Longterm Consequences of Traumatic Brain Injury

Rutherford, George W. MD; Corrigan, John D. PhD, ABPP

Section Editor(s): Rutherford, George W. MD, Topical Editor

Journal of Head Trauma Rehabilitation:
doi: 10.1097/HTR.0b013e3181c13439
Author Information

Institute for Global Health, University of California, San Francisco, Issue Editor (Rutherford)

Editor-in-Chief, Journal of Head Trauma Rehabilitation (Corrigan)

Article Outline

THE National Academy of Sciences (NAS) was created by Congress and President Abraham Lincoln in 1863 to ensure that government decisions were informed by the best possible scientific evidence, and its scope was subsequently expanded by presidents Wilson, Eisenhower, and G.H.W. Bush. In 1970, the Institute of Medicine (IOM) was created as a component of NAS to provide scientific insight in matters of biomedical science, medicine, and health. Like the rest of NAS, IOM brings together committees of experts who serve pro bono to address important national issues:

The Institute provides a vital service by working outside the framework of government to ensure scientifically informed analysis and independent guidance.... The Institute provides unbiased, evidence-based, and authoritative information and advice concerning health and science policy to policymakers, professionals, leaders in every sector of society, and the public at large. (www.iom.edu. Accessed June 1, 2009)

In 2008, IOM published 47 separate reports, on subjects ranging from the state of health indicators in the United States to global climate change and extreme weather events to intermittent preventive therapy for malaria in infants.

In 1998, in response to the growing concerns of the ill Gulf War veterans, Congress passed the Persian Gulf War Veterans Act and the Veterans Programs Enhancement Act. These laws directed the Veterans Administration to enter into a contract with NAS to review and evaluate the scientific and medical literature regarding associations between illness and exposure to toxic agents, environmental or wartime hazards, and preventive medicines or vaccines associated with Gulf War service, and to consider the NAS conclusions when deciding about the compensation. Responsibility for implementation was assigned to the IOM, and to date 7 volumes have been published on the basis of the work of IOM committees.1–7 The most recent was in response to a Veterans Administration's request inquiring whether traumatic brain injury (TBI) has long-term health effects.7 This topical issue of the Journal of Head Trauma Rehabilitation (JHTR) is an outgrowth of that work.

The charge to the IOM's Committee on Gulf War and Health: Brain Injury in Veterans and Long-Term Health Outcomes was to examine the strength of the evidence of an association between TBI and potential long-term health effects. To implement its charge, the committee conducted a review of the scientific literature, including all relevant studies of human TBI in any population (civilian or military) caused by any mechanism (eg, motor vehicle crashes and falls). The committee sought to answer whether sustaining a TBI is associated with a specific health outcome. The full report of the committee's findings was published by the National Academies Press in 2009: Gulf War and Health Volume 7: Long-Term Consequences of Traumatic Brain Injury.7

The current JHTR topical issue—Long-Term Consequences of Traumatic Brain Injury—includes the results of the IOM committee's systematic reviews addressing cognitive,8 neurological,9 psychiatric,10 social,11 and other medical consequences12 of TBI. An introductory article13 describes the search process and criteria used to identify primary and secondary research studies that served as the basis for the committee's determination of whether an association exists between the types and severity of TBI and the conditions studied. Tabular summaries of the primary studies are available as Supplemental Digital Content.

Given the committee's findings have been reported, why is JHTR publishing this issue? It was our hope to accomplish 2 goals: (1) bring this important body of work into the knowledge base of researchers and clinicians in the field of brain injury rehabilitation and (2) provide those scientists who constituted the committee with the opportunity to discuss the implications of the findings for the rehabilitation of persons with TBI.

We leave it to the readers to determine our success in attaining our goals; however, several “higher order” observations are apropos. Most rehabilitation professionals would not be surprised by the conclusions that moderate to severe TBI is associated with later seizures, cognitive deficits, depression, aggression, unemployment, or social isolation. However, this systematic review of the literature also indicated that premature death, progressive dementia, Parkinson's disease, and endocrine dysfunction, particularly hypopituitarism, are also associated with TBI, particularly moderate to severe TBI. These conditions depart from the commonly cited long-term cognitive, behavioral, and social problems and suggest a chronic health condition that has a more physiological impact on the organism. These results lend support to the contention that TBI may not only be a long-term psychosocial problem but a chronic health condition as well. More important, this list may suggest potential new avenues for disease-management approaches to limit long-term consequences.

Another higher-order issue deserving comment is the relationship between type or severity of TBI and observed associations. Two of the 3 conclusions made with the highest level of certainty-–definitive evidence of a causal relationship-–were consequences of penetrating TBI. It was concluded that both unprovoked seizures and premature mortality are caused by penetrating TBI. Decline in cognitive functions associated with the region and volume of tissue loss and long-term unemployment were almost equally certain to be a consequence of penetrating injuries. Clearly, there are significant consequences to be expected for persons who survive these injuries. For nonpenetrating TBI, the degree of certainty regarding an association was very much a function of severity. With 3 notable exceptions, most conclusions for which sufficient evidence of an association was present were limited to moderate or severe, but not mild, TBI. For cognitive deficits, only severe TBI was listed as having sufficient evidence; however, the committee observed that inconsistencies in the definition of moderate TBI were largely to blame for the weak evidence. The 3 exceptions were depression, aggressive behaviors, and postconcussive symptoms-–for each, sufficient evidence was found to conclude that an association exists between any TBI (ie, mild, moderate, severe, or penetrating) and these conditions.

In addition to the above 3 long-term health consequences definitely associated with mild TBI, there was suggestive evidence for associations between mild TBI with loss of consciousness and unprovoked seizures, ocular or visuomotor deterioration, progressive dementia, parkinsonism, and post-traumatic stress disorder (the last was limited to Gulf War military populations). These results could be cited by proponents on both sides of the recent controversy about whether mild TBI is a condition distinct from moderate and severe TBI.14 Finding different levels of certainty should not be mistaken for evidence of different conditions. The nature, extent, and sensitivity of the available research can also be the source of this discrepancy. Indeed, the committee did not find sufficient evidence to conclude that there was no association between TBI and any of the examined health conditions. On the other side of the controversy, either definite or suggestive evidence of an association between mild TBI, particularly that involving loss of consciousness, was observed for a number of health consequences. First, it seems very plausible that severity is not the only mediating factor between nonpenetrating TBI and long-term health consequences. To the extent severity does mediate long-term consequences, it seems more intuitive that it has a gradient influence rather than there being a distinct cut-point below which long-term consequences are less likely and above which they are more likely. However, if there is such a cut-point, it also seems likely that we will need an indicator that is more sensitive than behavioral observations of obtunded arousal (ie, Glasgow Coma Scale, length of posttraumatic amnesia, or length of loss of consciousness) to measure it. Interested parties on both sides of the mild and/or moderate/severe controversy should be cheering for a definitive breakthrough in research on biomarkers of TBI.

We hope the readers find this topical issue interesting and informative. While the approach to systematic review used by the IOM is somewhat different than the now-familiar Cochrane Collaboration's approach, there is no less rigor that goes into the conclusions drawn. And, indeed, the IOM process is quite explicit about the criteria used to reach conclusions about presence of a causal relationship or strength of association (see Ishibe et al13 in this issue.) While some conclusions that resulted are “old news,” the IOM process has placed some new issues on the table for long-term management of the consequences of TBI.

George W. Rutherford, MD

Institute for Global Health, University of California, San Francisco, Issue Editor

John D. Corrigan, PhD, ABPP

Editor-in-Chief, Journal of Head Trauma Rehabilitation

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1. Institute of Medicine. Gulf War and Health: Volume 1. Depleted Uranium, Sarin, Pyridostigmine Bromide and Vaccines. Washington, DC: The National Academies Press; 2000.
2. Institute of Medicine. Gulf War and Health: Volume 2. Insecticides and Solvents. Washington, DC: The National Academies Press; 2003.
3. Institute of Medicine. Gulf War and Health: Volume 3. Fuels, Combustion Products and Propellants. Washington, DC: The National Academies Press; 2004.
4. Institute of Medicine. Gulf War and Health: Volume 4. Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press; 2004.
5. Institute of Medicine. Gulf War and Health: Volume 5. Infectious Disease. Washington, DC: The National Academies Press; 2006.
6. Institute of Medicine. Gulf War and Health: Volume 6. Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress. Washington, DC: The National Academies Press; 2007.
7. Institute of Medicine. Gulf War and Health: Volume 7. Long-term Consequences of Traumatic Brain Injury. Washington, DC: The National Academies Press; 2009.
8. Dikmen SS, Corrigan JD, Levin HS, Machamer J, Stiers W, Weisskopf MG. Cognitive outcome following traumatic brain injury. J Head Trauma Rehab. 24(6):430–438.
9. Bazarian JJ, Cernak I, Noble-Haeussiein L, Potolicchio SJ, Temkin NR. Long-term neurologic outcomes after traumatic brain injury. J Head Trauma Rehabil. 24(6); 439–451.
10. Hesdorffer DC, Rauch SL, Tamminga CA. Long-term psychiatric outcomes following traumatic brain injury: a review of the literature. J Head Trauma Rehabil. 24(6); 452–459.
11. Temkin NR, Corrigan JD, Dikmen SS, Machamer J. Social functioning after traumatic brain injury. J Head Trauma Rehabil. 24(6); 460–467.
12. Rutherford GW, Wlodarczyk RC. Distant sequelae of traumatic brain injury: premature mortality and intracranial neoplasms. J Head Trauma Rehabil. 24(6); 468–474.
13. Ishibe N, Wlodarczyk RC, Fulco C. Overview of the Institute of Medicine's committee search strategy and review process for Gulf War and health: long-term consequences of traumatic brain injury. J Head Trauma Rehabil 24(6); 424–429.
14. Hoge CW, McGurk D, Thomas J, Cox AL, Engel CC, Castro CA. Mild traumatic brain injury in U.S. soldiers returning from Iraq. N Engl J Med. 2008;358(5):453–463.
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