Neuroinflammation (eBook)

Front Cover 1
Neuroinflammation 4
Copyright Page 5
Contents 6
Preface 14
Contributors 16
Chapter 1. Multiple Sclerosis: Pathophysiology, Clinical Features, Diagnosis, and Management 22
Introduction 22
Epidemiology 23
Pathophysiology 24
Clinical Manifestations 27
Neuroimaging: A Concise Review 29
Diagnosis 36
Variants of MS 36
Differential Diagnosis 36
Management 37
Treatment of Acute Relapses 37
Disease-Modifying Agents 38
Prognosis 41
Conclusion 41
Chapter 2. Epstein–Barr Virus and Multiple Sclerosis: Wrong Place, Wrong Time? 46
Epstein–Barr Virus 46
EBV and Diseases 47
Multiple Sclerosis 48
Epidemiologic Evidence Linking EBV to MS 48
EBV Serology and MS 48
Is there a specific EBV Strain causing MS? 50
Control of EBV Infection by Host Immune Responses 50
Control of EBV Infection by Virus-Specific CD8+ T Cells 51
Control of EBV Infection by Virus-Specific CD4+ T Cells 52
Is EBV a characteristic feature of the MS Brain? 52
Conclusion 54
Chapter 3. Neutralizing Antibodies and Multiple Sclerosis 60
Immunogenicity of Beta-Interferons 60
Interferon Antibody Assays 62
Prevalence of NAbs to Beta-Interferons 65
Interferon Antibody Positivity and Persistence 67
Clinical Implications of Interferon NAbs 68
Antibodies to GA 70
Antibodies to Natalizumab 70
Conclusion 71
Chapter 4. Animal Models of Multiple Sclerosis 76
Etiology, Clinical Course, and Pathology 76
Immunology of MS, EAE, and TMEV Infection 80
Conclusions 87
Chapter 5. Neuroimaging of Multiple Sclerosis: An Update 102
Conventional Magnetic Resonance Imaging 102
Advanced Sequences, New Contrast Agents, High-Field MRI, Quantitative and Nonconventional MRI Techniques 107
Conclusions 119
Chapter 6. Role of IL-12/IL-23 in the Pathogenesis of Multiple Sclerosis 128
Introduction 128
IL-12 p40 Family 128
T-Helper-Cell Lineages and Immune Deviation 129
IL-12 and Th-1 Differentiation Pathways 130
IL-12 and T-Cell Encephalitogenicity 132
Myelin-Specific Th-1 Cells in MS 133
IFN-& #947
Genetically Deficient Mice of the p40 Family 134
The Discovery of IL-23 135
Critical Role of IL-23 in EAE 136
IL-23 Expression in CNS 137
Th-17 Differentiation Pathways 137
Molecular Mechanisms Regulating Th-17 Pathway 139
The Plasticity of Th-17 Cells 141
In Vitro Differentiation of Encephalitogenic Th-17 Cells 141
Human Th-17 Cells 142
Distinct Type of Inflammation Induced by Th-1 or Th-17 Cells 144
Anti-p40 Therapy 144
T-bet: A Potential Prognostic Marker and Therapeutic Target in MS 146
Chapter 7. Spinal Cord Injury and its Relationship to the Development or Worsening of Clinical Multiple Sclerosis 158
Introduction 158
Historical Review 159
Relationships of Plaques to Blood Vessels 161
Breakdown of the BBB in Plaque Formation 161
Inflammatory Cell Infiltrates 163
Astrocytic and Other Cellular Changes 164
Effect of Trauma on the BBB 164
Studies of Stress on the BBB 166
Studies Showing that the Site of the BBB Breakdown is related to the Formation of New Demyelinating Plaques 169
Effect of Electrical Injuries in the Precipitation or Worsening of MS 174
Therapeutic Trials of Breaking Down the BBB in Patients with MS 176
Effects of Radiation on the BBB 178
Bee and Wasp Sting Encephalopathy Reactions with Breakdown of the BBB 179
Congophilic Amyloid Encephalopathy with Breakdown of the BBB 180
Neurologic Disorders that may be Precipitated by Trauma 180
Conclusions 181
Chapter 8. Clinical Development and Benefit–Risk Profile of Natalizumab 188
Introduction 188
Mechanism of Action 188
Pharmacokinetics and Pharmacodynamics 189
Clinical Development 190
Efficacy 191
Subgroup Analysis Data 193
Novel Measures of Efficacy 197
Post hoc Analyses 201
Safety 204
Summary 208
Chapter 9. Remyelination in Multiple Sclerosis 214
Introduction 214
Remyelination in MS 214
The Role of Animal Models for the Study of Remyelination 216
Growth Factors in CNS Remyelination 218
Transcription Factors in Remyelination 223
Epigenetic Control of Oligodendrocytes 225
Clinical Trials for Remyelination in MS 227
Imaging of Remyelination in Clinical Trials 230
Obstacles for Regenerative Treatments in MS 231
Chapter 10. Transverse Myelitis 246
Introduction 246
Clinical Manifestations 247
Epidemiology 248
Pathogenesis 248
Neuropathology 249
Diagnosis 249
Differential Diagnosis 252
Course and Prognosis 253
Chapter 11. Neuromyelitis Optica 258
Definition and Epidemiology 258
Pathophysiology 258
Clinical Manifestations 259
Diagnostic Criteria 261
Differential Diagnosis 263
Treatment 264
Chapter 12. Optic Neuritis: Pathophysiology, Clinical Features, and Management 274
Introduction 274
Definition 275
Pathophysiology 275
Clinical Features 279
Assessment of the Optic Nerve 282
Prognosis 285
Management 287
Conclusion 291
Chapter 13. Ischemic Demyelination 298
Introduction 298
Manifestations of Hypertensive Microangiopathy 299
CADASIL 300
Binswanger’s Disease 304
White Matter Disease and Cerebral Hemorrhage 306
Migraine 306
Pathogenic Models of Ischemic Demyelination 307
Ischemic Demyelination and Ischemic Stroke Risk 309
Chapter 14. Inflammatory Mechanisms in Ischemic Cerebrovascular Disease 314
Inflammatory Cell Recruitment in Ischemic Stroke 314
Inflammatory Mechanisms in Cerebrovascular Thrombosis 328
Conclusions 338
Chapter 15. Protection Against Neuroinflammation by Promoting Co-activation of G Protein–Growth Factor Signaling and Metabolic Flexibility in the Brain 346
The Challenge of Neuroinflammation 346
MS: Neuroinflammation, Ionic Imbalance, and Energy Depletion 348
Metabolic Flexibility: Regulation of Energy Substrate Usage in the Brain 351
Co-activation of Trophic Factor Receptors in the Brain 352
Neuroprotection: Pharmacologic Approaches 353
Additional Issues for Neuroprotective Strategies 360
Chapter 16. Mesenchymal Stem Cells, Inflammation, and Neurodegenerative Diseases 368
Introduction 368
MSCs and Inflammation 371
MSCs and Dendritic Cells 372
MSCs and T Lymphocytes 373
MSCs and B Lymphocytes 374
MSCs and NK Cells 374
Immunogenicity of MSCs 375
MSC Migration into Inflamed Tissues and Tumors 376
MSCs and Tumors 378
Migration of Differentiated and Undifferentiated Stem Cells 379
Anti-Inflammatory Activities of MSCs in Clinical and Experimental Studies 380
MSCs and Neurodegenerative Diseases 381
The Routes and Timing of Injection of Stem Cells 387
Side Effects of Stem Cell Therapy 388
Chapter 17. Inflammatory Mediators in Obstructive Sleep Apnea 402
Introduction to Obstructive Sleep Apnea 402
Risk Factors and Epidemiology of OSA 403
Chapter Objectives 403
OSA and Cardiovascular Risk 405
OSA and the Metabolic Syndrome 405
OSA and Daytime Neurocognitive Impairment 406
The Overlap Between OSA, Obesity, and Asthma 407
OSA and Oxidative Stress 408
Systemic Inflammatory Mediators Associated with OSA 409
Summary 414
Chapter 18. The Role of Neuroinflammation in Parkinson’s Disease 424
Introduction to Parkinson’s Disease 424
Neuroinflammation in the Pathogenesis of PD 427
Evidence of Neuroinflammation in PD 429
Molecular Pathways Involved in Neuroinflammation of PD 431
Is Anti-Inflammatory Therapy the Answer for PD Prevention? 434
Chapter 19. Neuroinflammation and Pediatric Lupus 444
Introduction 444
Manifestations of NPSLE 444
Proposed Etiology of NPSLE Neurobehavioral Syndromes 446
Diagnosis of NPSLE 449
Diagnosis of Cognitive Dysfunction Syndromes in Children 451
Computer-Based Neurocognitive Testing 452
Imaging for Diagnosing Neurocognitive Dysfunction 453
Treatment of NPSLE 455
Chapter 20. Central Nervous System Vasculitis 460
Introduction to Vasculitides 460
The CNS in Primary Vasculitides 461
Secondary CNS Vasculitides 473
Conclusions 479
Chapter 21. Systemic Lupus Erythematosus—Vasculopathy/Vasculitis, Susac Syndrome, and Myasthenia Gravis 488
Introduction 488
Selected Etiologic Factors 490
Pathophysiology of Vasculopathy and Vasculitis in SLE 490
Susac Syndrome as an Example of a Rare Autoimmune Vasculopathy 495
Neurologic Symptoms Related to Vasculopathy and Vasculitis 498
SLE and Myasthenia Gravis 499
Chapter 22. Inflammatory Mechanisms in Guillain–Barré Syndrome 508
Chapter 23. Neurologic Manifestations of Herpes Zoster 518
Introduction 518
Primary VZV Infection 518
Herpes Zoster 520
Postherpetic Neuralgia 520
VZV Vasculopathy 521
VZV Meningoencephalitis 523
VZV Myelopathy 523
VZV Cerebellitis 523
VZV Retinal Necrosis 524
Zoster Sine Herpete 524
Vaccination 525
Molecular Aspects of VZV Infection and Latency 526
Development of Animal Models 529
Simian Varicella Virus 530
Conclusion 532