) territory > anterior zone (MCA/ACA territory). Specific toxins or circumstance involve specific brain areas. Carbon monoxide preferentially affects the medial globus pallidus, cortex and cerebellum. Isolation of speech areas, from perisylvian involvement has also been described. Strangulation or hanging preferentially involves the medial globus pallidus as reversible decerebration. A single hypoxic event may cause a delayed but progressive leukoencephalopathy that begins 4–10 days following the insult. Cognitive dysfunction, irritability and apathy are prominent as is rigidity of the limbs and ataxia of gait. Some patients with delayed hypoxic leukoencephalopathy have reduced aryl sulfatase A activity.
Consciousness
The integrity of the reticular activating system (RAS) is requisite for consciousness. The lateral medullary reticular formation, the dorsal pontine tegmentum, periaqueductal grey of the midbrain, intra laminar thalamic nuclei are the most important nuclear areas that maintain consciousness. Both cerebral hemispheres must be involved to lose consciousness. Bilateral vertebral disease or basilar artery infarction compromise the lateral medullary reticular formation and dorsal pontine tegmentum. Top of the basilar artery embolic stroke or thrombosis affects the midbrain periaqueductal grey or intra laminar thalamic nuclei. Hypoxic insults and prolonged hypoperfusion affect the cerebral hemispheres. Increased intracranial pressure (usually from edema) decreases cerebral perfusion at all levels and is a frequent concomitant of cardiac arrest.
Differential Susceptibility of Neurons to Hypoxia
1. Hippocampus a. Sumner’s section V, amygdaloid complex b. Pyramidal neurons c. CA I zone 2. Medial laminae of the cerebral cortex a. III–V b. Thalamic projecting neurons to the cortex 3. Globus pallidus/caudate/putamen a. Internal segment GPi 4. Thalamus
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a. Anteroventral nuclei c. Pulvinar b. Dorsomedial nuclei 5. Cerebellum a. Purkinje cells 6. Brainstem tegmental nuclei a. V, IX, X; c. Superior alive b. Inferior caliculus d. Vestibular nuclei 7. Spinal cord a. Renshaw cells b. Anterior 2/3 of the cord c. Distribution of the artery of Adamkiewicz
Border Zone Infarction
1. Anterior; ACA/MCA 2. Posterior; MCA/PCA 3. Vascular stripe (between descending pial blood vessels and ascending lenticula striate arteries) 4. Border zone of the cerebellum (level of the dentate) 5. Subinsular cortical areas 6. Cerebellar artery border zones a. SCA/PICA b. SCA/AICA
Clinical Patterns of Circulatory Arrest
Brain-Stem Coma
1. Prolonged hypoperfusion-anoxia a. Dilated pupils b. Absent corneal reflexes c. No doll’s eye response (absent vestibular ocular response) d. No response to ice-water caloric (absent VOR) e. Frequent loss of spontaneous respiration f. No spontaneous movement 1. decorticate or decerebrate posture may be seen 2. Selective necrosis of brainstem nuclei a. Affects children and infants most frequently; (Vth nerve involvement) occasionally seen in adults b. No oculocephalic eye movements (VOR) c. Loss of branchial muscle functioning including the gag reflex d. Stiff extremities; no spontaneous movement e. Automatic movements with stimuli f. Autonomic disinhibition a. Fluctuating blood pressure and cardiac rate g. Loss of spontaneous respiration 3. Brainstem coma secondary to bi-hemispheral coma a. Patients regain brainstem reflexes b. Spontaneous respiration occurs
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Coma due to Bilateral Hemispheric Dysfunction
a. b. c. d. e.
Unresponsive to noise, bright light or voice Respond to painful stimuli Spontaneous movements of the extremities Pupils are normal or small; react to light Eye movements: 1) Roving from side to side 2) Midline 3) Deviated upward 4) Hyperactive doll’s eyes a) Loss of ocular fixation reflexes that inhibit the vestibular ocular reflex 5) Vertical eye movements present to VOR maneuvers: a) May be difficult to deviate downward if patient has fixed upward deviation f. Gag reflex intact g. Branchial innervated movements are intact 1. Spontaneous blink and swallow reflexes
Posterior Border Zone Infarction
1. Bilateral infarction of the MCA/PCA overlap territory a. Parieto-occipital junction 2. Complete or partial Balint’s Syndrome a. Simultagnosia 1. Inability to see all objects in the visual field 2. Inability to see all components of one object 3. Inability to maintain components of an object into a whole 4. Optic ataxia: a. Damage to parietal area 5 and 7. Patients under reach for objects. They have poor eye/hand coordination 5. Apraxia of gaze a. Poor initial scanning of a visual field b. Inability to look at a specific object on command c. Inability to break a fixed gaze
Anterior Border Zone Infarction Corticospinal Tract Dysfunction
1. Patients may have preserved: a. Adduction/flexion of the shoulder, arms and wrists 2. Noxious stimulation of extensor or flexor upper extremity surface: a. Elicits flexion/adduction of the arms and shoulder 3. Noxious stimulation of lower extremities a. Extension/adduction of the lower limbs 4. External rotation of the foot; cortical thumb
Intact Corticospinal Tract Signs
a. Noxious stimuli elicits movements away from afferent input b. Movement of individual fingers c. Spontaneous or reactive extension of the upper extremity d. Abducting movements of the arm or forearm e. Lower limb noxious stimuli elicits 1. Flexion/adduction f. Supination of the arm at rest and normal position of the foot (extension) g. Thumb abducted
Progression from Bi-Hemispheral Coma
Specific features of selective vulnerability to the anoxicischemic episode may become prominent. Many patients demonstrate agitation, restlessness, confusion and delirium as they regain consciousness. If the insult has been primarily hypotensive with less generalized anoxia, border zone infarction may be prominent.
1. Bilateral infarction of the anterior and middle cerebral artery border zone territories 2. “Man in the Barrel” Syndrome a. Shoulder and arm are primarily affected; hand stronger than shoulder; legs spared b. Frontal eye fields involved (area 8, 10) 1. Roving cortical eye movements (disinhibited from gaze centers) 2. Too easily obtained doll’s eye maneuvers (uninhibited VOR) 3. Asymmetries have been described: a. Unilateral arm paralysis b. Head and eye deviation to the more affected side 4. Stupor from extensive bilateral lesions
Memory Loss
1. Severe damage to the pyramidal cells of the hippocampus a. CA I; Sumner’s section V b. Amygdaloid complex c. Medial temporal lobes 2. Clinical sequelae a. Severe short term memory loss. Poor encoding of new memories over 3 minutes. Registration is intact (object recall 15 seconds). Long term memory and retrieval relatively spared
Laminar Necrosis
1. Layers III–V of the cortex are damaged throughout. Speech, motor, and visual areas affected clinically more prominently than the parietal lobe.
Chapter 5. Hypoxic-Ischemic Encephalopathy
2. Isolation of the speech areas a. Combination of laminar necrosis and anterior and poster border zone infarction b. Transcortical motor and sensory aphasia c. Complete perisylvian involvement 1. Patient can only repeat; cannot initiate or perceive speech d. Severe dysarthria 1. Damage to corticobulbar fibers for speech emanating from the frontal operculum 3. Clumsiness and dysarthria 4. Ideomotor, limb kinetic, ideational apraxias a. Laminar necrosis of area 6, 8 (ideomotor; callosal apraxia); posterior parietal areas (ideational apraxia) 5. Cortical blindness a. Laminal necrosis of the occipital cortex b. Anton’s Syndrome 6. Seizures a. Most often generalized b. Difficult to treat 7. Myoclonus a. Multifocal b. Generalized c. Exaggerated by stimuli or movement d. Repetitive and generalized > 30 minutes a bad prognostic sign following cardiac arrest 8. Persistent Vegetative State a. Severe laminar necrosis 1. Appear awake and have brain stem function 2. No response to stimuli a. Eyes may track a moving object 3. Retain sleep-wake cycle 4. Eyes are open 9. Cerebellar dysfunction a. Metronomic eye movements; eyes rhythmically oscillate side to side b. generalized ataxia c. Lance Adams Syndrome 1. Spontaneous, arrhythmic fine and course movements 2. Exaggerated by voluntary movement 3. Action myoclonus 4. Associated with gait ataxia 5. Damage to dorsal raphe serotonergic neurons in addition to Purkinje cells and cerebellar pathways 6. Probable associated border zone cerebellar infarcts of the PICA/SCA and AICA 7. May progress after the initial insult
Basal Ganglia and Thalamus
1. Prolonged partial ischemia: a. Hypoxia precedes circulatory insult
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b. Damage most severe in globus pallidus interna, caudate, putamen AV, DM and pulvinar nuclei of the thalamus c. Hanging, strangulation, carbon monoxide produce a similar dissociation between blood flow and oxygenation d. Clinical sequelae 1. Eyes open and fixate 2. Abnormal twitches and movements 3. Rigidity of extensor and flexor muscles 4. Decorticate posturing 5. Mute and unresponsive
Delayed Leukoencephalopathy
1. Generally young patients who have suffered strangulation, drowning, inhalation of noxious gases or carbon monoxide poisoning 2. Pathology: a. Diffuse demyelination to hemorrhagic white matter necrosis b. Basal ganglia involvement (GP) c. Possible relationship to decreased Arylsulfatase A in some patients 3. Clinical features: a. Initial coma associated with: 1. Quadriparesis 3. Involuntary limb movements 2. Atonia b. Progression to: 1. Dystonic rigid state a. Relative preservation of the cortex b. Severe damage to basal ganglia c. Generalized demyelination c. Delayed deterioration started between 4–10 days in some patients
Hypoxic-Ischemic Spinal Cord Damage
1. Selective vulnerability of the spinal cord a. Upper and lower thoracic cord most often involved b. Territory of the great radicular artery of Adamkiewicz 1. Origin T10–T12 to L-2; supplies lumbar cord and the conus medullaris c. Upper and lower thoracic regions border zones of anterior feeding vessels (those that comprise the unpaired anterior spinal artery) ASA d. Sulcal arteries from the ASA supply the ventral horns; circumferential arteries from the posterior paired spinal arteries and the circumferential branches of the ASA supply the lateral components of the cord. The internal spinal cord watershed is the corticospinal tracts, the border zone between the sulcal and circumferential arteries. Paired dorsal spinal arteries supply the posterior columns
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e. Clinical Sequelae: 1. Spinal cord hypotensive damage is unusual as the cord is perfused at a much lower pressure than the cerebral circulation (approximately 60 mg Hg) 2. Ischemic injury involves the anterior 2/3 of the cord 3. Flaccid paralysis of the lower extremities is noted early; spasticity supervene: a. Loss of bowel and bladder continence b. Sensory level to temperature and pin prick at lower thoracic levels c. Atrophy and fasciculation of the legs/supervenes 4. Rare acute rigidity: a. Renshaw cell involvement b. Loss of glycine spinal cord inhibition
Prognostic Indicators In Patients that Have Suffered Ischemic-Hypoxic Injury
A. Early (minutes to 6 hours) Vital signs 1. Blood pressure a. Severe hypertension 1. Increased ICP 2. Normal cardiac function b. Profound hypotension 1. Severe cardiac damage 2. Vasomotor center damage (brainstem) c. Fluctuating blood pressure 1. Vasomotor center or connections are damaged (dorsolateral medulla) 2. Autonomic disruption (posterior hypothalamus afferents to inter mediolateral column of the spinal cord) d. Herniation 1. Hypertension to sudden hypotension a. Disruption of the vasomotor center and its connections in the dorsolateral medulla 2. Pulse a. Regular full slow pulse (50–60/min) 1. Kocher–Cushing reflux of ICP b. Thready rapid pulse (120 minute) 1. Cerebral herniation 2. Cardiac failure 3. Disruption of vasomotor center and its connections at a brainstem level 3. Respiratory pattern by CNS Level a. Cheyne’s–Stoke-basal ganglia/thalamic b. Periodic breathing-BG/thalamic c. Central neurogenic-hyperventilation-midbrain a. Acidosis b. Low pO2 c. Uninhibited Kölliker–Fuchs nucleus 1) Pneumotaxic center d. Apneic-pons (grave sign)
e. Cluster-medullary f. Ataxic-medullary g. Biot’s – medullary (couplet breathing) 4. Temperature General rule is that temperatures above 105 degree F◦ are central rather than from sepsis
Hyperthermia
a. Anterior hypothalamic damage b. Drugs: D2 (dopamine receptor D2 agonists or their sudden withdrawal) agonists, INH cocaine, amphetamine, phenothiazine (rare) c. Blood in the 3rd ventricle
Hypothermia
a. 92–93 degree F◦ (posterior hypothalamic damage) 1. Hypothyroidism; pan hypopituitarism 2. Drugs (phenothiazine based) b. 97–98 degrees 1. Endocrine failure 3. Liver and renal failure 2. Hypoglycemia 4. Phenobarbital Level of Consciousness
Profound coma implies damage to the lateral medullary reticular formation, the dorsal pontine tegmentorum periaquaductal grey of the midbrain, intralaminar nuclei of the thalamus or bilateral cerebral cortex. The brainstem is much less vulnerable to hypoperfusion and anoxia than the cortex and therefore severe brainstem dysfunction implies hemispheric damage with a poor prognosis for a good functional recovery. A patient who is fully alert and awake 6 hours after a cardiac arrest or hypoxic-ischemic event improves rapidly over twelve hours and has a good prognosis. Twenty four hours to alertness may be a very important prognostic assessment time. Levels to be assessed are: 1. Fully alert 4. Stuporous 2. Lethargic 5. Comatose 3. Obtunded
Brainstem Reflex Assessment at 6 hours
1. Gag reflex – IX, X (medulla) 2. Corneal – V – pons 3. Vestibuli ocular reflexes (VOR) a. VIII nerve b. Medial longitudinal fasciculus c. VI and III nerve 4. Pupils
Chapter 6. Chronic Small Vessel Disease
1. Dilate to 4–5 mm after 3–4 minutes of cardio-pulmonary arrest a. Rule out atropine or sympathomimetics during resuscitation 2. Cortical or pretectal level a. Non-reactive to light 3. 3 mm and non-reactive to light or noxious stimuli a. Midbrain b. cadaveric 4. 2–3 mm a. Reactive to light b. Thalamic basal ganglia level 5. 0.5 mm a. Pontine level b. Reactive to light 6. 1 mm a. Medullary level b. Sympathetically denervated R/O narcotics 1) Demerol may not affect pupils. 1/3 of the time it does. R/O drugs with parasympathomimetic action 5. Persistent pupillary dilatation poor prognostic indicator. Return of brainstem reflexes early is a good prognostic sign.
Evoked and Spontaneous Limb Movements
1. Spontaneous limb movement – good prognostic sign 2. Evoked decerebration and decortication – poor prognostic indicator 3. Myoclonus: a. Persistent and stimulus sensitive – poor prognostic sign 1. Loss of cortical inhibition 2. Damage to the nucleus gigantiocellularis of the brainstem 4. Seizure a. First 24 hours not prognostic b. Status epilepticus – poor prognostic sign at anytime after an ictus Late Prognostic Signs > 24 hours
Good 1. Awake and alert 2. Return of brainstem reflexes 3. Eye opening with ocular fixation reflexes 4. noxious stimuli evoke withdrawal reflexes Bad 1. Persistent depressed level of consciousness 2. Absent brainstem reflexes 3. Noxious stimulation evoke decortication or decerebration 4. Eyes open with: a. Roving eye movements b. Uninhibited doll’s eye maneuver c. Persistent vertical ocular deviation
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5. Spontaneous and evoked myoclonus 6. Status epilepticus 7. Persistently dilated pupils Laboratory Evaluation
1. MRI: a. Watershed infarcts of cortical and deep territories b. Cortical infarcts c. Blurring of the grey white junction d. Obliteration of the perimesencephalic cisterns with midbrain compression e. T2 weighted signal abnormalities of laminar necrosis 2. EEG a. Diffuse slowing in the delta and theta range 1. All survivors at some point b. Periodic lateralizing epileptiform discharge 1. Isolated areas of cortex c. Epileptiform activity d. Alpha coma (bad prognostic sign) 1. 9–12 cycles/second 2. Transitory 3. Frontal central parietal rather than occipital distribution 4. Does not vary with external stimuli 3. Brain Death a. Absence of intracranial circulation by angiography, Doppler or SPECT
Chapter 6 Chronic Small Vessel Disease Poorly controlled hypertension and diabetes are associated with small vessel disease both by MRI and neuropathologically. The aging process itself and chronic migraine also are associated with probable microinfarctions. CADASIL, Binswanger’s Disease and amyloid angiopathy are well delineated syndromes associated with small vessel disease. Multiple small vessel infarction is associated with a subcortical dementia characterized by apraxia and slowness of information processing. Pseudobulbar palsy and spasticity are common concomitant features. Congophilic angiopathy is usually differentiated from just small vessel infarction by superficial cortical hemorrhages. Binswanger’s Disease frequently is preceded by severe uncontrolled hypertension and is posterior periventricular predominant. Migraine most frequently presents with the T2 weighted lesions rarely associated with neurological deficit. CADASIL is associated with severe migraine and early onset dementia. 1. Most patients with lacunar infarction suffer more than one lacune a. Multiple penetrating arteries are involved
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2. Extensive lacunar infarction a. Cystic lesions of the basal ganglia, thalamus, internal capsule and pons known as “état lacunaire.” 3. Traditional clinical feature of “état lacunaire” a. Pseudobulbar palsy 1. Emotional dyscontrol; “laughter without mirth”, “crying without tears” inappropriate to the patients environment 2. Difficulty with swallowing combined with hyperactive gag reflex 3. Subcortical dementia 4. Rigidity 5. Cautious small stepped gait (Well’s dementia gait) 6. Bilateral Babinski signs b. Mild focal motor or sensory signs 4. Evolving concepts: a. Many patients with multiple lacunes are asymptomatic (common) b. Severe generalized while matter disease: 1. Associated with subcortical dementia 2. Spasticity c. Ventriculomegaly (ex vacuo) d. New concept: 1. Lacunes, white matter gliosis and atrophy exemplified by ventriculomegaly occur concomitantly and constitute a chronic brain micro vasculopathy
a. Fibrous thickening b. Hyaline degeneration of the intima c. Reduplication of the internal elastic lamina d. PAS positive material deposition in the vessel 2. Clinical features: a. Onset in the early 40’s b. Migraine headaches c. Chromosome 19q 12 d. Dementia; abulia; behavioral disturbances 1. subcortical > cortical type e. Lacunar strokes f. Pseudobulbar palsy g. Long periods of clinical stability 3. MRI evaluation a. Periventricular T2 -weighted lesions are prominent b. Patchy areas of myelin abnormality
Amyloid Angiopathy
1. Clinical features: a. Subcortical lobar hemorrhages b. Multiple lobes c. Rare TIA during the course of the illness d. Seizures more common than with HCVD
MRI White Matter Lesions from Microangiopathy Chronic White Matter Changes of Micro Vasculopathy (Binswanger’s Disease)
1. Occipital lobes and periventricular white matter involvement are predominant location a. Anterior ventricles are affected. The lesions are close to the ependymal surface 2. Patchy demyelination that may be confluent 3. Cerebellar white matter affected 4. Thin corpus callosum 5. Cortex is relatively spared
1. Vascular stripe a. Periventricular internal border zone 1. Between arterial penetrating vessel from superficial pial arteries and ascending lenticulostriate arteries 2. Ventricular caps of increased T2 -weighted lesions a. Anterior and occipital horns of the lateral ventricles 3. Periventricular rims a. Gliosis possibly secondary to trans ependymal CSF flow (approximately 30% of all CSF bulk flow) 4. Centrum semiovale and corona radiata lesions a. Multiple and discrete b. Rarely syncytial
Pathology
1. Islands of pallid decreased myelinization surrounded by normal myelin a. Necrosis and cavitation occur in severe cases 2. penetrating arteries are thickened and hyalinized a. Usually patent b. Rare amyloid deposition in vessels of hemisphere, cortex and leptomeninges
CADASIL (Cerebral AD Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
1. Pathology of penetrating arteries:
Epidemiology of Hemorrhagic Vascular Disease
Hypertension is the major cause of intracranial hemorrhage. The age of the patient and underlying medical condition point to the specific etiology of hemorrhagic vascular disease. Spontaneous intracranial and subarachnoid hemorrhage cause approximately 10% of strokes. In patients less than 40 years of age, vascular malformations, aneurysms, cavernous angioma, illicit drugs and head trauma are the usual causes. In elderly patients, congophilic angiopathy accounts for approximately 10% of hemorrhages. Approximately 10% of patients treated with fibrinolytic agents after myocardial infarction bleed. Approximately 5–10% of patients on warfarin or
Chapter 7. Hemorrhagic Vascular Disease
heparin bleed at some point during their therapy. The rate of ICH on anticoagulation is approximately 0.3% per year. Evidence of prior vascular disease is common as patients with ICH have T2 weighted hyper intensities in cerebral white matter, lacunes and old infarction 68% of the time. There is a correlation of spontaneous ICH with small chronic hemorrhage and ischemic lesions in elderly patients.
Chapter 7 Hemorrhagic Vascular Disease The major categories of hemorrhagic vascular disease are: 1. Hypertension 2. Aneurysm, arteriovenous malformation, venous malformation, cavernous hemangioma 3. Medical causes of platelet or clotting factor dysfunction 4. Hemorrhagic transformation of ischemic stroke 5. Anticoagulation 6. Drug abuse (methamphetamine, cocaine, PPA) 7. Thrombolytic agents 8. Congophilic angiopathy (CCA) 9. Cold exposure 10. Post carotid endarterectomy syndrome 11. Severe migraine 12. Tumor 13. Surgery 14. Moyamoya disease 15. Trauma 16. Alcohol
Hypertensive Hemorrhage
Hypertensive hemorrhage occurs in very specific places the most common of which are: a. Basal ganglia – 60% (caudate 10%; putamen 50%; GP1 40%) b. Thalamus – 20% c. Cerebellum – 15% d. Pons – 5% e. Lobar – 10% f. Pontine – 5% g. Medulla – rare <1% h. Midbrain – rare <1% If hemorrhages are not found in these locations, they are most likely caused by systemic illness, congenital vascular anomalies, anticoagulation or drugs.
Clinical Manifestations of Intraparenchymal Hemorrhage
The onset of intraparenchymal hemorrhage is most often during wakefulness as a patient pursues the usual activities of
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daily living. Maneuvers that cause a sudden rise in blood pressure such as heavy lifting, coitus, prolonged vomiting, coughing or straining at stool have been noted to cause hemorrhage with increased frequency. Unusual causes of hemorrhage are related to specific circumstances. Approximately 30% of ICH from aneurysm, AVM, and cavernous angioma occur during sleep. Most patients when first examined are alert (50%) with the remaining being lethargic (25%), stuporous or comatose (25%). The onset is gradual over minutes to hours and the neurologic deficit is steadily progressive. CT and MRI serial evaluations have demonstrated that expansion occurs in the first 6 hours in approximately 20% of patients while 15% expand during the next 6–12 hours and 6% between 6–24 hours. Expansion may be dramatic. In patients who suffer hemorrhage from a bleeding diathesis expansion may occur insidiously over days. Focal deficits and consciousness are preserved at the ictus. Headache and vomiting may be absent. In subarachnoid hemorrhage, headache is severe, reaches maximum intensity almost instantly and focal neurologic signs are minimal. Loss of consciousness in SAH is much more frequent at the ictus than that which occurs with intraparenchymal hemorrhage. Embolism produces the greatest neurologic deficit at onset, is accompanied by a higher percentage of seizures than ICH and a lesser degree of headache. Patients who suffer emboli, particularly to the stem of the left MCA appear stunned. Ischemic vascular disease is more frequent during sleep or the early morning and is accompanied frequently with deficits of a cortical nature such as aphasia or denial of contralateral space. Headache is common in ischemic disease with posterior circulation ischemia causing it more frequently than that from the anterior circulation. Rarely is it a predominant feature. Headache from intraparenchymal lesions occurs frequently as the hematoma develops and stretches the overlying dura, displaces the sinuses and major blood vessels at the base of the brain or spills into the subarachnoid space. Early in the course of the hemorrhage, the stretched dura may project pain to the overlying skull and scalp but most often the headache is projected frontally. The anterior and middle fossa dura and the forehead are innervated by V1 (somatic visceral convergence) and thus lesions in these fossa project to somatic representations of V1. Displacement of the posterior 1/3 of the sagittal sinus may also cause frontal headache. The dura of the posterior fossa is innervated by the posterior roots of C1–C2 and cranial nerves IX and X. Hematomas in the posterior fossa usually project pain to the basiocciput, posterior cervical areas or the trapezius ridge. They may project to the brow, the somatic representation of C2. Displacement of the tentorium and irritation of it’s under surface (innervated by C1–C2, IX and X) may cause pain in the inner ear. The upper leaflet of the tentorium is innervated by V1. Many patients who have suffered an intraparenchymal bleed are too lethargic to describe their headache accurately. Headache is most
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common with lobar and cerebellar hematomas due to their close approximation to the dura and may be accompanied by signs of meningeal irritation. Headache increases with hematoma enlargement and is associated with vomiting and deterioration of the level of consciousness. Head tilt to the side of the hematoma, unilateral forced eye closure (ipsilateral to the side of the hematoma) and C2 headache are most suggestive of a cerebellar hemorrhage. Severe neck stiffness, photophobia, sore eyes, Brudzinski and Kerning’s signs suggest caudate hemorrhage with direct rupture into the ventricular system. Hyperthermia, rarely greater than 103◦ may be present. Thalamic and cerebellar hemorrhage may also be associated with early ventricular extension. Larger putaminal hemorrhages rarely rupture into the ventricular system at onset. The focal deficits and topography of each type of hemorrhage will be described in detail. Specific neurological deficits suggest a characteristic hemorrhage: (1) a deeply comatose patient with head and eyes deviated to the side of the lesion, a flaccid hemiparesis and hemisensory defect with periodic breathing is characteristic of a deep pallidal hemorrhage; (2) inability to walk, dysarthria, nystagmus with quadriparesis not plegia suggests a cerebellar hemorrhage; (3) a patient whose eyes are down and in with a greater sensory than motor deficit is sentinel for a thalamic bleed; (4) an elderly patient with arm, face weakness who has suffered a seizure suggests a lobar congophilic hemorrhage. Vomiting and nausea may occur at the ictus of an intraparenchymal hemorrhage due to the sudden increase of ICP that is transmitted to the mechanosensitive emetic center of the floor of the IV ventricle or distortion of the IV ventricle itself. Vomiting stops as pressure is relieved by displacement of CSF into the spinal subarachnoid space, overbreathing that effects a decrease of pCO2 and consequent reduction of cerebral blood flow as well as intracranial shifts of brain parenchyma. As the hematoma expands further, vomiting and nausea return due to exhaustion of compensatory mechanisms. Persistent vomiting out of proportion to dizziness is suggestive of an ischemic lesion of the brainstem. Vomiting with change of head position is characteristic of a mass in the IVth ventricle. Inability to vomit in the face of a strong urge to do so is characteristic of an intrinsic medullary lesion. A smooth gradual deterioration of neurological function over minutes to hours with concomitant headache and vomiting is most consistent with supratentorial intraparenchymal hemorrhage. Headaches are most often seen with larger hemorrhages whereas deep parenchymal lesions may be asymptomatic. Approximately 30% of patients suffer headaches at the ictus, another 20% develop it during evolution of their neurologic deficits and up to 40% may have no headache. Many of the latter patients are lethargic or obtunded at the time of evaluation. Lobar and cerebellar hemorrhages have the highest incidence of headaches due to their proximity to the meninges. Patients with cerebellar hemorrhage vomit
shortly after the ictus. Approximately 50% of patients with posterior circulation headaches vomit. Ischemia in this distribution causes vomiting in 1/3 of patients which tends to be more persistent and is not associated with obtundation and stupor. Patients with migraine have severe persistent vomiting accompanied by dizziness and vertigo but minimal focal deficits and no depression of consciousness. Bickerstaff’s migraine (vasospasm of the vertebrobasilar arteries) may be associated with transient loss of consciousness and there have been reports of migraine patients who become comatose. Seizures occur in approximately 15% of patients who suffer an intraparenchymal bleed. They are most common in lobar hemorrhages which occur at the grey-white junction and excite the overlying cerebral cortex. Seizures are rare in putaminal hemorrhages. They suggest an underlying cavernous angioma, arteriovenous malformation or transformed embolic stroke. A 10 ml hemorrhage is minimal, 45 ml is severe and greater than 60 ml is usually fatal. Topographical Syndromes
Caudate Hemorrhage (Approximately 7% of ICH)
1. Medial hemorrhages: a. Blood dissects into the ipsilateral frontal horn b. Dense hemorrhage is noted at the caudate head c. Ventricular dilatation occurs ipsilaterally > contralaterally Clinical Features: 1. Small hemorrhage: no prominent motor, sensory or visual loss 2. Symptoms: mimic intraventricular bleed or SAH: neck stiffness, severe headache, nausea and vomiting, decreased level of consciousness Lateral Caudate Hemorrhage
1. Larger than medial hemorrhage 2. Spreads laterally or posterolaterally into the putamen or anterior or posterior limb of the internal capsule Clinical Features
a. Headache, vomiting, decreased level of consciousness b. Hemiparesis, hemisensory loss, ipsilateral conjugate deviation of the eyes with inability to look to the contralateral side (may be dolled across the midline in 12 to 24 hours); in general, minimal sensory loss c. Less severe and transient signs if the hemorrhage is limited to the internal capsule d. If blood spreads inferiorly; Horner’s syndrome 1) Horner’s syndrome (ipsilaterally) e. R caudate hemorrhage: neglect or mania f. L caudate hemorrhage: aphasia, confusional state, disorientation g. Memory loss (if hemorrhage involves internal capsule and AV nucleus of the thalamus
Chapter 7. Hemorrhagic Vascular Disease Differential Diagnosis
1. HCVD 2. Infarct with hemorrhagic transformation (lenticulostriate, recurrent artery of Heubner) 3. Arteriovenous malformation 4. Carotid aneurysm rupture 5. Moyamoya disease (with hemorrhage) 6. Ependymal vascular malformation Striatocapsular Hemorrhage
Clinical features: 1. Mild dysarthria 2. Contralateral hemiparesis 3. Contralateral hemisensory deficit 4. Lacunar type syndrome Anterior type: 1. 11%; Heubner’s artery territory 2. Small caudate hematoma 3. Ruptures into lateral ventricle 4. Clinical presentation: a. Severe headache (similar to subarachnoid hemorrhage) b. Contralateral hemiparesis <50% c. Acute confusion; abulia; (approximately one week) d. DH: transcortical motor aphasia (transient) Middle type: 1. Medial lenticulostriate artery territory 2. <10%; moderate in size (<30 cc; spreads anterolaterally) 3. Primary involvement globus pallidus and medial putamen 4. Conjugate deviation of the eyes to the side of the lesion 5. Contralateral hemiparesis (mild to moderate) 6. Anomia; global aphasia (transient) Posteromedial type 1. Anterior choroidal artery territory 2. 4% of striatocapsular hemorrhage 3. Small hematoma in posterior limb of internal capsule (anterior ½) 4. Spreads rostrally; pressure on medial putamen or lateral thalamus Posterolateral type: 1. Posterior medial branches of the lateral lenticulostriate arteries territory 2. Approximately 33% of striatocapsular hemorrhage 3. Areas affected a. Posterior 50% of the putamen; moderate in size (35 cc); extend often to the anterior putamen b. Posterior limb of the internal capsule (retrolenticular portion); rupture into anterior horn of the lateral ventricle 4. Clinical presentation: a. Impaired consciousness b. Cheyne–Stokes or periotic respiration c. 2–3 mm reactive pupils
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d. Severe flaccid contralateral hemiparesis 1) Arm, leg, face, equally involved e. Dominant hemisphere 1) Anterior > posterior aphasia f. Non-dominant hemisphere 1) Severe visuospatial neglect Lateral type: 1. Lateral branches of the lateral lenticulostriate arteries 2. Approximately 20% of striatocapsular hemorrhage 3. Areas involved: a. Elliptical hematoma between the putamen and insular cortex b. Often ruptures into the lateral ventricle 4. Clinical features a. Contralateral hemiparesis b. Neglect for contralateral space (NDH) c. Language dysfunction (DH) Massive Hemorrhage
1. Approximately 25% of lenticulo striato hemorrhage 2. Entire striatocapsular territory involved 3. Clinical features a. Severe flaccid contralateral hemiparesis 1) Arm, face, leg equally involved b. Lethargy to coma c. Ipsilateral conjugate eye variation 1) Wrong way eyes observed in a percentage of patients d. Poor prognosis Putaminal Hemorrhage
General characteristics: 1. Most common location for basal ganglia hemorrhage in hypertensive patients (40%) 2. Largest hemorrhages involve: a. Medial and most anterior portion of the posterior putamen b. Anterior 2/3 of the posterior limb of the internal capsule c. Putative mechanism: rupture of Charcot–Bouchard aneurysms of the large lateral lenticulostriate arteries Clinical Manifestations 1. Abrupt onset of neurologic deficit while awake 2. Approximately 30% have headache at onset and 20% more develop it as the process evolves 3. Vital signs: a. Level of consciousness: 1) 50% alert at presentation; others obtunded to comatose 2) Blood pressure elevated: 220–240 to 110–140 mmHg 3) Pulse rate tends to be slow and full at 60–70/minute, a rapid thready pulse appears with herniation
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4.
5.
6.
7.
8.
9.
SECTION I. Vascular Disease
4) Respiratory pattern a) Most often periodic respiration, inspiratory and expiratory build up and decline with irregular apneic periods. The longer the apneic periods the graver the prognosis. Rarely Cheyne–Stokes pattern. 5) Pupils: a) At presentation are usually diencephalic at 2– 3 mm and reactive to light, change with evolution of the hematoma and consequent herniation Posture: a. Early at presentation: 1) Pronated arm with early cortical thumb (adducted) contralateral to the lesion; externally rotated leg contralaterally 2) Right-sided lesion (a) Patient angled in bed neglecting contralateral space (nondominant hemisphere) Mental status: (1) Left sided lesion (dominant hemisphere) a. Fluent aphasia with intact repetition unless the arcuate fasciculus is disrupted right sided lesion (2) Non-dominant hemisphere a. Visual neglect for left space b. Motor impersistence c. Constructional dyspraxia Cranial nerve examination: a. Contralateral VII paralysis b. Head deviated to the side of the lesion c. Eyes slightly below the midline if the midbrain oculomotor center for upgaze riMLF is compressed 1) Conjugate deviation of the eyes to the side of the lesion 2) If the patient is alert pupils may be normal; as obtundation supervenes pupils are diencephalic at 2– 3 mm Motor examination: a. Flaccid contralateral hemiparesis 1. Internal capsule involvement with brain shock 2. More anteriorly in the posterior limb faciobrachial paresis; leg less involved (topographically and bilaterally innervated) 3. Rarely patients may have contralateral increased tone if the putamen is primarily involved 4. Rarely; ipsilateral adventitial movement occur (descending pyramidal or extrapyramidal pathways are stimulated) 5. Motor impersistence with right sided lesions Sensory examination: a. Contralateral hemisensory deficit to all modalities b. Neglect of left sided space with right sided lesions Reflexes: a. Depressed on the paretic side b. Positive Babinski or intermediate toe on the paretic side; bilateral Babinski signs if there is severe pressure
Transtentorial Herniation
1. Anatomy: a. Compression and torque of the midbrain at the level of the tentorium 1) Obliterated ambient cisterns 2) Trapped contralateral temporal horn 3) Rupture of midline penetrating arteries of the pons, midbrain and thalamus (Duret’s hemorrhage) 4) Compression and infarction of the PCA under the ipsilateral tentorium 5) Lateral pineal shift of 10 mm 6) Downward pineal shift of 7 mm Clinical Manifestations
1. Vital signs: a. Stupor to coma b. Blood pressure of 90–60 mm/Hg as herniation occurs c. Central neurogenic hyperventilation (20–40 breaths/ minute) d. Thready pulse at 100–120 beats/minute e. Temperature 103–105◦ Fahrenheit dependent on presence of intraventricular blood or posterior hypothalamic damage 2. Cranial nerve impairment: a. Paralyzed horizontal gaze; eyes below the midline b. Ipsilateral pupil smaller then dilates; may become oval as III nerve is compressed under P-COM 3. Posture and reflexes: a. Bilateral decerebrate posture b. Bilateral Babinski response Anterior Putaminal Hemorrhage
1. Anatomy: a. Anterior putamen b. Anterior limb of internal capsule 2. Clinical characteristics a. Mild hemiparesis b. No sensory loss Posterior Putaminal Hemorrhage
1. Anatomy a. Involves posterior 1/3 of the internal capsule b. Extreme posterior extension of the putamen 2. Clinical manifestation a. Hemisensory loss greater than hemiparesis b. Inferior quadrantanopia or hemianopia with left dominant posterior putaminal hemorrhage 1) Wernicke’s type aphasia: a) If the hemorrhage extends into the isthmus of the temporal lobe b) Undercuts or involves posterior speech areas. Inferior temporal gyrus thought to be involved in semantic aphasia. Dissection of blood into periventricular white matter
Chapter 7. Hemorrhagic Vascular Disease Rare Presentations of Putaminal Hemorrhage
1. Pure motor hemiplegia 3. Hemiballism 2. Hemichorea 4. Sensorimotor stroke Asymptomatic Putaminal Hemorrhage
1. 1.5% of stroke patients (hemorrhagic transformation) 2. 9.5% of putaminal hemorrhage Globus Pallidus Hemorrhage
1. Medial lenticulostriate artery territory 2. Hypertensive patient with Cushing reflex a. BP 220/120 – 240/120–130 mmHg b. Approximately 50% obtunded within minutes to hours after ictus. Progressive deterioration of level of consciousness 3. Periodic or Cheyne’s-Stokes respiration 4. Pupils 2–3 mm poorly reactive to light 5. Pulse rate of 50–60 beats/minute full at onset 6. Eyes conjugately deviated below the horizontal 5–10◦ 7. Head and eyes deviated to the side of the lesions 8. Dense contralateral hemiparesis: arm, face, and leg relatively equally involved; flaccid tone (destruction of medial components of posterior limb of the internal capsule) 9. Dense hemisensory deficit to all modalities (disruption of medial portion of the posterior limb of the internal capsule); thalamic projections 10. Depressed reflexes contralaterally; may be increased ipsilaterally 11. Contra or bilateral Babinski’s signs 12. Progression to decerebrate rigidity and central herniation Thalamic Hemorrhage
1. General characteristic a. 4 major categories dependent on involved vascular territories 1) Thalamogeniculate artery (P1) 2) Thalamoperforate or thalamic subthalamic perforate artery (P1) 3) Tuberothalamic (polar arteries) a) originate from the P-COM 4) Lateral posterior choroidal artery (P3) b. Most hemorrhages are posterior to descending pyramidal tracts 1) Sensory loss greater than motor 2. Sentinel clinical characteristics: a. Ocular manifestations b. Thalamic sensory loss c. Thalamic aphasia d. Behavioral or cognitive deficits e. Thalamic motor abnormalities Ocular Clinical Findings:
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1. Paralysis of upgaze (pressure at the level of the superior colliculus, oculomotor center for upgaze the ri MLF (rostral interstitial nucleus of the medial longitudinal fasciculus) 2. Eyes “down” and “in” in primary gaze (as if looking at the tip of the nose) 3. Vertical skew deviation a. Eyes are down on the side of the lesion b. Abnormal displacement is constant in all fields of gaze 4. Disconjugate gaze: a. Limited abduction (pseudo VI nerve palsy) b. Visual fixation from the adducted eye c. Increased convergence vectors neutralize abduction (visual fibers descend into the anterior medial thalamus) and cause eyes to look down and in 5. Pupils: a. 2–3 mm poorly responsive to light b. Afferent arc disrupted 6. Hemorrhage may extend into: a. Diencephalic mesencephalic junction b. Quadrigeminal plate 7. Wrong way eyes Thalamic sensory loss: 1. All primary modalities affected including vibration: a. Rarely also occurs with lesion of the dorsal column nuclei b. May split the frontal bone of the forehead 2. Patient aware of a line that bisects the body: a. Bilateral sensory loss around the umbilicus b. 20% of patients describe the quality as numb or heavy; 80% describe active paresthesias, formication or burning (VPL) c. May have bilateral intraoral numbness or sensory loss (VPM) d. Tips of all fingers may be numb (VPI as fibers destined for VPL are separated here) e. After 6 weeks to 3 months Déjérine Roussy syndrome may appear: 1) Decreased primary modality sensation in the involved area 2) Static and dynamic mechano allodynia of the involved area 3) Thermal hyperalgesia particularly to cold in some component of the area of sensory loss 4) Hyperpathia in some component of the area of sensory loss: a) Pain threshold increased b) Once threshold is exceeded in pain reaches maximum intensity too rapidly c) Pain is overwhelmingly severe d) Poorly localized with a deep visceral quality e) Not stimulus bound (continues after the stimulus is withdrawn) f) Occurs spontaneously
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Thalamic aphasia: 1. Nuclear involvement a. Anterior ventral c. Pulvinar b. Dorsomedial 2. Clinical characteristics: a. Normal conversation early b. Fluent aphasia c. Jargon intrusions d. Relatively good comprehension e. Repeat or duplicate words or syllables at the ends of words in spoken and written language f. Paraphasic errors g. Anomia h. Perseveration Behavioral and cognitive dysfunction: 1. Anterior ventral nuclear lesion a. Abulia b. Waxing and waning levels of consciousness throughout the day 2. Dorsomedial nuclear lesion a. Amnestic syndrome c.Visual spatial dysfunction b. Anosognosia Thalamic motor dysfunction 1. Thalamic drift: prominent metacarpal pharyngeal flexion with the thumb adducted into the palm 2. Ataxia of stance (area x involved) 3. Mild limb ataxia (disruption of frontal cortical – thalamic distributed network); Brun’s ataxia variant 4. Contralateral choreatic or dystonic movements 5. Contralateral severely abnormal posture (patient lying on an arm behind his back) Topographic Hemorrhages of the Thalamus
Posterolateral (thalamogeniculate artery territory) 1. Largest and most common thalamic hemorrhage 2. Tthalamic sensory and motor involvement 3. Internal capsule may be compressed with consequent sensorimotor deficits 4. Leg sensation and eye movements transiently and minimally involved Anterior or anterior lateral hemorrhage: 1. Tuberothalamic (polar artery) territory 2. Apathy 3. Abulia 4. Hypersomnolence 5. Waxing and waning level of consciousness 6. Thalamic aphasia Posteromedial (thalamoperforate or thalamic subthalamicthalamoperforate arteries) 1. Thalamic eye signs: a. Pupillary involvement b. Vertical gaze dysfunction
2. 3. 4. 5.
Impaired consciousness Ruptures into the III ventricle Compresses the diencephalic mesencephalic junction Early hydrocephalus
Posterior dorsal lesions: 1. Posterior choroidal artery territory 2. Pulvinar involved 3. Aphasia 4. Minimal transient sensorimotor involvement (overlap blood supply to posterior limb of the internal capsule) 5. Rare: neglect, apraxia, amnesia Lobar Hemorrhage
General characteristics: 1. 10% of ICH; higher frequency in patients <45 years 2. Develop beneath the grey white junction 3. After absorption of blood products there is a “slit like scar” 4. Expand linearly along white matter pathways 5. Undercuts the overlying cerebral cortex a. Epileptic genic b. 15–30% seizures at onset 6. Parietal and occipital lobes more frequently affected than frontal lobes Clinical signs and symptoms of lobar hemorrhage: 1. Sudden onset during activity 2. Headache 3. Vomiting in 30–40% during the first hour 4. Seizures 15–30% at onset, focal and status epilepticus (frontal lobe most common) 5. 5–20% present in coma Differential diagnosis of lobar hemorrhage 1. HCVD (patients <45 years) 2. Cerebral amyloid angiopathy (>65 years) 3. Arteriovenous malformation (<30 years) 4. Cavernous angioma 5. Coagulopathy 6. Illicit drug use 7. Trauma 8. Aneurysm Frontal Hematoma
General Clinical Manifestation 1. Headache – 80% 2. Vomiting – 80% 3. Seizure – 25–30% 4. Impaired consciousness (lethargy to obtundation) – 50% 5. Gaze preference 30–40% Topographic Diagnosis of Frontal Hematoma
Dorsal anterior 1. Cognitive behavioral features a. Abulia
Chapter 7. Hemorrhagic Vascular Disease
2.
3.
4.
B.
C.
b. Initiate nothing c. If stimulated: 1) Short terse answers 2) Slow processing of information Frontal eye field involvement (area 8,10) a. Eyes conjugately deviated to the side of the lesion; may be dolled across the midline after 12–24 hours from the ictus Dorsolateral prefrontal cortex involvement (DLPC) a. Left sided executive frontal lobe dysfunction 1) Poor memory retrieval b. Right side (nondominant) 1) Disinhibition 2) Poor judgment 3) Witzelsucht (inappropriate jocularity) 4) bilateral lesions, bowel and bladder incontinence (second frontal gyrus) Area 4 involvement a. Brachiocephalic hemiparesis b. Head and eye deviation to the side of the lesion (if extends to area 8 and 10) c. Lesions above the frontal horn or the lateral ventricle 1) Frontal headache 2) Contralateral predominant leg weakness Inferior Frontal Hematoma 1. Below frontal horns of lateral ventricle 2. Impaired consciousness 3. Contralateral brachiocephalic hemiparesis and hemisensory loss 4. Rare presentation a. No motor or sensory loss b. Abulia Orbital Frontal Hematoma 1. Impaired consciousness 2. Agitated delirium 3. Most often etiology is head trauma a) Windshield injury in MVA b) Falls (associated basilar skull fracture) 4. Semantic language dysfunction 5. Autonomic dysregulation a) Cardiac arrhythmia (area 11,12) b) Hypertension
Paracentral Hematoma
1. Primary involvement of Brodmann’s area 4,3,1 and 2 2. Contralateral brachiocephalic motor and sensory deficits 3. Anterior (area 44) aphasia a. Transcortical motor b. Decreased ability to write out of proportion to weakness (Exner’s area 45) 4. Focal and generalized seizures 5. Lesion above the frontal horn a. Geadache (frontal and primarily ipsilateral) b. Contralateral leg weakness
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Differential Diagnosis of Frontal Hematoma
1. 2. 3. 4. 5. 6. 7. 8.
HCVD – 20% AVM – 25–30% Cavernous angioma – 25–30% Aneurysm – 25–30% Anticoagulation – 10% Congophilic angiopathy – 5–10% Trauma – 10% Illicit drug use – 10%
Parietal Hematoma
1. General manifestations: a. Unilateral headache 1) Temporoparietal early; then frontal projection b. Seizures (20–30% at onset) c. Contralateral cortical sensory loss d. Contralateral parietal motor dysfunction (loathness to move extremity) e. Neglect of the contralateral visual field Topographic Parietal Hemorrhage
1. Anterolateral parietal hemorrhage a. Parietal movement disorder 1) Updrift of the affected hand with “piano playing” fingers 2) Loathness to move 3) Sensory ataxia during all components of movement 4) Abnormal arm position at rest 5) Imprecise fine movement b. Noncongruent inferior quad anopsia in 50% of patients (lesion must extend greater than a depth of 1 cm) c. Posterior aphasia (dominant hemisphere) d. Neglect of contralateral space (nondominant hemisphere) 2. Anterior medial parietal hemorrhage a. Similar clinical syndrome to lateral hemorrhage b. Depressed consciousness c. May extend into the thalamus Large Posterior Parietal Hematoma
1. Seizure at onset a. Aura of contralateral spacial tilt 2. General deficit: a. Posture copy b. Two point discrimination c. Graphesthesia d. Stereognosis e. Localization of a body part or limb in space f. Extinction of double simultaneous stimulus (contralateral to the lesion) g. Alloesthesia h. Point localization
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Nondominant Parietal Hemisphere Hematoma
1. 2. 3. 4. 5. 6. 7. 8.
Constructional apraxia Dressing apraxia Posterior type of alien hand (NDH > DH) Contralateral spatial neglect Anosognosia Asomatognosia Geographical confusion (NDH > DH) Depression of opticokinetic nystagmus (eyes deviate to side of the lesion) 9. Geometric and colored patterns that move in contralateral visual field (NDH = DH) Dominant Left Parietal Lobe Hemorrhage
1. Transcortical sensory aphasia 2. Von Gerstmann syndrome components a. Right left confusion b. Finger agnosia c. Acalculia d. Dysgraphia e. Failure to cross the midline 3. Dysgraphia and dyslexia (area 37,40,41) 4. Alexia without agraphia (area 39,40) 5. Bilateral failure to localize body parts 6. Poor visual manual dexterity (5,7 projects to area 4) 7. Parietal motor dysfunction 8. Bilateral parietal hemorrhage a. Parietal avoidance behavior Left Inferior Parietal Hematoma
1. Deficits of reading, writing and calculation 2. Nominal aphasia (supramarginal gyrus)
a. Confusion without focal signs 4. Posterior left hematoma: a. Wernicke’s aphasia b. Right homonymous quadrantanopsia c. Minimal hemiparesis or hemisensory deficit 5. 20% of temporal lobe hematomas have seizure 6. Inferior basal temporal hematoma a. Blood in the basal cisterns or cortical sulci suggests AVM or aneurysm 7. Medial extension of temporal lob hematoma a. Basal ganglia internal capsule compression or destruction b. Contralateral hemiplegia and hemisensory deficit c. Wernicke’s or transcortical sensory aphasia d. Horizontal gaze palsy contralaterally e. Right temporal lobe hematoma with extension to the parietal lobe 1) Left sided spatial hemi inattention and neglect f. Partial III nerve paralysis 1) Poor pupillary light response 2) Partial III nerve paralysis (uncal entrapment of the nerve; compression under the posterior communicating artery) Occipital Lobe Hematoma
1. General characteristics a. Headache in or around the ipsilateral eye b. If visual fields’ deficit is present: (1) Patient is aware of visual loss but may ascribe it only to the contralateral temporal field (may miss ipsilateral nasal cut) c. Visual neglect of contralateral field if the hematoma extends into the parietal lobe d. Rare weakness
Right Inferior Parietal Hematoma
1. Constructional dyspraxia 2. Poor visual spatial relationships 3. Inability to draw or copy Temporal Hematoma
1. General characteristics: a. Agitation and/or delirium (R > L) b. Wernicke’s type aphasia (DH) c. Herniation with slight or without hemiparesis d. Insidious decline of consciousness followed by III nerve paralysis e. Headache 1) Preauricular 2) Periorbital 2. Left temporal lobe hematoma a. Fluent aphasia b. Anomia, paraphasic errors, poor comprehension 3. Right (nondominant) temporal hematoma
Medial Occipital Hemorrhage
1. Headache (C2 distribution or radiates to the ipsilateral eye) 2. Congruent homonymous hemianopia if above and below the calcarine fissure a. Dense b. Respects the midline 3. Visual field variants depend on topography a. Checkerboard deficit (lesions above and below calcarine sulcus) b. Superior or inferior quadrantanopsia c. Anterior lesions (spared temporal crescent) d. Occipital pole lesions (loss of macular vision) 4. No depression of consciousness 5. No memory loss 6. No weakness Lateral Occipital Hemorrhage
1. Headache at onset (similar to medial occipital lobe radiation)
Chapter 7. Hemorrhagic Vascular Disease
2. No visual field deficit 3. No sensorimotor or behavioral deficit 4. if extension to parietal lobe or medially: a. Depressed level of consciousness b. Contralateral neglect c. Agitation d. Congruent contralateral homonymous hemianopia Primary Intraventricular Hemorrhage
1. Differential diagnosis: a. Subependymal vascular malformation b. Cavernous angioma c. Dissection of caudate hematoma d. Angioma of the choroid plexus (children) e. Vertebral artery aneurysm (IV ventricle) Clinical Signs and Symptoms 1. Similar to subarachnoid hemorrhage a. Stiff neck d. Bilateral hyperreflexia b. Early vomiting e. Positive Babinski’s sign c. Lethargy Infratentorial Intraparenchymal Hemorrhage
Cerebellar Hemorrhage 1. 10% of intracranial hemorrhage 2. Anatomy a. Initiated in the area of the dentate nucleus b. At the level of the anastomosis of distal PICA and SCA c. Long perforating branches of the SCA may be involved d. Rarely: 1) Vermis hemorrhage: a) Medial branches of PICA and the SCA 2) Hemorrhage extension a) Ipsilateral hemisphere b) Opposite hemisphere or vermis c) Rarely to the brainstem d) Cerebellar peduncles with rupture into IVth ventricle Symptoms and Signs: 1. Early a. Inability to walk, rarely to sit or stand (pressure on descending pontine and middle cerebellar peduncle fibers) b. Falling to the side of the lesion c. Vomiting d. Headache (occipital, neck, C2 radiation) e. Dysarthria f. Rotary nystagmus (greater to the side of the lesion, occasionally gaze paretic to the opposite side); floccular nodular lobe involvement g. Rare loss of consciousness at the ictus Evolving Neurologic Signs: 1. VI nerve palsy (side of the lesion) a. Ipsilateral forced eye closure (to prevent diplopia)
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b. Head tilt (C2 root irritation) to the ipsilateral side 2. Smaller ipsilateral pupil 3. Failure to check greater than dysmetria or terminal 1/3 ataxic arm movement 4. Severe gait ataxia 5. Quadriparesis without quadriplegia 6. Increased lower extremity reflexes without Babinski’s signs Large Hemorrhage
1. Early brainstem compression: a. All signs and symptoms noted with smaller lesions but telescoped in time b. Stupor to coma c. Lateral gaze palsy (eyes deviated to side of the lesion) pressure on the para pontine reticular formation paralyzes contralateral conjugate gaze) d. Quadriparesis (basilar strokes there is severe quadriplegia) e. Bilateral Babinski’s signs f. Bilateral pontine pupils (<0.5 mm; reactive to light) g. Central neurogenic hyperventilation (CNH) Terminal Signs and Symptoms
1. Caudal cerebellum involved a. Medullary cardiovascular and respiratory centers involved 1) Respiratory arrest 3) Decerebration 2) Vasomotor collapse 4) Coma 2. Radiographic evaluation a. Obliteration of the cerebellopontine angle cisterns b. Displacement of the IV ventricle c. Hydrocephalus d. Rarely upward herniation with vermian compression of the collicular plate 1) Gaze palsy > pupillary defects e. Hydrocephalus of lateral and third ventricles Small Hemorrhages with Survival
a. Mild gait ataxia b. Rotary nystagmus c. Signs and symptoms of hydrocephalus 1. Dementia 2. Abulia 3. Gait ignition failure in addition to ataxia 4. Hyperreflexia legs > arms Lateral Cerebellar Hematoma
1. Cranial nerve involvement a. V,VI, VII and VIII b. Concomitant ataxia
SECTION I. Vascular Disease
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Cerebellar Vermian Hemorrhage
a. b. c. d. e. f.
Medial PICA and SCA vessels rupture Rare Severe headache Vomiting Quadriparesis Coma
Differential Diagnosis of Cerebellar Versus Basilar Artery Occlusion
Basilar Artery Occlusion 1. herald hemiplegia 2. quadriplegia 3. “ocular bobbing”
Cerebellar Hemorrhage 1. sudden onset 2. quadriparesis 3. rotary or horizontal nystagmus 4. horizontal gaze paralysis 4. conjugate deviation to the ipsilateral side 5. no cerebellar signs 5. failure to check > dysmetria 6. collapse 6. severe gait ataxia 7. Early Central Neurogenic 7. late CNH Hyperventilation 8. Early pupils changes 8. 1 mm pupils ipsi > <0.5 mm contralateral side 9. Early coma 9. late coma Differential Diagnosis of Cerebellar Hemorrhage
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
HCVD (PICA/SCA vessels; dentate nucleus) AV malformation Hemangioblastoma (lateral lobes) Cavernous angioma (may be multiple) Associated with Von Hippel Lindau (retinal and spinal angiomas) Metastasis Anticoagulation (INR > 5 on Coumadin) Ischemia transformation of infarct Trauma Venous malformation (usually don’t bleed)
Primary Pontine Hemorrhage
1. Location: a. Midventral pons (at the level of Vth nerve or junction of basis pontis and tegmentum) b. Oval shape: destroys the center of the ventral tegmentum and basis pontis c. Dissects: 1) Rostrally to the midbrain 2) Rarely to the medullary 3) Commonly into the IVth ventricle 4) Rarely ruptures through the pial surface with spread to the clivus 2. Caused by rupture of paramedian basilar penetrating artery Clinical Signs and Symptoms:
1. Decreased level of consciousness or coma early in the course 2. Hypertension early to vascular collapse during evolution (pressure on vasomotor center of lateral medulla) 3. Central neurogenic ventilation early (20–40 breaths/min to apneustic gasp prior to death) 4. Early hemiparesis 5. Quadriplegia with increased tone of all extremities during evolution 6. Headache (basiocciput) and vomiting (occasional) 7. Gradual asymmetric onset (occasional) 8. Asymmetric weakness of face and extremities 9. Abnormal movements: a. Shaking tremors (partial decerebration) b. Shivering and fasciculation (chest wall) c. Dystonic posture versus decerebration 10. Weakness or paralysis of the face, pharynx, palate and tongue 11. Ocular manifestations a. Pinpoint pupils <0.5 mm that are reactive to light (destruction of descending sympathetics vs activation of parasympathetics) b. Anisocoria c. Skew deviation (greater part of hemorrhage to the side of down eye) d. Bilateral paralysis of horizontal gaze 1) Destruction of the PPRF e. Ocular bobbing (eyes driven down and float up; vestibular tonic drive of upgaze mechanism) 1) May be unilateral f. Up-bobbing (may be unilateral) g. Ocular dipping (rapid down and upward movements), may be unilateral h. 1 and 1½ syndrome (ipsilateral destruction of the PPRF with concomitant destruction of the posterior crossing fibers of the MLF; patient can only abduct the contralateral eye) i. Pontine exotropia (lateral and down deviation of the contralateral eye), the only voluntary eye movement is contralateral abduction j. Posterior MLF syndrome (convergence is preserved) k. Paralysis of upgaze if there is midbrain extension and destruction of the riMLF Rarer Symptoms and Signs: 1. Prior to coma: a. Bilateral deafness (trapezoid body) b. Severe dizziness and vertigo c. Gustatory abnormalities (dysgeusia) d. Preservation of reflex horizontal gaze e. Locked in syndrome f. Hallucinations (between 3–50 days following the ictus) g. Hyperhidrosis h. Neurogenic bladder (destruction of the pontine micturition center)
Chapter 7. Hemorrhagic Vascular Disease
i. Hypo or hyperthermia (>105◦ Fahrenheit) Prognosis 1. Most often death in 24–48 hours, rarely a patient survives 7–10 days Unilateral Basilar or Tegment basilar Hemorrhage
A. Paramedian hemorrhage 1. Exclusively or predominantly on one side of the pons 2. Basotegmental hemorrhage is usually larger than those confined to one side of the pons 3. Small lateral basal hematomas a. Present as: 1) Pure motor hemiparesis 2) Ataxic hemiparesis 3) Clumsy hand dysarthria syndrome b. Dissection of lateral basal lesions into the tegmentum 1) Cranial nerve V, VI, VII deficit 2) Contralateral hemiparesis Differential Diagnostic Points Separating Hemorrhage Versus Lacunar Strokes 1. Occipital headache (hemorrhage) 2. Nausea or vomiting (hemorrhage) Paramedian Tegmental Hemorrhage
1. Position and higher sensory modality loss in the contralateral arm, face and leg 2. Ipsilateral 1½ syndrome 3. Motor dysfunction of the contralateral extremities a. Ataxia c. Dystonia b. Decerebration Lateral Pontine Tegmental Hemorrhage
1. Rupture of small penetrating vessels from long circumferential arteries 2. Pupillary defects: a. Anisocoria (smaller ipsilateral pupil, normal reactivity) 3. Ocular motility defects: 1. Paralysis of ipsilateral conjugate gaze 2. 1½ syndrome (if posterior MLF affected) 3. Intranuclear ophthalmoplegia (posterior type) 4. Ipsilateral VIth nerve deficit 5. Pontine exotropia 6. Ocular bobbing, dipping 4. Cranial nerve deficits: a. V, VI, VII 5. Moderate hemiparesis a. Bilateral weakness may occur at ictus; ipsilateral deficit clears b. Limb and truncal ataxia, ipsilateral > contralateral, may be bilateral
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Clinical Differential Points of Lateral vs Paramedian Lesion
1. Quadriparesis or quadriplegia (paramedian) 2. Contralateral hemisensory deficit: (lateral) a. Lemniscal modalities and spinothalamic deficits contralaterally 3. Rare findings: a. Decreased hearing (trapezoid body); paramedian lesion b. Dysarthria (posterior 1/3 of ventral tegmentum) c. Dysphagia (corticobulbar fibers X, XII) d. Decreased ipsilateral V (corresponding decrease of corneal reflex) e. Bilateral ptosis (rare) f. Convergent and divergent eye movements associated with: 1) Ipsilateral facial numbness 2) Contralateral sensory deficits 3) No motor abnormality Differential Diagnosis of Primary Pontine Hemorrhage
1. Hypertensive cardiovascular disease a. Middle aged patients 2. Vascular malformations (younger patients) a. Von Hippel Lindau disease b. Zona Bannayan syndrome c. Cobb’s syndrome d. Cavernous angioma e. Capillary telangiectasia (rarely bleed) 3. Anticoagulation 4. Coagulopathy 5. Trauma (associated with basilar skull fracture) Medullary Hemorrhage
1. Approximately 0.5–1% of ICH 2. Bleeding can occur from: a. Direct penetrating arteries of the distal vertebral artery b. Branch arterial rupture from PICA, AICA or anomalies of the vertebral artery (basilarization of the vertebral artery) 1) Hemorrhage may be involved with concomitant cerebellar infarct c. Dorsal branches of PICA 1) Supply the dorsal medulla 2) Concomitant cerebellar infarction if these arteries rupture Clinical Signs and Symptoms 1. Partial or complete lateral medullary syndrome depending on specific arterial rupture Secondary Pontine Hemorrhage
1. Diencephalic herniation a. Sretch and rupture of paramedian pontine penetrators from the basilar artery (Duret’s hemorrhage)
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b. Associated midline thalamic and midbrain hemorrhages 2. Blood dyscrasia 3. Coagulopathy 4. Sudden severe increase of intracranial pressure Prognostic Factors for Intraparenchymal Hemorrhage
1. Size and level of consciousness a. <10 cm3 – excellent prognosis b. <45 cm3 – fair to good prognosis c. >60 cm3 – poor prognosis d. >85 cm3 – death 2. Other predictors of prognosis a. intraventricular hemorrhage c. edema b. hydrocephalus 3. 30 day mortality – approximately 45% a. 50% of deaths occur in the first 48 hours 4. Pineal displacement laterally <10 mm, <5 mm ventrally good prognostic sign 5. Lower mortality in lobar ICH than deep hemispheric hemorrhage Neurologic Deterioration in Non-comatose Patients with Supratentorial Intra-Parenchymal Hemorrhage
1. Occurs in approximately 1/3 of patients 2. Greatest first hospital day 3. Neurologic deterioration: a. >45 ml (60%) b. 10 ml (19%) 4. 30 day mortality of patients with neurologic deterioration approximately 50%; 3% in those that are stable 5. Cerebral edema related to large established hemorrhages is the predominant cause of deterioration 6. Prognosis by size of hematoma volume a. 50 ml or > – 78% deteriorated b. 20–50 ml – 33% deteriorated c. <20 ml – 16% deteriorated 7. Hemorrhage growth 0.8–13% a. Progressive deterioration 1) Secondary to perifocal edema Major Diagnostic Features of Intraparenchymal Hemorrhage
1. Gradually progressive neurologic deficit a. Minutes to hours b. Headache and vomiting 2. Exceptions: severe early headache a. Caudate hemorrhage with intravascular extension b. Primary intraventricular hemorrhage c. Early severe motor deficits 1) GPe/GP1 hemorrhage 2) Large putaminal hemorrhage (usually mid portion) Imaging Analysis (CT/MRI) 1. Early < 24 hours a. regular and smooth
2. First 48 hours a. blood fluid levels 3. First 72 hours a. Mild edema and mass effect 4. 3–20 days a. Resolution of the mass which starts at the periphery b. Irregular contents that enhance to be differential from metastatic lesion, lymphoma (particularly in an HIV patient), abscess and inflammatory lesion; often hemorrhage is ring enhancing 5. Specific locations a. Multiple subcortical white matter hemorrhage 1) Leukemia 2) Coagulopathy 3) Disseminated intravascular coagulation b. Cerebellum 1) Anticoagulation (Coumadin) c. Lobar in the elderly (65–90 years) 1) Congophilic angiopathy 6. Nine weeks: a. Enhancement and mass effect have dissipated
Hypertension
1. General features: a. Most common cause of ICH b. Blood pressure is 220–240 mmHg systolic and 110– 120 mmHg diastolic 1) In several studies the peak systolic pressure is 160– 190 mmHg c. Pressure may be confounded by the Kocher–Cushing reflex; secondary hypertension due to the effects of pressure on the vasomotor center d. Many patients present without a prior history of hypertension 1) Examination may reveal: a) Enlarged aortic knob (uncorked) b) Thickened and tortuous peripheral blood vessel (radial and axillary arteries) c) Hypertensive changes in the retinal arteries d) Loud A2 and S4 gallop e) Sustained cardiac impulse 2) Hypertension induced degenerative changes in vessel walls a) Fibrinoid degeneration b) Microaneurysm: (1) Penetrating arteries of the basal ganglia, pons, thalamus and cerebellum (2) Also noted in arteries that supply the greywhite junction (3) Associated concomitantly with lipohyalinosis and fibrinoid degeneration (4) Possible relationship exists between iris microaneurysms and those found on cerebral blood vessels
Chapter 7. Hemorrhagic Vascular Disease Non-Hypertensive Causes of Intracranial Hemorrhage (ICH)
General Characteristics 1. Acute changes in blood pressure and blood flow: a. Precipitate rupture of penetrating arteries without prior hypertension b. Microaneurysm on penetrating vessels rupture: Predilection for lenticulostriate arteries (CharcotBouchard aneurysm). c. Fibrinoid degeneration of penetrating vessels after sustained hypertension rupture. d. Microaneurysms: 1) May bleed repeatedly (hemosiderin laden macrophages) 2) Located in penetrating vessels of: a) Lenticulostriate (MCA) b) Pons c) Cerebellum d) Grey white cortical junction e. Penetrating arteries may rupture: 1) Not at the site of microaneurysms 2) Generalized lipohyalinosis of entire artery 2. Exposure to cold weather. a. Stimulation of the sympathetic vasoconstrictor response 3. Dental procedures. a. Traction on the trigeminal nerve. 1) Changes in heart rate and blood pressure 4. Increased cerebral blood flow: a. Carotid endarterectomy (hyperperfusion syndrome) b. Following surgical repair of congenital heart defects c. Cardiac transplantation d. Post migraine 5. Older patients: a. ICH at lower pressure than younger patients: 1) Possible relationship to amyloid angiopathy 6. Biphasic presentation of ICH. a. Onset of new hypertensive state. b. Prolonged hypertension. Underlying medical conditions that are associated with ICH: a. Coagulopathy. b. Vasculitis. c. Subacute bacterial endocarditis. d. Tumor. e. Trauma. f. Thrombolytic treatment. g. Transformed ischemic stroke. 1. Frequently multiple 2. Not in classic hypertensive ICH locations. (centrum semiovale)
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Vascular Malformations
The major vascular malformation that are clinically relevant are: 1. Arterio-venous malformations 2. Dural arteriovenous malformation 3. Cavernous hemangiomas 4. Venous malformations 5. Capillary telangiectasia Parenchymal arteriovenous malformations are abnormal connections of arteries and veins with no capillary bed. The arteries themselves have poorly developed internal elastic lamina and often become stenotic and occluded. In a sizable percentage, these vessels harbor aneurysms. The natural history of an AVM is to enlarge, recruit blood vessels from neighboring circulations and to bleed. They most often present with seizures due to the abnormal neurons and glial tissue within the malformation. They may present with seizures, hydrocephalus or chronic migrainous headaches. These headaches are stereotyped and do not switch sides during different attacks Some patients note fluctuating bruits concomitant with their pulse. Approximately 2% have a progressive neurologic deficit. Dural arteriovenous malformations are abnormal arteriovenous shunts within leaflets of the dura mater usually within or near walls of the dural venous sinuses. Headache may be migrainous or localized to the side of the lesion. Patients suffer increased intracranial pressure, hemorrhage, pulsatile, tinnitus and seizures. Headache may be worse in the supine position. They may become symptomatic during pregnancy. Cavernous angiomas have no entrapped brain tissue, appear anywhere in the brain, but are often periventricular. They are frequently multiple and especially common in Mexican Americans. They usually are not associated with vascular headache. They most often clinically present with recurrent bleeding with focal neurologic deficit (parenchymal type) seizures and subarachnoid hemorrhage. They have a characteristic “popcorn” appearance in MRI from the mixed signal of old and new hemorrhage. They often hemorrhage at night. Venous hemangiomas are the most common type of vascular malformation. They are composed of anomalous veins and have no direct arterial input. They most often are linear tubular structures in the cerebellum with connection to the IVth ventricle and may demonstrate a “caput medusa”. They most often are asymptomatic except when occluded during surgical procedures. In these instances, they may cause cortical infarction. Telangiectasia are comprised of capillaries separated by normal brain parenchyma. They are most often seen in the cortex and the pons. They are rarely symptomatic. Perimesencephalic hemorrhage has recently been recognized as a form of hemorrhage that presents frequently as a subarachnoid bleed without focal findings. Blood on CT is most prominent in prepontine and perimesencephalic listerics. The process only seems to occur once and has an excellent prognosis. It may represent venous hemorrhage.
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SECTION I. Vascular Disease
Parenchymal Arteriovenous Malformations
General Features: 1. 10% as common as subarachnoid hemorrhage 2. Peak presentation in 2nd and 3rd decade 3. Increased incidence of aneurysms with AVM; usually along feeding blood vessels 4. Some afferent vessels become stenotic and occluded 5. Arteries within the arteriovenous malformation are thin walled with poorly developed internal elastic lamina; there is hypertrophy of the media and endothelial thickening of the afferent vessels 6. The natural history of arteriovenous malformation a. Enlarge, grow and recruit vessels from neighboring circulations 7. Composition of the arteriovenous malformation: a. Abnormal gliotic parenchyma is intermixed between component blood vessels b. No capillary bed c. Abnormal neurons 8. Parietoccipital > frontal > temporal lobe B. Clinical Signs and Symptoms: 1. 48% present with seizures 2. 2% have progressive neurologic deficits 3. Chronic headache: a. Migrainous; often are stereotyped and do not switch sides b. May have associated increased ICP and papilledema 4. Rare presentation with hydrocephalus: a. Common with great vein of Galen location in children b. Prior small bleeds block CSF absorption 5. Fluctuating bruit: a. Concomitant with heart beat b. Rarely heard over the malformation c. Jugular venous hum (heard in the neck) 6. Hemi asymmetry of the side opposite the lesions a. Most severe if the parietal lobe is involved 7. Hemorrhage is not strictly limited to the subarachnoid space 8. Cortical or ventricular surfaces most likely to rupture 9. Focal deficits specific to location 10. May have asymptomatic bleeds (hemosiderin deposits on gradient ECHO MRI sequence) 11. Rupture 2.2% per year 12. Mean risk of death from rupture is 29% 13. Meningeal signs if rupture is primarily in the subarachnoid space
Imaging Evaluation
1. MRI a. Honey combed areas
2.
3.
4.
5.
b. Serpiginous flow voids c. Brain atrophy and ventricular dilatation d. Adjacent cysts f. Intralesional calcification Arteriographic features definitive a. Enlarged feeding vessels from several circulations (most frequent) b. Tortuous enlarged draining veins c. Central arterial venous complex of vessels d. Rapid arterial to venous shunts Negative arteriogram with AVM malformations: a. Spontaneous thrombosis b. Obliteration with hemorrhage c. Cavernous angioma or dural anterior venous malformation 1) No feeding arteries d. Spinal AVM 1) May mimic intracranial signs and symptoms a) Headache and stiff neck Features Increasing the Risk of Hemorrhage: a. Small malformation b. Exclusively deep venous drainage c. High intranidal pressure AVM of the lateral ventricle: a. <40 years of age b. Small c. Intraventricular hemorrhage d. Lateral ventricle usually normal sized e. Caudate and choroid are other sources of intraventricular hemorrhage
Dural Arteriovenous Malformation
General Features: 1. Abnormal arteriovenous shunts within leaflets of the dura mater. a. Usually within or near the walls of dural venous sinuses. 2. Comprise 10–15% of AVM’s. 3. Pattern of drainage: a. Intradural sinuses. b. Cortical or deep venous system. 4. DAVM’s with prominent cortical venous systems have a higher incidence of bleeding than those without. 5. Symptoms of these malformations are primarily those of venous hypertension that is due or related to: a. Increased arterial input and therefore increased flow through the draining veins. b. Venous outflow obstruction. 6. Congenital DAVM’s. a. Vein of Galen type. 1) Due to retention of en embryonic median parencephalic vein; if it persists it becomes the sac for the aneurysmally enlarged vein of Galen.
Chapter 7. Hemorrhagic Vascular Disease Etiology of DAVM
1. Trauma; associated with skull fractures. 2. Female hormones: influence placental and uterine vascular growth. 3. Dural sinus thrombosis; female > males 2 : 1 with thrombosis of the lateral sinus and increased venous drainage enlarging dural veins. 4. May become symptomatic with pregnancy. 5. Thrombosis or stenosis within the draining dural sinus: a. Enlarges the DAVM. b. Increases venous hypertension. Clinical Signs and Symptoms
1. Headache (global and frontal); may be migrainous or localized to the side of the lesion. 2. Increased intracranial pressure. 3. Hydrocephalus. 4. Hemorrhage. a. Signs and symptoms depend on the drainage pattern: 1) Solely dural 2) Drainage pattern into the cortical or deep venous system b. Intraparenchymal > subdural > subarachnoid in location c. 30% mortality d. Pulsatile tinnitus. e. Seizures. f. Cerebral edema with venous hypertension and sinus occlusion. g. Postural headache (worse in supine position). Location of DAVM
1. Most common are related to the lateral sinus and involve the transverse or sigmoid portions; approximately 60% of DAVM’s. a. Feeding vessels of lateral sinus fistulae: 1) Occipital, middle meningeal, accessory meningeal from the external carotid. 2) Ascending pharyngeal (arch of the aorta) 3) Meningohypophyseal trunk of the cavernous carotid artery. 4) Dural branches of the vertebral arteries.
Cavernous Sinus DAVM
General Features: 1. Occur in approximately 16% of DAVM; 2% of patients with head trauma. 2. Abnormal shunting of blood from the internal and external carotid into the cavernous sinus. a. Type A 1) Direct carotid cavernous fistula
3.
4. 5. 6.
7.
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2) Large shunted blood volume 3) Dramatic symptoms b. Type B; indirect CCF 1) No direct communication between ICA-cavernous sinuses 2) Branches of ICA or ECA and the cavernous sinus 3) Type C a) Fed by dural branches of ECA 4) Type D a) Branches of ICA/ECA c. Orbital venous hypertension causes: 1) Proptosis 2) Scleral arterialized venous blood; the arteries reach the iris whereas in infection they don’t. 3) Chemosis. 4) Papilledema. 5) Glaucoma. d. Cavernous sinus drainage into: 1) Petrosal veins and sinuses 2) Basal vein of Rosenthal 3) Results in brainstem venous hypertension e. Cranial nerve III, IV, VI and first division of V (V1) may be compromised. f. Etiology. 1) Trauma. a. MVA with head injury b. Gunshot wounds 2) Rupture of ICA infraclinoid aneurysm. Etiology a. Ehlers Danlos type IV c. Arteriosclerosis b. FMD d. HCVD Indirect Fistulas a. Post menopausal b. Spontaneous Direct Fistulas a. Trauma Differential Diagnosis Tumors a. Pituitary adenoma d. Nasopharyngeal cancer b. Metastasis e. Hyperthyroidism c. Craniopharyngioma f. Retrobulbar masses 1) Hemangioma 3) Mucocele 2) Bone tumor Rare DAVM’s a. Incisura of the tentorium 8% b. Cerebral convexity – sagittal sinus c. Orbital-anterior falx d. Drainage into the vein of Galen, straight sinus or posterior falx e. Acquired adult vein of Galen – DAVM 1) Related to dural sinus occlusion 2) Supplied by middle meningeal and vertebral artery, PCA and meningohypophyseal branches of the ICA 3) Shunt is into the wall of the vein of Galen 4) Occasional association of a vein of Galen aneurysm with DAVM has been noted
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Prognosis and Natural History
1. An aggressive course is correlated with a. Drainage into subarachnoid and parenchymal veins b. Retrograde flow away from the lesion 2. Spontaneous closure may occur 3. Minimal symptoms for prolonged periods a. Headache b. Pulsatile tinnitus
Spinal AVM
General Features: 1. Subarachnoid bleeding may occur with cervical dural AVM a. Vertebral artery blood supply b. Cervicomedullary junction in location 2. Thoracic, lumbar and sacral malformations rarely bleed; epidural hemorrhage is presentation if they rupture Some dural fistulas are located in the in spine or paravertebrally. 3. Clinical signs and symptoms: a. Pain occurs in approximately 40% of patients; may be radicular b. Symptoms may worsen after exercise c. May present with Brown-Sequard distribution d. Usual course is progressive weakness with bladder involvement e. Local back pain f. Headache (intracranial meningeal irritation) g. Those in spine or paravertebral location 1) Compressive myelopathy 4. Hemorrhage may be initiated by coagulopathy or anticoagulation 5. Blood may be seen: a. Intraventricularly b. Basal cisterns c. Re bleeds occur in 50% of patient d. 90% of patients have neurologic deficits Type I Malformation Dural Form of Spinal AVM
1. Dural location most frequent 2. Blood supply derives from arteries located in the dural sleeves of spinal roots 3. Arteriovenous malformation fed by dural branches of a radicular artery 4. Fistula drained intradurally by: a. Enlarged tortuous vein (seen partially on the dorsal cord) b. Usually above the arterial feeder 5. Men > women 4 : 1 6. Age at onset of symptoms between 40–70 7. Usually located at lower thoracic and lumbosacral levels 8. Not associated with arterial or venous aneurysms a. Low flow
Cavernous Angiomas
A. General Features: 1. No entrapped brain parenchyma (well encapsulated) 2. Hyalinization and thickening of peripheral vessels 3. Often multiple 4. Familial (Mexican-American) 5. Zonula – Bannayan syndrome 6. Higher incidence of associated cavernous hemangioma 7. Cavernous hemangiomas are located in the posterior fossa in this circumstance 8. Associated with dural AVM a. Most common location in this instance is the posterior fossa 9. May appear anywhere in brain parenchyma 10. Often periventricular location 11. May occur: a. Spinal cord b. Subarachnoid space c. Dura d. Multiple locations simultaneously 12. Compact sinusoidal vessels Clinical Signs and Symptoms
1. Recurrent bleeding with focal neurologic deficit (parenchymal) 2. Seizures 3. SAH 4. Usually no correlation with vascular type headache 5. Rare occurrences: a. Visual loss from chiasmatic lesions b. Simultaneous bleeding from two lesions c. Hemigeusia from pontine lesions d. Associated with hippocampal sclerosis 6. May bleed intraventricularly MRI Imaging
1. Multiple lesions 2. “Pop corn” appearance of the lesion a. Mixed signal on T1; old blood (10–14 days) and new blood (<4 days) b. Hemosiderin ring around the lesion with low intensity signal on T1 sequences
Venous Angioma
1. General Features: a. Most common type of vascular malformation b. Composed of anomalous veins; no direct arterial input c. Venous varix: 1) Often linear tubular structure in the cerebellum with connection to the IVth ventricle
Chapter 7. Hemorrhagic Vascular Disease
2) May demonstrate a “caput medusa” 3) Cortical infarction if operated (occurs in the territory drained by the malformation) 4) There is normal brain parenchyma around the malformation d. Imaging characteristics of venous angioma 1) Linear on MRI 2) Frequently near a ventricle 3) Large prominent central draining vein a) May be dilated into a varix b) Hyalinized walls Clinical Features
1. Usually asymptomatic 2. Surgical removal may be associated with: a. Infarction of the territory they drain b. Venous angiomas should be preserved 3. Rare associations with: a. Hydrocephalus (midbrain) b. Spontaneous hemorrhage 1) Thrombosis of central draining vein c. Developmental venous anomalies d. Cerebral hemiatrophy e. Aqueductal compression
Telangiectasia
1. Comprised of capillaries separated by normal brain parenchyma 2. Most common locations: a. Pons b. Cortex 3. Sudden VIth or VIIth nerve palsy 4. Rarely symptomatic 5. Often multiple
Non-Hypertensive Causes of Parenchymal and Subarachnoid Hemorrhage
There are multiple causes of parenchymal and subarachnoid hemorrhage that are not caused by idiopathic hypertension. Many are caused by induced hypertension in patients with underlying cystic aneurysms and vascular malformations. They frequently have very specific clinical profiles that are diagnostic. Idiopathic perimesencephalic hemorrhage may account for approximately 10% of all SAH. It rarely occurs with congenital aneurysms and seems more likely to be caused by leakage of blood from the prepontine venous plexus. Most patients have no focal neurologic deficits on admission. The headache associated with this bleed reaches maximum intensity within minutes rather than seconds. There is no loss of consciousness with the ictus and no rebleeding or delayed ischemia.
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Mycolic aneurysm most often occur in the distal branches of the MCA and cause both intraparenchymal and SAH. They may be the initial presentation of SBE. Drug abuse with sympathomimetic agents and cocaine induce hypertension and cause hemorrhage as well as ischemic stroke. Cocaine in particular is associated with approximately 20% of ICH from an underlying aneurysm or vascular malformation. Drug abuse and SBE are coextensive. Elderly nonhypertensive patients with superficial lobar hemorrhages should be suspected of having congophilic angiopathy. These hemorrhages are often recurrent which can be demonstrated by gradient ECHO MRI (demonstrates hemosiderin from prior bleeds). Traumatic intracranial hemorrhage frequently are delayed to 4–7 days after ictus. They occur in the originally damaged brain issue. Venous thrombosis with hemorrhage should be suspected in pregnant patients and those in a hypercoagulable state. Preceding sense headache lethargy and seizures are common. Vasculopathy or vasculitis may also cause nonhypertensive hemorrhage. Differential Diagnosis of Perimesencephalic Hemorrhage
1. Venous or capillary leak 2. Caudate hemorrhage that extends into the subarachnoid space 3. Subependymal AVM or malformations 4. Trauma 5. Blood dyscrasias 6. Leakage from small nonaneurysmal arteries on the brain surface 7. Ruptured aneurysms; site of rupture is thrombosed and not identified 8. Dural AVM 9. Cocaine 10. Sympathomimetic drugs 11. Pituitary apoplexy 12. Spinal AVM 13. Traumatic LP Parenchymal Trauma With SAH
1. SAH often located in the superficial areas of the cortical sulci 2. Adjacent to a fracture site or area of intracerebral contusion 3. Basal frontal contusion a. hemorrhage may mimic rupture of AcoA aneurysm 4. Direct neck trauma a. tear of vertebral arteries or their feeders in the transcervical canals b. basilar hemorrhage 5. May be delayed a. occur 4–7 days in the contused area
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Mycotic Aneurysm
1. A common cause of nonaneurysmal SAH and intraparenchymal hemorrhage a. infective endocarditis b. aspergillosis 2. Most common location a. distal branches of the MCA b. 10% have a proximal location 3. Most patients suffer ICH at the site of rupture; some present with typical SAH 4. May re bleed 5. May be the initial presentation of bacterial endocarditis 6. Mycotic aneurysms secondary to aspergillosis: a. Proximal carotid location b. Proximal vertebrobasilar system c. Rupture is frequently fatal
Drug Abuse
1. General characteristics a. 25% of drug related strokes are ICH b. 6% related to recreational drug abuse 2. Location a. Subcortical 3. Hemorrhage in a first time user a. Occurs in minutes to hours 4. ICH responsible for approximately 50% of cocaine related stroke 5. Cocaine Abuse Crack cocaine 1) Aqueous cocaine HCL with NH3 and baking soda 2) Smoked or inhaled a) Aseptic necrosis of the nasal septum 3) Reaches the brain 10 seconds after it is smoked (1 circulatory pass) 4) Most rapid “high” f. Effects of cocaine 1) Blood pressure increase 2) Increases temperature 3) Increases metabolism a) Severe weight loss in chronic abusers g. Signs and symptoms immediately after use: 1) Loss of consciousness 2) Headache 3) Focal neurological signs (vasospasm of specific blood vessels) 4) Frequent signs and symptoms due to concurrent alcohol use 5) Hemorrhages 6) Strokes occur shortly after use 7) Predilection for the brainstem 8) Bowel and myocardial ischemia may be associated
h. Approximately 20% of patient with ICH after cocaine use have an underlying vascular lesion: AVM or aneurysm 1) SAH occurs in approximately 48–80% of patients with an underlying aneurysm after cocaine use 2) Rebleed may occur even with normal angiography 3) Vessels do not show signs of vasculitis 4) Deep hemorrhage is less likely to be caused by an underlying vascular lesion 5) Some patients present with hypertensive encephalopathy a) Usual pressure is 110–140 mmHg; 210–240 mmHg b) Multiple hemorrhages c) Cerebral edema Heroine Abuse
1. General characteristics: a. Cerebral or spinal cord ischemic stroke b. FCH from SBE (IV route) 2. Clinical features a. Stroke occurs with use after a period of abstention b. Ischemia of cerebral vessels: 1) Immediately after use 2) 6–24 hour delay c. Pulmonary edema and transverse myelitis d. If hemorrhage occurs: 1) Heroine altered or used concomitantly with: a) Cocaine or methamphetamine 3. Laboratory evaluation: a. Eosinophilia b. Comb’s positive hemolytic anemia c. Increased immune globulins d. False positive serology e. Antibodies to hepatitis C Amphetamine Abuse
1. General Features: a. Hemorrhages occur a few minutes after drug use b. Associated abuse of alcohol and other drugs c. Focal ICH may be associated with: 1) Diffuse vasculopathy 2) Brain edema 3) Ischemic lesions d. Clinical presentation: 1) Thin patients 2) Characteristics of adult attention disorder (chronic abusers) 3) Negative presentation: a) Hypertension b) Fever c) Tachycardia e. Fibrinoid necrosis of the media and intima of small and medium sized arteries
Chapter 7. Hemorrhagic Vascular Disease
f. Arteriographic evidence of segmental constriction and “beading” of intracranial arteries (superficial cortical arteries) g. Amphetamine and methamphetamine more likely to cause hemorrhage than dextroamphetamine h. Hemorrhage may occur with doses as small as 20 mg i. Solid form of D-methamphetamine base that can be smoked 1) Street name is “ice” 2) May reach the brain in <20 seconds in one CBF pass 2. Clinical Signs and Symptoms a. Clinical presentation: 1) Symptoms occur a few minutes after use 2) Headache 3) Seizures 4) Focal neurological signs from ICH 5) Average age of patients 25.4 years 6) Intracerebral lobar hemorrhage most common a) <5% have underlying vascular lesion 3. Laboratory Evaluation: a. Comb’s positive hemolytic anemia b. Increased immune globulins c. False positive serology d. Antibodies to Hepatitis C Phencyclidine (PCP)
1. Angel dust 2. Signs and symptoms a. ICH b. Hypertensive encephalopathy c. Self destructive behavior d. Dramatic nystagmus LSD
1. Hypertension 3. Vasoconstriction but no ICH 2. Hallucinations Phenylpropanolamine (PPA)
1. May be combined with caffeine or antihistamine 2. Partial α-adrenergic agonist 3. Clinical signs and symptoms a. <30 years of age; female > male b. SAH may occur c. ICH d. Blood pressure on admission 1) 160/104–210/110 mgHg e. Segmental angiographic beading of intracranial vessels (similar to amphetamines) f. Location: lobar > basal ganglia > thalamic g. Reactions to PPA are often idiosyncratic h. Risk of hemorrhage with PPA use occurs with: 1) Post partum use
2) 3) 4) 5) 6) 7)
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Caffeine Higher than recommended doses Alcohol Caffeine Prior hypertension Monoamine oxidase inhibitors1 a) Multiple simultaneous hemorrhages
Ethanol
1. Mechanisms predisposing to hemorrhage a. Platelet abnormalities b. Impaired production of clotting factors with concomitant liver disease c. Hypertension associated with chronic alcoholism d. Binge drinking 1) Acute elevations of blood pressure e. Concomitant use of cocaine in face of liver dysfunction 1) May potentiate vasoconstrictor effects Pentazocine and Pyribenzamine (“T’s” and “blues”)
1. IV use: associated with: starch, methylcellulose crystals, take pulmonary emboli 2. Pulmonary hypertension: a. Destruction of pulmonary arterioles with right sided hypertension b. Embolic material reaches the cerebral circulation c. Damaged cerebral vessels result in ICH 3. crystals and talc may be noted in cerebral vessels Methylphenidate
1. Associated with ICH
Cerebral Congophilic Angiopathy as Cause of Non-Hypertensive Hemorrhage
General Features: 1. Elderly non-hypertensive patients 2. Parietoccipital lobe subcortical location most frequent 3. 2–9% of ICH 4. 5% occurs 7th decade; 43% in 8th decade; 57% after 90 years of age 5. Location of CAA lobar hematoma a. Frontal 35% d. Deep central grey 4% b. Parietal 26% e. Cerebellum 2% c. Occipital 19%
Clinical Characteristics
1. Large and may be multiple 2. Recurrent ICH or SAH 3. Gradient ECHO MRI: multiple old bleeds (hemosiderin noted); old slit like hemorrhages
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SECTION I. Vascular Disease
4. Rarer clinical presentation: a. Insidious; similar to anticoagulant hemorrhage b. Nausea and vomiting c. Headache
Traumatic ICH
1. Concomitant contusions of the frontal and temporal lobes a. Gyral contusions near bony prominences 2. Patients are frequently amnestic 3. Late hemorrhage a. 4–7 days after trauma 1) Hemorrhage into damaged brain tissue
Metastatic Brain Tumors that Bleed
1. Most common hemorrhagic metastases: a. Hypernephroma b. Melanoma c. Papillary cancer of the thyroid d. Lung and breast 1) No specific proclivity to bleed but very common e. Choriocarcinoma 1) Often metastatic to the dura 2. Many metastatic tumors have petechial hemorrhages; rarely bleed a. New onset headache or seizures
Vasculopathy or Vasculitis as a Cause of Non-Hypertensive Hemorrhage
1. Rupture of affected vessels
Sinus Thrombosis
1. Post partum 2. Sagittal sinus most common: a. Ill patient b. Seizure in the contralateral leg c. Bloody CSF d. Cerebral edema 3. Dural AVM a. Form as a consequence of sinus thrombosis; collateral venous pathways
Subarachnoid Hemorrhage
Subarachnoid hemorrhage is a devastating neurologic illness that carries a mortality of 30% with each bleed and very significant mortality in survivors.
The ictus is frequently characteristic as patients suffer a severe headache that reaches maximum intensity instantly. The headache is frequently basioccipital and then shifts to frontal areas. It is associated with vomiting in a significant number of patients with attendant loss of consciousness in approximately 30–50%. The neck is stiff, patients have positive Kearnig’s and Brudzinski’s signs and focal deficits depending on the location of the bleed. The patients’ eyes are sore and photophobia is present. Seizures occur in 20% of patients. A sentinel bleed prior to the rupture of an aneurysm occurs in a significant proportion of patients. There is controversy whether enlargement of the aneurysm with stretch of the dura can cause a sentinel headache. Clearly at surgery there are often signs of hemosiderin and a prior bleed. Familial aneurysm, polycystic kidney disease, Turner’s syndrome and associated AVM are clear clinical settings for aneurysm. Acquired aneurysms have been noted both with trauma, atrial myxoma and SBE (mycotic) on peripheral arteries. Cigarette smoking and vasculitis may predispose at the circle of Willis. The role of hypertension in causation is controversial, but not in regard to rupture. Some autopsy series have demonstrated 0.9% of patients with a congenital aneurysm. An aneurysm of 7–10 mm is the most likely to bleed. Those less than 3 mm in general do not. An infundibulum at the take off of cerebral arteries is usually less than 2 mm and do not bleed. The use of coiling and interventional neuro-radioquaphic techniques has made aneurysm care much safer and successful for many patients. Unfortunately, vasospasm is still a major problem. The differential diagnosis for subarachnoid hemorrhage is wide and includes vascular malformations as well as trauma, congophilic angiopathy, hemostasis dysfunction and diseases of the blood vessel wall. 1. General characteristics a. Headache 1) Severe: 10/10 on a visual analogue scale 2) Reaches maximal intensity immediately (“worst headache of my life”) 3) Cervical-occipital location with frontal radiation; primarily C2 distribution 4) Lasts 4–6 weeks 5) Associations: a) Vomiting b) Loss of consciousness 30–50% c) pain and soreness of the neck, shoulders and upper back (1) If there is never head pain suggests spinal AVM d) Light sensitivity e) Sore eyes f) Focal motor or sensory deficits depending upon the etiology of the bleed g) Seizures in 20% b. Decreased level of consciousness c. Vomiting: 30–50% of patients d. Restlessness
Chapter 7. Hemorrhagic Vascular Disease
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Differential Diagnosis of SAH
Natural History of Unruptured Aneurysms
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.
a. 1.4% annual rate of rupture; other studies 3% bleed/year (untreated) b. 10% have ruptured at 10 years; 20% at 20 years and 32% at 30 years c. Multiple aneurysms 1) risk of rupture universally proportional to age d. Aneurysmal growth is not associated with: 1) Sex 3) Patient’s age 2) Blood pressure 4) Initial size E. Associations with Hereditary Diseases of Collagen a. Ehlers–Danlos (type IV; COL 1A gene, type III collagen) b. Pseudoxanthoma elasticum (COL2A gene) c. Marfan’s syndrome d. Osteogenesis imperfecta e. Polycystic kidney disease (PKD gene chromosome 12) f. Tuberous sclerosis g. Neurofibromatosis I (chromosome 17) h. Fibromuscular dysplasia (FMD)
Ruptured aneurysm Arteriovenous malformation Cavernous angioma Congophilic angiopathy Capillary, telangiectasia (very rare) Dural arteriovenous malformation Venous infarctions with hemorrhage Sinus thrombosis Head injury Hemorrhagic metastasis ICH with subarachnoid extension Coagulopathies Hemophilia Amphetamines; cocaine; other sympathomimetic drugs Migraine (extremely rare) Intracranial arterial dissection
Specific Vascular Malformations
Congenital Aneurysms
General manifestations: 1. 0.9–6% of the general populations in autopsy series 2. 3.6% prospective autopsy series 3. 3.7% in retrospective angiography series 4. 6.0% in prospective angiography series in those undergoing arteriography Incidentally discovered aneurysms by artery a. Internal carotid – post communicating artery – 64% 1) internal carotid ophthalmic artery 19.9% 2) IC – anterior choroidal – 12.8% 3) IC – cavernous portion – 10% b. Anterior communicating artery – 12.2% c. Middle cerebral artery – 6.3% d. Basilar artery (rare) e. PICA – vertebral (rare) f. AICA – basilar (rare) Meta analysis of 23 studies of prevalence 1. 0.4% in retrospective autopsy series Incidence of Unruptured Aneurysms by Age
a. b. c. d. e. f. g.
1.1%: 0–29 years of age 3/5%: 40–49 years of age 5.7%: 50–59 years of age 7.4%: 60–69 years of age 6.1%: 70–79 years of age 9.3%: 80–89 years of age 37.5%: >90 years of age
Associated Other Diseases
a. Coarctation of the aorta b. Congenital anomalous blood vessels c. Arteriovenous malformation (arteries feeding the malformation) d. Moyamoya syndrome e. Takayasu syndrome The Defect Underlying Aneurysm Formation
a. Occur at branch points of arteries of the Circle of Willis b. Decrease of type III collagen c. Defect of the arterial media and localized loss of muscular elements d. Loss or breakage of the internal elastic membrane Familial Aggregation of Congenital Aneurysms
a. 7–10% of patients with aneurysmal rupture have first or second degree relatives with an aneurysm b. Among first degree relatives of those with ruptured aneurysms risk of SAH is four times that of the population at large c. Risk highest among siblings of the index patient d. Most families have 2–3 members that are affected if there is familial aggregation e. Inheritance patterns are unclear; autosomal dominant most probable Incidence of SAH with Aneurysms
a. 1/10,000 people b. At risk for development of new aneurysm (after rupture of the first)
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SECTION I. Vascular Disease
c. Each year: new aneurysms develop in 2% of patients with previously ruptured aneurysms, this group ruptures at an incidence of 6/10,000 in the general population d. Morbidity and mortality 1. 12% die prior to medical attention 2. 40% die in the hospital within 1 month after the ictus 3. 1/3 of survivors suffer major neurologic deficits Associated Clinical Features of Aneurysms with Underlying Collagen Defects
1. 2. 3. 4. 5. 6.
They are in typical locations Bilateral Associated with enlarged tortuous extracranial vessels Occur at supra clinoid level Associated with A-V fistulas Associated with dural ectasia
Familial Aneurysms
a. Rupture at an earlier age than sporadic aneurysms b. Smaller when they rupture c. More often followed by the formation of new aneurysms Multiple Aneurysms
a. b. c. d.
Usually 2–3 in patients Occur in 20–30% of patients Rarely > 10 Occur with AVMs and other associated congenital anomalies of blood vessels
1. 9% risk in first degree relatives if 2 or more members have aneurysms 2. Life time risk for SAH in persons with an affected first degree relative is 1% at age 50; 2% at age 70 i. Familial predisposition 4.0% (2.7–6%) j. Atherosclerosis 2.3% k. 8% of aneurysms detected >8 mm in size l. Incidence of rupture increases after the third decade; average age of rupture is fifty years of age, increases with age until 80 1. Female > male risk of rupture after 40 2. Male > female risk of rupture < 40 a) Anterior communicating aneurysms female > male m. 75% of unruptured aneurysms <10 mm; 80% < than 6 mm 1. Median time from diagnosis of unruptured aneurysms to rupture <2 years 2. Linear association of risk of rupture with increasing size n. Younger patients at greater risk of rupture in the setting of multiple aneurysms o. Aneurysms that were followed and found to have ruptured had gown in size p. Multiple aneurysms female > males q. Setting of hypertension 1. Rupture more common in older patients 2. Hemiparesis, hemihypesthesia, and hemianopsia have been described in 4. 6–25% of unruptured aneurysms Precipitating Factors Associated with Rupture
Factors Influencing Aneurysmal Rupture
a. Risk of rupture 1.9–3%/year b. Aneurysms of <10 mm 0.7% rupture/year; usual size 7– 10 mm at rupture c. Aneurysms >10 mm 5.5% risk of rupture d. Risk of rupture > in women than men e. Incidentally found aneurysms lower risk of rupture than those found in addition to one that has ruptured f. Aneurysmal SAH; male > female 1. Premenopausal female low risk of rupture 2. Postmenopausal female with hormone replacement (intermediate risk) 3. Postmenopausal female without hormone replacement (highest risk) 4. Alcohol consumption g. Cigarette smoking; 3–10× greater risk than nonsmoker 1. Smoking increases chance of developing a new aneurysm 2. Decreases alpha antitrypsin (inhibits proteases) 3. Inherited decrease of alpha antitrypsin causes increased risk of aneurysms h. ADPCK disease (autosomal dominant polycystic kidney disease) 4.4% (2.7–7.2%) chance of aneurysm
1. 2. 3. 4. 5. 6. 7. 8.
Valsalva maneuvers Pregnancy (release of elastases) Sleep (30% rupture during sleep) extreme sudden hypertension (amphetamines; cocaine, PPA) Weight lifting Coitus Defecation 30% rupture during normal activity
The Clinical Spectrum of Unruptured Intracranial Aneurysms
1. Mean age at diagnosis 50 years (11–77 years) 2. Mean aneurysm diameter 2.1 cm Group I – Acutely Symptomatic Patients
1. Headache a. Sentinel hemorrhage 1) Possibly 30% of aneurysmal SAH 2) Minute tear of the aneurysm: a) Sudden onset “thunderclap” headache b) Maximum intensity instantly
Chapter 7. Hemorrhagic Vascular Disease
c) Resolves in 48 hours, but may last weeks d) Radiation to shoulder, neck and back; “flu-like” symptoms (with SAH) e) Aneurysm thrombosis; meningeal inflammation 3) Ischemia (vasoconstriction of the parent vessel) 4) Seizure (rare) 5) Cranial neuropathy (III most common) Group II – Chronic Symptoms (giant aneurysms)
a. b. c. d. e. f.
Average size of giant aneurysms 2.1 cm Headache (mass effect) Visual loss (optic nerve or chiasmatic compression) Pyramidal tract dysfunction (MCA giant aneurysm) Facial pain (V1 involvement in cavernous sinus) Diplopia 1. III and IV nerve – giant basilar tip aneurysm 2. P-COM; III nerve compression 3. AICA – VI nerve rare 4. Cavernous sinus VI nerve > III > IV nerve
Asymptomatic Patients
1. Aneurysm size 1.1 cm Unruptured Aneurysm Major Clinical Presentations
a. b. c. d. e. f.
Mass lesion Stroke Seizure 77.4% at ICA and PCA sites More common in women than men MCA aneurysms; approximately 15% are symptomatic
Clinical Presentation of SAH From A Ruptured Aneurysm
1. General manifestations a. Severe headache (noted above) b. 50% of patients lose consciousness or are stunned c. Photophobia d. 30–50% have suffered a sentinel headache days to weeks prior to the rupture e. Neck stiffness 1) Kernig’s sign 2) Brudzinski’s sign f. Subhyaloid hemorrhage (Torsten’s syndrome) 1) Side of the ruptured aneurysm (if there are multiple); sudden increased ICP with rupture of the preretinal veins 2) Shoulder, back or sciatic pain 3) Pain across the shoulders with “flu-like” symptoms g. <5% pain is limited to the low back or neck without headache h. Lethargy; inability to follow four part commands or perform visual praxis i. Sore eyes to movement or palpation
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Specific Clinical Presentation of Congenital Aneurysms
1. P-COM (posterior communicating carotid) a. Pain in or behind the affected eye b. Slowly reactive, oval or paralyzed pupil 1) Pressure sensitive parasympathetic fibers affected early or 2) Parasympathetic fibers localized to outer area 12-3 o’clock of the IIIrd nerve c. Partial ptosis; lampshade ptosis secondary to infarction of the III nerve from medical diseases d. Blood in the suprachiasmatic cisterns 1) Localized to the side of the bleed
A-COM Artery Complex (Anterior Communicating Artery Complex)
a. Mental status changes 1) Acutely: agitation (with no or minimal motor or sensory signs) 2) Several days following the ictus: a) Abulia b) Akinetic mutism c) Amnesia d) Decrease of executive function 3) Slight contralateral leg weakness and sensory loss 4) DH: Broca’s type aphasia (SMA involvement) b. CT/MRI evaluation 1) Blood in medial frontal lobe 2) Intra hemispheric fissure anteriorly and extending posteriorly c. Anterior communicating artery syndrome 1) Amnesia 3) Personality change 2) Confabulation
Middle Cerebral Artery Trifurcation Aneurysm
a. Anterior temporal headache b. Contralateral hemiparesis and hemisensory defect 1) Embolus from giant aneurysm 2) Vasoconstriction 3) Mass affect from hematoma following rupture c. Rare seizure (compression or irritation of the cortex) d. Aphasia (DH) e. Weakness arm and face > leg f. Aneurysm may be > 2 cm (giant aneurysm) g. Large amount of blood in Sylvian fissure, vasoconstriction of MCA h. Giant MCA aneurysm: seizures, dysphasia, hemiparesis
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SECTION I. Vascular Disease
Internal Carotid Artery Aneurysm
Superior Cerebellar-Basilar Artery Aneurysm
a. b. c. d. e.
a. b. c. d.
Pain behind the eye Ptosis (partial) and pupillary paresis Rare complete IIIrd nerve palsy Contralateral hemiparesis and hemisensory deficits Nasal visual field deficit 1) Homonymous 2) Compression of the lateral chiasm
Ophthalmic artery aneurysm
a. b. c. d.
Pain in or behind the eye Painless loss of central vision Rare bitemporal VF deficit Chiasmatic syndrome (anterior)
Anterior choroidal artery aneurysm
a. b. c. d. e. f. g.
Contralateral hemiparesis Contralateral hemisensory defect Central sector VF deficit Transient focal ischemia of the internal capsule Limb shaking (ischemia of internal capsule) Tonic spasm (ischemia of internal capsule) Rupture with: 1. Intracranial or intraventricular hemorrhage
III nerve palsy Ipsilateral dysmetria Dysarthria Blood in the perimesencephalic cistern
Top of the Basilar-PCA Bifurcation
1. 2. 3. 4.
Pain in the back of the neck or basiocciput III nerve palsy (peduncular) Visual field deficit (embolus to PCA) Hemiparesis or quadriparesis (emboli or pressure on the cerebral peduncles) 5. Movement disorder (emboli or vasoconstriction of the thalamoperforate artery) 6. Thalamic sensory deficit (emboli or vasoconstriction of the thalamogeniculate artery) 7. Blood in the perimesencephalic cisterns; intra peduncular blood PCA-P1 (posterior communicating artery)
1. Similar to top of the basilar–PCA aneurysm Specific Clinical Signs Denoting Specific Aneurysms
Posterior Circulation Congenital Aneurysm
A. Vertebral Artery Aneurysm 1. PICA symptoms 2. Anterior spinal artery symptoms (VA-ASA) a. Hemiparesis b. Proprioception and vibration loss 3. Pain in the side of the neck 4. Rarely pain radiates to lateral eyebrow 5. Acute blood in the IV ventricle B. PICA-Vertebral Artery Aneurysm 1. Dysphagia and hoarseness 2. Lateral pulsion (ipsilateral side) 3. Inability to stand 4. Nausea and vomiting 5. Pain in the basiocciput; lateral eyebrow or side of the face 6. Crossed hemisensory loss to pain and temperature 7. Oscillopsia 8. Acute rotary nystagmus (greatest ipsilaterally) 9. Ipsilateral Horner’s syndrome 10. Blood in the IV ventricle and the posterior fossa AICA-Basilar Artery Aneurysm
1. 2. 3. 4.
Sudden hearing loss or tinnitus Peripheral ipsilateral facial weakness Ipsilateral pain in the face Contralateral pain and temperature loss (below the clavicle) 5. Contralateral hemiparesis 6. Blood in the posterior fossa
1. Giant MCA aneurysm a. Seizure (focal motor) c. Hemiparesis b. Dysphasia 2. IIIrd nerve compression a. ICA (hemiparesis often associated) b. P-COM c. Superior cerebellar artery 3. Isolated VIth nerve following aneurysmal SAH a. Blood b. Increased intracranial pressure 4. Cavernous sinus aneurysm a. VIth nerve first sign b. Severe Vth nerve facial pain c. Late: IIIrd, IVth, VIth 5. Basilar tip a. Forward pointing 1) Destroys the pituitary (endocrine failure) 2) Visual field deficits b. Vertical 1) IIIrd, IVth nerve 2) Compresses the IIIrd ventricle
Rare Clinical Signs of Aneurysms
1. Transient neurologic signs: a. Ischemia of the parent vessel b. Embolization: 1) Usually from giant aneurysms 2) Cause strokes in the affected territory 2. Torsten’s syndrome
Chapter 7. Hemorrhagic Vascular Disease
a. b. c. d.
Subhyaloid hemorrhage (preretinal) Hemorrhage is moveable with changing head positions Due to sudden increased pressure Occurs on the side of the ruptured aneurysm (20% of patients harbor two or more aneurysm) e. Secondary to rupture of a preretinal vein 3. Prognosis of SAH from an aneurysm is better if no aneurysm is demonstrated Radiological features of an aneurysm that has ruptured if more than one is present by arteriography: 1. The largest aneurysm most often has bled a. Most commonly between 7–10 mm b. Giant aneurysm usually do not bleed 2. Aneurysm with the most excrescences 3. Local vasospasm 4. Local hemorrhage or hematoma
Aneurysmal Rebleeding
1. Clinical manifestations a. Sudden abrupt severe headache (described above) b. Meningismus c. Focal signs secondary to early hemorrhage d. Late 1) Vasospasm of the parent vessel with focal expected signs and symptoms e. Associated ICH leads to rapid coma f. Aneurysms that cause neurologic symptoms rupture at a higher rate 1) 15% of rebleeding within 6 months g. Fewer re bleeds in patients with Hunt grades I and II 2. Time of aneurysmal rebleeding a. 0.8–4% re bleed the first 24 hours b. 20% re bleed the first 2 weeks c. 30% re bleed by the end of the first month d. 40% by the end of 6 months e. >6 months 3%/year 3. Vasospasm concurrent with rebleeding a. Occurs from day 3–5 b. Peaks between days 5–9 c. Resolves after the second week d. Directly related to the amount of blood surrounding the artery e. Configuration of the arteries 1) Focal vasoconstriction approximate to area of the bleed 2) Diffuse vasoconstriction of the artery f. Lumen of the affected artery <0.5 mm g. May occur at a distance from the rupture 4. Early clinical signs of vasospasm a. Tachycardia b. EKG changes 1) Inverted T waves leads V3–V6 2) ST depression or elevation without q waves
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3) Atrial and ventricular arrhythmia c. Decreased level of consciousness d. Deficits corresponding to the affected artery 5. Early clinical signs of hydrocephalus a. Decreased spontaneity b. Constant headache (often frontal) c. Lethargy d. Incontinence e. Increased reflexes legs > arms
Medical Complications of Aneurysmal Subarachnoid Hemorrhage
1. General manifestations a. Seen at 3 months 1) Symptomatic vasospasm – 46% 2) Rebleeding 7% 3) Total mortality 19% b. Frequency of at least one severe (life threatening) medical complication 1) 40% 2) Death from medical complications 23% (of those that die) a) Rebleeding 22% of these deaths 3) Vasospasm with stroke 23%
Cardiac Arrhythmia
1. 50% have an abnormal admission EKG 2. 25% have ST segment or T wave abnormalities 3. 15% have prolonged QT interval associated with at least one episode of moderate or severe arrhythmia 4. 35% of all aneurysms have one episode of cardiac arrhythmia on day 0–14; 66% of these are mild; 29% moderate and 5% are severe 5. Onset of arrhythmias usually first 7 days (peak day 2–3) 6. 17% of patients suffer moderate or severe arrhythmia on the day of rupture 7. Cardiac arrhythmia on the day after surgery a. Life threatening 5% of patients b. Less serious 30% of patients 8. Moderate arrhythmias a. Sinus bradycardia c. Atrial extrasystole b. Sinus tachycardia d. Atrial fibrillation 9. Severe arrhythmia a. Asystole b. Ventricular tachycardia c. Atrial fibrillation with hypotension d. AV block e. Supraventricular tachycardia f. Ventricular extrasystole 10. EKG changes with SAH a. ST depression or elevation without q waves
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b. c. d. e.
Deeply caved T waves (Pardee T waves) V3–V6 u waves Hyperpolarized T waves Pathogenesis 1) Myocytolysis a) Contraction band necrosis b) Myofibrillar degeneration c) Effects of increased sympathetic discharge
Grading Scale for Subarachnoid Hemorrhage
Grade I Grade II
15 13 or 14
Grade III Grade IV
12 or 13 7–12
Grade V
3–6
Glasgow Coma Scale headache only no motor deficit, may have cranial nerve deficit motor deficit, cranial nerve deficit motor deficit, cranial nerve deficit, obtunded cranial nerve and motor deficit, comatose
Pulmonary Edema
1. Occurs in 6% of patients (day 3 to 7) 2. Probable sudden increase in ICP 3. Water and electrolyte disturbance a. Particularly with anterior communicating artery aneurysms 4. Increase of atrial natruretic factor 5. Discharge of substance P containing afferents in lung capillaries
Hepatic Dysfunction
Giant Aneurysms > 2 Centimeters
1. General characteristics a. Do bleed but rarely b. Symptoms are caused by: 1) Pressure on local structures 2) Emboli distally 3) Seizure activity 4) Endocrine dysfunction (erosion into the pituitary)
Giant Carotid Aneurysm
1. Occurs in 7% of patients 2. Usually 24% of patients have mild enzyme abnormalities 3. 4% severe hepatic impairment
1. Pain behind or around the eye 2. May erode into the pituitary with endocrine failure 3. Compression of the optic chiasm with nasal VF deficit or chiasmal syndrome 4. III nerve palsy
Renal Dysfunction
Middle Cerebral Artery Giant Aneurysm
1. Occurs in 7% of patients 2. 1.2% severe life threatening renal failure
1. Anterior temporal or retroauricular headache 2. Seizure activity 3. Contralateral hemiparesis
Thrombocytopenia
Top of the Basilar Giant Aneurysm
1. Occurs in 4% of patients a. Usually associated with sepsis
Sensitivity of Computed Tomography in Detecting SAH
1. Sensitivity of new generation CT scans for patients screened < 24 hours from the ictus is 93% 2. Sensitivity of new generation CT scans in patients after 24 hours from the ictus is 90% 3. L.P. remains the gold standard to rule out SAH
1. 2. 3. 4. 5.
Occipital headache III, IV nerve palsy (if extends dorsally) Compression or invasion of the III ventricle May cause obstructive hydrocephalus Associated with emboli to the posterior cerebral artery territories with VF deficits 6. Hemiparesis (compression of the cerebral peduncle)
Acquired Aneurysms
1. General manifestations a. Peripheral arterial location (not at the Circle of Willis)
Chapter 7. Hemorrhagic Vascular Disease
b. May be multiple on superficial conducting vessels c. Cause of peripheral lobar hemorrhage 2. Differential diagnosis 1. Fusiform (secondary to hypertension; basilar artery) 2. Subacute bacterial endocarditis 3. Trauma 4. Atrial myxoma 5. Collagen vascular disease 6. Cigarette smoking (women > men)
Basilar Fusiform Aneurysm
1. Occurs in elderly hypertensive patients with associated atherosclerosis 2. Dysarthria (pontine compression) 3. Hydrocephalus (blocks ventral CSF pathways) 4. Spastic gait (pressure on ventral pontine motor fibers) 5. XII nerve palsy (dysarthria) 6. Spastic quadriparesis (ventral pontine compression)
Closed Head Injury
1. Aneurysms of superficial subarachnoid conducting vessels 2. Rarely basilar artery is traumatized after cervical or basilar skull fracture with aneurysmal formation 3. May be multiple
Atrial Myxoma
1. Multiple peripheral aneurysms 2. MCA territory most common 3. Myxomatous emboli may grow through the wall of the blood vessel
Traumatic Peripheral Carotid Artery Aneurysm (Pharyngeal Portion)
1. Knife or gunshot wound to the neck 2. Sympathetic ocular paralysis (complete Horner’s syndrome) 3. Abnormal neck pulsation 4. Embolization in carotid territory 5. Pain in the side of the face 6. Carotodynia (pain in the artery itself) 7. Associated connective tissue disease: a. Ehlers Danlos type IV and VI b. Marfan’s disease c. COLIA gene mutations d. Fibromuscular dysplasia e. May be bilateral
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Traumatic Vertebral Artery Peripheral Aneurysm
1. Trauma to the neck a. Often minimal and unrecognized when it occurs 2. Pain in the posterior or side of the neck a. Mastoid pain b. Occipital headache 3. Chiropractic manipulation (horizontal C2 portion most vulnerable) 4. Congenital connective tissue disorders (particularly if bilateral) 5. Signs and symptoms: a. Distribution of the vertebral or basilar artery b. Due to emboli at the site of the vessel tear c. Rarely flow limiting pathogenesis for signs and symptoms 6. Cancer or cancer treatment (surgical trauma)
Subacute Bacterial Endocarditis
1. May be multiple 2. MCA territory most frequent locations 3. Hemorrhage is common a. Cause of peripheral ICH b. May be delayed after successful antibiotic treatment (destruction of the vessel wall) 4. Seizures are common 5. Focal motor deficits: the symptomatology depends on location 6. Streptococcus viridans; gram negative organisms most common 7. Following dental work 8. In association with deformed values a. Congenital bicuspid calcified valves b. Rheumatic fever deformed valves c. Rarely mitral valve prolapse Differential diagnosis of subarachnoid hemorrhage without detectable aneurysm 1. General features a. 15–20% of spontaneous SAH no aneurysm is detected by 4 vessels arteriography b. There is a better prognosis in these patients than in those in which an aneurysm is found
Diseases
1. Idiopathic perimesencephalic hemorrhage 2. Venous trauma 3. Diffuse or anteriorly located hemorrhage in the basal cisterns 4. Incomplete visualization of the posterior circulation 5. Occult aneurysm
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6. 7. 8. 9. 10. 11. 12. 13. 14. 15.
Carotid artery dissection Vertebral artery dissection Dural arteriovenous malformation Spinal AVM Parenchymal trauma Mycotic aneurysm Cocaine abuse Sickle cell disease Coagulopathies Subarachnoid blood in the basal cisterns a. Pituitary apoplexy b. Cervical tumor c. Rupture of circumferential artery (penetrators) in the pontine cisterns d. Trauma e. Mycotic aneurysm f. Coagulopathies (rare) g. Cocaine or sympathomimetic drug abuse
Incomplete Visualization of the Posterior Circulation
1. Ruptured aneurysm of the posterior circulation is suspected from the early CT scan 2. 85% of patients demonstrate blood in the IV ventricle and to a lesser extent the IIIrd and lateral ventricles 3. IVH is the only abnormality on CT scan in 25% of posterior circulation aneurysms 4. Subarachnoid blood is noted in the midbrain cisterns with spread to the anterior basal cisterns
Occult Aneurysm
1. Approximately 20% of aneurysms are detected on the second arteriogram (after 2 weeks; vasospasm has cleared) 2. Aneurysmal rupture is likely if there is blood in the Sylvian or interhemispheric fissure
Idiopathic Perimesencephalic Hemorrhage
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.
Approximately 10% of all SAH Comprise 2/3 of patients with normal arteriograms Occur in older patients (>6th decade) Few patients with HCVD Rarely concomitant with congenital aneurysm 1/3 have history of strenuous exercise prior to the bleed Headache reaches maximum intensity within minutes rather than seconds No loss of consciousness with the ictus No focal neurological deficits No rebleeding or delayed ischemia Normal on admission other than headache 20% have hydrocephalus with no other clinical deficits Excellent prognosis Some evidence of capillary bleed as cause
Venous Trauma
1. Shearing head injury 2. Blood most often seen in the posterior part of the ambient cistern (superior cerebellar-quadrigeminal cisterns) at the level of the tentorium 3. Vein is torn against the tentorium Diffuse or Anteriorly Located Hemorrhage with Rupture into the Basal Cisterns
1. 2. 3. 4.
Patients are lethargic to stuporous Focal neurologic deficits are present Symptomatic hydrocephalus Nidus of bleeding medial frontal lobe a. Blood dissects into the inter hemispheric fissure b. May re bleed 5. Deterioration from associated ischemia
Carotid Artery Dissection
1. Rare cause of SAH 2. Clinical features: a. Severe neck pain; subacute or acute onset b. Facial pain c. Oculosympathetic paralysis d. MCA or carotid embolic stroke e. May be associated with depressed level of consciousness f. Rebleeding may occur within hours of the initial hemorrhage
Vertebral Artery Dissection
1. Autopsy series – comprises 4% of patients who died from SAH 2. Primarily middle aged patients 3. 1/3 have HCVD 4. Common after neck movement or minor trauma a. Patient may be going to a chiropractor because he has neck pain from the dissection 5. Rarely associated with lower cranial nerve palsies; symptoms from occlusion or embolus of the PICA 6. May be bilateral if the cause is an underlying collagen defect 7. Rebleed occurs in 30% of patients; may occur within hours of the initial hemorrhage
Anticoagulation with Warfarin or Heparin
Risk factors for ICH or systemic bleeding
Chapter 7. Hemorrhagic Vascular Disease
1. Prolongation of prothrombin time beyond the therapeutic range a. hemorrhages occur occasionally in the therapeutic range 2. Large size of infarcted area (ischemic stroke) 3. Uncontrolled hypertension 4. Age related (relative risk); primarily for subdural hematoma Clinical Features
1. Gradual and insidious onset a. Hours to days 2. Predilection for the cerebellum and central lobes 3. High morbidity and mortality Patients Requiring Long Term Anti Coagulation after Bleed; Reinstitution of Rx:
1. 10–14 days possibly safe; 2–3 weeks heparin or warfarin probably safe 2. First year of anticoagulation most dangerous MRI Evaluation
1. Inhomogeneous infarction mixed signal on T2 weighted images suggest acute bleeding and clots
Primary Tumors that Hemorrhage
1. Glioblastoma multiforme 1. In general petechial hemorrhage 2. Bleeding and edema may be initiated by minimal trauma 2. Pituitary apoplexy a. Most often MRI demonstrates blood confined to the pituitary 3. General Characteristics a. Bleeding into tumors account for 5–10% of ICH b. 1% of tumors bleed c. Hemorrhagic metastatic tumors 1) Melanoma 2) Choriocarcinoma 3) Papillary Ca of the thyroid 4) Bronchogenic Ca d. Tumors that bleed are overwhelmingly malignant
Clinical Characteristics Suggesting ICH is Secondary to a Tumor
1. Underlying systemic cancer 2. Focal symptoms prior to hemorrhage 3. Unusual site: a. Corpus callosum (glioma) 4. Multiple simultaneous hemorrhages
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Bleeding Diathesis
1. General manifestations a. Platelet abnormalities 1) Associated with petechial hemorrhage in the lower extremities 2) Bleeding from the gums 3) Vaginal bleeding prior to cerebral hemorrhage may occur 4) Hemorrhage starts at <30–40 thousand/mm3 b. Waldenström’s macroglobulinemia 1) Associated abnormalities of platelets with lower extremity petechiae 2) Bleeding from mucous membranes c. Disseminated intravascular coagulation 1) Associated bleeding from all former venous puncture sites 2) Acrocyanosis d. Hemophilias 1) Joint involvement 2) Associated SDH 3) Internal bleeding 4) Bleeding may develop gradually 5) Recurrent ICH less likely after 14 days e. Liver transplantation 2. Differential Diagnosis a. Coagulopathies (inherited and acquired) b. Anticoagulation (INR > 5) c. Thrombolytic treatment (TPA; urokinase) d. Connective tissue disease e. Sickle cell disease Specific Diseases of Blood Vessels That Hemorrhage
1. Cerebral amyloid angiopathy a. AD (Icelandic; Dutch variants) b. Sporadic; incidence increases with age c. Concomitant Alzheimer’s disease and variants 2. Granulomatous angitis of the CNS 3. Lymphomatous granulomatosis 4. Benign appearing immunoproliferative vasculitis 5. Angiocentric lymphoma 6. Periarteritis nodosa 7. SLE (with and without lupus anticoagulant) 8. Connective tissue diseases 9. Sickle cell disease a. 30% of sickle cell disease SAH occur in children b. Blood is in the superficial sulci c. Mechanisms 1) Distal branch occlusions 2) Collateral leptomeningeal vessels 3) Moyamoya disease (bilateral carotid occlusion) d. Adult patients may have: a) Underlying aneurysm b) Blood in the basal cisterns
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SECTION I. Vascular Disease
Thrombolysis Related Intracranial Hemorrhage
1. 2. 3. 4. 5. 6. 7.
Hemorrhages are large (approximate mean of 70 ml) Solitary in 66% Lobar 77% Confluent 80% Intraparenchymal 80% Mortality 44–83% Increased risk of subdural hematoma
Clinical Features
1. 2/3 of hemorrhages are supratentorial and solitary 2. 1/3 subtentorial or multifocal 3. Peri hemorrhage edema is minimal a. Less in those hemorrhages with a blood fluid level b. Mottling and a blood fluid level is indicative of continuing fibrinolysis 4. TPA > hemorrhage risk than from streptokinase Thrombolysis Induced Hemorrhage Occur in 6% of Treated Patients
a. 7% may be asymptomatic; noted on follow-up CT scan b. Main comorbidities associated with ICH thrombosis: 1) History of diabetes melitis and cardiac disease 2) Use of antiplatelet agents other than ASA prior to stroke related hemorrhage 3) Elevated pretreatment blood pressure 4) Age c. Criteria that utilized CT findings and laboratory findings that predict ICH: 1) Ischemic changes on CT exceeding 1/3 of the MCA territory 3) diabetes 4) Elevated serum glucose 5) Low platelet counts d. Pretreatment diffusion-weighted MRI parameters and laboratory values predictive of ICH after thrombolysis 1) High systolic blood pressure 2) Severity of the stroke 3) Elevated serum glucose 4) Volume of initial DWI lesion 5) Voxels with decreased ADC value e. Predictive CT findings for thrombolytic hemorrhage: 1) Large arterial territory involved 2) Obscuration of caudate nucleus 3) Loss of the insular stripe 4) Sulcal effacement
a. b. c. d. e.
Hypertension Size of the ischemic area Age of the patient Embolic > thrombotic stroke Endothelial cells of blood vessels are sensitive to hypoxia 3. Unfavorable prognostic signs a. Intraparenchymal hemorrhage b. Extraparenchymal bleeding (often occurs after streptokinase) c. Cerebral edema d. Size of the hematoma 1) Increased cerebral edema e. Hemorrhagic transformation of an ischemic stroke has a better prognosis than a hematoma for ICH
Recurrent Intracerebral Hemorrhage
1. 1.8–5% of patients in Asia 2. 2–24% of European patients 3. 6% of ICH are recurrent in the USA; 2.4%/year for primary ICH 4. Mean age is 64.7 years 5. Interval between bleeds is 48 months 6. Recurrent hemorrhages occur at different locations 7. Patterns of recurrences a. Basal ganglionic in hypertensive patients b. Lobar in patients with congophilic angiopathy 8. Younger age and lobar hemorrhage increase the risk of recurrence of ICH 9. Recurrent ICH a. Poor prognosis b. Severe cognitive deficits c. Risk is 4× higher in lobar hemorrhage
Post-Partum Cerebral Angiopathy
1. Cause of recurrent intracerebral hemorrhage in young women 2. Rsually a vasospastic process 3. Rsually benign and non-relapsing 4. Several intracranial vessels involved; often bilaterally 5. Similarities to benign isolated CNS angiitis: a. Young women b. Headache, seizures, neurologic deficits c. Angiogram consistent with vasospasm
Hemorrhage After an Acute Ischemic Stroke
Mechanisms of Recurrence of Intracranial Hemorrhage
1. All ischemic infarctions have petechial hemorrhages microscopically 2. Hemorrhagic transformation determinants:
1. Young patients – hypertension 2. Older patients > 65 years – congophilic angiopathy 3. Approximately 50% are secondary to hypertension
Chapter 7. Hemorrhagic Vascular Disease Differential Diagnosis of Multiple ICH
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Underlying malignancy Hypertension Coagulopathies Subacute bacterial endocarditis Vasculitis of collagen disease Congophilic angiopathy Venous sinus occlusion Multiple cardiac emboli Artery to artery emboli Multiple hemorrhage from thrombolysis therapy (IV after myocardial infarction)
Multiple Hemorrhages From Thrombolysis Therapy (IV After Myocardial Infarction)
1. Multiple hemorrhages are unusual in spontaneous ICH 2. Multiple hemorrhages occur earlier than solitary hemorrhages after thrombolytic therapy
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3. Multiple hemorrhages a. 0.47% for streptokinase (CSK) with sc. heparin b. 0.57% for SK with iv heparin c. 0.7% accelerated TPA with iv heparin d. 0.95% for SK with both accelerated TPA and intravenous heparin 4. Time from thrombolytic treatment to ICH a. Streptokinase – 17.5 hours b. TPA – 10 hours c. TPA + SK – 13 hours 5. Factors associated with increased risk of hemorrhage after thrombolysis for MI a. Age b. Congophilic angiopathy c. Facial and head trauma 1) Risk increases if syncope had occurred < 2 days prior to treatment
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Section II EPILEPSY
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Chapter 1. Introduction
Chapter 1 Introduction
Definition: Gordon Holmes
A seizure as defined by the eminent British neurologist Gordon Holmes is a “sudden, involuntary, time limited attenuation in function, secondary to an abnormal discharge of neurons in the central nervous system”. They may be due to an acute systemic or focal neurologic lesion. Idiopathic seizures have no known underlying definitive cause. Modern imaging techniques and volumetric analysis are now revealing various migrational disorders and focal microdysgenesis of the cortex which is shrinking the percentage of truly idiopathic patients. Epileptic Seizures
1. Discrete epileptic events due to transient hypersynchronous abnormal neuronal discharges 2. Epilepsy: recurrent unprovoked seizures General Epidemiology
Overall incidence: 40–70 : 100,000 in developed countries Single seizure; 0.5–5% of the population over a lifetime Greatest incidence occurs during the first year of life Western Europe and USA: a. By the age of 20, 3% of children may have had a seizure; 25% of these will develop epilepsy b. 80% of these children are seizure free within five years; most by one year c. Approximately 20–30% of newly diagnosed epilepsy patients will develop medically refractory seizures d. Secondary rise in incidence after 60 years of age 5. Risk factors for epilepsy: a. Mental retardation b. Perinatal disorders c. Cerebral palsy d. Cerebrovascular disease e. Infection of the central nervous system f. Neoplasm g. Neurodegenerative disease h. Drug abuse i. Men 1–2.4 times at greater risk than women
1. 2. 3. 4.
Classification of Epilepsy
The International Classification of Epileptic Seizures
I. Partial Seizure: The first clinical and or EEG changes indicate initial involvement of one hemisphere. Partial seizures are classified on the basis of impairment of consciousness.
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a. Simple partial: No impairment of consciousness b. Complex partial: Impairment of consciousness c. Partial with secondary generalization II. Generalized Seizures: The first clinical and or EEG changes indicate initial involvement of both hemispheres. Consciousness is impaired. 1. Tonic clonic 4. Myoclonic 2. Absence 5. Tonic 3. Clonic 6. Atonic III. Unclassified: 1. Neonatal seizures IV. Epileptic Syndrome: A. Heterogeneous groups of disorders with specific manifestations. Classification is based on: 1. Cluster of signs and symptoms 2. Seizure type 3. Age at onset 4. EEG findings 5. Prognosis 6. Response to antiepileptic drugs (AED) Seizures Classified by Etiology
1. Idiopathic: Seizures that occur in the absence of an acute precipitating central nervous system insult, systemic metabolic dysfunction or a history of prior neurologic insult. 2. Acute Symptomatic: Seizures that occur only during the first week after an acute central nervous system lesion or are concurrent with: a. Metabolic disturbance c. Alcohol withdrawal b. Febrile episode 3. Remote Symptomatic: Seizures in a patient with a history of central nervous system insult associated with an increased risk of seizure.
Epilepsies, Epileptic Syndromes and Related Seizure Disorders; International League Against Epilepsy Classification
1. Localization-Related (focal or partial) a. Seizure semiology, EEG or MRI implicate a focal origin 2. Primary Idiopathic: a. Definition: an idiopathic disorder is one not preceded by another disorder 1) Benign childhood epilepsy with Centro-temporal spikes 2) Childhood epilepsy with occipital paroxysms 3) Primary reading epilepsy 3. Secondary symptomatic: a. Secondary to a known or suspected central nervous system disorder 4. Chronic progressive epilepsia partialis continua of childhood:
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a. Rasmussen’s Syndrome 5. Epilepsies by cortical localization: a. Temporal lobe epilepsy b. Frontal lobe epilepsy c. Parietal lobe epilepsy d. Occipital lobe epilepsy
Generalized Epilepsies and Syndromes
Idiopathic generalized epilepsies: 1. Benign neonatal familial convulsions 2. Benign neonatal convulsions 3. Benign myoclonic epilepsy in infancy 4. Childhood absence epilepsy (pyknolepsy or petit mal) 5. Juvenile absence epilepsy 6. Juvenile myoclonic epilepsy 7. Epilepsies with grand mal seizures 8. Generalized tonic clonic seizures (GTCS) on awakening
Specific Syndromes 1. Malformations 2. Inborn errors of metabolism Seizures with both Generalized and Focal Features 1. Neonatal seizures 2. Severe myoclonic epilepsy in infancy 3. Epilepsy with continuous spike-and-waves during slow wave sleep 4. Acquired epileptic aphasia (Landau–Kleffner Syndrome) Situation-Related Seizures 1. Febrile convulsions 2. Seizures occurring only when there is an acute metabolic or toxic event 3. Alcohol 4. Drugs 5. Eclampsia 6. Nonketotic hyperglycemia Isolated Seizures or Isolated Status Epilepticus
Epilepsies with Seizures Characterized by Specific Modes of Presentation
Reflex epilepsies: Specific mental or somatic events that trigger seizures: 1. Temperature change 2. Photic stimulation 3. Math (simple calculations) 4. Chess 5. Somatic (proprioception or touching the skin surface) 6. Reading 7. Auditory (specific tones) 8. Chemical smells 9. Eating 10. Walking 11. Singing Symptomatic (age-related) 1. West Syndrome (infantile spasms) 2. Lennox–Gastaut Syndrome (infancy) 3. Epilepsy with myoclonic-astatic seizures 4. Epilepsy with myoclonic absence Symptomatic Generalized Epilepsies and Syndromes: Often Associated with Diffuse Encephalopathy 1. Generalized seizures 2. Supportive EEG findings 3. Many different types of seizures in the same patient 4. Neuroradiological signs may be positive Non-Specific Etiology (age-related) 1. Early myoclonic encephalopathy 2. Early infantile epileptic encephalopathy with suppression bursts
The major problems in the epilepsies suffered by adult patients are major motor seizures and complex partial seizures. The varying auras and descriptions of complex partial seizures make them difficult to diagnose in many instances. Occasionally primary childhood seizure types extend into adolescence and adulthood and will be discussed. Congenital and pediatric seizures will not be discussed in detail, but may be mentioned for completeness.
Chapter 2 Generalized Seizures
Generalized Tonic-Clonic Seizures (GTCS)
Different cortical areas are more likely to initiate the paroxysmal depolarization shift (PDS) that initiates a generalized tonic clonic seizure (GTCS) than others. Approximately 85% of GTCS are secondarily generalized. The usual cortical area that initiates the generalized seizure is the temporal lobe followed by the frontal lobe. Frontopolar and occipital areas of the cortex are less likely to initiate a major motor seizure. The primary motor and sensory area (MI and SI) are very seizurogenic and propagate to the basal ganglia and thalamus quickly. The bilateral projections from the reticular nuclei of the thalamus to the motor cortex initiates the tonic phase of the seizure. Inhibitory interneurons in the cortex and reticular formation and cerebellar volleys terminate the tonic phase and initiate the clonic phase. Oscillatory activity between the cortex and the thalamus sustain the GTCS.
Chapter 2. Generalized Seizures
1. Clinical characteristics of generalized tonic-clonic seizures a. Prodrome: 1) Extreme fatigue several days to a week prior to seizure onset 2) Increase of nocturnal myoclonic jerks 3) Mood change 4) Increased irritability and headache b. Pretonic-clonic phase (at the initiation of the seizure): 1) Myoclonic jerks 2) Brief clonic seizures 3) Deviation of the head and eyes (frontal and rarely occipital cortical focus) c. Tonic phase: 1) Tonic contraction of the axial musculature 2) Upward eye deviation 3) Pupillary dilatation 4) Tonic limb contraction 5) “Epileptic cry” a) Sudden contraction of intercostal muscles forcing air through the larynx 6) Tongue and jaw contraction a) Tongue biting (side opposite a focal lesion) 7) Cyanosis d. Clonic phase: 1) Gradual onset 2) Low amplitudes of clonic activity 3) Frequency of eight jerks per second 4) Progressive increase in amplitude that then decreases in frequency to four jerks per second 5) Atonic inhibition supervenes: a) Loss of continence b) Atonia of somatic muscles 6) Seizures usually lasts 30 seconds to 1 ½ minutes e. Post ictally: 1) Post ictal sleep (30 minutes to one hour) 2) Confusion on awakening (minutes to one hour) is usual; may last for 1–2 hours 3) Dull pounding headache (occipital predominance) 4) Todd’s paralysis (if there is underlying structural lesion) 5) Tongue biting (more severe the side opposite a focal onset) 6) Soreness of the paraspinal muscles and large leg extensor muscles 7) Rarely bilateral posterior dislocation of the shoulders (younger patients) 8) Fracture of a thoracic vertebrae (older patients) 9) Increased blood pressure (during a seizure) 10) Severe hyperhydrosis for minutes to hours 11) Temperature to 101◦ F (sustained seizure) 12) Cerebral spinal fluid (cells up to 100 neutrophils per mm3 ) 13) Post ictal psychosis (fighting constraint)
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14) Myoglobinuria and renal failure (prolonged seizure) 15) May briefly awaken and then fall back asleep 16) Rarely trismus or opisthotonos is maintained 17) Tonic seizure more common with secondary generalized epilepsy 18) Tonic seizures of adults usually a variant of GTCS 19) Increased prolactin levels (temporal lobe focus) f. Some generalized seizures are just tonic or clonic. Sudden death may occur during sleep Rare Sequelae: 1. Neurogenic pulmonary edema 2. Cardiac arrhythmias with EKG abnormalities 3. Bleeding from the first portion of the duodenum (through and through penetrating ulcer) 4. Myoglobinuria with renal failure 5. Severe acidosis pH < 7.0 6. Posterior shoulder dislocation 7. Sudden unexplained epileptic death (SUDEP) a. Tonic clonic seizures are important proximate cause b. Incidence is 0.7–1.3/10,000 patient years c. Disease severity is the primary determining factor for sudden death d. Independent risk factors: 1) Mental retardation 2) Number of anticonvulsant drugs used 3) Increased seizure frequency Differential Diagnosis of Causes of GTCS
Generalized Epilepsy with Febrile Convulsions 1. Genetics: a. Reported loci for febrile convulsions with GTCS 1) Chromosome 5 q 14–15 2) Chromosome 8 q 13–21 3) Chromosome 19 p 13.3 (SCN 1B) 4) Chromosome 2 (SCNIA/2A genes) 2. SCN 1B and SCN 2B genes a. Modulate the expressions of Na channel alpha-subunits 3. Clinical Features: a. Benign childhood onset b. Tonic-clonic seizure without fever c. 1/3 of patients have: 1) Atonic; myoclonic; astatic seizures d. Seizures with fever after six years of age e. Simple febrile seizure (FS) 1) Followed more frequently by GTCS f. Complex FS 1) Prolonged duration 2) Followed by TLE in 25% of patients g. AD febrile seizures 1) Occur after six years of age (noted above) Generalized Epilepsy with Focal Seizures Plus (GEFS+) 1. Genetics: chromosome 19q 13.1
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a. Codes for a voltage gated sodium channel (subunit B1) b. Na channel mutation cause febrile convulsions 2. Associated with afebrile seizures 5. Metabolic Disease
1. Hypoglycemia: cerebral spinal fluid sugar is approximately 2/3 of blood sugar. Patients will have seizures when the cerebral spinal fluid sugar is less than 30 mg/dl. This occurs between 40–60 mg/dl of peripheral blood sugar. The rate at which the sugar falls may also be a determinant if a seizure will be provoked. As the blood sugar starts to fall, a nonadrenergic response causes hunger, piloerection, hyperhidrosis and abnormal behavior. Parasympathetic discharge occurs frequently when the peripheral sugar is 30 mg/dl. The temperature of the patient may drop to 97◦ Fahrenheit. 2. Hypocalcemia: a. The usual setting is renal failure b. Fasciculation of muscle may occur spontaneously or with mechanical stimuli c. Peripheral nerves may discharge to mechanical stimuli (Chvostek’s sign VIIth nerve) or to ischemia (Trousseau’s sign) d. Long QT interval; non-specific T wave change on EKG 3. Hypomagnesemia: a. Often occurs concomitantly with hypocalcemia b. Secondary to prolonged enteral feeding c. Burn patients d. Clinically similar to hypocalcemic seizures e. Increased neuro excitability; increased reflexes throughout f. EKG changes similar to hypomagnesemia; often both electrolyte abnormalities occur concomitantly. 4. Uremia: a. BUN usually between 90–120 dl% when seizures occur b. Following rapid osmotic shifts (post dialysis) c. Need to rule out intracranial blood: 1) Uremic platelet dysfunction 2) Hypertensive hemorrhage from the uremic state 3) Incomplete reversal of anticoagulation (following hemodialysis) 4) Subarachnoid hemorrhage (platelet dysfunction; combination of pathologies) d. Infection (gram bacilli negative, fungus, HIV) as cause of seizures e. Seizures are often short f. Pupillary abnormalities may occur; (usually dilated) and are often associated with uremic optic neuritis (pallor, loss of the cup) which may complicate the exam
6.
7.
8.
9.
g. Rare central pontine myelinolysis occurs (if low sodium corrected too rapidly); which may be seen in ectopic areas: midbrain, thalamus, periventricularly; and is rarely associated with seizures Hepatic encephalopathy: a. May occur with anticonvulsant medications (valproic acid and phenobarbital) b. Dilantin (Steven Johnson’s syndrome, severe arteritis with lobar hepatic infarction) c. Carbamazepine: 1) Hepatotoxicity 2) Seizures also caused by inappropriate antidiuretic hormone secretion d. Valproic acid (VPA) 1) May have hyperammonia without hepatic failure; accompanied by seizures and worsening EEG 2) Phenobarbital, phenytoin valproic acid induced encephalopathy occur with combined use 3) Vigabatrin, gabapentin and topiramate all can contribute to Valproic acid encephalopathy 4) VPA and topiramate cause hyperammonemic encephalopathy 5) Clinical features of VPA induced encephalopathy: a) Acute onset of impaired consciousness b) Focal neurological signs c) increased seizure frequency d) EEG; pronounced slowing and increased epileptiform discharges e) Patients at most risk: those with liver disease, congenital enzyme deficiencies 6) Cirrhosis Hyponatremia a. Frequently seizures are dependent on the rate at which the sodium falls b. Seizures usually occur at levels less than 110 mEq/ml c. Hyporeflexia: severe weakness are concomitant features Acute intermitted porphyria: a. Major motor seizures occur due to porphyrins themselves (mechanisms not certain) b. Inappropriate ADH c. May cause status epilepticus d. Usually associated with abdominal pain and severe motor neuropathy Inappropriate ADH: a. Usually serum sodium is between 120–130 mEq/dl b. Initiated by: 1) Head trauma 2) Metabolic abnormalities 3) Drugs (carbamazepine) 4) Paraneoplastic (rare) 5) Intracranial surgery c. May cause status epilepticus Hyperosmotic states:
Chapter 2. Generalized Seizures
a. Nonketotic-diabetic coma (blood sugar often between 2000–3000 mg/dl) b. Renal failure c. Hyperlipidemia d. Insufficient free water with PEG feedings e. Clinical manifestations: 1) Multiple movement disorders; often segmental myoclonus 2) Asterixis 3) Focal and generalized seizures 10. Pulmonary failure: a. pCO2 > 70 torr; pO2 < 80 torr b. Clinical manifestations: 1) Suffused optic disease; dilated veins; papilledema 2) Asterixis 3) Fasciculations, muscle hyperexcitability 4) Generalized seizures 11. Drugs/Toxin-associated features with GTCS: a. Often osmotic gap noted on electrolyte evaluation (with toxin) b. Specific features of different drugs and toxins: 1) Methanol: hemorrhagic optic neuritis 2) INH: hyperthermia: hyperglycemia 3) Phenothiazine: hypo or hyperthermia 4) Insulin: severe hypoglycemia 5) Anesthetics a) Propofol c) Enflurane b) Halothane d) Sevoflurane 6) Theophylline (jitteriness) 7) Disopyramide 8) Amphetamine (psychosis) 9) Tricyclic anti depressants (parasympathomimetic effects 10) Lithium (tremor) 11) Antimalarials (muscle and macular degeneration) 12) Cocaine: a) Hypertension with cerebral hemorrhage b) Severe cortical and coronary artery vasospasm c) Hemorrhage if underlying vascular abnormality is present 13) Heroin: pulmonary edema, transverse myelitis 14) PCP: hallucinations, self destructive behavior, changing nystagmus 15) Anticonvulsants: liver failure, ophthalmoplegia (phenytoin; rarely carbamazepine) 16) Penicillin: large IV doses; setting of renal failure 17) Alcohol withdrawal: hypothalamic disinhibition, delirium, tremens
Infections Associated with GTCS
1. The cortex must be involved to initiate a major motor GTCS
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a. Diffuse inflammation of the meninges occurs with infections that spread to the arachnoid and pia mater b. Cortical stroke is caused by: 1) Tuberculosis (endarteritis, meningeal involvement) 2) Cryptococcosis (meningeal) 3) Mucormycosis (sinus spread) 4) Aspergillus (venous spread); often lung abscess is the source 5) HIV (blood vessel involvement directly; endothelial cell damage) 6) Syphilis (proliferative endarteritis); often brainstem 7) Subacute bacterial endocarditis (aneurysms; late focal hemorrhage) 8) Cysticercosis (calcification with adjacent cysts) 9) Toxicants (toxocana canis); primarily children 2. Direct cortical involvement: a. SBE (gram negative or positive) b. HIV c. Toxoplasmosis d. Opportunistic infections in an HIV infected patient e. Parasitic infections (tropical) (setting of metabolic dysfunction) 3. Other causes of GTCS: a. Venous infarction (often postpartum) b. Vascular (infarction, hemorrhagic, malformation) c. Tumor (primary and metastatic) d. Head injury (acute or distant past) e. Prior cortical scar (setting of metabolic dysfunction) f. Prior stroke (at least 10% of stroke patients) g. Anticonvulsant withdrawal h. Alcohol withdrawal 4. Precipitating factors for GTCS: a. Failure of drug compliance b. Alcohol withdrawal c. Specific drugs that cause seizures: 1) Cocaine 2) Antihistamines 3) High doses of penicillin (renal failure) 4) Phenothiazine (particularly if there is a preexisting structural lesion) 5) Phosphodiesterase inhibitors (asthma) d. Hypoglycemia (missing breakfast then administering insulin in a diabetic) e. Stress f. Lack of sleep Differential Diagnosis of GTCS by Age
1. Adolescent: a. Idiopathic b. Noncompliance with drug therapy c. Drugs (cocaine, PCP, barbiturate, and alcohol withdrawal) d. Metabolic (hypoglycemia) e. Vascular (infarction embolus, hemorrhage malformations)
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f. g. h. i.
Tumor (rare) Encephalitis Head injury Migrational disorders (nodular and band heterotopia; microdysgenesis) j. Hippocampal sclerosis with secondary generalization k. Syndromic (tuberous sclerosis); Chromosal defects l. Mitochondrial disease 2. Adult < 40 a. Lack of AED drug compliance b. Drugs (cocaine) c. Vascular (embolus, hemorrhage, infarction) d. Tumor (primary greater than secondary) e. Infection (HIV associated) f. Head injury g. Cardiac arrhythmia (global cerebral ischemia) h. Metabolic causes i. Migrational disorders 3. Adult > 40 a. Vascular; embolus > infarction > hemorrhage b. Lack of drug compliance (AED’s) c. Cardiac arrhythmia d. Tumor (metastatic > primary) e. Metabolic causes f. Drugs (hypnotic sedative withdrawal; elicit) g. HIV (associated opportunistic infection) h. Herpes simplex infection (TLE with secondary generalization) i. Migrational disorders 4. Adult > 60 a. Cardiac arrhythmia b. Cerebrovascular disease (infarction > embolus > hemorrhage) c. Metabolic dysfunction d. Prior CNS structural lesion e. Tumor (metastatic > meningioma > lymphoma) f. Herpes simplex infection (bitemporal and frontal lobe involvement) g. Rarely migrational disorder
Absence Seizures
1. General features: a. Onset between 3–6 years of age b. Most prevalent in first 10 years of life c. Rarely persist into adulthood d. Petit mal status is rare in adults e. Seizures are short, less than 30 seconds f. Never associated with an aura or post ictal confusion 2. Clinical Types: a. Simple typical absence: 1) Sudden onset of impaired consciousness associated with absence of facial expression and without motor or behavioral manifestations
2) Approximately 10% of absence seizure patients have this type b. Complex typical absence seizure: 1) Accompanied by motor, behavioral or autonomic features 3. Clinical features: a. Sudden onset of a blank stare b. Arrest of motor activity c. Clonic components: eye blinking, nystagmus, rapid jerking of the arms d. Tonic postural contraction causing flexion or hypertonic extension postures e. Loss of tone causes head nodding or dropping of objects f. Patients rarely fall g. Automatisms: 1) Occur in approximately 40% of typical absence seizures 2) Automatisms are semi-purposeful movements and behaviors which the patient cannot recall. They are perseverative or de novo: a) De novo: simple acts such as hand rubbing, licking the lips, chewing, scratching, picking at clothes b) Perseverative: dealing cards, handling an object or playing a hand game c) Speech is usually dysarthric, it may be normal or perseverative h. Autonomic manifestations: 1) Pupillary dilation 4) Piloerection 2) Hyperhidrosis 5) Urinary incontinence 3) Salivation 4. Atypical Absence Seizure: a. Onset prior to age 5 b. Associated with other generalized seizure types and mental retardation EEG: 1.5–2.5 Hz spike-and-wave discharges or multiple spike-and-waves that are irregular or asymmetrical; interictal EEG is unusually slow and demonstrates multifocal epileptiform features. c. Average seizure is longer than typical absence; onset is less abrupt d. Diminished postural tone; tonic or myoclonic activity is more frequent than in typical absence seizures: 1) Automatisms are more perservative in atypical absence seizures than in typical absence seizures (AS) 2) Postural tone changes are more frequent in atypical absence seizures (AAS) than typical absence seizures (TAS) 3) A blank stare or change in facial expression > AAS than TAS 4) Smiling automatism common in AAS 5) Hyperventilation may induce absence seizures; this rarely occurs in CPS or GTCS 6) Photic stimulation may induce GTCS, absence, atypical absence or CPS
Chapter 2. Generalized Seizures
e. Adult petit-mal status occurs rarely and usually presents as confusion or stupor f. Between 40–60% of patients with TAS have GTCS 1) First absence to first CTS: 1 to 16 years 2) AAS: almost always have GTCS’s, myoclonic, tonic and TAS seizures concomitantly 3) Partial seizures are uncommon in AAS and TAS 5. Absence Syndromes: a. Generalized idiopathic epilepsies: 1) Childhood absence 2) Juvenile absence 3) Juvenile myoclonic b. Generalized symptomatic epilepsies: 1) Lennox–Gastaut Syndrome 2) Epilepsy with myoclonic astatic seizures 3) Epilepsy with myoclonic absences 6. Generalized idiopathic Epilepsies: a. Childhood absence: 1) Typical absence (simple and complex) 2) Onset: 3–5 years and puberty 3) Genetic predisposition 4) Girls more frequently affected 5) Frequent: up to several hundred per day and may cluster 6) EEG: bilateral symmetrical synchronous 3 Hz spikes and wave discharges; normal interictally 7) Absences may remit during adolescence: 25–30% develop GTCS b. Juvenile absence Epilepsy: 1) starts around puberty 2) seizures are more sporadic 3) fewer retropulsive movements 4) generalized tonic-clonic and myoclonic seizures occur upon awakening 5) males equally affected 6) EEG: spike-and-wave is faster than 3 Hz Juvenile Myoclonic Epilepsy of Jansen: 1. Starts 12–18 years of age (few patients start in the late 20’s) approximately 4–10% of epilepsy 2. Genetics: a. AD b. Chromosome 6q; 15q 3. Early morning: mild to moderate myoclonic jerks of the neck, shoulders and arms 4. Patients may just notice shakiness or nervousness upon awakening or drop or throw objects (hair brush) 5. GTCS occur in 90% of patients: 1/3 suffer absence seizures 6. Myoclonic jerks may culminate in GTCS 7. Seizures precipitated or increased by awakening, fatigue, alcohol or by recreational drugs; 30–35% of patients suffer absence attacks 8. EEG: interictal 3.5 to 6 Hz, irregular spike and wave and multiple spike and wave complexes 9. Rapid 10–16 Hz spikes followed by irregular slow waves are noted during the myoclonic seizures
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10. EEG activated by sleep deprivation and photic stimulation 11. JME persists for life 12. Drinking on the weekend in adults may initiate myoclonic seizures with GTCS on Monday morning Epilepsy with Generalized Tonic-Clonic Seizures on Awakening 1. General features: a. Onset occurs in the second decade b. 90% of seizures occur on awakening at any time of the day c. May occur with relaxation in the evening d. Associated with absence and myoclonic seizures
Generalized Symptomatic Epilepsies Lennox–Gastaut Syndrome
1. Onset usually prior to age 5 (may start as late as age 8) 2. Tonic, atonic and absence seizures are most typical. May also have myoclonic, GTCS or partial seizures 3. EEG: slow spike-and-wave less than 3 Hz; abnormal background multifocal abnormalities 4. Pathology: both structural and metabolic 5. Seizures are refractory 6. Developmental outcome guarded Epilepsy with Myoclonic-Astatic Seizures 1. Onset between the ages of 7 months to 6 years (usually between 2–5 years) 2. Normal developmental background 3. Hereditary predisposition 4. Boys are affected twice as often as girls (unless onset is within the first year) a. Seizures: myoclonic, astatic; myoclonic-astatic, absence or tonic-clonic, frequent status epilepticus 5. EEG: initially normal, but with 4–7 Hz theta/rhythms; evolves into irregular fast spike-or-multiple spike-andwave complexes Epilepsy with Myoclonic Absences 1. Onset usually at 7 years of age 2. Boys more affected than girls 3. EEG: similar to absence seizures 4. Seizures are frequent and less responsive to medication than with childhood absence seizures 5. Mental deterioration and evolution to Lennox–Gastaut occurs Landau–Kleffner Syndrome 1. General features: a. Presents between 3–9 years b. An acquired aphasia associated with seizures c. Seizures may be GTCS, myoclonic or partial d. Word deafness with normal hearing is the seminal feature
SECTION II. Epilepsy
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2. EEG: a. Spike activity over the central temporal regions b. Multifocal spike and slow wave patterns may occur
3) 4) 5) 6) 7)
Absence Status Epilepticus
Clinical features: 1. Sustained impairment of consciousness 2. Patients are confused 3. Partially responsive and able to perform activities of daily living 4. Facial twitching 5. Eye blinking 6. Staring 7. Automatisms 8. EEG: generalized irregular approximately 3 per second spike-and-wave discharges; prolonged generalized bursts of spike-and-wave discharges or irregular slow spikeand-wave discharges 9. Ictal stupor in adolescents with history of childhood absences after seizure free interval 10. Most commonly arms, neck and facial muscles are involved 11. More common in children than adults Electrical Status Epilepticus During Slow Wave Sleep 1. General features: a. Present between 1–12 years of age b. Cognitive regression c. Patient may not have clinical seizures 2. EEG: a. Seizures are commonly nocturnal b. Continuous spike and slow wave during NREM sleep c. Seizures and EEG changes may disappear during the second decade d. Continued cognitive and language deficits
Chapter 3 Progressive Myoclonic Epilepsy 1. General features: a. Primarily a heterogenous group of genetic disorders caused primarily by inborn errors of metabolism b. Major clinical features: 1) Myoclonus 2) Seizures 3) Cognitive decline 4) Progressive neurologic deficits c. Differential diagnosis: 1) Lysosomal storage disease 2) Mitochondrial disorders
8) 9) 10) 11) 12) 13) 14) 15)
Unverricht–Lundborg disease Lafora body disease Hallervorden–Spatz disease Action myoclonus renal failure syndrome Dentatorubral pallidal Luysian Sylvian atrophy (DRPLA) Sialidosis Adult onset polyglucosan body disease Gaucher’s Disease Celiac Disease Neuroaxonal dystrophy Dawson’s encephalopathy Biotin responsive encephalopathy Familial adult myoclonic epilepsy
Myoclonic Syndromes
1. General Features: a. Myoclonic Seizures: 1) Sudden, lightening like contractions of groups of muscles 2) Faster than contractions of muscles noted with clonic seizures 3) Any group of muscles may be affected 4) Patients may fall 5) Myoclonic jerks may occur as a component of an absence seizure or at the onset of a GTCS Early Infantile Myoclonic Encephalopathy (Otohara Syndrome) 1. General features: a. Initial seizures are myoclonic b. Myoclonic seizures prior to 3 months have severe underlying pathology c. No established link with immunization d. Myoclonic seizures are followed by partial seizures, tonic spasms and GTCS e. Psychomotor deterioration 2. EEG: a. Burst suppression b. Neonate presents with burst suppression and evolves to intermittent high amplitude spike and wave complexes West Syndrome 1. Clinical features: a. Infantile spasms b. Arrest of psychomotor development c. Hypsarrhythmia on EEG d. Onset prior to one year (3–7 months) e. Spasms occur in clusters; sudden flexion or extension of the trunk; jack knife pattern (flexion of the head and neck and adduction of the arm) Familial Adult Myoclonic Epilepsy 1. Genetics:
Chapter 3. Progressive Myoclonic Epilepsy
a. Chromosome: 8 q 24; AD b. European family described without linkage to 8 q 24 c. Baltic familial myoclonic epilepsy and familial adult myoclonic epilepsy are on chromosome 8 q 23.3–q 24.1 2. Clinical features of FAME: a. Adult onset of extremity myoclonus b. Infrequent seizures c. Non progressive d. Giant SEP (somatosensory evoked potentials) e. Enhancement of C reflex f. Pre-myoclonus spike g. Onset greater than 30 years of age h. Familial cortical tremor 1) Variant of cortical reflex myoclonus 3. Some Japanese families have: a. FAME; BAFME (Baltic Familial Myodemic Epilepsy); FCT (familial cortical tremor) 4. Lafora body disease a. AR: both sexes equally affected; chromosome 6q b. Clinical features: 1) Seizures 2) Myoclonus a) Affects any area of the body b) Startle sensitive c) Absent during sleep 3) Dysarthria 4) Rigidity 5) Spasticity 6) Dementia follows seizures in two to three years 7) Onset in adolescence or in late childhood; progresses to death between 17–24 years in 90% of patients 8) Generalized tonic-clonic seizures are presenting features; status epilepticus in terminal stage 9) Visual seizures occur in 50% of patients: a) Scotomata c) Occipital CPS b) Simple hallucinations 10) Fluctuating course associated with episodes of cortical pseudo blindness c. EEG: bilaterally synchronous spike and wave complexes noted in association with the myoclonic jerks d. Lafora bodies: 1) PAS positive intracellular inclusions < 3 μm to 30 μm 2) Located in the neuronal perikarya; cerebral cortex, substantia nigra, thalamus and globus pallidus 3) Lafora bodies are found in: heart, skeletal muscle, skin, retina, liver 4) Branched polysaccharide Unverricht–Lundborg Disease (Baltic myoclonus) 1. Genetics: located on chromosome 21q 22.3; AR 2. Mutation in EPM 1 gene a. Encodes cystatin B b. Inhibits cathepsins
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1) Intralysosomal cystine proteases 3. Clinical features: a. Stimulus sensitive; action myoclonus b. Age at onset 8–13; begins insidiously c. Tonic clonic seizures d. Ataxia, dysarthria, decreased swallowing e. Mild dementia f. Exacerbated by phenytoin g. Myoclonus is incapaciting 4. MRI: a. Atrophy of the medulla, pons and cerebellar b. OPCA has V shape of the pons hemispheres 5. Pathology: a. Loss of Purkinje cells, dentate and olivary neurons
Sialidosis
1. 2. 3. 4.
Melioidosis 1 Oligosaccharide sialidosis deficiency Genetics: juvenile Type III; chromosome 10 Clinical features: a. Onset at 6 months b. Mild Hurler’s features (facial dysmorphism) c. Corneal clouding d. Macular cherry red spot e. Mental retardation f. Myoclonic jerks g. Seizures h. Neuropathy
MERRF (Mitochondrial Encephalomyopathy with Ragged Fibers)
1. 2. 3. 4. 5. 6. 7.
Short stature Diabetes mellitus Sensory neural hearing loss Abnormal collection of mitochondria on muscle biopsy Proximal weakness Progressive myoclonic epilepsy Other mitochondrial diseases have myoclonic epilepsy
Neuronal Ceroid Lipofuscinosis
A. Juvenile variant (Spielmeyer–Sjögren Disease) 1. Genetics: AR; chromosome 16p 2. Abnormal lipopigments found in abnormal cytosomes (curvilinear and finger print bodies); abnormalities seen in skin, muscle, peripheral nerve in addition to central nervous system 3. Clinical features: a. Onset 5–10 years of age b. Begins with progressive visual loss
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SECTION II. Epilepsy
c. Pigmentary degeneration of the retina d. Myoclonic and generalized seizures e. Death by end of the second decade B. Adult variant (Kufs disease) 1. Genetics 2. Clinical features: a. Onset in third or fourth decade b. Progressive dementia c. Seizures d. Myoclonus e. Ataxia f. No blindness or retinal degeneration Rare Causes of Progressive Myoclonic Epilepsy: 1. Gaucher’s Disease 2. GMI gangliosidosis 3. Biotin responsive encephalopathy 4. DRPLA-SCA-7 5. Atypical inclusion body disease (Derision’s encephalopathy) 6. Action myoclonus renal failure syndrome 7. Neuroaxonal dystrophy 8. Hallervorden-Spatz Disease 9. Celiac Disease 10. Dutch mt-DNA deficiency (fatal myoclonus epilepsy) 11. HARP
Tonic Seizures
Clinical Features: 1. Brief, usually less than 10 seconds; may last 60 seconds 2. Sudden onset of increased tone in extensor muscles; may be preceded by a myoclonic jerk 3. Patients fall; may be limited to only this manifestation 4. There is impairment of consciousness during the seizure 5. Frequently seen with Lennox–Gastaut Syndrome (mental retardation, mixed seizure disorder, slow spike-and-wave EEG pattern) 6. Apnea due to involvement of the intercostal muscles 7. Long seizures appear to have a clonic component (more frequent at night) 8. Only the axial muscles may be involved
Clonic Seizures
1. Similar to GTCS 2. Rhythmic or semi-rhythmic contractions of a group of muscles 3. Jerks can involve any group of muscles: arm, face > legs Atonic Seizures: 1. Begin in the late infancy; may start in adolescence 2. Sudden loss of muscle tone; no aura 3. Last 1–2 seconds
4. No postictal impairment 5. If trunk is involved the patient falls; if only the neck extensors are involved there is head drop; may be limited to eye blink 6. Longer atonic seizure are associated with loss of consciousness 7. May be seen as component of other seizures 8. Absence seizures often have an atonic component 9. Myoclonic jerk may precede or accompany the seizure 10. Long seizures cause seconds of flaccid paralysis 11. EEG: poly spike and wave or generalized spike and wave are associated with myoclonic jerks Focal Akinetic Seizure: 1. Focal paresis precedes convulsive activity in the affected part 2. Focal paresis may affect one part of the body; convulsive activity may then occur in the affected part 3. Somatosensory sensations may occur before or at the onset of the focal paresis in the same body region 4. Structural lesions have been documented in central parietal regions 5. Patient is motionless with impaired consciousness Epileptic Negative Myoclonus: 1. Action-activated motor activity (jerks) limited to one arm or leg 2. Rarely may be multifocal 3. Patients may demonstrate motor neglect of the affected part 4. Most patients have history of seizures 5. Paroxysmal epileptic activity is seen in areas of the sensorimotor cortex
Chapter 4 Partial Seizures 1. Simple motor partial seizure: a. Motor signs and symptoms depend on the area of the motor cortex activated b. Motor cortex (patterns of spread of the primary motor cortex): 1) Thumb initiates clonic movements followed by twitching of the corner of the mouth and arm; spread is then to the distal leg, the shoulder is often spared 2) Distal leg to proximal leg. The trunk may be spared. Spread is next to the hand, thumb and face 3) Simple partial motor seizure, particularly of the upper extremity may last for days to weeks a) Menshikoff’s syndrome b) Usually follows old vascular lesion c) Very difficult to treat
Chapter 4. Partial Seizures Simple Sensory Partial Seizures
1. Jacksonian march very similar to that noted with motor seizures 2. Face and hand particularly involved (low threshold of neurons to fire; large cortical area) 3. Trunk is involved in a sensory “march” or spread with simple sensory seizure 4. Areas of origin: usually primary homunculus of S1 or posterior parietal sensory area 5 and 7 5. Occasionally sensory seizures may begin in proprioceptive components of the sensory cortex with consequent posturing of the affected extremity; may be initiated by a specific posture 6. Posterior partial sensory seizures may initiate a feeling of tingling in a parietal sensory distribution. Patients may also feel tired 7. SII involvement: causes a sensation of heat that spreads from the feet and envelops the body bilaterally. Most often from spread of a temporal lobe focus
Occipital Lobe Seizures
Seizures emanating from the occipital lobe present a variety of neurological signs and symptoms. In general, forced eye versive movements are a frontal lobe phenomena, but may also occur from seizures of the parietal occipital junction. Oculogyric or oculoclonic eye movements (tonic or clonic contraversive gaze deviation) may occur from occipital seizure foci. Visual symptoms are the most common symptoms of occipital lobe seizures. Area 17 is associated with non-colored flashes of light, teichopsia, scotomata, hemianopia or blindness. Area 18 and 19 association area seizures are associated with moving geometric forms that are colored or patterned (photopsia). If the seizure spreads to the temporal-parietal occipital junction complex visual images may be noted. These consist of visual distortions, micropsia, macropsia, perception abnormalities or visual hallucinations. The later usually are images of past experiences that also may be distorted.
Occipital Lobe Visual Simple Partial Seizure
1. Occipital pole area 17 a. Patients’ experience simple non-colored flashes of light (dots or stars or flashes; in general they do not move across the visual field) 2. Area 18 and 19 visual association cortex: a. Colored (red, green, yellow, blue) geometric figures are experienced b. Figures move across the contralateral visual field 3. Posterior temporal/parietal/occipital junction: a. Specific distortions of the visual object occur
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b. Images are colored c. Associated with other temporal lobe semiologic phenomena 4. Unilateral eye blinking 5. May have cortical blindness 6. Epileptic akinetopsia a. Illusory motion perception b. Occurs in the contralateral field from the focus 7. Epileptic monocular nystagmus
Non-Tumoral Occipital Temporal Epilepsy
1. Seizures from occipital lobes demonstrate heterogeneous patterns of spread a. Spread through inferior longitudinal fasciculus to the temporal lobe This is sufficient spread to activate cortical mediotemporal structures b. Occipital lobe signs and symptoms: 1) Forced eye blinking 2) Blurred vision 3) Flashing lights 4) Ictal blindness 5) Elementary visual hallucination (rare) 2. Signs of occipital seizure spread to temporal lobe: a. Visual component d. Dizziness b. Psychical aura e. Somatosensory aura c. Olfactory aura 3. Seizures with occipital lobe symptoms: a. Approximately 2/3 have temporal auras b. 1/3 have both temporal and frontal auras 4. Periventricular subcortical nodular heterotopias present with temporal-parieto-occipital semiology 5. Focal cortical dysplasia includes polymicrogyria, heterotopias and abnormal lamination. Migrational disorders tend to occur posteriorly. The causes of these disorders if post migrational are: a. Watershed MCA/PCA hypoperfusion b. Prenatal occlusion of the precuneus branch of the PCA (parieto-occipital area) 6. Clinical features of bilateral parasagittal and parietooccipital polymicrogyria induced seizures are: a. Complex partial seizures with minor automatisms b. Patients maintain an average IQ or suffer mild mental retardation 7. Photo sensitive epilepsy with absence and absence status: a. Clinical features: 1) Usually children 2) Early or late onset of benign childhood partial seizures with occipital paroxysms 3) Seizures are elicited by elimination of central vision and fixation 4) Seizures persist as long as the eyes are closed 5) Seizure activity inhibited by patterned vision
SECTION II. Epilepsy
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6) Seizure types: a) Brief absences c) Atypical absence status b) GTCS
Differential Diagnosis between Occipital Seizures versus Migraine Headaches
1. Vomiting may be ictal (right temporal lobe) or part of migraine 2. Hemicranial headache: a. Seizure focus is in the amygdala or hippocampal formation (ipsilateral) b. May also be accompanied by nausea and vomiting (most often migraine) 3. Rapid onset and resolution of symptoms are most often an epileptic discharge 4. Points favoring migraine: a. Prolonged attack b. Severe nausea and vomiting preceded by a visual aura c. Slight impairment of processing rather than complete unresponsiveness
Fixation-Off Sensitive Seizures (FOS) a. Elimination of central vision and fixation induces spikes on EEG 1) Unilateral or bilateral 2) High amplitudes
Division A: Temporal Lobe Epilepsy
The major seizure problem in adults and the source of 75% of intractable epilepsy is complex partial epilepsy of temporal lobe orgin. The spectrum of symptoms is wide and the semiology differs from patient to patient. The symptoms reported may be the only ones remembered and not in the area that initiated the seizure. MRI techniques, PET and SPECT evaluations as well as intraparenchymal recordings now demonstrate significant abnormalities in medial temporal lobe areas and migrational defects that involve the germinal matrix, and focal dysplasia (abnormal lamination) within the cortex itself. Many intractable patients suffer the dual pathology complex of medial hippocampal sclerosis and migrational disorder. Extra temporal foci with spread from the frontal parietal and occipital lobe are a major clinical phenomenon.
Photosensitive Epilepsy (PSE) Genetics of Temporal Lobe Epilepsy
1. 2. 3. 4.
Affects 1 : 4000 seizure patients Most prevalent in adolescence High incidence of family history of epilepsy in PSE General features: a. Stimuli are flashing lights or high contrast patterned stimuli b. Chromatic sensitivity c. Stimulus frequency: 10–30 Hz d. Pattern sensitivity: 0.5 to 6 cycles/degree 1) Chromatic sensitive seizure variant 2) Photoparoxysmal response to rapid color frame changes (blue to red; monochromatic light)
Epilepsy Provoked by Television and Video Games 1. EEG activated by: a. Video screens b. Flickering screen light c. Patterns produced parallel lines that form the image d. Frequency of 25 Hz activate 75% of patients e. Seizure types: 1) Absence 3) Tonic clonic 2) Myoclonic 4) Occipital lobe partial 2. Sensitivity to seizures increases: a. Screen brightness b. Highly contrasted pattern c. Fatigue d. Fever e. Close distance f. Sleep deprivation
Autosomal Dominant Partial Epilepsy with Auditory Features (ADPEAF): 1. Chromosome 10q: gene LG 1 I (leucine rich glioma inactivated protein) 2. Clinical features: a. Onset in the first to third decades b. Not preceded by febrile convulsions c. MRI shows no focal lesions d. Some patients have a receptive aphasic e. Some patients have visual symptoms f. May be developmental abnormality in the affected cortex in 50% of patients 3. LG 1 I gene mutations: a. First described in glial tumors; deletions or rearrangements b. Cause protein truncation; putative loss of function Familial Mesial Temporal Lobe Epilepsy (FMTLE) 1. Clinical features: a. Onset in the second to fifth decade b. No MRI lesions in the temporal lobe or hippocampal formation c. No prior febrile convulsions d. Autonomic and psychic auras; high incidence of déjà vu as an aura FMTLE Associated with Hippocampal Sclerosis: 1. Genetics: a. Some families AD inheritance
Chapter 4. Partial Seizures
2. Hippocampal sclerosis may be caused by: a. Prolonged childhood convulsion b. Encephalitis c. Developmental or migrational defect d. Putative genetic component FMTLE Associated with Febrile Convulsions 1. Genetics: a. One French family-digenic inheritance 1) First to second decade of life onset of seizures 2) Benign course 3) No MRI or temporal lobe lesions b. ADTLE with FS 1) Young age at onset 2) Multiple febrile convulsions 3) No déjà vu, auditory or visual hallucination 4) No hippocampal sclerosis Febrile seizures with medial TLE 1. Genetics: a. Families may have many members with febrile convulsions and a few with TLE 2. Clinical features: a. Association in some patients between prolonged febrile convulsion and HF sclerosis HIMAL 1. Possible familial occurrence 2. Incomplete inversion of the hippocampus 3. Normal size and hippocampal MRI signal 4. Blurred internal structure TLE in the Spectrum of Partial Epilepsy Syndromes 1. Clinical features: a. Familial partial epilepsies: TLE is part of the seizure spectrum A. Specific Syndromes: 1. Familial partial epilepsy with variable foci (FPEVF) a. Onset first to third decade b. Heterogeneous seizure types c. No associated MRI defects or febrile convulsions 2. Genetics of FPEVF a. Possible linkage to 2q b. Two large Canadian families linkage to 22q 11–q12 B. Partial epilepsy with pericentral spikes (PEPS) 1. Clinical features: a. Benign b. Onset first to second decade c. Brazilian family d. Pericentral spikes on EEG e. No MRI or febrile convulsions 2. Genetics: a. Linkage to 4p 15 C. Miscellaneous genes putatively important for TLE: a. IL1B gene b. Subunit opioid gene
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c. Prodynorphin gene 1) Chromosome 20 d. 8q epilepsy e. FAME (familial adult myoclonic epilepsy) f. BAFME (Baltic familial myoclonic epilepsy) g. FCT (familial cortical tremor) h. Epileptic monocular nystagmus General features of TLE 1. May begin at infancy or in old age; most patients have their first seizure in late childhood or early adulthood 2. 75% of patients experience auras of simple partial seizures originating in the temporal lobe 3. Genetic forms: a. Familial b. Chromosome localization as noted above 4. Risk factors for TLE a. Head trauma b. Difficult birth (prolonged delivery, forceps, obstetric complications) c. Genetics d. Family history e. Neuronal migration defects 5. Auras are experienced either independently or as the first phase of a complex partial seizure 6. 50% of patients have unilateral or bilateral secondary generalized tonic; clonic or tonic-clonic seizures 7. Secondary generalization may cause a tonic drop attack; greater than 80% of GTCS are secondarily generalized from TLE Clinical features: 1. Prodrome; an awareness of an impending seizure days in advance. Prodromes consist of: a. Headache d. Personality change b. Irritability e. Depression c. Insomnia 2. Complex partial seizures are either: a. Initiated by an aura b. Start with impairment of consciousness
Auras
An aura: That portion of the CPS that occurs before consciousness is lost (if it is) and is remembered. The aura is an ictal event. General Features of Automatisms: 1. Involuntary motor activity occurring during the period of impaired consciousness 2. Patient is partially or totally amnestic for the behavior 3. May continue or begin in the post ictal period 4. May be a continuation of movements that occurred prior to the seizure (perservative) or may be a new (de novo) movement
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SECTION II. Epilepsy
5. Motor activity is usually fragmentary; rarely are these sequential coordinated movements 6. Automatisms vary from patient to patient, but are stereotyped for an individual patient 7. May occur with absence seizures and in the post ictal phase of a generalized tonic-clonic seizure 8. HF-amygdala complex; rarely meso orbital frontal lobe and ungulate gyrus are the initial site of origin of motor automatisms. Oral buccal automatisms most often originate from the amygdala frontal operculum. Patterns of Clinical Automatisms 1. Oro-buccal lingual: smacking of the lips, chewing, swallowing, choking, eating, spitting abnormal tongue movements and water drinking (amygdala; frontal operculum) 2. Gestural: repetitive movements of the hands and fingers; may be semi purposeful (drawing, playing cards) rubbing the nose (ipsilateral focus) 3. Sexual: masturbation, pelvic thrusting 4. Expressional: facial expressions of fear anxiety, confusion or anger 5. Motor: walking (poriomania), running (cursive); circling with arms raised 6. Speech: crying (dachrymistic), laughing (gelastic); repeating phrases; screaming The Sequence of Motor Automatisms 1. Arrest phenomena: a. Patient stops activity and maintains a posture for a few seconds 2. Autonomic phenomena a. Loss of facial expression associated with pallor 3. Onset of motor phenomena a. Motor automatisms originate most often in the amygdala and amygdala fugal pathways as well as pre-motor and supplementary motor cortex patterns from temporal lobe and frontal lobe Psychic symptoms: 1. Often preceded by alterations in consciousness a. Important in localization b. General rules: 1) Severe anxiety: anterior temporal lobe 2) Complex phenomena (neocortical) lateral temporal lobe 3) Fear, impending doom: medial temporal lobe 2. Complex cognitive emotional states (lateral temporal lobe; right side greater than the left) a. Dream state b. Detachment and strangeness c. Autoscopy: feeling as if you are watching the event d. Time distortion (usually too slow) e. Feelings of unreality f. Forced thinking (continued thinking of a specific thought or phrase) g. Blocking thought
3. Affective symptoms a. Ictal fear; poorly localized, may be associated with abdominal sensation, impending doom, an overwhelming quality (amygdala or medial HF) b. Sadness (common) c. Depression (common) d. Embarrassment (usually medial frontal lobe) e. Joy (rare) f. Ecstasy (rare) g. Crying (dachrymistic): often bilateral temporal lobe foci (mirror focus); may be ictal or post ictal h. Sexual feelings (orgasm right temporal hemisphere) i. Altered body sensation j. Gelastic (laughing): more common with hypothalamic lesions (particularly hamartomas); laughter without mirth, not elaborated correctly; patient may be fearful while laughing 4. Distortion of memory: a. Déjà vu: as if the experience had occurred before: 1) déjà-vu: visual experience 2) Entendu: auditory experience 3) Jamais-vu: prior experience or place is experienced as new or unfamiliar 4) Vivid “flashbacks” of past events 5) Special sensory symptoms 5. General features: a. Alterations of perception 1) Unusual clearness 2) Heightened sensitivity 3) Premature poorly formed hallucinations (primary visual and auditory receptive areas) 4) Complex hallucinations from association areas 6. Fear as a main feature of an epileptic seizure a. Localization of the primary epileptic zone: 1) Right temporal 3) Frontal 2) Bitemporal b. Behavior: 1) Sensation of fear 3) Coordinated behavior 2) Autonomic symptoms c. Neuroanatomical Networks Involved 1) Orbito frontal cortex 2) Anterior cingulate gyrus 3) Temporal limbic system a) Amygdala to the anterior cingulate gyrus d. Clinical features of a panic attack (psychiatry): 1) Sudden spontaneous onset (rarely a trigger) 2) Intense fear and discomfort 3) Impending doom thoughts of dread 4) Feelings of being trapped; losing control 5) Last for a few minutes 6) Full recognition and remembrance of the attack e. Fear as a manifestation of amygdala seizure: 1) Anticipatory anxiety 2) Expression of impending doom 3) Buccal automatism
Chapter 4. Partial Seizures
4) 5) 6) 7)
Autonomic disturbance Complex behavioral automatisms Early in the seizure a call for help; anxiety Incomplete recall for the event
Visceral Auras 1. Olfactory (uncus of the hippocampal gyrus); uncinate fits a. Unpleasant smells; burning rubber, garbage, fecal material, acid; rarely pleasant (usually an exaggeration of the pleasant quality) b. May be produced by stimulation of: 1) Amygdala 2) Olfactory bulb 3) Uncus 4) Posterior orbital frontal cortex c. Olfactory auras may be associated with: 1) Intellectual aura 2) Gustatory, visual and auditory auras 2. Taste (enterorhinal cortex of the temporal lobe) a. Unpleasant: blood, bitter, chemical, rotting, metallic b. Rare pleasant (usually a too sweet taste) 3. Abdominal aura: a. General characteristics: 1) Occurs in 20–60% of patients with TLE 2) Approximately 20% of patients with extra temporal epilepsy 3) Approximately 65% with mesial temporal lobe origin on 35% with neocortical origin 4) Occurs in extratemporal locations: a) 5% perirolandic b) 17–20% parieto occipital c) 3% frontal lobe 5) Occurs primarily from posterior insular cortex; frontal orbital areas connect to anterior insular cortex b. Specific simple sensations: 1) Epigastric rising sensation 2) Feeling of having to defecate 3) “flip flop” of the stomach 4) Automatism follow abdominal auras c. Associated symptoms with abdominal aura 1) Epigastric aura a) Ictal vomiting 2) Subjective fear 3) Oro-alimentary symptoms d. May evolve into clonic seizures 1) Occurs in 2/3 patients with frontal lesions e. Abdominal pain in TLE 1) Pain occurs in 5% of all abdominal auras 2) Pain occurs in 50% of all abdominal auras that originate from the frontal lobe 3) Painful abdominal auras may originate from parietal areas 4. Rare visceral auras: a. Burning, tingling, gnawing, choking, throat sensations
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b. Ictal hunger (right temporal lobe) c. Ictal thirst (amygdala to hypothalamus) d. Severe pain or unusual genital sensations e. Severe vomiting (right temporal focus) f. Goose bumps g. Coldness-shivering (left temporal lobe) h. Expectorations (left temporal lobe) 5. Cardiac and chest aura (anterior insular cortex) a. Heart racing or pounding b. Pain in the central chest (no cardiac radiations) c. Cardiac arrhythmias (atrial or ventricular) 6. Post ictal coughing and nose rubbing a. Ictal activation of central autonomic pathways b. Post ictal coughing 1) Reaction to increased respiratory secretions c. Postictal coughing > postictal nose rubbing d. Post Ictal Coughing 1) Earlier in onset than PIN rubbing 2) PIC just prior to ictal off set 3) PIC > temporal lobe than extra temporal focus 4) Right sided mesial temporal lateralization 5) Ipsilateral to moving hand (postictal nose rubbing) Visual Auras
1. 2. 3. 4. 5. 6.
Blurred vision Micropsia (objects too small) Macropsia (objects too large) Perceptual illusions: objects too far or too close Distorted objects Rare: clear visual hallucinations (evergreen tree in temporal field) 7. Kinesogenic illusions of movement (medial temporal gyrus) Auditory Auras
1. Sound or voices not clearly perceived 2. A1 auditory receiving area aura: clicking, roaring, wind blowing, rumbling sounds 3. Receptive aphasia (left sided areas 22 or 23) 4. Distorted or muffled sounds 5. Sounds too loud or too soft 6. Extremely rare: auditory hallucination (most often a psychiatric or drug withdrawal phenomenon) 7. Macropsia or micropsia Vestibular Auras
1. Non-specific dizziness or light-headedness. One of the most frequent TLE aura’s (probable superior temporal area or intraparietal gyrus) 2. Tornado seizures: severe vertigo, with patient spinning rapidly and falling to the ground (superior temporal lobe or intraparietal gyrus)
SECTION II. Epilepsy
164 Cephalic Auras
1. 2. 3. 4. 5.
Head too big or small Off of the body Ice pick (stabbing) headache (also occurs with migraine) Squeezing compression of the head Unusual position on the neck
Post Ictal Signs and Symptoms of CPS of Temporal Lobe Origin
1. 2. 3. 4. 5.
6. 7. 8. 9. 10.
11.
Gradual transition between the seizure and postictal state Automatisms may continue during post ictal period Deep sleep is unusual Severe fatigue that may last for hours (“drained”) Period of confusion and disorientation following the event (less than one-minute usually, but may last for 30 minutes) Moderate dull headache, occasional vomiting or nausea Post ictal thirst; (common); hunger is rare Postictal hyperhidrosis Aimless wandering (poriomania) Simple partial seizure from the temporal lobe (dizziness, abdominal sensations, déjà vu or jamais vu) last less than 60 seconds and has no postictal symptoms Postictal psychosis
Medial Temporal Lobe Localizing Features: 1. Uncinate auras (abnormal smells and tastes) 2. Impending doom 3. Automatisms (licking of lips, chewing, swallowing) 4. Arrest response (sudden freezing) 5. Searching head movements 6. Contralateral dystonia, body shifting 7. Cough or sigh 8. Amnesia (hippocampal formation) 9. Gustatory a. Nausea c. Borborygmi b. Butterflies Lateral Temporal Lobe Localizing Features: 1. Wernicke’s aphasia; speech arrest left side 2. Psychical auras (right temporal lobe > left) a. Jamais vu b. Déjà vu 1) Auditory experiences (entendu) c. Forced thinking (episodes from past life experience) d. Dreamy state e. Heightened sensations f. Feelings of pleasure or extreme pleasure g. Depression or euphoria h. Epileptic rage i. Detachment j. Unreality
Anterior Temporal Lobe Cortex 1. Panic attacks, anxiety 2. No precipitating cause (precedes the event) 3. Stereotyped 4. Associated with autonomic features: a. Sweating c. Pupillary dilatation b. Hyperventilation Medial temporal lobe syndrome 1. Hippocampal sclerosis: a. MRI findings: 1) Hippocampal atrophy 2) Increased T2 signal 3) Disrupted internal structure of the hippocampal formation 4) Increased size of ipsilateral temporal horn 5) Focal thickening of the fimbria b. Dual pathology: 1) Neuronal loss within the hippocampal formation (HF) 2) Extra hippocampal lesion: a) Migrational defects b) Scar c) Tumor d) Vascular malformation e) Porencephaly f) Hamartoma 3) Occurs in approximately 30% of patients with hippocampal sclerosis 4) 16% of hippocampal sclerosis patients have bilateral abnormalities on MRI in the hippocampal formation 5) Loss of cells primarily CA1 and CA3 in the HF c. Hippocampal sclerosis occurs without hippocampal formation atrophy in 5–10% of patients; normal volume of hippocampal formation d. Younger children less than 12 years with hippocampal formation atrophy 1) Dysplastic lesions and hamartomas more common than astrocytic tumors e. Clinical features of hippocampal sclerosis: 1) Early age at onset of seizures 2) Prolonged febrile convulsions important in etiology; seizure free interval after initial febrile convulsion 3) Material specific memory deficit 4) Executive and attention attributes are intact 5) Deficits in: a) Verbal comprehension b) Perceptual organization c) Verbal memory d) Some visual spatial abilities e) No generalized cognitive impairment f) Impairment of access to an array of cognitive functions rather than restricted pattern of memory loss
Chapter 4. Partial Seizures
6) 7) 8) 9) 10)
Postictal psychosis common Autonomic auras Automatisms (oro-buccal-pharyngeal) Ictal fear Limbic seizures occur in the late afternoon and early evening 2. Amygdala sclerosis: a. 10% evolve into medial temporal lobe seizures b. Amygdala and hippocampal formation involvement: 50% origin of ictal events in MTLE c. Pathology of amygdala sclerosis: 1) Microdysgenesias (microscopic variant of cortical dysphasia) 2) Vascular lesions 3) Cortical dysplasia 4) Abnormal glial cells (large hyperchromatic) 5) Hamartoma (abnormal clusters of neurons and neuroblast cells) 6) Tumor d. Clinical features: 1) Seizure onset later than that of hippocampal sclerosis 2) Amygdala sclerosis on the same side as hippocampal sclerosis in 50–70% of patients 3) More secondary generalization than hippocampal sclerosis 4) In general, same ictal manifestations and auras as those with hippocampal sclerosis 3. Endofolium Sclerosis: a. Neuron loss and gliosis confined to the end folium
Neocortical Temporal Lobe Epilepsy (NCTLE)
A. General features: 1. Older at onset of habitual seizures than medial temporal lobe epilepsy (MTLE) 2. Seizures are shorter than MTLE 3. No seizure free interval once it is initiated B. Clinical manifestations: a. Déjà vu b. Jaime vu c. Depersonalization d. Forced thinking e. Autoscopy f. Automatisms of the contralateral arm; bilateral upper extremity automatisms g. Heightened sensitivity h. Psychical i. Experiential j. Often normal MRI k. Vertigo or tinnitus l. Auditory hallucinations
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Seizure Onset
1. 2. 3. 4. 5.
Motionless stare Upper extremity automatisms (ipsilateral to seizure focus) Dystonic posture of contralateral arm Bilateral upper extremity automatisms Contralateral tonic or clonic activity of the face or extremities; never an early manifestation of seizure
General-Differential features between MTLE and NCTLE 1. MTLE: a. Fear b. Visceral sensations c. High frequency of bitemporal interictal epileptiform abnormality 2. NCTLE a. Psychical b. Experiential c. More frequently contralateral (from the seizure focus or bilateral automatisms than ipsilateral) d. Normal MRI e. Neocortical TLE; well lateralized interictal EEG
Epileptic Forced Thinking
1. Forced thinking definitions: a. Recurrent intrusive thoughts, crowding of thoughts 2. Differential diagnosis is temporal lobe vs frontal lobe origin Differential Diagnosis of Epileptic Forced Thinking: 1. Obsessive thoughts 2. Auditory hallucinations 3. Auditory perservations 4. Temporal lobe limbic illusions (new thoughts not previously experienced) Clinical features of frontal lobe forced thinking 1. Speech arrest a. Seizure of motor language areas (primarily Broca’s) b. Speech arrest or disturbance with intrusive thoughts (urge to shout) 3. Forced thoughts less stereotypic (whatever words or thoughts used by the patient at time of the seizure) 4. Variability of thought 5. Context dependency 6. Experiential imagery characteristic Clinical features of temporal lobe forced thinking 1. Depth electrode stimulation of the amygdala induces: a. Emotional immediacy b. Perceptually vivid features c. Emotional tone in response to remembering 2. Temporal lobe forced thinking
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a. Out of context to environment prior to the seizure (a need to think of letters that begin with “L”; need to think of numbers) 2. Obscene thoughts: a. Patient feels a need to resist or negate the irrational thought b. Obsessive-compulsive status epilepticus 1) Temporal limbic focus c. Temporal limbic seizure focus may spread: 1) Through the uncinate funiculus and cingulum to the frontal lobe 2) Connects the frontal anterodorsal convexities to the temporal lobe
3.
Unusual Manifestations and Localizing Value of Specific Clinical Presentations of CPS
Cardiac Arrhythmia (Anterior Insular Cortex)
1. 2. 3. 4. 5. 6. 7.
Supraventricular tachycardia Sinus tachycardia (L temporal lobe insular cortex) Sinus bradycardia (L temporal lobe/ insular cortex) Sinus arrest AV block Rarely accompanying chest pain SUDEP (sudden unexplained death in epileptic patients)
Aphasia caused by seizure in the fusiform gyrus 1. Fusiform gyrus a. Basal temporal language area; primarily like Wernicke’s; unable to name categories of objects 2. Speech disorders in TLE: a. Paroxysmal dysphasia (Wernicke’s area) b. Speech automatism 3. Paroxysmal dysphasia 4. Wernicke’s area (left side); receptive aphasia 5. Speech automatism (either side) 6. Functional link between left fusiform gyrus and Wernicke’s area Reproductive Dysfunction 1. Left TLE a. Polycystic ovaries 2. Right TLE a. Hypothalamic amenorrhea 3. Decreased pulsatile LH (Luteinizing hormone); locus can be either side Differential Diagnosis of TLE: 1. Facial blankness and staring may resemble absence seizures 2. CPS vs affective psychosis: TLE associated with: a. Geshwind’s Syndrome (CPS personality traits) 1) Schizoid (bilateral temporal lobe involvement) 2) Hyperreligious (three religious conversions)
4.
5.
6.
7.
3) Hypergraphia (lists of every seizure event) 4) Viscous (unable to terminate appropriate question or a personal interaction) b. Rarely TLE manifests: 1) Hallucinations 2) Agitation, anger, fear, irritability and confusion 3) Usually these are of short duration, stereotyped and intermittent 4) Associated with speech arrest, impaired consciousness and autonomic phenomena 5) Patients have insight that symptoms occur incongruously TLE versus episodic dyscontrol syndrome: a. Episodic dyscontrol syndrome: 1) Uncontrolled rage 2) Occurs with provocations 3) Out of character for the patient 4) May have central nervous system deficits 5) May have documented seizures 6) May lose minutes to hours 7) Followed by fatigue and confusions 8) Often amnesia for the event 9) Violence against individuals is common b. CPS: 1) Personally directed violence (very rare) 2) Stereotyped 3) Associated signs and symptoms of seizure activity Migraine with abdominal pain and nausea vs TLE: a. In children with migraine; the abdominal symptoms may be associated with headaches b. TLE, the abdominal auras are followed by impairment of consciousness or other epileptic phenomena TLE versus cardiac arrhythmia: a. Anterior insular cortex CPS may cause chest pain and cardiac arrhythmia that may be difficult to differentiate from cardiac disease b. TLE: 1) Attacks are not associated with usual cardiac precipitants 2) Associated with other epileptic phenomena 3) Impairment of consciousness 4) Post ictal phenomena (fatigue, thirst, headaches) 5) Chest pain not in a cardiac distribution TLE vs syncope (vago vagal) a. Clinical characteristics of vago vagal syncope: 1) Characteristic pallor 2) Precipitating event (for vago vagal; specific sight or stress) 3) Slow pulse (less than 40 beats per minute) 4) Less than 30 seconds in duration; usually lasts less than 10 seconds 5) No confusion or other post event phenomena 6) May have few myoclonic jerks TLE vs vaso depressor syncope: a. Vaso depressor syncope clinical characteristics:
Chapter 4. Partial Seizures
1) Precipitating event (prolonged bed rest; hypertensive medications, upright posture, prolonged parade rest on a hot day) 2) Rapid pulse 3) No confusion 4) May have occasional myoclonic jerks
Special Aspects of TLE
1. Reproductive Dysfunction: a. 50% of women with TLE 1) Have sexual dysfunction 2) Hormonal abnormalities 3) 14–20% have amenorrhea 4) Fertility reduced by 30% b. Men with TLE 1) Approximately 50–70% have sexual dysfunction (lack of libido) 2) Rarely satyriasis occurs c. Associated reproductive conditions reported in TLE 1) Hypogonadotrophic and hypergonadotropic hypogonadism 2) Functional hyperprolactinemia 3) Polycystic ovary disease 4) Anovulatory cycles 2. Prolactin surge after medial temporal lobe seizure: a. Levels peak approximately 20 minutes after the seizure b. Often elevated, but frequently no baseline measurements are available to make this determination accurately c. Amygdala has a direct connection to the VM (ventromedial) nucleus of the hypothalamus 1) Post ictal elevation of hypothalamic releasing and luteining hormone have been noted 2) Post ictal psychosis with CPS 3) Post ictal bradycardia and asystole after CPS 4) Post ictal aphasia (basal temporal area) Interictal personality traits of TLE 1. Diagnostic specificity and validity of specific personality traits in TLE is controversial a. Existence of these traits in patients with other seizure disorders b. Prevalence is variable c. Common in general population 2. Noted interictal traits: a. Catastrophic overemphasis (left temporal lobe) b. Ideational traits (left temporal lobe) c. Overly emotional (right temporal lobe) d. Denial (right temporal lobe) e. Inclusiveness f. Hypersexuality (rare); usually hyposexuality g. Dependence
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h. Obsessive/compulsive behavior i. Hypergraphic j. Hyperreligious k. Oppressiveness l. Hypermorality m. Circumstantiality n. Philosophical interests 3. TLE personality traits and psychopathology: a. Most adult TLE patients are well adjusted and functional b. Personality traits noted primarily with bilateral temporal lobe involvement 4. Dual pathology causative of the personality disorder (ipsi or contralaterally) a. Medial temporal sclerosis with migrational disorder b. Mirror foci (frequent seizures; interictal spiking) c. Trauma (bilateral temporal lobe involvement) d. Surgery on one temporal lobe; remaining temporal lobe dysfunctional e. X-ray (particularly for pituitary tumors) f. Viral involvement (Herpes Simplex encephalitis) 5. Klüver–Bucy Syndrome: a. Hyperorality: all objects are placed in the mouth b. Hypermetamorphopsia: all objects are examined with the same degree of interest and intensity c. Short term memory deficit d. Hypersexuality (attempted intercourse with same sex or inanimate objects) e. Sham rage: trivial provoking events; anger reaches maximum intensity instantly; patient returns to baseline immediately Psychopathology 1. Patients with seizure disorders have a higher incidence of psychiatric disorders than a control population 2. Psychosis resembling paranoid schizophrenia reported in TLE patients a. Better preservation of affect in TLE vs schizophrenia patients b. Less personal isolation than schizophrenic patients 3. Temporal lobectomy may cause: a. New onset of psychosis b. Improvement of instability and aggressiveness 4. Aggressive violent behavior in TLE: a. Non-directed b. Short lived c. Fragmentary d. May be a stereotyped manifestation of some temporal lobe seizures 5. Predictive variables of interictal psychosis in epilepsy a. Earlier age at onset of epilepsy b. Family history of psychosis c. Borderline intelligence d. CPS and GTCS are seizure type
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Amnesia in TLE patients 1. Short term memory loss (dysfunction of medial temporal lobe structures) 2. Defect in confrontational naming 3. Decreased word fluency Temporal Lobe Pathology
Glioma, arteriovenous malformations, cavernous hemangiomas, hematomas or traumatic scars all cause complex partial seizures. The advent of MRI scanning with associated volumetry of medial temporal lobe structures and the hippocampal formation as well as PET, SPECT, and MRI spectroscopy have provided a much better understanding of congenital abnormalities that underlie these conditions. There are a variety of migrational disorders that can be diagnosed by MRI scanning. These are caused by abnormal neuronal migrations of germinal plate neurons from the ventricle to the cortex and disrupted gyration and apoptosis of the neurons that have migrated. Nests of subependymal neurons are noted in the frontal, parietal and temporal white matter, in periventricular heterotopia. This may be seen unilaterally or bilaterally. The walls of the ventricles demonstrate nodules of subependymal neurons that have not migrated. Radial glial fibers from the ventricles to the cortex may be seen in tuberous sclerosis. Migration of these subependymal cells occurs in the 20–22nd week of gestations. A double cortex or thickened band heterotopia may be seen in those patients who have suffered failure of apoptosis and no remodeling of the cortex. The extremes of this condition are schizencephaly and lissencephaly. Failure of architectural remodeling may be seen in focal cortical dysplasia in which the orderly laminar structure of the cortex is disrupted. These focal dysplasias may be further characterized as a laminar heterotopia, simplified gyral pattern and focal microgyri. There are genetic syndromes with X-linked heterotopias and double cortex as well as sporadic genetic forms of abnormal migrational patterns. Agyria, polymicrogyria, macrogyria, and sublobar dysplasias have all been seen with complex partial seizures of temporal lobe origin. Focal cortical dysplasia may demonstrate abnormal giant neurons and balloon cells in a addition to the dysmyelination. The syndrome of medial temporal sclerosis is suspected if the patient has suffered prolonged febrile convulsions as a child. Medial temporal sclerosis may also be seen in conjunction with migrational defects a situation known as dual pathology. Bilateral anatomic abnormalities with a unilateral temporal lobe seizure focus have been seen in 20–40% of patients with medial temporal lobe sclerosis. Mesial temporal sclerosis may extend throughout the temporal lobe and involves both the cortex and white matter. The temporal pole is frequently atrophic ipsilateral to the side of seizure onset in seizure patients.
Bilateral parasagittal, parieto-occipital and episylvian, polymicrogyria as well as hemi megacephaly are other patterns of cortical dysplasia. These migrational defects are frequently associated with contralateral hemiasymmetry of the arms, face and leg. If the face is obviously involved, the process is termed the Parry–Romberg Syndrome. If the seizure disorder is associated with an intrauterine stroke of a vascular territory, severe trauma a porencephalic cyst or arteriovenous malformation, the contralateral hemiatrophy is severe and obvious. Limbic encephalitis not associated with neoplasm is a cause of temporal lobe seizures. Perivascular lymphocytic infiltration is noted. The CSF demonstrates a mild pleocytosis. IgG is demonstrated in 20% of patients and oligoclonal bands in 50%. The differential diagnosis includes Rasmussen’s encephalitis, Hashimoto’s disease, SLE and paraneoplastic limbic encephalitis. Perivascular clustering and cortical neuronal clustering (micro dyseneias) is associated with mossy fiber sprouting into the dentate supragranular layer. Congenital porencephaly may absorb concordant with hippocampal sclerosis. Insular Cortex Seizures
1. General features: a. Hippocampal seizure foci spread to the insular cortex; general afferents from and efferents to: 1) Amygdala 2) Enterorhinal cortex 3) Hippocampus 4) Cingulate cortex 5) Orbito frontal cortex 2. Clinical symptoms: a. Respiratory 1) Modulates the amplitude and frequency of respiratory movements 2) Chest fullness is experienced b. Viscerosomatic 1) Chest constriction ascending to the anterior cervical region; associated with nausea 2) Abdominal constriction and heaviness 3) Intense distressing abdominal pain 4) Throat constriction c. Somatosensory (opposite the side of the focus) 1) Ascending retrosternal sensation of heat 2) Brisk nonpainful heat sensation of the trunk and both upper and lower limbs d. Oroalimentary manifestations 1) Chewing and swallowing 2) Mastication
Division B: Fontal Lobe Seizures
General Clinical Characteristics: Fontal lobe seizures begin abruptly, are often brief, are associated with minimal post ictal confusion, come out of sleep
Chapter 4. Partial Seizures
and may occur in clusters. The clinical features depend on the areas of the frontal lobe that are affected. Seminal features are motor, automatisms, and vocalization. Frontal Lobe Seizures: 1. General Characteristics 2. Genetics: ADNFLE; autosomal dominant nocturnal frontal lobe epilepsy (chromosome 20) 3. Clinical features of localization related frontal lobe seizure: a. Prerolandic cortex (area 6) 1) Speech arrest or impairment 2) Tonic-clonic movement of contralateral face 3) Repetitive swallowing 4) Contralateral flaccidity without movement (suppressor strip of Hines) b. MI (area 4) 1) Jacksonian march; mouth and thumb are affected early; motor neurons here have a wide area of representation and low threshold; often the thumb and corner of the mouth initiate the march 2) Rapid secondary generalization particularly if the focus is in MI or SI 3) Occur during sleep 4) May occur in clusters 5) Inferior second frontal convolution (Broca’s area) cause speech arrest, stammering or stuttering with the seizure 6) Seizures often are brief less than 75 seconds 7) No prolonged ictal state 8) Movements occur with progression of the seizure 9) Bilateral purposeful and non-purposeful movements (motor automatism-bicycle pedaling) 10) High monthly seizure rate 11) Motor arrest 4. Supplementary motor area seizure (SMA): a. SMA area eight of the frontal cortex b. Brief c. May cluster at night d. Preservation of consciousness e. Speech arrest f. Vocalization g. Fencing posture: extended contralateral arm; flexed ipsilateral arm; contraversive head and eye movement h. Versive movement away from the side of ictal onset i. Sudden paratonic posturing of one or more extremities 5. Cingulate cortex: a. Aura; fear and panic b. Emotional outbursts c. Increased sympathetic tone d. Complex motor, gestural, or automatic manifestation with change of mood and affect 6. Orbitofrontal cortex: a. No aura until the seizure spreads into the cingulate or insular cortex
7.
8.
9.
10.
11.
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b. After the spread: 1) Autonomic signs 2) Olfactory hallucinations and illusions 3) Oroalimentary auras 4) Can have persistent vocalization 5) Violent dramatic automatisms 6) Motor and gestural automatisms Dorsolateral prefrontal cortex: a. Tonic posturing of head and upper extremities b. Contraversive head and eye movements c. Clonic facial contractions (rare) d. Speech arrest Frontal eye field (FEF areas 8, 10): a. Head and eye turned side away from the lesion b. Horizontal jerk nystagmus to the contralateral side c. Often impaired consciousness d. Pupillary dilatation of the contralateral eye (early at onset) Paracentral lobule: a. Tonic movement of the ipsilateral foot b. Contralateral leg involvement Opercular areas: a. Ipsilateral clonic facial movements b. Mastication, salivation, swallowing Frontopolar cortex: a. Vocalization b. Hyperventilation c. Truncal flexion d. Complex gesture automatisms e. Sudden awakening after seizure f. Bimanual/bipedal automatisms g. Forced thinking h. Axial clonic jerks (that may cause falling)
Extra Frontal Seizure: 1. Behavioral arrests or automatisms typically precede head deviation Hyperkinetic Frontal Lobe Seizures: 1. Location of seizure focus: a. Orbitofrontal cortex b. Dorsolateral prefrontal cortex c. Frontomesial cortex 2. Clinical features: a. Complex bimanual and bipedal movements b. Kicking, thrashing, clapping, rubbing c. Sexual automatisms d. Autonomic hyperactivity (piloerection, pupillary dilatation, micturition) e. Preserved consciousness f. Usually positive EEG correlate g. Status epilepticus Division C: Parietal Lobe Seizures
Simple partial sensory seizures are usually of parietal lobe origin and often relate to lesions in specific components of the
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sensory homunculus. Abnormal tongue sensations (coldness, stiffness, numbness) are often bilateral. This may also occur with thalamic lesions (VPM). A patient’s awareness of a sensory deficit in 1/2 of the tongue suggests an intraparenchymal brainstem lesion. Fifth nerve lesions from collagen vascular disease such as scleroderma and Sjögren’s disease are usually perceived as numbness. Commonly cervical plexus (posterior roots of C2, C3 – the preauricular nerve) may also cause tongue (unilateral) numbness. Bilateral facial paresthesias and numbness may also emanate from SI. Other positive sensory phenomena emanating from the parietal lobe are the feeling that a body part is being moved or the patient has a desire to move the body part. Nondominant parietal sensory sensations from seizure activity manifest the feeling that a body part is absent. Inferior and lateral parietal lobe seizures may cause feelings of nausea, choking or sinking. Inferior parietal lobe seizures may cause a feeling of the body being tilted or severe disorientation in space or vertigo (intraparietal sulcus). Seizures from this area may also cause epileptic skew deviation (Brodmann’s 19/37/39 and 40) Bilateral heat sensations arising from the feet and sweeping upwards over the body and may emanate from SII (that is at the base of SI). SII seizures may also be associated with poorly localized cold and pain. These sensations may be bilateral, contralateral or ipsilateral to the seizure focus. Dominant parietal lobe seizure activity may cause a receptive or conduction aphasia. Painful contralateral parietal lobe auras have been described. Division D: Febrile Convulsion
Definition: A seizure occurring in infancy and childhood that occurs between three months and five years of age in association with fever, but without evidence of intracranial infection or defined cause. General features: 1. Just one febrile convulsion in the majority of children less than three years of age (18–22 months; boys > girls) 2. Usually generalized clonic-tonic; may be of any type 3. Low incidence of acquired motor or intellectual abnormality following a febrile seizure; low mortality rate 4. Recurrences: a. Approximately 1/3 of children have recurrence; 12– 15% of these children have further recurrences b. Risk factors for a recurrence: 1) Age of onset of first febrile seizure less than 13 months of age 2 : 3 chance of developing recurrence 2) 14–22 months of age, 1 : 2 chance of recurrence 3) Greater than 32 months, 1.5 risk 4) 75% of recurrences within one year; 90% within two years 5. Risk of developing epilepsy after febrile seizure four times the control population 6. Risk for developing epilepsy after a febrile convulsion:
a. b. c. d.
Seizure duration greater than 15 minutes Greater than one seizure in 24 hours Focal features of the seizure Prior neurological deficit before febrile convulsion. Increased risk of epilepsy by age seven is 3x control population e. Not established that children with recurrent febrile seizure have increased risk of epilepsy f. Increased risk of epilepsy if febrile seizures began in infants of 6 months, 5.7% vs 1.5% after the first year g. Family history of febrile convulsions not established as a risk factor for development of epilepsy 7. Genetics: GTCS + febrile convulsions a. Chromosome – gene
Chapter 5 Status Epilepticus Major Motor Status Epilepticus
1. General features: a. 40–80/100,000 patients b. Mortality of 22% c. Occurs in 14% of patients after control of GCTS has been established 2. Repetitive tonic-clonic movements or components that last for seconds to minutes 3. Consciousness is not regained within three minutes prior to the onset of a new seizure 4. Associated features: a. Autonomic changes: 1) Increased heart rate, greater than 120 beats/minute 2) Pupillary changes (dilated) 3) Hyperhidrosis 4) Temperature to 103 degrees Fahrenheit (rarely > 104◦ F) 5. Rare sequelae: a. Cardiac arrest b. Neurogenic pulmonary edema c. Duodenal ulcer (first segment of the duodenum) 6. Serum evaluation: a. Severe acidosis: pH 7.1–7.2 in the serum b. Hyperkalemia > 5 mEq/dl 7. CSF evaluation: a. Up to 100 neutrophils/mm3 b. Acidosis (pH of 6.8) Differential Diagnosis of Adult Major Motor Status Epilepticus
1. Non-compliance with medication 2. Frontal lobe brain tumor
Chapter 5. Status Epilepticus
3. Metabolic abnormalities from organ failure or hypoglycemia 4. Illicit drugs (cocaine, amphetamines) 5. Vascular malformation or infarction 6. Infectious disease: a. Opportunistic organisms (HIV associated) b. Herpes simplex encephalitis c. Meningitis 7. Remote cerebral scar 8. Alcohol related (withdrawal)
Psychomotor or Complex Partial Seizure (temporal lobe) Status Epilepticus
Clinical features: 1. Confused dazed appearance 2. Patient partially responsive to verbal commands 3. De novo or perservative automatisms 4. Myoclonic jerks and eye twitches (intermittent) 5. Patient is ambulatory 6. May last for hours 7. Fugue state: a. Prolonged temporal lobe status epilepticus b. Patient able to perform activities of daily living or more complex tasks such as driving c. Sudden recovery d. Amnestic for the event e. Usually less than 30 minutes; may last for hours
Differential Diagnosis of Adult Complex Partial Status Epilepticus of Temporal Lobe Origin
1. Non-compliance with mediations in a temporal lobe seizure patient 2. Astrocytic tumors of the temporal lobe 3. Medial temporal lobe sclerosis 4. Vascular malformation 5. Severe head trauma 6. Hematoma 7. Migrational disorders: chromosomally linked and sporadic
Focal Motor Statis Epilepticus in an Adult
Differential diagnosis: 1. Stroke or vascular insult (Menshikoff’s syndrome) 2. Arteriovenous malformation 3. Cavernous hemangioma (that has recently bled) 4. Rasmussen’s encephalitis (children and adolescents most often affected) 5. Mitochondrial encephalomyopathy (children and adolescents) 6. Opportunistic infection in a patient with HIV
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Status Epilepticus of the Occipital Cortex (status epilepticus amauroticus)
1. Cortical blindness 2. Unilateral nystagmus
Epilepsia Partialis Continua (EPC)
1. General features: a. Spontaneous focal jerking of a body part b. Duration: days, months, or years c. Aggravated by: 1) Movement 2) Sensory stimuli d. May occur in isolation e. 40% of patients with EPC 1) Cognitive or neurologic decline 2. EPC in children: a. Rasmussen’s encephalitis b. Migrational disorder c. mt-DNA disorders d. Autoantibodies against GluR3 and munc-18 3. EPC in adults: a. Stroke or vascular insult (Menshikoff’s Syndrome) b. Arteriovenous malformation c. Cavernous hemangioma d. Brain tumor (meningioma) e. Mitochondrial encephalomyelopathy (most often children or in adolescents) f. Kuf’s disease late onset form) 1) Type A progressive myoclonic epilepsy 2) Type B: a) Dementia b) Behavior disorder c) Facial dyskinesia d) Absence of generalized epileptiform discharges
Non-Convulsive Status Epilepticus (NCSE)
1. Types a. Generalized NCSE b. Partial NCSE c. Diagnosed by the ictal EEG 2. Generalized NCSE (absence status; “petit mal status”) a. Definition: Multiple seizures or continuous seizure activity on EEG with non-convulsive clinical correlate b. Fluctuating confusion of varying intensity c. Mirror-facial myoclonus d. Cognitive and behavior change e. 50% of patients demonstrate bilateral myoclonus during the ictus f. EEG: symmetric ictal activity g. Precipitating factors of absence status (nonconvulsive status epilepticus) 1) Carbamazepine
SECTION II. Epilepsy
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2) Hyperventilation 3) Inadequate drug levels 4) Infections 5) Noncompliance with medication 6) Benzodiazepine withdrawal 7) Hypoparathyroidism 8) Menses 9) Generalized convulsions 10) Head trauma 11) Alcohol 12) Recent surgery 13) Sleep deprivation 14) Emotional upset 15) Renal failure 16) Pregnancy 17) Methohexital h. Occurs in 8% of comatose patients 3. Partial NCSE: a. Various non-convulsive symptoms with or without confusion b. Continuous or recurrent focal epileptiform EEG pattern 4. Parietal NCSE: a. Symptoms 1) Somatosensory 5) Psychic 2) Visual 6) Cognitive 3) Auditory 7) Affective 4) Vegetative b. No loss of consciousness 5. NCSE of frontal lobe origin a. Prolonged periods of continuous confusion without visible ictal signs b. May have focal lesions in the frontal lobe c. May occur in the middle aged or elderly d. Absence status may occur without overt confusion
Flagrant major motor seizure patterns are the characteristic clinical symptom complex, but any form of seizure may be simulated. Approximately 40–60% of patients with pseudo seizures have documented real seizures. The personality traits and psychopathology noted with complex partial seizures are frequently noted.
Differential Diagnosis of Absence Status
Epileptic Seizure May Progress into Non-Epileptic Conversion Seizures
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Prolonged post ictal encephalopathy Depression Acute or interictal psychosis Factitious disorders Medication overdose Psychotropic drug withdrawal Toxic metabolic encephalopathy Amnesia and automatisms syndrome (from TLE) Transient global amnesia Transient unresponsiveness in the elderly
Patterns of Involvement of Facial Muscles during Epileptic and Non-Epileptic Events
1. Eyes are wide open in greater than 90% of patients during the tonic phase of tonic-clonic seizures 2. Eye closure in any form is uncommon during the ictal phase of an epileptic seizure with motor manifestations 3. Psychogenic seizure have sustained eye closure with active opposition to opening 4. Mouth is open during the tonic phase of a generalized seizure; injury to the tongue and side of the mouth is common (usually side of the tongue is bitten) 5. During seizure: eyes may have upward gaze deviation; empty stare, pupillary dilatation and absence of the corneal reflex 6. Rapid forced blinking with no other facial movementfocus is occipital lobe in origin 7. Focal seizure with tonic contraction of corner of the mouth or zygomaticus muscles (cheek) M1 of the frontal lobe 8. Rhythmic forced contraction of the face occurs with seizures 9. Tongue biting (side of the tongue) contralateral to seizure focus; occurs in the clonic phase of GTCS 10. Cheek biting occurs during automatisms
1. Common for epileptic seizures to become functionally elaborated into a conversion seizure; possibly 30–60% of true seizures have pseudo seizures 2. Precipitating factors: a. Physical and sexual abuse b. Life stressors c. Disability
Features Associated with Pseudoseizures
Chapter 6 Pseudoseizure One of the great diagnostic difficulties of complex partial seizures of temporal or frontal lobe origin is pseudo seizures.
1. 2. 3. 4. 5.
Absence of usual provoking event Abnormal distribution and pattern of movement Pelvic thrusting Thrashing of the arms Forced eye closure that is maintained during examinations
Chapter 7. Genetic Aspects of Seizures
6. 7. 8. 9. 10. 11. 12. 13. 14. 15.
Absence of post ictal phenomena Preictal pseudo sleep Gradual onset Induced by suggestion Crying Opisthotonus Asynchronous Emotional triggers Associated with psychiatric diagnosis Side to side head movements
Chapter 7 Genetic Aspects of Seizures
1. Increase in the prevalence of epilepsy in families with epilepsy a. 3–8% in idiopathic epilepsy b. 0.5–15% in symptomatic epilepsy c. Rate in the control population is 0.5% 2. Seizures in close family members a. 3.5 to 29% 3. Twin studies: a. Concordance rates 11% with acquired brain lesions; 70% in those without lesions b. Dizygotic twins: 1) Concordance rate of 3–10% 4. Pedigree analysis: a. Mendelian pattern of metabolic disease with seizures: AR b. Genetic causes of seizures: 1) Absence epilepsy: AD 2) Generalized spike and wave: AD 3) Febrile convulsion: AD 5. Mosaicism a. Presence of more than one distinct cell line in a single individual b. Mutations arise post fertilization c. Somatic mosaicism important in: 1) AD disorders 2) Sex-linked disorders 3) Survival of lethal phenotypes 4) Postzygotic alterations 5) DCX gene on Xq22
X-Linked Metabolic Disorders with Seizures
1. Pyruvate dehydrogenase deficiency 2. Glycerol kinase deficiency 3. OTC (ornithine transcarbamylase deficiency)
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Chromosomally Determined Epilepsies
1. Generalized epilepsy: benign familial neonatal convulsions: a. Genetics: 1) Chromosomes 20q, (EBN-1, KCNQ 2 genes) 2) Code for voltage gated K+ channel 3) Some families map to: a) Chromosome 8q (EBN-2, KCNQ3 gene) (1) Codes for K+ channel gene b. Clinical features: 1) Brief multifocal convulsions 2) Onset first week of life 3) Resolves spontaneously within six weeks 4) Some have febrile convulsions in childhood 5) 10–15% develop epilepsy in adult life 6) Normal neurologic exam 7) Positive family history for febrile convulsions or neonatal seizures 2. Juvenile myoclonic epilepsy (JME) a. Onset in adolescence or early teenage years b. Male equals female incidence c. Interictal generalized bursts of 3.5–6 Hz poly spike and wave on EEG d. Genetics: 1) AD 2) AR 3) Multifactorial 4) Most families have a chromosome 6q defect 5) Some families have a chromosome 15q defect e. Ach receptor (alpha 7 subunit dysfunction) f. Myoclonus on awakening; associated with GCTS and absence seizures 3. Mental retardation epilepsy syndrome, p38 a. X chromosome (TM45F2 gene) b. Generalized seizures c. No regression in mentation or milestones after seizure onset d. Macrocephaly 4. Bilateral periventricular nodular heterotopia in boys with mental retardation and syndactyly a. Clinical features: 5. Idiopathic generalized seizures: a. Chromosome 8 q (EPN2) gene locus b. Also associated with same locus (adjacent to BFNC) benign frontal nocturnal convulsion 1) Febrile convulsions 2) JME 3) Childhood absence epilepsy 4) Asymptomatic generalized spike waves EEG activity c. Idiopathic generalized epilepsy (IGE) 1) Specifically in occurring with JME a) Chromosome 15q (muscarinic Ach receptor alpha 7 subunit gene)
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2) ADNFLE locus (autosomal dominant frontal lobe epilepsy) a) Ach receptor alpha 4 subunit gene b) Chromosome 20q c) Putative IGE locus 6. Progressive Myoclonic Epilepsy (PME) a. Unverricht–Lundberg Disease 1) Baltic myoclonus 2) Major cause of PME in North America 3) Genetics: a) AR b) Chromosome 21 q c) EPM1 gene d) Cysteine-proteinase inhibitor (cystatin B gene) is coded e) Inactivates proteases that leak out of lysosomes f) Dodecanes expansions of the gene b. Point mutation in 14% of patients c. Expansion of a dodecane nucleotide repeat: 1) Normally 2–3 copies 2) Symptomatic patients >60, copies 3) Expansion is 70 nucleotides upstream of a transcription initiation factor (5 flanking promotor) 4) results in decreased RNA for the cysteineproteinase inhibitor 5) Paternally based (repeats more unstable during spermatogenesis) d. Clinical features: 1) Onset between 6–15 years of age; less frequent with age 2) Progressive dementia 3) Ataxia 4) Intention tremor 5) Stimulus sensitive myoclonus 6) Photosensitivity e. Differential Diagnosis of Photosensitivity in Epilepsy 1) Unverricht–Lundborg and Lafora body disease 2) Neuronal ceroid lipofuscinoses 3) MERRF - 4) Sialidosis (cherry red spot epilepsy ±) with occipital lobe seizures Ramsey Hunt Syndrome
1. A form of PME 2. High incidence in Mediterranean region 3. Genetics: a. Possibly mitochondrial b. EPM1 gene Mitochondrial Defects (Seizures and Myoclonus)
1. MERRF 2. Leigh’s disease
3. NARP 4. MNGIE 5. Double mutation (A8296G and Q8363A) a. Transfer RNA for Lys b. VIIIth nerve; cardiomyopathy; myoclonus seizures Progressive Myoclonic Epilepsy of the Lafora Type
1. Genetics: a. AR (consanguinity) b. Chromosome 6q 24 (Lafora) c. Encodes for tyrosine phosphatase 2. Polyglucosan storage disorder 3. Clinical features: a. Onset in late childhood or adolescence b. Myoclonus c. Seizures d. Rapidly progressive dementia Progressive Epilepsy with Mental Retardation
1. Genetics: AR: chromosome 8q 2. “Northern Epilepsy” (Northern Finland) 3. Clinical features: a. Age at onset 5–10 years of age b. Early normal development c. GTCS until adolescence d. Cognitive decline starts later and seizures abate
Genetic Partial Epilepsies
1. Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) a. Genetics chromosome 20q 13.2–13.3 alpha 4 subunit (CHRNII) 1) Gene for the RNA nicotinc Ach receptor alpha 4 subunit 2) May be allelic to EBN 1 gene b. Childhood onset: first two decades of life c. Clinical features: 1) Seizures occur during light sleep 2) May occur during daytime nap 3) Occur in clusters of up to 20; typically last 30–40 seconds 4) Interictal EEG is usually normal 5) Gasping; groaning, tonic stiffening, restless, agitation during seizure, changes of positions, vocalizations 2. Ring Chromosome 20 Epilepsy a. Genetics: MCR3 gene on chromosome 20 b. Clinical features: 1) Subtle nocturnal seizures
Chapter 7. Genetic Aspects of Seizures
2) Semiologic variability of seizure pattern: a) NCSE c) Simple and CPS b) GTCS c. Refractory to CBZ 3. Benign centrotemporal (Rolandic) and benign occipital epilepsy a. Genetics: AD: gene and locus not identified b. Possible phenotype variants of the same disease c. Clinical features: 1) Onset 4–10 years of age 2) Seizures stop at age 12–14 d. Possible chromosome micro-deletions; possible chromosome deletions e. Ach R subunit deficits f. Chromosomes: Chromosome 1 (B-2 subunit) coding for B-2 subunit of Ach receptor Chromosome 8 (B3 subunit) coding for B3 subunit of Ach receptor Chromosome 15 (a3, a7, B4 subunit) Chromosome 15q (susceptibility locus) 4. Familial temporal lobe epilepsy (FTLE) a. Genetics: AD 1) Lateral temporal variant a) Partial epilepsy with auditory features (ADTLEAF) b) Chromosome 10 2) Medial temporal variant a) Families linked to chromosome 7 b) Possible reduction of GABA-A subunit
Genetic Syndromes with Epilepsy (Chromosomal)
A. Metabolic 1. Juvenile ceroid lipofuscinosis a. Genetics: AR; chromosomes 16p (infantile and juvenile onset and adult onset patients) b. Over production of autofluorescent lipopigments (ceroid and lipofusion) within the brain, retina and visceral organs c. Clinical features: 1) Onset 4–7 years of age 2) Ocular findings: a) Retinal atrophy b) Optic atrophy c) Granular discoloration of the macula d) Blindness 3) Dementia a) Associated delusions and hallucinations 4) Dysarthria and rigidity develop over time 5) Myoclonic epilepsy begins several years after onset 6) Death within 15 years of onset
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7) Skin biopsy: “Fingerprint bodies” within cytoplasm of epithelial cells 2. Sialidosis juvenile form (Type III) a. Genetics: chromosome 10q b. Deficiency of alpha neuraminidase (sialidoses) c. Clinical features: 1) Type I: congenital; congestive heart failure 2) Type II: infantile form with ataxia mental retardation, myoclonus and seizures 3) Type III: (cherry red spot myoclonus) a) Cherry red spot in the retina (absence of ganglion cells) b) Myoclonus c) Seizures d) Onset is late childhood e) Urine contains oligosaccharides f) Enzyme deficiency can be identified in cultured fibroblasts
Angelman Syndrome
1. Genetics: a. Maternally imprinted micro deletion in chromosome 15q 11–12 1) Non-deleted patients (<5%) b. Paternal (uni parenteral) disomy (both chromosomes originate from the father) 1) Deleted area codes for GABA-A receptor-beta3 subunit 2. Clinical features: a. Seizures b. Severe mental retardation c. Absence of speech d. Jerking gait and inappropriate laughter (happy puppet) e. Enlarged jaw f. Protruding tongue g. Upheld arms 3. Microcephaly a. Mid face hypoplasia b. Ataxia; tremulousness
Prader–Willi Syndrome
1. Genetics: allelic to the paternally inherited defect in the same region of chromosome 15q 11–12 as Angelman Syndrome 2. 70% have a deletion in paternal chromosome 15q 11–13 3. Non-deletion cases (20–25%) have maternal disomy (both chromosome 15 are from the mother) 4. Clinical features: a. 1/10,000 of live births b. Hypogonadism c. Mental retardation d. Severe hunger (hyperphagia)
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e. f. g. h. i.
Short stature Massive obesity Hypotonia Hypotrophy of Type II muscle fibers No seizures
Tuberous Sclerosis
1. Genetic: AD with variable expression, unrecognized affected parents in 25% of patients 2. Some families linked to chromosome 9; others to chromosome 16; tumor suppressor gene 3. Clinical features: a. Seizures; may start as infantile spasms b. Hypopigmented oval skin nevi (18% are linden leaf shaped) c. Shagreen spot (often over the buttocks but may be anywhere) develop in late infancy (50% of patients) d. Angiokeratoma (adenoma sebaceum) appear over the bridge of the nose and face during childhood. e. Retinal tumors, rhabdomyosarcoma of the heart, renal tumors (Leiomyomata) bone and liver cysts f. MRI: 1) Subependymal nodules (usually periventricular) 2) Large poorly differentiated cortical gyri (tubers) 3) Anterior IIIrd ventricular giant cell subependymal astrocytic tumor with consequent obstructive hydrocephalus
INV Duplication 15 Syndrome
1. Genetics: INV (inversion) duplication of chromosome 15 results in trisomy 15P 2. Clinical features: a. Developmental delay b. Severe seizures c. Mental retardation d. Stereotypies e. Lack of interaction f. Poor development of language g. Down slanting palpebral fissures h. Coarse facies i. Hypopigmented skin areas j. Epicanthic folds
Trisomy 9P Syndrome
1. Genetics: Trisomy 9P 2. Clinical features: a. Microcephaly c. Kyphosis b. Short stature d. Severe seizures 3. Dysmorphisms:
a. Prominent brow and nose coarseness b. Maxillary hypoplasia c. High arched palate d. Down turned mouth e. Small chin f. Blunt fingers and toes g. Hypoplastic nails 4. MRI: a. Hippocampal formation abnormalities b. Hypoplastic cerebellar vermis c. Dilatation of IVth ventricle d. Normal to hypoplastic brainstem e. Syringomyelia f. Myelomeningocele g. Gliosis of the centrum semiovale h. Atrophy of the corpus callosum 5. Trisomy 9P a. Multifocal independent spike foci 6. Association of trisomy 9P a. Band heterotopia
Trisomy 12P Syndrome
1. Trisomy 12P: generalized 3 Hz spike and wave; 2/3 of patients have myoclonic seizures Grey–Matter heterotopias 1. Heteropsia are secondary to improper migration of neurons from the subependymal ventricular zone 2. Over migration of neurons is implicated in: a. Seizure disorders b. Fetal alveolar syndrome c. 18p-syndrome d. Some congential muscular dystrophies 3. The three major forms of heterotopia are: a. Subependymal (SEH); nodular b. Band heterotopia (double cortex) c. Subcortical 4. Subependymal heterotopia a. In symptomatic women: 1) Partial complex seizures that start in the second decade b. In symptomatic males: 1) xq28: gene is filamin 1 (FLN1) a) Actin filament (is coded) b) Links membrane protein to actin 2) Clinical features: a) Strokes in early life a) Neurodevelopmental delay c) Seizure patterns: (1) Temporal lobe (mesial and neocortical) (2) Parietal and occipital foci
Chapter 7. Genetic Aspects of Seizures Subependymal Band Heterotopias (SBH) in Women
1. Genetics: mutation of the DCX gene a. Missense mutations in familial patients b. Sporadic mutations: 1) Protein truncation mutations c. DCX carrier mothers (not including germline or mosaicism mutations) 1) Minimally affected 2) Milder SBH phenotype 3) Mutations are R196H of exon 5 (pep-2) repeat on X chromosome 4) Majority of DCX mutations are (pep ½) 2. Clinical features: a. Mental retardation b. Developmental delay c. Complex partial seizures d. Atypical absence seizures e. Severely affected patients suffer drop attacks f. Sporadic cases more severely affected than familial g. Most severely affected women: 1) Mental retardation 2) CPS 3) Demonstrate the ILS (isolated lissencephaly) sequence 3. Males with mutations of the X lissencephaly (XLIS) or double cortin DCX gene a. Suffer severe brain anomalies b. Die in utero (in general) c. X-linked isolated lissencephaly/SBH 1) Genetics: mutations within the DCX gene a) Familial form b) Sporadic −80% are females c) Allelic-ILS/SBH 2) ILS in boys 3) SBH in girls
Males with Epilepsy, Complete Subcortical Band Heterotopia and Somatic Mosaicism for DCX Gene
1. Genetics: a. Mutation in the double cortin gene (DCX or XLIS gene on the X chromosome) b. Bilateral symmetric bands of grey matter in central white matter of cerebral hemispheres 2. Females with DCX mutation a. Complete subcortical heterotopic bands (double cortex) 1) Small amount of polygyria 2) Normal gyrational pattern b. Clinical features: 1) Mild mental retardation 2) Complex partial seizures 3. Males with DCX mutations
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a. SBH is not observed b. Classic lissencephaly noted: 1) Complex partial seizures 2) Mental retardation c. Mutated gene is on the inactivated X-chromosome 1) This single copy of the mutated DCX gene affects all developing neurons-lissencephaly is produced d. SBH can occur in males who have a somatic mosaicism LIS1 gene: chromosome 17p 13.3 a. Both males and females b. Posterior greater than anterior brain malformations compared to SBH/DCX mutations
Bilateral Diffuse Heterotopia
1. Genetics: Xq 28 2. Clinical features: a. May have normal IQ b. Mental retardation is usual c. Seizure type as noted with unilateral Xq 28 syndrome d. Cerebellar hypoplasia e. Syndactyly f. Short gut syndrome g. Frontonasal dysplasia h. Congenital nephrosis 3. Associated malformations: a. Megalencephaly c. Encephaloceles b. Hemimeganencephaly d. Polymicrogyria 4. Variants a. Bilateral periventricular nodular heterotopia (BPNH) with associated MR 1) Genetics: micro deletions/micro duplications in Xq28 b. BPNH 1) Associated with Ehlers–Danlos c. BPNH 1) VLes absence of the corpus callosum syndrome; X-linked d. Clinical features: 1) MR 2) Pyramidal tract signs MASA Syndrome
1. Genetics: LICAM gene mutation 2. Clinical features: a. Adducted thumbs c. Aphasia b. Spasticity Isolated Subependymal Heterotopia (SE)
1. X-linked and non X-linked 2. Unilateral focal group a. Seizures b. Decreased cognition
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Associations of Subependymal Heterotopia
1. 2. 3. 4.
Chiari II malformations Basilar cephaloceles Agenesis of the corpus callosum Metabolic disorders a. Zellweger Syndrome b. Neonatal adrenoleukodystrophy
AD Subependymal Heterotopia in Males
1. Similar to female presentations of SEH Subcortical Heterotopias
1. Males and females are equally affected 2. Congenital defects 3. Complex partial seizures a. start at age 15–20 years
a. Abnormalities of glial proliferation b. Neuronal migration disorder c. Dysplasia of cortical organizations
Familial Partial Epilepsy with Variable Foci
1. Genetics: chromosome 2q; penetrance 60% 2. Clinical features: a. Onset a 13–43 years of age b. Distinguished from other inherited epilepsies because partial seizures may have different orgin (frontal, temporal, parietal or occipital) in different members of the same family c. Familial temporal lobe epilepsy: 1) Affected members have a medial or lateral origin 2) Medial temporal lobe: chromosome: 10 3) Lateral temporal lobe with auditory features: AD
Bilateral periventricular nodular heterotopia (BPNH)
1. Genetics: a. Xq28 (females) b. Distal arms of Xq28 (males) 2. Clinical features in female children: a. Epilepsy b. Normal intelligence 3. Clinical features in male children: a. Seizures c. Mental retardation b. Syndactyly 4. Clinical male variants of BPNH associated with: a. Short gut b. Congenital nephrosis 5. BPNH with fronto nasal malformations; clinical features: a. Anterior cranium bifidum occultum b. Hypertelorism c. Broad neck d. Poorly formed nasal tip e. Widows peak f. Frontal bossing g. Low set eyes h. High arched palate/cleft palate i. Strabismus j. Epicanthal folds k. Micropenis l. Triorchidism m. Proximal implantation of 5th toe n. Clinodactyly i. Mental retardation 6. MRI a. Cortical dysplasia c. Atrophic vermis b. Ventriculomegaly 7. Associated intracranial cystic malformations a. Midline brain defects b. Hematoma and lipoma of corpus callosum c. Anterior encephalocele d. Holoprosencephaly 8. Pathology (25 syndromes with BPNH)
The Epileptic Spectrum in the Congenital Bilateral Perisylvian Syndrome
1. Clinical features: a. Pseudobulbar palsy b. Bilateral perisylvian polymicrogyria c. Onset of illness: age 4–12 d. Seizures in 87% of patients: 1) Atypical absence with atonic component 2) Tonic clonic 3) Partial 26% 4) Drop attacks 5) Bilateral focal seizure involving the lips e. Facio-pharyngeal-masticatory diplegia (opercular syndrome of Foix–Chavany–Marie) f. Mental retardation
Epilepsy in the Nevoid Basal Cell Carcinoma Syndrome (Gorlin’s’ Syndrome)
1. Genetics: AD; chromosome 9q 22.3–q31 full penetrance 2. Clinical features: a. Onset: puberty to early adulthood b. 80% of patients, one basal cell tumor by age 20 c. Planar plantar pits d. Odontogenic cysts in the mandible e. Optic nerve compression f. Facial paresthesiae g. Abnormal taste 3. Dysmorphism: a. Large stature b. Macrocephaly; broad nasal root c. Frontoparietal bossing d. High arched palate
Chapter 8. Unusual Seizures and Concomitant Medical Conditions
e. Sloping narrow shoulders f. Bifid hypoplastic ribs g. Polydactyly syndactyly h. Calcified bilateral ovarian cysts i. Pseudocystic bone lesions j. Cardiac fibroma k. Spina bifida l. Agenesis of the odontoid 4. Central nervous system associations: a. Intracranial calcifications of the: 1) Falx 3) Petroclinoid ligament 2) Diaphragma sella b. Meningioma c. Medulloblastoma (3–5%) d. Agenesis of the corpus callosum e. Seizures f. Fusion of the hemispheres g. Thick cortical mantle
Progressive Facial Hemiatrophy and Epilepsy (Parry–Romberg Syndrome)
1. Age of onset 24–70 years of age 2. Clinical features: a. Facial dysmorphism b. Upper face affected; subcutaneous tissue and bone atrophy c. Starts first two decades d. Possibly localized linear scleroderma e. Seizures prior to age 20; simple or complex partial seizures; masticatory spasms f. Vascular proliferation g. Cystic infarcts of the brain underneath the focal mesodermal lesions 3. Pathology: a. Cortical laminar disruption under the skull defect b. Intracranial calcification c. Midline non-specific gliosis d. Leptomeningeal abnormalities e. Dysgenetic embryoplastic neuroepithelial tissue (DNT) 1) Focal glial cortical neoplasia 2) Intracortical or subcortical heterogenous lesions
Adult and Adolescent Chronic Encephalitis and Epilepsy (Variant of Rasmussen’s Syndrome)
1. Mechanism a. Persistent viral infection b. Viral infection with local immune response; antibodies to GLUR3 receptor 2. Clinical manifestations: a. Epilepsia partialis continue 50% of patients
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b. Simple partial seizures c. 85% of patients have seizure prior to age 10 3. Adult patients: a. More benign course b. More occipital lobe involvement c. May be bilateral
Epilepsy Syndromes with Single Gene Mutations
1. Generalized epilepsy with febrile seizures plus (GEFS+) gene a. SCN 1B – sodium channel subunit b. SCN 1A – sodium channel subunit c. SCN 2A – sodium channel subunit d. GABRG2 – GABAA – receptor subunit 2. Benign familial neonatal convulsions gene a. KCN Q2 – potassium channel b. KCN Q3 – potassium channel 2. Autosomal Dominant Neuronal Frontal Lobe Epilepsy Gene a. CHRNA4 – Neuronal nicotinic acetylcholine receptor subunit b. CHRNB2 – Neuronal nicotinic acetylcholine receptor subunit 3. Childhood absence epilepsy and febrile seizures gene a. GABRG2 – GABA – receptor subunit 4. Autosomal dominant partial epilepsy with auditory feature gene (ADTLEAF) a. LG IV b. Leucine rich transmembrane protein
Chapter 8 Unusual Seizures and Concomitant Medical Conditions
Lateralizing Signs in Partial Seizures
The percentage of identifying focal seizure foci with the following lateralizing signs: 1. Version – 94% 2. Dystonic posture – 93% 3. Ictal speech deficit – 83% 4. Automatism with preserved responsiveness (right hemisphere) 5. Ictal vomiting – right temporal lobe 6. Early head turning – 89% (to the ipsilateral hemisphere) 7. Dystonic limb posturing – 88% 8. Blinking (wink-like rather than clonic); more common in left temporal lobe than from the right temporal lobe 9. Ipsilateral seizure focus: a. Unilateral automatism b. Early head turning
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10. Motor events contralateral to the seizure focus: a. Bilateral automatisms interrupted by dystonic trunk posturing (contralateral) to the seizure focus 11. Blinking representation (parietal 7a) a. Blinking in one eye 1) Focus is ipsilateral (occipital lobe) b. Bilateral blinking 1) Focus is in the posterior parietal area 7a 12. Post ictal dystonia, dystonic posturing: ictal speech, upper extremity automatisms a. May be seen from either temporal lobe 13. Forced sustained head deviation, dystonic arm posture, jaw and mouth deviation a. Occur contralateral to frontal seizure focus b. Unilateral automatism of the upper extremity (ipsilateral focus) c. Post ictal dysnomia (speech dominant hemisphere) d. Ictal dysnomia (not reliable)
Cardiac Arrhythmias that Occur During Complex Partial Seizures:
1. 2. 3. 4. 5. 6. 7.
Supraventricular tachycardia Sinus tachycardia Sinus bradycardia Sinus arrest AV block Asystole Reduced heart rate variability
General features of cardiac arrhythmias during seizures
1. Seizure induced arrhythmia is a cause of death in epilepsy patients 2. Ictal tachyarrhythmias are more common than bradyarrhythmias 3. Bradyarrhythmias occur with both the left or right temporal lobe seizures 4. Intraoperative stimulation of the insular cortex a. Tachyarrhythmias and a pressor response right anterior insular cortex b. Bradycardia and depressor response: left anterior insular cortex 5. Sinus arrest with asystole: left temporal cortex 6. Ictal bradycardia: increased parasympathetic out flow through the vagus 7. Stimulation of the amygdala causes bradycardia 8. Insular projections a. Lateral hypothalamus b. Amygdala 9. Simulation of the orbital frontal cortex and cingulate gyrus cause brady and tachyarrhythmias
Photosensitive Temporal Lobe Epilepsy
1. True temporal lobe epilepsy can be photosensitive 2. General photosensitive epilepsy a. AD trait b. Age dependent penetrance c. Wave length dependent
Unusual Seizures
Gelastic Seizures
1. Ictal laughter (gelastic seizure) 2. Hypothalamic hamartoma is the usual cause: a. Seizures begin in infancy or childhood b. Intellectual decline c. Precocious puberty d. Behavioral problems 1) Aggressive 3) Autistic features 2) Disinhibited 4) Hyperactive e. Diabetes insipidus and pan hypopituitarism following resection f. Symptomatic (ictal laughter) or secondary generalized seizures g. Laughter: 1) Unmodulated 2) Not associated with mirth 3) Machine gun quality 4) Sudden onset 5) Inappropriate 6) Gelastic attacks may occur when the hypothalamus or adjacent structures are displaced; nodules attached to the tuber cinereum or mamillary bodies have been seen 7) Drop attack a) Preceded by brief gelastic episode or clonic seizure h. EEG slow spike and wave may occur in first decade; tonic and atonic GTCS i. Poor response to anticonvulsants j. Atonic k. High incidence of drop attacks l. Epileptic activity from the hamartoma itself Dachrymistic Seizures
1. 2. 3. 4. 5.
Continual crying Unmodulated (monotonic) Inappropriate May have associated tears Bilateral temporal lobe disease
Differential Diagnosis: Inappropriate Laughter or Crying
1. Bilateral corticormedial lesions (internal capsule) 2. Pontine lesions 3. Bilateral cortical (insular cortex) lesions
Chapter 8. Unusual Seizures and Concomitant Medical Conditions Catamenial Epilepsy
1. Usually occurs at midcycle (10–14 days) 2. Estrogen is excitatory to cortical neurons and progesterone is inhibitory 3. Water retention
Focal Akinetic Seizure
1. Focal paresis precedes convulsive activity in the affected part 2. Focal paresis may affect one part of the body; convulsive activity may occur in that part 3. Somatosensory sensations may occur before or at the onset of the focal paresis in the same body region 4. Structural lesions have been documented in central parietal regions
Epileptic Negative Myoclonus
1. Action-activated motor activity (jerks) limited to one arm or leg 2. Rarely may be multifocal 3. Patients may demonstrate motor neglect of the affected part 4. Most patients have history of seizures 5. Paroxysmal epileptic activity in areas of the sensorimotor cortex Epilepsy in the Elderly
1. Incidence of new epilepsy patients greater than 60 years of age a. 77/100,000 persons 2. Clinical features: a. Altered mental status b. Episodes of unresponsiveness c. Blackouts 3. Frontal and parietal lobe involvement a. Dizziness is the most common symptom 4. Younger patients a. Post ictal confusion lasts 5–10 minutes 5. Elderly patients a. Postictal confusion may last days Ictal Paralysis that Resembles Todd’s Paralysis
1. Clinical features: a. EEG during Todd’s paralysis is normal or demonstrates slow waves b. Ictal paralysis:
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1) Generalized (ictal or epileptic negative myoclonus is followed by epileptic drop attacks) 2) Focal motor seizures can be followed by an inhibitory atonic seizure a) Seizure starts in the motor area and spreads to suppressor strip (premotor area 6) b) Focal paralysis is seen SUDEP (sudden unexplained death in epileptic patients) 1. Insular cortex 2. Multiple drugs 3. Severity of the seizures 4. GTCS 5. 40% of patients have ST depression on EKG 6. Increased heart rate Seizures During Pregnancy
A. Occurrence: 1. Seizure frequency increased in 24% of women during pregnancy 2. Most frequent at the end of the first trimester and beginning of the second 3. Increased seizure activity is not dependent on: a. Seizure type b. Seizure frequency prior to pregnancy c. Sex of the fetus 4. Increased seizure activity dependent on: a. Distribution, protein binding, metabolic rate, and renal excretion of anticonvulsants b. Clearance returns to baseline at approximately three months post partum c. Clearance change evident in the first trimester and is maximum at term B. Intestinal Absorption 1. Clearance of anticonvulsants (increased) due to changes in GI absorption and blood volume 2. Gastric emptying and intestinal motility slowed during pregnancy 3. Increased gastric pH and buffering capacity 4. Malabsorption from the baby is not significant in the change of drug clearance C. Hepatic Metabolism: 1. Progesterone stimulates hepatic activity D. Protein binding: 1. Albumin levels decline during pregnancy, which decreases protein binding of the drug; lower albumin level results in proportional reduction of protein binding. This mechanism is most significant in highly bound drugs. An increase in the free fraction of the drug may change very little. Measurement of the free fraction is the best method of monitoring effective drug concentrations. E. Volume of distribution: 1. Body weight increases
SECTION II. Epilepsy
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2. Intravascular volume increases 3. Volume into which the drug is distributed increases during pregnancy which tends to lower plasma levels F. Urinary excretion: 1. Renal blood flow increases during pregnancy 2. Unbound drugs (lowest protein binding) may have increased excretion G. Hormone variability: 1. Estrogen increases cortical excitability 2. Progesterone suppress epileptic discharges 3. Estriol, estradiol and progesterone increase during pregnancy 4. Ratio of estrogen to progesterone is greatest between weeks 6 to 16, the time seizures increase in frequency
Epilepsy and Reproductive and Endocrine Dysfunction
1. 50% of women with TLE a. Sexual dysfunction c. 14–20% have amenorrhea b. Hormonal abnormality d. Fertility reduced 30% 2. Men with TLE a. Approximately 50–70% sexual dysfunction 3. Associated medical and hormonal conditions reported in TLE a. Hypogonadotropic and hypergonadotropic hypogonadism b. Functional hyperprolactinemia c. Polycystic ovary disease d. Anovulatory cycles
Issues in the Use of Generic Preparations as a Cause of Loss of Seizure Control
1. Narrow therapeutic window (carbamazepine) 2. Differences in bioavailability between manufactured forms result in variations in serum concentrations: a. FDA criteria for bioequivalence allow for a +20% difference in bioavailability between generic and brandname products b. US plus criteria specify that capsule content be within +% (93–107%) of the stated content of the preparation c. Bioequivalence studies are performed in healthy adult volunteers; this population does not conform to many patients
Chapter 9 Differential Diagnosis of Seizure Disorder vs Syncope The differential diagnosis of seizure disorder from other conditions with temporary loss of consciousness depends primar-
ily on the history from the patient and any additional information obtainable from bystanders. The neurological and general medical examination may elicit the specific diagnosis. In children a variety of abnormal movements and breath holding spells may be confused with seizures and will not be considered further. In adults, the differential diagnosis most frequently depends on the differential of true epileptic seizures from the varied causes of syncope, paroxysmal kinesogenic and other forms of abrupt choreoathetosis, myoclonus, and panic and rage attacks. Syncope occurs from an abrupt or gradual reduction of cerebral blood flow. It is characterized by the clinical symptoms of a feeling of lightheadedness or faintness, visual and auditory symptoms, muscle weakness and gastrointestinal symptoms. The specific forms of syncope frequently have historical or physical findings that are very specific and allow for an accurate differential diagnosis. Vago-vagal syncope refers to an increase of vagal tone initiated from the orbital frontal cortex to the lateral hypothalamus and dorsal vagal nucleus. The patient experiences emotional upset or a visual trigger. There is a premonitory feeling of light headedness, paleness is observed and the patient may fall. The heart rate is slow, the patient often is hyperhidrotic and respiration is labored. The event characteristically lasts for less than 30 seconds. There is no post event confusion and there is amnesia for the event. Rarely sphincter incontinence and myoclonic jerks are noted and complete return of consciousness is greater than two minutes. Vaso depressor syncope is caused by failure of the vasomotor center in the lateral pontine tegmentum to maintain peripheral vascular resistance. Usually, the patient has been in bed for longer than 2–3 weeks or is taking medication for hypertension that blocks sympathetic outflow peripherally or centrally. The patient is able to stand for 30 seconds, blood pressure is maintained for up to one minute and then the patient feels light headed and collapses. The pulse is rapid; consciousness is regained quickly with no residual deficits. No headaches and no post event confusion are noted. The blood pressure may be very low in both vago-vagal and vasodepressor syncope. Carotid sinus hypersensitivity is a rare cause of syncope in elderly patients. It occurs most frequently in elderly male patients concomitantly with head turning rather than a tight collar. Right carotid sinus massage has been associated more frequently than left with cardiac arrest. Most often the patient is standing when syncope occurs and the patient may be unconscious for longer than two minutes. Vasodepressor syncope from glossopharyngeal neurologia occurs in the context of severe lancinating pain in the tonsillar fossa, throat, deep ear and rarely causes severe bradycardia or asystolic. If prolonged it may cause generalized tonic clonic seizures. There are usually triggers such as chewing, swallowing and speaking and the lancinating pain precedes the cardio depressor syncope. Irritation of the vagus nerve in the neck from esophageal diverticular masses tumors or aneurysms that
Chapter 9. Differential Diagnosis of Seizure Disorder vs Syncope
compress the carotid sinus and carotid body tumors (chromaffin) may present with syncope. Decreased cardiac out flow from both congenital and acquired causes may decrease cerebral perfusion sufficiently to cause syncope. The tetralogy of Fallot is now rarely seen due to early corrective surgery. Tetrad attacks occurred with exercise which causes right to left shunting and cerebral hypoxia. Patients would characteristically squat, after exercise and occasionally lose consciousness. Pyramidal tract dysfunction with spasticity and bilateral Babinski signs are noted. Severe right to left shunting from large ASD’s and VSD’s may cause deepening cyanosis with exercise and syncope. Obstructive valvular heart disease, particularly aortic stenosis is, associated with syncope during exercise. The cause may be either poor cerebral perfusion (walking up the second flight of stairs) or associated AV node dysfunctions which may occur concomitantly with calcific aortic stenosis (one of Leriche’s Syndromes). Hypertrophic subaortic stenosis usually causes syncope at the end of vigorous exercise. The patient has climbed four flights of stairs, is resting, breathing heavily and then loses consciousness. The infundibulum beneath the aortic valve contracts due to release of norepinephrine and epinephrine released from the adrenal medulla, dilates peripheral resistance vessels in the legs to cause cerebral hypoperfusion. The patient collapses at the top of the stairs. Pulmonic stenosis occurs from a domed valve with a pinhole orifice. Young patients collapse during vigorous exercise (during track or basketball). This must be differentiated from the long QT syndrome that also occurs with vigorous exercise. Patients with severe mitral stenosis are too weak to exercise vigorously. They present with syncope due to cardiac cerebral embolus. Cerebral perfusion fails with a cardiac ejection fraction of less than 30%. This situation is also prime for cardiac embolus. Cardiac tumors such as atrial myxomas are a rare cause of valve obstruction and decreased cardiac output. Left atrial myxomas most often cause mitral insufficiency rather than stenosis. Syncope is more often secondary to embolus. Syncope from mitral valve prolapse is most often due to ventricular arrhythmia. Right sided myxomas are characterized by postural obstruction of the tricuspid valve. The patient demonstrates postural shortness of breath (hypopnea), cyanosis and syncope. Once the patient falls, the myxoma block of the tricuspid orifice is relieved and the patient regains consciousness. Cardiac inflow obstruction with consequent syncope occurs with superior and inferior vena cava obstruction. The former most often occur in the context of lung or other thoracic cancer, X-RT or hypercoagulable states. Swelling and collateral venous channels over the chest wall are evident. Pregnant women may have poor enough venous return from uterine compression of the inferior vena cava to cause syncope. Renal cell cancer may also occlude the inferior vena cava and cause syncope.
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Tension pneumothorax, poorly regulated ventilators, neck surgery with superior vena cava obstruction, jugular vein occlusion, and cardiac tamponade may all decrease cardiac filling severely enough to cause syncope. Aortic dissection either alone or below the subclavian artery is associated with syncope at ictus. The former is associated with carotid occlusion and tamponade and the later with spinal cord infarction with consequent vasoconstriction and peripheral vascular resistance. Cardiac arrhythmias are a major cause of syncope and always need to be differentiated from true seizure activity. In general, atrial arrhythmias cause syncope by increased ventricular rate fast enough to compromise filling. The atrial kick only accounts for approximately 15% of cardiac filling. Ventricular tachycardias are often clearly evident to the patient by a feeling of palpitations and a recognition of a rapid heart rate. As cerebral hypoperfusion supervenes during ventricular tachycardia, patients feel as if they are going to faint, vision closes in from the side, sounds become distant and the patient loses of consciousness. Usually the patient is unconscious for less than 30 seconds if severe cerebral hypoperfusion supervenes but the patient may suffer a major motor convulsion. As a general rule, cardiac syncope can occur in any position, is sudden and may be induced by exercise, and is longer than other benign causes. A heart rate of greater than 140/minutes suggests an ectopic rhythm and a rate of less than 40 minutes suggests heart block. Stokes Adams attacks refer to loss of consciousness due to complete AV block. The onset is sudden. Rarely there may be visual, sensory, or premonitory auras. The pulse and heart sounds are lost. Patients fall, may have labored respiration, and if greater than 45 seconds, urinary incontinence, clonic jerks and generalized seizures. Focal neurologic signs and symptoms may be evident as there is frequently widespread cerebral vascular disease. The mechanism is distal field ischemia. Sinoatrial block is most frequent in elderly patients. Patients often note dizziness, light headedness and palpitations. The patients are pale and have a slow or irregular pulse. The most common supraventricular brady tachycardias are AF, Wolf Parkinson White (WPW) and atrial flutter. The rapid ventricular response with inadequate cardiac filling is the cause of inadequate cerebral perfusion. WPW rarely causes syncope. This is more frequent with the Lown–Ganong– Levine syndrome. Ventricular arrhythmias cause the most serious loss of consciousness and occur in less than 5 seconds in the context of ventricular fibrillation. There is virtually no reserve cerebral ATP. They usually occur in elderly patients with generalized vascular disease. Long QT syndromes are associated with VIIIth nerve dysfunction and are now known to be due to KCN (potassium channelopathies) and rarely sodium channel dysfunction. Syncope occurs often during vigorous exercise. Episodes usually begin in the first decade of life, but may be seen in the second or third decade.
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SECTION II. Epilepsy
Hypotension from any cause if severe enough to curtail cerebral perfusion may cause syncope. In general, standing causes an immediate systolic drop of blood pressure (10 mmHg) and a diastolic rise of blood pressure of 5 mmHg. The autonomic neuropathies in which both sympathic and parasympathetic innervations are impaired demonstrate no compensatory increase of heart rate concomitant with the systemic fall in pressure. Patients have the usual visual, auditory and light headed feeling, but also often complains of a “coat hanger headache” (trapezius ridge and posterior cervical areas) prior to loss of consciousness. If the person is suffering from hereditary autonomic neuropathy or multiple system atrophy, the patient’s hands are cold, cyanotic, and demonstrate poor capillary reperfusion. Sly–Dräger patients appear parkinsonian, but have no response to dopamine and suffer iris atrophy. Younger patients with Riley–Day Syndrome demonstrate congenital insensitivity to pain, livedo reticularis, and have poor tearing and temperature control. The hereditary autonomic neuropathies may demonstrate distal ulcerations from small fiber pain and temperature dysfunction as well as poor distal circulations. Orthostatic hypotension is common with tricyclic antidepressants, arterial vasodilators, anti-hypertensive medications, diuretics, calcium channel blockers, alcohol, levodopa, phenothiazine as well as any cause of venous pooling or hypovolemia. Any central nervous system disease that interrupts descending sympathetic fibers, usually at a spinal cord level, causes hypotension. Most patients with a thoracic level above T6 suffer hypotension. Patients with chronic spinal cord transection may be able to maintain consciousness at blood pressures of 90/60 mmHg. The autonomic variant of Guillain Barré Syndrome, beriberi, severe, diabetic neuropathy, hepatic porphyrias, alcoholism, and rarely B12 deficiency may have severe orthostatic hypotension. In general, vertebrobasilar disease causes drop attacks without true loss of consciousness. Patients may appear stunned and respond poorly but are not unconscious. This mental state usually lasts for less than 20 seconds. The subclavian steal syndrome rarely causes loss of consciousness. This is particularly apparent in studies of patients with Takayasu’s disease who demonstrate severe arterial disease, but do not lose consciousness. The usual clinical symptomatology is dizziness, dysarthria, and incoordination with left arm use. Vasospasm of the vertebrobasilar arterial system in Bickerstaff’s migraine often is associated with a brief loss of consciousness of less than 10 seconds. Patients most often suffer paresthesias of the hands, incoordination and basiocciput headache. Turning the head to one side occludes the vertebral artery of that side. If the other vertebral artery is atretic, patients may have momentary loss of consciousness. A few patients lose consciousness with bending their head backwards (“clothes line syndrome”-hanging wash). This is
rare and lasts for less than 10 seconds. Sudden carotid occlusion may cause dizziness, a presyncopal feeling, a shaking TIA and loss of consciousness. Patients appear stunned and mute with supplementary motor area stem MCA and thalamic infarction which may last for minutes to hours. Hypoglycemic symptoms occur in stages. Early as the blood sugar falls, an epinephrine response is elicited. This consists of hunger, piloerection and behavioral change. As the sugar falls to within 30–40 mg%, a parasympathetic response is seen with salivation, smaller pupils, loss of consciousness and seizures. Pulse and blood pressure are minimally decreased. Severe anoxia may produce syncope, but is usually preceded by lethargy or asterixis if associated with hypercarbia. It may also cause vasodepressor syncope. Hyperventilation to syncope is preceded by perioral and extremity paresthesias, light headedness and rarely blurred vision, dry mouth, and chest tightness. Tussive syncope usually occurs after a severe bout of paroxysmal coughing. It may rarely occur often one cough. Recent transcranial Doppler studies have demonstrated decreased cerebral perfusion. This may occur from a cardiac depressor mechanism or from poor ventricular filling from increased intrathoracic pressure. The patient may have a congested face due to poor venous outflow from the head and then become pale. There may be a feeling of presyncope. The syncopal attack lasts for less than 5–10 seconds with complete recovery. Micturition syncope occurs most often in young men who have been drinking. The bladder is over stretched and stimulates the posterior hypothalamus that activates the vasomotor center and then sequentially the intermediolateral columns of the spinal cord to effect sympathetic constriction of the peripheral vasculature. Patients strain to initiate micturition, further compromising venous return to the heart. Once the hypothalamic drive (associated with slight shivering and piloerection) is decreased with bladder emptying, the peripheral vascular resistance collapses with consequent hypotension and decreased cerebral perfusion. An epinephrine secreting pheochromocytoma of the bladder has also been associated with micturition syncope. Contributory factors for micturition syncope may be vasodilatory effect of alcohol and its nocturnal occurrence at which time blood pressure is lowest. Defecation syncope is rare and occurs with straining at stool. The same pathophysiology is posited. Charcot’s syncope occurs with eating rapidly and swallowing a large bolus. The posterior pharynx is unduly stimulated which activates cardiodepressor nerves from cranial nerve IX. Patients awaken within seconds with no confusion or residual. Chiari malformations with caudal brainstem compression occasionally are accompanied by episodes of syncope. The patient coughs or exercises a Valsalva maneuver and often suffers a lancinating C2 headache. Rarely, this scenario is followed by a brief loss of consciousness. Obstruction of cerebral spinal fluid flow, particularly at the foramen of Monroe by a colloid cyst, subependymal giant
Chapter 9. Differential Diagnosis of Seizure Disorder vs Syncope
cell astrocytoma vascular malformation, or aqueductal stenosis may present with a severe postural headache and loss of consciousness. Parasitic masses from cysticercosis or schistosomiasis may also obstruct the ventricles. Patients characteristically lie flat immediately after the obstruction and hold their head. Atonic episodes characterized by weakness may occur suddenly. Some patients report accompanying tinnitus. Syringomyelia of the cervical spine has been associated with precipitate micturition (involvement of the bladder center at C8–T1, ciliary center of Budge) and short repeated syncopal episodes. Cataplexy, a component of the narcolepsy complex, may be associated with atonia and falling. This phenomenon occurs with sudden stimulation and is not associated with loss of consciousness. A rare dissociated state in which the patient can function, but is not fully alert may be associated with the narcoleptic attack. This may last for minutes to hours. Systemic conditions that produces hormone or neurotransmitter release such as pheochromocytoma, systemic mastocytosis and the carcinoid syndrome, may cause a momentary loss of consciousness due to alterations in blood pressure. Pheochromocytomas usually are associated with a normal blood pressure. When the tumor is activated, the blood pressure may be dramatically high 250/150 mmHg and is associated with shortness of breath and very loud A2 and P2 heart sounds. Headaches are severe and patients may have short syncopal episodes. Mastocytosis is a heterogeneous group of disorders in which there is abnormal growth and accumulation of mast cells in different organ systems. Cutaneous mastocytosis is generally benign. Mastocytosis that involves the skin and visceral organs may cause hypotension due to the release of chemical mediators primarily cytokines (IL-6 and other inflammatory mediators) that may open up the systemic circulation with consequent hypotension. Carcinoids are neuroendocrine tumors of the intestines, pancreatic islets and retroperitoneum. The carcinoid syndrome involves flushing (frequently and inch below the hairline on the forehead is spared), bronchospasm and hypotension. The major differential points between seizures and syncope are the following: Seizures have no relation to posture and may occur at any time of the day or night. They often have autonomic signs and are associated with incontinence and tongue biting (major motor). They last for 30 seconds, but are associated with postictal confusion, headache and fatigue. They may be associated with Todd’s paralysis or other neurological deficits affecting speech or movement. Tachycardia during the seizure is common and thirst is prominent in some complex partial seizures of temporal lobe origin. Syncopal episodes are frequently posturally related, take longer to develop than seizures and may have specific initiating sights or psychical triggers. They are associated with striking pallor and in general are shorter than seizures. They
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have no postictal confusion, headache or fatigue. A few convulsive jerks may be noted. There is rare urinary incontinence, no focal neurologic deficits, and prominent cardiovascular signs noted during the ictus. There is no injury from the event.
Cardiac Arrhythmias
1. 2. 3. 4. 5. 6. 7. 8. 9.
Sinoatrial node (sick sinus syndrome) AV node (Stokes Adams) Purkinje system disease of the heart (Mobitz Type II) Long QT syndrome Atrial fibrillation (fast ventricular rate) Atrial flutter (fast ventricular rate) Right atrial failure Wolf Parkinson White Lawn–Ganong–Levine
Reflex Brachycardia
1. Glosso pharyngeal neuralgia (IX) 2. Charcot’s syncope (IX, X) 3. Hypersensitive carotid sinus syndrome
Decreased Cardiac Output
1. Hypertrophic cardiomyopathies (HCM) a. Idiopathic hypertrophic subaortic stenosis b. Familial HCM gene encoding Troponin II chrom1q3 c. Familial HCM gene encoding B cardiac myosin chromo 14q 11–12 d. Mitochondrial myopathies e. Friedreich’s ataxia
Restrictive Cardiomyopathies
1. 2. 3. 4. 5.
Sarcoidosis Scleroderma PXE Storage disease Distal myopathy with rimmed vacuoles
Ventricular Filling Defects
1. 2. 3. 4.
Superior and inferior vena cava obstruction Cardiac tumor (myxoma, fibroelastoma) Thrombus Increased intrathoracic pressure
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SECTION II. Epilepsy
Cardiomyopathy
1. Familial dilated cardiomyopathy; AD chromosome 1p1– q21 2. AD Emery–Dreifuss 3. Dilated cardiomyopathy without conduction defect; chromosome 1, 9, 10, 15 4. Desmin related myopathy 5. Duchenne and Becker muscular dystrophies 6. Limb Girdle muscular dystrophies
5. Vagovagal syncope 6. Vasodepressor syncope 7. Cough/micturition/defecation syncope
Cerebrovascular Disease
1. Anemia 3. Acute blood loss 2. Dehydration
1. 2. 3. 4. 5. 6. 7. 8. 9.
Hypotension
Metabolic/Toxic
1. 2. 3. 4.
1. 2. 3. 4. 5.
Hypovolemia
Small fiber neuropathies Hereditary autonomic neuropathies Drugs (antihypertensive, diuretics, beta blockers) Associations with neurodegenerative disease a. Sly Drager Syndrome b. Riley Day Syndrome c. Multiple system atrophy d. Parkinson’s Disease
Anterior and posterior circulation ischemia Cerebral hemorrhage Cerebral embolus (stem MCA; SMA; thalamus) Subarachnoid hemorrhage Subclavian steal (rare) Vasospasm from Bickerstaff’s migraine Takayasu’s disease Aortic arch syndrome Aortic dissection
Hypoglycemia Anemia Anoxia Cocaine Solvent inhalation a. Glue sniffing c. Gasoline (Huffer’s disease) b. Paint
Section III ANTERIOR HORN CELL DISEASE THAT AFFECTS ADULT PATIENTS
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Chapter 1. Spinal Muscular Atrophies Linked to Chromosome 5q11.12–13.3 Introduction
The hereditary anterior horn cell diseases most often affect children. In the past, infectious poliomyelitis was seen throughout the Western World, but now is limited to parts of the third word. The major anterior horn cell spectrum that confronts adult clinicians is that of late onset spinal muscular atrophies, adolescent Kugelberg–Welander disease, overlaps with amyotrophic lateral sclerosis and metabolic variants of storage and degenerative disease that affect anterior horn cells. The primary example of the latter is hexosaminidase A deficiency. The exciting new aspects of this old differential diagnosis are autoimmune forms of anterior horn cell and axonopathies such as GMI neuropathy and those neuropathies with conduction block that appear to be lower motor neuron in origin but are treatable. Unfortunately, most often the adult clinician will be faced with various forms of amyotrophic lateral sclerosis to diagnose. There are many variants of both ALS and anterior horn cell disease that complicate hereditary degenerative diseases that must be differentiated for genetic counseling and prognosis. Autoimmune attack on both motor axons, their terminal twigs and anterior horn cells themselves are now routinely sought and are an early hopeful sign for the future treatment of these diseases.
Chapter 1 Spinal Muscular Atrophies Linked to Chromosome 5q11.12–13.3
A. General considerations: 1. Most cases of SMA are autosomal recesssive and are linked to chromosome 5 a. Survival motor neuron gene (SMN): 1) SMN telomeric or SMNI 2) SMN centromeric or SMNII b. Loose pair exchanges of exons 7 and 8 distinguish the two genes c. SMNt is deleted in 95% of SMA I, II, III d. Neuronal apoptosis inhibitory protein gene: 1) Deleted in 70% of SMA I 2) 2% of SMA II and III e. Less well characterized are BFT 2p44 gene deletions in 15% of SMA patients f. Genotype-phenotype correlation possibilities: 1) SMAt to SMAc milder phenotype 2) Deletion of NAIP gene occurs with increased severity g. Function of SMN protein may be ribonucleoprotein synthesis
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h. Autopsy of SMA patients reveals loss of anterior horn cells and those from bulbar cranial nerves nuclei B. Clinical features: SMA I (Werdnig Hoffman Disease) 1. Age of onset is birth to six months 2. Floppy infant; poor swallowing and sucking reflexes 3. Normal heart 4. Extraocular muscles are spared 5. Finger tremor 6. Death in less than two years SMA II 1. Can sit independently; onset after six months 2. Normal cognition 3. Deep tendon reflexes retained in up to 25% of patients 4. May live to second or third decade 5. Scoliosis supervenes SMA III (Kugelberg Welander) 1. Diagnosed by age 18 months due to pelvic girdle weakness 2. Some may walk independently; may resemble DMD (Duchenne Muscular Dystrophy) 3. Normal life span 4. Fasciculations > 50% of patients (often proximal muscles) B. Laboratory evaluation: 1. CK may be up to 10x normal 2. EMG: a. Positive sharp waves b. Reduced interference pattern c. No persistent MUAP d. Motor NCV are normal SMA IV 1. Onset after age 20; mean onset mid 30’s 2. Slowly progressive 3. Proximal limb weakness with fasciculations 4. Some patients have more aggressive course and are unable to walk by age 20 5. Scoliosis Differential Diagnosis of SMA
The differential diagnosis of SMAIII (Kugelberg Welander disease) includes DMD or BMD. In this instance there are no fasciculations and the CK is usually much higher. Congenital myopathies frequently have ptosis, generalized thinness of muscle, cardiac defects, extraocular muscle palsies and dysmorphisms that readily differentiate them from SMAs. Limb girdle muscular dystrophies have pelvic and shoulder girdle weakness, but stronger muscles with less diminution of reflexes. They also may have specific cardiac, laryngeal, and muscle pattern weakness as well as genetic patterns that make them discernible on clinical grounds. Distal SMA, share pes cavus with CMT, but lack the distal 1/3 of quadriceps wasting (“champagne bottle legs”) and sensory loss. They also have normal SNAPs.
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SECTION III. Anterior Horn Cell Disease that Affects Adult Patients
SMA II and III patients frequently live to adulthood and therefore must be considered in the differential diagnosis of adult motor neuron disease. The CK level maybe markedly elevated in Kugelberg Welander disease (SMA III) up to 10 times normal and are minimally elevated in SMA II and III. EMG reveals persistent motor unit activity most often in SMA I, rarely in SMA II and not in SMA III. Fasciculations are common in SMA II and III. Denervation is seen in all forms of SMA. SMA III and IV show signs of reinnervation. All have normal SNAPs and motor nerve conduction velocities are normal. Those patients with high CK require that inflammatory muscle disease be ruled out. Extraocular muscle and facial involvement exclude SMAs. The differential diagnosis of the “floppy infant” includes a host of central nervous system and congenital myopathies and applies primarily to SMA I Werdnig–Hofmann’s disease that do not reach adulthood.
SMA Variants Linked to Chromosome 5q
Arthrogryposis multiplex congenita A. General considerations: 1. Forms linked to muscle abnormalities, joint, and anterior horn cell disease 2. Anterior horn cell form associated with deletion of the telomeric motor neuron survival gene (SMNt) B. Clinical features: 1. Severe joint deformities 2. Poor muscle tone 3. Poor movement in utero 4. Bilateral congenital hip dislocations
Congenital Axonal Neuropathy
A. General considerations: 1. Homogeneous deletion of SMA gene in the paternal haplotype 2. Mutations in the MP2 gene B. Clinical features: 1. Early onset CMT 1B 2. HSP associated with ataxia, thin corpus callosum, cataracts and axonal neuropathy
Spinal Muscular Atrophies Not Linked to Chromosome 5q
Late Onset Tay Sach Disease A. General considerations: 1. Autosomal recessive 2. Loss of hexosaminidase A; a lysosomal enzyme whose deficiency causes accumulation of GM2 ganglioside in neurons
3. Gene coding for the α or β chain is located on chromosome 15 or 5 respectively; dysfunction of either causes decreased hexosaminidase A 4. Partial deficiency of hexosaminidase causes late onset anterior horn cell disease 5. Various forms of mutations: a. Homozygosity for a single mutation b. Compound heterozygotes with two abnormal alleles on the same chromosome B. Clinical features: 1. Age of onset is the second decade; between 11 to 67 years 2. Dysarthria and truncal ataxia precede appendicular ataxia often the earliest sign 3. Lower motor neuron involvement is prominent 4. Lower extremities > upper extremities 5. Proximal > distal muscle involvement that simulates Kugelberg–Welander disease 6. Recurrent psychosis which may precede or follow the neurologic manifestations 7. Psychosis may be the sole manifestation 8. Rare neurologic features: a. Extrapyramidal tract disease b. Dementia c. Dystonia C. EMG evaluation: 1. Neurogenic; normal motor NCV; normal sensory nerve conduction velocities
Monomelic Muscular Atrophy
A. General considerations: 1. Primarily cervical muscles affected B. Clinical features: 1. Non progressive 2. Asymmetric 3. Usually one upper extremity affected more than the other 4. Rarely the tongue may be affected
Fazio-Londe Disease (see ALS)
A. General considerations: 1. AR B. Clinical features: 1. Limited to the lower cranial nerves 2. Death in 1–5 years
Distal SMA
A. General considerations: 1. Phenotypic CMT
Chapter 1. Spinal Muscular Atrophies Linked to Chromosome 5q11.12–13.3
2. Juvenile or early adult onset with variable rates of progression 3. AD and AR recessive variants B. Clinical features: 1. Distal muscular wasting with pes cavus 2. Proximal musculature is involved with time to a lesser degree 3. No sensory loss
Adult Onset SMA
A. General considerations: 1. AD inheritance B. Clinical features: 1. Proximal limb girdle weakness C. EMG: 1. Normal sensory nerve action potentials
Scapuloperoneal Syndrome
A. General considerations: 1. Both myopathic and neurogenic forms 2. AD inheritance B. Clinical features: 1. Scapuloperoneal distribution of muscle wasting and weakness 2. Variable onset and progression
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a. Wasting of intrinsic hand muscles 4. Exercised induced muscle cramps (neurogenic cramps) 5. Hand tremor may occur prior to weakness (phenotypical of ET) 6. Facial fasciculations (most prominent around the mouth and chin); noted at rest and with contraction 7. Weakness and atrophy of facial muscles and those of mastication; tongue wasting and fasciculation may precede that of other muscles 8. Rare complaints of dysarthria and dysphoria early; they are prominent after 10 years of disease 9. Sensory examination is usually normal 10. Gynecomastia and impotence are present 11. Absent or hypoactive deep tendon reflexes 12. Congenital fractures 13. Some patients with joint contractures C. Laboratory evaluation: 1. Elevated CK (900 to 8000 units/dl) higher than any other AHC disease 2. Muscle biopsy characteristic of denervation D. EMG evaluation: 1. Normal NCSs; CMAP is low from weak and wasted muscle; low amplitude or absent SNAPs 2. Needle EMG demonstrates denervation of extremity muscles; facial and mentalis muscles demonstrate grouped repetitive discharges with activation
Differential Diagnosis of Kennedy’s Disease Fascioscapulohumeral Form of SMA
A. General considerations: 1. Adolescent onset 2. AD inheritance
Non-Immune Lower Motor Syndrome
1. Spinal muscular atrophies (see above) 2. X-Linked Recessive Bulbar Neuronopathy (Kennedy’s disease) Kennedy’s Disease A. General considerations: 1. X-linked recessive inheritance; CAG repeat in the first exon of the androgen receptor gene 2. Phenotypic expression varies within families and does correlate with CAG length; the more repeats the earlier the age of onset 3. Intranuclear androgen receptor protein found in the brainstem and anterior horn cells B. Clinical features: 1. Presents in men in the 3rd to 5th decade 2. Proximal > distal weakness and wasting 3. Distal weakness upper > than lower extremities
The primary differentials are progressive muscular atrophy variants of ALS; facial fasciculations, essential tremor, bulbar involvement make an easy distinction from inflammatory myopathy or any congenital neuropathy. The extremely high CK differentiates it from anterior horn cell disease. Myokymia and neuromyotonia occur spontaneously while mild voluntary contraction produce fasciculations in Kennedy’s disease.
Monomelic Amyotrophy (Hirayama’s Disease)
A. General considerations: 1. World wide distribution; most patients are from Japan and India 2. Putative mechanisms: a. Spinal cord ischemia b. Abnormal neck movement with secondary ischemia c. Traction of the cord due to increased neck flexion d. Abnormal cervical ligaments B. Clinical features: 1. Overwhelmingly a sporadic disease 2. Unilateral weakness and atrophy of intrinsic hand muscles
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SECTION III. Anterior Horn Cell Disease that Affects Adult Patients
3. 4. 5. 6.
Progresses for 1–3 years then stops in 75% of patients Fine tremor of extended fingers in 10% of patients Normal deep tendon reflexes; no upper motor signs Sensation is normal; rarely a rare mild sensory loss over the dorsum of the hand C. Laboratory evaluation: 1. Slightly elevated CK 2. Normal blood chemistries and CSF D. EMG evaluation: 1. Motor NCVs are normal; may have asymmetrical low median and ulnar CMAP amplitudes 2. Preserved SNAPs 3. Signs of denervation in most patients, 20% demonstrate reinnervated units 4. EMG abnormalities may be seen contralaterally (“mirror pattern”) E. MRI evaluation: 1. Cervical and upper thoracic cord atrophy
Differential Diagnosis of Monomelic Amyotrophy
Few diseases resemble one extremity with atrophy that is out of a nerve or root distribution without sensory loss. Syringomyelia invariably has sensory loss (dissociated), inherited or sporadic distal myopathies are not this asymmetric and progress; adult onset SMA is not asymmetrical and is adult onset while this is a disease of young people; spinal cord infarction is not asymmetrical and has specific sulcal artery patterns (most often follows X-RT), asymmetry and lack of sensory loss is not compatible with either posterior medullary (dorsal column) or anterior spinal artery infarction. Tumors progress, are more symmetrical and swell the cord. ALS demonstrates hyperactive reflexes in a wasted extremity. MMN neuropathy is remarkable for little or no atrophy.
Brachial Amyotrophic Diplegia
A. General considerations: 1. Adult onset B. Clinical features: 1. Bilateral proximal arm and shoulder girdle weakness and atrophy 2. Pure LMN weakness; legs are not affected 3. Slower progression than typical ALS 4. Some patients have distal arm involvement 5. Respiratory and bulbar muscles are spared C. EMG evaluation: 1. Denervation of the upper extremities D. Pathology: 1. One autopsied case a. Degeneration of pyramidal tracts and anterior horn cells
Differential Diagnosis of Brachial Amyotrophic Diplegia
Hirayama’s disease or monomelic atrophy is unilateral with strictly arm involvement. Rare adult onset SMAs have lower extremity involvement and are AD. Watershed infarcts (“man in the barrel”) between ACA/MCA territories affect shoulder muscles more than those of the hand and other central features are present such as ideomotor apraxia with hyperactive reflexes. There is no hand wasting. Cervical spondylosis is primarily a C5–C6 disease which is asymmetric and usually is associated with lumbosacral disease and increased knee jerks. Spinal artery infarctions have sensory loss and a different pattern of motor involvement. Post radiation amyotrophy has (obvious history) fasciculations (if the plexus is involved). EMG reveals no evidence of conduction block that are seen with MMN. Progressive Muscular Atrophy
A. General considerations: 1. Considered an ALS variant B. Clinical features: 1. Middle aged patients 2. Slowly progressive asymmetric weakness of upper and lower extremities 3. Fasciculations with wasting 4. Progresses for years 5. No upper motor neuron signs 6. Phenotypically mimics FSHD C. EMG evaluation: 1. Denervation and reinnervation
Chapter 2 Immune Mediated and Genetic Lower Motor Neuron Syndrome (see Neuropathy Section) 1. Multifocal motor neuropathy with conduction block (MMN); less than 50% CMAP is required with specific conduction blocks 2. Differential diagnosis of low titer IgM anti GM1 antibodies (less than 1–400 μg/liter) is: a. GBS b. ALS c. Sensorimotor neuropathy d. CIDP e. MG f. SLE g. Normal patients 3. High titers (greater than 1 to 6400 μg/dl) of GM1 antibodies have 80–90% specificity for clinical disease 4. High titers of IgG anti-GM1 antibodies are found in lower motor nerve syndromes and acute axonal neuropathy secondary to Campylobacter jejuni
Chapter 2. Immune Mediated and Genetic Lower Motor Neuron Syndrome Differential Diagnosis of Immune Mediated Motor Neuropathies
The major clue to this diagnosis is upper extremity asymmetric distal weakness with no sensory loss or upper motor neuron features. The onset may be rather sudden, but progression is insidious. The distal adult SMAs are autosomal dominant and are less asymmetric. Progressive muscular atrophy is proximal rather than distal, monomelic amyotrophia is primarily a disease of Indian and Japanese patients and affects the intrinsic muscles of the hand (more wasting) than immune processes. It is associated with MRI evidence of an atrophic lower cervical and upper thoracic spinal cord. Brachial amyotrophic diplegia affects proximal muscles more than distal and is symmetrical to a large degree. Hereditary sensory motor neuropathy Type II may involve individual upper extremity muscles, but these are usually proximal rather than distal. Distal myopathies that affect the upper extremity can be distinguished by genetic patterns, symmetry of upper extremity involvement, associated features (myotonia) and relative preservation of reflexes. EMG establishes a neurogenic or myopathic process (hexosaminidase A deficiency in the former and glycogen storage disease type 6) in the latter. Muscle biopsy rules out specific forms of congenital myopathy and storage syndromes. Conduction block, significant titers of GM1 antibodies and other signs of demyelination secure the diagnosis of a demyelinating process. Immune neuropathy is differentiated from early ALS on clinical grounds by: 1. Onset prior to age 35 2. An indolent course 3. Absence of significant wasting in the hand (ALS frequently involves the first dorsal interosseus and the 4th and 5th intrinsic hand muscles) 4. Non myotomal pattern of weakness 5. Absence of upper motor signs and no bulbar involvement
Other Immune Mediated Lower Motor Nerve Syndromes
A. General considerations: 1. Many of these patients have high titers of anti-GM1 antibodies B. Clinical features: 1. Most have distal presentation 2. Patients with proximal presentation: a. Later age of onset b. Men > women c. LMN atrophy of extremities that is static for 3–5 years C. Laboratory evaluation: 1. High titers of IgM or IgG or asialo antibodies are present
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Genetic Lower Motor Nerve Syndromes
1. Spinal muscular atrophies (chromosome 5q linked and non-linked) 2. Kennedy’s syndrome (X-linked recessive bulbospinal neuropathy) 3. Monomelic amyotrophy 4. Brachial amyotrophic diplegia 5. Progressive muscular atrophy (ALS variant) 6. Progressive bulbar palsy (ALS variant) 7. Fazio–Londe Disease (ALS variant)
Multiple System Disorders with Anterior Horn Cell Involvement
1. Hereditary spastic paraparesis (HSP) (I-20) complicated and uncomplicated variants 2. Adult hexosaminidase A deficiency 3. Spinocerebellar degeneration: a. OPCA variants b. SCA III (Machado Joseph Disease) 1) AD 2) AR
Adult Polyglucosan Body Disease
A. General considerations: 1. Sporadic and familial cases; high proportion of patients are Ashkenazi Jews 2. In Jewish patients a mutation of the glycogen branching gene is noted but may have more than one basis as non-Jewish patients, have an identical phenotype without the mutation 3. Polyglucosan bodies are also seen in glycogenosis type IV and Lafora body disease a. Noted in astrocytes, subpial and subependymal layer as well as the cerebellum and myelinated nerves; systemically in liver, heart, lung, smooth and skeletal muscle; loss of anterior horn cells B. Clinical features: 1. Onset in the 5th or 6th decade 2. Sensory peripheral neuropathy 3. Abnormal gait 4. Dementia 5. Urinary incontinence 6. Corticospinal tract dysfunction 7. Severity of disease various amongst patients 8. All features are not present in every patient 9. Normal pressure hydrocephalus presentation without other upper or lower motor signs 10. An ALS presentation with only corticospinal and anterior horn cell signs C. EMG evaluation:
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SECTION III. Anterior Horn Cell Disease that Affects Adult Patients
1. Slowing of motor NCVs; low amplitude or absent SNAP’s (sural nerve biopsy demonstrates intra-axonal polyglucosan bodies D. MRI evaluation: 1. Periventricular and subcortical white matter abnormalities on T2 weighted images; no anterior or posterior predilection
Differential Diagnosis of Adult Polyglucosan Body Disease
Primary lateral sclerosis has severe spasticity affecting extremities and cranial nerves. ALS has no sensory loss and in 60% of patients no dementia. There are rarely bladder abnormalities with ALS. Severe demyelinating disease has optic atrophy, an intranuclear ophthalmoplegia and bilateral severe cerebellar ataxia. B12 deficiency has cranial nerve I abnormalities, a frontal lobe affect and active paresthesias in upper and lower extremities. Dorsal column dysfunction predominates the sensory symptoms. Metachromatic leukodystrophy at the age of presentation of APBD has more spasticity and intact u fibers on MRI. ALD is X-linked recessive, has a much earlier onset, and no peripheral neuropathy. Adrenomyeloneuropathy starts in middle age, there is no bladder symptomatology and mentation is much better preserved. The difficult differential diagnosis to make is that of NPH. Prominent features in this entity not noted with APBD are falling backward and gait apraxia. Ventricular enlargement, the temporal horn out of proportion to the lateral ventricles with a mostly intact cortex are distinguishing features. Olivopontocerebellar degeneration, including retinal, dorsal column and brainstem variants have much more ataxia.
b. Anterior horn cell involvement 6. Pick’s disease a. Broca’s aphasia in a patient with otherwise ALZ phenotype 7. HSP a. Spasticity and lower motor neuron features 8. Shy Drager a. Akinetic rigid dementing illness b. Autonomic dysregulation is seminal feature c. Some amyotrophy
Paraneoplastic Motor Neuron Disease
A. General considerations: 1. Occurs with multiple cancers; most often small cell carcinoma of the lung 2. Rarely removal of the tumor stabilizes the MND; most often there is no change 3. Antigenic overlap between tumor cells and motor neurons (molecualr mimicry) 4. MND occurs with other well established paraneoplastic syndromes
Antibodies Associated with MND
1. Anti-Hu with small cell lung cancer; antinuclear neuronal antibody1; ANNA1 2. MND maybe associated with encephalomyelitis; dorsal root ganglionitis and large fiber sensory neuropathy 3. The motor neuron disease may precede the cancer by 4–10 months 4. In general, both removal of the tumor and immune treatment fail to reverse the neurological signs and symptoms
Rare MSA with Anterior Horn Cell Involvement
1. Hallervorden Spatz disease (PANK-2) a. Akinetic rigid syndrome b. “Eye of the tiger” in GPi by MRI 2. Guamanian–Parkinsonian – ALS (Lubag) a. Severe dystonia (particularly of the mouth) b. Lubag (Dystonia 7) c. Dementia d. X-linked 3. Huntington’s disease a. Choreoathetosis of body; choreatic eye movements b. Dementia c. Amyotrophy 4. Creutzfeldt–Jacob a. Classic disease has prominent fasciculations b. Speed of the dementing process plus the myoclonus makes the diagnosis 5. Alzheimer’s variant a. Spastic paraparesis
Hodgkin’s and Non-Hodgkin’s Lymphoma
1. 2. 3. 4. 5.
Subacute painless lower motor neuron syndrome Rare sensory symptoms Anti MA antibodies Variable progression Upper motor neuron symptoms develop over time similar to ALS
ALS Like Syndrome from Multiple Cancers
1. Hodgkin’s lymphoma, breast, uterine, ovarian, non-small cell lung cancer 2. Both upper and lower motor neuron symptoms and signs 3. LMN > UMN manifestations 4. Neurologic symptoms may precede or follow the diagnosis
Chapter 4. Rare Causes of Motor Neuron Disease Primary Lateral Sclerosis Syndrome with Breast Cancer
1. Neurologic manifestations occur prior to the diagnosis 2. Slowly progressive course 3. Upper motor neuron signs are usually first which then evolve into a lower motor neuron syndrome
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b. Tremor c. Spasticity d. Weakness e. Atrophy are often concurrent 7. Death often occurs within three years in some patients
Postradiation Motor Neuron Syndrome Specific Antibodies Identified with Motor Neuron Syndromes
1. Anti-Yo-cerebellar degeneration, primarily Purkinje cell; few patients with MND 2. Anti-Hu-limbic encephalitis, dorsal root ganglionitis, rarely MND 3. M proteins with lymphoproliferative disease 4. GDlb with thyroid adenoma; most often this is correlated with Campylobacter jejuni and CM Fisher syndrome or motor axonopathy 5. Breast cancer patients may have a motor axonopathy and antibodies to nodes of Ranvier; anti-Ri antibodies 6. Testicular-anti Ta antibodies
Chapter 3 Motor Neuron Disease Associated with Physical Agents Electrical Injury
A. General considerations: 1. Causes a delayed upper and lower motor neuron syndrome after both electrical injury or lightening 2. Starts at the site of trauma and then spreads 3. Transient weakness and paraplegia following electrical injury which usually clears after hours to 4 days 4. Permanent sequelae occurs with symptoms starting with years after the accident 5. The pathology is not the same as autopsies of executed criminals B. Clinical features: 1. The source of the current is usually from household circuits, high voltage lines or lightening (usually causes severe burns and cardiac arrest) 2. Electrical current specifically travels down the corticospinal and bladder pathways 3. Weakness and atrophy often begins at the site of injury 4. Weakness spreads in a contralateral pattern 5. Bulbar signs and upper motor neuron weakness and spasticity occur over time 6. Chronic regional pain syndrome (CRPS) frequently occurs with its motor manifestations of: a. Inability to initiate movement
A. General considerations: 1. Delayed occurrence after X-RT 2. Dosages to the cervical spine that cause the syndrome are: approximately 3000 rads; lumbosacral spine 5000–6000 rads 3. Associated with treatment of many different types of tumors B. Clinical features: 1. Occurs months to years after treatment 2. Atrophy of affected muscles with fasciculations 3. No sphincter involvement 4. Normal sensation 5. Lower extremities are preferentially involved 6. Weakness usually stabilizes, but has been described to progress over years 7. A similar process occurs in the lower cranial nerves with head and neck irradiation. The carotid artery is often involved in this situation with a long segment of the artery involved and consequent stroke C. EMG evaluation: 1. Fibrillation potentials are present in the lower extremities 2. Myokymic discharges occur D. Laboratory evaluation: 1. CSF usually normal 2. Protein may be slightly elevated
Differential Diagnosis
The myokymic potentials in the lower extremities and usual lack of involvement of the upper extremities make the diagnosis. Tumor recurrence does occur on this background. This is particularly important with sarcomas of the brachial plexus after X-RT of the breast. The same problem occurs following X-RT involvement for a variety of brachial plexus conditions.
Chapter 4 Rare Causes of Motor Neuron Disease Hyperparathyroidism
A. General considerations:
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SECTION III. Anterior Horn Cell Disease that Affects Adult Patients
1. Several series and isolated case reports associate an ALS picture with hyperparathyroidism 2. Skepticism about the nature of the correlation persists due to lack of EMG correlation of wide spread denervation and failure to halt progression of the disease with removal of the parathyroid glands B. Clinical features: 1. Symmetrical proximal weakness with cramps 2. Hyperactive reflexes and spasticity 3. Inconsistent tongue fibrillations and dysphagia 4. Inconsistent sensory loss 5. Several patients had bladder urgency C. EMG evaluation: 1. Widespread denervation in some patients
Repeated Hypoglycemia
A. General considerations: 1. The syndrome of anterior horn cell disease has occurred in patients with repeated episodes of hypoglycemia B. Clinical considerations: 1. Wasting of extremities 2. Fasciculations
Motor Neuron Disease with HIV/HTLV-I
A. General considerations: 1. HIV frequently causes a vacuolar cervical myelopathy; and severe axonal neuropathy 2. HTLV-I causes a severe chronically progressive cervic/thoracic myelopathy with spasticity and bladder involvement B. Clinical features: 1. A few patients with HIV present with ALS or a primary lateral sclerosis syndrome 2. Most patients have severe lower extremity spasticity and bladder involvement
Postpoliomyelitis Syndrome
A. General considerations: 1. Approximately 500,000 Americans suffer from the diseases 2. Last great epidemic occurred in 1952 3. A few isolated cases have occurred from vaccination; most cases now occur from unvaccinated communities or immigrants B. Clinical features: 1. Further weakening of muscles that had previously been affected 2. Fasciculations in affected muscles
3. Fatigue 4. No upper motor neuron signs 5. Weakness of bulbar and respiratory muscles does occur 6. Patients who have survived polio often have fasciculation for a prolonged period in affected muscles
Drugs Associated with Motor Neuron Disease
Lead A. General considerations: 1. Most often encountered in battery workers, mechanics (car radiator repair) 2. Often associated with systemic signs of anemia, lead lines in gum and bone 3. Renal cortex involvement 4. Basophilic stippling of RBC B. Clinical features: 1. Lower motor involvement of wrist and finger extensors 2. One report of both upper and lower motor neuron involvement C. Rare forms: 1. Dapsone 2. Nitrofurantoin may present with dose dependent reversible lower motor neuron syndrome 3. Guamanian ALS dementia complex has been linked to toxic amino acid ingestion from the cycad nut (Brn methylamine BNXAA). Now not thought to be etiologic
Chapter 5 Amyotrophic Lateral Sclerosis
A. General considerations: 1. Incidence varies from 0.2 to 2.4 per 100,000 people in the world excluding the Western Pacific 2. Prevalence rate is between 0.8 and 7.4 people per 100,000 3. Age is the greatest risk factor with peak mortality between 55 to 75 years of age 4. Peak onset is between 65–70 years of age; earlier onset has greater survival time 5. Male to female ratio is 1.5–2.5 : 1 6. Survival from time of diagnosis a. 50% die within 3 years b. 75% die within 5 years c. 10% live longer than 10 years 7. 85–90% of ALS is sporadic: a. 10–15% of familial ALS have a mutation in the gene for cu/zn superoxide dismutase (SoD1)
Chapter 5. Amyotrophic Lateral Sclerosis
8. Genes for cytoskeletal molecules that may be linked to ALS: a. Neurofilament-Heavy (NF-H) mutation 1) 1% in sporadic ALS 2) 0.3% of familial ALS 9. Possible involvement of the fast conducting corticospinal pathways to a greater degree than polysynaptic pathways 10. Twenty percent of familial forms are manifestations of mutations of the copper/zinc (Cu/ZN) superoxide dismutase 1 (SOD1) gene on chromosome 21 C. Clinical features: 1. May start as atrophy of intrinsic hard muscles in various patterns: a. First dorsal interosseous b. Lateral hand split c. Medial hand benediction sign. The fourth and fifth fingers are involved first as they are with syringomyelia. IN CRPS the fourth and fifth fingers are dystonia 2. Atrophy and fasciculations in a muscle group with increased reflexes 3. Segmental spread: a group of muscles in one extremity that then demonstrate contralateral weakness and atrophy (mirror patterns) 4. Onset in a bulbar distribution (12% of patients) 5. Painless foot drop; clawhand; wrist drop 6. Prominent fasciculations associated with cramps on exercise of the affected muscle 7. Spasticity, hyperreflexia, Babinski signs, retention of cremasteric and abdominal reflexes 8. Fasciculations and fibrillations in a scalloped atrophic tongue 9. A significant number of patients have dementia; other cognitive deficits noted 10. Poor facility of corticospinal type movements
Rare Signs
1. Extraocular movement abnormalities are an exception; may be a decrease of vertical saccades 2. Sphincter dysfunction (occurs late in disease in those on ventilators) 3. Sensory loss (there does appear to be some dorsal column dysfunction) 4. Extrapyramidal signs in 5%; impairment of postural reflexes 5. Autonomic involvement a. Blood pressure, heart rate, GI function
Associated Features
1. Sleep apnea; morning headache
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2. 3. 4. 5. 6.
Sialorrhea Silent and asymptomatic aspiration Disturbance of sleep architecture Decline of voice power with speech Cachexia greater than that expected from decreased nutrition 7. Absence of expected bed sores (possible changes in type III procollagen) 8. Pseudobulbar palsy
ALS Variants
Bulbar Presentation A. General considerations: 1. Growing evidence that ALS is a multisystem degeneration B. Clinical features: 1. Most common in post menopausal women 2. Poor prognosis; in past death occurred in approximately one year 3. Possibly up to 25% of ALS patients present with this onset 4. Spread to the lower cervical upper thoracic myotomes; later to lumbosacral muscles 5. Rarely, it remains bulbar
Primary Lateral Sclerosis
A. General considerations: 1. Does not involve the lower motor neuron B. Clinical features: 1. Age of onset is usually between 50 and 55 years 2. Progresses very slowly 3. May start as spastic paraparesis 4. Severe generalized spasticity, bilateral Hoffman and Babinski signs 5. Pseudobulbar palsy 6. Cognitive impairment is common; overt dementia is rare
Progressive Muscular Atrophy
A. General considerations: 1. Rarest variant of ALS 2. Occurs in approximately 2.5% of patients B. Clinical features: 1. Slowly progressive with better outcome than in classic disease 2. A pure lower motor neuron disease 3. Differential is between this and lower motor onset of SMA
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SECTION III. Anterior Horn Cell Disease that Affects Adult Patients
Flail Arm Syndrome (Bibrachial Diplegia)
A. General considerations: 1. Relatively symmetric proximal and distal wasting of the upper extremities 2. Hyperactive reflexes in both upper and lower extremities 3. Corticospinal tract dysfunction with Babinski signs
3. Excitotoxic cell death from B-N-methylamine BMAA, derived from the cycad nut is not causative 4. ALS form of the complex has declined B. Clinical features: 1. Parkinsonism presents primarily as akinetic rigid variety 2. Dystonia is prominent (“Lubag”); particularly of the mouth 3. ALS in combination with Parkinsonian features; patients may have severe dementia
Mill’s (Hemiplegic Variant)
A. General considerations: 1. Rare; possibly 5% of patients B. Clinical features: 1. Corticospinal and lower motor neuron involvement of one side
Familial ALS
A. General considerations: 1. Approximately 5–10% of ALS patients 2. AD inheritance: a. 20% of patients have mutations in the Cu/Zn SOD1 gene on chromosome 21; all 5 exons are involved b. Gain of function deficit c. Recessively inherited ALS occurs: 1) Apparent single founder for these patients (D90A mutation) 2) Tunisian families with 2q33–35 mutations
Chronic Juvenile ALS
A. General considerations: 1. Chronic juvenile ALS 2. Slow progression 3. Onset approximately 12 years of age B. Clinical features: 1. Earlier onset; approximately 12 years of age 2. Less male predominance 3. Initial manifestations occur in the lower extremities 4. Slow progression C. Pathology: 1. No perikaryal or axonal spheroids 2. Greater involvement of Clarke’s columns
Guam Parkinsonian ALS Dementia Complex
A. General considerations: 1. Endemic areas for this clinical complex are: Western Pacific, Kii peninsula of Japan; West New Guinea 2. No gene has been identified
Differential Diagnosis of ALS
Since ALS and its variants may strike all levels of the neuraxis the differential diagnosis is extremely wide. In reality, the diagnosis is restricted, as there are few illnesses that strike the upper and lower motor neurons simultaneously. The clinician must not miss the illnesses that simulate ALS but are treatable. The most common of these is cervical spondylosis. This is primarily a disease of the motion segments of the spinal segments and occurs in both cervical and lumbar areas concomitantly. It is asymmetrical, biceps jerks are lost, knee jerks are increased ankle reflexes may be asymmetrically decreased. If the ventral roots are severely constricted in the cervical canal fasciculations are noted in the upper extremities. It does not involve the cranial nerves, the neck is in a forward flexed posture and cannot be moved to lateral, anterior and posterior planes. The hands are usually spared, whereas in ALS the first dorsal interosseous is often affected very early. Mentation is normal. The problem arises when the patient has both diseases. Cervical spondylosis does not affect paraspinal muscles. MRI of the cervical spine and back corroborate the diagnosis. The pure motor autoimmune neuropathies may simulate the lower motor form of ALS. The causative antibodies are GMI, MAG, and Gdlb. Serum protein electrophoresis and immune focused electrophoresis often demonstrates an IgM peak (particularly for MAG). Most importantly EMG identifies a conduction block. Wasting is not nearly as prominent as in progressive muscular atrophy (which is most often proximal). Hexosaminidase A deficiency is extremely rare and has prominent psychiatric and cerebellar features. There still is controversy over the link between lymphoma and leukemia with ALS. Clearly, there is a strong association between many malignancies and destruction of various parts of the neuraxis (anti-Hu, anti-Yo, anti-Ri, anti-Ma and antianti TA). A careful evaluation of the bone marrow is in order if there is a suspicion of a lymphoproliferative disorder. Hyperparathyroidism, hyperthyroidism, benign fasciculations, and hyperexcitable syndromes all may produce wide spread fasciculation. A fasciculation must be accompanied by wasting and weakness to be significant. Neurogenic cramps induced by exercise, if in the lower extremity are most often
Chapter 5. Amyotrophic Lateral Sclerosis
due to disc or spondylitic disease in the lumbar roots particularly S1. This rarely occurs in the upper extremity. Neurogenic cramps of the upper extremity suggest the cramp fasciculation syndrome or motor neuron disease. The differentiation can easily be made by EMG. Acid maltase deficiency may give exercise induced cramps with muscle weakness. There is some evidence that anterior horn cell disease may occur in anterior horn cells formerly affected by a polio virus infection. The post polio syndrome is painful and most probably represents accelerated cell death in those anterior horn cells that had compensated for the death of their neighbors. Monomelic ALS seems to affect all muscles of the affected extremity rather than particular muscles of the hand which occurs in ALS (benediction sign of 4th and 5th finger or the lat-
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eral hand). There are frequently EMG findings in unaffected muscles in ALS. Amyotrophy of extremities occurs with multiple system atrophies. The most severe is spinocerebellar atrophy (SCA3) or Machado–Joseph disease. The amyotrophy is never the dominant component of these syndromes. Kennedy’s disease, a bulbar neuronopathy, is X-linked and distinguished by facial fasciculations, genetics and gynecomastia. The CK is usually high and there are diminished SNAPs. The late onset spinal muscular atrophies may overlap with ALS. They usually have symmetric proximal weakness and some are distal with pes cavus.
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Section IV SPINAL CORD DISEASE
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Chapter 1. Introduction
Chapter 1 Introduction
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spinal cord compression. In the lumbar area, roots are involved as the spinal cord ends at T12–L1 (conus medullaris). Differential diagnosis of spinal cord pathology depends on location and pattern of involvement as well as the course of the process.
Spinal Cord Disease
The spinal cord is frequently involved in specific patterns and at characteristic levels that is extremely helpful in differential diagnosis. The lamination of both the dorsal column and the spinal thalamic tracts is such that the patient’s symptoms may not reflect the true level of involvement. This is particularly true with sensory levels. Pain afferents enter the cord and are distributed approximately two segments above and below their level of entry by Lissauer’s tract. Propriospinal fibers connect adjacent spinal dermatomes. The corticospinal tract is arranged so that the fibers innervating the legs are lateral to those of the arm. Bladder fibers are between arm and leg fibers. The spinothalamic fibers are laminated such that sacral fibers are most lateral and leg, trunk and arm fibers are medial and cross at their level of entry. Thus a lateral cord lesion at cervical levels will affect the contralateral sacral and leg sensory fibers prior to arm fibers. The clinical and neuropathological division of the cord is into three spaces: (1) epidural; (2) intraparenchymal and; (3) intradural and extramedullary. Processes that compress the spinal cord cause ataxia, a sensory level, then bilateral motor weakness below the level of the lesion and bladder involvement. If epidural processes are acute, such as metastasis, intradural hematoma or fracture, there will be spinal shock. If this supervenes all sensation, motor function, bowel, and bladder control and reflexes will be lost below the level of the lesion. Long standing intraparenchymal spinal cord disease causes spasticity below the level of the lesion with a neurogenic bladder. There is a segmental sensory loss with normal sensation above and below the lesions. Occasionally, reflexes will be increased above the level of the lesion (Schiff– Sherrington reflex). This is due to disinhibition of excitatory ascending fibers. Cystic intraparenchymal lesions and tumors often cause minimal bladder dysfunction. Epidural compression affects bowel, bladder and then ability to walk, rarely ataxia present initially. Predominantly as the dorsal and ventral spinocerebellar tracts are in the periphery of the cord and they both subserve cerebellar functions of the legs. The patient is ataxic prior to becoming paralyzed. The cuneocerebellar tract conveys proprioception from the upper extremities and is located at cervical levels C1–C4. Propioceptive loss has to be sought by the examiner, although there is frequently a lateral drift of the ipsilateral extremities. Intradural extramedullary lesions are few and comprise meningiomas, neurofibromas, dropped metastasis and enlarged nerve roots from congenital hereditary motor sensory neuropathies. If a neurofibroma or meningioma occurs in the thoracic or cervical area there is often concomitant root and
Specific Patterns of Involvement
1. 2. 3. 4.
Transverse (in fact these are usually longitudinal) Longitudinal hemisection (Brown–Sequard syndrome) Epidural compression Intramedullary (usually inflammatory or tumor and cause a longitudinal lesion on MRI)
The specific diagnostic radiographic features for these patterns are: 1. Transverse myelitis involves more than one segment and expands the spinal cord. If involvement is more ventral a viral etiology is expected. Dorsal column involvement suggest Sjögren’s, B12 deficiency, Tabes dorsalis or toxins. 2. Brown–Sequard: This is a longitudinal division of the cord. The patient suffers ipsilateral proprioceptive, touch and vibratory loss in association with contralateral pain and temperature deficits. There is ipsilateral paralysis below the lesion. The usual etiology is trauma (knife or bullet) or X-RT therapy in which individual sulcal arteries are involved. 3. Intramedullary: The cord is swollen over several segments in an ovoid pattern. Central or asymmetric cysts suggest a syrinx. A post traumatic syrinx occurs above the level of the lesion. Tumors that are associated with intramedullary syrinxes are cystic astrocytomas (frequently an enhancing nodule is seen), hemangioblastomas as well as astrocytomas that occur in the wall of syrinxes. 4. Epidural compression: A saw-toothed or paint brush pattern on myelography is seen with epidural processes. Bony destruction suggests metastatic disease. This is often only at one segment. Disc involvement, with gadolinium enhancement, denotes infection. The anterior and posterior ligament often enhance with gadolinium with infection. Lymphomas often start in the epidural fat. Epidural compression is noted with extra medullary hematopiesis, as well as by fat in patients on steroids. Dural AVMs are epidural and are most common dorsal in the thoracic segments of the cord. Meningitis of all forms may be dorsal and invades the spinal parenchyma through draining veins or exit foramina. Sarcoid often invades the dura at cervical and thoracic levels. Processes that thicken the spinal dura itself are lymphoma, tuberculosis, cryptococcus; rheumatoid arthritis and idiopathic pachymeningitis which simultaneously affect intracranial dura. Carcinomatosis of the meninges characteristically thickens the dura and is seen in the sulci of the cerebellum and cortex. Angioplastic endotheliosis may affect cerebral blood vessels and
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SECTION IV. Spinal Cord Disease
those of the dura. Amyloid may greatly thicken the dura of intracranial and spinal compartments and occasionally forms mass lesions.
Intradural Extramedullary Lesions
The most common of these are Schwannomas that form “dumbbell tumors.” The neuronal exit foramina are expanded and the tumor is seen to compress the spinal cord. Myelography reveals a “cap” sign. Neurofibromas grow through the nerve root, as opposed to Schwannomas which can be separated from the nerve root. Plexiform neurofibromas may involve multiple nerve roots and are characteristic of neurofibromatosis type I (chromosome 17). Hereditary motor sensory neuropathy particularly Dejerine–Sottas disease (HSMN III) greatly enlarge nerve roots and may compress the cord. Meningiomas characteristically are found in the intradural extramedullary space of the thoracic cord in women and are extremely rare in men. A free fragment of a disc may migrate in this space for several cord segments, while arachnoid cysts may fill, in a ball valve fashion, and compress the spinal cord intermittently. Prior to MRI this process was often misdiagnosed as multiple sclerosis. Medulloblastomas, spinal cord, metastases and leukemia frequently seed the spinal cord in the intradural extramedullary space. Spontaneous, traumatic and anticoagulation induced subdural hematomas of the spinal cord also occur here.
Locations
The area of the spinal cord involved is a major clue in the differential diagnosis. The examination is quite specific for each entity. A forward flexed neck with limitation of movement to the lateral planes suggests cervical spondylosis. Degenerative changes in the spine occur at movement segments such as C5–C6, C4–5, while C8–T1 is not affected. All patients above 40 years of age get some degree of cervical spondylosis. The exam will often demonstrate an inverted radial or inverted supinator reflex, increased knee jerks, as well as inability to tandem walk due to lateral pressure on the dorsal and ventral spinocerebellar tracts. A short neck suggests Turner’s syndrome, platybasia, Chiari malformation or abnormalities of C1–C2, basilar invagination or Klippel Feil syndromes. There are five ossification centers of C2, and anomalies and fractures occur in these areas. A long neck is suggestive of the “droopy shoulder syndrome” and brachial plexus traction injuries, but may also be associated with homocystinuria, Marfan’s or Ehlers Danlos syndrome. Lhermitte’s sign is most often associated with demyelinating disease, but also occurs with any lesion that irritates the dorsal columns. Characteristic pathology involving the cervical cord includes HIV infection and B12 myelopathy (both give a vacuolar myelopathy) Sjögren’s syndrome, as well as, spondylosis, disc disease, stenosis, and demyelinating disease. This
is very frequently associated with a dropped sensory level to T4–T6 due to lamination of the sensory systems of the spinal cord. A level here invariably draws an MRI at this level, but most often pathology will be at cervical levels. Hirayama’s disease, abnormal movement of the cervical spinal cord with consequent pathology at C8–T1, and calcification of the posterior longitudinal ligament with cord compression is common in Asian patients. Syrinxes and cavernous hemangiomas are common parenchymal lesions although demyelinating inflammatory lesions are by far the most common. Rarely sarcoid presents with both inflammatory and dural lesions at this level. A ventral AVM of the anterior spinal artery, the “Foix Alajouanine syndrome” lesion, can be found from cervical to thoracic areas.
Thoracic Spinal Cord
Inflammatory lesions at this level are usually demyelinating, but sarcoid may thicken the dura here as well as inflame the cord. Dural AVMs, if spinal, are most common in the dorsal cord. Disc disease is rare, but protrusions here are very dangerous, as the spinal canal is tight (12–24 mm) and the cord is easily compressed. Diabetes, a syrinx and amyloid may destroy propioceptive and pain fibers which produce a “Charcot joint”. This is more common at the shoulder joint, particularly for a syrinx. Metastatic disease with a pathologic fracture and meningioma in women are characteristic. Osteoporosis with anterior vertebral body fracture are most common in elderly women at this level. Ganglioneuromas and chordoma, Weing’s sarcoma are rare tumors of the thoracic cord. An astrocytoma may grow a long distance and destroy anterior horn cells of the thoracic spine asymmetrically giving rise to a “C” form of scoliosis. An “S” shaped scoliosis is congenital (with compensatory curves) and is often asymptomatic. Diastematomyelia, a fibrous band that splits the spinal cord, and reduplication of the cord (two spinal cords with their own dural cover) are rare congenital anomalies. A devastating infection of the thoracic spinal cord is herpes type 6, which leads to necrosis with minimal recovery. West Nile virus, as well as polio, may severely affect this part of the cord, but not to the same degree. Axonal necrosis of the cervical cord with optic neuritis (Devic’s) disease is more common in the cervical cord, but dose occur in the thoracic cord as well. The many forms of hereditary spastic paraparesis affect the thoracic cord severely. In uncomplicated variants, only the spinal cord is affected while complicated variants are also associated with optic, cerebellar, cortical and peripheral nerve deficits.
Lumbar
The lumbar level is most affected with mechanical problems such as disc disease, spinal stenosis, spondylolisthesis and
Chapter 1. Introduction
spondylosis. In general, L5–S1 (the major motion segment) suffers disc disease, while L4–L5 is more frequently the site of spinal stenosis. Synovial cysts of the facet joint is rare, but is often seen in older patients with severe degenerative disease. Facet hypertrophy with tropism (rotation of the inferior facets into the foraminal exit zone) is a common cause of radiculopathy in older patients. In adult populations, meningomyelocele and its variations are rare. A tethered cord, in which the filum terminal is short and the spinal cord is lower than its usual vertebral level at L1, is associated with bladder abnormality, pes cavus and radiculopathy. An abnormally formed lamina or pedicle often is associated with radiculopathy at this level. The lateral recess, particularly at L4–L5 and L5–S1, may be congenitally narrowed with nerve root compression. Lipoma, glioma of the filum terminale, and chordomas are particular to the lumbosacral cord. Lymphomas may occur anywhere in the spine, but tend to envelop the nerve roots of the cauda equina at this level. Sarcomatous degeneration of a lipoma cannot be operated, as it is interdigitated within the nerve roots. Plexiform neurofibromas (NFI) occur in the lumbosacral cord. CMV infections in very ill (CD4+ count of less than 200 mm3 ) HIV patients are characteristic of the lumbosacral cord.
Epiconus
Anatomically, this area is at a spinal level T12–L1 and affects the lower end of the spinal cord segment above the conus medullaris which comprises S1–S5. Lesions here cause involvement of the bowel, bladder and sexual function as well as pain and weakness. A Babinski sign is present. Trauma, congenital defects, such as spinal stenosis in achondroplasia, demyelinating disease or a syrinx may be prominent pathology at this level.
Conus Medullaris
The hallmark of lesions here is the early involvement of bowel, bladder, and sexual function without loss of sensation or weakness. The cauda equina and epiconus are often concomitantly involved. The most common pathologies are trauma, demyelinating disease, vascular malformation, syrinx and, rarely, a tumor. Characteristic of a parenchymal tumor is weakness of the gastrocnemius muscle with spared anterior tibialis and extensor hallucis longus muscle function. Sexual dissociation may also occur whereby a patient may have an erection, but is unable to ejaculate or vice versa.
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Cauda Equina
The cauda equina comprises of the nerve roots that have exited the lumbosacral spinal cord. A cauda equina lesion produces asymmetric severe pain, numbness in the perineal or “saddle distribution” and weakness of the lower extremities. Bladder, bowel and sexual function are affected. The usual pathology of a cauda equina lesion is disc disease, trauma or metastasis.
Spinal Block
In the past, spinal block was most often seen by myelography. The characteristic brush like defect of the contrast column in epidural disease and the meniscus sign of an intradural extramedullary lesion were carefully sought. The block is due to obstruction of the passage of spinal fluid. MRI now allows visualization of water in discs, as well as inflammation and swelling of nerve roots (gadolinium enhancement), while CT allows exquisite detail of the bony exit foramina. The advantage of a myelogram with CT to following is the ability to visualize the relationship of the nerve root both to the pedicle and within its exit foramina. A far lateral disc cannot be visualized with myelography. A spinal block causes a Freund’s reaction in which the protein is very high, while cells and sugar remain normal. A CSF protein of one gram suggests a block as few diseases can raise a protein to this level. The usual protein of an autoimmune process is 80–120 mg%. Deep fungus infections such as blastomycosis may raise the protein to 1 gram/dl, but this is very rare. Most spinal blocks are caused by epidural tumors. Degenerative disc disease is easily seen by desiccation and less signal on T2 weighted MRI images. A lesion in the pedicle or one eroding the end plates of the vertebral body is most often metastatic. A star vertebral fracture may protrude a bone fragment into the spinal canal and cause a spinal block.
Anatomical–Clinical Correlations
1. Dropped sensory levels: a. Thoracic compression causes a dropped sensory level of about two segments. The posterior level is usually slightly higher than the anterior level. b. Cervical cord lesions cause a dropped sensory level of many segments. As noted above, this is due to the lamination primarily of the spinothalamic tract. c. A lateral drift and severe proprioceptive loss suggest dorsal column tract or nuclei involvement. 2. Motor deficits: a. In general, spinal cord lesions cause bilateral motor deficits which may be asymmetrical. X-RT characteristically does this by producing a proliferative end arteritis of a sulcal artery. Another cause of asymmetrical
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3.
4.
5.
6.
7.
8.
SECTION IV. Spinal Cord Disease
motor weakness includes trauma specifically knife or bullet wounds. Most blunt trauma to the cord causes an oblong longitudinal lesion. Bladder involvement may have characteristic features depending on the level of involvement. a. Cervical cord (long standing): 1) Frequency and urgency 2) Loss of urine with a valsalva maneuver. The lesion is often at the ciliary nucleus of Budge at the C8–T1 level and is most often a syrinx. 3) Inability to initiate micturition in the face of urgency. Detrusor dyssynergia is most often seen with demyelinating disease. b. Thoracic cord (long standing): 1) Urgency, frequency, small amounts voided 2) Detrusor dyssynergia. There has to be coordination between contraction of Onuf’s nucleus (S2–S4) and the external sphincter (L5–S1). c. Lumbar cord: 1) Frequency (often irritation of L5–S1 roots) 2) Incomplete emptying of the bladder (30–40 cc residual) stimulates the trigone. Incomplete emptying with large residuals (>300 cc) causes overflow incontinence. Severe infections such as tabes dorsalis and CMV can affect the roots and cause failure of bladder contraction as well as insensibility. Severe neuropathies such as diabetes and toxins are also noted as causes of an overflow bladder. Conus Medullaris: a. Severe inability to contract the detrusor muscle. This does not occur with ALS as Onuf’s nucleus does not degenerate. In many multiple system atrophies, glial inclusions are seen in this nucleus which is occasionally reflected as incontinence. b. Bladder retention with constant overflow incontinence Ataxia of the Legs: a. Often an overlooked complaint with external compression of the spinal cord. b. Caused by pressure on dorsal and ventral spinocerebellar pathways which occupy the lateral components of the spinal cord c. Over shadowed by leg weakness Mass reflex with long standing spasticity: a. Flexion withdrawal (spontaneous or stimulus induced) b. Defecation c. Urination d. Rarely reflex erection and ejaculation e. Usually often spinal cord injury Lhermitte’s sign: a. Dorsal column irritation most often, but not limited to the cervical cord b. Paresthesias may be felt in the arms, legs or straight down the spinal column Sacral sensory sparing:
a. Occurs with central cord lesions: tumors, syrinx, demyelinating disease 9. Thoracic-abdominal signs: a. Beevor’s sign, thoracic umbilical reflex, superficial umbilical reflex; intercostal contraction with breathing-all help to localize a lesion at the thoracic level. Unilateral segmental sweating has been noted with thoracic lesions. Severe segmental dynamic and static allodynia is often associated with HZ that presents without rash (“sine herpeticum”). Rarely tabes dorsalis causes shooting thoracic and abdominal pain as do the neurological causes of porphyria. The most commonly missed thoracic nerve lesion is the intercosticobrachial nerve that is derived from the medial cord of the brachial plexus. The upper component of the nerve innervates the anterior chest wall while the lower component subserves the lateral chest wall and radiates under the breast to the epigastrium.
Cervical Drifts
A lateral drift of the outstretched upper extremities may be seen with cervical cord lesions (decreased proprioception from the cuneocerebellar tract). Severe updrift with ataxia through all components of movement in association with polyminimyoclonus (abnormal finger movements) is characteristic of dorsal column nuclear lesions from Richter’s variant of GBS or DRG large neuropathies.
Babinski Sign
If the sign is elicited by stroking just to the midfoot, the pathology is either very long standing or in the spinal cord. The toe is frequently spontaneously extended. Severe basal ganglia disease may give a dystonic extensor plantar response.
Segmental Atrophy
This sign is most often seen with intramedullary lesions such as a syrinx. The patient may be anesthetic in this area due to destruction of the dorsal horn.
Fasciculations
The more fasciculations noted, the closer the lesion is to the anterior horn cell.
Chapter 2. Congenital Defects of the Spinal Cord Crossed Adductor Reflex
This implies a deficit of spinal cord inhibition. When noted, the patient is suffering from long standing cervical or thoracic cord disease. It may, of course, be seen in any long standing corticospinal tract lesion.
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2) Bony defects secondary to axial mesodermal development without a persistent open neural tube. These are encephaloceles and meningoceles in which there is herniation of the neural tube through a bony defect. In spina bifida occulta and diastematomyelia the defects are entirely skin covered.
The Clavicular Biceps Reflex
Neural Tube Closure Defects
Striking the clavicle and obtaining a hyperactive biceps reflex allows the examiner to note that the lesion must be above C5–C6. (If there is hyperreflexia of the jaw jerk, the process is most likely diffuse and degenerative. A hyperactive jaw jerk means disinhibition of the mid pons). The inverted radial reflex and supinator reflex are characteristic of C5–C6 cervical cord lesions.
Craniorachischisis 1. General Considerations: a. Most severe dysraphism b. Brain and spinal cord are exposed to CSF 2. Clinical Features: a. Necrosis degeneration and angioma-like formation of the cord b. May have preserved optic nerve development
Cape Sensory Loss Myelomeningocele
Decreased sensation of the trapezius ridge, cap of the shoulder and anterior chest wall is strong evidence for a syrinx or other intramedullary lesion.
Dissociated Sensory Loss
Dorsal column modality loss that occurs acutely suggests infarction of the paired posterior medullary arteries. Loss of pain and temperature occurs with ventral cord (anterior spinal artery) or anterior commissure lesions such as a syrinx, intramedullary tumor, demyelinating disease, or compression from a disc.
Chapter 2 Congenital Defects of the Spinal Cord
Dysraphic Disorders (Neural Tube Defects)
General considerations: a. Primary neurulation occurs throughout the brain and spinal cord, to upper sacral levels. It occurs by a process of neural folding. b. Secondary neurulation occurs in the sacral and coccygeal regions by a process that canalizes a solid cord of cells. c. Axial malformations: 1) Failure of neural tube closure that is associated with skeletal modeling defects that occur around a malformed neural tube are anencephaly, meningomyelocele and craniorachischisis
1. General considerations: a. Meninges and spinal cord are herniated through a large vertebral defect 1) Distended meningeal sac filled with CSF and covered by a thin membrane or by skin 2) The spinal cord may be closed or there may be dilatation of the central canal with herniation of the posterior cord b. Myelocoele 1) A flat open spinal cord exposed to CSF 2) The spinal cord at the site of the defect is a flat, discoidal highly vascular mass known as the area medullovasculosa 3) The posterior spinal cord is open at birth 4) The nerve roots end within the vascular mass c. Clinical features: 1) Associated spinal anomalies are: a) Syringomyelia; hydromyelia; diastematomyelia, diplomyelia and double central canal 2) Hydrocephalus is common in association with Chiari Type II malformations 3) Lesions above T12 have a high incidence of other spinal cord malformations; more common in females than males 4) Low lesions have equal sex incidences; but are less severe clinically
Meningocele
1. General considerations: a. A variant of spina bifida cystica
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SECTION IV. Spinal Cord Disease
b. Vertebral defect combined with a cystic lesion of the back c. Usually at the lumbosacral level d. The dura and arachnoid are herniated through the vertebral defect; the spinal cord remains in the canal e. Narrow canal connects the cyst with the vertebral canal 2. Clinical features: a. Associated diastematomyelia, tethered cord and hydromyelia b. Insensibility of lower extremities; bladder; bowel and sexual dysfunction; weakness and wasting of all muscles below the knees; areflexia at the knee and ankle.
Spina Bifida Occulta
1. General considerations: a. Least severe of the neural tube defects b. Closed defect of the embryonic neural bud that undergoes secondary canalization 3. Clinical features: a. Associated sacral agenesis; anomalies of the anorectal and urogenital systems b. Associated spinal cord anomalies are: hydromyelia, diplomyelia (longitudinal splitting or duplication of the cord); tethering e. Defects are low lumbar and sacral f. Associated sacrococcygeal teratoma and lipoma g. Pes cavus and neurogenic bladder occur; other abnormalities of micturition; wasting and sensory loss of the affected roots
Syringomyelia
1. General considerations: a. Lower cervical cord is the most common location; lumbar may cause the most pronounced deficits b. Found in association with Type I Arnold-Chiari malformations in 40% of patients; can be asymmetrical c. Incomplete fusion of the posterior columns or the persistence of the large canal of the embryonic state; may be focal and asymptomatic d. Normal ependymal lining becomes gliotic: e. The syrinx may originate at the base of the posterior horn and extend into the central grey and anterior commissure 2. Clinical features: a. Loss of pain and temperature at the segmental level. A suspended sensory loss: normal sensation above and below the lesion b. Light touch, vibration, position sensibility is relatively spared
c. Amyotrophy of muscles innervated by specifically involved anterior horn cells (cervical cord-intrinsic hand muscles; frequently the 4th and 5th finger extensors; benediction sign) d. Claw hand in late stages (both thenar and hypothenar eminences are involved-“main en Graeffe”) e. Weakness and atrophy is often asymmetric f. Horner’s sign (C8–T1 involvement); destruction of the sympathetic ciliary center of Budge g. Bowel and bladder involvement is late h. Loss of segmental reflexes at the involved level; hyperactive reflexes below this level i. Babinski sign is present with corticospinal tract involvement j. Pain may be severe early in the course of the illness; deep ache or burning quality k. Associated syringobulbia may occur; usually at the junction of the alar and basal palate (level of the vestibular nuclei laterally in the medulla) l. Severe thoracic scoliosis is common m. Rarely there is extension into the centrum semiovale (syringoencephalia) n. Charcot joints occur (shoulder, thoracic spine or hip; rarely at the elbow and wrist) due to lack of proprioception, pain and from repeated trauma o. Autonomic dysfunction of the hands; diffuse swelling and subcutaneous edema (neurogenic edema) p. Associated with Chiari I, small posterior fossa
Lumbar Syrinx
1. Clinical features: a. Atrophy of proximal and distal leg muscles b. Dissociated sensory loss in lumbar and sacral dermatomes c. Loss of deep tendon reflexes d. Bowel and bladder dysfunction; severe if Onuf’s nucleus S2–S4 is involved e. Extensor toe signs
Diplomyelia (Duplication of the Cord)
1. General consideration: a. Two complete spinal cords wrapped in their own dura b. May coexist with diastematomyelia 2. Clinical features: a. Spasticity with a neurogenic bladder
Diastematomyelia
1. General features:
Chapter 2. Congenital Defects of the Spinal Cord
a. A fibrous band that splits the spinal cord; attached from the superior dura to the spinal canal b. More common: thoracic > cervical > lumbar 3. Clinical features: a. Spasticity of the legs b. Bowel and bladder dysfunction c. Loss of lower extremity deep tendon reflexes
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Neurogenic Cyst
1. General considerations: a. Occur in the ventral thoracic cord b. Early developmental defeat 2. Clinical features: a. Compression of the cord with weakness, spasticity and bladder dysfunction
Tethered Cord
1. General considerations: a. Fibrous filum terminale attaches to the sacrum; cord is pulled down; conus medullaris is then below L1 2. Clinical features: a. Often first manifest in middle age b. Women may have lower leg weakness if maintained in the dorsal lithotomy position (childbirth or prolonged vaginal procedures) c. Pes cavus (asymmetric) d. Bladder dysfunction e. Hyperactive reflexes f. Often associated with lipoma of the sacral cord (bright on T1 weighted MRI) Chiari Malformations
1. General considerations: a. Chiari I 1) Cerebellar tonsillar herniation 2) Tonsils are often atrophic, sclerotic and connected by fibrous adhesions to the back of the medulla 3) Cervical roots angled slightly upwards (by myelography) 4) May be asymptomatic 5) Often associated with late onset hydrocephalus and cerebellar ataxia 6) 50% of patients have syringomyelia; 90% of idiopathic syringomyelia patients have a Chiari I malformation 7) Rare familial occurrence of Chiari I and syringomyelia occurs. It is also associated with craniocervical anomalies (platybasia, basilar impression, Klippel–Feil suboccipital dysplasia, and craniosynostosis) 2. Clinical features: a. Signs of a cervical syrinx b. Severe C2 headache with any Valsalva maneuver, but particularly with cough c. Ataxia of upper and lower extremities. Often symptomatic in mid-life; ataxia of gait is the most prominent feature in this instance d. Small slanted posterior fossa, short neck, low set hairline e. Occasional down beat nystagmus exacerbated on lateral gaze
Off Midline Skin Malformations with Underlying Developmental Defects
1. Dimples (dysraphism) 2. Hair patch (AVM, dysraphism) 3. Large hairy mole (malignant melanosis of the dura)
Congenital Bony Defects that Compromise the Spinal Cord or Root Exit Foramina
Developmental Spinal Stenosis 1. General considerations: a. Measurements: 1) Cervical cord C2–C7, 24–26 mm 2) Thoracic cord > than 14 mm 3) Lumbar cord L1–L2 > 24–26 mm 2. Block vertebrae (all achondroplasia patients) 3. Short pedicle syndrome (lumbar) 4. Trefoil configuration of the canal (lumbosacral levels) 5. Lateral recess stenosis (primarily at L5–S1 levels)
Achondroplasia
1. General considerations: a. Block vertebrae at all levels of the spinal cord b. Stenosis at the foramen magnum and lower thoracic levels 2. Clinical features: a. Stenosis of T10–T12, L1–L2 1) Severe pain in an upper lumbar distribution 2) Bowel and bladder dysfunction b. Stenosis of the foramen magnum causes: 1) Automatic breathing deficit (Ondine’s curse); most frequently seen after foramen magnum decompression 2) Spastic quadriparesis
Congenital Abnormalities of the Cervical Vertebrae and Foramen Magnum
A. General considerations: 1. Anatomy of the atlas and axis:
SECTION IV. Spinal Cord Disease
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a. The atlas has a ring like structure, but no vertebral body b. It has synovial articulations with the occipital condyles of the skull and caudally with the odontoid process c. The odontoid process has 3 major ligaments that anchor it to the skull: 1) Posterior cruciate (most important) 2) Two lateral alar ligaments 3) In an adult during flexion the atlas should not move more than 3 mm from the axis. In children the separation is 5 mm d. The tip of the odontoid process should not extend rostrally more than 3 mm above a line from the hard palate to the inner table of the skull at the foramen magnum (Chamberlain’s line). Bull’s and the digastric line are other measurements of this parameter that are rarely used
Occipitalization of the Atlas
A. General consideration: 1. A congenital fusion of the atlas and foramen magnum 2. Neurological symptoms occur when the anterior– posterior diameter of the spinal canal posterior to the dens is less than 19 mm B. Clinical features: 1. Spastic quadriparesis 2. Ataxia of legs greater than arms
Basilar Invagination
A. General considerations: 1. The odontoid process is > 3 mm above Chamberlain’s line 2. The cervical spinal cord is compressed B. Clinical features: 1. Paresthesias of the hands 2. Lhermitte’s sign with neck flexion 3. Sudden medullary compression with cardiac arrhythmia, respiratory arrest and sudden death 4. Symptoms develop in childhood or early adult life 5. The head may be elongated with a decreased vertical diameter 6. Short neck; decreased range of motion to all planes 7. Ataxia; legs > arms 8. Spastic quadriparesis 9. Rarely, papilledema (CSF obstruction); subarachnoid block in many patients 10. Increased CSF protein in 50%
Platybasia
A. General considerations: 1. A flattening of the base of the skull. The normal angle between the planum sphenoidale and the clivus is 135◦ If this angle is increased to >135◦ there is platybasia 2. Possible AD inheritance males > females 3. Associated with other skull base defects: a. Maldevelopment or hypoplasia of the basiocciput b. Partial or complete atlanto-occipital fusion c. Atlantoaxial dislocation d. Stenosis of the foramen magnum 4. Distortion of the pons, medulla, cerebellum; traction on lower cranial nerves 5. Vertebral artery obstruction with head turning B. Clinical features: 1. Vertigo and drop attacks with head turning (obstruction of the vertebral artery) 2. Intermittent hoarseness and swallowing abnormalities due to traction of the lower cranial nerves 3. Spastic quadriparesis; ataxia legs > arms 4. Can be acquired with: a. Paget’s disease b. Osteogenesis imperfecta c. Rickets’ d. Rheumatoid arthritis
Malformations of the Axis and Atlas
A. General considerations: 1. There are five ossification centers in the axis and atlas that may develop abnormally: a. The body and tip of the axis b. The lateral mass of C1 and the central part of the axis c. A fracture through the most rostral ossification center of the odontoid separates the tip from the body and is frequently asymptomatic d. These malformations may occur concomitantly with basilar impression or independently
Dens Atresia
A. General considerations: 1. Part of the odontoid process is fused to the body of C2 2. Anterior dislocation of the axis with cord compression B. Clinical features: 1. Spastic quadriplegia 2. IX, X, XI (spinal accessory component XII involved by traction) 3. Head movement causes pain 4. Mild sensory loss or paresthesias in cervical dermatomes 5. Respiratory involvement
Chapter 3. Vertebral Column Bony Trauma Odontoid Process ossification defects
1. Tip of the odontoid process fracture; usually asymptomatic and occurs with violent head flexion 2. Base of the odontoid fails to ossify; concomitant basilar invagination
Gorlin’s Syndrome
1. Short atlas 2. Odontoid malformations
Congenital Fusion of Cervical Vertebrae
A. General considerations: 1. Congenital fusion of cervical vertebrae is most common at C4–C5 2. Fusion of the upper thoracic and entire cervical spine occurs 3. AD and AR inheritance B. Clinical features: 1. Short neck and low hair line 2. Limitation of neck movement to the lateral planes 3. Spinal stenosis occurs above and below the congenital fusion 4. Associated clinical signs: a. Syringomyelia b. Cardiovascular defects 4% c. Genitourinary anomalies 2% d. Congenital deafness (faulty development of the osseous inner ear) e. Sprengel’s deformity (branchiomeric deformity at C4–C5; elevation and maldevelopment of the shoulder and scapula)
Spina Bifida
A. General considerations: 1. Mild dysraphic defect 2. Asymptomatic unless associated with other congenital deficits: a. Myelomeningocele b. Neurenteric or other cysts c. Lipoma d. Tethered cord
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the usual acquired causes are present such as Paget’s disease, osteogenesis imperfecta (blue sclera) and rheumatoid arthritis (ulnar hand deviation) and rarely rickets, the diagnosis should be suspected. Intermittent lower cranial nerve involvement, particularly hoarseness is common as intermittent brainstem vascular insufficiency with movement of the head to the lateral planes causes vertebral artery occlusion. In a patient with increased reflexes induced by neck flexion, there may excess mobility of the spine at C1–C2. This is often accompanied by paresthesias of the hands. A short neck with low hairline and a shallow posterior fossa should also be sought which is common with osseous cervical congenital malformations. Chiari I malformation are often associated with a cervical syrinx. Hoarseness and ataxia point to this diagnosis as does a severe C2 headache with cough. An acquired thoracic spine scoliosis or kyphoscoliosis point to a reduplication or diastematomyelia of the cord. If the scoliosis is C shaped, there is disruption of paraspinal musculature unilaterally. If there is an S shaped defect, it is a congenital defect with compensation. An astrocytoma may also grow asymmetrically and motor neuron disease and primary muscle disease may affect paraspinal musculature asymmetrically causing a “C” scolioisis. Severe scoliosis and kyphosis are also seen with Emery–Dreifuss muscular dystrophy, fiber type disproportion and limb girdle muscular dystrophy type II B (LGMDIIB). Syrinxes are frequently asymmetric and may extend from the cervical to the sacral cord, producing a C shaped scoliosis. Burns on the hands and arms, as well as suspended sensory loss and segmental atrophy, identify this diagnosis. A tethered cord often is announced in young adults during delivery. A prolonged dorsal lithotomy position during a difficult birth may cause paralysis of the legs. Tufts of hair and strawberry hemangiomas of the skin often have underlying spinal and vertebral body defects. These include spinal bifida, A-V malformations and myelomeningoceles. A tuft of hair off the midline may be the marker of a neurogenic cyst that connects with the intradural space. A patient with a short neck and abnormally raised and malformed shoulder and scapula has Klippel Feil syndrome with Sprengel’s deformity.
Chapter 3 Vertebral Column Bony Trauma Mechanisms of Injury
Differential Diagnosis of Congenital Spine Defects
The general physical examination is most helpful with this differential diagnosis. A patient with a short neck with limited lateral movement suggests basilar impression or platybasia. If
1. Sudden violent flexion (cervical vertebrae): a. Anterior compression fracture of vertebral bodies b. Unilateral or bilateral facet joint dislocation c. Kinking and rupture of the longitudinal and interspinous ligaments
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2.
3.
4. 5.
SECTION IV. Spinal Cord Disease
d. Extrusion of discs has also occurred while holding patients in flexion in preparation for an LP. Severe compression injures: a. Affecting the thoracic lumbar area (ski injuries, falls) b. Burst vertebral bodies (central area of compression with fracture lines radiating outwardly) c. Bone splinters and disc material may extrude into the spinal canal and compress the spinal cord d. Common in elderly osteoporotic women from minimal trauma (opening a window). Usually only local pain with no neurologic deficit (anterior wedge fracture of the thoracic vertebrae) Rotational injury: a. Unilateral pars interarticularis fracture or facet injury b. Rotary facet dislocation. Very difficult to see radiologically. Must be suspected from increased intraspinal distance at that level and persistent focal spine pain (rupture of an interspinal ligament). Jumped facets; the superior facets are displaced anteriorly Hyperextension injury: a. Fracture of the posterior elements with evolving spondylolisthesis at the affected level.
Parenchymatous Cord Trauma
A. General considerations: 1. Incidence 30–40/1,000,000 population 2. Prevalence 900/1,000,000 population 3. 65% of patients are less than 35 years of age 4. Male to female ratio of 3 : 1 5. Second peak occurs between 55–59 years of age 6. Greatest during the summer months and on weekends B. Causes: 1. Motor vehicle accidents a. Single and multiple vehicular accidents b. Motorcycle c. Injuries to pedestrians d. Industrial accidents e. Diving into shallow water f. Sports injuries g. Gunshot wounds h. Stabbing i. Non-industrial falls (elderly patients); cement stairs leading to the basement
Patterns of Spinal Cord Injury Fracture and Dislocations
1. 2. 3. 4. 5. 6. 7. 8.
Jefferson’s fracture (fracture of the atlas) A ring fracture Vertebral body burst fracture Hangman’s fracture (C2–C3 spondylolisthesis) Jumped and locked facet joints Bony canal fracture with cord compression Rotary facet subluxation Odontoid fracture: a. Tip (distal 2–3 mm) b. Base (ossification center) c. Disruption of the cruciate, alar and lateral ligaments 9. Post surgical: a. Severe neck deformity b. Posterior displacement of a bone c. Two level instability d. Overgrowth of a lateral bone graft with stenosis of the canal 10. Rotary injury: atlantooccipital subluxation
Hyperflexion Injury
1. Subluxation 2. Facet joint dislocation 3. Compression of the anterior portion of the vertebral body with fracture and bone fragments that compress the spinal cord
1. 2. 3. 4.
Cord concussion Spinal shock Complete cord transaction (rare) Incomplete cord transaction: a. Brown–Sequard syndrome b. Central cord syndrome c. Anterior cord syndrome d. Posterior cord syndrome 5. Associated injuries: a. Vertebral artery occlusion (cervical cord injury) b. Cauda equina injury c. Conus medullaris injury d. Mixed epiconus, conus and cauda equina lesions 6. Spinal cord concussion: a. Transient neurological symptoms with full recovery in minutes to hours b. Signs develop below the level of injury
Spinal Shock
A. Clinical features: 1. Complete flaccid paralysis below the level of the lesion 2. Anesthesia below the level of the lesion 3. Incontinence of bowel and bladder 4. Areflexia below the level of the lesion 5. Babinski response plantar (muscles are paralyzed); maybe present or intermediate toes are seen (quivering extension/flexion movements); probably equivalent to a Babinski response.
Chapter 3. Vertebral Column Bony Trauma
6. Areflexic hypotonic state changes to hyperreflexia within six weeks (in general) 7. Complete transection of the cord: a. Rare; they are most often caused by a high velocity missile, knife wound or vehicular accident b. Most injuries are bruises that evolve their pathology (ovoid) and extend over time c. Motor, sensory and autonomic dysfunction occurs below the level of the injury d. In chronic patients: 1) Autonomic dysreflexia occurs if not treated with adrenergic blocking drugs. The syndrome consists of: a) Severe hypertension 250–300 mmHg/200 mmHg b) Hyperhidrosis c) Severe headache that is vascular in nature d) Seizures (during the headache phase) e) Intracranial hemorrhage
Brown–Sequard Syndrome
A. General considerations: 1. X-RT to the cord from the treatment of malignancy; usually Hodgkin’s disease, Ewing’s sarcoma, chordoma or non-Hodgkin’s lymphoma. Usual dose is >3000 rads. There is little soft tissue in the neck to absorb radiation. Pathology is a proliferating endarteritis of the sulcal arteries 2. Rarely a knife, bullet or accidental cause has been described. If occurs with demyelinating disease, tumor and tuberculoma. 3. Vertical hemisection of the cord: a. Ipsilateral paralysis below the level of the lesion b. Ipsilateral loss of vibration proprioception, and light touch sensibility (partial) c. Contralateral loss of pain and temperature sensibility d. Bowel, bladder and sexual function is intact e. Ipsilateral segmental loss of sensation or weakness at the appropriate level (destruction of the spinal grey matter at the level of injury)
Central Cord Syndrome
A. General considerations: 1. Usually caused by a hyperextension injury of the neck (fall or automobile accident) 2. Clinical features: a. Hands and arms are more affected than the legs due to lamination of the corticospinal tracts within the cord; brachial plexus traction injury may contribute to the arm weakness.
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b. Sensory loss in the legs and arms is incomplete with sacral sparing. Pressure sensation may be lost in adductor muscles while pin prick and cold can be appreciated (lamination of the spinothalamic tract) c. Acute urinary retention occurs in 50% of patients. Most patients regain bowel, bladder and sexual function d. Visceral pain may be diminished due to its ventral position in the dorsal columns e. Hyperactive reflexes and Babinski sign are present
Anterior Cervical Cord Syndrome
A. General considerations: 1. Acutely ruptured disc with or without fracture 2. Abnormally prolonged and tight neck flexion (children or adults forcibly flexed during an LP) 3. Fracture dislocation of the cervical cord B. Clinical features: 1. Immediate paralysis 2. Loss of pain and temperature sensibility below the lesion 3. Preservation of proprioception and vibration sense below the lesion 4. Urinary retention
Posterior Cord Syndrome
A. General considerations: 1. Differential diagnosis: a. Demyelinating disease b. Sjögren’s syndrome c. B12 deficiency d. Trauma e. Tabes dorsalis (most often a root entry zone lesion) f. Tumor B. Clinical features: 1. Loss of vibration and proprioception. Often may best be determined by placing the tuning fork over the spinous processes. 2. Severe proprioceptive loss in the arms and legs; patients are unable to walk in the dark 3. Updrift of the arms with minimyoclonus of the fingers; a lateral drift occurs bilaterally 4. Dorsal column nuclear involvement causes wild movement of the arms 5. Trauma as a cause may have associated burning pain and paresthesia of the hands 6. Lhermitte’s sign is noted with structured lesions irritating the posterior columns.
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SECTION IV. Spinal Cord Disease
Associated Cervical Cord Traumatic Injuries
A. General considerations: 1. Vertebral artery occlusion from injury in the transcervical canal 2. Dissection may occur at the C2 level B. Clinical features: 1. Rotary nystagmus is ipsilateral > contralateral 2. Involvement of cranial nerves IX, X, XI; XII is involved if the hypoglossal canal is injured at the foramen magnum 3. Pain in the side of the neck; rarely projects specifically to the lateral eyebrow 4. Ipsilateral peripheral or central Horner’s syndrome; peripheral origin is from trauma to the carotid sheath or artery; sympathetics to the eye originate from C8–T1 and wrap around the carotid artery. 5. Ipsilateral Vth nerve involvement; VIth passes through the foramen magnum (upper division VI ) 6. Contralateral loss of pain and temperature below the clavicle 7. Ipsilateral ataxia; leg > arm; patients have lateral pulsion (feeling of being pushed) to the ipsilateral side 8. Nausea and vomiting; hoarseness; infarction of the nucleus ambiguous 9. Prolonged depressed level of consciousness
Epiconus Lesions
A. General considerations: 1. Traumatic; sudden compression injuries of the thoracic spine; falls, ski and motor vehicular accidents 2. Metastatic tumor of the spinal cord 3. Embolic occlusion of the great radicular artery of Adamkiewicz (origin is T10–T12–L1–L2). 4. Aortic surgical procedures; iliac artery or ligature of the ilioinguinal branch that is the origin of the radicular artery of Adamkiewicz 5. T10–T12 is involved primarily B. Clinical features: 1. Bilateral symmetrical leg weakness 2. Sensory level at L1–L2 3. Bowel, bladder and sexual dysfunction 4. Babinski signs are present; the spinal cord ends at the spinal level of S5, but the vertebral level is L1–L2
c. Enlarged nerve roots (congenital peripheral neuropathies) d. Metastatic tumors: colon, lung, breast, lymphoma, prostate are common e. Vertebral fractures with posterior displacement of bone fragments into the spinal canal B. Clinical features: 1. Asymmetric motor and sensory loss 2. Severe pain (usually L5–S1 distribution) 3. Perineal sensory anesthesias (“saddle distribution”) 4. Bowel and bladder dysfunction (obstipation and retention respectively) 5. Areflexic paralysis and sensory loss of the affected roots
Conus Medullaris Lesions
A. General considerations: 1. Differential diagnosis of these lesions is: a. Demyelinating disease in younger patients b. Glioma and chordoma are the primary tumors; metastatic tumors similar to those for the cauda equina c. Syrinx d. Disc fragment e. Lipoma f. Liposarcoma g. Glioma of the filum terminale B. Clinical features: 1. Symmetric if adjacent roots are involved 2. Painless 3. Bowel, bladder and sexual dysfunction are the earliest manifestation 4. Dissociated sexual dysfunction may occur. Patients may have erection without ejaculation or vice versa
Post Traumatic Syringomyelia
A. General considerations: 1. A syrinx appears in a region of spinal cord injury due to phagocytosis of tissue debris; the cavities are surrounded by gliosis and have connective tissue in their walls (not seen in a congenital syrinx) B. Clinical features: 1. A syrinx cavity after injury may extend cephalad into previous uninjured tissue with the expected deficits
Cauda Equina Level Arachnoiditis
A. General considerations: 1. The differential diagnosis for lesions at this level is: a. Disc protrusion b. Spinal stenosis
A. General considerations: 1. Arachnoiditis is a chronic inflammatory response of the spinal arachnoid and pial membrane
Chapter 4. Vascular Anatomy of the Spinal Cord
B. Clinical features: 1. Burning patchy pain over several nerve root distributions 2. Motor power of the roots is relatively well maintained 3. Bladder and bowel may be involved 4. Reflexes are decreased or absent in a patchy distribution C. Pathology 1. The spinal cord and roots are encased by leptomeningeal fibrous tissue and loculated cysts. Rarely, the walls of arteries and veins are thickened (demonstrated by an autopsy series of arachnoiditis patients whose illness was caused by contaminated diluent in an anesthetic solution). D. Imaging evaluation: 1. MRI evaluation reveals clumped nerve roots in the center of the dural sac. Myelography with contrast demonstrates a featureless dural sac.
Chapter 4 Vascular Anatomy of the Spinal Cord
A. General considerations: 1. The arterial blood supply to the spinal cord can be divided into a superior, intermediate and inferior zone B. The superior territory: 1. The cervical cord (C1–T1–T2) receives its blood supply from branches of the vertebral arteries that derive from the subclavian arteries. At the level of the foramen magnum, the vertebral arteries give off medial branches that join to form the anterior spinal artery which lies ventrally in the midline. a. The anterior portion of the anterior spinal artery supplies C1–C4 spinal segments b. Two to four radicular arteries from the vertebral arteries in the transcervical canal or from cervical branches of the subclavian artery contribute to the blood supply of the mid and lower cervical segments. c. C8–T1 is the most vulnerable level of the cervical cord for ischemic injury. C. The intermediate territory (T3–T8): 1. Is supplied by the dorsal radicular artery that travels with the 5th, 6th or 7th thoracic anterior root. D. The Inferior Arterial Territory 1. T8–S5 is supplied by the great radicular artery of Adamkiewicz. a. Usually derives from radicular arteries from T1– L1–L2.
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Intrinsic Vascular Anatomy of the spinal cord
1. Radicular arteries enter at each spinal level: a. They divide and accompany the dorsal and ventral roots b. Ventral root branches join along the midline to form the anterior spinal artery c. Paired posterior spinal arteries form from anastomosis of the dorsal radicular branches d. Circumflex arteries anastomose with the anterior and posterior circulations at the lateral margins of the cord 2. Anterior sulcal arteries a. Arise from the anterior spinal artery and alternately supply: 1) The spinal grey matter 2) The anterior and lateral funiculi 3) Each anterior sulcal artery supplies one segment of the hemi chord 4) The greatest distance between sulcal arteries is in the thoracic cord b. Posterior spinal artery penetrating branches supply: 1) The dorsal columns 2) Upper most Rexed layers of the dorsal horn (I–IV) c. Circumflex anastomotic vessels (the anastomosing plexus of small arteries between the anterior and posterior vessels) supply the superficial white matter
Venous Drainage of the Spinal Cord
1. Radial veins drain the inner cord to form a coronal plexus 2. Deep parenchymal veins drain into central sulcal veins in the median fissure 3. Parenchymal veins drain both sides of the cord 4. Sulcal veins have intrasegmental anastomosis 5. Anterior median spinal vein: a. Drains the sulcal vein b. There may be two veins instead of one 6. Extramedullary venous channels: a. Common on the dorsal cord 7. Eight-twelve anterior radicular veins arise from the anterior to median vein: a. Drain the anterolateral anastomosis from the coronal venous plexus b. The junction of the anterior radicular vein and the coronal venous plexus is at the nerve roots prior to their exit through the dura 8. The lumbar enlargement is drained by the vena radicularis magna 9. Posterior radicular veins are most prominent in the cervical cord 10. Spinal cord venous blood drains into: a. Epidural and paravertebral plexus 1) This is a valveless system b. It extend from the occipital bone to the sacrum
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SECTION IV. Spinal Cord Disease
Causes of Spinal Cord Ischemia
1. Transient ischemic attacks of the cord occur (weakness and numbness that lasts 2–15 minutes) a. Cholesterol emboli b. Fibrocartilaginous emboli 2. Venous occlusion (secondary to severe cervical stenosis or spondylosis) is posited to cause progressive myelopathy 3. Spinal cord infarction: a. Paresis within minutes of the ictus b. Recovery of function is rare if total paralysis lasts for 24 hours 4. Watershed infarction with hypoperfusion is usually overshadowed by cerebral signs and symptoms. The spinal cord is perfused at a much lower pressure than the brain.
Clinical Features of Spinal Cord Ischemia
1. Weakness: a. May be gradual or maximal at onset b. Paraparesis > quadriparesis (midthoracic T4–T6 watershed) 2. Sensory loss: a. Numbness or paresthesias will parallel the weakness; may precede it b. Aching back pain with radicular features is common c. Thoracic band like sensation or abdominal radiations are common d. Some form of sensory loss is invariant e. Suspended sensory loss with sulcal artery occlusions 3. Urinary and bowel dysfunction: a. Urinary retention > than incontinence b. Bowel incontinence later in the course 4. Flaccid paralysis noted early: a. Loss of superficial reflexes (cremasteric and abdominal) b. Areflexia below the lesion is usual: 1) Schiff–Sherrington response may occur above the lesion. Slightly increased reflexes (release of ascending inhibition) above the level of the lesion. 2) Hyperactive reflexes with Babinski’s response may occur if only a few spinal segments are ischemic.
Arterial Syndromes
4) Crural plegia (arm ipsilateral and leg contralateral) 2. Low anterior spinal artery infarction: a. Involvement of the ventral 2/3 of the spinal cord b. Weakness of extremities below the lesion c. Loss of temperature and pain below the lesion d. Bladder involved in 50% of patients e. Intact dorsal column sensory function
Causes of Anterior Spinal Artery Syndrome
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.
Atherosclerosis of the artery or its feeding vessels Vertebral artery dissection Syphilis (Erb’s spastic paraparesis) Compression from extruded disc or bone fragment Sarcoid (meningeal involvement or vasculitis) Vasculitis (SLE, Wegener’s granulomatosis, collagen vascular disease) Embolus (heart, atrial myxoma, atrial fibrillation); cholesterol emboli Idiopathic pachymeningitis Aortic dissection Giant cell arteritis Takayasu’s disease Bends (nitrogen bubbles) Ischemic atherosclerotic emboli less frequent than asymptomatic emboli Hypoperfusion: a. Lumbosacral > cervical > cervicothoracic Fibrocartilaginous emboli: a. Women > men b. Mid to low thoracic levels
Ischemia of Lower Thoracic Cord and the Lumbar Enlargement by Involvement of the artery of Adamkiewicz
1. 2. 3. 4. 5.
Renal arteriogram Surgical procedures (cross clamping the aorta) Aortic dissection Atherosclerosis Emboli: heart; cholesterol; air; nitrogen bubbles, fibrocartilaginous 6. Aortic dissection
Anterior Spinal Artery Ischemia
1. Origin of the anterior spinal from the vertebral artery a. Atherosclerosis of the vertebral artery b. Medial medullary syndrome 1) Ipsilateral XII nerve paralysis 2) Contralateral proprioceptive and vibratory deficit 3) Contralateral weakness of arm and leg (above the decussation of the pyramidal tract at C2)
Watershed Infarction of T4–T6
A. General considerations: 1. The spinal cord is perfused at a much lower pressure 60–70 mmHg than the brain 2. Infarction of the spinal cord is frequently overshadowed by cerebral signs and symptoms
Chapter 4. Vascular Anatomy of the Spinal Cord
3. Dropped sensory levels to T4–T6 frequently occur from cervical cord disease (lamination of the spinothalamic tract) 4. Internal watershed zones in the spinal cord are the: a. Corticospinal pathways b. Rexed layers V–VI 5. Selective grey matter necrosis does occur 6. Most susceptible region to low flow states is T4–T6 7. Causes of thoracic watershed infarction: a. Systemic hypotension b. Prolonged surgical procedures c. Cardiac arrest d. Anoxia e. Vertebral artery occlusion (primary involvement may be C8–T1) f. Aortic dissection g. Carbon monoxide poisoning
Posterior Spinal Artery Ischemia
A. General considerations: 1. Extremely rare 2. Atherosclerosis 3. Dissection or occlusion of the vertebral arteries B. Clinical features: 1. Severe sensory ataxia (particularly without vision) 2. Loss of vibration and position sense C. Medical Causes of Ischemic Spinal Cord Disease 1. Atherosclerosis 2. Systemic hypotension 3. Collagen vascular disease (PAN, SLE) 4. Thromboangiitis obliterans (Buerger’s Disease) 5. Aortic arch syndrome; coarctation of the aorta 6. Dissection of the aorta (infarction of grey matter; superficial white matter) 7. Neoplastic endarteritis (malignant angioendotheliosis) 8. Infective endarteritis: a. Syphilis c. HIV b. Cryptococcus 9. Fungal invasion of blood vessels: a. Mucormycosis c. Aspergillosis b. Nocardia 10. Illicit drugs: a. Cocaine c. Amphetamine b. Propalolamine 11. Disseminated intravascular coagulation 12. Prothrombotic states 13. Aortic atherosclerosis (feeding vessels; emboli) 14. Aortic aneurysm 15. Aortic surgery (particularly cross clamping > 18 minutes) a. Abdominal aortic aneurysms; cord and cauda equina may be infracted
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16. Ligation of lower thoracic intercostal vessels 17. Nonpenetrating abdominal trauma (torsional occlusion of vessels supplying the cord) 18. X-RT (intraspinal vessels from proliferative endarteritis)
Embolic Disease of the Spinal Cord
1. Atheromatous aortic plaque a. Blue toe syndrome (abdominal aorta) b. Digital arteries of the toes are occluded 2. Cardiac source: a. Atrial fibrillation b. Embolus c. Infective endocarditis (bacteria; fungi) d. Mitral valve prolapse e. Valvular clots f. Atrial myxoma 3. Fibrocartilaginous debris (disc) a. Anterior portion of the cervical cord b. May occlude veins c. Women > men d. Rapidly evolving tetra or paraparesis e. Rarely following trauma f. Anterior spinal artery territory most often affected; mid to low thoracic level 4. Angiography: a. Catheterization for dural AVM 5. Fat: a. Broken bones (long bones) in young patients b. Hip replacement (older patients) c. Diabetic ketoacidosis 6. Tumor cells 7. Nitrogen bubble (Caisson’s disease) 8. Air bubbles a. Diving accidents (scuba) b. Cardiac surgery c. Surgical procedures in sitting position (ENT) 9. Therapeutic renal artery embolization
Venous Infarction of the Spinal Cord
A. General considerations: 1. Venous infarctions without hemorrhage are hard to distinguish from arterial infarction B. Causes of venous infarction of the spinal cord: 1. Extension of thrombophlebitis of pelvic veins 2. Associated with chronic obstructive pulmonary disease 3. Polycythemia vera 4. Associated thrombophlebitis: a. Propagates into cord via venous plexus 5. Subacute necrotizing myelitis:
SECTION IV. Spinal Cord Disease
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6. 7. 8.
9. 10. 11. 12. 13. 14.
a. Associated with spinal cord thrombophlebitis b. No systemic foci c. Association with chronic obstructive pulmonary disease Associated with epidural abscess Endoscopic sclerotherapy (reported for esophageal varices) Coagulopathy: a. Factor V Leiden with protein C resistance b. Anti-thrombin III c. Factor C deficiency d. Factor S deficiency e. Anti-phospholipid syndrome f. Lupus anticoagulant Cancer (prothrombotic states); breast and pancreas Subacute necrotizing myelopathy (paraneoplastic) Birth control pills Pregnancy Disseminated intravascular coagulation (LIC) Dehydration
b) Ischemia of the cord d. Onset of symptoms to diagnosis may be delayed e. Severe weakness in 20% of patients by six months after presentation; 50% by three years f. After onset of leg weakness further disability is rapidly progressive g. Pain may be local or radicular h. Spinal bruit (extremely rare) i. Upper and lower motor neuron weakness
Cobb’s Syndrome
A. General considerations: 1. Cutaneomeningospinal angiomatosis 2. Angiomas on large portions of the trunk 3. Dural angioma with cutaneous angioma in the corresponding dermatome or over many dermatomes B. Clinical features: 1. Spastic paraparesis at the appropriate level 2. Usually at thoracic level
Hemorrhagic Spinal Cord Disease
Angiomas
A. General considerations: 1. Spinal vascular malformations B. Tortuous group of dilated arteries and veins: 1. No intervening capillary network (cavernous hemangioma) a. May involve spinal cord, leptomeninges or both 2. Veins predominance (venous angioma) 3. Arterial predominance (arterial venous malformation) 4. Telangiectasis (capillaries) C. Epidemiology of angiomas: 1. Incidence is not known: a. Occur in 3–11% of spinal cord masses b. Men > women 2 : 1 c. Clinical presentation between 30–70 years of age d. Lower thoracic and lumbar angiomas are the most frequent e. Posterior or posterior lateral intraspinal location 2. Clinical signs and symptoms: a. Onset with pain, weakness and sensory symptoms b. Later bowel and bladder dysfunction c. Cervical lesions produce symptoms earlier d. Onset associated often with: 1) Exercise 2) Trauma 3) Pregnancy 4) Menstruation 5) May bleed during sleep 6) Angiomas may cause: a) Increased local venous pressure
Foix Alajouanine syndrome (Angiodysgenetic Necrotizing Myelopathy)
A. General considerations: 1. Men of middle to late adulthood 2. Clusters or masses of enlarged engorged subarachnoid veins; anterior predominance 3. Lower thoracic and lumbosacral segments are most commonly involved 4. Proliferation of small blood vessels (veins or capillaries) 5. Associated with a dural arteriovenous shunt generally within or near a root sleeve; arterialized venous shunts that drain into the venous system of the cord B. Clinical features: 1. Intermittent and progressive course 2. Asymmetrical clinical findings 3. Pain and sensory loss of the lower limbs 4. Bowel, bladder and sexual dysfunction 5. Spastic and amyotrophic lower extremities
Bannayan–Zonana Syndrome
A. General considerations: 1. AD spinal AVM 2. Most common in Mexican Americans 3. May hemorrhage B. Clinical features: 1. Spastic paraparesis at the appropriate spinal level 2. Associated with intracranial lesions
Chapter 4. Vascular Anatomy of the Spinal Cord
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Klippel–Weber–Trenaunay
Hematomyelia
A. General considerations: 1. AD B. Clinical features: 1. Enlarged extremity with dilated veins and telangiectasias 2. Corresponding AVM at the cervical or lumbosacral level with spastic paraparesis or radiculopathy
A. General considerations: 1. Trauma a. Direct injury to the spine (penetrating and nonpenetrating) b. Hyperextension of the cervical spine 2. Bleeding of a vascular malformation 3. Hemorrhage into a tumor 4. Hemorrhage into a syrinx 5. Coagulopathy 6. Anticoagulation (particularly coumadin) 7. Venous infarction 8. Syphilis B. Clinical features: 1. Presents as spinal shock associated with severe back pain 2. Autonomic instability 3. Gray matter more affected than white matter 4. Spasticity develops below the level of the lesion 5. Atrophy and fasciculations of affected segments occurs with time 6. Babinski’s sign is prominent 7. Sensory level: a. Two segments lower than the lesion (if thoracic) b. Higher in back than front (follows patterns of intercostal nerves) c. Dropped sensory level (T4–T6) following cervical lesions is common (lamination of spinothalamic tract) d. Rare suspended sensory loss (interruption of segmental dorsal horn at the level of injury with preserved long tract sensory function) e. Mass reflex late in the course of the illness
Differential Diagnosis of Spinal Angioma
1. 2. 3. 4. 5. 6. 7. 8.
Multiple sclerosis Neoplasm Herniated disc Spondylolisthesis Intracranial SAH (5% present with neck and back pain) Subacute combined degeneration (B12 deficiency) Transverse myelitis (all causes) Meningovascular syphilis
Spinal Hemorrhage
Differential diagnosis by location: 1. SAH 3. Subdural 2. Intramedullary 4. Epidural
Subarachnoid Hemorrhage in the Spinal Cord
A. General considerations: 1. Spinal SAH < 1% of all SAH 2. Most common cause is rupture of a spinal angioma (10%) B. Clinical features: 1. Acute onset 2. Severe back pain at the level of the hemorrhage 3. Pain quickly becomes diffuse with signs of meningeal irritation 4. Radiculopathy at the site of the lesion 5. If blood diffuses above the foramen magnum: a. Headache b. Cranial neuropathy c. Depressed level of consciousness d. Decreased ankle jerks with increased knee and upper extremity reflexes e. Increased intracranial pressure with papilledema (rare) 6. CSF: a. Hemorrhage (1,000,000 RBCs/mm3 ) b. Within days may have hypoglycorrhachia (severely depressed glucose <20 mg%); may occur with all forms of SAH
Spinal Epidural and Subdural Hemorrhage
A. General considerations: 1. Epidural hemorrhage occurs with greater frequency than subdural hemorrhage 2. Peak occurrence during childhood and fifth to sixth decade 3. Cervical lesions more common in childhood; thoracic and lumbar lesions in adults 4. Frequently occur with trivial trauma or exertion B. Clinical features: 1. Similar for both subdural and epidural hematoma 2. Severe back pain at the level of the bleed 3. Myelopathy (compressive) 4. Cauda equina syndrome 5. Radicular pain (involved segment) 6. Progresses over hours to days 7. Acute transverse myelitis (presentation of epidural hematoma)
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SECTION IV. Spinal Cord Disease
C. MRI imaging: 1. T1 weighted image a. Signal intensity of the epidural hematoma is primarily isointense to the spinal cord 2. T2 weighted images of epidural hemorrhage a. Heterogenous hyperintensity as compared to the cord b. Focal hypointensity (acute blood; deoxyhemoglobin) 3. Capping of epidural fat 4. Direct continuity with adjacent osseous structures 5. Compression of epidural fat, subarachnoid sac and spinal cord 6. Posterolateral location in the spinal cord 7. Spontaneous spinal epidural hematomas located in the ventral space a. Premembranous hematoma b. Posterior longitudinal ligament hematoma D. Differential Diagnosis: 1. Epidural anesthesia 2. Lumbar puncture 3. Blood dyscrasia 4. Anticoagulation 5. Neoplasm 6. Vascular malformations 7. Thrombocytopenia 8. Following heparinization after lumbar surgery
a. Cerebellum b. Retinal 3. Associated systemic manifestations: a. Renal cysts b. Renal carcinoma c. Pheochromocytoma (specific alleles of VHL disease) d. Increased levels of vascular endothelial neurotrophic factor (VENGF) B. Clinical features: 1. 80% in cerebellum 2. 20% in spinal cord 3. 35% of patients with hemangiomas have VHL disease; 60% of those patients who are symptomatic are less than 30 years of age 4. Spinal hemangioblastoma: a. Relationship to VHL is greater when in an infratentorial location 5. VHL patients are younger than sporadic cases 6. VHL patients develop endolymphatic sac tumors (tinnitus or deafness as clinical manifestations) 7. Spinal hemangioblastoma: a. Often associated with cerebellar hemangioblastoma b. May be multiple c. May be extramedullary in a spinal root location d. Renal cell carcinoma may metastasize to the hemangioblastoma
Arteriovenous Malformations Differential Diagnosis of Specific Spinal Cord Malformations
1. 2. 3. 4. 5. 6.
Hemangioblastoma (Von Hippel–Lindau Syndrome) Arteriovenous malformation Dural arteriovenous fistula Intramedullary spinal cord cavernous malformations Bannayan–Zonana Syndrome Occult vascular malformation of the spinal cord
A. General considerations: 1. Males more than females 2. Thoracolumbar location (dorsal) 3. Associated with: a. Cobb’s syndrome b. Wyburn Mason syndrome c. Kartagener’s syndrome
Spinal Dural Arteriovenous Malformations Hemangioblastoma
A. General considerations: 1. May arise in isolation 2. Major manifestation of Von Hippel–Lindau disease (VHL) a. Prevalence 1/36,000 population
Von Hipple–Lindau Syndrome (VHL)
A. General considerations: 1. AD: chromosome 3p25–3p26 deletions or mutations 2. Associated central nervous system hemangioblastomas:
A. General considerations: 1. Most frequent spinal arteriovenous malformation 2. Posterior and posterolateral spinal cord is the most common location B. Clinical features: 1. Diagnosis established after months of intermittent symptoms 2. Progressive myelopathy 3. Cauda equina and conus medullaris dysfunction 4. Low back pain (pseudo radicular pain) 5. Lower extremity weakness 6. Sphincter disturbance (early involvement of micturition; later involvement with disc disease) 7. Combined upper and lower motor neuron signs
Chapter 4. Vascular Anatomy of the Spinal Cord
8. Symptoms may vary with posture; menses and exercise C. Evaluation of dural arteriovenous fistula (DAVF) 1. Patients may demonstrate enlarged spinal perimedullary veins with intracranial DAVF images by MRI 2. Angiographic evaluation of spinal dural arteriovenous fistula (SDAVF) a. Anterior spinal vein draining SDAVF (spinal dural AV fistula) b. Opacification of other medullary veins of the ASV (anterior spinal venous system) c. Distortion of the hairpin turn of the artery of Adamkiewicz 3. MRI evaluation of spinal dural arteriovenous fistula: a. Intramedullary high intensity signal changes on T2 weighted images (after hemorrhage) b. High intrinsic area of T2 weighted intensity decreases within 1–4 months after treatment 4. CSF: a. Abnormal in > 75–90% of patients 5. Some angiographic evidence for vascular steal phenomenon as a cause of symptoms 6. Dural arteriovenous fistula at the craniocervical junction: a. MRI evaluation: dilated perimedullary veins around the spinal cord C1–C2 b. High intensity T2 weighted signal in the spinal cord at appropriate levels on T2 weighted images D. Clinical presentations: 1. Present with SAH 2. Progressive myelopathy that may interfere with respiration 3. Intramedullary arteriovenous malformation may occur with lipomyelomeningocele a. MRI: 1) Hypervascular intradural lesion; fatty component extradurally
Intramedullary Spinal Cord Cavernous Malformation (IMSCM)
A. General considerations: 1. Cervical and thoracic cord most common level; rare in the conus medullaris 2. Intramedullary spinal cavernous malformations are associated with cryptic venous malformations 3. May develop tethering of the cord following surgery 4. Episodic, acute or subacute spinal cord dysfunction 5. Appropriately 50% of patients, may have multiple cavernous malformations in the neuraxis B. Clinical features: 1. Myelopathy 2. Radicular pain 3. Conus medullaris syndrome
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Bannayan–Zonana Syndrome
A. General considerations: 1. AD 2. Hamartomatous disorder 3. Macrocephaly 4. Multiple lipomas 5. Male > female 6. Rare extradural spinal hemangiomas occur
Angiographically Occult Vascular Malformations of the Spinal Cord (AOVMS)
1. Cavernous malformations are the most common type of AOVM of the spinal cord 2. Insidious onset with limb asymmetry has been noted 3. Deterioration putatively from repeated hemorrhages around vessels or from intrahumeral thrombosis Differential Diagnosis of AOVMS
1. Primary hemorrhagic tumors of the spinal cord: a. Ependymoma b. Astrocytoma c. Medulloblastoma 2. Hemorrhagic transverse myelitis: a. Lung metastasis (small cell) 3. Paraneoplastic spinal cord hemorrhagic necrosis: a. Small cell lung carcinoma b. Anti-Hu antibody syndrome 1) Occurs at the thoracic level 4. Bleeding diathesis: a. Coagulation defects b. Anticoagulation (coumadin/heparin) c. Platelet disorders d. Leukemia/lymphoma e. Hemorrhagic leukoencephalitis (acuteautoimmune disease) f. Subdural hematoma g. Parenchymatous bleed (trauma) 5. Systemic Conditions Affecting the Spinal Cord a. Whipple’s disease b. Gluten sensitive enteropathy c. Kohlmeier–Degos disease d. Sjögren’s disease e. B12 deficiency 1) Acute following nitrous oxide anesthesia (cobalamin deficiency) 2) High serum B12 level noted with leukemia and lymphoma f. Vitamin E deficiency 1) Dietary 2) Alpha tocopherol transporter defect g. Pure spinal angitis
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SECTION IV. Spinal Cord Disease
Rare Spinal Cord Abnormalities
Werner’s syndrome (Progeria)
A. General considerations: 1. Childhood age of onset 2. Accelerated aging 3. AR B. Clinical features: 1. Balding 2. Atherosclerosis of all circulations 3. Premature graying 4. Osteosclerosis 5. Diabetes mellitus 6. Juvenile cataracts 7. Hypogonadism 8. Rare spastic paraparesis a. Many patients with increased reflexes
Spinal Pseudoathetosis
A. General considerations: 1. Occurs after protracted severe loss of proprioception with acute painful crisis 2. Secondary to: a. Lesions of the dorsal columns or their nuclei b. Lesions of the dorsal root ganglia c. Lesions of the dorsal root entry zone B. Clinical features: 1. Lateral and updrift with polyminimyoclonus 2. Rare flinging of the arms and legs (hemiballism) 3. Severe proprioceptive loss partially compensated 4. Pain may precede the pseudoathetosis C. Differential diagnosis of spinal pseudoathetosis: 1. Tabes dorsalis 2. Spinal trauma (dorsal column destruction) 3. Demyelinating disease 4. Syringomyelia 5. SLE myelitis 6. Friedreich’s ataxia
Stiff Leg Syndrome
A. General considerations: 1. Suspected autoimmune etiology B. Clinical features: 1. Onset in middle age 2. Stiffness and painful spasms of the lower limbs 3. Spasms are spontaneous 4. Reduced by movement 5. Rigidity and abnormal postures of both legs occur 6. No brainstem pyramidal tract or sensory dysfunction C. EMG abnormalities:
1. Repetitive grouped discharge of motor units D. Differential diagnosis of stiff leg syndrome: 1. Stiff man syndrome 2. Idiopathic encephalomyelitis with rigidity 3. Spinal interneuronitis
Venoocclusive Disease
A. General considerations: 1. Associated with spinal cord vascular malformations 2. Associated with acute compressive epidural processes: a. Hematoma b. Epidural abscess Hemorrhagic venous occlusive disease: 1. Back pain at the level of involvement 2. Rapidly progressive (days to weeks) 3. Multiple spinal segments involved Non-hemorrhagic venous occlusive disease: 1. Course is over weeks to months 2. Less pain 3. Fewer spinal segments involved Embolic venous infarction: 1. Fibrocartilaginous 2. Sudden onset 3. Pain at the level of involvement 4. Asymmetric deficit Venous infarction in association with vascular malformations: 1. Subacute neurologic syndrome 2. Foix–Alajouanine syndrome a. Step wise dysfunction due to thrombosis of supplying vessels 3. Intramedullary hypertension due to spinal dural arterial venous fistula Sclerotherapy: 1. Direct penetration of epidural veins 2. Occlusion of the anterior spinal artery 3. Cirrhosis (acquired or congenital) is often the systemic defect a. Related AV shunts b. Inadvertent arterial access following esophageal vein injection
Chapter 5 Spastic Paraparesis
Anatomical Feature of Transverse Myelitis
1. Spinothalamic tract (STT)
Chapter 5. Spastic Paraparesis
a. Lissauer’s tract distributes afferent information two levels above and below the entry level (important in thoracic cord) b. Sacral fibers distributed most laterally in STT; cervical fibers most medially 2. Dorsal column system: a. Leg fibers medially (fasciculus gracilis); arm fibers more laterally (fasciculus cuneatus) b. Sacral fibers outermost most dorsally c. Visceral pain ventrally in both fasciculi 3. Cervical cord involvement frequently causes dropped sensory level to T4–T6 or the abdomen; rarely a discrete far lateral lesion may cause leg or sacral sensory symptoms 4. Associated spinocerebellar or cuneocerebellar (C1–C4) compromised with the sensory abnormalities
Clinical Features of Transverse (Longitudinal Myelopathy Myelitis)
1. Heralded by band like pressure or pain at the segmental level 2. Paresis below the level 3. Bladder affected if both sides of the cord are involved: a. Epidural involvement-earlier and more severe urinary dysfunction than intramedullary lesions b. Cervical Intramedullary lesion: 1) Sudden loss of urine with Valsalva maneuver c. Transverse lesion: 1) Urgency with difficulty in initiation of micturition (lesion between the pontine or cervical bladder micturition centers and the parasympathetic supply to the detrusor muscle (Onuf’s nucleus) Incoordination of ignition of micturition and release of the external sphincter. 4. Conus medullaris level: a. Loss of initiation of micturition and a paralyzed bladder that is insensate to filling pressures
Hereditary Spastic Paraparesis (Strümpell–Lorrain Syndrome)
A. General considerations: Hereditary spastic paraparesis is a clinically and genetically heterogenous disorder with inter and intra familial variation. It is divided into AD, AR, X-linked and syndromic forms. In addition, spastic paraparesis complicates many acquired forms of spinal cord pathologies and is a major component of both demyelinating and dysmyelinating conditions. At present, 18 genetic loci have been reported of which ten are AD, three X-linked and five are autosomal recessive. The pure form is an insidiously progressive spastic paraparesis with a neurogenic bladder and distal vibratory loss in the legs.
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Uncomplicated HSP refers to the pure form in which both the corticospinal and dorsal column systems are involved. Complicated HSP has additional neurological deficits that include optic neuritis, macular and cerebellar degeneration, ichthyosis, seizures, cataracts, cognitive dysfunction, and extrapyramidal signs. B. Genetic features: The average age of onset of symptoms is due to which genetic locus may be involved in uncomplicated HSP; otherwise they present similarly. 1. HSP linked to 2p (SPG4 and SPG13) overlap in time of onset with other early symptomatic forms (SPG10, SPG3 and SGP 12). 2. The average age of onset after age 20 is most typical of SGP8 and SGP 6 3. Approximately 50% of AD uncomplicated HSP are linked to SPG4 4. Approximately 50% of AR HSP is SPG 11 on chromosome 15q13–q15. 5. A rare AR HSP has been mapped to chromosome 16q; the protein product is known as paraplegin. Some kindreds have other neurological deficits such that this mutation leads to a complicated form. 6. Two genes have been identified for an X-linked form of complicated HSP C. Clinical features of uncomplicated HSP: 1. Bilateral lower extremity weakness; anterior tibialis, hamstrings and iliopsoas muscles are most involved 2. Deep tendon reflexes are increased; Babinski signs are prominent (often at rest and by midfoot) the legs are spastic 3. Upper extremity strength, bulk, facility of movement and tone are normal 4. Pes cavus is frequent (if not there other diagnosis should be sought) 5. Gait is abnormal due to limited thigh flexion and dorsiflexion of the feet; circumduction maybe prominent as is increased adductor tone. Hyperlordosis and a short swing phase during gait is prominent. 6. Decreased muscle bulk of the lower extremities 7. Progressive mild loss of proprioception and vibratory sense in the distal lower extremities Autosomal dominant HSP chromosomes SPG4 (Spastin) SPG8 SPG9 SPG10 (kinesin SA) SPG13
pure spinal pure spinal complicated pure spinal pure spinal
2p22 8q23–q24 10q23.3–q24.2 12q13 2q24–34
AD Hereditary Spastic Paraparesis
A. General considerations: 1. Two forms based on age at presentation a. Type 1 < age 35
SECTION IV. Spinal Cord Disease
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b. Type II > age 35 2. Sib-Sib correlation in age of onset is high; onset occurs in the same decade in 2/3 of families 3. Mean age of onset in males and affected offspring is earlier than females 4. Penetrance is variable; inter and intra familial phenotypic variation is normal Clinical features of AD HSP type 1
1. Onset occurs in the first to fourth decade 2. Initial presentation: a. Motor delay c. Leg weakness b. Abnormal gait d. Asymptomatic 3. Upper extremity: a. Weakness < 26% c. Mild ataxia 15% b. Hyperreflexia 45% Lower Extremity Signs and Symptoms of Type 1
1. 2. 3. 4. 5. 6. 7.
Spasticity – 90% Weakness – 55% Distal sensory loss – 20% Urinary symptoms – 15% Pes cavus – 30% Disease duration 20–35 years Wheelchair bound by age 60
Clinical Presentation AD Type II
1. Onset third to seventh decade 2. Initial presentation: a. Abnormal gait 3. Upper extremity signs and symptoms: a. Weakness – 47% c. Ataxia – 20% b. Hyperreflexia – 50% Lower Extremity Signs and Symptoms
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
Spasticity – 100% Weakness – 90% Distal sensory loss – 80% Urinary symptoms – 50% Pes caves – 20% Disease duration – 15 to 25 years Loss or depression of ankle reflexes 15% Sexual dysfunction rare and a late occurrence Increased abdominal reflexes early No bowel dysfunction Type II more severe symptoms than Type 1 in general Babinski signs are present Decreased strength of iliopsoas, hamstrings an anterior tibialis muscles
Specific AD Diseases
SPG3 A. General considerations: 1. Chromosome 14q; 10–15% of all AD patients with AD HSP 2. Anticipation occurs B. Clinical features: 1. Pure form 2. Anticipation has been noted SPG 3A A. General considerations: 1. AD a. Atlastin 1 mutation 2. Early onset 3. Disease of African Americans B. Clinical features: 1. Age of onset, 4–14 years 2. Primarily pure spastic gait disorder 3. No spasticity in upper limbs 4. Rare tongue fibrillation, decreased visual acuity 5. Decreased visual acuity Differential point from SPG4: 1. Delayed auditory and visual evoked potentials SPG4 A. General considerations: 1. Chromosome 2p22 a. Spastin gene 2. Most common form of AD spastic paraparesis B. Clinical features: 1. Pure form 3. Urinary symptoms 2. Decreased vibration SPG6 A. General considerations: 1. Chromosome 15q B. Clinical features: 1. Pure form 2. Pes cavus SPG8 A. General considerations: 1. Chromosome 8q B. Clinical features: 1. Pure form SPG9 A. General considerations: 1. Chromosome 10q 23.3–q24.2 B. Clinical features: 1. Cataracts 3. Motor neuropathy 2. Gastrointestinal reflux SPG10 A. General considerations: 1. Chromosome 12q13 2. Kindred described coding for kinesin
Chapter 5. Spastic Paraparesis
a. Possible microtubule binding activity B. Clinical features: 1. Pure form SGP12 A. General considerations: 1. Chromosome 19q13 B. Clinical features: 1. Pure form SGP13 A. General considerations: 1. Chromosome 2q24–34 B. Clinical features: 1. Pure form
Autosomal Recessive HSP
SPG5 A. General considerations: 1. Chromosome 8q B. Clinical features: 1. Pure form 2. Onset first decade; disease duration of 10–30 years 3. Initial sign is a spastic gait 4. Upper extremity weakness (30%) and hyperreflexia – 50% 5. Lower extremity signs and symptoms: a. Spasticity 100% b. Weakness of legs 90% c. Distal sensory loss < 20% d. Urinary symptoms 30% e. Pes cavus 50% f. Sib-sib correlation of time of onset less than AD form of HSP SPG7 A. General considerations: 1. Chromosome 16q; paraplegin gene a. Associated with mitochondrial abnormalities of skeletal muscle b. Nuclear encoded c. Proteolytic and chaperone activities d. Many but not all patients have ragged red fibers and cytochrome oxidase negative fibers B. Clinical features: 1. Pure form 2. Complicated form associated with: a. Dysphagia and dysarthria b. Optic atrophy c. Axonal neuropathy d. Cerebellar and cerebral atrophy e. Evidence of vascular lesions f. Mitochondrial defects on muscle biopsy SPG14
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A. General considerations: 1. Chromosome 3q 28 B. Clinical features: 1. Complicated form associated with: a. Mental retardation b. Distal motor neuropathy
Autosomal Recessive Spastic Paraparesis with a Thin Corpus Callosum
A. General considerations: 1. AR; primarily in Japanese patients; linked primarily to chromosome 15q13–15 B. Clinical features: 1. Mental retardation 2. Spastic paraparesis 3. Symptoms start in second decade 4. Associated sensory loss and urinary incontinence develop with age C. MRI evaluation: 1. Thinned corpus callosum D. Magnetic stimulation demonstrate abnormalities in central motor pathways
Differential Diagnosis of AR HSP with Thin Corpus Callosum
1. Corpus callosum agenesis with peripheral neuropathy (Andermann syndrome) a. Mental and physical retardation b. Seizures c. Sensorimotor polyneuropathy d. Optic atrophy 2. CRASH Syndrome
X-Linked Recessive HSP
SPG1 A. General considerations: 1. LICAM gene (neural cell adhesion molecule) a. Variably expressed in females b. Allelic to MASA cell adhesion syndrome whose clinical features are: 1) Mental retardation 3) Spastic paraplegia 2) Aphasia 4) Adducted thumbs c. Other LICAM gene mutation syndromes B. Clinical features: 1. Thin corpus callosum 4. Spastic paraparesis 2. Mental retardation 5. Hydrocephalus 3. Adducted thumbs C. Complicated form associated with: 1. Hydrocephalus 3. Adducted thumb 2. Aphasia
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SGP2 A. General considerations: 1. Chromosome Xq11.2 2. Proteolipid protein gene (PLP) a. Encodes an intrinsic myelin protein b. Allelic to Pelizaeus–Merzbacher disease B. Clinical features: 1. Early onset severe and slowly progressive phenotypes have been noted in the same families 2. Associated CNS white matter lesions 3. Pure form: a. Onset up to the second decade b. Disease duration 10–25 years c. Initial presentation 1) Spastic gait d. Upper extremity signs and symptoms: 1) Weakness-none 2) Hyperreflexia < 10% e. Lower extremity signs and symptoms 1) Spasticity – 80% 2) Weakness – none 3) Rare distal sensory loss 4) No urinary symptoms 5) No pes cavus
X-Linked Recessive HSP Allelic to Pelizaeus–Merzbacher Disease (PMD)
A. Clinical features: 1. Progressive dementia 2. Nystagmus noted in infancy 3. Choreoathetosis 4. Spasticity 5. Diffuse cerebral hypomyelination by MRI Differential Diagnosis
Complicated hereditary Spastic Paraparesis 1. Spectrum of genetically distinct diseases 2. Spastic paraparesis is associated with other neurological deficits that may be predominant
2. Mast’s Syndrome: a. Dysarthria c. Athetosis b. Dementia d. Spastic paraparesis 3. Troyer’s Syndrome a. Short stature d. Amyotrophy b. Mental retardation e. Spastic paraparesis c. Ataxia 4. Sjögren–Larsson Syndrome a. Ichthyosis c. Spastic paraparesis b. Mental retardation 5. Hellin’s Syndrome a. Mental retardation b. Macular degeneration
AD Complicated Hereditary Spastic Paraparesis
1. Signs associated with spastic paraparesis a. Cerebellar degeneration b. Amyotrophy of the hands c. Peroneal muscular atrophy d. Sensory neuropathy e. Intention tremor f. Extrapyramidal signs g. Muscular dystrophy h. Abnormal skin pigmentation 2. Symptom complexes associated with hereditary spastic paraparesis a. Dystonia, athetosis, dementia, amyotrophy b. Retinal degeneration, dementia, dysarthria, amyotrophy c. Optic atrophy
Associated Neurologic Signs and Symptoms with X-Linked Recessive Complicated Hereditary Spastic Paraplegia
a. Mental retardation and optic atrophy b. Deafness c. Dysarthria, athetosis, amyotrophy
AR Complicated HSP
1. Associated neurological signs a. Cerebellar degeneration b. Sensory neuropathy c. Optic atrophy and dysarthria d. Amyotrophy resembling ALS e. Deranged skin pigmentation Associated neurologic syndromes associated with AR HSP 1. Charlevoix–Saquennay a. Dysarthria d. Spastic paraparesis b. Ataxia e. French Canada c. Distal amyotrophy
Differential Diagnosis of Hereditary Forms of Spastic Paraplegia
Machado–Joseph Disease (SCA3) A. General considerations: 1. Chromosome 14 a. AD 2. CAG repeat disease B. Clinical features: 1. Ataxia 4. Bulging eyes 2. External ophthalmoplegia 5. Amotrophy 3. Spastic paraparesis
Chapter 5. Spastic Paraparesis X-Linked ALD
Werner’s Syndrome
A. General considerations: 1. Disease of CNS white matter and the adrenal cortex: a. ABCD1gene 2. Incidence of 1 in 50,000 people 3. Four major subgroups in affected males: a. Childhood form (severe) b. Adolescent form 1) Onset between 10–21 years c. Adrenomyeloneuropathy (AMN) 1) Onset in the late twenties 2) Sphincter disturbances 3) Distal sensory loss 4) Progressive paraparesis d. Primary adrenal insufficiency 1) Slowly progressive over decades 2) No neurologic abnormalities e. ALD has X-linked inheritance 1) Carrier females have neurological signs and symptoms (usually AMN phenotype) 2) Mean age of onset 38 years; later onset than males 3) Reduced penetrance; milder phenotype in females B. Clinical features: 1. No real distinction clinically between HSP and AMN C. Laboratory features of ALD: 1. Plasma concentrations of very long chain fatty acids are increased in 99% of males; greater than 85% in females D. EMG evaluation: 1. AMN, a subtype of ALD frequently demonstrates decreased nerve conduction velocities
A. General considerations: 1. Chromosome a. AR B. Clinical features: 1. Premature balding 2. Severe atherosclerosis 3. Osteoporosis 4. Hypogonadism
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5. Juvenile cataracts 6. Diabetes mellitus 7. Spastic paraparesis 8. Peripheral neuropathy
Mitochondrial defects A. General considerations: 1. AD B. Clinical features: 1. Spastic paraparesis Familial Paroxysmal Dystonia I (see Movement Disorder Section)
Globoid Cell Leukodystrophy (Krabbe’s Disease)
A. General considerations: 1. AR 2. Deficiency of galactosylceramidase B. Clinical features: 1. Adult onset variant 3. Seizures 2. Optic atrophy 4. Spastic paraparesis C. Laboratory evaluation: 1. Marked slowing of NCV by EMG 2. High CSF protein 3. Multinucleated macrophages or globoid cells in CNS white matter
Metachromatic Leukodystrophy Adrenomyeloneuropathy (AMN)
A. General considerations: 1. Subtype as noted above of X-linked ALD B. Clinical features: 1. Onset after the second decade 2. Progressive spastic paraparesis 3. Prominent sensory loss in the legs 4. Sphincter disturbances 5. Female carries have spastic paraparesis 6. Hypoadrenalism 7. Hypogonadism C. laboratory evaluation: 1. Very long chain fatty acids 2. Choreoathetosis Spasticity Syndrome 3. Planto–Palmar Keratoderma (PPK)
A. General considerations: 1. ARSA gene 2. Lysosomal enzyme arylsulfatase A deficiency B. Clinical features: 1. Late infantile, onset 6 months to 2 years 2. Juvenile, onset 3 to 16 years 3. Adult MLD presentation: a. Behavioral abnormalities (psychosis) b. Spastic paraparesis c. Pathology: 1) Metachromatic inclusions within Schwann cells and macrophages 2) Segmental peripheral nerve demyelination abnormality thin myelin sheaths 4. AB Variant a. Activator protein deficiency b. Normal in vitro activity of arylsulfatase A
SECTION IV. Spinal Cord Disease
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Dentato-Rubral-Pallido-Luysian Atrophy (DRPLA)
A. General considerations: 1. Chromosome 12p; usually 49–88 repeat CAGA nucleotides 2. Homozygosity for an allele carrying intermediate CAG repeat number B. Clinical features: 1. Adult onset > 40 years of age a. Ataxia c. Dementia b. Choreoathetosis 2. Specific patient with paraparesis and: a. Truncal ataxia b. Dysarthria c. 41 CAG repeats d. No dementia, seizure, myoclonus or other involuntary movements
2. 3. 4. 5.
Krabbe’s Disease Hyperlysinemia Pyruvate dehydrogenase deficiency (complex IV mtDNA) Leigh’s Disease (COX deficiency complex III)
Homocarnosinosis
A. General considerations: 1. AR 2. Abnormalities of histidine metabolism 3. Lack carnosinase activity B. Clinical features: 1. Spastic paraparesis 2. Mental retardation 3. Increased homocarnosine in the CSF
Abnormal Vitamin B12 Binding Protein Familial Hyperlysinemia
A. General considerations: 1. AR; AASS gene 2. Deficiency of alpha-amino adipic semialdehyde synthases essential for lysine degradation B. Clinical features: 1. Intellectual impairment 2. Epilepsy 3. Progressive spastic paraparesis C. Laboratory evaluation: 1. Hyperlysinemia 2. Hyperlipinuria
Adult Onset Alexander’s Disease
A. General considerations: 1. AR; mutation affects GFAP 2. Intermediate filament glial fibrillary acidic protein (GIAP) 3. Astrocytic cytoplasmic inclusions called Rosenthal fibers B. Clinical features: 1. Onset third to fifth decade 4. Cerebellar dysfunction 2. Early exacerbations 5. Hyperreflexia 3. Palatal myoclonus 6. Spastic paraparesis
Chapter 6 Enzyme and Metabolic Disorders Affecting the Spinal Cord 1. Metachromatic leukodystrophy
A. General considerations: 1. Abnormal plasma vitamin B12 binding protein 2. High serum B12 level 3. Low CSF S-adenosylmethionine level 4. Low RBC B12 level B. Clinical features: 1. Spasticity of all extremities 2. Subacute combined posterior and corticospinal tract signs and symptoms
Combined System Degeneration (Corticospinal Tract and Posterior Column) after Nitrous Oxide Anesthesia
A. General considerations: 1. Nitrous oxide anesthesia precipitates acute B12 deficiency 2. Cobalamin CO2+ inactivated to CO3+ 3. Methyl cobalamine is a Co-factor for methionine synthetase; failure of conversion of homocysteine to methionine B. Clinical features: 1. Combined posterior and lateral column degeneration 2. Approximately six hours of exposure is required for those that are not B12 deficient prior to exposure; symptoms may appear 2–6 weeks after exposure
B12 Deficiency
A. General considerations: 1. Multiple mechanisms are causative: a. Malabsorption of B12 due to lack of intrinsic factor most commonly b. 5 mcg is needed per day
Chapter 6. Enzyme and Metabolic Disorders Affecting the Spinal Cord
c. Antibodies to gastric parietal cells may accompany all autoimmune diseases d. May occur from tetrahydrobiopterin deficiency and B12 activator deficiency e. The biochemical reactions that depend on B12 are: 1) Folate-dependent reaction that transfers a methyl group from methyltetrahydrofolate to homocysteine that produces methionine 2) Homocysteine to methionine reaction (methionine synthase required; cobalamin is a cofactor). Reduced cofactor activity leads to decreased DNA synthesis f. Spongy degeneration with both myelin and axon destruction are seen in both the central and peripheral nervous system B. Clinical features: 1. Paresthesias with primarily large fiber greater than small fiber neuropathy 2. Dorsal column demyelination with loss of position, light touch and vibration sensitivity 3. Demyelination of subcortical frontal white matter that leads to frontal lobe personality charge 4. Loss of smell 5. Optic neuropathy 6. Cerebellar ataxia 7. Spasticity 8. An extremity that may be wasted with loss of sensation but has hyperactive reflexes 9. Absent reflexes in the ankle with pathological hyperactive reflexes at the knee and in the upper extremities
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11. Babinski sign is present; sparing of superficial reflexes (abdominal; cremasteric) C. Laboratory evaluation: 1. EMG: a. Slow sural nerve conduction velocity; denervation of lower extremity muscles II. Nitrous Oxide (pp. 74) III. Konzo A. General considerations: 1. Occurs in West Africa 2. Cyanide toxicity B. Clinical features: 1. Optic atrophy 2. Spastic paraparesis IV. Ethylene Oxide A. General considerations: 1. Used in gas sterilizations; operating room packs B. Clinical features: 1. Generalized spasticity V. Subacute Myelo-Optic Neuropathy A. General considerations: 1. Caused by ingestion of outdated tetracycline 2. Major epidemics in Japan and Mexico B. Clinical features: 1. Optic neuritis 2. Spasticity from spinal cord involvement
Metabolic Causes of Spinal Cord Dysfunction Selected Toxins Affecting the Spinal Cord
I. Lathyrism A. General considerations: 1. Consumption of the unripe chick pea or grass pea (Lathyrus sativus) 2. Contaminate; used instead of cereals or lentils during periods of great economic stress; need 15–150 mg/day for toxicity 3. Toxin: Beta-N-Oxolamine-L-Alazanine (BOAS) B. Clinical features: 1. Onset during the first four decades 2. Sudden onset of heaviness and leg weakness 3. Subacute onset over months can occur 4. Stiffness in lower extremities – 70% 5. Leg cramps – 50% 6. Paresthesias – 30% 7. Urinary symptoms – 5% 8. Nocturnal erections; ejaculations; urinary urgency may occur 9. Symmetrical spasticity; ankle clonus 10. Mild lower extremity weakness
Hyperparathyroidism
A. General considerations: 1. Occurs with primary and secondary hyperparathyroidisms (usually renal failure) B. Clinical features: 1. Proximal muscle weakness, fatigue and cramps 2. Rarely a fibrillating tongue has been noted 3. Rare urinary frequency 4. Severe hyperreflexia arms greater than legs C. Laboratory evaluation: 1. Erosion of the radial side of the index finger and the acromial head of the clavicle 2. EMG: neurogenic Hyperthyroidism (Davidoff Syndrome)
A. General considerations: 1. Syndrome is seen in the face of severe hyperthyroidism B. Clinical features: 1. Spastic paraparesis 3. Babinski signs are present 2. Ophthalmoplegia
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SECTION IV. Spinal Cord Disease
Portocaval Shunt
A. General considerations: 1. The spinal cord features are usually seen in a setting of severe liver failure 2. Hyperammonia is the rule; neurological features have been seen with normal ammonia levels B. Neurological features: 1. Relapsing intermittent encephalopathy 2. Spastic paraparesis 3. Generalized hyperreflexia C. MRI demonstrates 1. Increased T2 weighted signal in the caudate and putamen
b. Cortical layers III–V that receive thalamic projection c. Purkinje cells of the cerebellum d. Globus pallidus interna cells (GP) e. Cranial nerves of the brainstem (particularly V in children) f. Peripheral nerves B. Clinical features of spinal cord anoxia: 1. Severe rigidity of the extremities 2. Selective death of Renshaw cells (decreased glycine) 3. Loss of inhibitory interneurons of the spinal cord (GABAergic B cells) 4. Clinical spinal cord findings are over shadowed by deficits from other areas of the CNS
Chapter 7
Liver Failure
A. General considerations: 1. Neurological features are seen from hepatic failure from all causes 2. Swelling of Alzheimer type II glia in the brain with increased intracranial pressure 3. MRI findings of increased signal on T2 weighted images (caudate and putamen) B. Neurological features: 1. Clinical stages: a. Acute I: 1) Personality change (active psychosis) 2) Acute increased intracranial pressure 3) Reye’s syndrome (increased ICP, vomiting, low glucose, decortication) b. Subacute stage II: 1) Brainstem involvement 2) Reversible decerebration 3) Spasticity of all extremities 4) Pupils < 1 mm but are reactive to light 5) Babinski signs are present c. Stage III: 1) Coma 2) Fetor hepaticus 3) Failure of Doll’s eye and ice-water calorics C. Laboratory evaluation: 1. Increased serum ammonia may be the best clinical correlation; increased CSF glutamine occurs D. Pathology: 1. Increased prominence of Alzheimer type II glia
Cardiac Arrest and All Forms of Anoxia
A. General considerations: 1. The following structures of the neuraxis are the most vulnerable to lack of oxygen: a. Sumner’s sector V of the hippocampal formation
Autoimmune Causes of Spinal Cord Dysfunction A. General considerations: 1. Maybe ethnically and genetically determined; more common in African American and Asian patients than Caucasians 2. Axonal destruction in the spinal cord greater than demyelination B. Clinical features: 1. Bilateral optic neuritis 2. Affects young patients 3. Severe spastic paraparesis 4. Axonal injury appears early
Multiple Sclerosis
A. General considerations: 1. Spinal cord involvement may be predominant feature in middle aged women; almost always occurs in all forms of MS. The MRI coils to evaluate spinal cord pathology are not as well developed or accurate as those for cerebral imaging B. Clinical features: 1. The process is most often relapsing remitting which slowly evolves into secondary progressive disease; primary progressive and variants occur 2. The spinal lesions are most often occurring at cervical levels which cause a dropped sensory level to T4–T6 rather than at a thoracic level 3. The demyelinating lesions are often longitudinal rather than transverse and occur over several levels 4. Paresthesias of the palms rather than the fingers (the latter more characteristic of nerve or brachial plexus sensory loss)
Chapter 7. Autoimmune Causes of Spinal Cord Dysfunction
5. Lower extremity spasticity 6. Bladder involvement: a. Neurogenic b. Dyssynergy between detrusor contraction and sphincter opening 7. Associated neurological findings: a. Intranuclear ophthalmoplegia b. Afferent pupillary defect c. Bilateral cerebellar ataxia d. Bilateral corticospinal tract dysfunction e. Cognitive decline f. Early loss of superficial abdominal reflexes
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Acute and Chronic Acquired Demyelinating Inflammatory Polyradiculopathy
A. General considerations: 1. The major autoimmune attack is on peripheral myelin 2. GQ1b and other epitopes identified 3. Molecular mimicry is a possible mechanism; overlap between peripheral and central antigens (same epitopes) are responsible for the central manifestations B. Clinical features: 1. Longitudinal myelitis at cervical levels 2. Rarely brainstem and cerebral demyelination occurs
Acute Disseminated Encephalomyelitis
Systemic Lupus Erythematosus
A. General considerations: 1. 75% evolve into multiple sclerosis B. Clinical features: 1. One episode of demyelination 2. May follow a viral illness 3. Brunt of the demyelination is in the brain 4. Age of all lesions is similar 5. Spinal cord involvement is manifest by spasticity, bladder dysfunction and weakness 6. Optic nerve may be involved 7. Adrenocorticoid stimulating hormone may be more effective than intravenous steroids for treatment 8. A great percentage evolve into MS
A. General considerations: 1. Spinal cord involvement occurs in association with arthralgia, skin and visceral involvement 2. Usually systemic markers of activity are high B. Clinical features: 1. Longitudinal myelitis at cervical levels 2. Maybe recurrent 3. Usually a dropped sensory level at T4–T6 4. Corticosplinal tract dysfunction
Acute Hemorrhagic Leukoencephalitis
A. General considerations: 1. Hyperacute demyelination B. Clinical features: 1. One clinical episode 2. Usually affects the left cerebral hemisphere 3. CSF may have up to or greater than 150 RBC cells/mm3 4. Spinal cord maybe affected
Sarcoid
A. General considerations: 1. Lung, cardiac, joint, muscle and nerve involvement B. Clinical features: 1. Dural involvement is common 2. Primarily affects the thoracic cord 3. Compression myelopathy more common than parenchymal vasculitis 4. CSF: a. Sugar 30–40 mg% b. Protein 80–150 mg% c. Lymphocytic cellular response d. Associated cranial nerve and CNS involvement
Post Vaccination Myelitis Stiff Man Syndrome
A. General considerations: 1. Occurs 7–14 days following vaccination 2. Measles and hepatitis B virus are the most common viral vaccinations. Rabies is a rare cause now due to recombinant vaccines. B. Clinical features: 1. More common in children 2. Associated with cerebral periventricular demyelination 3. Longitudinal myelitis occurs most frequently at cervical levels
A. General considerations: 1. Slightly more common in females (50%) 2. Associated with diabetes mellitus, hyper and hypothyroidism, epilepsy in 10% of patients 3. GAD 67-kD isoform appears to be the antigen 4. May be associated with breast cancer; the antigen may be a non-intrinsic membrane protein of 128 kD (amphiphilic) B. Clinical features:
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1. Fluctuating progressive muscle stiffness and painful spasms of the trunk 2. Insidious onset; 4th to 5th decades 3. Axial musculature affected more than appendicular; lower extremities are more affected than the upper 4. Respiratory, facial and bulbar muscles are affected in advanced disease 5. Patients have normal strength and sensation; reflexes maybe increased 6. Lumbar hyperlordosis occurs 7. Hereditary form has been described: a. Stiffness is present at birth; resolves by age 3 and returns in adolescence b. Stiffness precipitated by movement 8. Muscle spasms maybe induced by acoustic, somatosensory or emotional stress C. EMG: 1. Continuous motor unit activity in at least one axial muscle; normal silent period after a painful stimulus
Differential Diagnosis of Autoimmune Diseases Associated with Longitudinal Myelitis
1. Wegener’s granulomatosis (severe sinopulmonary involvement; mononeuritis multiplex) 2. Rheumatoid arthritis (small muscle involvement of the hands, C1–C2 spondylolisthesis with spinal cord compression) 3. Mixed connective tissue disease (elements of polymyositis, scleroderma and SLE). The latter component frequently associated with transverse myelitis. 4. Regional enteritis (usually associated with stroke or cerebral sinus thrombosis loss of clotting factors through the gut causes a prothrombotic state) 5. Ulcerative colitis (most often associated with cerebrovascular accidents, cerebral sinus thrombosis, eye and joint involvement). 6. Relapsing polychondritis (most often associated with disc disease, collapses of the larynx or optic neuritis)
Variants of Stiff Man Syndrome
1. Progressive encephalomyelitis with rigidity a. Rare b. Rapidly progressive (few months) to death 2. Stiff limb syndrome: a. Rigidity and abnormal fixed posturing b. Painful spasms of distal lower extremities c. Sphincter and brainstem involvement in 50% of patients 3. Women with breast cancer a. Antibodies to synaptic vesicle protein amphiphilin I 4. Jerking Stiff Main Syndrome a. Myoclonic jerking is prominent Differential Diagnosis of stiff man syndrome
The symptom complex is rigidity of axial greater than appendicular musculature, action induced spasms and continuous motor unit activity: 1. Isaac’s syndrome 2. Corticobasal ganglionic degeneration 3. Focal spinal cord lesions 4. Tetanus 5. Encephalomyelitis
Sjögren’s Syndrome
A. General considerations: 1. Antibodies to salivary and lacrimal glands; red eyes and serosal surface irritation 2. Peculiar Vth nerve involvement (numb face) B. Clinical features: 1. Primarily posterior column involvement 2. Associated with primary progressive multiple sclerosis
Differential Diagnosis of Arteritic Syndromes Affecting the Spinal Cord
1. Syphilitic proliferative end arteritis a. Occlusion of the vertebral or anterior spinal arteries b. Meningoencephalitis (stage II) c. In association with HIV (all stages appear simultaneously) d. Pachymeningitis cervicalis 2. Anti phospholipid syndrome a. Primary b. In association with SLE 3. Takayasu’s disease a. Vertebral artery and anterior spinal artery occlusions b. Anterior > posterior spinal artery syndromes 4. Isolated angiitis of the spinal cord a. No associated features or laboratory evidence of systemic arteritis 5. Giant cell arteritis a. Rarely can affect all arteries of the internal carotid system b. A component of the aortic arch syndrome (both carotids and vertebral arteries may slowly be occluded) 6. Köhlmeier–Degos Disease a. Characteristic atrophic skin lesions b. Severe retinal arterial spasm c. Spinal cord infarction Paraneoplastic Syndromes
a. anti-Hu antibody (ANNAI) 1) Primarily an antinuclear antibody b. Associated with limbic encephalitis c. Associated primarily with small cell cancer of the lung d. Burning sensory neuropathy and limbic encephalitis e. Longitudinal myelitis
Chapter 8. Infections Affecting the Spinal Cord Vitamin Deficiencies
1. B12 2. Vitamin E deficiency A. General considerations: 1) Dietary (associated with severe diarrhea and malabsorption) 2) Alpha tocopherol transporter deficiency B. Clinical features: 1) Primarily dorsal column dysfunction 2) Associated cerebellar ataxia and large fiber neuropathy
Chapter 8 Infections Affecting the Spinal Cord
A. General considerations: 1. Epidural abscess a. Predisposing factors: 1) Compromised immune system 2) Hematogenous spread from other infections 3) IV drug abuse 4) Prolonged epidural anesthesia B. Clinical features: 1. Severe back or neck pain 2. Intramedullary spread 3. Occasional radicular pain that may precede the myelopathy 4. May present as a Brown–Sequard Syndrome 5. Sudden paralysis from spinal cord infarction C. Laboratory evaluation: 1. Elevated sed rate the most important test; reliable however in only 25–40% of early patient infections. D. MRI evaluation: 1. Increased signal from the disc space on T2 weighted sequences often the first sign of discitis 2. Enhancement of the anterior and posterior longitudinal ligaments; paraspinal muscles and the abscess itself
Gram Negative Infections
1. Occur following post surgical procedures 2. At times one month to six weeks delay from the surgical procedure
Staph Aureus
A. General considerations: 1. Predisposing causes:
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a. IV drug abuse c. HIV b. SBE B. Clinical features: 1. Discitis with severe pain on any movement 2. Several segments are involved 3. Sudden paralysis from infarction of the cord C. MRI evaluation: 1. Disc space enhancement 2. Enhancement along anterior and posterior ligaments
Tuberculosis
A. General considerations: 1. Lumbar spine > thoracic spine in American patients 2. Cervical > thoracic > lumbar infections in Asian patients B. Clinical features: 1. Associated with thoracic Pott’s disease and spinal collapse with spinal cord compression 2. Spinal cord infarction (endarteritis) 3. Cold paravertebral abscess (L1–L4); often minimally painful C. Imaging evaluation: 1. Disc space infection; pus along anterior and posterior ligaments 2. Eburnation of the vertebral end plates
Viral Infections with myelitis
1. Myelitis may follow polio or other enterovirus infections of the anterior horn cells 2. Varicella virus attacks the dorsal root ganglia and nerve roots as well as the adjacent cord (most often thoracic) 3. Parenchymal cord involvement occurs with rabies, HSV, CMV (HIV co infected) HTLV I and II, EBV, simian B virus, and tick borne encephalitis; des encephalitides
Herpes Viruses
A. General considerations: 1. Cause acute infections but also have the capacity for latency 2. Reactivated near the site of the original infection 3. Neurological diseases in humans are caused by the following herpes viruses: a. HHV6 b. Herpes simplex type 1 and 2 c. Varicella virus d. CMV e. EBV f. Simian herpes (“monkey”) B-virus
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Herpes Simplex Type 1
Cytomegaloviruses
A. General considerations: 1. HSV-1 encephalitis is the most common cause of sporadic encephalitis in the US; approximately 10% of encephalitis cases 2. Acquired by respiratory or salivary contact; the cause of oral herpes 3. 30% of HSV-1 encephalitis occurs by spread into the brain from the nasal epithelium B. Clinical features: 1. Encephalitis 2. Myelitis 3. CSF: a. Increased pressure b. Lymphocytic pleocytosis 10–1000 WBC/mm3 c. Glucose is normal or slightly low (30–40 mg%) d. Protein is elevated (usually 60–80 mg%) 4. PCR has sensitivity of 95% 5. Cowdry A intranuclear inclusions
A. General considerations: 1. Common congenital viral infection; possibly up to 2% of the population 2. Deafness or developmental delay 3. Sexual transmission is route of infection in adults B. Clinical features: 1. In immunocompetent adults: a. Aseptic meningitis b. Mononucleosis syndrome c. Asymptomatic d. GBS e. Encephalitis 2. In association with HIV or immunosuppression: a. Retinitis c. Encephalitis b. Lumbosacral radiculitis d. Lumbosacral myelitis C. Laboratory evaluation: 1. Serology or PCR
Varicella Zoster
Epstein–Barr Virus
A. General considerations: 1. Children may suffer: a. Self-limited cerebellar ataxia b. Rare fatal encephalitis c. Post infections encephalomyelitis 1) One in 2500 patients d. Reye’s Syndrome e. Congenital varicella 2. Virus is latent in DRG cells 3. Reactivated by: a. Injury b. Immunosuppression (disease) c. Cancer d. Immunosuppressive drugs e. HIV f. Systemic illness B. Clinical features: 1. Most often T5–T12 are the affected dermatomes 2. Thoracic cord myelitis 3. Lumbosacral ganglia involvement causes bladder dysfunction and ileus 4. Zoster sine herpete: a. Prolonged radicular pain b. No zoster rash c. Detectable VZV DNA in CSF 5. Associated neurologic features include: a. Post herpetic neuralgia: b. Segmental motor atrophy c. Large vessel stroke (most often the MCA) d. Multifocal leukoencephalitis e. Cerebral vasculopathy
A. General considerations: 1. Primary infection is usually infectious mononucleosis; nervous system involvement occurs in less than 1% of patients 2. B-cell transforming virus: a. Associated with CNS and Burkitt’s lymphoma 3. Meningoencephalitis has occurred after bone marrow transplantation B. Clinical features: 1. Transverse myelitis 2. GBS syndrome; small fiber neuropathy; autonomic neuropathy; aseptic meningitis and rarely isolated cranial neuropathy C. Laboratory evaluation: 1. CSF, EBV specific antibodies or PCR
Human Herpesvirus Type 6
A. General considerations: 1. T-lymphotrophic virus 2. Childhood exanthema subitum 3. Opportunistic infection in HIV and other immunocompromised conditions: a. May cause T-cell immunodeficiency B. Clinical features: 1. Ascending necrotizing myelitis of the thoracic cord 2. B-Variant most commonly isolated from immunocompromised patients
Chapter 8. Infections Affecting the Spinal Cord Cercopithecine Herpes Virus 1 (B Virus)
A. General considerations: 1. Carried by old world monkeys 2. Veterinarians and animal handlers at risk; 70% fatality rate 3. Transmitted by animal bit or virus contaminated fomites 4. 70% fatality rate B. Clinical features: 1. Ascending paralysis (longitudinal myelitis) 2. Associated medullary and cortical signs and symptoms occur early
Rabies
A. General considerations: 1. Occurs along the Mexican–American border 2. Reservoirs are: dogs, skunks, bats, raccoons, and fox in the USA 3. Usual transmission is by a bite; rarely aerosol transmission (spelunkers) 4. Incubation period is usually 1–2 months B. Clinical features: 1. Prodrome of headache, fever, paresthesia at the inoculation site 2. Acute neurological phase with severe bulbar and autonomic features which progresses to coma 3. Paralytic or myelitic form: a. Most often from bat bites b. Paresthesias and weakness of the inoculated extremity c. Quadriplegia from spinal cord involvement C. CSF: 1. High titers of neutralizing antibodies in the serum and CSF 2. PCR of CSF is positive
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B. Clinical features: 1. 7–14 day incubation period 2. Prodromal phase of headache and meningeal symptomatology 3. An asymmetric flaccid paralysis occurs; may involve small groups of anterior horn cells (individual finger weakness) 4. Progresses for 3–5 days 5. Dromedary fever, curve maybe seen (two peaks) 6. Transverse myelitis and cerebellitis occur; rare facial weakness 7. Diaphragmatic involvement 8. Severe back pain often occurs 2–3 day C. Laboratory evaluation: 1. CSF: a. Polymorphonuclearcytosis occurs early with a shift to lymphocytosis after 2 days b. Slight elevation of protein (100–300 mg/dl) c. Sugar is normal 2. Virus isolated from CSF, stool, or throat D. Differential diagnosis of viral spinal cord infection: 1. Aseptic meningitis: a. Viruses b. Drug induced chemical meningitis 2. Other viral induced paralysis with cellular CSF: a. CMV b. Carcinomatosis of the meninges 3. Medullary involvement with cellular CSF a. Russian spring and summer encephalitis b. Rabies 4. GBS Syndrome: a. Antecedent rather than concurrent infection b. Cranial nerve VII always involved when quadriparesis supervenes c. CSF cytoalbuminologic dissociation d. Loss of reflexes except triceps (peculiarly often spared)
Coxsackie A and B Polio Virus and Other Enteroviruses
A. General considerations: 1. Enteroviruses are the leading cause of aseptic meningitis that can be identified
Polioviruses
A. General considerations: 1. Infections most common in late summer 2. Transmitted by fecal-oral contact; pharyngeal spread during epidemics 3. Most clinically apparent infection causes aseptic meningitis (8%); paralytic form is 1%
A. General considerations: 1. These viruses account for most cases of viral induced disease in the USA 2. West Nile virus must now be considered in this differential as it is spreading across the USA (first cases outside of LaGuardia airport NYC). B. Clinical features: 1. Aseptic meningitis 2. Encephalitis (rare) 3. Cerebellar ataxia (rare) 4. Paralytic spinal cord disease (rare) 5. CSF a. Poly morphonucleositose 250/mm3 b. Lymphocytic pattern in 2–4 days
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SECTION IV. Spinal Cord Disease
Flavivirus (West Nile)
A. General considerations: 1. Now spreading across the USA 2. Distributed in Asia, Middle East, parts of Europe, former Soviet Union 3. Rash, lymphadenopathy and pharyngitis are premonitory 4. Crows a reservoir (dead crows a clue to its presence) B. Clinical features: 1. Polio-like spinal cord syndrome with myelitis and flaccid paralysis 2. Aseptic meningitis 3. GBS Syndrome 4. Papillitis 5. Radiculitis
Retrovirus Infection
A. General considerations: 1. HIV binds to CD4 receptor 2. Infected macrophages transport the virus into the CNS 3. Vacuolar myelopathy occurs in 25–55% of HIV patients at autopsy 4. CNS a probable reservoir B. Clinical features: 1. Gait dysfunction 2. Spasticity 3. Leg weakness 4. Impaired proprioception and vibration 5. Sphincter dysfunction 6. Evolves over months 7. Associated often with dementia and painful distal symmetrical neuropathy 8. Babinski sign is common 9. Arms are involved late 10. Rare back pain C. Pathology: 1. Vacuolar myelopathy most prominent in the dorsolateral thoracic and cervical cord 2. Vacuolar changes in myelin sheaths with relative sparing of axons
Associated Myelopathies in HIV Patients
1. 2. 3. 4.
Back and radicular pain more prominent More rapid progression than HIV myelopathy CMV affects lumbosacral cord in very ill patients Varicella and Herpes simplex occur concomitantly: a. MRI may show T2-weighted images of a swollen cord 5. Concomitant HTLV1 and infections occur with HIV 6. Epidural abscess is seen with IV drug users
7. B12 deficiency may be a contributing factor to myelopathy in HIV 8. Rare spinal cord involvement occurs with M. tuberculosis and T gondi 9. Epidural metastasis from systemic lymphoma occurs in this setting
HTLV 1 and 2
A. General considerations: 1. Primarily seen in the Caribbean basin, Asia, Indian Ocean 2. May coexist with HIV 3. Sexual transmission B. Clinical features: 1. Longstanding slowly progressive course 2. Cervical > thoracic > lumbar cord involvement 3. Severe spasticity 4. Bladder > bowel and sexual dysfunction
Spirochetes
Syphilis
A. General considerations: 1. Caused by T. pallidum 2. Spread by sexual contact or vertically from mother to child 3. Untreated 1–5% go on to develop tabes dorsalis; usually is seen 15–20 years after the original infection B. Clinical features: 1. Lightening pains (often thoracic or abdominal); dorsal root ganglia involvement 2. Urinary incontinence 3. Sensory ataxia (positive Romberg’s sign) 4. Pupils are abnormal in 90% of patients 5. Argyll Robertson pupils are seen in 50%; other ophthalmological features include: a. Optic atrophy b. Ophthalmoplegia and ptosis c. Uveitis, chorioretinitis and vasculitis 6. Associated disorders: a. Gastric pharyngeal, laryngeal, genitourinary, intestinal, rectal crisis 7. Stamping gait Other Causes of Syphilitic Spinal Cord Involvement
1. Dorsal root entry zone and dorsal roots are sites of pathology a. Hitzig spots (dorsal root posterior rami) cause oval areas of anesthesia on the trunk 2. Pachymeningitis cervicalis: a. Compression of the cord by thickened dura
Chapter 8. Infections Affecting the Spinal Cord
3. Anterior and posterior spinal artery occlusion a. Proliferative endarteritis 4. Laboratory evaluation: a. Oligoclonal bands are present b. IgM and IgG antibodies are seen in the CSF c. PCR > 95% positive
Lyme Disease
A. General considerations: 1. Borrelia burgdorferi 2. Transmitted by the deer tick Ixodes domini, pacificus, ricinus B. Clinical features: 1. Early disease: a. Meningitis c. Bilateral VIIth nerve b. Cranial neuropathy 2. Late disease: a. Encephalomyelitis b. Dementia
Unusual Infections Affecting the Spinal Cord
Actinomycosis
A. General considerations: 1. Caused by a gram positive anaerobic or microaerophilic rod 2. Normal in the mouth and genital flora 3. Most infections are cervical, thoracic, pelvic or abdominal 4. “Lumpy jaw” follows dental procedures or oral mucosa trauma 5. Occurs in immunocompetent patients B. Clinical features: 1. Forms draining sinuses with “sulphur granules” 2. Spinal epidural abscess follows vertebral osteomyelitis a. Primary lung infection
Nocardia Asteroides
A. General considerations: 1. Occurs in immunocompromised patients; dental procedures or inhalation 2. Disseminated disease often invades the CNS 3. Spread from pneumonia with cavity pulmonary lesions B. Clinical features: 1. Concomitant cerebral abscess or meningitis 2. Spinal cord involved by vertebral osteomyelitis
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Hepatitis B Virus
A. General considerations: 1. Associated with fulminant hepatic failure and polyarteritis nodosa 2. Neurological deficits have occurred following hepatitis vaccination B. Clinical features: 1. Transverse cervical or thoracic myelitis 2. Acute cerebral edema 3. Guillain Barré Syndrome 4. Inflammatory neuropathy
Mycoplasma
A. General considerations: 1. M. pneumoniae most often causes pulmonary disease 2. Associated with occlusive cerebral vascular disease, arthralgias, rash, cardiac disease 3. Neurologic features are more common in hospitalized patients: B. Clinical features: 1. Transverse myelitis 4. GBS syndrome 2. Leukoencephalitis 5. Meningoencephalitis 3. Peripheral neuropathy 6. Aseptic meningitis C. Laboratory evaluation: 1. Cold agglutinins 2. Complement fixing antibodies HIV is associated with secondary infective myelopathy 1. Toxoplasmosis 4. CMV 2. Tuberculosis 5. Herpes Simplex 2 3. Syphilis 6. Mycobacterium avium
Chlamydial Diseases
A. General considerations: 1. C. psittaci, C. trachomatis; C. pneumonia are human pathogens 2. Birds to humans by aerosol route B. Clinical features of C. psittaci: 1. Fever, cough, myalgia and hepatomegaly 2. Transverse myelitis 3. Meningoencephalitis 4. Cerebellar ataxia 5. Cranial nerve palsy 6. Seizures C. Laboratory evaluation: 1. CSF: a. >5 lymphocytes b. Normal protein and sugar 2. Diagnosed by serology
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SECTION IV. Spinal Cord Disease
Brucellosis
Spinal Osteomyelitis
A. General considerations: 1. Caused by B. melitensis primarily 2. Multisystem illness with fever joint pain, sacroiliitis and osteomyelitis 3. Transmitted to humans by unpasteurized milk B. Clinical features: 1. Undulant fever pattern occurs in a 2–4 week cycle 2. Lumbosacral radiculitis (L5–S1) is common 3. Meningitis 4. Epidural abscess with myelitis from vertebral, paravertebral or psoas abscess source 5. Meningovascular disease 6. Encephalitis 7. Subdural empyema C. Laboratory evaluation: 1. CSF: a. Lymphocytic pleocytosis b. Low to normal glucose c. Elevated protein d. Positive Brucella agglutination tests
A. General considerations: 1. Predisposing factors: a. Elderly debilitated patients b. Diabetes mellitus c. Rheumatoid arthritis d. Catheter placement (epidural for pain management) e. Surgical procedures 2. Spread: a. Genitourinary tract b. Hematogenous spread 1) Batson’s plexus (perivertebral venous plexus) c. Decubitus ulcer: 1) LP through its periphery may cause inadvertent meningitis d. Phlebitis: 1) Infection spreads to spinal cord by medullary veins e. Endocarditis: 1) Meningeal seeding often occurs early 3. Infections are initiated by: a. Neurosurgical and orthopedic procedures most commonly: 1) Discitis; positive T2 weighted image in the disc space and along the anterior and posterior spinal ligaments
Toxoplasmosis
A. General considerations: 1. Always in an HIV patient with generalized cerebral disease 2. Retinal involvement B. Clinical features: 1. May selectively involve the conus medullaris of the spinal cord 2. CMV involves the lumbosacral roots
Coccidiomycosis
A. General considerations: 1. C. immitis; primarily inhalational route of infection 2. “Valley fever”, dry cough with large joint arthralgia; disseminated infection occurs in 1% of patients 3. Osteoarticular and lytic skull and vertebral lesions 4. Occurs in South Western USA B. Clinical features: 1. Lumbosacral spinal cord and root involvement from contiguous vertebral or sacroiliac osteomyelitis 2. Meningitis occurs within six months of
