Veteran’s affairs traumatic brain injury conference: State of the art

Concern about the frequency of traumatic brain injury sustained during operations Enduring Freedom, Iraqi Freedom and New Dawn (OEF/OIF/OND) prompted screening of all Veterans serving in theatre and presenting to The Veterans Health Administration (VHA) beginning in 2007. As of 30 September 2016, 1066,474 Veterans had been screened; 201,997 screened positive (mainly for mild Traumatic Brain Injury (TBI)), and 147,744 completed a comprehensive traumatic brain injury examination. Among these 83,318 received a confirmed diagnosis of TBI, mainly mild TBI. Additionally about 49,000 veterans reported to VHA with a prior confirmed TBI diagnosis from military medical services and other entities. Mild traumatic brain (mTBI) concussion was called a ‘signature injury’ of these conflicts and its late effects characterized as ‘an invisible injury’ in that conventional imaging usually failed to reveal specific pathology. This special edition of Brain Injury focuses upon combat-related TBI occurring during OEF/OIF/OND conflicts. Due to differing injury mechanisms, often repetitive and including blast exposure, late mTBI symptoms are not limited to typical cognitive or motor deficits usually associated with more severe brain injuries. A proportion of Service Members and Veterans develop a chronic, complex combination of symptoms. These may involve mental health issues (Post Traumatic Stress Disorder (PTSD), depression, and impulsivity), sensory defects (central processing deficits that affect perception), chronic headaches and pain, sleep disorders, as well as metabolic and endocrine dysfunction.

When Veterans Administration (VA) Secretary, Robert McDonald requested a follow-up to the 2008 State-of-the-Art (SOTA) conference published in 2009 (1), a multidisciplinary workgroup decided that the overall theme of 2015 conference would describe research progress dating from that time. The conference focused upon a number work groups exploring critical subtopics. Each group derived an initial consensus statement that was submitted for peer reviewed by other subject matter experts. The initial submissions were revised in detail and subsequently accepted for publication.

Progress in understanding of TBI occurred since the first SOTA in 2008. Although the problem of combat-related TBI was recognized by the VA and Department of Defense (DOD) in 2007, the scope and magnitude of chronic disabilities described above later received enhanced attention. In fiscal year 2007, VA TBI research funding for TBI approximated $2.7 million. This commitment more than doubled in fiscal year 2008 to approximately $5.7 million. During seven years since that SOTA, VA research funding for TBI research increased over 7-fold to almost $40 million. Extensive VA research focused upon lifetime brain health, quality of life, and efforts to manage the long-term impacts of TBI upon Veterans and their families.

Another contributing advance was the 2014 National Research Action Plan (NRAP) which aligned major research funding agencies together to a focus upon understanding TBI, the extent that TBI is a problem, how to detect TBI, develop therapies for TBI, and how to improve care with those with TBI, including assisting caregivers and reintegration of the Veteran back into their community. The NRAP working group also realized that this would not be possible unless the agencies and the researchers shared information. The resulting enhanced information sharing accelerated TBI research. The benefits of increased communication across agencies and researchers initiated an exciting, productive era in TBI and brain research generally.

Based upon the NRAP structure, the 2015 SOTA group sessions were based upon the categories outlined in the NRAP, including injury mechanisms and their sequellae over time, epidemiology of varying injuries, injury detection screening and diagnosis, clinical progression, complex sensory-related comorbidities, and late clinical care and rehabilitation. This special issue covers topics related to understanding injury mechanisms in terms of therapeutic development, influence of TBI on progressive neurodegenerative conditions, clinical advances in managing TBI, along with its long-term effects upon families and caregivers

Cernak et al. first provide an in-depth discussion experimental animal model to study injury mechanisms in military brain injury. These include blunt and blast injuries mainly investigated in rodents and to a lesser extent in larger animals (e.g. pigs or primates). Although the animal models of militarily relevant TBI have advanced since 2008, translational successes in prevention and treatment have yet to be realized in clinical trials. Cernak et al. offer recommendations on how the field of experimental modelling might progress along with specific concepts that experimentalists might agree upon and standardize.

Dekosky and Asken then consider a critical question: What is the risk and possible aetiology of TBI-related neurodegeneration? Dr Dekosky early recognized that repetitive brain injuries increase the risk for a progressive degenerative brain conditions known at Chronic Traumatic Encephalopathy (CTE). This condition was newly proposed back in 2008 with Bennet Omalu’s initial case report of a retired National League Football player whose brain exhibited this unique pathology (2). While the prior SOTA considered the possibility of early onset dementia and Parkinson’s disease in combat exposed Veterans, CTE had not entered into the public lexicon in 2008. These authors critically discuss the supporting and opposing evidence for CTE. The authors also offer a way forward to bring higher level of scientific investigation to bear on this unique problem.

Pogoda et al. provide an understanding of the extent of the problem that military-related TBI continues to affect Veterans long after their service has ended. This review is a comprehensive combination of the epidemiology and the health economics of TBI in the VA patient population. They provide an in-depth insight into the complexity of military-related TBI transcending psychological health issues and polytrauma clinical triad first recognized 2008. These authors consider complex epidemiology effects upon overall physical and mental health associated comorbidities and the service utilization and costs that these conditions require. They suggest use of technology to reduce the cost of care delivery, as well as to expanding access by use of smart phones and broadband-based telerehabilitation. This emphasis on care delivery is timely, particularly for Veterans living in rural area.

The next two articles consider pressing clinical diagnostic questions: How might clinical effects of TBI be detected months to years after the injury? It is known that TBI is heterogeneous and associated with several complex and overlapping comorbidities. Imaging, considered in 2008 SOTA, but has had extensive advances in imaging technology, both in hardware (strength of magnets) and software (improved algorithms), and, as a result of longitudinal sequential studies, a better understanding of potential lesion evolution. The comprehensive review by Salat et al. from the Boston TRACT group provides the reader with an outstanding background of where neuroimaging has been its current capabilities and where it might go in the future. The technology regarding magnetic resonance imaging (MRI) using diffusion tensor imaging (DTI) has reached the level of sensitivity that DTI can now detect the effects of brain injury previously invisible to imaging using conventional CT and MRI scanning. Additional technologies, such as combining Electroencephalography (EEG) with DTI or magnetoencephalography (MEG) which images magnetic fields generated by electrical activity now offer real time direct measurement of brain activity to detect disruptions in connectivity and abnormal brain signalling after TBI.

The technology for chemical detection of minute quantities of specific proteins in both serum and cerebrospinal fluid was underdeveloped till 2008. Agoston et al. now provide a detailed descriptive analysis of biofluid biomarkers of traumatic brain injury. They conclude that serial sampling, particularly examination of cerebrospinal fluid biomarkers, may be particularly useful to characterize TBI severity and temporal profiles while ultra-high sensitivity detection methods and CNS-derived exosomes have a potential to identify blood biomarkers during a range of TBI severity and time course. Currently, a number of biotech start-ups are competing to provide validated markers for detection and staging of TBI. This field is nearing a stage where the assays are becoming reliable enough to detect injury not just in the acute, but also in later injury stages. Together, imaging, physiological, and fluid biomarkers should provide the clinician information about injury severity, as well as objective measures to evaluate effects of treatment in future clinical therapeutic trials.

Gallun et al. and Akin et al. consider two of the more frequent sensory complaints of Veterans with military-related TBI: auditory dysfunction and balance impairments. The impact of repeated blasts can disrupt both delicate sensory modalities, both at the peripheral sensory organ and, in the case of TBI, the perception of sensory information from these sense organs. The science in recent years has progressed such that sense organ damage can be distinguished from the brain damage. Although injury to peripheral sensory organs may cause permanent sensory deficits, TBI-related effects on sensory perception can be ameliorated through various rehabilitative techniques. For instance, use of technology to selectively enhance the sound of the speaker over the background noise is an important option for those with central auditory difficulties, while behavioural-based therapies have been shown to help with both auditory and balance dysfunctions.

Scholten et al. review the newly released Clinical Practice Guideline and Clinical Practice Recommendations for mild TBI that recently released by the Departments of Veterans Affairs and Defense. This group delineates the considerable improvement over previous guidelines with evidence-based evaluations to support addition or deletion of certain measures. This contribution highlights gaps in areas that need attention by brain injury researchers to improve care injured Service Members and Veterans along with steps needed to advance the scientific basis of TBI/concussion care.

Malbec et al. review emerging research concerning caregivers for Veterans with chronic traumatic brain injuries. These insights are critical in improving the care of patients with chronic brain injuries. This unique review examines a novel area of clinical concerns that, until quite recently, has been neglected. Caring for the caregiver and training the caregiver to be more effective and resilient is crucial to long-term patient care. Their sensitive, caring recommendations fill a crucial gap in continuum care for returning injured Veterans as well as assisting them with community reintegration.

Finally, Colonel Geoffrey Ling provides a call to arms for ‘The Imperative for a Cure for Traumatic Brain Injury’. While recognizing that no cure yet exists, he lauds the long and successful research effort of the Veterans Administration and the Office of Research and Development, particularly in its ability to mount successful long-term prospective trials. Recognizing the importance of the NRAP concept, he stresses the promise of the collective collaboration of the VA, DOD, and National Institutes of Health (NIH) in achieving this imperative.

This peer reviewed special issue of Brain Injury captures the main themes of the 2015 TBI SOTA Summit Proceedings. In addition to contributions to the current publication, the meeting itself resulted in scholarly, collegial dialogues, plenary considerations, and provided important stimuli for ongoing research, particularly as related to obligations for Service Members engaged in current combat, now including Operation Inherent Resolve (OIR) to defeat ISIS along with Operation Freedom Sentinel (OFS) related to continued operations in Afghanistan.

Declaration of interest

The authors are employees of the Department of Veterans Affairs and report no financial conflicts or interests. The opinions expressed are those of the authors and not necessarily those of the Department of Veterans Affairs of the Government of the United States.

Acknowledgments

We thank former VA Secretary, Robert McDonald and our former Chief Research and Development Officer, Dr. Timothy O’Leary for their inspiration and support for initiating and supporting this effort, and importantly, to our scientific contributors.