Table of Contents

Introduction: Normal Development and Basic Reactions 1

1. Gross and Microscopic Development of the Central .... 2

Timing of Early Embryonal Landmarks 2. — Mass Growth of the 3. — Cerebral Gyri 4. — Lamination of 4. — Superficial Granular Layer 5. — Cells of Cajal-Retzius 5. — Ammon's Horn 5. — Periventricular Germinal Layer 6. — Volume of 7. — Myelination and Development of 7. — Myelination 8. — Regional Timing of Myelination 8. — Basal Ganglia 9. — Mineralization of Cerebral Tissue 9. — Ventricular System 10. — Brain Stem Nuclei 12. — Melanization of Nuclei 12. — 12. — 16. — References 17.

2. Some Features of Basic Reactions Characteristic for Immature Nervous Tissue 21

Reaction of Immature Nervous Tissue to Necrosis 21. — Age-Dependent Variation in Anoxic Tissue Damage 21. — Anoxic Neuronal Necrosis 21. — Myelination Gliosis 22. — Reactive Gliosis 22. — Fibrillary Gliosis 23. — Differentiation of in the Germinal Layer 23. — Metabolic Astrocytosis 23. — Macrophage Responses 24. — References 24.

First Part: Acquired Lesions in Newborns and Infants 27

3. Porencephaly, , Multicystic Encephalopathy 28

Porencephaly 28. — Hydranencephaly 31. — Basket 34. — Hydranen­ cephaly or Porencephaly Related to Fetal Infections 35. — Hydranencephaly with Proliferative Vasculopathy 35. — Cavitated Cerebral Lesions in Twins 35. — Multicystic Encephalopathy 36. — Global Hemispheric Necrosis in Infants 38. — Pathogenetic Considerations 39. — References 40.

4. Hemorrhages in Asphyxiated Premature Infants 44

Subependymal and Intraventricular Hemorrhages 45. — Choroid Plexus Hemorrhages 47. — Subarachnoid Hemorrhages 49. — Subpial Hemorrhages 49. — Hemorrhages into the Falx 50. — Cerebellar Hemorrhages 50. — Hemorrhages at Other Sites 51. — Residual Lesions 52. — Posthemorrhagic 53. — Other Residua 54. — Pathogenetic Considerations 54. — References 55.

http://d-nb.info/881184314 VIII Table of Contents

5. Lesions of Traumatic Birth and Other Causes of Hemorrhage

Intradural Hemorrhages 59. — Lacerations of Tentorium or Falx 59. — Bone Injuries 60. — Epidural and Subdural Hemorrhages 61. — Embolism of Cere­ bral Tissue 61. — Injuries of the Spinal Cord 61. — Intracerebral Hematomas 62. — Hemorrhagic Disease of the Newborn 62. — Erythrocyte Disorders 64. — Herniation of Cerebral Tissue from Increased Intracranial Pressure 64. — References 66.

6. Perinatal Lesions of White Matter

Periventricular Infarcts (Periventricular Leukomalacia) 69. — Gross and Mi­ croscopic Features of Periventricular Infarcts 70. — Hemorrhages into Infarcts 72. — Residual Lesions of Periventricular Infarcts 72. — Differential Diagno­ sis of Periventricular Cavitated Lesions 74. — Pathogenetic Considerations 74. — Subcortical Infarcts 74. — Lesions in Areas of Primary Myelination 75. — Perinatal Telencephalic Leukoencephalopathy 75. — Cerebral White Matter Hypoplasia 75. — Diffuse Fatty Change ofWhite Matter 75. — References 78.

7. Perinatal Lesions of Gray Matter

Ulegyria of Cerebral Cortex - Definition 82. — Acute and Subacute Lesions of Ulegyria 84. — Residual Lesions of Ulegyria 84. — Regional Distribution of Ulegyria 85. — Associated Cerebellar Lesions 86. — Status Marmoratus of Basal Ganglia - Definition 86. — Early Lesions of Status Marmoratus 87. — Late Lesions of Status Marmoratus 87. — Association of Status Marmoratus with Other Lesions 89. — Nature of the Lesions in Status Marmoratus 89. — Symmetrical Thalamic Sclerosis in Infants 89. — Other Lesions of Basal Ganglia 89. — Lesions Causing Specific Sensory Defects 90. — Pontosubicular Necrosis - Definition 90. — Lesions of Pontosubicular Neuron Necro­ sis 91. — Pathogenetic Considerations on Perinatal Asphyxial Cerebral Damage 92. — References 94.

8. Postnatal Lesions of Gray Matter

Cardiac Arrest Encephalopathy 98. — Spinal Cord Necrosis 99. — Retrolental Fibroplasia 99. — Hypoglycemic Lesions 100. — Sudden Infant Death Syn­ drome 101. — Hemorrhagic Shock Encephalopathy 101. — Postconvulsive Brain Damage - General Aspects 101. — Postconvulsive-postanoxic Diffuse Cerebral Cortical Sclerosis - Definition of Lesions 102. — Postconvulsive Cerebral Damage - Clinical Course and Types of Lesions 102. — Hemiatrophy 103. — Cerebellar Lesions 105. — Patterns of Transneuronal Degeneration- Crossed Cerebellar Atrophy 106. — Aplasia Versus Atrophy of the Cerebellar Granular Layer 107. — Superficial Siderosis 108. — Familial Degeneration of the Pallidonigral System 110. — Infantile Bilateral Striatal Necrosis 110. — Congenital Pick Cell Encephalopathy 111. — References 111. Table of Contents IX

9. Kernicterus (Bilirubin Encephalopathy) 115

Metabolism of Bilirubin 115. — Etiologies of Kernicterus 116. — Gross and Microscopic Features of Kernicterus 117. — Posticteric Encephalopathy 118. — Kernicterus, Status Dysmyelinisatus and Lesions of Perinatal Anoxia 120. — Pathogenetic Considerations 120. — References 122.

10. Arterial Diseases in Infancy 125

Occlusion of Stems of Major Cerebral Arteries in Newborns 125. — Smaller, Randomly Disposed Infarcts in Newborns 127. — Arterial Calcification in In­ fants 128. — Disseminated Vascular Disease in the Congenital Rubella Syn­ drome 129. — Secondary Changes in Atrophic Arteries near Residual Perina­ tal Lesions 130. — Vasculo-occlusive Processes in Childhood 130. — Moya- moya Disease 131. — Vasculo-occlusive Disease in Homocystinuria 132. — Fibromuscular Dysplasia 132. — Dissecting Aneurysms of Cerebral Arteries 133. — Congenital Aneurysms of Cerebral Arteries 133. — References 134.

11. Thrombosis of Intracranial Sinus and Veins 138

Phlebothrombosis Complicating General Diseases 138. — Gross and Micro­ scopic Features of Phlebothrombosis 139. — Residual Lesions of Phlebo­ thrombosis 141. — Pathogenetic Considerations 143. — Thrombophlebitis from Local Propagation of Infections 144. — References 145.

12. Cerebral Lesions in Congenital Cardiac Disease 147

Abscesses 147. — Phlebothrombosis 148. — Infarcts 148. — Aneurysms 149. — Other Lesions 149. — Subendocardial Fibroelastosis 150. — References 150.

13. Craniocerebral Trauma in Infancy 152

Cerebral Lesions from Blunt Trauma in Early Infancy 152. — Subdural Hema­ tomas 153. — Widening Fracture of Childhood 153. — References 155.

14. Infections of the Fetus 156

Rubella Embryopathy 156. — Generalized Cytomegalic Inclusion Disease 158. — Other Viral Infections 160. — Toxoplasmosis 161. — Connatal Syphilis 164. — HTLV-III Virus (AIDS) 165. — Experimental Malformations Pro­ duced by Fetal Infections and Their Bearing on Human Disease 165. — Ref­ erences 166.

15. Purulent Leptomeningitis in Newborns and Infants 169

Neonatal Leptomeningitis 169. — Gross and Microscopic Features of Neonatal Leptomeningitis 170. — Postmeningitic Encephalopathy 173. — X Table of Contents

Pathogenetic Considerations 174. — Neonatal Listeriosis 174. — Intrauterine Meningitis 175. — Leptomeningitis in Infants 175. — Subdural Effusions in Meningitis 176. — Postmeningitic Lesions in Infants 176. — Abscesses and Empyemas 177. — References 177.

16. Meningoencephalitic Processes in the Peri- and Postnatal Periods, Including CNS Involvement by some Hematologic Diseases 180

Candida 180. — Mucor 182. — Aspergillus 182. — Cryptococcus 182. — Coc- cidioides 182. — Helminths 182. — Herpes Simplex 183. — Coxsackie Virus 184. — Poliomyelitis 185. — Aseptic Meningitis due to Enteroviruses 186. — Arthropod-borne Viruses 186. — Unclassified Chronic Encephalitis 186. — Tuberculosis 186. — HTLV-III Virus (AIDS) 187. — Hypo- and Agamma­ globulinemia 187. — Chronic Granulomatous Disease of Childhood 187. — Chediak-Higashi Disease 190. — Familial Lymphohistiocytosis (Erythro- phagocytic or Hemophagocytic Lymphohistiocytosis or Reticulosis) 192. — References 194.

17. Subdural Hematomas, Hygromas and Effusions 198

Structure and Reactions of the Subdural Space 198. — Subdural Hemorrhage in Infancy 200. — Supratentorial Hematomas 200. — Infratentorial Hematomas 201. — Pathology of Chronic Subdural Hematomas 201. — Sub­ dural Hygromas 203. — Chronic Subdural Hematomas and Hydrocephalus 203. — Subdural Hemorrhage upon Dehydration 204. — Chronic Subdural Hematomas Coexisting with Atrophic Hemispheric Lesions 204. — Benign Subdural Effusions 205. — Subdural Effusions in Leptomeningitis 205. — Traumatic Subdural Effusions 205. — Subdural Hemorrhages in General Diseases 206. — Congenital Subdural Cysts 206. — Pathogenetic Consider­ ations 206. — References 207.

18. Meningeal Cysts 209

Arachnoid and Glioependymal Cysts - General Features and Classification 209. — Structure of Arachnoid Cysts 209. — Structure of Glioependymal Cysts 210. — Topographic Survey: Cysts of the Cerebral Hemispheres 211. — Intracerebral Cysts 213. — Basal Midline Cysts 213. — Supracollicular and Paramesencephalic Cysts (Cysts of Cisterna Ambiens) 214. — Retrocerebellar and Basal Infratentorial Cysts 214. — Spinal Cysts 215. — Syndromes with Arachnoid or Glioependymal Cysts 216. — Choroid Plexus Cysts 216. — Dural Cysts 216. — References 217.

19. Hydrocephalus - Basic Concepts and General Pathology 220

Circulation of CSF in Small, Primitive Brains 220. — Circulation of CSF in Large Brains 221. — CSF and Extracellular Tissue Compartment 222. — Pathophysiology of Disturbed CSF Circulation 222. — Compensatory Mecha­ nisms of CSF Resorption 223. — Changes in Production of CSF 223. — Effects of CSF Composition 223. — Effects of Pressure Pulses 224. — General Pathol­ Table of Contents XI

ogy of Hydrocephalus 224. — Redundant Gyration 225. — Secondary At­ rophy 225. — Secondary Cortical Defects and Diverticles 226. — Postshunting Changes 226. — References 227.

20. Hydrocephalus - Special Pathology 231

Hypersecretory Hydrocephalus 231. — Local Entrapment of Lateral Ventri­ cles 232. — Obstruction of the Foramen Monro 232. — Obstruction of the Third Ventricle 232. — Anatomy and Development of the Aqueduct 233. — Congenital Versus Acquired Obstruction of the Aqueduct - Definitions 234. — Secondary Hydrocephalic Aqueduct Obstruction 236. — Congenital Sex- Linked Stenosis of the Aqueduct 236. — Congenital Atresia of the Aqueduct 237. — Gliotic Obstruction of the Aqueduct 237. — Septum of the Aqueduct 238. — Experimental Obstruction of the Aqueduct 238. — Compression of the Aqueduct by Other Lesions 238. — Obstruction of the Cerebellar Foramina 238. — Obstruction by Impaction into the Foramen Magnum 239. — Noncanalization of the Subarachnoid Space 239. — Subarachnoid Obstruction by Heterotopic Tissues 240. — Secondary Fibrotic Obstruction of the Sub­ arachnoid Space 240. — Diseases of Arachnoid Granulations 240. — Func­ tional Impairment of the Absorption of CSF 241. — Increased Venous Pres­ sure and Hydrocephalus 241. — Hydrocephalus Associated with Dysplasia of Cranial Bones 242. — Disturbances of Intracranial Pressure Induced by an Abnormal Supply of Vitamin A 242. — References 243.

Second Part: Malformations 247

21. and Related Spinal Lesions 248

Spina Bifida: Classification and Biologic Statistics 248. — Clinical Features of Spina Bifida 249. — Bone and Associated Lesions of Spina Bifida 250. — Spina Bifida Occulta 250. — Spina Bifida Cystica 250. — Myelocystocele 253. — Tethering of the Spinal Cord 254. — 254. — Hydromy- elia 255. - Dermoid Sinus 255. — Pathogenetic Considerations 256. - Refer­ ences 259.

22. Forms of Hindbrain Crowding, Including the Arnold- . 263

Clinical Features of Hindbrain Crowding 263. — Infantile Versus Adult Le­ sions 264. — Pathology of the Arnold-Chiari Malformation 264. — Pathoge­ netic Considerations 269. — Chronic Ascending Herniations 270. — Chronic Tonsillar Herniations 271. — References 274.

23. , , and Related Lesions, Syndromes with Encephaloceles 277

Anencephaly 277. — Gross Features of Anencephaly 278. — 279. — Microscopic Features of Anencephaly 279. — Acalvaria 282. — XII Table of Contents

Encephaloceles and Cranial Meningoceles 282. — Typical Sites of En­ cephaloceles 282. — Pathology of Encephaloceles 283. — Pathology of Menin­ goceles 285. — Intradiploic Heterotopias of Neural Tissue 285. — Frontonasal Dysplasia (Median Cleft Face Syndrome) 285. — Meckel Syndrome 285. — Occasional Association of Encephaloceles or Anencephaly with Other Mal­ formations or Malformation Syndromes 286. — Amniotic Band Syndrome 286. — Apert Syndrome 286. — Cantrell-Haller-Rawitsch Syndrome 286. — Cryptophthalmos Syndrome 286. — Knobloch Syndrome 286. — Van Voss Syndrome 286. — Dyssegmental Dwarfism 287. — Hemifacial Microsomia/ Goldenhar-Gorlin Syndrome 287. — References 287.

24. Ventral Dysraphic and Various Sacral Lesions 291

Neurenteric (Enterogenic) Cysts 291. — Cystic Teratomas (Teratomatous Cysts) 293. — Anterior Sacral Meningoceles 293. — Occult Intrasacral Menin­ goceles 293. — References 294.

25. Disturbances in Bulk Growth: , Micrencephaly, Atelencephaly and Others 296

Megalencephaly - Definitions 296. — Upper Range of Brain Weight 296. — Megalencephaly Syndromes 296. — Pathology of Megalencephaly 297. — 297. — Quasi-neoplastic Forms of Megalencephaly 299. — Pathogenesis of Megalencephaly 299. — Micrencephaly-Definitions 299. — Clinical Features of Micrencephaly 299. — Pathology of Micrencephaly 300. — Pathogenesis of Micrencephaly 301. — Atelencephaly (Atelencephalic ) 302. — Fetal Alcohol Syndrome 302. — Syndromes with Microcephaly 302. — References 306.

26. Dysplasias of the Cerebral Hemispheres 309

Arhinencephaly, , Olfactory Aplasia 309. — Clinical Fea­ tures of Arhinencephaly 309. — Pathologic Findings of Arhinencephaly 310. — Pathogenesis 313. — Combined and Overlapping Cerebral Malformations 314. — Malformations of the Chiasma Opticum 315. — Opticoseptal (Sep- tooptic) Dysplasia 315. — Pituitary Aplasia 316. — Duplication of Pituitary Gland Callosal Agenesis (a Syndrome?) 316. — Hydrolethalus Syndrome 316. — Agenesis of the Corpus Callosum 317. — Aicardi Syndrome (Agenesis of the Corpus Callosum, Infantile Spasms and Ocular Anomalies) 321. — Partial Callosal Agenesis with Seizures and Retardation (Menkes) 321. — Sensorimo­ tor Neuropathy with Agenesis of the Corpus Callosum (Andermann) 321. — Agenesis of the Corpus Callosum with Bouts of Hypothermia 321. — Callosal Defects Other than Agenesis 322. — Colpocephaly 322. — Dorsal Fornix 322. — Absence of the Septum Pellucidum 322. — Cysts of the Septum Pellucidum 322. — Temporal Lobe Dysplasia in Tanatophoric Dwarfism or with Clover- leaf Skull 325. — Duplication Malformations 325. — References 326. Table of Contents XIII

27. Dysplasias of Cerebral Cortex 330

Agyria () and 330. — Laminar Heterotopias 333. — Nodular Heterotopias 334. — Multiple Nodular Heterotopias in a Familial Syndrome of Amentia and Ventricular Calcifications 335. — Scattered Sub­ cortical 335. — 335. — Agyria-Polymicrogyria Pat­ terns 338. — Syndromes of Cerebro-Ocular Dysplasia and Muscular Dys­ trophy 339. — Nodular Cortical Dysplasia 340. — Leptomeningeal Glioneuronal Heterotopias 341. — Meningeal Heterotopia of Striated Muscle 341. — Persistence of the Subpial Granular Layer 341. — Persistence of Hor­ izontal Cells of Cajal 341. — Columnar Arrangement of Nerve Cells 342. — Archicortical Laminar Structure 342. — Focal Dysplasia of the Cerebral Cor­ tex in 342. — Abnormal Gyration of Malformed Brains 342. - Refer­ ences 343.

28. Dysplasias of Cerebellum 347

Cerebellar Development as a Guide to the Classification of Cerebellar Dysplasias 347. — The Dandy-Walker Malformation 347. — Joubert Syn­ drome 351. — Aplasia of Vermis with Occipital (Tectocerebel- lar Dysraphia) 352. — 353. — Other Patterns of Vermis Aplasia 354. — Neocerebellar Aplasia and Total Cerebellar Aplasia 354. — Atresia of the Fourth Ventricle 357. — Atresia of Cerebellar Foramina 357. — References 359.

29. Dysplasias of Cerebellar Cortex 361

Development of Cerebellar Cortex 361 — Principles of Classification 361. — Heterotopias 361. — Dysplasias of Cerebellar Nuclei 362. — Trivial Dysplasias in Newborns 363. — Focal and Diffuse Cortical Dysplasias 363. — Persistence of the Superficial Granular Layer 365. — Lesions from Selective Damage to the Superficial Granular Layer - Basic Concepts 366. — Granular Layer Aplasia 367. — Diffuse Hypertrophy of Cerebellar Cortex (Lhermitte- Duclos) 369. — References 370.

30. Dysplasias of Brain Stem and Spinal Cord 372

Dysplasias of the Inferior Olivary Nuclei 372. — Anomalies of Crossing of the Corticospinal Tracts 375. — Aplasia of the Corticospinal Tracts 376. — Hyper­ trophy of the Corticospinal Tracts 376. — Aplasia of the Dorsal Spinal Tracts 377. — Congenital Facio- and Ophthalmoplegia (Mobius Syndrome) 378. - Arthrogryposis multiplex congenita 378. — Arthrogryposis with Pena-Shokeir Syndrome 379. — Arthrogryposis with Lesions of Motor Neurons 379. — Ar­ throgryposis with Malformations or Degenerative Lesions 379. — Arthro­ gryposis with Severe Encephaloclastic Lesions 380. — Thalidomide-induced Deformities 380. — Congenital Absence of Abdominal Muscles (Prune Belly Syndrome) 380. — Sacral Agenesis 380. — The Floppy Infant Syndrome 382. — Spinal Cord Changes in Congenital Hereditary Sensory Neuropathies 382. — References 384. XIV Table of Contents

31. Dysplasias in Chromosome Anomalies 387

Trisomy 21 - Down Syndrome (Mongolism) 387. — Trisomy 22; 389. — Trisomy 18 (Edwards Syndrome) 389. — Other Anomalies of Chromosome 18 390. — Trisomy 13 (Patau Syndrome) 390. — 13q Syndrome 391. — Trisomy 9; 391. — Loss of the Short Arm of Chromosome 4 (Wolf-Hirschhorn Syndrome) 391. — Sex Chromosome Anomalies 391. — References 392.

32. Dysplasias ofCerebral Vessels 395

Development of Cerebral Vasculature 395. — Persistent Fetal Meningeal Vas­ cularization 395. — Persistence of the Primitive Trigeminal Artery 396. — Per­ sistence of the Primitive Hypoglossal Artery 397. — Agenesis of the Internal Carotid Artery 397. — Arteriovenous Aneurysm of the Vein of Galen 397. — Shunting of Arteries into the Intracranial Sinus 399. — Diffuse Meningocere- bral Angiodysplasia 399. - Involvement of in Multiple Neonatal Angiomata 401. — Arteriovenous Malformations 401. — Refer­ ences 402.

Third Part: Metabolic Diseases 405

33. Diseases of Carbohydrate 406

Glycogen Storage Diseases - General Comments and Classification 406. — Glycogenosis Type II (Pompe Disease); Acid Maltase Deficiency 406. — Glycogenosis Type IV 409. — Glycogenosis Type VIII 409. — Galactosemia 409. — Aspartylglucosaminuria 410. — Fucosidosis 410. — a-Mannosidosis 410. — Carpine-/3-Mannosidosis 411. — Mucopolysaccharidoses (Glucos- aminoglycan Storage Diseases) 411. — Sialidosis (a-Neuraminidase Deficien­ cy) 418. — I-Cell Disease (Mucolipidosis II) 420. — Mucolipidosis III 420. — References 420.

34. Sphingolipidoses 425

n an Types of GM2"ga gliosidosis 425. — Infantile GM2-g gli°sidosis 427. —

Juvenile G [^-gangliosidosis 427. — Pathology of GM2-gangliosidoses 428. —

GMrgangliosidosis 433. — GM3-gangliosidosis 435. — Niemann-Pick Disease 435. — Juvenile Dystonic Lipidosis 437. — Storage of Ceramide Lactoside 437. — Gaucher Disease 437. — References 441.

35. Ceroid-Lipofuscinosis and Miscellaneous Lipidoses 448

Neuronal Ceroid-Lipofuscinosis 448. — Clinical Course of Ceroid-Lipofus- cinosis 449. — Pathology of Ceroid-Lipofuscinosis 449. — Pigment Variants 455. — Congenital Amaurotic Idiocy 455. — Cephalin Lipidosis 456. — Lac- tosylceramidosis 456. — Wolman Disease 456. — Storage Disease with Os­ teopetrosis 457. — References 457. Table of Contents XV

36. Metachromatic Leukodystrophy (Sulfatase A Deficiency) and Multiple Sulfatase Deficiency 461

Types of Arylsulfatase Deficiencies 461. — Pathology of Metachromatic Leukodystrophy 462. — Pathogenetic Considerations 465. — Multiple Sul­ fatase Deficiency (O-Variant) 466. — References 467.

37. Globoid Cell Leukodystrophy 470

Clinical Course of Globoid Cell Leukodystrophy 470. — Pathology of Globoid Cell Leukodystrophy 471. — Pathogenetic Considerations 474. — References 475.

38. Peroxisomal Diseases 478

The Historical Concept of Schilder Disease 478. — Adrenoleukodystrophy/ Adrenomyeloneuropathy 479. — Neonatal Adrenoleukodystrophy 482. — Cerebro-Hepato-Renal Syndrome of Zellweger 484. — Hyperpipecolic Acidemia 485. — Infantile Refsum Disease 486. — References 486.

39. Mitochondrial Diseases 490

Introduction 490. — General Histopathology of Mitochondria 492. — Princi­ ples of Classification ofMitochondriopathies 493. — Group I: Defects of Pyru­ vate Utilization 494. — Subacute Necrotizing Encephalomyelopathy (Leigh Disease) 496. — Infantile Wernicke Disease 498. — Group II: Defects of Fatty Acid Utilization 499. — Group III: Defects of Oxidative Phosphorylation Coupling 499. — Group IV: Defects of the Respiratory Chain - Subclassifica- tion 499. — Fukuhara Myoclonus Syndrome with Ragged-Red Fibers 499. — Fatal Infantile Mitochondrial Myopathy 500. — Menkes Disease - Trichopoliodystrophy 500. — Progressive Cerebral Poliodystrophy (Alpers Disease) 502. — Adolescent or Adult Mitochondrial Myoencephalopathies 503. — Retardation, Myopathy and Multiple Cerebral Infarcts 504. - Other Syndromes 504. — References 504.

40. Spongy Myelinopathies 510

Introduction 510. — Differential Diagnosis of Spongy Tissue States 510. — Spongy Degeneration of the Central Nervous System (Van Bogaert-Bertrand or Canavan Disease) 511. — Pathology of Spongy Degeneration 511. —

Pathogenetic Considerations 515. — Kearns-Sayre Syndrome 517. — GM3- gangliosidosis 518. — Reye Syndrome 518. — Hexachlorophene ­ opathy 519. — Other Neurotoxic Spongy Myelinopathies 519. — References 520.

41. Diseases of Amino Acid Metabolism 524

General Comments 524. — (Phenylpyruvic Oligophrenia) 524. — Hyperprolinemia 526. — Tyrosinosis 526. — Glutaric Acidemia 527. — Maple Syrup Urine Disease (Branched-Chain Ketoaciduria) 527. — Oast XVI Table of Contents

House Disease 528. — Hyperglycinemia 528. — Gamma-Aminobutyric Acid Transaminase Deficiency 528. — Homocystinuria 528. — Sulfite Oxidase De­ ficiency 529. — Combined Sulfite and Xanthine Oxidase Deficiency 529. — Hartnup Disease 529. — Diseases of the Urea (Krebs-Henseleit) Cycle 530. — References 531.

42. Patchy Myelinopathies: Pelizaeus-Merzbacher Disease, Cockayne Syndrome, and Others, also Including a Review of Primary Cerebral Mineralizations 534 Pelizaeus-Merzbacher Disease - Classic Infantile or Late Infantile Form 534. — Pelizaeus-Merzbacher Disease - Connatal Form 536. — Intermediate Forms of Pelizaeus-Merzbacher Disease 537. — Pelizaeus-Merzbacher Dis­ ease - Adult Form 537. — Patchy Myelin Defects in Malformed Brains 537. — Unclassified Sudanophilic Leukodystrophic Processes of Infancy 537. — Cockayne Syndrome 537. — Syndromes Similar to Cockayne Syndrome 539. — Patients Without Basal Ganglia Mineralization 539. — Patients with En­ cephalopathy and CSF Pleocytosis 539. — Patients with Cerebellar Minerali­ zation, Dysplasias and Arachnoid Cysts 540. — White Matter Changes and Mineralization upon Chemotherapy and X-Irradiation 540. — Membranous Lipodystrophy (Nasu-Hakola Disease) 540. — Differential Diagnosis of Cere­ bral Mineralizations 540. — References 542.

43. Alexander Disease 546

Clinical Features of Alexander Disease 546. — Pathology of Alexander Dis­ ease 547. — Pathogenetic Considerations 550. — References 550.

44. Axon Dystrophies 552

Axon Swellings - Basic Concepts 552. — Classification of Axon Dystrophies 552. — Age-Dependent Axon Dystrophy 553. — Precocious Axon Dystrophy in Mucoviscidosis and Biliary Atresia 554. — Infantile Neuroaxonal Dys­ trophy (Seitelberger Disease) 555. — Clinical Features of Neuroaxonal Dys­ trophy 555. — Pathology of Neuroaxonal Dystrophy 555. — Infantile Haller- vorden-Spatz Disease 557. — Axon Dystrophy Associated with Various Dis­ eases 558. — References 558.

Subject Index 561