Advances in Multiple Sclerosis and Experimental Demyelinating Diseases (eBook)

Moses Rodriguez (Herausgeber)

eBook Download: PDF

2007 | 2008
XIV, 362 Seiten
Springer Berlin (Verlag)
978-3-540-73677-6 (ISBN)

Infos

Controversy still exists regarding how early disease-modifying agents (DMA) should be commenced and whether all patients with relapsing-remitting MS should in fact be treated. To answer these questions, it is also important to know the natural history of the disease. MS affects nearly 400,000 people in the United States. With their novel, multifaceted approach to basic science, the authors of this book offer help to clinicians and hope to patients.

Inhalt

Preface 5
Contents 11
Contributors 13
Benign Multiple Sclerosis: A Distinct Clinical Entity with Therapeutic Implications 15
1 Introduction 16
2 Natural History of Multiple Sclerosis: Disability Progression 16
3 Benign MS: A Fallacy or a Distinct Clinical Entity? 17
4 Does Benign MS Stay Benign with Increasing Disease Duration? 18
5 Other Clinical Predictors of MS Outcome 20
6 Neuroimaging Studies in Benign MS 21
7 The Currently FDA-Approved Disease-Modifying Agents: Efficacy, Mode of Action, and Side Effects 23
8 Should All MS Patients Be Treated with Disease- Modifying Therapies? 27
References 28
Pathological Heterogeneity of Idiopathic Central Nervous System Inflammatory Demyelinating Disorders 32
1 Introduction 33
2 Heterogeneity of Multiple Sclerosis White Matter Lesions 34
3 Remyelination in MS 44
4 The Clinicopathologic Spectrum of CNS Idiopathic Inflammatory Demyelinating Disorders 45
Conclusions 51
References 51
Multiple Sclerosis Genetics 57
1 Introduction 58
2 Major Histocompatibility Complex and Multiple Sclerosis 59
3 Genetic Analyses 61
4 Microarray Studies 69
5 Future Directions 73
References 75
Imaging of Remyelination and Neuronal Health 85
Abbreviations 86
1 Introduction 86
2 Conventional MRI of Remyelination 88
3 Magnetization Transfer Imaging of Remyelination 92
4 Diffusion Imaging of Remyelination 95
5 Spectroscopy of Remyelination 98
6 Other Imaging Modalities 100
Conclusions 102
References 102
Immunological Aspects of Axon Injury in Multiple Sclerosis 105
1 Introduction 106
2 Changes in Axon Function During Demyelination 106
3 Axonal Degeneration During Demyelination 115
4 Immune-Mediated Mechanisms of Axon Injury During Demyelination 119
5 Stress and the Naked Axon – A Hypothesis 130
References 130
The Multiple Sclerosis Degradome: Enzymatic Cascades in Development and Progression of Central Nervous System Inflammatory Disease 144
1 Introduction 145
2 Multiple Classes of Protease Implicated in MS 146
3 Functional Roles of Proteases in MS 158
4 Novel Hypothesis Regarding Role of Proteases in MS 167
5 Proteases as Targets for Rationale Drug Design 168
Conclusion 170
References 170
Genetic Analysis of CNS Remyelination 187
1 Introduction 188
2 Mouse Models of Demyelinating Disease 189
3 Cellular Events in Remyelination 190
4 Genetic Analysis in the Mouse 190
5 Reverse Genetic Analysis of CNS Remyelination 192
6 Forward Genetic Analysis of CNS Remyelination 197
References 200
Remyelination in Experimental Models of Toxin- Induced Demyelination 203
1 Introduction 204
2 Demyelinating Toxins 206
3 What is the Place of Toxin Models in the Study of CNS Demyelination and Remyelination? 215
References 218
Remyelination-Promoting Human IgMs: Developing a Therapeutic Reagent for Demyelinating Disease 223
1 Multiple Sclerosis is a Disease of Myelin 224
2 Remyelination as a Normal Reparative Response 224
3 Strategies to Augment Remyelination 226
4 Antibodies Directed Against CNS Antigens Can be Pathogenic or Reparative 229
5 Human Antibodies that Promote Remyelination 231
6 Role of Anti-CNS Antibodies in Endogenous Repair 233
7 A Recombinant Human IgM Promotes Remyelination in vivo at Doses Comparable to Growth Factors 233
8 The IgM Character of Remyelination Promoting Antibodies is Vital for Function 236
9 Mechanisms of Antibody-Mediated CNS Repair 237
10 Therapeutic Goal: Alter the Balance of Inflammation to Favor Regeneration 239
References 240
Neuroimaging of Demyelination and Remyelination Models 250
1 Introduction 251
2 Conventional MRI Studies 253
3 Advanced MRI Methods for Visualizing Demyelinating Diseases 260
4 T1 and T2 Relaxometry 264
5 Magnetic Resonance Spectroscopy 265
6 Cell-Specific Contrast Agents 266
7 Imaging of Remyelination in MS Models 269
8 Conclusions and Future Directions 271
References 272
Hormonal Influences in Multiple Sclerosis 276
1 Introduction 277
2 Glucocorticoids 278
3 Female Hormones of Reproduction and MS 284
4 Testosterone and DHEA 295
5 Vitamin D 298
6 Thyroid Hormone 301
7 Leptin and Ghrelin 305
8 Conclusions 307
References 308
Statins and Demyelination 321
1 Introduction 322
2 Mechanism of Action 322
3 Statins in Treatment of Experimental Autoimmune Encephalomyelitis 323
4 Statins in Treatment of MS 326
References 329
Role of Uric Acid in Multiple Sclerosis 333
1 Uric Acid in Evolution 333
2 Uric Acid and Free Radicals 335
3 Role of Free Radicals in Multiple Sclerosis: Lessons from Experimental Allergic Encephalomyelitis and Other Models 336
4 Serum Uric Acid Levels in Patients with Multiple Sclerosis 338
5 Possible Mechanisms of Uric Acid Action in Multiple Sclerosis, Protection of Blood– Brain Barrier Integrity 343
6 Treatment of MS Patients by Raising UA Levels 344
Conclusions 346
References 346
Neuromyelitis Optica: Clinical Syndrome and the NMO- IgG Autoantibody Marker 351
1 All that Relapses is not MS 352
2 NMO is Distinct: The Clinical Clues 354
3 A Tool: Discovery of a Biomarker and Its Target 355
4 Uncertainties (Boundaries, Forme Frustes, OSMS vs NMO, etc.) 357
5 Toward an Understanding of NMO Pathogenesis 359
6 How Has Current Knowledge Affected the Therapeutic Approach to NMO? 361
Conclusion 362
References 363
Index 365

Produkt-Details

• Erscheint lt. Verlag: 24.12.2007
• Reihe/Serie: Current Topics in Microbiology and Immunology
• Reihe/Serie: Current Topics in Microbiology and Immunology
• Zusatzinfo: XIV, 362 p.
• Verlagsort: Berlin
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Schlagworte: axon injury • interferon therapies • major histocompatibility complex • oligodendrocytes • pathophysiology • Physiology • Proteases • remyelination • statins
• ISBN-10: 3-540-73677-8 / 3540736778
• ISBN-13: 978-3-540-73677-6 / 9783540736776