CONTENTS

1. Microscopic Neuroanatomy...... 1 Regional Neuroanatomy ...... 1 Meninges...... 1 Cerebral Cortex ...... 4 White Matter...... 9 Deep Gray Matter...... 11 Pineal Gland...... 14 Brain Stem ...... 15 Cerebellum ...... 15 Cranial Nerves...... 18 Spinal Cord...... 19 CNS Cell Types...... 21 Neurons...... 21 Astrocytes ...... 23 Oligodendrocytes and Myelin ...... 24 Ependyma ...... 24 Choroid Plexus...... 27 Microglia ...... 28 Vasculature ...... 28 2. Microscopic Neuropathology...... 29 Glia ...... 29 Astrocytosis ...... 29 Other Glial Cells...... 41 Neurons ...... 42 Hypoxia/Ischemia ...... 43 Mineralization...... 43 Spongiform Change ...... 43 Chromatolysis ...... 43 Axonal Spheroids...... 48 Wallerian Degeneration ...... 48 Central Neuroma...... 48 Neuronophagia and Other Signs of Neuronal Loss ...... 48 Aging and Pigment ...... 49 Inclusions and Storage Material...... 50 Meninges ...... 50 Blood Vessels ...... 52

ix Non-Neoplastic Diseases of the Central Nervous System

Schwann Cells ...... 52 Inflammation ...... 52 Cerebral Edema ...... 55 3. Technical Considerations in the Handling of Surgical Specimens ...... 57 Basic Approaches...... 57 Specimen Triage ...... 57 Frozen Section...... 57 Smear Preparation ...... 58 Electron Microscopy ...... 58 Snap Freezing ...... 58 Fixation and Processing ...... 60 Staining ...... 60 Specimen Types ...... 60 Stereotactic Biopsies...... 61 Open Biopsies...... 61 Resection/Lobectomy Specimens...... 62 Meningeal Biopsies ...... 63 4. Diagnostic Approach to Brain Biopsy Interpretation ...... 65 General Comments ...... 65 Clinicopathologic Correlation...... 65 Location ...... 66 Current Clinical Course, Physical Findings, and Medications...... 69 Age and Gender...... 69 Past Medical and Family History...... 70 Laboratory Findings ...... 71 Neuroimaging Features ...... 71 5. Ischemia, Infarct, and Intracerebral Hemorrhage...... 73 Cerebral Ischemia...... 73 Global Ischemia ...... 74 Cerebral Infarct ...... 80 Intracerebral Hemorrhage ...... 92 6. Vascular Disorders ...... 101 Vascular Malformations ...... 101 Arteriovenous Malformation ...... 101 Cavernous Angioma (Cavernous Malformation) ...... 108 Venous Angioma ...... 111 Capillary Telangiectasia ...... 112 Dural Arteriovenous Fistula (Foix-Alajouanine Syndrome)...... 112 Vasculitides...... 113

 Contents

Giant Cell Arteritis ...... 114 Primary Angiitis of the Central Nervous System...... 116 Systemic Vasculitides Involving the Central Nervous System ...... 117 Noninflammatory Vasculopathies ...... 120 Cerebral Amyloid Angiopathy ...... 120 Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy...... 123 Arteriolar Sclerosis...... 125 Brain Embolism and Thrombosis ...... 126 7. Infectious Diseases...... 131 Basic Definitions...... 131 General Approach to CNS Infections...... 132 Meningeal Infections ...... 134 Acute Bacterial Meningitis ...... 134 Acute Viral Meningitis...... 137 Chronic Bacterial Meningitis ...... 139 Tuberculosis...... 139 Viral Infections...... 140 Herpes Simplex Encephalitis...... 142 Varicella Zoster...... 144 Progressive Multifocal Leukoencephalopathy ...... 145 Human Immunodeficiency Virus ...... 147 Cytomegalovirus ...... 148 West Nile Virus...... 150 Other Arbovirides...... 150 Bacterial Infections...... 152 Acute Meningoencephalitis...... 152 Brain Abscess...... 152 Actinomycosis ...... 154 Nocardia ...... 154 Neurosyphilis ...... 156 Leptospirosis...... 158 Lyme Disease...... 159 Whipple Disease...... 159 Fungal Infections...... 160 Mucormycosis ...... 160 Aspergillosis...... 162 Cryptococcosis ...... 163 Coccidioidomycosis ...... 165

xi Non-Neoplastic Diseases of the Central Nervous System

Blastomycosis ...... 166 Candidiasis ...... 167 Histoplasmosis ...... 168 Chromoblastomycosis...... 169 Parasitic Infections ...... 171 Toxoplasmosis ...... 171 Cysticercosis...... 173 Amebiasis ...... 174 Schistosomiasis...... 176 Malaria...... 178 8. Inflammatory Diseases...... 183 General Diagnostic Approach ...... 183 Processes with Discrete Mass Lesions: Granulomatous Lesions ...... 185 Sarcoidosis ...... 186 Rheumatoid Disease...... 193 Histiocytic Lesions...... 196 Langerhans Cell Histiocytosis...... 196 Rosai-Dorfman Disease ...... 200 Chester-Erdheim Disease ...... 203 Juvenile Xanthogranuloma...... 206 Choroid Plexus Xanthogranuloma...... 208 Extramedullary Hematopoiesis of the Dura Mater ...... 210 Castleman Disease...... 212 Inflammatory Myofibroblastic Tumor/Inflammatory Pseudotumor/Plasma Cell Granuloma ...... 216 Other Entities ...... 220 Processes with Diffuse Dural Abnormalities ...... 221 Intracranial Hypotension...... 221 Idiopathic Hypertrophic Pachymeningitis ...... 223 9. Demyelinating Diseases...... 231 Acute Demyelinating Diseases...... 231 Acute Demyelinating Disease and Multiple Sclerosis...... 232 Postinfectious/Inflammatory Demyelinating Diseases: Acute Disseminated Encephalomyelitis and Acute Hemorrhagic Leukoencephalitis (Weston Hurst Syndrome)...... 243 Hereditary Demyelinating Diseases...... 250 “Secondary” Demyelinating Diseases ...... 250 10. Dementia ...... 253 General Diagnostic Approach ...... 253

xii Contents

Deposits and Inclusions ...... 255 Plaques...... 255 Tangles and Other Tau Immunoreactive Deposits...... 257 Lewy Bodies and Other Alpha-Synuclein Immunoreactive Deposits...... 260 Ubiquitin Immunoreactive Deposits ...... 263 Other Immunologically Identified Deposits...... 263 Classic Neurodegenerative Diseases...... 263 Alzheimer Disease ...... 263 Dementia with Lewy Bodies ...... 271 Tauopathies ...... 275 Argyrophilic Grain Disease ...... 282 Other Inclusion Body Diseases...... 283 Prion Diseases...... 283 Subacute Sclerosing Panencephalitis ...... 293 Inflammatory and Immune-Mediated Diseases...... 296 Paraneoplastic Syndromes ...... 296 Other Inflammatory Processes...... 299 Metabolic Disorders...... 300 Vascular Diseases ...... 300 Vasculitis ...... 301 Cerebral Amyloid Angiopathy with Inflammation ...... 301 Hypertension/Binswanger Disease...... 301 CADASIL...... 301 11. Trauma ...... 309 Contusion...... 309 Epidural Hematoma...... 318 Subdural Hematoma...... 320 12. Metabolic Diseases...... 329 General Diagnostic Approach ...... 329 Neuronal Storage Disorders...... 332 Neuronal Ceroid Lipofuscinosis...... 333 Gangliosidoses...... 335 Niemann-Pick Disease...... 336 Leukodystrophies ...... 337 Adrenoleukodystrophy and Adrenomyeloneuropathy ...... 338 Metachromatic Leukodystrophy...... 340 Krabbe Disease...... 341 Pelizaeus-Merzbacher Disease ...... 342 Alexander Disease ...... 343

xiii Non-Neoplastic Diseases of the Central Nervous System

Canavan Disease ...... 345 Vanishing White Matter Disease...... 345 Other Rare Leukodystrophies...... 346 Mitochondrial Encephalopathies...... 349 Other Metabolic Diseases...... 349 13. Seizure Disorders and Malformations ...... 355 Hippocampal Sclerosis ...... 355 Malformative Lesions...... 360 Cortical Dysplasia ...... 360 Cerebral Heterotopia...... 366 Hemimegalencephaly ...... 371 Meningioangiomatosis...... 374 Other Hamartomas...... 376 Tuberous Sclerosis...... 377 Sturge-Weber Syndrome...... 386 Rasmussen Syndrome...... 389 Chaslin Gliosis, Alexander Disease, and Trauma...... 392 Neural Tube Closure Abnormalities...... 393 Anterior Neural Tube Closure Abnormalities: Cephalocele, Encephalocele, and Nasal Glioma...... 394 Caudal Neural Tube Closure Abnormalities: Myelomeningocele and Spinal Meningocele...... 397 Spina Bifida Occulta: Tethered Cord Syndrome, Dermal Sinuses, and Spinal Lipomas...... 403 14. Reaction to Neoplasms and Antineoplastic Therapies...... 413 Reaction to Gliomas...... 413 Diffuse Gliomas...... 413 Well-Demarcated Gliomas ...... 414 Optic Nerve Glioma ...... 415 Reaction to Lymphoma and Steroid Therapy...... 416 Reaction Adjacent to Meningiomas...... 418 Reaction to Other Neoplasms ...... 419 Reaction to Antineoplastic Therapies ...... 420 Cerebral Radiation Damage...... 420 Reaction to Chemotherapy...... 426 Disseminated Necrotizing Leukoencephalopathy...... 426 Reaction to Gene Therapy ...... 428 Index ...... 431

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