Neurobiology of Disease (eBook)

Front Cover 1
Title Page 4
Copyright Page 5
Table of Contents 6
Contributors 10
Editors 17
Preface 18
PART A. CENTRAL NERVOUS SYSTEM 20
Section I. Metabolic Diseases 20
Chapter 1. Lysosomal Disorders of the Nervous System 20
I. Introduction 20
II. Classifying Lysosomal Storage Diseases by Their Clinicopathological Features 21
III. Classifying Lysosomal Diseases by Their Defective Proteins 25
IV. The Greater Lysosomal System as a Central Coordinator of Neuron Metabolism and Function 28
V. Dysfunction of the Lysosomal System in Neurons Leads to Complex Pathogenic Cascades 31
VI. Understanding Lysosomal Disease Pathogenesis Provides Key Insight for Development of Therapy 35
References 36
Chapter 2. Neurobiology of Peroxisomal Disorders 38
I. History and Nomenclature 38
II. The Peroxisomal Disorders 39
III. Etiology 40
IV. Molecular Pathogenesis and Pathophysiology 40
V. Human Pathology and Pathogenesis 42
VI. Mouse Models and Pathogenesis 49
VII. Clinicopathological Correlations 50
References 50
Chapter 3. Creatine Deficiency Syndromes 52
I. History and Nomenclature 52
II. Etiology and Biochemical Pathogenesis 53
III. Pathophysiology 55
IV. Natural History 59
V. Prospects 59
References 59
Chapter 4. Leukodystrophies 62
I. Introduction 62
II. Lipid Metabolism Disorders 62
III. Myelin Protein Disorders 65
IV. Organic Acid Disorders 65
V. Other Leukodys 65
References 66
Section II. Neurodegenerative Disorders 70
Chapter 5. Parkinson’s Disease 70
I. Brief History 70
II. Epidemiology 71
III. General Pathology (and Basic Structural Detail) 73
IV. Pathogenesis 74
V. Pathophysiology 76
VI. Pathophysiology of Symptoms 79
VII. Pharmacology, Biochemistry, Molecular Mechanism 80
VIII. Natural History of Parkinson’s Disease and Its Realationship to Pharmacology 83
References 84
Chapter 6. Alzheimer’s Disease 88
I. History and Nomenclature 88
II. Epidemiology 89
III. Etiology and Risk Factors 89
IV. Pathogenesis 89
V. Neuropathology of AD (Relevant Structural Details) 91
VI. Pathophysiology 94
VII. Biochemistry and Molecular Mechanisms 95
VIII. Explanation of Symptoms in Relation to Pathophysiology 97
IX. Natural History 99
X. Management of AD 100
References 100
Chapter 7. Multiple System Atrophy 102
I. Brief History and Nomenclature 102
II. Epidemiology 103
III. Pathogenesis 103
IV. Structural Details 104
V. Biochemical and Neuropharmacological Findings 106
VI. Molecular Biology 107
VII. Animal Models 108
VIII. Clinical Picture 108
IX. Clinical Diagnosis and Clinical Diagnostic Criteria 110
X. Natural History of the Disease 110
XI. Conclusion 111
References 111
Chapter 8. Olivopontocerebellar Atrophy (OPCA) 114
I. Brief History and Nomenclature 114
II. Etiology and Pathogenesis 116
III. Diagnosis 121
IV. Treatment 122
References 123
Chapter 9. Neurobiology of Progressive Supranuclear Palsy 124
I. History and Nomenclature 124
II. Etiology 125
III. Pathogenesis 126
IV. Relevant Structural 126
V. Pharmacology, Biochemistry, Molecular Mechanisms 127
VI. Explanation of Symptoms in Relation to Pathophysiology 127
VII. Natural History 128
References 128
Section III. Genetic Diseases 130
Chapter 10. Protein Aggregation Disorders 130
I. Protein Folding and Misfolding 130
II. Protein Aggregation Disorders 131
III. “Natively Unfolded’’ Proteins and Other Structural Determinants of Protein Aggregation 138
IV. Cellular Quality Control Systems for Protein Folding as Targets for Therapeutic Intervention in Neurodegenerative Diseases 139
V. Conclusions 139
References 140
Chapter 11. RNA-Based Disorders of Muscle and Brain 144
I. Overview 144
II. Myotonic Dystrophy Type 1 and Type 2 145
III. Fragile X–Associated Tremor/Ataxia Syndrome 148
IV. Prospects for RNA Pathogenic Mechanisms in Other Neuromuscular Disorders 151
References 152
Chapter 12. Ion Channel Disorders 154
I. Introduction 154
II. Epilepsy 155
III. Ataxia 162
IV. Neuromuscular Disorders 163
References 166
Chapter 13. Spinocerebellar Ataxia Type 1 168
I. SCA1: The Disease 168
II. SCA1 Pathogenesis: Regional Involvement 169
III. SCA1 Pathogenesis: Molecular Mechanisms 170
IV. SCA1: Recovery from Disease 172
V. Linking Pathology to Pathophysiology 173
VI. Concluding Comments 173
References 174
Chapter 14. Mitochondrial Genetic Diseases 176
I. Mutations in Mitochondrial Protein-Encoding Genes 177
II. Mutations in Mitochondrial Protein Synthesis Genes 177
III. Defective Mitochondrial Function Caused by Nuclear DNA Mutations 178
References 179
Section IV. Neuroimmunological Disorders 182
Chapter 15. Paraneoplastic Neurological Disorders 182
I. Introduction 182
II. History and Nomenclature 183
III. Etiology and Pathogenesis 183
IV. Pathophysiology 184
V. Symptoms and Natural History 187
VI. Summary 187
References 187
Chapter 16. Systemic Lupus Erythematosus: Descriptive Past and Mechanistic Future 190
I. Introduction 190
II. Epidemiology, Etiology, and Pathogenesis 191
III. Neuropsychiatric SLE 193
IV. Neuroimaging in SLE 194
V. Pathogenesis of NPSLE 195
VI. Anti-Phospholipid Antibodies and Anti-Phospholipid Syndrome 196
VII. Summary 199
References 199
Chapter 17. Progressive Multifocal Leukoencephalopathy 204
I. Brief History and Nomenclature 204
II. Etiology 205
III. Pathogenesis 207
IV. Lymphocyte Control on Latency 208
V. Pathophysiology 209
VI. Molecular Mechanisms 211
VII. Explanation of Symptoms in Relation to Pathophysiology 211
VIII. Natural History 212
References 213
Chapter 18. Immunopathogenesis of Multiple Sclerosis 216
I. Introduction 216
II. Immune Surveillance of the CNS 217
III. Animal Models of CNS Inflammation 217
IV. Immunology of the Multiple Sclerosis Lesion 219
References 223
Chapter 19. Immune-Mediated Neuropathies 224
I. Introduction 224
II. Acute Immune-Mediated Neuropathies 225
III. Chronic Immune-Mediated Neuropathies 228
IV. Systemic Autoimmune Disease Affecting the Peripheral Nerve 232
V. Immune-Mediated Exacerbation of Nonimmune Peripheral Nerve Disease 233
References 234
Chapter 20. Hashimoto Encephalopathy 236
I. History and Nomenclature 236
II. Clinical Features 237
III. Etiology 237
IV. Pathogenesis 239
V. Clinical Course 239
References 239
Section V. Cerebrovascular Diseases 242
Chapter 21. Vascular Cognitive Impairment 242
I. Introduction 243
II. Nomenclature, Epidemiology, and Natural History 243
III. Etiology of Vascular Cognitive Impairment 244
IV. Causes of Hereditary Vascular Cognitive Impairment 244
V. Causes of Sporadic Vascular Cognitive Impairment 246
VI. Cardiovascular Causes of Sporadic Vascular Cognitive Impairment Independent of Structural Brain Abnormality 248
VII. Pathophysiology of Vascular Cognitive Impairment 248
VIII. Clinical Features 249
IX. Summary 250
References 250
Chapter 22. Cardioembolism 254
I. Nomenclature 254
II. Etiology 254
III. Pathophysiology 255
IV. Molecular Mechanisms 258
References 259
Chapter 23. Clinical and Neurobiological Aspects of Stroke Recovery 260
I. Introduction 260
II. Brief History: The “General Course of Recovery’’ 261
III. Emergence after Brain Injury of Progressive and Mutable Reflexive Motor Power 261
IV. Unmasking: Phenomena of Altering Ineffective Synaptic Potential 264
V. Bench to Bedside: Experimental Precedents Fuel Clinical Treatment 264
VI. Evidence for Functional Reorganization in Stroke Recovery: Neuroimaging Tools 266
VII. Motor Systems Cortical Physiology: Influences from the Bench 266
VIII. From Mutable Motor Maps to Neuroimaging to Magnetism 268
IX. Motor Learning as a Guide to Pharmacological Interventions 270
X. Conclusions 270
References 271
Chapter 24. Nonatherosclerotic Cerebral Vasculopathies 274
I. Introduction 274
II. Noninflammatory Arteriopathies 274
III. Inflammatory Arteriopathies 277
IV. Conclusion 281
References 281
Chapter 25. Subarachnoid Hemorrhage 284
I. Introduction 284
II. Etiology 284
III. Epidemiology and Genetics 285
IV. Aneurysm Pathogenesis 285
V. Pathophysiology of Aneurysm Rupture 286
VI. Pathophysiology of Delayed Cerebral Ischemia 286
VII. Cerebral Salt Wasting Syndrome 288
VIII. Conclusion 288
References 289
Chapter 26. Cerebral Ischemia: Molecular Mechanisms and Protective Therapies 290
I. Introduction 290
II. Definitions: Ischemic Core and Penumbra 291
III. Cellular and Biochemical Responses to Focal Cerebral Ischemia 291
IV. The Neurovascular Unit 292
V. Blood-Brain Barrier Damage in Cerebral Ischemia 292
VI. Postischemic Necrosis and Apoptosis 293
VII. Molecular Events Underlying Ischemic Cell Death 294
VIII. Gene Expression Following Cerebral Ischemia 294
IX. The Inflammatory Response to Cerebral Ischemia 295
X. Hyperglycemia and Hemorrhagic Infarct Conversion 295
XI. Acute Treatments for Cerebral Ischemia 295
XII. Global Cerebral Ischemia 297
References 297
Chapter 27. Intracerebral Hemorrhage and Intraventricular Hemorrhage–Induced Brain Injury 300
I. Introduction 300
II. Etiology 301
III. Pathophysiology 301
IV. Mechanisms of Intracerebral Hemorrhage–Induced Brain Injury 302
V. Mechanisms of Intraventricular Hemorrhage–Induced Brain Injury 304
VI. Therapeutic Interventions for Intracerebral Hemorrhage–Induced Brain Injury 305
VII. Therapeutic Interventions for Intraventricular Hemorrhage–Induced Brain Injury 305
VIII. Summary 305
References 305
Section VI. Paroxysmal Disorders 308
Chapter 28. Idiopathic Generalized Epilepsy 308
I. Clinical Overview 308
II. Animal Models 309
III. Genetic Models of Absence Seizures 310
IV. Pharmacological Models of Absence Seizures 310
V. The Nature of Thalamocortical Synchronized Activity 311
VI. Genetics 313
VII. Concluding Remarks 315
References 315
Chapter 29. Paroxysmal Dyskinesia 316
I. Brief History and Nomenclature 316
II. Paroxysmal Kinesigenic Dyskinesia (Formerly Paroxysmal Kinesigenic Choreoathetosis) 317
III. Paroxysmal Nonkinesigenic Dyskinesia (Formerly Familial Paroxysmal Dystonia or Paroxysmal Dystonic Choreoathetosis) 320
IV. Paroxysmal Exercise–Induced Dystonia 321
V. Paroxysmal Hypnogenic Dyskinesia 321
VI. Conclusion 322
References 322
Chapter 30. Myoclonus 324
I. History and Nomenclature 324
II. Pathophysiology 325
III. Pharmacology and Molecular Genetics 330
IV. Relationship between Pathophysiology and Symptoms 335
V. Natural History 335
References 336
Chapter 31. Channelopathies of the Nervous System 338
I. Introduction 338
II. Channelopathies: Defects of Ion Channel Function 338
III. Channelopathies of the Peripheral Nervous System 342
IV. Channelopathies of the Central Nervous System 347
V. Acquired Channelopathies of the Nervous System 350
References 350
Chapter 32. Migraine as a Cerebral Ionopathy with Abnormal Central Sensory Processing 352
I. Migraine: A Common, Disabling, Episodic Disorder 352
II. The Migraine Attack: Clinical Phases and Pathophysiology 353
III. The Migraine Trigger Threshold: Repeated Recurrence of Attacks 358
IV. Conclusions 363
References 363
Chapter 33. Temporal Lobe Epilepsy 368
I. Historical Background 368
II. Pathology of Temporal Lobe Epilepsy 370
III. Pathophysiological Mechanisms 376
IV. Summary and Future Directions: Developing a Comprehensive Hypothesis for the Pathology and Pathophysiology of Temporal Lobe Epilepsy 383
References 383
Section VII. Neoplastic Diseases 390
Chapter 34. Central Nervous System Metastases 390
I. Overview 390
II. Brief History and Nomenclature 390
III. Natural History of CNS Metastasis 392
IV. Etiology and Pathogenesis: The Brain Metastatic Process 392
V. Pathophysiology: An Unique Environment? 394
VI. Conclusion 397
References 397
Chapter 35. Meningioma 400
I. History 400
II. Incidence and Etiology 401
III. Meningioma Morphology and Subtypes 401
IV. Clinical Aspects 404
V. Pathogenesis and Molecular Mechanisms 405
VI. Special Forms of Meningioma 409
VII. Pathophysiology 410
VIII. Cell Lines and Animal Models 411
IX. Future Directions 411
References 412
Chapter 36. Primary Central Nervous System Lymphoma 414
I. Introduction 414
II. Epidemiology 415
III. Pathology and Biology 416
IV. Clinical Features of PCNSL 422
V. Treatment Options for PCNSL 424
VI. Summary 428
References 428
Chapter 37. Neurofibromatosis 1 432
I. History 432
II. Nomenclature 433
III. Etiology 433
IV. Pathogenesis 433
V. Natural History 437
VI. Structural Detail 438
VII. Biochemistry and Molecular Mechanisms 439
VIII. Symptoms in Relation to Pathophysiology 440
References 441
Chapter 38. Medulloblastoma and Primitive Neuroectodermal Tumors 444
I. Historical Concepts and Definitions 444
II. Neuroembryogenesis of the Cerebellum: Clues to the Origin of Medulloblastoma 445
III. Histopathology of Medulloblastoma 445
IV. Molecular Genetics of Medulloblastoma 446
V. Medulloblastoma and Inherited Cancer Syndromes 447
VI. Developmental Signaling Pathways and Medulloblastoma 447
VII. Molecular Profiling and Patient Outcome in Medulloblastoma 448
VIII. Treatment of Medulloblastoma: The Promise of New Pharmacotherapeutics 450
IX. Summary 450
References 450
Chapter 39. Glioma 452
I. Introduction 452
II. Nomenclature 453
III. Locations and Symptoms 453
IV. Epidemiology 453
V. Etiology 453
VI. Histopathology 454
VII. Genetic Alterations 455
VIII. Cell of Origin 457
IX. Signaling Pathways 458
X. Pharmacology 460
XI. Future Therapeutic Interventions 461
References 463
Section VIII. Infectious Diseases 464
Chapter 40. Bacterial and Fungal Infections of the Nervous System 464
I. History and Nomenclature 464
II. Etiology 465
III. Pathogenesis 465
IV. Relevant Structural Detail 465
V. Pathophysiology 465
VI. Pharmacology 468
VII. Signs and Symptoms 468
VIII. Natural History 469
References 470
Chapter 41. Parasitic Infections 472
I. Introduction 472
II. Protozoans 474
III. Helminths: Cestodes 483
IV. Helminths: Nematodes 485
V. Helminths: Trematodes 489
References 491
Chapter 42. Prion Diseases 492
I. History of Prion Diseases 492
II. The “Protein-Only’’ Hypothesis (What Is a Prion?) 494
III. Prion Diseases of Animals and Humans 494
IV. Animal Models of Prion Diseases 498
V. Peripheral Prion Pathogenesis 499
VI. Therapy 500
References 501
Chapter 43. Central Nervous System Viral Infections: Clinical Aspects and Pathogenic Mechanisms 504
I. Introduction 504
II. Neuropathogenesis of CNS Viral Infections 505
III. Diagnostic Considerations 510
IV. Acute CNS Viral Infection: Herpes Simplex Encephalitis 510
V. Chronic CNS Viral Infection: Neurocognitive Syndromes in HIV Infection 512
VI. Future Perspectives 514
References 514
Section IX. Motor Neuron Diseases 520
Chapter 44. Spinal Muscular Atrophy 520
I. Introduction 520
II. Spinal Muscular Atrophy 520
III. Genetic Basis of SMA 521
IV. SMN Gene Expression 522
V. Splicing of SMN Transcripts 523
VI. SMN Protein 523
VII. Animal Models of SMA 524
VIII. Therapeutic Strategies for SMA 526
IX. Remaining Questions 529
References 529
Chapter 45. Amyotrophic Lateral Sclerosis–Like Syndromes Associated with Malignancy 532
I. Brief History and Nomenclature 532
II. Etiology 533
III. Pathogenesis, Pathophysiology, and Relevant Structural Detail 534
IV. Pharmacology, Biochemistry, and Molecular Mechanisms 536
V. Explanation of Symptoms in Relation to Pathophysiology 536
VI. Natural History 537
References 538
Chapter 46. Amyotrophic Lateral Sclerosis: Idiopathic and Inherited 540
I. History and Nomenclature 540
II. Epidemiology 541
III. Etiology and Pathogenesis 541
IV. Pathophysiology 542
V. Symptoms in Relation to Pathophysiology and Natural History 542
VI. Structural Detail 543
VII. Molecular Mechanisms 543
VIII. Pharmacology and Treatment 548
References 550
Chapter 47. Hereditary Spastic Paraplegia and Primary Lateral Sclerosis 556
I. Definitions 556
II. Historical Aspects 557
III. Epidemiology 557
IV. Clinical Features of HSP 557
V. Neuropathology of HSP 558
VI. Molecular Genetics of HSP 559
VII. Nosology of PLS 562
VIII. Common Molecular Mechanisms Underlying HSP and PLS 562
References 563
Chapter 48. Poliomyelitis 564
I. Background 564
II. Epidemiology 565
III. Pathophysiology 566
IV. Treatment 567
V. Summary 569
References 569
Chapter 49. Spinobulbar Muscular Atrophy (Kennedy’s Disease) 572
I. Introduction 572
II. Clinical Features 573
III. Pathological Features 573
IV. Kennedy’s Disease as a Polyglutamine Disease: Molecular Pathogenesis 574
V. Female Carriers of Kennedy’s Disease 577
VI. Pharmacology: The Role of Ligand in the Pathogenesis 577
VII. Genetically Modified Animal Models 578
VIII. Symptoms in Relation to Pathophysiology 578
IX. Potential for Therapy 578
X. Conclusions 579
References 579
Section X. Malformations and Developmental Disorders 582
Chapter 50. Neurobiology of Genetic Mental Retardation 582
I. Introduction 582
II. Dendritic and Synaptic Abnormalities: Fundamental Features of Genetic MR 583
III. Down Syndrome 584
IV. X-Linked MR Disorders 586
V. Other Genetic MR Disorders 591
VI. Conclusion 591
References 592
Chapter 51. Cerebral Palsy 594
I. Brief History and Nomenclature 594
II. Etiology 595
III. Pathogenesis 597
IV. Pathophysiology 597
V. Relevant Structural Detail 597
VI. Pharmacology, Biochemistry, and Molecular Mechanisms 598
VII. Symptoms in Relation to Pathophysiology 598
VIII. Natural History 598
References 598
Chapter 52. Autism 600
I. Brief History and Nomenclature 600
II. Etiology 601
III. Pathogenesis 601
IV. Pathophysiology 604
V. Brain Structure 606
VI. Pharmacology, Biochemistry, and Molecular Mechanisms 607
VII. Explanation of Symptoms in Relation to Pathophysiology 608
VIII. Natural History 609
References 609
Chapter 53. Neurobiology of Dyslexia 612
I. Definition and History 612
II. Natural History 613
III. Behavioral Models of Dyslexia 613
IV. Neurobiology of Dyslexia 614
V. Relating Neurobiology to Reading Behavior 615
VI. Summary 616
References 616
Chapter 54. Neonatal Brain Injuries 618
I. Nomenclature 618
II. Etiology and Pathogenesis 619
III. Pathophysiology: Relevant Structural Detail and Molecular Mechanisms 620
IV. Explanation of Symptoms in Relation to Pathophysiology and Natural History 623
V. Summary 626
References 627
Chapter 55. Spina Bifida 630
I. Brief History and Nomenclature 630
II. Etiology 631
III. Pathogenesis 632
IV. Pathophysiology 632
V. Relevant Structural Details 634
VI. Pharmacology, Biochemistry, and Molecular Mechanisms 635
VII. Natural History 636
References 637
Chapter 56. Circuits to Synapses: The Pathophysiology of Tourette Syndrome 638
I. Introduction 638
II. Brief History and Nomenclature 639
III. Natural History 639
IV. Relevant Structural Detail and Neurophysiology 640
V. Location of the Primary Dysfunction 643
VI. Neurochemical Basis for TS 646
VII. Autoimmunity as a Mechanism for TS 648
VIII. Summary 648
References 649
Chapter 57. Attention-Deficit Hyperactivity Disorder 650
I. History and Nomenclature 650
II. Etiology 651
III. Pathogenesis and Pathophysiology 653
IV. Relevant Neurological Findings 653
V. Pharmacology, Biochemistry, and Molecular Mechanisms 655
VI. Natural History 655
References 658
Chapter 58. Congenital Hydrocephalus 660
I. Brief History and Nomenclature 660
II. Etiology 661
III. Pathogenesis 661
IV. Pathophysiology 663
V. Relevant Structural Details 664
VI. Pharmacology, Biochemistry, and Molecular Mechanisms 664
VII. Natural History 664
References 665
Section XI. Neurologic Manifestations of Medical Diseases 668
Chapter 59. Neurological Manifestations of Hematological Disease 668
I. Vitamin B12 Deficiency 668
II. Paraproteinemias: Syndromes Associated with a Monoclonal Immunoglobulin 670
III. Hemoglobinopathies 672
IV. Acute Porphyrias 674
V. Thrombotic Thrombocytopenic Purpura 675
VI. Myeloproliferative Syndromes 676
References 677
Chapter 60. Neurological Manifestations of Renal Disease 678
I. Introduction 678
II. Neurological Syndromes in Chronic Kidney Disease 679
III. Neurological Complications of Dialysis 681
IV. Renal Complications of Neurological Syndromes 683
V. Neurological Manifestations of Electrolyte Imbalances 683
VI. Drug Toxicities 684
References 685
Chapter 61. Diabetes and Endocrine Disorders 688
I. Diabetes Mellitus 688
II. Diabetic Neuropathies 688
III. Other Endocrine Disorders 694
References 698
Chapter 62. Mechanisms and Consequences of Central Nervous System Hypoxia 700
I. Cerebral Energy Metabolism 701
II. Cerebral Oxygen Supply 701
III. Cerebral Blood Flow 702
IV. Ventilatory Control 703
V. Oxygen-Sensing Mechanisms 703
VI. Neurobiology of Hypoxic-Ischemic Injury 704
VII. Clinical Consequences of Hypoxia 705
VIII. Conclusions 706
References 706
Chapter 63. Neurological Manifestations of Gastrointestinal and Hepatic Diseases 708
I. Introduction 708
II. Diseases of the Alimentary Tract 709
III. Hepatic Diseases 714
IV. Vitamin and Mineral Deficiencies 717
V. Conclusion 719
References 719
Chapter 64. Neurosarcoidosis 722
I. Neurosarcoidosis 722
II. Neurosarcoidosis: Sites of Involvement 724
III. Conclusion 726
References 726
Section XII. Sleep Disorders 728
Chapter 65. REM Sleep Behavior Disorder 728
I. Brief History and Nomenclature 728
II. Etiology 729
III. Pathogenesis 731
IV. Pathophysiology 732
V. Pharmacology, Biochemistry, and Molecular Mechanisms 732
VI. Explanation of Symptoms in Relation to Pathophysiology 732
VII. Natural History 733
References 733
Chapter 66. Neurobiology of Narcolepsy and Hypersomnia 734
I. Narcolepsy-Cataplexy 735
II. Narcolepsy without Cataplexy 739
III. Idiopathic Hypersomnia 740
References 741
Chapter 67. Restless Legs Syndrome and Periodic Limb Movements in Sleep 742
I. Natural History of Restless Legs Syndrome 743
II. Etiology of Restless Legs Syndrome 743
III. Pathophysiology and Molecular Mechanisms of Restless Legs Syndrome 746
IV. Explanation of Restless Legs Syndrome Symptoms in Relation to Pathophysiology 748
V. Periodic Limb Movements 750
VI. Conclusion 751
References 751
Chapter 68. Neurobiology of Insomnia 754
I. Introduction 754
II. Definition of Insomnia 755
III. Theoretical Perspectives on Insomnia 756
IV. Brief Review of the Neurobiology of Sleep and Wakefulness 757
V. Neurobiology of Sleep and Wakefulness: Implications for Insomnia 758
VI. Neurophysiologic, Neuroendocrine, and Neuroimaging Measures of Insomnia 759
VII. Call for an Integrative Perspective on Insomnia 760
References 761
Section XIII. Substance Abuse and Basic Toxicology 764
Chapter 69. Organic Chemicals 764
I. History and Nomenclature 764
II. Epidemiology 765
III. Risk Factors 767
IV. Pathogenesis: Etiological Agents and Factors Affecting Mode of Action 768
V. Neuropathology of Organic-Chemical-Induced Neurotoxicity 771
VI. Pathophysiology 772
VII. Biochemistry and Molecular Mechanisms 773
VIII. Explanation of Signs and Symptoms in Relation to Pathophysiology 775
IX. Natural History 776
X. Management of Organic-Chemical-Induced Neurotoxicity 777
References 777
Chapter 70. Metals 778
I. Introduction 778
II. Metals Causing Nervous System Disease 779
III. Pathophysiology 781
IV. Targets 782
V. Biochemical and Molecular Mechanisms 783
VI. Nature of Neurotoxic Syndromes 785
VII. Age-Related Variables 787
References 787
Chapter 71. Neurobiology of Drug Addiction 790
I. Drug Addiction versus Dependence 791
II. Traditional Conceptions of Drug Addiction: The Hedonic Model 791
III. Dopamine as the Hedonic Signal 791
IV. Incentive Salience Model of Drug Addiction 792
V. Aberrant Learning Model of Drug Addiction 793
VI. Drug Addiction Involves Multiple Neural Circuits, Transmitter Systems, and Processes 793
VII. Drug Addiction Reflects the Interaction of Neurobiological, Genetic, and Environmental Factors 794
VIII. Stress and Vulnerability to Drug Abuse 796
References 797
Section XIV. Imaging the Nervous System 800
Chapter 72. Assessment of Neurobiological Diseases with Magnetic Resonance Spectroscopy 800
I. Introduction 800
II. History, Nomenclature, and Basic Technological Concepts 800
III. Biochemistry and the Interpretation of Magnetic Resonance Spectra 805
IV. Pathophysiology of Neurological Diseases of the Brain and Magnetic Resonance Spectroscopy 807
V. Summary 810
References 810
Chapter 73. Magnetic Resonance Imaging 812
I. History of Magnetic Resonance Imaging 813
II. Magnetic Resonance Imaging Hardware 813
III. Basic Principles of Magnetic Resonance Imaging 814
IV. Image Analysis 815
V. Basic Clinical Magnetic Resonance Imaging 816
VI. Perfusion and Diffusion Magnetic Resonance Imaging 816
VII. Other Sources of Image Contrast in Proton Magnetic Resonance Imaging 818
VIII. Exogenous Contrast Agents 818
IX. Imaging Nuclei Other Than Protons 819
X. Conclusion 819
References 819
Chapter 74. Neurovascular Computed Tomography Angiography 820
I. Introduction 820
II. Fundamentals 821
III. Specific Neurovascular Clinical Scenarios 823
IV. Conclusions and Future Directions 835
References 835
Chapter 75. PET Imaging in Parkinson’s Disease and Other Neurodegenerative Disorders 840
I. Introduction 840
II. Diagnosis of Parkinson’s Disease 841
III. Treatment 844
IV. Cognitive Impairment: New Imaging Approaches 845
V. PET Imaging and Clinical Diagnosis 846
VI. Conclusion 846
References 847
Chapter 76. Single-Photon Emission Computed Tomography 848
I. Brief History and Method 848
II. SPECT in Diseases of the Brain 850
References 856
Chapter 77. Functional Magnetic Resonance Imaging 858
I. Overview and Methods 858
II. Functional Magnetic Resonance Imaging of Cognition and Cognitive Deficits 860
III. Clinical Application in Neuronavigation 864
IV. Monitoring Recovery of Function 865
V. Phenotyping and Genotyping 866
VI. Conclusion 866
References 866
PART B. PERIPHERAL NERVOUS SYSTEM 868
Section XV. Peripheral Neuropathies 868
Chapter 78. Impaired Glucose Regulation and Neuropathy 868
I. Introduction 868
II. Spectrum of Impaired Glucose Regulation 868
III. Pathophysiology of Neuropathy Related to Impaired Glucose Regulation 869
IV. Symptoms in Relation to Pathophysiology 875
V. Natural History 876
VI. Conclusion 876
References 877
Chapter 79. Acquired Inflammatory Demyelinating and Axonal Neuropathies 878
I. Acute Inflammatory Neuropathies 879
II. Chronic Inflammatory Neuropathies 883
III. Chronic Inflammatory Demyelinating Polyneuropathy and Closely Related Neuropathies 883
IV. Neuropathies Associated with Monoclonal Gammopathies 885
V. Treatment 886
VI. Summary 887
References 887
Chapter 80. Toxic and Drug-Induced Neuropathies 890
I. Antimicrobial Agents 892
II. Nucleoside Reverse Transcriptase Inhibitors 892
III. Cardiovascular Drugs 893
IV. Statins 893
V. Disulfiram 893
VI. Colchicine 894
VII. Chloroquine 894
VIII. Gold Salts 894
IX. Leflunomide 894
X. Tacrolimus (FK506) 894
XI. Interferons 895
XII. Antiepileptic Drugs 895
XIII. Antineoplastic Drugs 895
XIV. New Generation Antineoplastic Drugs 901
References 902
Chapter 81. Inherited Peripheral Neuropathies 904
I. Introduction 904
II. Classification 905
III. Different Types of Hereditary Neuropathies: Clinical, Genetic, and Pathological Features and Pathomechanisms 905
IV. Hereditary Motor Neuropathies 913
V. Hereditary Sensory and Autonomic Neuropathies 915
VI. Hereditary Brachial Plexus Neuropathy 916
VII. Rare Forms of Hereditary Peripheral Neuropathies 916
References 916
Chapter 82. Neurological Manifestations of Vasculitis 920
I. Introduction 920
II. History and Nomenclature 921
III. Pathogenesis 921
IV. Primary Vasculitides 922
V. Secondary Vasculitides 926
VI. Central and Peripheral Nervous System Manifestations 927
References 929
Chapter 83. Neuropathies Associated with Infections 932
I. Introduction 932
II. Peripheral Neuropathy Syndromes Related to Bacterial, Mycobacterial, and Spirochetal Infections 932
III. Peripheral Neuropathy Syndromes Related to Viral Infections 937
IV. Conclusion 941
References 942
Section XVI. Myopathies and Neuromuscular Junction Disorders 944
Chapter 84. Muscular Dystrophies 944
I. Introduction 944
II. Duchenne’s and Becker’s Muscular Dystrophies 945
III. Limb-Girdle Muscular Dystrophies 946
IV. Congenital Muscular Dystrophies 948
V. Myotonic Dystrophy 950
VI. Facioscapulohumeral Muscular Dystrophy 951
VII. Conclusion 952
References 952
Chapter 85. Myasthenia Gravis and Myasthenic Syndromes 954
I. Neuromuscular Junction 954
II. Autoimmune Neuromuscular Junction Disorders 956
III. Congenital Myasthenic Syndromes 962
IV. What Determines the Phenotypic Variability in Neuromuscular Junction Disorders? 963
References 964
Chapter 86. Metabolic Myopathies 966
I. Brief History and Nomenclature 966
II. Etiology 967
III. Pathogenesis 967
IV. Pathophysiology 967
V. Pharmacology, Biochemistry, and Molecular Mechanisms 968
VI. Explanation of Symptoms in Relation to Pathophysiology 974
VII. Natural History 974
References 975
Chapter 87. Immunobiology of Autoimmune Inflammatory Myopathies 976
I. Introduction 976
II. Epidemiology and Immunogenetics 977
III. Clinicohistological Features 977
IV. Immunopathogenesis 979
V. Treatment: Present and Future 986
References 987
Section XVII. Autonomic Disorders 988
Chapter 88. Central Autonomic Network 988
I. Introduction 988
II. Functional Anatomy 989
III. Neurotransmitters and Neuromodulators 994
References 996
Chapter 89. Autonomic Neuropathies 998
I. Introduction 998
II. History and Nomenclature 998
III. Etiology 999
IV. Pathogenesis and Pathophysiology 1000
V. Structural Basis 1002
VI. Pharmacology, Biochemistry, Molecular Mechanisms 1003
VII. Pathophysiological Basis of Symptoms 1003
VIII. Natural History 1003
References 1004
Chapter 90. Thermoregulation and Its Disorders 1006
I. Chapter Overview 1006
II. Human Thermoregulation 1007
III. Pyrogens and Fever 1010
IV. Effect of Aging on Human Thermoregulation 1010
V. Some Disorders of Thermoregulation 1011
VI. Thermoregulatory Failure Due to Degenerative Disorders 1014
References 1015
Chapter 91. Control of Blood Pressure—Normal and Abnormal 1016
I. History and Nomenclature 1016
II. Key Elements of Short-Term Blood Pressure Regulation in Humans 1017
III. The Physiological Problem of Upright Posture in Humans 1018
IV. Failure of Blood Pressure Regulation during Orthostatic Stress 1019
V. Ideas about Physiological “Causes’’ of Common Fainting 1019
VI. Who Faints, How Often, and When? 1022
VII. Summary 1023
References 1023
Section XVIII. Pain 1026
Chapter 92. Neoplasm-Induced Pain 1026
I. Introduction 1026
II. Etiology 1026
III. Pathogenesis 1027
IV. Pain Characteristics 1027
V. Assessment 1029
VI. Pain Syndromes 1030
VII. Pharmacological Treatment 1033
VIII. Interventional Procedures 1037
References 1039
Chapter 93. Pain Associated with the Autonomic Nervous System 1040
I. Introduction 1040
II. Pain Generated by the Sympathetic Nervous System: Evidence from Experimental Investigations of Human Patients 1041
III. Excitation of Afferent Neurons Dependent on Activity in Sympathetic Neurons 1042
IV. Sensitization of Nociceptors Mediated by Sympathetic Terminals Independent of Excitation and Release of Noradrenaline 1043
V. Sensitization of Nociceptors, Nerve Growth Factor, and Cytokines Mediated by Sympathetic Terminals 1045
VI. Mechanical Hyperalgesic Behavior in the Rat Controlled by the Sympathoadrenal (SA) System 1046
VII. Synopsis 1048
References 1048
Chapter 94. Postherpetic Neuralgia 1050
I. Brief History and Nomenclature 1050
II. Etiology and Molecular Mechanisms 1051
III. Pathology and Natural History 1052
IV. Pathophysiology, Biochemistry, and Pharmacology 1054
V. Explanation of Symptoms in Relation to Pathophysiology 1055
References 1055
Chapter 95. Central Post-Stroke Pain 1058
I. Introduction 1058
II. Incidence and Prevalence 1060
III. Pain Onset 1060
IV. Pain Characteristics 1061
V. Somatosensory Deficit 1061
VI. Autonomic Changes 1062
VII. Natural Course of the Disease 1062
VIII. Treatment 1062
IX. Possible Mechanisms of CPSP 1063
References 1063
Index 1066