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PART III: THERAPIES—CURRENT AND FUTURE

10. Managing the Symptoms of Multiple Sclerosis 271

Randall T. Schapiro

Introduction 271

Fatigue 271

Spasticity 272

Weakness 273

Urinary Dysfunction 274

Bowel Dysfunction 274

Sexual Dysfunction 275

Pain 275

Tremor 276

Visual Dysfunction 276

Pathological Laughing/Crying . . . . 277

References 278

11. Rehabilitation: Its Role in Multiple Sclerosis 281

George H. Kraft and Anjali N. Shah Introduction 281 Fatigue . . . . 282 Weakness and Spasticity . . . . 284 Body Cooling 289 Ataxia and Tremor 291 Sensory Loss and Pain . . . . 292 Depression 293 Cognitive Impairment . . . . 293 General Fitness . . . . 294 Assistive Technology . . . . 295 Vocational Issues . . . . 296 Conclusion . . . . 296 References . . . . 297

12. Acute Treatments 301

Brian G. Weinshenker and Nima Mowzoon Introduction 301 Treatment with Corticosteroids 304 Intravenous Immunoglobulin . . . . 306 Therapeutic Plasma Exchange . . . . 308 Mitoxantrone . . . . 310 Cyclophosphamide 311 Conclusions . . . . 312 References . . . . 313

13. Treatment of the Clinically Isolated Syndromes 317

Giancarlo Comi

Introduction 317

Rationale for Early Treatment 317

Conclusion 327

References 327

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

Sclerosis 333

Biological Consequences of IFNb Administration 335 Assessing the Clinical and MRI Effects of IFNb in

MS Patients 336 Conclusions 346 References 347

15. Glatiramer Acetate (Copaxone®) 351

Yang Mao-Draayer and Hillel S. Panitch

Immunological Activity of GA 361

The Place of GA in MS Therapy 365

16. Mitoxantrone 373

Oliver Neuhaus, Bernd C. Kieseier, and Hans-Peter Hartung Introduction . . . . 373

Evidence Leading to the Approval of Mitoxantrone for Use in

Multiple Sclerosis . . . . 373 Current Clinical Aspects of Mitoxantrone . . . . 376 Putative Mechanisms of Action of Mitoxantrone 379 Conclusions 381 References 381

17. Monoclonal Antibodies, T-Cell Receptors, and

T-Cell Vaccines 385

Flavia Nelson and Jerry S. Wolinsky Introduction . . . . 385 Monoclonal Antibodies 385 T-Cell Vaccines 398 Conclusion 401 References 402

18. Immune Therapy for Multiple Sclerosis: Altered Peptide

Ligands and Statins 409

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

Introduction 409

Is the Use of APLs Still a Viable Approach for Treatment of MS? ... . 409 Are Statins a Treatment Option for MS? 413 References 419

19. Immunosuppression 423

Harold Atkins and Mark Freedman Introduction 423 Cyclophosphamide 424

Complete Immunoablation and Autologous Stem Cell

Transplantation 426 Transplant Studies in MS 427 Stem Cell Transplantation 429 MS Outcomes Following Transplantation 433 Patient Selection 434 Future Directions—Beyond Cytotoxic

Immunosuppression . . . . 434 Future Directions—Beyond Repair of the Immune

System 435 Conclusion 435 References . . . . 435

20. Combination Therapy in Multiple Sclerosis 443

Mark J. Tullman and Fred D. Lublin Introduction 443

Selecting Agents for Combination Therapy . . . . 443 IFNp and GA . . . . 445

IFN, Methylprednisolone, and Methotrexate 447 Mitoxantrone and Methylprednisolone 448 Conclusions . . . . 449 References . . . . 450

21. Regeneration Strategies for Multiple Sclerosis 453

Arthur E. Warrington and Moses Rodriguez Introduction . . . . 453

Remyelination as a Normal Reparative Response . . . . 454

Present Treatments for MS Target Inflammation,

Not Repair 454 Inflammation Hinders as well as Facilitates

CNS Repair . . . . 455 Growth Factors for MS Lesion Repair and Regeneration 456

Cell Transplantation for MS Lesion Repair and Regeneration 457 Pathogenic Antibodies Directed Against CNS

Antigens 459 Reparative Antibodies Directed Against CNS

Antigens . . . . 459 Glatiramer Acetate, an Established Treatment for MS,

May Act via a Humoral Immune Response 463 Mechanism of Antibody-Mediated CNS Repair 464 Remyelination Promoting mAbs Target the

Damaged CNS . . . . 466 The Challenge of Balancing Inflammation for

22. Axonal Injury in Multiple Sclerosis .

Gerson A. Criste and Bruce D. Trapp Introduction 477 Axonal Pathology in MS Lesions . . Mechanism of Axonal Injury in MS Strategies for Axonal Protection . . . Surrogate Markers of Axonal Loss . Clinical Implications 495 Conclusion 496 References . . . . 497

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