Handbook of Multiple Sclerosis, Fourth Edition

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ISBN: 9781574448276 | 1574448277
Cover: Hardcover
Copyright: 3/13/2006

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Univ. of Medicine and Dentistry of New Jersey, Newark. Text spans the etiology, epidemiology, clinical features, diagnosis, pathology, and treatment of multiple sclerosis. Provides recommendations and research updates on genetics, neuroimaging, and more. Previous edition: c2001. For clinicians. DNLM: Multiple sclerosis.

Preface

Acknowledgment

vii

Contributors

xvii

PART I: ETIOPATHOGENESIS

1. Etiopathogenesis and Epidemiology: Clues to Etiology

(40)

William Pryse-Phillips and Scott Sloka

Introduction

(1)

Familial Factors and Genetic Susceptibility

(4)

Prevalence and Incidence Studies

(7)

Intercurrent Factors with Possible Association

(9)

Natural History and Clinical Variability

(3)

Clues to Etiology

(5)

References

(11)

2. Genetics: Susceptibility and Expressivity

(24)

Thomas Masterman and Jan Hillert

Susceptibility

(8)

Expressivity

(1)

Prospects

(6)

References

(9)

3. Evidence for an Infectious Etiology of Multiple Sclerosis

(30)

Stuart D. Cook

Introduction

(1)

Historical Perspective

(2)

Evidence for an Infectious Etiology

(3)

Possible Mechanisms of Virus-Induced Demyelination

(3)

Candidate Agents in MS

(12)

Conclusion

(1)

References

(10)

4. Multiple Sclerosis: An Autoimmune Disease of the Central Nervous System?

(18)

John R. Rinker II, Robert T. Naismith, and Anne H. Cross

Introduction

(1)

Epidemiology

(1)

Pathology Suggests an Autoimmune Etiology

(1)

Genetic Evidence Supporting Autoimmunity in MS

(1)

Evidence for T-Cell Mediated Autoimmunity in MS

(3)

Humoral Immunity as Indirect Evidence for Autoimmunity in MS

101

(2)

Response to Immunosuppressive Therapies Suggests an Autoimmune Etiology

103

(1)

The Autoimmune Hypothesis Is Supported by Animal Models

103

(1)

Summary

104

(1)

References

105

(8)

PART II: CLINICAL–PATHOLOGIC CHARACTERISTICS

5. Pathology: What May It Tell Us?

113

(40)

Claudia F. Lucchinetti and Joseph E. Parisi

Introduction

113

(1)

How Does Stage of Demyelinating Activity Relate to Clinical Phase of the Disease?

114

(5)

What Is the Pathogenic Role of Inflammation in MS?

119

(2)

What Is the Fate of the Oligodendrocyte and Extent of Remyelination in MS Lesions?

121

(2)

Is There Evidence for Pathologic Heterogeneity in MS?

123

(5)

Does Pathologic Heterogeneity Reflect Pathogenic Heterogeneity in MS?

128

(2)

What Is the Substrate of Irreversible Disability in MS?

130

(1)

The Inflammatory Demyelination/Neurodegeneration Paradox

130

(6)

What Is the Spectrum of Idiopathic Inflammatory Demyelinating Diseases?

136

(5)

What Do New Molecular Studies Tell Us About the MS Lesion?

141

(2)

Conclusion

143

(1)

References

143

(10)

6. Clinical Features

153

(26)

Aaron E. Miller

Introduction

153

(1)

Diagnosis

153

(5)

Age of Onset

158

(1)

Clinical Manifestations

158

(8)

Course

166

(2)

Pregnancy

168

(1)

References

169

(10)

7. MRI Techniques in Multiple Sclerosis: Role in Diagnosis, Pathophysiology, and Therapy

179

(44)

Massimo Filippi, Federica Agosta, Beatrice Benedetti, and Maria A. Rocca

Introduction

179

(3)

A Brief Review of Basic Aspects of Nonconventional MRI Techniques

182

(3)

The Role of MRI in the Diagnosis and Prognosis of MS

185

(9)

The Role of MRI in Understanding MS Pathophysiology

194

(10)

MRI in Monitoring Treatment Efficacy in MS Trials

204

(3)

Conclusions

207

(1)

References

208

(15)

8. Multiple Sclerosis Biomarkers

223

(20)

P.K. Coyle

Introduction

223

(3)

Potential Biomarkers

226

(9)

Neuroimaging

235

(1)

Conclusion

236

(1)

References

236

(7)

9. Evoked Potentials

243

Marc R. Nuwer

Introduction

243

(1)

Visual Evoked Potentials

244

(3)

Brainstem Auditory Evoked Potentials

247

(2)

Somatosensory Evoked Potentials

249

(3)

Motor EPs

252

(1)

Event-Related Potentials

253

(1)

Multimodality EP Testing

253

(3)

Use of EPs in MS Therapeutic Trials

256

(4)

References

260

(11)

PART III: THERAPIES—CURRENT AND FUTURE

10. Managing the Symptoms of Multiple Sclerosis

271

(10)

Randall T. Schapiro

Introduction

271

(1)

Fatigue

271

(1)

Spasticity

272

(1)

Weakness

273

(1)

Urinary Dysfunction

274

(1)

Bowel Dysfunction

274

(1)

Sexual Dysfunction

275

(1)

Pain

275

(1)

Tremor

276

(1)

Visual Dysfunction

276

(1)

Paroxysmal Spasms

277

(1)

Pathological Laughing/Crying

277

(1)

Depression

277

(1)

Conclusion

277

(1)

References

278

(3)

11. Rehabilitation: Its Role in Multiple Sclerosis

281

(20)

George H. Kraft and Anjali N. Shah

Introduction

281

(1)

Fatigue

282

(2)

Weakness and Spasticity

284

(5)

Body Cooling

289

(2)

Ataxia and Tremor

291

(1)

Sensory Loss and Pain

292

(1)

Depression

293

(1)

Cognitive Impairment

293

(1)

General Fitness

294

(1)

Assistive Technology

295

(1)

Vocational Issues

296

(1)

Conclusion

296

(1)

References

297

(4)

12. Acute Treatments

301

(16)

Brian G. Weinshenker and Nima Mowzoon

Introduction

301

(3)

Treatment with Corticosteroids

304

(2)

Intravenous Immunoglobulin

306

(2)

Therapeutic Plasma Exchange

308

(2)

Mitoxantrone

310

(1)

Cyclophosphamide

311

(1)

Conclusions

312

(1)

References

313

(4)

13. Treatment of the Clinically Isolated Syndromes

317

(16)

Giancarlo Comi

Introduction

317

(1)

Rationale for Early Treatment

317

(10)

Conclusion

327

(1)

References

327

(6)

14. The Use of Interferon Beta in the Treatment of Multiple Sclerosis

333

(18)

Douglas S. Goodin

Introduction

333

(2)

Biological Consequences of IFNβ Administration

335

(1)

Assessing the Clinical and MRI Effects of IFNβ in MS Patients

336

(10)

Conclusions

346

(1)

References

347

(4)

15. Glatiramer Acetate (Copaxone®)

351

(22)

Yang Mao-Draayer and Hillel S. Panitch

Introduction

351

(1)

Clinical Studies of GA

351

(10)

Immunological Activity of GA

361

(4)

The Place of GA in MS Therapy

365

(1)

Conclusion

366

(1)

References

366

(7)

16. Mitoxantrone

373

(12)

Oliver Neuhaus, Bernd C. Kieseier, and Hans-Peter Hartung

Introduction

373

(1)

Evidence Leading to the Approval of Mitoxantrone for Use in Multiple Sclerosis

373

(3)

Current Clinical Aspects of Mitoxantrone

376

(3)

Putative Mechanisms of Action of Mitoxantrone

379

(2)

Conclusions

381

(1)

References

381

(4)

17. Monoclonal Antibodies, T-Cell Receptors, and T-Cell Vaccines

385

(24)

Flavia Nelson and Jerry S. Wolinsky

Introduction

385

(1)

Monoclonal Antibodies

385

(13)

T-Cell Vaccines

398

(3)

Conclusion

401

(1)

References

402

(7)

18. Immune Therapy for Multiple Sclerosis: Altered Peptide Ligands and Statins

409

(14)

Fu-Dong Shi, Denise I. Campagnolo, and Timothy L. Vollmer

Introduction

409

(1)

Is the Use of APLs Still a Viable Approach for Treatment of MS?

409

(4)

Are Statins a Treatment Option for MS?

413

(6)

References

419

(4)

19. Immunosuppression

423

(20)

Harold Atkins and Mark Freedman

Introduction

423

(1)

Cyclophosphamide

424

(2)

Complete Immunoablation and Autologous Stem Cell Transplantation

426

(1)

Transplant Studies in MS

427

(2)

Stem Cell Transplantation

429

(4)

MS Outcomes Following Transplantation

433

(1)

Patient Selection

434

(1)

Future Directions—Beyond Cytotoxic Immunosuppression

434

(1)

Future Directions—Beyond Repair of the Immune System

435

(1)

Conclusion

435

(1)

References

435

(8)

20. Combination Therapy in Multiple Sclerosis

443

(10)

Mark J. Tullman and Fred D. Lublin

Introduction

443

(1)

Selecting Agents for Combination Therapy

443

(2)

IFNβ and GA

445

(2)

IFN, Methylprednisolone, and Methotrexate

447

(1)

Mitoxantrone and Methylprednisolone

448

(1)

Conclusions

449

(1)

References

450

(3)

21. Regeneration Strategies for Multiple Sclerosis

453

(24)

Arthur E. Warrington and Moses Rodriguez

Introduction

453

(1)

Remyelination as a Normal Reparative Response

454

(1)

Present Treatments for MS Target Inflammation, Not Repair

454

(1)

Inflammation Hinders as well as Facilitates CNS Repair

455

(1)

Growth Factors for MS Lesion Repair and Regeneration

456

(1)

Cell Transplantation for MS Lesion Repair and Regeneration

457

(2)

Pathogenic Antibodies Directed Against CNS Antigens

459

(1)

Reparative Antibodies Directed Against CNS Antigens

459

(4)

Glatiramer Acetate, an Established Treatment for MS, May Act via a Humoral Immune Response

463

(1)

Mechanism of Antibody-Mediated CNS Repair

464

(2)

Remyelination Promoting mAbs Target the Damaged CNS

466

(1)

The Challenge of Balancing Inflammation for Regeneration

467

(1)

References

467

(10)

22. Axonal Injury in Multiple Sclerosis

477

(30)

Gerson A. Criste and Bruce D. Trapp

Introduction

477

(1)

Axonal Pathology in MS Lesions

477

(4)

Mechanism of Axonal Injury in MS

481

(5)

Strategies for Axonal Protection

486

(3)

Surrogate Markers of Axonal Loss

489

(6)

Clinical Implications

495

(1)

Conclusion

496

(1)

References

497

(10)

Index

507

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Handbook of Multiple Sclerosis, Fourth Edition

Summary

Table of Contents

Supplemental Materials