Front Cover 1
Neurology and Clinical Neuroscience 4
Copyright Page 5
CONTENTS 22
SECTION I: Consciousneess, Cognitiun, and Special Senses 28
CHAPTER 1. Clinical Assessment of Mental Status 29
NEUROCOGNITIVE HISTORY 29
FUNCTION IN NEUROCOGNITIVE DOMAINS 31
FUNCTION IN NEUROBEHAVIORAL DOMAINS 33
OTHER ABNORMAL BEHAVIORS 35
RELEVANT HISTORY 36
NEUROBEHAVIORAL RATING SCALES 37
NEUROCOGNITIVE EXAMINATION 37
STANDARDIZED COGNITIVE ASSESSMENT INSTRUMENTS 42
COGNITIVE ASSESSMENT BEYOND THE BEDSIDE 43
ASSESSING THE UNASSESSABLE PATIENT 43
THE NEUROCOGNITIVE FORMULATION 43
CONCLUSION 44
CHAPTER 2. Principles of Neuropsychometric Assessment 49
COGNITIVE DOMAINS AND NEUROPSYCHOLOGICAL TESTS 49
BASIC PRINCIPLES OF PSYCHOMETRICS 50
MEASURING DEFICITS AND CHANGES 54
STRATEGIES IN NEUROPSYCHOLOGICAL ASSESSMENT 55
OPTIMAL USE OF NEUROPSYCHOLOGY 55
SUMMARY 56
CHAPTER 3. Disorders of Language 58
LANGUAGE PRODUCTION 58
APHASIA SYNDROMES 60
PRIMARY PROGRESSIVE APHASIA 65
ACQUIRED DISORDERS OF READING: THE ALEXIAS 66
ACQUIRED NEUROGENIC AGRAPHIA 67
CHAPTER 4. Disorders of Memory 70
DEFINITIONS AND TERMINOLOGY 70
NEUROBIOLOGY OF LEARNING AND MEMORY 72
ASSESSMENT OF MEMORY 74
SYNDROMES OF MEMORY DISTURBANCE 75
CHAPTER 5. Higher Visuoperceptual Disorders and Disorders of Spatial Cognition (Excluding Hemi-Inattention/Neglect) 86
EPIDEMIOLOGY 86
THE TWO-SYSTEMS APPROACH TO HIGHER VISUOSPATIAL FUNCTIONING 86
ANATOMY AND PHYSIOLOGY 86
DIAGNOSIS 91
TREATMENT AND ASSISTANCE 93
CONCLUSIONS 95
CHAPTER 6. The Neglect Syndrome 100
TERMINOLOGY AND PHENOMENOLOGY 100
EXAMINATION FOR THE NEGLECT SYNDROME 102
ANATOMICAL SUBSTRATE, AND THEORIES OF CAUSATION 104
THE FREQUENCY AND IMPORTANCE OF NEGLECT 106
TREATMENT OF THE NEGLECT SYNDROME 107
CONCLUSION 107
CHAPTER 7. Executive Function and Its Assessment 110
EXECUTIVE FUNCTION 110
FORMAL ASSESSMENT OF EXECUTIVE FUNCTION 113
QUALITATIVE OBSERVATIONS AND BEDSIDE TESTS 117
CONCLUSION 118
CHAPTER 8. Coma and Brain Death 124
CONSCIOUSNESS 124
COMA 125
BRAIN DEATH 133
CHAPTER 9. Thepersistent Vegetative State (Prolonged Postcoma Unresponsiveness) and Posthypoxic Brain Injury 144
CRITERIA 144
EPIDEMIOLOGY 145
PATHOLOGY 145
DIAGNOSIS 146
NEUROPHYSIOLOGICAL ASSESSMENT 146
SOMATOSENSORY EVOKED POTENTIALS 147
BIOCHEMICAL MARKERS 150
IMAGING STUDIES 150
PROGNOSTIC, MANAGEMENT, AND ETHICAL CONSIDERATIONS 150
CHAPTER 10. Autism and Attention Deficit/ Hyperactivity Disorder 156
EPIDEMIOLOGY 157
CLINICAL FEATURES 157
ETIOLOGY AND PATHOPHYSIOLOGY 159
TREATMENT 161
CONCLUSIONS AND RECOMMENDATIONS 162
CHAPTER 11. Delirium 168
DEFINITION 168
EPIDEMIOLOGY 168
RISK FACTORS 170
PATHOPHYSIOLOGY 172
CLINICAL FEATURES 173
MANAGEMENT 174
CONCLUSION 177
CHAPTER 12. Motor Speech and Swallowing Disorders 182
ANATOMY 182
DISORDERS OF MOTOR SPEECH 183
CLINICAL ASSESSMENT OF SPEECH 186
MANAGEMENT OF MOTOR SPEECH DISORDERS 187
NEUROGENIC DYSPHAGIA 188
CHAPTER13. Disorders of Smell and Taste 198
DISORDERS OF SMELL 198
DISORDERS OF TASTE 202
SECTION II: Sleep and Sleep Disorders 206
CHAPTER 14. The Physiology of Sleep 207
NATURE OF SLEEP 207
REGULATION OF SLEEP AND WAKEFULNESS 208
NEUROBIOLOGICAL CONTROLS OF WAKE AND SLEEP 209
SUMMARY 210
CHAPTER 15. Primary Disorders of Sleep 212
INSOMNIA 212
PERIODIC LIMB MOVEMENT DISORDER 216
EXCESS DAYTIME SLEEPINESS 217
NARCOLEPSY 220
IDIOPATHIC HYPERSOMNIA 222
KLEINE-LEVIN SYNDROME 222
IDIOPATHIC RECURRENT STUPOR 222
CIRCADIAN RHYTHM DISORDERS 222
PARASOMNIAS 223
CHAPTER 16. Sleep Apnea 230
OBSTRUCTIVE SLEEP APNEA-HYPOPNEA 230
CENTRAL SLEEP APNEA 234
CONCLUSIONS 236
SECTION III: Neuropsychiatry 240
CHAPTER 17. Tourette S Syndrome, Tics and Obsessive-Compulsive Disorders 241
TICS AND GILLES DE LA TOURETTE SYNDROME 241
OBSESSIVE-COMPULSIVE DISORDER 244
CHAPTER 18. Schizophrenia and Schizophrenia-Like Psychosis 250
SCHIZOPHRENIA 250
SCHIZOPHRENIA-LIKE PSYCHOSIS IN NEUROLOGICAL ILLNESS 255
CHAPTER 19. Affective Disorders 262
DEPRESSION 262
MANIA 266
APATHY 268
CHAPTER 20. Conversion and Dissociation Syndromes 276
PROBLEMS WITH DEFINITION 276
EPIDEMIOLOGY 277
CLINICAL FEATURES 277
PROGNOSIS 280
MANAGEMENT 280
SECTION IV: Neuro-Ophthalmology 286
CHAPTER 21. Examination of the Visual System 287
VISUAL ACUITY 287
VISUAL FIELD EXAMINATION 287
PUPILS 296
EYELIDS 298
OCULOMOTOR SYSTEM 298
EXAMINATION OF DIPLOPIA 299
CHAPTER 22. Genetic Causes of Blindness 301
HOW DO PATIENTS WITH NEURAL GENETIC BLINDNESS PRESENT? 301
CLASSIFICATION OF GENETIC DISEASE 301
AGE AT ONSET AND COURSE 302
EVALUATION 302
RETINAL DISEASES\u2014CONGENITAL 302
RETINAL DISEASES\u2014ONSET IN CHILDHOOD AND ADULTHOOD 304
OPTIC NERVE DISEASES\u2014CONGENITAL 305
OPTIC NERVE\u2014ONSET IN CHILDHOOD AND ADULTHOOD 306
RETINOPATHY AND OPTIC NEUROPATHY ASSOCIATED WITH SYSTEMIC AND NEURODEGENERATIVE DISEASE 307
RETINOPATHY AND OPTIC NEUROPATHY ASSOCIATED WITH DERMATOLOGICAL DISEASE, SKELETAL ANOMALIES, HEARING LOSS, OR RENAL DISEASE 309
CHAPTER 23. Optic Neuropathies 312
OPTIC DISC SWELLING WITHOUT VISUAL LOSS 312
SUDDEN VISUAL LOSS WITH AND WITHOUT OPTIC DISC SWELLING 313
INSIDIOUS VISUAL LOSS WITH OR WITHOUT OPTIC DISC SWELLING 317
OTHER OPTIC NEUROPATHIES 319
CONCLUSION 320
CHAPTER 24. Retinal Disease 322
UVEOMENINGEAL SYNDROMES 322
RHEUMATOLOGICAL DISEASES AND THE SYSTEMIC VASCULITIDES 324
MULTIPLE SCLEROSIS 325
INFECTIONS 326
MITOCHONDRIAL DISEASES 329
NEOPLASIA 330
MOVEMENT DISORDERS AND ATAXIA 332
MUSCLE DISEASES 332
PHACOMATOSES 333
CEREBROVASCULAR DISEASE 334
METABOLIC DISEASES IN CHILDREN 337
SECTION V: Neuro-Otology 344
CHAPTER 25. Examination of Hearing and Balance 345
HEARING EXAMINATION 345
BALANCE EXAMINATION 349
CHAPTER 26. Auditory System Disorders 356
CONDUCTIVE HEARING LOSS 356
SENSORINEURAL HEARING LOSS 356
CENTRAL HEARING LOSS 357
CAUSES OF CONDUCTIVE HEARING LOSS 357
CAUSES OF SENSORINEURAL HEARING LOSS 359
SUMMARY 360
CHAPTER 27. Vestibular System Disorders 364
DEFINITIONS 364
EPIDEMIOLOGY 364
VESTIBULAR ANATOMY AND PHYSIOLOGY 364
AGING AND THE VESTIBULAR SYSTEM 366
PERIPHERAL VESTIBULAR DISORDERS 367
DIAGNOSIS OF VESTIBULAR DISORDERS 369
BILATERAL VESTIBULAR FAILURE 373
CENTRAL VESTIBULAR DISORDERS 374
MANAGEMENT OF VESTIBULAR DISORDERS 375
CONCLUSION 377
SECTION VI: Autonomic Nervous System Diseases 380
CHAPTER 28. Orthostatic Hypotension 381
PATHOPHYSIOLOGY 381
DIAGNOSIS AND EVALUATION OF ORTHOSTATIC HYPOTENSION 382
CAUSES OF AUTONOMIC FAILURE 384
MANAGEMENT 385
CHAPTER 29. Bladder and Sexual Function and Dysfunction 389
BLADDER FUNCTION 389
BLADDER DYSFUNCTION 390
SEXUAL FUNCTION 393
CONCLUSION 395
CHAPTER 30. Primary Autonomic Failure 399
CLASSIFICATION 399
NEUROPATHOLOGY 399
CLINICAL PRESENTATION 401
LABORATORY ASSESSMENTS 405
THERAPY 409
SECTION VII: Motor System and Motor Diseases 422
CHAPTER 31. Organization: Pyramidal and Extrapyramidal System 423
THE EXTRAPYRAMIDAL MOTOR SYSTEMS 423
THE MOTOR CORTICES AND PYRAMIDAL SYSTEM 425
COMMENTS ON FUNCTION AND CONCLUSIONS 427
CHAPTER 32. Apraxia 429
LIMB APRAXIAS 429
DISTRIBUTION OF THE APRAXIAS IN OTHER BODY PARTS 439
CHAPTER 33. Tremor 444
CLINICAL DEFINITIONS 444
ENHANCED PHYSIOLOGICAL TREMOR 444
ESSENTIAL TREMOR 446
ORTHOSTATIC TREMOR 449
PARKINSONIAN TREMORS 449
DYSTONIC TREMOR SYNDROMES 451
CEREBELLAR TREMOR SYNDROMES 451
HOLMES' TREMOR 452
PALATAL TREMOR SYNDROMES 453
TREMOR SYNDROMES IN PERIPHERAL NEUROPATHY 453
PSYCHOGENIC TREMOR 454
DRUG-INDUCED AND TOXIC TREMORS 454
MYOCLONUS 455
CONCLUSIONS 455
CHAPTER 34. Myoclonus 462
CLASSIFICATION 462
CLINICAL FEATURES 462
UNDERLYING DISEASES 464
PHYSIOLOGICAL MECHANISMS 465
LABORATORY TESTS 466
EXPERIMENTAL MODEL 468
TREATMENT 468
CHAPTER 35. Dystonia 470
DEFINITION AND CLASSIFICATION 470
EPIDEMIOLOGY 470
CLINICAL FEATURES 471
INVESTIGATIONS 475
PATHOPHYSIOLOGY OF DYSTONIA 475
TREATMENT OF DYSTONIA 477
PAROXYSMAL DYSKINESIAS 479
CONCLUSIONS 480
CHAPTER 36. Gait Disturbances and Falls 482
LOCOMOTION, EQUILIBRIUM, AND THE SUPPORT SYSTEMS 482
ASSESSMENT OF GAIT 484
GAIT AND MENTAL FUNCTION 490
CUEING 493
SUMMARY 495
CHAPTER 37. Restless Legs Syndrome 498
CLINICAL FEATURES AND DEFINITION OF RESTLESS LEGS SYNDROME 498
EPIDEMIOLOGY 498
DIAGNOSTIC CRITERIA FOR RESTLESS LEGS SYNDROME 500
EVALUATION OF RESTLESS LEGS SYNDROME 501
DIFFERENTIAL DIAGNOSIS OF RESTLESS LEGS SYNDROME 503
TREATMENT 503
SECTION VIII: Spine and Spinal Diseases 514
CHAPTER 38. Spine and Spinal Cord: Developmental Disorders 515
NORMAL DEVELOPMENT OF THE NERVOUS SYSTEM 515
DEVELOPMENTAL DISORDERS AFFECTING THE SPINE 516
DEVELOPMENTAL DISORDERS AFFECTING THE SPINAL CORD AND NEURAL TISSUES 519
CONCLUSION 532
CHAPTER 39. Primary Myelopathies (Degenerative, Infective, Metabolic) 534
ACUTE MYELOPATHIES 534
CHRONIC MYELOPATHIES 535
CHAPTER 40. Spinal Disease: Neoplastic, Degenerative, and Infective Spinal Cord Diseases and Spinal Cord Compression 538
IMAGING 538
SPINAL CORD INFECTIONS 539
DEGENERATIVE DISEASES OF THE SPINAL CORD 549
TUMORS OF THE SPINAL CORD 553
SECTION IX: Cerebrovascular Disease 566
CHAPTER 41. Anatomy and Physiology of Cerebral and Spinal Cord Circulation 567
ANATOMY OF THE CEREBRAL CIRCULATION 567
CHAPTER 42. Ischemic Stroke: Mechanisms, Evaluation, and Treatment 578
DEFINITION 578
TRANSIENT ISCHEMIC ATTACK 578
ISCHEMIC STROKE 579
STROKE CLASSIFICATION BY MECHANISM (STROKE SUBTYPES) 579
CLINICAL SYNDROMES 583
STROKE EVALUATION 592
SECONDARY PREVENTION 601
CHAPTER 43. Intracranial Hemorrhage: Aneurysmal, Idiopathic, and Hypertensive 614
ANEURYSMAL INTRACRANIAL HEMORRHAGE 614
HYPERTENSIVE INTRACRANIAL HEMORRHAGE 617
IDIOPATHIC INTRACRANIAL HEMORRHAGE 618
CHAPTER 44. Arteriovenous Malformations of the Brain and Spinal Cord 622
BRAIN ARTERIOVENOUS MALFORMATION 622
SPINAL CORD ARTERIOVENOUS MALFORMATIONS 629
CONCLUSION 634
CHAPTER 45. Prothrombotic States and Related Conditions 636
THE HEMOSTATIC SYSTEM 636
PATHOLOGY OF EXCESSIVE HEMOSTASIS 636
NEUROLOGICAL CONSEQUENCES OF EXCESSIVE HEMOSTASIS 637
VESSEL WALL DEFECTS 638
STASIS 642
CHAPTER 46. Cerebral Venous Thrombosis 648
ANATOMY OF THE INTRACRANIAL VENOUS SYSTEM 648
EPIDEMIOLOGY 650
PATHOPHYSIOLOGY 650
DIAGNOSIS AND CLINICAL FEATURES 651
DIAGNOSTIC METHODS 652
RISK FACTORS 653
TREATMENT 655
PROGNOSIS 656
CONCLUSION 657
CHAPTER 47. Vascular Dementia 662
DEFINITIONS 662
EPIDEMIOLOGY 662
CLINICAL FEATURES 664
DIAGNOSIS 667
TREATMENT 668
PREVENTION 668
CHAPTER 48. Rehabilitation After Stroke 672
COMPLEX ORGANIZATIONAL INTERVENTIONS 672
MANAGEMENT OF NEUROLOGICAL IMPAIRMENTS 675
MANAGEMENT OF SYSTEMIC COMPLICATIONS 679
FUTURE DEVELOPMENTS 680
SECTION X: Epilepsy 688
CHAPTER 49. Developmental Defects and Pathophysiology 689
DEFINITION AND CLASSIFICATION 689
NEUROGENETICS 690
NEUROIMAGING 691
ELECTROPHYSIOLOGICAL-CLINICAL DATA AND RELEVANCE TO EPILEPSY SURGERY 695
CHAPTER 50. Clinical Spectrum 700
DEFINITIONS AND EPIDEMIOLOGY 700
CLINICAL APPROACH TO EPILEPTIC DISORDERS 701
EPILEPTIC SEIZURES 702
EPILEPSIES AND EPILEPTIC SYNDROMES 704
PROGNOSIS: FROM BENIGN CONDITIONS TO DEVASTATING DISEASES 706
CHAPTER 51. Genetics of Epilepsy 708
MONOGENIC INHERITED EPILEPSIES 708
COMPLEX INHERITANCE OF EPILEPSY 714
CONCLUSIONS 714
CHAPTER 52. Assessment and Management Principles 718
DIAGNOSIS STEP 1: DEFINING THE SEIZURE TYPE(S) 719
CONCLUSION 732
ACKNOWLEDGMENTS 733
CHAPTER 53. Drug Treatment 734
TREATMENT WITH ANTIEPILEPTIC DRUGS 734
COMMON CLINICAL SITUATIONS AND SPECIFIC SYNDROMES 740
LESIONAL EPILEPSY 741
SPECIAL ISSUES RELATED TO EPILEPSY IN WOMEN 742
TOXEMIA OF PREGNANCY 743
SEIZURES AND EPILEPSY IN ELDERLY PERSONS 744
MEDICATION WITHDRAWAL 744
KETOGENIC DIET 744
RESECTIVE SURGERY 744
PALLIATIVE PROCEDURES 745
COMPLEMENTARY AND ALTERNATIVE THERAPIES 745
CHAPTER 54. Management of Status Epilepticus 746
DEFINITION 746
CLASSIFICATION 746
INCIDENCE, ETIOLOGY, AND MORTALITY 748
PHYSIOLOGICAL CHANGES IN GENERALIZED CONVULSIVE STATUS EPILEPTICUS 749
PATHOPHYSIOLOGY OF NEURONAL INJURY 749
MANAGEMENT AND TREATMENT OF STATUS EPILEPTICUS 750
PHARMACOTHERAPY 751
REFRACTORY STATUS EPILEPTICUS 752
NEW PHARMACOLOGICAL DEVELOPMENTS 753
NONCONVULSIVE STATUS EPILEPTICUS 754
SECTION XI: Headache 760
CHAPTER 55. Headache Pathogenesis 761
ANATOMY OF HEADACHE 761
HEADACHE PAIN 761
PERIPHERAL MECHANISMS AND NOCICEPTOR ACTIVATION 762
SENSITIZATION IN MIGRAINE 763
PAIN MODULATION 763
GENETICS AND MIGRAINE 764
SUMMARY 764
CHAPTER 56. Migraine 766
EPIDEMIOLOGY 766
PATHOPHYSIOLOGY 766
DESCRIPTION OF THE MIGRAINE ATTACK 768
FORMAL DIAGNOSTIC CRITERIA 769
TREATMENT 770
PREVENTIVE TREATMENT 773
SUMMARY 777
CHAPTER 57. Tension-Type Headache 784
DEFINITION 784
EPIDEMIOLOGY 784
CLINICAL FEATURES 784
ETIOLOGY AND PATHOPHYSIOLOGY 784
TREATMENT 785
CONCLUSION AND RECOMMENDATIONS 787
CHAPTER 58. Chronic Daily Headache 790
EPIDEMIOLOGY OF THE CHRONIC DAILY HEADACHE 790
CLINICAL CHARACTERIZATION 790
PATHOPHYSIOLOGY 793
THE TREATMENT OF CHRONIC DAILY HEADACHE 794
CHAPTER 59. Trigeminal Autonomic Cephalalgias: Cluster Headache and Related Conditions 800
PATHOPHYSIOLOGY OF TRIGEMINAL AUTONOMIC CEPHALALGIAS 800
DIFFERENTIAL DIAGNOSIS OF TRIGEMINAL AUTONOMIC CEPHALALGIAS 801
CLUSTER HEADACHE 802
PAROXYSMAL HEMICRANIA 809
SHORT-LASTING UNILATERAL NEURALGIFORM HEADACHE ATTACKS WITH CONJUNCTIVAL INJECTION AND TEARING 811
SECONDARY SUNCT 811
CHAPTER 60. Other Secondary Headache Disorders 820
HEADACHE SECONDARY TO CEREBROVASCULAR DISORDERS 820
HEADACHE SECONDARY TO NONVASCULAR INTRACRANIAL DISORDERS 826
HEADACHE SECONDARY TO DISORDERS OF THE NECK OR CRANIAL STRUCTURES 828
HEADACHE SECONDARY TO INTRACRANIAL INFECTION 829
HEADACHE SECONDARY TO DISORDERS OF HOMEOSTASIS 829
CHAPTER 61. Idiopathic Intracranial Hypertension 834
DEFINITION 834
EPIDEMIOLOGY 834
CLINICAL FEATURES 834
DIAGNOSTIC TESTING 835
SECONDARY CAUSES 837
PATHOPHYSIOLOGY 837
TREATMENT 838
PROGNOSIS 840
CHAPTER 62. Low Cerebrospinal Fluid Headache 844
BACKGROUND AND TERMINOLOGY 844
ETIOLOGY OF SPONTANEOUS CEREBROSPINAL FLUID LEAKS 844
CLINICAL MANIFESTATIONS 844
CLINICAL MANIFESTATIONS OTHER THAN HEADACHES 844
DIAGNOSIS 844
MECHANISMS OF MAGNETIC RESONANCE IMAGING ABNORMALITIES 847
CONSIDERABLE VARIABILITY 848
TREATMENT 848
PROGNOSIS 849
COMPLICATIONS 849
CHAPTER 63. Hydrocephalus, Including Normal-Pressure Hydrocephalus 852
CEREBROSPINAL FLUID PRODUCTION, FLOW, AND ABSORPTION 852
HYDROCEPHALUS 852
NORMAL-PRESSURE HYDROCEPHALUS 857
CHAPTER 64. Trigeminal Neuralgia and Other Facial Pain 862
HISTORICAL CONSIDERATIONS 862
THE CLINICAL SYNDROME 862
TESTING 863
DIFFERENTIAL DIAGNOSIS 863
TREATMENT 864
COMPLICATIONS AND PITFALLS 867
CONCLUSIONS 867
SECTION XII: Neurodegenerative Diseases 872
CHAPTER 65. Alzheimer's Disease 873
DEFINITION 873
EPIDEMIOLOGY 873
RISK AND PUTATIVE PROTECTIVE FACTORS FOR ALZHEIMER'S DISEASE 873
PATHOLOGY 876
DIAGNOSIS 877
CHAPTER 66. Amyotrophic Lateral Sclerosis 886
BACKGROUND 886
CLINICAL FEATURES 887
DIFFERENTIAL DIAGNOSIS 889
AMYOTROPHIC LATERAL SCLEROSIS WITH ATYPICAL FEATURES 892
PATHOGENESIS 892
DIAGNOSTIC STUDIES 893
MANAGEMENT 895
CHAPTER 67. Huntington's Disease 906
HISTORY 906
GENETICS AND MOLECULAR PATHOGENESIS 906
CLINICAL FEATURES 907
COGNITIVE FEATURES 908
MOTOR FEATURES 907
PSYCHIATRIC FEATURES 908
OTHER FEATURES 908
VARIANTS 908
PATHOPHYSIOLOGY OF SIGNS AND SYMPTOMS 909
DIFFERENTIAL DIAGNOSIS 909
EVALUATION AND GENETIC TESTING 909
TREATMENT OPTIONS 909
PROGNOSIS 911
CHAPTER 68. Inherited Ataxias 914
BRIEF DESCRIPTION 914
EPIDEMIOLOGY AND RISK FACTORS 914
CLINICAL FEATURES 915
DIAGNOSTIC STRATEGY 919
EVALUATION, TESTS, AND LABORATORY FINDINGS 919
DIFFERENTIAL DIAGNOSIS 921
TREATMENT 921
SUPPORTIVE CARE AND LONG-TERM MANAGEMENT 922
PROGNOSIS 923
FUTURE CONSIDERATIONS 923
CHAPTER 69. Hereditary Spastic Paraplegias 926
EPIDEMIOLOGY 926
GENETIC CLASSIFICATION: MODE OF INHERITANCE AND HSP LOCUS 926
CLINICAL CLASSIFICATION: \ 926
NEUROPATHOLOGY: DISTAL AXON DEGENERATION INVOLVING LONGEST MOTOR AND SENSORY FIBERS IN THE CENTRAL NERVOUS SYSTEM 926
EMERGING CONCEPTS OF HSP PATHOGENESIS 928
NEUROLOGICAL EXAMINATION: UPPER MOTOR NEURON SIGNS IN THE LEGS; IMPAIRED VIBRATION SENSATION IN THE TOES 929
SYNDROME VARIABILITY 930
LABORATORY STUDIES, NEUROIMAGING, AND NEUROPHYSIOLOGICAL EVALUATION 931
DIAGNOSTIC CRITERIA 931
TREATMENT 932
PROGNOSIS 932
GENETIC COUNSELING 932
CONCLUSIONS 933
CHAPTER 70. Dementia with Lewy Bodies 938
HISTORICAL PERSPECTIVE 938
TERMINOLOGY 938
EPIDEMIOLOGY 938
CLINICAL FEATURES 938
DIAGNOSTIC CRITERIA 941
DIAGNOSTIC EVALUATION 941
MANAGEMENT 945
CONCLUSIONS AND FUTURE DIRECTIONS 950
CHAPTER 71. Parkinson's Disease 954
HISTORICAL PERSPECTIVE 954
EPIDEMIOLOGY 954
PATHOLOGY 954
CLINICAL FEATURES 963
DIFFERENTIAL DIAGNOSIS 964
INVESTIGATION 965
TREATMENT 966
NEUROPROTECTION 975
CHAPTER 72. Parkinson Plus Disorders 988
MULTIPLE SYSTEM ATROPHY 988
PROGRESSIVE SUPRANUCLEAR PALSY 995
CORTICOBASAL DEGENERATION 1000
CHAPTER 73. Frontotemporal Dementia 1010
CLINICAL FEATURES 1010
PATHOLOGY 1011
GENETICS 1012
CLINICAL VIGNETTES 1014
IMAGING 1018
THERAPY 1018
FUTURE DIRECTIONS 1018
SECTION XIII: Multiple Sclerosis and Demyelinating Disorders 1022
CHAPTER 74. Epidemiology and Genetics of Multiple Sclerosis 1023
DISEASE HETEROGENEITY 1023
POPULATION PREVALENCE 1023
FAMILIAL AGGREGATION 1025
SUSCEPTIBILITY GENES 1025
THE HUMAN LEUKOCYTE ANTIGEN GENE COMPLEX 1026
FUTURE DIRECTIONS 1027
CHAPTER 75. Pathophysiology of Multiple Sclerosis: Demyelination and Axonal Injury 1029
DEMYELINATION 1029
REMYELINATION 1030
ADAPTIVE CHANGES IN THE EXPRESSION OF ION CHANNELS IN DEMYELINATION 1031
PLASTIC CHANGES 1032
POSITIVE SYMPTOMS: AXONAL HYPEREXCITABILITY 1032
THE ROLE OF INFLAMMATION 1033
DISABILITY AND AXONAL DEGENERATION 1034
CHAPTER 76. Clinical Spectrum: Definition and Natural Progression 1042
DEFINITION 1042
CLINICAL PHENOTYPES OF MULTIPLE SCLEROSIS 1042
CLINICAL FEATURES OF MULTIPLE SCLEROSIS 1044
PROGRESSIVE MULTIPLE SCLEROSIS 1050
DISABILITY IN MULTIPLE SCLEROSIS 1051
PREDICTORS OF PROGNOSIS, LONG-TERM OUTCOME 1052
MORTALITY IN MULTIPLE SCLEROSIS 1053
CHAPTER 77. Investigations in Multiple Sclerosis 1058
BLOOD INVESTIGATIONS 1058
LUMBAR PUNCTURE 1058
RESEARCH PROTOCOLS 1064
ATROPHY 1066
NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 1066
MAGNETIC RESONANCE IMAGING DIAGNOSIS OF MULTIPLE SCLEROSIS 1067
CHAPTER 78. Treatment of Multiple Sclerosis 1072
TREATMENT FOR ACUTE RELAPSES 1072
COURSE-MODIFYING TREATMENT 1073
SYMPTOMATIC THERAPY 1076
CONCLUSIONS 1078
CHAPTER 79. Acute Disseminated Encephalomyelitis and Progressive Multifocal Leukoencephalopathy 1084
ACUTE DISSEMINATED ENCEPHALOMYELITIS 1084
ACUTE HEMORRHAGIC NECROTIZING LEUKOENCEPHALITIS 1086
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY 1087
TREATMENT 1088
CONCLUSIONS 1089
CHAPYER 80 The Leukodystrophies 1092
X-LINKED ADRENOLEUKODYSTROPHY 1092
METACHROMATIC LEUKODYSTROPHY 1096
GLOBOID LEUKODYSTROPHY 1098
PELIZAEUS-MERZBACHER DISEASE 1100
CANAVAN'S DISEASE 1101
ALEXANDER'S DISEASE 1103
CEREBROTENDINOUS XANTHOMATOSIS 1105
SJ脰GREN-LARSSON SYNDROME 1106
VANISHING WHITE MATTER DISEASE5 1107
MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS 1108
MEMBRANOUS LIPODYSTROPHY 1109
RIBOSE-5-PHOSPHATE ISOMERASE DEFICIENCY 1109
LEUKODYSTROPHIES IN WHICH THE GENETIC DEFECT IS NOT YET DEFINED 1110
DISORDERS THAT RESEMBLE LEUKODYSTROPHIES BUT IN WHICH THE PRIMARY DEFECT DOES NOT AFFECT MYELIN OR MYELINATING CELLS 1110
SUMMARY AND CONCLUSIONS 1110
SECTION XIV: Neuromuscular Diseases: Nerve 1120
CHAPTER 81. Anatomy and Physiology of Muscle and Nerve 1121
NERVE 1121
MUSCLE 1121
CHAPTER 82. Inherited Neuropathies 1126
CLINICAL DIAGNOSIS 1126
DISEASE PHENOTYPES 1126
CLASSIFICATION 1128
GENETICS 1129
GENETIC TESTING 1133
MANAGEMENT 1135
GENETIC COUNSELING 1135
SUMMARY 1135
CHAPTER 83. Metabolic, Immune-Mediated, and Toxic Neuropathies 1140
NEUROPATHIES ASSOCIATED WITH DIABETES MELLITUS 1140
SELECTED CHRONIC IMMUNE-MEDIATED NEUROPATHIES 1143
IATROGENIC AND TOXIC NEUROPATHY 1146
ACKNOWLEDGMENTS 1151
CHAPTER 84. Infective Neuropathies 1154
LEPROUS NEURITIS 1154
HUMAN IMMUNODEFICIENCY VIRUS 1159
CYTOMEGALOVIRUS 1160
VARICELLA ZOSTER VIRUS 1163
HEPATITIS C VIRUS 1163
HUMAN T-LYMPHOTROPIC VIRUS TYPE 1 1163
GUILLAIN-BARR脡 SYNDROME 1164
SECTION XV: Neuromuscular Diseases: Muscle 1168
CHAPTER 85. Muscular Dystrophies 1169
DYSTROPHINOPATHIES 1172
LIMB GIRDLE MUSCULAR DYSTROPHIES 1175
CONGENITAL MUSCULAR DYSTROPHIES 1176
NUCLEAR ENVELOPATHIES 1182
FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY 1183
OCULOPHARYNGEAL MUSCULAR DYSTROPHY 1184
HEREDITARY INCLUSION BODY MYOPATHIES 1185
TREATMENT OF MUSCULAR DYSTROPHIES 1186
CONCLUSIONS AND RECOMMENDATIONS 1188
CHAPTER 86. The Congenital Myopathies 1195
EPIDEMIOLOGY 1195
CLINICAL FEATURES 1195
INVESTIGATIONS 1196
CENTRAL CORE DISEASE 1197
MULTI-MINICORE DISEASE 1200
NEMALINE MYOPATHY 1202
CENTRONUCLEAR (MYOTUBULAR) MYOPATHY 1203
OTHER CONGENITAL MYOPATHIES WITH STRUCTURAL DEFECTS 1205
CHAPTER 87. Channelopathies of Muscle (Including Myotonic Dystrophies) 1214
NONDYSTROPHIC MYOTONIAS AND PERIODIC PARALYSES 1214
MYOTONIC DYSTROPHIES 1218
CHAPTER 88. Metabolic Myopathies (Including Mitochondrial Diseases) 1222
GLYCOGEN STORAGE DISORDERS 1222
FATTY ACID OXIDATION DISORDERS 1225
DEFECTS OF MITOCHONDRIAL OXIDATIVE PHOSPHORYLATION 1228
CHAPTER 89. Inflammatory Myopathies 1238
CLINICAL PRESENTATION 1238
DIAGNOSIS 1240
TREATMENT 1244
PROGNOSIS 1246
CHAPTER 90. Neuromuscular Junction Disorders 1250
MYASTHENIA GRAVIS 1250
THE LAMBERT-EATON MYASTHENIC SYNDROME 1256
ACQUIRED NEUROMYOTONIA 1257
CONGENITAL MYASTHENIC SYNDROMES 1258
CONCLUSIONS AND RECOMMENDATIONS 1258
SECTION XVI: Infections and Granulomatous Diseases 1262
CHAPTER 91. Bacterial Meningitis 1263
BACTERIAL MENINGITIS 1263
MENINGITIS ASSOCIATED WITH TUBERCULOSIS, SYPHILIS, AND LYME DISEASE 1270
CHAPTER 92. Viral Meningitis and Encephalitis 1276
EPIDEMIOLOGY 1276
CLINICAL FEATURES AND INVESTIGATIONS 1277
ETIOLOGY AND PATHOGENESIS 1282
TREATMENT 1282
CONCLUSIONS AND RECOMMENDATIONS 1283
CHAPTER 93. Neurological Disorders Associated with Human Immunodeficiency Virus Infection 1288
NEUROLOGICAL DISORDERS OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION 1288
HUMAN IMMUNODEFICIENCY VIRUS NEUROPATHOGENESIS AND NEUROPATHOLOGY 1288
NEUROCOGNITIVE SYNDROMES IN HUMAN IMMUNODEFICIENCY VIRUS INFECTION 1291
MYELOPATHY 1293
PERIPHERAL NEUROPATHIES 1294
MYOPATHIES 1296
SEIZURE DISORDERS 1296
HEADACHE 1296
FUTURE PERSPECTIVES 1296
CHAPTER 94. Parasitic and Fungal Infections 1300
PARASITIC INFECTIONS OF THE CENTRAL NERVOUS SYSTEM 1300
FUNGAL INFECTIONS OF THE CENTRAL NERVOUS SYSTEM 1316
CHAPTER 95. Prion Diseases 1324
ETIOLOGY AND PATHOGENESIS 1324
HUMAN PRION DISEASES 1324
TREATMENT 1328
CONCLUSION 1328
CHAPTER 96. Neurosarcoidosis and Neuro-Beh脟Et's Disease 1330
NEUROSARCOIDOSIS 1330
NEURO-BEH脟ET'S DISEASE 1336
CONCLUSIONS AND RECOMMENDATIONS 1337
CHAPTER 97. The Neurological Vasculitides 1340
MECHANISMS OF TISSUE DAMAGE 1340
CEREBRAL VASCULITIS 1344
GIANT CELL VASCULITIDES 1347
VASCULITIS OF THE PERIPHERAL NERVOUS SYSTEM 1347
SECTION XVII: Neuro-Oncology 1350
CHAPTER 98. Tumors of the Brain 1351
EPIDEMIOLOGY 1351
ETIOLOGY 1351
PATHOGENESIS 1352
CLINICAL FEATURES 1352
DIAGNOSIS 1353
PATHOLOGY 1354
GENETICS 1355
SUPPORTIVE TREATMENT 1360
INTRA-AXIAL TUMORS 1361
PROGNOSIS 1363
ACKNOWLEDGMENTS 1365
CONCLUSIONS 1365
CHAPTER 99. Tumors of the Spinal Cord 1368
EPIDEMIOLOGY 1368
CLINICAL MANIFESTATIONS 1368
DIAGNOSTIC TESTS 1370
MANAGEMENT 1372
CONCLUSION 1377
CHAPTER 100. Neurological Complications of Cancer Treatments 1380
TIMING OF NEUROLOGICAL COMPLICATIONS 1380
NEUROLOGICAL COMPLICATIONS OF CHEMOTHERAPY 1380
CHEMOTHERAPEUTIC AGENTS 1381
NEUROLOGICAL COMPLICATIONS OF CRANIAL IRRADIATION 1383
CHAPTER 101. Paraneoplastic Disorders of the Nervous System 1388
IMMUNOPATHOGENESIS OF PARANEOPLASTIC NEUROLOGICAL DISORDERS AND EFFECTS ON THE TUMOR 1388
GENERAL APPROACH TO THE DIAGNOSIS OF PARANEOPLASTIC NEUROLOGICAL DISORDERS 1390
SPECIFIC PARANEOPLASTIC SYNDROMES 1393
CHAPTER 102. Tumors of the Peripheral Nerves 1402
BIOPSY 1402
THE BENIGN SCHWANNOMA 1403
THE SOLITARY NEUROFIBROMA 1405
NEUROFIBROMATOSIS 1407
SECTION XVIII: Trauma 1412
CHAPTER 103. Head Trauma 1413
PREVENTION 1413
TRAUMA CARE SYSTEMS 1413
TRAUMATIC BRAIN INJURY CLASSIFICATION 1413
IMAGING OF TRAUMATIC BRAIN INJURY 1414
TYPES OF TRAUMATIC BRAIN INJURY 1414
SPECIFIC INJURIES 1415
CLINICAL ASSESSMENT 1418
TREATMENT 1419
OUTCOMES 1421
CONCLUSIONS AND RECOMMENDATIONS 1422
CHAPTER 104. Spinal Trauma 1424
EPIDEMIOLOGY 1424
DEFINITIONS 1424
HISTOLOGY OF SPINAL CORD INJURY 1428
SPINAL CORD SYNDROMES 1430
MANAGEMENT OF SPINAL TRAUMA 1431
CONCLUSION 1434
CHAPTER 105. Peripheral Nerve Injury 1436
ANATOMY AND PHYSIOLOGY OF PERIPHERAL NERVE INJURY 1436
CLASSIFICATION OF PERIPHERAL NERVE INJURY 1437
EVALUATION OF NERVE TRAUMA 1438
CAUSES OF PERIPHERAL NERVE TRAUMA 1441
TREATMENT OF NERVE TRAUMA 1445
CONCLUSION AND RECOMMENDATIONS 1447
CHAPTER 106. Neurorehabilitation 1450
ASSESSMENT 1450
ACUTE ILLNESS REHABILITION 1450
FUNDAMENTAL REHABILITATION INTERVENTIONS 1452
COMMON MEDICAL AND REHABILITATION ISSUES 1456
SUMMARY 1458
SECTION XIX: Metabolic Diseases 1460
CHAPTER 107. Encephalopathies 1461
CONCEPT AND CONTEXT OF NEUROMETABOLIC DISEASES 1461
MANIFESTATIONS UNFOLD IN TIME 1461
STATIC, EPISODIC, OR PROGRESSIVE DISEASES? 1462
A COMPLEX GENETIC LANDSCAPE 1462
A PLEOMORPHIC PHENOMENOLOGY 1462
DIAGNOSIS AND ITS VALUE 1464
GROUNDWORK FOR FUTURE THERAPIES 1464
CLASSIFICATION OF THE METABOLIC ENCEPHALOPATHIES 1465
ACKNOWLEDGMENTS 1471
CHAPTER 108. Wilson Disease 1474
EPIDEMIOLOGY 1474
CLINICAL FEATURES 1474
NEUROIMAGING 1475
ETIOLOGY AND PATHOPHYSIOLOGY 1476
TREATMENT 1477
CHAPTER 109. Vitamin Deficiencies and Other Nutritional Disorders of The Nervous System 1482
VITAMIN DEFICIENCIES 1482
OTHER NUTRITIONAL SYNDROMES 1491
CHAPTER 110. Urea Cycle Disorders 1496
DEFINITION 1496
EPIDEMIOLOGY 1496
CLINICAL FEATURES 1497
ETIOLOGY AND PATHOPHYSIOLOGY 1499
TREATMENT 1501
CONCLUSION AND RECOMMENDATIONS 1503
CHAPTER 111. Environmental Toxins and Disorders of the Nervous System 1504
METAL INTOXICATION 1504
ORGANIC SOLVENTS 1508
GASES 1510
PESTICIDES 1511
ANIMAL TOXINS 1512
PLANT TOXINS 1512
BACTERIAL TOXINS 1513
ACKNOWLEDGMENT 1514
SECTION XX: Neurology in General Medicine 1516
CHAPTER 112. Neurology of Pregnancy and the Puerperium 1517
PHYSIOLOGY OF PREGNANCY 1517
CLINICAL TOPICS 1520
CHAPTER 113. Neurology of Cardiology 1532
CHAPTER 114. Neurology of Gastroenterology and Hepatology 1538
GASTROINTESTINAL DISEASE 1538
CONCLUSION 1547
CHAPTER 115. Neurology of Hematology 1552
THE ANEMIAS 1552
THE HEMOGLOBINOPATHIES 1554
MYELOPROLIFERATIVE DISORDERS 1554
HEMORRHAGIC DIATHESIS 1555
PARAPROTEINEMIAS 1557
THE HYPERCOAGULABLE STATES 1558
CHAPTER 116. Neurology of Common Electrolyte Disorders 1560
HYPEROSMOLALITY AND HYPERTONICITY 1560
HYPONATREMIA 1561
HYPERKALEMIA 1562
CHAPTER 117. Neurology of Drug and Alcohol Addictions 1564
DEFINITIONS 1564
ILLICIT DRUG DEPENDENCE 1564
ETHANOL 1566
CHAPTER 118. Neurology of Endocrinology 1572
CLASSIFICATION OF HORMONES 1572
MECHANISMS OF HORMONE ACTION 1572
REGULATION OF HORMONE LEVELS AND RHYTHMS 1575
NEUROENDOCRINOLOGY 1576
CHAPTER 119. Neurology of Rheumatology, Immunology, and Transplantation 1584
PRIMARY SJ脰GREN'S SYNDROME 1584
PROGRESSIVE SYSTEMIC SCLEROSIS 1585
RHEUMATOID ARTHRITIS 1586
INFLAMMATORY SPONDYLOARTHROPATHIES 1588
SYSTEMIC LUPUS ERYTHEMATOSUS 1588
ORGAN TRANSPLANTATION 1591
GRAFT-VERSUS-HOST DISEASE 1594
SUMMARY 1594
CHAPTER 120. Neurology of Pulmonology and Acid-Base Disturbance 1596
NEURAL CONTROL OF RESPIRATION 1596
ABNORMAL RESPIRATORY PATTERNS IN NEUROLOGICAL DISEASES 1598
NEUROLOGICAL CONSEQUENCES OF RESPIRATORY INSUFFICIENCY 1600
CONCLUSIONS 1602
ACID-BASE BALANCE AND RESPIRATION 1602
CHAPTER 121. Neurology of Cerebral Palsy 1604
CLASSIFICATION AND CLINICAL FEATURES 1604
ASSOCIATED DISORDERS 1605
DIAGNOSIS 1605
NEUROIMAGING 1606
INVESTIGATIONS 1606
ETIOLOGY 1606
ACQUIRED POSTNATAL CAUSES 1607
PROGNOSIS 1607
MANAGEMENT 1607
Index 1610