CDMRP Links Epilepsy and Traumatic Brain Injury

Arthur T. Downey addresses members of the Fort Detrick Silver Caduceus Society

Dr. Anthony Pacifico, ERP program manager, welcomes investigators during the introduction at a recent meeting held at CDMRP. (Photo by: Erin Bolling, CDMRP Public AffairsO)

Soldiers on the battlefield face many dangers related to potential injuries and challenges that can be both physical and mental. The U.S. Army Medical Research and Materiel Command provides support to the medical needs of the Warfighter, leading the advancement of military medicine. Due to the recent military conflicts in Iraq and Afghanistan, we have seen an increase in the number of cases of Traumatic Brain Injury sustained by our active duty Service Members.

What we must realize from this recent increase of TBI related injuries and the need for greater medical support is that additional complications can often occur following the initial injury. In response to this, the Congressionally Directed Medical Research Programs' Epilepsy Research Program is currently funding Epilepsy research and, more specifically, Post-Traumatic Epilepsy research.

The correlation between TBI and PTE is well established, but we have to understand how one can lead to the next. We know that a TBI occurs when an injury to the head causes damage to the brain. TBI is extremely complex and difficult to diagnose due to the varying degrees (mild, moderate, severe) of injury and, sometimes, a lack of immediate symptoms.

When an injury or illness occurs that affects the brain, this can alter brain activity. The affected individual may experience early or late occurring seizures with high frequency. Generally, PTE is a form of epilepsy resulting from physical damage to the brain. Just as all brains are different, all injuries are different, and each individual will experience different symptoms and recovery.

This brings us to the real focus: How do we understand the link between TBI and PTE? How can science determine if an individual will experience PTE after a brain injury, and can this be prevented?

"The Epilepsy Research Program was developed in July 2015 to address the inherent need to further our understanding of the relationship of TBI and PTE," said Col. Wanda Salzer, CDMRP director.

"The more we know about this relationship, the closer we can come to preventing PTE in our Service Members, Veterans and the American public. The CDMRP was established to manage this type of groundbreaking research."

We are aware of a relationship between TBI severity and the risk for PTE, but the mechanisms by which this occurs are not yet fully characterized.

"One of the biggest things changing is that we are making very steady gains in understanding how the various types of brain cells communicate with each other," said Dr. Anthony Pacifico, ERP program manager.

"There are many types of brain cells, besides neurons," he continued. "We know that in PTE, the communication is somehow altered due to injury. New advances in methods such as optogenetics, advanced MRI and datasharing/analysis promise to bring us closer to translating new medicines or interventions for PTE, and therefore help to expand our understanding of epilepsy in general."

As part of the ERP's planning, the CDMRP works closely with federal partners at the National Institutes of Health, National Institute of Neurological Disorders and Stroke, as well as the Citizens United for Research in Epilepsy consortium. These partnerships are essential to advancing the research that can lead to the development of the most high-impact medical solutions.

During a recent meeting between CDMRP and investigators funded through the ERP, Dr. Mary Jo Pugh, research scientist at the VA Salt Lake City Health Care System and professor in the Department of Medicine at the University of Utah, discussed her currently funded project.

"What we know about post-traumatic epilepsy comes from a long deep history of research involving Veterans going back to World War I," said Pugh.

"In fact, the Vietnam Head Injury Study has been one of the most prolific studies of severe and penetrating TBI, and has informed what we know about post-traumatic epilepsy in ways that include neuroimaging and neuropsychological measures," she added.

Pugh discussed how post-9/11 military engagements have a high number of documented mild TBIs. The long term consequences of these injuries, especially when repetitive, need to be characterized in order to improve the quality of care for Service Members and Veterans alike. Understanding PTE therefore is an important research initiative.

"Our initial exploration of the relationship between mild TBI and epilepsy revealed a significant but weak relationship between mild TBI and epilepsy; however, the data used for this study was from VA [Department of Veterans Affairs] electronic health records that are collected in the course of clinical care and not for research purposes," continued Pugh. "While providing a valuable glimpse at the population, there is a fundamental need for additional data to understand this problem."

The risk for TBI is present in sports, military training and deployment, as well as outside of military service in civilian life (car accidents, workplace injuries, etc.). This is why this research is focusing on the individuals' lifetime TBI history, so we may better understand the linkage between TBI and any resulting complications, including PTE.

"This foundational study provides the first step in that line of inquiry, by more closely examining this question," said Pugh. "We will combine Trauma Registry and health system data from the DOD and the VA, with survey and interview data from Veterans, to better understand how deployment-related experiences and lifetime TBI exposure are related to epilepsy. We view this as a signal-finding expedition, as we expect this study to inspire at least as many questions as it answers. We can then drill down further into clinically rich data or develop more focused clinical studies to address hypotheses developed within the course of this study."

This research will be the first to use a national sample of Veterans to examine the impact of epilepsy on the social, emotional, physical and functional status. The information gathered will provide a foundation for determining how well the needs of our Veterans with epilepsy are currently being met, as well as any areas for improvement.

"With the program just around two years old, we're still waiting for many of our first projects to have early outcomes," explained Pacifico. "That doesn't mean we can't have immediate impact by coordinating activities with our partners interested in PTE."

This research is certain to have an impact on past, present and future Service Members, as well as civilians. This truly is what military medical research is all about –working on medical solutions to improve and save lives.

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Last Modified Date: 22-Nov-2017