From NEUROSCIENCE To NEUROLOGY: Neuroscience, Molecular Medicine, and the Therapeutic Transformation of Neurology

545 Pages·2004·14.33 MB·English

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From NEUROSCIENCE
To NEUROLOGY
Neuroscience, Molecular Medicine, and the Therapeutic Transformation
of Neurology
Edited by
STEPHEN WAXMAN, MD, PhD
Yale University
AMSTERDAM • BOSTON • HEIDELBERG • LONDON
NEW YORK • OXFORD • PARIS • SAN DIEGO
SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO
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Elsevier Academic Press
th
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Contents
Preface vii 7. Botulinum Toxins: Transformation
Contributors ix of a Toxin into a Treatment 125
I. Clinical Rewards From Neuroscience,
Molecular Medicine, and Translational 8. Prospects for Slowing the Progression
Research of Parkinson’s Disease 141
1. Seeing the Brain So We Can Save It: 9. Current Neurosurgical Treatments
The Evolution of Magnetic Resonance for Parkinson’s Disease:
Imaging as a Clinical Tool 3 Where Did They Come From? 159
2. Advances in the Acute Treatment and 10. Treatable Peripheral Neuropathies:
Secondary Prevention of Stroke 21 Plasma Exchange, Intravenous
Immunoglobulin, and Other Emerging
Therapies 175
3. Preserving Function in Acute Nervous
System Injury 35
11. Molecular Pharmacology and the
Treatment of Tourette’s Syndrome
4. Slowing the Progression of Multiple and Attention Deficit-Hyperactivity
Sclerosis 61 Disorder 183
5. The Emergence of Neurosurgical 12. Neuroscience, Molecular Medicine, and
Approaches to the Treatment of New Approaches to the Treatment of
Epilepsy 81 Depression and Anxiety 193
6. The Neurobiology of Migraine and
Transformation of Headache Therapy 107
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vi Contents
II. Moving Toward The Clinic: 22. Cellular Plasticity of the Adult Human
Evolving Themes and Technologies Brain 375
13. Genomics, Proteomics, and 23. Harnessing Endogenous Stem Cells for
Neurology 217 Central Nervous System Repair 387
14. Neuroprotection: Where Are We 24. Neuropathies—Translating Causes
Going? 237 into Treatments 405
15. Prospects for Gene Therapy for Central 25. Therapeutic Potential of Neurotrophic
Nervous System Disease 267 Factors 419
16. Therapeutics Development for Hereditary 26. Promoting the Regeneration of Axons
Neurological Diseases 285 within the Central Nervous System 433
17. Inherited Channelopathies of the CNS: 27. Alzheimer’s Disease: Clinical Features,
Lessons for Clinical Neurology 293 Neuropathological and Biochemical
Abnormalities, Genetics, Models,
and Experimental Therapeutics 445
18. Inherited Channelopathies of Muscle:
Implications for Therapy 303
28. Behavioral Intervention and Recovery
from CNS Damage 459
19. Transcriptional Channelopathies of the
Nervous System: New Targets for
Molecular Medicine 319 29. What Functional Brain Imaging Will Mean
for Neurology 471
20. New Molecular Targets for the Treatment Index 493
of Neuropathic Pain 339
21. Therapeutic Transfer and Regeneration
of Neural Progenitors or Neurons
in Gray Matter of the Adult Brain 357
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Preface
When I was a boy about five years old, I asked a grownup “will advances in neuroscience, tells the stories of how neuro-
men ever be able to travel to the moon?” and the answer was logical therapeutics were developed—or are being devel-
“it’s impossible.” oped. The first part of this book reviews the development
Less than two decades later, as a medical student working in of new therapies in neurology, from their inception in
London, I watched on television as a man walked on the moon.
terms of basic science to their introduction into the clin-
The “impossible” had become possible.
ical world. Within the first section, authors address the
This book focuses on the remarkable transformation questions: How has the revolution in neurology occurred?
that has occurred within neurology, a transformation from What lessons can we learn from past successes? Can these
the “impossible” to the possible. lessons help us to ensure progress in the future? The second
Twenty-five years ago computed tomography had just part of this volume explores evolving themes and new
become available and was rapidly evolving, but magnetic technologies. Changes in the practice of neurology have
resonance imaging was not yet feasible in the clinical been driven by advances in the laboratory. But, in paral-
realm. Medical students at some institutions were taught lel with the transformation of clinical neurology, neuro-
to try not to make the diagnosis of multiple sclerosis science and molecular medicine are moving forward
early in its course, since there was little that could be rapidly and are generating new information and perspec-
done. Some senior neurologists—good clinicians—made tives at an ever-increasing rate. The chapters in the sec-
the diagnosis of MS and then walked away from the bed- ond part of the book explore rapidly-advancing areas of
side, since there was little to offer in the way of effective research which may hold the key to still other therapeu-
therapy. Peripheral neuropathies were regarded as tic advances. Hopefully these chapters will provide a
untreatable. Strokes were treated with bed rest, and not roadmap for the future.
much else. Who knows what neurology will be like twenty-five
Now, only a few decades later, we have access to imag- years from now? There will undoubtedly be additional,
ing techniques that portray the brain and spinal cord— and very powerful, diagnostic methods. And there will
noninvasively—in elegant detail. There are five approved almost certainly be new, and more effective, therapies for
drugs for MS, which favorably modify its course. Plasma patients with disorders of the nervous system. Some of
exchange is routinely and effectively used to treat these advances will be outgrowths of research that is
Guillain-Barré syndrome. Strokes are prevented by ongoing at this time, while others may come from
aggressive diagnosis and treatment of hypertension, and advances that have not yet been imagined. We cannot
are sometimes reversed with thrombolysis. These changes know for sure, at this time, which diseases of the nervous
in our therapeutic armamentarium are only the tip of system will be cured, and which symptoms will be totally
an iceberg. New and more effective treatments for alleviated in two decades. We can, however, predict with
Parkinson’s disease, migraine, spasticity, and dystonia at a high degree of certainty that, as each year passes, the
all at hand, and there is more to come. therapeutic transformation of neurology will continue
The goal of this book is to capture the trajectory, and so that, in each new decade, an increasing number of
the creative processes, underlying the revolution that is neurological disorders will yield to therapy. That is
going on in neurology. This book, rather than being a almost a certainty. And it is to that goal that this book is
compendium of neurological therapeutics or of recent dedicated.
vii
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viii Preface
ACKNOWLEDGEMENTS the scenes, have been partners in the battle against dis-
abling neurological disorders. I also extend my thanks to
This book could not have been written without the Sheila MacMillan who guided most of the chapters
efforts of its chapter authors and to them I am most through early stages of the editing process, to my col-
grateful. On their behalf, I express deep thanks to the leagues who encouraged me at every juncture, and to my
many individuals and organizations that have supported family who endured the closed door of my study while I
research on disorders of the nervous system. The worked on this book. Finally, I am indebted to Academic
Paralyzed Veterans of America, the United Spinal Press and, particularly, to Karen Dempsey who very ably
Association, and their leadership deserve special thanks handled the editorial process at Academic Press, and
for unwavering commitment and support. I am especially Jasna Markovac whose encouragement helped make this
grateful to Dan Flaherty and Sandra Kulli who, behind book a reality.
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Contributors
Amy Arnsten, Department of Neurobiology, Yale Fred H. Gage, Laboratory of Genetics, The Salk
University School of Medicine, New Haven, Institute for Biological Studies, La Jolla, California
Connecticut
Daniel H. Geschwind, Department of Neurology,
Aviva Abosch, Department of Neurology and Surgery, University of California Los Angeles School of
Center for Neurodegenerative Disease, Emory Medicine, Los Angeles, California
University School of Medicine, Atlanta, Georgia
Steve Goldman, Department of Neurology, University
Arthur A. Asbury, Department of Neurology, Hospital of Rochester Medical Center, Rochester, New York
of the University of Pennsylvania, Philadelphia,
Edward D. Hall, Spinal Cord and Brain Injury
Pennsylvania
Research Center, University of Kentucky Chandler
Hayrunnisa Bolay, Department of Neurology, Gazi Medical Center, Lexington, Kentucky
University Hospitals, Ankara, Turkey
Mark Hallett, Human Motor Control Section, National
Sophia A. Colamarino, Laboratory of Genetics, The Institute of Neurological Disorders and Stroke,
Salk Institute for Biological Studies, La Jolla, California National Institutes of Health, Bethesda, Maryland
Cynthia L. Comella, Department of Neurology, Rush Jill Heemskerk, Technology Development, National
Presbyterian St. Lukes Medical Center, Chicago, Illinois Institute of Neurological Disorders and Stroke,
National Institutes of Health, Bethesda, Maryland
Theodore R. Cummins, Stark Neuroscience Research
Institute, Indiana University School of Medicine, George R. Heninger, Department of Psychiatry,
Indianapolis, Indiana Connecticut Mental Health Center, New Haven,
Connecticut
Gary H. Danton, Department of Neurological Surgery,
University of Miami School of Medicine, Miami, Amie W. Hsia, Department of Neurology, Stanford
Florida University School of Medicine, Palo Alto, California
W. Dalton Dietrich, The Miami Project and Ole Isacson, Neurorenegeration Laboratories, Harvard
Department of Neurological Surgery, University of Medical School/McLean Hospital, Belmont,
Miami School of Medicine, Miami, Florida Massachusetts
Jerome Engel, Reed Neurological Research Center, Joseph Jankovic, Department of Neurology, Baylor
Neurology Department #1250, Los Angeles, California College of Medicine, Houston, Texas
Kenneth H. Fischbeck, National Institute of Dmitri M. Kullman, Experimental Epilepsy Group,
Neurological Disorders and Stroke, National Institutes Institute of Neurology, London, United Kingdom
of Health, Bethesda, Maryland
D. Chichung Lie, Laboratory of Genetics, The Salk
R.S.J. Frackowiak, Wellcome Department of Cognitive Institute for Biological Studies, La Jolla, California
Neurology, Institute of Neurology, London, United
Kingdom
ix
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x Contributors
Kenneth L. Marek, The Institute for Neurodegenerative Lance Simpson, Department of Biochemistry and
Disease and Yale University School of Medicine, New Molecular Pharmacology, Jefferson Medical College,
Haven, Connecticut Philadelphia, Pennsylvania
Christiane Massicotte, Department of Clinical Studies, Hongjun Song, Institute for Cell Engineering,
School of Veterinary Medicine, University of Department of Neurology, Johns Hopkins University
Pennsylvania, Philadelphia, Pennsylvania School of Medicine, Baltimore, Maryland
John C. Mazziotta, Brain Mapping Center, University Stephen Strittmatter, Department of Neurology, Yale
of California Los Angeles School of Medicine, Los University School of Medicine, New Haven,
Angeles, California 90095 Connecticut
Stephen B. McMahon, Center for Neuroscience, King’s Patrick G. Sullivan, Spinal Cord and Brain Injury
College—London, London, United Kingdom Research Center, University of Kentucky Chandler
Medical Center, Lexington, Kentucky
Michael A. Moskowitz, Stroke and Neurovascular
Regulation Laboratory, Department of Neurosurgery, Mark H. Tuszynski, Department of Neurology,
Massachusetts General Hospital, Charlestown, University of California, San Diego, La Jolla,
Massachusetts California
Beth Murinson, Department of Neurology, Johns Jerrold L. Vitek, Center for Neurological Restoration,
Hopkins School of Medicine, Baltimore, Maryland Cleveland Clinic Foundation, Cleveland, Ohio
James H. Park, Department of Neurology, Yale Bernhard Voller, Human Motor Control Section,
University School of Medicine, New Haven, National Institute of Neurological Disorders and
Connecticut Stroke, National Institutes of Health, Bethesda,
Maryland
Donald L. Price, Department of Pathology, The Johns
Hopkins University, Baltimore, Maryland Benjamin L. Walter, Center for Neurological
Restoration, Cleveland Clinic Foundation, Cleveland,
Richard A. Rudick, The Mellen Center, Cleveland
Ohio
Clinic Foundation, Cleveland, Ohio
Steven Warach, Stroke Diagnostics and Therapeutics,
Robert L. Ruff, Neurology Service, Cleveland Veteran’s
National Institute of Neurological Disorders and
Affairs Medical Center, Cleveland, Ohio
Stroke, National Institutes of Health, Bethesda,
Peter D. Schellinger, Stroke Diagnostics and Maryland
Therapeutics, National Institute of Neurological
Steven G. Waxman, Department of Neurology and the
Disorders and Stroke, National Institutes of Health,
Center for Neuroscience and Regeneration Research,
Bethesda, Maryland
Yale University School of Medicine, New Haven,
Steven Scherer, Department of Neurology, The Connecticut
University of Pennsylvania Medical Center,
John N. Wood, Department of Anatomy and
Philadelphia, Pennsylvania
Developmental Biology, University College, London,
Lorelei D. Shoemaker, Neuroscience Interdepartmental United Kingdom
PhD Program, University of California Los Angeles,
Los Angeles, California
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P A R T
I
Clinical Rewards From Neuroscience, Molecular
Medicine, and Translational Research