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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
GULF WAR and HEALTH
VOLUME 7
Long-Term Consequences of Traumatic Brain Injury
Committee on Gulf War and Health: Brain Injury in Veterans and Long-Term Health Outcomes
Board on Population Health and Public Health Practice
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
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 V101(93) P-2136, Task Order 8 between the National Academy of Sciences and Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
International Standard Book Number-13: 978-0-309-12408-9
International Standard Book Number-10: 0-309-12408-5
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 2009 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
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.
Suggested citation: IOM (Institute of Medicine). 2009. Gulf War and Health, Volume 7: Long-term Consequences of Traumatic Brain Injury. Washington, DC: The National Academies Press.
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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
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. Ralph J. Cicerone 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. Charles M. Vest 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. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
COMMITTEE ON GULF WAR AND HEALTH: BRAIN INJURY IN VETERANS AND LONG-TERM HEALTH OUTCOMES
GEORGE W. RUTHERFORD, MD (Chair) Salvatore Pablo Lucia Professor and Vice Chair,
Department of Epidemiology and Biostatistics;
Director,
Prevention and Public Health Group, Global Health Sciences, University of California, San Francisco School of Medicine
JEFFREY J. BAZARIAN, MD, MPH, Associate Professor,
Departments of Emergency Medicine and Neurology, University of Rochester School of Medicine and Dentistry
IBOLJA CERNAK, PhD, MD, Medical Director,
Johns Hopkins University, Applied Physics Laboratory
JOHN D. CORRIGAN, PhD, Professor,
Department of Physical Medicine and Rehabilitation, Ohio State University
SUREYYA S. DIKMEN, PhD, Professor,
Department of Rehabilitation Medicine and
Adjunct Professor of Neurological Surgery and Psychiatry and Behavioral Sciences,
University of Washington
M. SEAN GRADY, MD, Chairman,
Department of Neurosurgery, University of Pennsylvania School of Medicine
DALE C. HESDORFFER, PhD, MPH, Associate Professor of Clinical Epidemiology,
Gertrude H. Sergievsky Center, Columbia University
JESS F. KRAUS, PhD, MPH, Director,
Southern California Injury Prevention Research Center,
Professor of Epidemiology,
University of California, Los Angeles, School of Public Health
HARVEY S. LEVIN, PhD, Professor, Director of Research,
Cognitive Neuroscience Laboratory, Department of Physical Medicine and Rehabilitation, Baylor College of Medicine
LINDA NOBLE, PhD, Professor,
Department of Neurological Surgery and Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco
SAMUEL J. POTOLICCHIO, MD, Professor,
Department of Neurology, George Washington University Medical Center
SCOTT L. RAUCH, MD, Chair,
Partners Psychiatry and Mental Health;
President and Psychiatrist in Chief,
McLean Hospital;
Professor of Psychiatry,
Harvard Medical School
WILLIAM STIERS, PhD, ABPP, Assistant Professor,
Department of Physical Medicine and Rehabilitation, Johns Hopkins University
CAROL A. TAMMINGA, MD, Professor,
Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas
NANCY TEMKIN, PhD, Professor,
Departments of Neurological Surgery and Biostatistics, University of Washington
MARC G. WEISSKOPF, PhD, ScD, Mark and Catherine Winkler Assistant Professor,
Departments of Environmental Health and Epidemiology, Harvard School of Public Health
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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
STAFF
CAROLYN FULCO, Senior Program Officer
ABIGAIL MITCHELL, Senior Program Officer
ROBERTA WEDGE, Senior Program Officer
NAOKO ISHIBE, Program Officer
JENNIFER SAUNDERS, Senior Program Associate
DEEPALI PATEL, Senior Program Associate (until October 2007)
RENEE WLODARCZYK, Senior Program Associate
JOE GOODMAN, Senior Program Assistant
NORMAN GROSSBLATT, Senior Editor
CHRISTIE BELL, Financial Officer
HOPE HARE, Administrative Assistant
ROSE MARIE MARTINEZ, Director,
Board on Population Health and Public Health Practice
CONSULTANTS
MIRIAM DAVIS, Independent Medical Writer,
Silver Spring, MD
JOAN MACHAMER, Independent Consultant,
University of Washington, Seattle, WA
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REVIEWERS
This report has been reviewed in draft form by persons 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 of 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 thank the following for their review of this report:
Dan G. Blazer, Duke University Medical Center
Linda Cowan, Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center
Ramon Diaz-Arrastia, Department of Neurology, University of Texas Southwestern Medical School
Sandro Galea, Center for Social Epidemiology and Population Health, University of Michigan
Tessa Hart, Moss Rehabilitation Research Institute, Albert Einstein Healthcare Network
Janice L. Krupnick, Department of Psychiatry, Trauma and Loss Program, Georgetown University Medical Center
James L. Levenson, Department of Psychiatry, Virginia Commonwealth School of Medicine
Kathryn Saatman, Spinal Cord and Brain Injury Research Center, University of Kentucky Chandler Medical Center
Murray B. Stein, Department of Psychiatry, University of California, San Diego
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 Dr. Johanna T. Dwyer, Tufts University School of Medicine and Friedman School of Nutrition Science and Policy, Frances Stern Nutrition Center, Tufts-New England Medical Center and Dr. Robert S. Lawrence, Center for a Livable Future, Johns Hopkins Bloomberg School of Public Health. Appointed by the National Research Council and the Institute of Medicine, they were responsible for making certain that an independent examination of the report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of the report rests entirely with the author committee and the institution.
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CONTENTS
PREFACE
xiii
SUMMARY
1
1
INTRODUCTION
13
Background
13
Traumatic Brain Injury
14
Operation Enduring Freedom and Operation Iraqi Freedom
15
Charge to the Committee
15
Scope of the Report
15
Organization of the Report
16
References
17
2
BIOLOGY OF TRAUMATIC BRAIN INJURY
19
Pathobiology of Traumatic Brain Injury
19
Traditional Classifications of Traumatic Brain Injury
25
Classification According to Extent of Pathology
25
Classification According to Biomechanics of Injury
27
Therapeutics and Traumatic Brain Injury
28
Summary of Pathobiology of Traumatic Brain Injury
29
Traumatic Brain Injuries Relevant to the Military
30
Basic Mechanisms of Explosive Injuries
31
Severity Scoring of Blast Injuries and Traumatic Brain Injury
41
References
46
3
EPIDEMIOLOGY OF ADULT TRAUMATIC BRAIN INJURY
59
Incidence of Traumatic Brain Injury
61
Brain Injury Severity
63
Risk Factors for Traumatic Brain Injury
64
Recurrent Traumatic Brain Injury
67
Traumatic Brain Injury and Short-Term Outcomes
68
Summary
69
References
96
4
CONSIDERATIONS IN IDENTIFYING AND EVALUATING THE LITERATURE
103
Identification of the Literature
103
Types of Evidence
104
Inclusion Criteria
110
Considerations in Assessing the Strength of Evidence
112
Limitations of Studies
113
References
115
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5
MAJOR COHORT STUDIES
117
General Limitations of Cohort Studies
117
Organization of the Chapter
118
Military Studies
118
Population-Based Studies
127
Other Cohort Studies
133
Studies of Sports-Related Traumatic Brain Injury
140
References
166
6
NEUROCOGNITIVE OUTCOMES
173
Penetrating Brain Injury
173
Closed Head Injury
181
References
194
7
NEUROLOGIC OUTCOMES
197
Seizure Disorders
197
Postconcussion Symptoms
210
Ocular and Visual Motor Deterioration
224
Endocrine Disorders
227
Neurodegenerative Diseases
237
Dementia of the Alzheimer Type
237
Dementia Pugilistica
243
Parkinsonism
246
Multiple Sclerosis
251
Amyotrophic Lateral Sclerosis
254
References
256
8
PSYCHIATRIC OUTCOMES
265
Mood Disorders
266
Suicide
276
Anxiety Disorders
281
Other Psychiatric Outcomes
289
Aggressive Behaviors
289
Drug and Alcohol Abuse Disorders
291
Psychotic Disorders
292
References
297
9
SOCIAL FUNCTIONING
301
Primary Studies of Military Populations
301
Primary Studies of Civilian Populations
303
Secondary Studies
307
Summary and Conclusions
314
References
328
10
OTHER HEALTH OUTCOMES
333
Mortality and Traumatic Brain Injury
333
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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
Primary Studies
333
Secondary Studies
336
Summary and Conclusions
339
Brain Tumors and Traumatic Brain Injury
350
Primary Studies
350
Secondary Studies
354
Summary and Conclusions
355
References
364
11
CONCLUSIONS AND RECOMMENDATIONS
367
Quality of the Studies
367
Overview of Health Outcomes
368
Recommendations
370
INDEX
373
TABLES AND FIGURES
TABLE 2.1
Safety Recommendations for Standoff Distances from Different Types of Exploding Bombs
31
TABLE 2.2
Overpressure Effects on Surrounding Materials and Unprotected Persons
33
TABLE 2.3
Summary of Most Important Body-System Injuries Induced by Concomitant Primary, Secondary, Tertiary, and Quaternary Effects of Blast
34
TABLE 3.1
Glasgow Coma Scales and Glasgow Outcome Scales
70
TABLE 3.2
US TBI Incidence Studies: Case Identification, Data Source, and TBI Severity Scoring
71
TABLE 3.3
Non-US Incidence Studies: Case Identification, Data Source, and TBI Severity Score
75
TABLE 3.4
US TBI Incidence Studies
79
TABLE 3.5
Non-US TBI Incidence Data
81
TABLE 3.6
US TBI Deaths and Mortality Rates
84
TABLE 3.7
Non-US TBI Deaths and Mortality Rates
85
TABLE 3.8
Percent Severity Distributions of Hospitalized Patients in US and Non-US Incidence Studies
87
TABLE 3.9
Highest Age-Specific TBI Rates and Gender Rate Ratios: US Studies
89
TABLE 3.10
Highest Age-Specific TBI Rates and Gender Rate Ratios: Non-US Studies
90
TABLE 3.11
Percent Distributions of TBI Incidence Cases by External Cause: US Studies
91
TABLE 3.12
Percent Distributions of TBI Incidence Cases by External Cause: Non-US Studies
92
TABLE 3.13
TBI In-Hospital Case Fatality Rates (CFR) from US Population-Based Studies
93
TABLE 3.14
TBI In-Hospital Case Fatality Rates (CFR) from Non-US Population-Based Studies
94
TABLE 3.15
Percent Distribution of GOS Outcome Categories at Hospital Discharge Rate for US and Non-US Studies
95
TABLE 5.1
Major Cohort Studies (Shaded)and Derivative Studies
143
TABLE 6.1
Penetrating Head Injury and Neurocognitive Outcomes
178
TABLE 6.2
Closed Head Injury and Neurocognitive Outcomes
189
TABLE 7.1
Seizure Disorders and TBI
204
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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
TABLE 7.2
Symptoms After Deployment According to Type of Injury During Deployment
211
TABLE 7.3
Frequency of Symptoms on RPCS Questionnaire
214
TABLE 7.4
Prevalence of Subjective Complaints 5 Years After Injury
216
TABLE 7.5
Postconcussive Symptoms and TBI
219
TABLE 7.6
Ocular and Visual Motor Deterioration and TBI
226
TABLE 7.7
Endocrine Disorders and TBI
233
TABLE 7.8
Dementia of the Alzheimer Type and TBI
242
TABLE 7.9
Parkinsonism and TBI
249
TABLE 7.10
Multiple Sclerosis and TBI
253
TABLE 8.1
Psychologic Outcomes—Mood-Disorder Studies
270
TABLE 8.2
Psychologic Outcomes—TBI and Suicide
279
TABLE 8.3
Psychologic Outcomes—Anxiety Disorder Studies
285
TABLE 8.4
Psychologic Outcomes—Personality Disorder Studies
294
TABLE 9.1
Social Function
316
TABLE 10.1
TBI and Mortality
340
TABLE 10.2
TBI and Brain Tumors
356
FIGURE 2.1
Pathologic classification of TBI
26
FIGURE 2.2
Classification of TBI based on primary insult
28
FIGURE 2.3
Potential consequences of blast exposure
30
FIGURE 2.4
Explosion-induced shock waves
32
FIGURE 2.5
Examination and diagnosis algorithm for blast injuries
36
FIGURE 2.6
Complex mechanisms of blast-induced neurotrauma
37
FIGURE 2.7
Brief Traumatic Brain Injury Screen
45
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PREFACE
The Institute of Medicine (IOM) has a long-standing role of providing assistance to the Department of Veterans Affairs (VA) with regard to veterans’ health. The current series of studies on Gulf War and Health, of which this study is one, began in 1998 when Congress passed two laws on Gulf War veterans’ health in response to the recognition that many Gulf War veterans returning from the 1991 Persian Gulf War were suffering from a multisymptom illness of poorly understood pathogenesis that proved difficult to diagnose and treat.
The United States is once again engaged in a military conflict in the Middle East. The conflicts in Afghanistan (Operation Enduring Freedom [OEF]) and in Iraq (Operation Iraqi Freedom [OIF]) have been characterized by a type of combat different from that seen in the 1991 war, in that there have been many more deaths, polytrauma, and traumatic brain injury (TBI). The VA, under authorization granted in the 1998 legislation, has asked IOM to determine long-term health outcomes associated with TBI. TBI has been called the signature injury of OEF and OIF primarily due to blast exposure that is characteristic of this conflict. Exposure to blast might cause instant death, injuries with immediate manifestation of symptoms, or injuries with delayed manifestation. Blast-induced neurotrauma, however, has not been studied sufficiently to confirm reports of long-term effects.
That many returning veterans have TBI will likely mean long-term challenges for them and their family members. Veterans will need support systems at home and in their communities to assist them in coping with the long-term sequelae of their injuries. Further, many veterans will have undiagnosed brain injury because not all TBIs have immediately recognized effects or are easily diagnosed with neuroimaging techniques.
In an effort to detail the long-term consequences of TBI, the committee read and evaluated some 1,900 studies that made up its literature base, and it developed criteria for inclusion of studies to inform its findings. It is clear that brain injury, whether penetrating or closed, has serious consequences. The committee sought to detail those consequences as clearly as possible and to provide a scientific framework to assist the brave men and women who have fought in OEF and OIF as they return home. We are honored to have been of service.
I am deeply appreciative of the expert work of our committee members and their extraordinary commitment to the task at hand. The committee extends its appreciation to the many people who presented information at its open meeting and to the IOM staff. In particular we would like to thank Renee Wlodarczyk, Jen Saunders, and Naoko Ishibe who helped with a myriad of tasks including literature searches, retrieving articles, entering data into the numerous tables in the document, and for their contributions in the development of several chapters of the report. We appreciate Joe Goodman’s attention to our meeting and travel needs; and to Carolyn Fulco for her guidance and oversight.
George W. Rutherford, MD, AM
Chair, Committee on Gulf War and Health: Brain Injury in Veterans and Long-Term Health Outcomes
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