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Spinal Cord Injury: Progress, Promise, and Priorities SPINAL CORD INJURY Progress, Promise, and Priorities Committee on Spinal Cord Injury Board on Neuroscience and Behavioral Health Catharyn T. Liverman, Bruce M. Altevogt, Janet E. Joy, and Richard T. Johnson, Editors INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu
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Spinal Cord Injury: Progress, Promise, and Priorities THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This study was supported by Contract No. C018427 between the National Academy of Sciences and the State of New York Department of Health. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project. Library of Congress Cataloging-in-Publication Data Spinal cord injury : progress, promise, and priorities / Committee on Spinal Cord Injury, Board on Neuroscience and Behavioral Health ; Catharyn T. Liverman … [et al.], editors. p. ; cm. Includes bibliographical references and index. ISBN 0-309-09585-9 (hardcover) 1. Spinal cord—Wounds and injuries. 2. Spinal cord—Wounds and injuries—Research—United States. [DNLM: 1. Spinal Cord Injuries—United States. 2. Health Policy—United States. 3. Research—United States. 4. Research Support—United States. 5. State Government—United States. WL 400 S757764 2005] I. Liverman, Catharyn T. II. Institute of Medicine (U.S.). Committee on Spinal Cord Injury. RD594.3.S6694 2005 617.4′82044—dc22 2005010581 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu. Copyright 2005 by the National Academy of Sciences. All rights reserved. Printed in the United States of America. Cover image: Mehau/Kulyk/Science Photo Library The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
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Spinal Cord Injury: Progress, Promise, and Priorities “Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES Adviser to the Nation to Improve Health
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Spinal Cord Injury: Progress, Promise, and Priorities THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org
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Spinal Cord Injury: Progress, Promise, and Priorities COMMITTEE ON SPINAL CORD INJURY RICHARD T. JOHNSON (Chair), Johns Hopkins University School of Medicine, Baltimore, MD ALBERT J. AGUAYO, McGill University, Montreal, Canada JEREMIAH A. BARONDESS, New York Academy of Medicine, New York, NY MARY BARTLETT BUNGE, The Miami Project to Cure Paralysis; University of Miami Leonard M. Miller School of Medicine, Miami, FL FRED H. GAGE, The Salk Institute for Biological Studies, La Jolla, CA SUZANNE T. ILDSTAD, Institute for Cellular Therapeutics, University of Louisville, Louisville, KY JOHN A. JANE, University of Virginia, Charlottesville LYNN T. LANDMESSER, Case Western Reserve University, Cleveland, OH LINDA B. MILLER, Volunteer Trustees Foundation, Washington, DC P. HUNTER PECKHAM, Case Western Reserve University, Cleveland, OH ROBERT T. SCHIMKE, Stanford University, Palo Alto, CA CHRISTOPHER B. SHIELDS, Norton Hospital, University of Louisville School of Medicine, Louisville, KY STEPHEN G. WAXMAN, Yale University School of Medicine, New Haven, CT Expert Consultants JESSE M. CEDARBAUM, Regeneron Pharmaceuticals, Tarrytown, NY GERALD D. FISCHBACH, Columbia University College of Physicians and Surgeons, New York, NY WISE YOUNG, Rutgers University, Piscataway, NJ Liaison to the IOM Board on Neuroscience and Behavioral Health SID GILMAN, University of Michigan Medical School, Ann Arbor Study Staff CATHARYN T. LIVERMAN, Study Director (from August 2004) JANET E. JOY, Study Director (until August 2004) BRUCE M. ALTEVOGT, Program Officer (from June 2004) MICHAEL T. ABRAMS, Program Officer (until March 2004) KATHLEEN M. PATCHAN, Research Associate LORA K. TAYLOR, Senior Program Assistant ANDREW M. POPE, Board Director CARLOS GABRIEL, Financial Associate AMY HAAS, Administrative Assistant (from September 2004) TROY PRINCE, Administrative Assistant (until September 2004) Consultant MIRIAM DAVIS, School of Public Health and Health Services, George Washington University, Washington, DC
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Spinal Cord Injury: Progress, Promise, and Priorities BOARD ON NEUROSCIENCE AND BEHAVIORAL HEALTH KENNETH B. WELLS M.D., M.P.H. (Chair), University of California, Los Angeles SID GILMAN, M.D. (Vice-Chair), University of Michigan, Ann Arbor NANCY E. ADLER, PH.D., University of California, San Francisco RHONDA J. ROBINSON BEALE, M.D., CIGNA Behavioral Health, Eden Prairie, MN WILLIAM E. BUNNEY, M.D., College of Medicine, University of California, Irvine HOWARD L. FIELDS, M.D., PH.D., University of California, San Francisco RICHARD G. FRANK, PH.D., Harvard Medical School, Boston, MA ALAN LESHNER, PH.D., American Association for the Advancement of Science, Washington, DC KAREN MATTHEWS, PH.D., University of Pittsburgh School of Medicine, Pittsburgh, PA BRUCE S. MCEWEN, PH.D., The Rockefeller University, New York, NY KATHLEEN R. MERIKANGAS, PH.D., National Institute of Mental Health, Bethesda, MD EMMANUEL MIGNOT, M.D., PH.D., Stanford University, Palo Alto, CA DAVID REISS, PH.D., George Washington University Medical Center, Washington, DC MICHAEL RUTTER, M.D., Institute of Psychiatry, University of London, England MARLEEN WONG, LCSW, Los Angeles Unified School District, Van Nuys, CA CHARLES F. ZORUMSKI, PH.D., Washington University School of Medicine, St. Louis, MO IOM Staff ANDREW M. POPE, Board Director CARLOS GABRIEL, Financial Associate AMY HAAS, Administrative Assistant (from September 2004) TROY PRINCE, Administrative Assistant (until September 2004)
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Spinal Cord Injury: Progress, Promise, and Priorities DEDICATION This report is dedicated to the memory of Christopher Reeve, whose tireless efforts galvanized the spinal cord injury research community and raised awareness of the issues involved in the care and cure of spinal cord injury and other chronic disabilities. His perseverance also gave hope to individuals with spinal cord injuries and caregivers. Continuing to advance toward curing spinal cord injuries is the ongoing challenge.
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Spinal Cord Injury: Progress, Promise, and Priorities REVIEWERS This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report: Thomas F. Budinger, Lawrence Berkeley National Laboratory Diana Cardenas, University of Washington Howard L. Fields, University of California, San Francisco Ralph F. Frankowski, University of Texas Health Science Center at Houston, School of Public Health Zach W. Hall, Keck School of Medicine of the University of Southern California Julian T. Hoff, University of Michigan Daniel P. Lammertse, CNS Medical Group Oswald Steward, Reeve-Irvine Research Center Steven M. Strittmatter, Yale University School of Medicine Paul Tobin, United Spinal Association Mark H. Tuszynski, University of California, San Diego
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Spinal Cord Injury: Progress, Promise, and Priorities William D. Whetstone, University of California, San Francisco Charles B. Wilson, Health Technology Center Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by Elena Nightingale, National Academies, and Enriqueta Bond, Burroughs Wellcome Fund. Appointed by the National Research Council and Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
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Spinal Cord Injury: Progress, Promise, and Priorities PREFACE How suddenly life can change—nowhere more dramatically than with a spinal cord injury: the robust young football player suddenly lying immobilized on the field; the child confined for life to a wheelchair after diving into a shallow pond; the vacationing family with a parent or child forever paralyzed after a skiing, bicycle, or car crash; the soldier left quadriplegic after a sniper shot to his neck; or anyone’s accidental tumble down stairs or from a ladder. We have all witnessed the tragedy of spinal cord injuries. It sometimes results from risky behavior, but most injuries result from unforeseen accidents in an active, healthy life. The time has come that we may be able to make a major change in how we deal with this frightening personal and public health problem. Survival from severe spinal cord injuries became a reality during and after World War II with the introduction of antibiotics that controlled the infections of the urinary tract and skin that had proved fatal in prior years. Subsequently, improved management with neck stabilization to minimize further damage and better respiratory support, autonomic regulation, and other supportive measures reduced the damage and improved the outlook for survival. The invention of mechanical devices improved independence and quality of life. These advances were largely in the fields of neurosurgery, intensive care, and physical medicine. These were significant advances, but they were made in an era when we could not dream of actually addressing repair and regeneration. Those of us who were trained in the 1950s and 1960s were taught that “the neurons you are born with are all you ever get,” that axonal regeneration and remyelination occurred only in the peripheral nervous system and not in the
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Spinal Cord Injury: Progress, Promise, and Priorities central nervous system, and that damage to the spinal cord was irreversible. New studies of regeneration and repair in the brains and spinal cords of experimental animals have challenged these dogmas. Central nervous system remyelination was recognized in the 1960s, the extension of central axons was observed in the 1980s, and neurogenesis in adult life was discovered in recent years. Enhancement of regeneration in the brain and spinal cord has become a rational goal, but not an easy one. The processes of regeneration are complex; there will likely be no magic bullet—such as antibiotics—to lift us over this next barrier. Nerve cells will need to be saved or replaced, the growth of their axons will need to be not only stimulated but also guided, and connections to distant neurons or muscle fibers will need to be assisted or preserved. In addition, barriers or scars will need to be prevented or penetrated to permit this regeneration. Solutions will require novel and creative thinking. It is a great and, indeed, exciting challenge to the neurobiologists whose studies show increasingly greater promise. However, translation of the findings from these cell culture studies and studies with laboratory animals to humans with spinal cord injuries will need a new cadre of clinician-investigators recruited from diverse clinical backgrounds—neurology, clinical pharmacology, biomedical engineering, transplantation medicine, neurosurgery, and rehabilitation medicine. Talent will need to be joined to undertake these new tasks. This report examines the field of spinal cord injury research and makes recommendations on future directions for the field in general and for the sponsors of the study, the New York State Spinal Cord Injury Research Board, in particular. The committee consisted of individuals with diverse backgrounds and opinions, but we all agreed that the problems were great and that knowledge has advanced to a level where opportunities abound. Dedicated work on the part of every committee member contributed to this report. Further, the committee benefited from the expertise of the consultants to the committee, Jesse Cedarbaum, Gerald Fischbach, and Wise Young. Experts from across the country volunteered to speak in symposia and give advice informally. The public and voluntary organizations participated. However, the acquisition of expertise in the field, the compiling and sorting of data, the tireless organization and reorganization of contents, and the optimistic enthusiasm of Catharyn Liverman, Bruce Altevogt, Janet Joy, Kathleen Patchan, and Lora Taylor of the Institute of Medicine staff were remarkable; they made this report possible. On behalf of every committee member, I salute them. Richard T. Johnson, M.D., Chair
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Spinal Cord Injury: Progress, Promise, and Priorities ACKNOWLEDGMENTS The committee acknowledges with appreciation the individuals who provided information to the committee. These individuals include Maria Amador, The Miami Project to Cure Paralysis; Doug Anderson, University of Florida College of Medicine; Michael Beattie, Ohio State University; Andrew R. Blight, Acorda Therapeutics, Inc.; John Bollinger, Paralyzed Veterans of America; Pak Chan, Stanford University; Moses V. Chao, New York University; Dennis W. Choi, Merck & Company, Inc.; Dalton Dietrich, The Miami Project to Cure Paralysis; V. Reggie Edgerton, University of California, Los Angeles; Alan Faden, Georgetown University; Marie Filbin, Hunter College of the City University of New York; Ralph Frankowski, University of Texas at Houston; Z. Alexander Gentle; William Heetderks, National Institute of Biomedical Imaging and Bioengineering; Maura Hofstadter, Reeve-Irvine Research Center; Susan Howley, Christopher Reeve Paralysis Foundation; Claire Hulsebosch, University of Texas Medical Branch; Naomi Kleitman, National Institute of Neurological Disorders and Stroke; Congressman James Langevin, Rhode Island; Fausto Loberiza, Jr., Medical College of Wisconsin; Curtis Meinert, Johns Hopkins University; Lorne Mendell, University of New York at Stony Brook; Geoff Raisman, National Institute for Medical Research, London; Cynthia Rask, Food and Drug Administration; Rajiv Ratan, Burke/Cornell Medical Research Institute; Jeffrey D. Rothstein, Johns Hopkins University; Evan Snyder, Burnham Institute, San Diego; Oswald Steward, University of California, Irvine; Paul J. Tobin, United Spinal Association; Lynne Weaver, Robarts Research Institute; Irving Weissman, Stanford University; and Scott Whittemore, Kentucky Spinal Cord Injury
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Spinal Cord Injury: Progress, Promise, and Priorities Research Center, University of Louisville School of Medicine. This study was sponsored by the New York State Spinal Cord Injury Research Board. We appreciate their support and especially thank Martin Sorin for his efforts on behalf of this study. We also thank Judy Estep for all of her expertise in formatting the report for publication.
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Spinal Cord Injury: Progress, Promise, and Priorities CONTENTS EXECUTIVE SUMMARY 1 1 INTRODUCTION 13 2 PROGRESSION OF SPINAL CORD INJURY 30 3 TOOLS FOR ASSESSING SPINAL CORD INJURY AND REPAIR 64 4 CURRENT THERAPEUTIC INTERVENTIONS 95 5 PROGRESS TOWARD NEURONAL REPAIR AND REGENERATION 121 6 DEVELOPING NEW THERAPEUTIC INTERVENTIONS: FROM THE LABORATORY TO THE CLINIC 152 7 RESEARCH ORGANIZATION: CREATING AN ENVIRONMENT TO ACCELERATE PROGRESS 183 8 STATE PROGRAMS IN SPINAL CORD INJURY 205
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Spinal Cord Injury: Progress, Promise, and Priorities APPENDIXES A STUDY PROCESS 243 B ACRONYMS 249 C GLOSSARY OF MAJOR TERMS 252 D TOOLS TO ASSESS SPINAL CORD INJURY OUTCOMES 260 E CLINICAL TRIALS OF METHYLPREDNISOLONE 268 F EXAMPLES OF ALTERNATIVE THERAPIES 275 G SPINAL CORD INJURY CLINICAL TRIALS PUBLISHED FROM 1998 TO 2003 278 H LEGISLATION SPONSORING STATE SPINAL CORD INJURY RESEARCH 320 I COMMITTEE AND STAFF BIOGRAPHIES 323 INDEX 333