The need for VA leadership in advancing traumatic brain injury care

ABSTRACT

Traumatic brain injury (TBI) afflicts veterans, active duty service members and the civilian community. An estimated 5.3 million US men, women, and children live with a permanent TBI-related disability. There is no cure for TBI, and the discovery of new and effective treatments is complicated by the fact that TBI is multifaceted and varies from individual to individual. Due to its established research centers, wealth of veteran health data, and commitment to veteran health, the VA should be considered a natural leader for expanded TBI research.

KEYWORDS:

• traumatic brain injury
• Veterans Affairs
• research
• technologies

The Dept. of Veterans Affairs (VA) has a rich, proud heritage of leading healthcare advances for their constituency of veterans (i.e., former US military service members). The impact of the VA’s medical contributions is not limited to veterans but extends throughout the world.

The VA conducted its first clinical trial following World War II, with studies to evaluate effective treatments, including streptomycin, for tuberculosis (1). These tuberculosis studies were among the first ever large-scale clinical trials, and were motivated by the challenge of treating thousands of veterans suffering from the disease.

In 1964, the VA initiated the first randomized controlled trial of hypertension treatment anywhere in the world. This groundbreaking study on antihypertensive agents was a major milestone in medicine. Study results showed clear benefit in reducing morbidity and mortality, most remarkably by reducing progression to accelerated/malignant hypertension in the treated group (2).

Since then, the VA has conducted numerous landmark clinical trials and observational studies, including one of the first studies to determine the long-term effects of coronary artery bypass surgery and an investigative study on the use of steroids to treat septic shock patients. Perhaps one of the most famous and impactful works is the VA Cooperative Study, showing that aspirin reduces the risk of myocardial infarction in patients with unstable angina (3).

These VA initiatives have fostered increased clinical knowledge and therapeutic options, improving health care for the military and civilian populations. While the VA has made great strides in traumatic brain injury (TBI) management, due to the devastating long-term impact on quality of life, additional R&D is urgently needed. The Center for Disease Control and Prevention (CDC) estimates 5.3 million US men, women, and children live with a permanent TBI-related disability (4).

TBI afflicts veterans, active duty service members, and the civilian community. Men and women across all age groups are at risk of TBI. An especially vulnerable group is those over age 65, for which TBI is a leading cause of death and disability (5). This age group represents close to 50% of the eligible VA beneficiaries (6). It is reported that 201,435 veterans from all eras participating in VA healthcare have a diagnosis associated with TBI, of which 56,695 are Operation Enduring Freedom in Afghanistan/Operation Iraqi Freedom (OEF/OIF) veterans (7).

The VA and the Department of Defense (DoD) define a TBI as a traumatically induced structural injury and/or the physiological disruption of brain function as a result of an external force, indicated by new onset or worsening of at least one of the following clinical signs immediately following the event (8): any period of loss of or a decreased level of consciousness, any loss of memory for events immediately before or after the injury (post-traumatic amnesia), any alteration in mental state at the time of the injury (e.g., confusion, disorientation, slowed thinking, alteration of consciousness/mental state), neurological deficits that may or may not be transient, or intracranial lesion.

There is no cure for TBI. There is no clinically available medication or therapy that effectively and specially rescues neurons or glia or reverses or halts the neuropathological processes of TBI. This is despite many decades of research with billions of research dollars spent. To this day, TBI treatment is supportive. The clinical goal of therapy is optimizing general physiology so that the brain is adequately perfused, oxygenated, and the metabolic needs are met.

The discovery of new and effective TBI treatments is complicated by the fact that TBI is multifaceted and varies from individual to individual. The type of injury, the force of injury, the location of injury as well as the time and level of medical care all impact TBI outcomes.

It is becoming better recognized that TBI has significant clinical consequences and is associated with a variety of co-morbid mental health and physical conditions. Headache, dizziness, and cognitive dysfunction are common following all severities of TBI. Mental health disorders associated with TBI include anxiety disorders and depressive disorders, although estimates of how often such conditions co-occur with TBI vary (9). TBI patients are also at increased risk of developing epilepsy and neurodegenerative diseases such as Alzheimer’s disease, Lewy body dementia, or Parkinson’s disease (10). Physical symptoms may also develop such as sleep disturbances, obstructive sleep apnoea, incontinence, sexual dysfunction, metabolic dysfunction, or musculoskeletal dysfunction.

Emerging evidence suggests that repetitive blows to the head can result in a tau neuropathy known as chronic traumatic encephalopathy (CTE) (11,12). Dr Ann McKee is a VA physician-scientist who is a pioneer in the study of CTE. She demonstrated that CTE is present in some former professional football and hockey players, professional wrestlers, and service members (13). Because CTE develops over time, symptoms may take years to manifest, further highlighting the need for long-term prospective studies.

Traditionally, the medical community and the lay public did not fully appreciate either the prevalence or the clinical significance of TBI. Recently, there has been an increasing concern about the impact of this condition on those afflicted. This new awareness can be largely attributed to the DoD’s clinical experience from OIF and OEF. Unlike the health impacts of previous conflicts, TBI blast injury symptoms were recognized relatively early in OIF/OEF (14). OIF and OEF data compiled by the Armed Forces Health Surveillance Center (AFHSC) with research conducted by and subsequent dissemination of findings by the Defense and Veterans Brain Injury Center (DVBIC) reveal the previously under-appreciated significance of TBI. From 2000 to 2016, more than 361,000 TBI cases were suffered by the US military personnel. About 80% were concussion injury (15). Dr Warden of the DVBIC noted, ‘TBI may be the signature injury of these wars’. (16)

An unfortunate consequence of the general lack of appreciation of the importance of TBI leads many patients to: (1) not seek immediate medical attention, if at all, (2) return to work prematurely, and (3) discount the need for adequate protective equipment.

Prior to OIF and OEF, there was a select group of medical professionals who did understand that TBI was a serious condition. In 1997, the American Academy of Neurology (AAN) issued clinical practice guidelines (CPGs) with return to play or work recommendations (17). The intent of these CPGs was to allow sufficient recovery time from the first injury and to avoid re-injury before that recovery was completed. In 1996, the American Association of Neurological Surgeons (AANS) and the Congress of Neurosurgery (CNS) published the first comprehensive CPG for the clinical management of moderate to severe TBI (18). These CPGs represented significant advancements in managing and treating TBI patients by applying evidenced-based standard approaches to clinical care. Both have recently been updated (19).

During OIF and OEF, the DoD recognized discrepancies in TBI diagnosis and management across the military network of care. Understanding that a patient’s quality of care should not be dictated by where and by whom care is rendered, evidenced-based CPGs were adopted when available from civilian practice. When CPGs had not yet been developed by civilians or were insufficient for military use, new CPGs were created. Notably, the DoD issued CPGs for the pre-hospital management of combat-related head injury in 2005 (8). The AANS/CNS moderate to severe TBI guidelines were adopted by DoD military physicians and modified for combat casualty care application (20). All of these guidelines were based on best available evidence, which was, at best, incomplete. However, it served as a foundation for which to build and improve upon.

The lack of a TBI cure does not obviate the responsibility medical care providers have to care for service members following TBI. To fill this void, the US military established standardized clinical recommendations for return to duty after concussion, including a six-stage progression of activities across the physical, cognitive, and vestibular domains (21). To help guide clinicians who were treating TBI either in the war theatre or at VA clinics, in 2009, the VA and DoD convened a working group to produce CPGs for managing concussion/mild TBI (22). This VA/DoD CPG became the first large-scale, system-wide common resource for treating mild TBI. It led to significant improvements in TBI clinical care. These CPGs have since been updated in 2016 (23).

While improved protocols and emerging products/interventions are important in caring for TBI patients, there is still a lack of progress across the spectrum of TBI: prevention, diagnosis, intervention, treatment, and follow-up. There is a critical need for leadership and focus in the scientific community to combat TBI. In an effort to reduce the many debilitating outcomes, a targeted national scientific strategy is needed. The VA is ideally poised to assume a leadership role in this effort.

In 2012, President Obama established a National Research Action Plan and signed Executive Order 13625: Improving Access to Mental Health Services for Veterans, Servicemembers, and Military Families. While the key focus was mental health, the order also recognized the need for cohesive TBI research, and in particular, the need for improved understanding concerning the underlying mechanisms of TBI injury (24).

Although other government agencies including the National Institutes of Health (NIH) and the National Institute of Neurological Disease and Stroke (NINDS) are conducting important TBI research, the VA is uniquely suited to unify and direct this research because 1) it is the only US programme focused on all aspects of Veteran health, 2) it has established centres across the country, 3) it has more than 1.4 million OEF/OIF veterans to evaluate, and 4) its policy requires that all OEF/OIF veterans receiving medical care in the VA healthcare system must be screened for possible TBI, which provides an ideal database (25). Key to improving outcomes from TBI is unified and shared research and resources; the VA could help increase research partnerships through sharing its Veteran health data. Collectively, the VA, DoD, and NIH could host symposiums and working groups to communicate and share data and resources to facilitate consistent, focused research.

The VA Medical Centers is a collection of federal hospitals dedicated to the care of service members who are no longer on active duty. This system spans across the US under one authority, making it ideal to conduct large multi-centre clinical studies. Furthermore, the VA has research infrastructure, such as established research design, statistical methods, and data management programmes, to support rigorous clinical investigation. In particular is the VA Cooperative Studies Program, a Division of the VA Office of Research and Development (ORD), responsible for planning and conducting large multi-centre clinical trials and epidemiological studies within the VA (26).

In 2014, the VA introduced the ‘Concussion Coach’, a mobile phone app for veterans, service members, and others who have suffered a mild or moderate TBI (27). The app features education about concussion symptoms and treatment options, tools for screening and tracking symptoms, relaxation exercises, tools for managing problems related to concussion, and direct links for community-based resources and support.

The VA’s Translational Research Center for TBI and Stress Disorders in Boston studies the impact of TBI and post-traumatic stress disorder (PTSD). Attending staff come from mental health, neuropsychology, neuroscience, and medicine and focus completely on the OEF/OIF veteran population (28).

The VA’s Brain Rehabilitation Resource Center in Gainesville, FL, develops and tests treatments to improve or restore motor skills, cognitive ability, and emotional impairments caused by brain disease or injury (29).

The VA’s Traumatic Brain Injury Center of Excellence in Houston focuses on mild TBI sustained in OEF, OIF, and Operation New Dawn (OND) (30).

The VA’s War Related Illness and Injury Study Center develops and provides post-deployment health expertise to Veterans and their healthcare providers through clinical programmes, research, education, and risk communication (31).

VA’s Polytrauma System of Care is a network of specialized rehabilitation programmes dedicated to serving Veterans and service members with TBI and poly-trauma (32).

The DVBIC serves active-duty military, their beneficiaries, and Veterans with mild, moderate, and severe TBI. The DVBIC is a network of 18 sites specializing in research, clinical affairs, and educational support related to TBI (33).

The VA has also established a Biorepository Brain Bank (VABBB) to collect, process, store, and distribute both normal and abnormal brain tissue samples for scientific studies. The VABBB currently provides central nervous system (CNS) tissue and health information to scientists studying disorders such as amyotrophic lateral sclerosis (ALS or Lou Gehrig’s Disease), disorders of Veterans of the 1990–91 Gulf War, and PTSD (34). Expanding tissue sample use for TBI research is a natural progression.

The Million Veteran Program (MVP) is a national, voluntary research programme funded entirely by the VA ORD. The objective of MVP is to partner with Veterans receiving their care in the VA Healthcare System to study how genes affect health. The MVP will build one of the world’s largest medical databases by collecting blood samples and health information from one million Veteran volunteers to study how genes affect health. Data collected from MVP will be stored anonymously for research on diseases like diabetes and cancer, and military-related illnesses, such as PTSD (35).

VA policy requires that all OEF/OIF veterans receiving medical care in the VA healthcare system must be screened for possible TBI, and that those who screen positive must be offered further evaluation and specialized treatment (36).

Efforts must continue to institute mandatory, standardized screening and management protocols into practice and develop new channels to rapidly transition new protective technologies to the marketplace. The staggering economic and quality-of-life costs stemming from TBI injury demand a cure.

Due to its established research centres, wealth of veteran health data, and commitment to veteran health, the VA is a natural leader for expanded TBI research. Expanding the VABBB and allowing researchers access to other electronic health data, while maintaining patient confidentiality, would help further elucidate the mechanisms of TBI and improve TBI prognosis. This research could result in new treatment protocols and injury prevention strategies for our soldiers. Peer-reviewed reports and seminars would facilitate the transfer of these new treatment modalities to the civilian population, improving outcomes for all. The VA has a cadre of experienced clinician-scientists and research tools as well as the infrastructure to lead this challenge. Thus, it is only reasonable that the VA take a leadership role in advancing the medical treatment of TBI.

Declaration of Interest

Professor of Neurology, Johns Hopkins, Professor of Neurology, USUHS, Interim Vice-Chair for Research, Inova Neuroscience and Spine Institute, Inova Fairfax Hospital,

NFL Health Foundation (volunteer Board member), NFLPA Mackey-White Health Committee (volunteer Committee member), Brainscope (volunteer scientific advisor), SAMUS Therapeutics (scientific advisor), Facebook B8 (Board member), KnoLimits, LLC (partner), SunQ, LLC (partner), DrsGSLing, LLC (partner).

Acknowledgements

The author gratefully acknowledges the assistance provided by Ms Nicole Draghic, who helped in the preparation and research of this article.