Progress made in traumatic brain injury treatment and diagnosis

September 1st, 2009

New research on traumatic brain injury (TBI) is being presented this week at the Military Health Research Forum (MHRF), a scientific meeting hosted by the Department of Defense (DOD) Congressionally Directed Medical Research Programs (CDMRP). Service men and women are particularly susceptible to TBI given the nature of combat.

TBI is a condition affecting a significant number of active-duty soldiers. The incidence of TBI among wounded military personnel is estimated at 20 percent. Often called the "signature injury" of the Iraqi war, TBI can lead to a range of symptoms, including headache, confusion, behavior change, memory trouble, repeated vomiting, convulsions, slurred speech and numbness in the extremities.

Studies on topics such as brain tissue regeneration, driving problems after mild TBI (mTBI), and the use of biomarkers to determine the extent of TBI are funded by the Psychological Health and Traumatic Brain Injury Research Program (PH/TBIRP) or by the Peer Reviewed Medical Research Program, both of which are programs within the CDMRP. The PH/TBIRP aims to prevent, mitigate, and treat the effects of traumatic stress and TBI on function, wellness, and overall quality of life for service members as well as their caregivers and families.

"We hope this research will address the nuances of combat-related TBI among our troops and offer physicians better tools for diagnosis and treatment of this unique population," says Captain E. Melissa Kaime, M.D., Director of the CDRMP. "Furthermore, the scope of this research could improve medical care for TBI in the civilian population."

Efficacy of Countermeasures against Traumatic Brain Injuries Sustained in Airborne Operations

Principal Investigator: John Crowley, M.D., U.S. Army Aeromedical Research Laboratory

A soldier's helmet provides protection against blunt head injury resulting from situations unique to military occupation (training for combat, actual combat) as well as hazards in civilian occupations (vehicle mishaps, falls). The U.S. Army Aeromedical Research Laboratory at Fort Rucker, Alabama, conducted a multiphase head injury prevention study to asses a prototype helmet designed to meet these challenges.

In Phase 1, two prototype helmet configurations that improved blunt-impact protection were identified and compared to the standard airborne troop helmet configuration. For Phase 2, these prototype helmets meeting safety requirements were fielded to airborne soldiers who, when surveyed following use of the prototype helmets, indicated a preference for the rate-sensitive "helmet pad" system used in the new Advanced Combat Helmet. In Phase 3, which also involved collaborators at the Defense and Veterans Brain Injury Center, self-reports from 585 paratroopers suggested the risk for TBI was 2.3 times greater when wearing the older Personnel Armor System for Ground Troops helmet compared to the newer Advanced Combat Helmet.

"Our research has shown the feasibility of improving blunt helmet protection for ground troops without compromising ballistic protection," said Principal Investigator John S. Crowley, M.D. "Additional research is underway to increase protection requirements to levels more reflective of actual combat exposure."

Post-Deployment Driving Problems: Survey of Scope and Timeline for Post-Deployment Soldiers with and without Mild Traumatic Brain Injury

Principal Investigator: Erica Stern, Ph.D., University of Minnesota School of Public Health

Soldiers deployed to Operation Iraqi Freedom and Operation Enduring Freedom (OIF/OEF) travel long distances to transport supplies and execute missions. In an effort to protect their vehicles and convoys during travel, soldiers often use specific driving behaviors to stay safe. For example, they straddle lanes or move off-road to avoid debris or objects at road side; drive erratically and very quickly; and continue through intersections regardless of a traffic signal or blocking vehicle to ensure that convoys are uninterrupted.

For many military personnel, these strategic driving patterns become automatic and associated with a sense of control and safety. But when these soldiers return home to the United States, these driving behaviors may endanger the soldiers, their families and their communities.

The CDMRP has funded a national study among soldiers, both deployed and never deployed. In a pilot survey of 198 Minnesota soldiers (150 who had been deployed and 48 never deployed to OIF/OEF), results showed a high incidence of carryover behaviors and driving-related anxieties among the soldiers who had been deployed. According to the survey, over the course of 30 days, about 25 percent of the deployed group had driven through a stop sign, compared to 5 percent of those who had not served, about 10 percent had driven erratically in a tunnel or an underpass compared to 3 percent , and nearly 25 percent of post-OIF/OEF soldiers had driven in the middle of the road or into oncoming traffic, compared to 8 percent. Driving in general caused anxiety for 20 percent of the post-deployment group, more than 30 percent said they were anxious when passed by other cars, and nearly 50 percent were anxious when other cars approached or "boxed" them in, compared with 0 percent, 8 percent and 25 percent, respectively, for those who had not been deployed.

In the course of 30 days, about 30 percent of post-deployed soldiers had been told they drove dangerously, while less than 10 percent of non-deployed compatriots received that feedback. While post-deployed soldiers' overall driving behaviors declined to that of non-deployed soldiers after 90 days of being back in America, these returning soldiers' driving anxieties remained significantly higher than non-deployed soldiers.

The investigators are eager to compare the results of the broader study to the pilot."The results of that survey will help us understand the national picture," says Principal Investigator Erica Stern, Ph.D., associate professor of occupational therapy at the University of Minnesota. "We can then use that information to develop initiatives to reduce driving behaviors and anxieties for post-deployment soldiers with and without TBI. It will also be useful to families and communities as soldiers are reintegrated at home."

Injectable Hydrogels for Brain Tissue Regeneration after Traumatic Brain Injury

Principal Investigator: Ning Zhang, Ph.D., Clemson University

When TBI occurs, brain tissue swells, leading to the release of compounds that cause damage to the healthy tissue around it. This cell deterioration, along with the brain's poor ability to regenerate, leads to the formation of a lesion or cavity at the site that causes prolonged neurological impairment.

Conventional TBI treatments focus on managing brain tissue swelling at the primary site and reducing the effects of the secondary injury to healthy brain tissue. The next step may be neural cell transplantation, but despite moderate progress with other diseases, it has had limited success for TBI repair due to poor donor cell survival and functionality. The ongoing tissue inflammation and scarring at the lesion site, in addition to the lack of supportive tissue structure within the cavity, present a hostile environment that jeopardizes the survival of transplanted cells.

Researchers at Clemson University developed an animal model for building a new vascular network, providing a viable structure in which to place transplanted cells in TBI patients. The study used a contusion model of TBI in adult male rats. Using an injected hydrogel at the TBI lesion cavity, a vasculature network was reconstructed to support the arriving cells. This is the first time a well-structured vasculature network was formed within an injected hydrogel at the TBI lesion cavity without using angiogenic growth factors. CDMRP-funded researchers took it a step further and transplanted neural stem cells with neural differentiation factors to the TBI lesion using the hydrogel as a carrier. Results showed that significant functional recovery was found in the laboratory rats after 8 weeks of treatment.

"For cell replacement at the TBI lesion cavity, there is a critical need to pre-condition the lesion site with a vasculature network to support subsequently arriving neural cells," said Principal Investigator Ning Zhang, Ph.D., Assistant Professor of Bioengineering, Microbiology and Immunology, and Cell Bology and Anatomy at Clemson University. "To this end, we developed an in-situ cross-linking hydrogel with similar mechanical property to that of native brain tissue and cell adhesive motifs so TBI can be treated more effectively."

Panel of Biomarkers Accurately Predicts the Probability of Intracranial Pathology in Mild Traumatic Brain Injuries

Principal Investigator: Gerald Grant, M.D., Duke University

Medical practitioners often experience challenges when initially evaluating and managing mild traumatic brain injury (mTBI) because some patients show no indication of the injury. In fact, approximately 8 percent of patients potentially have intracranial abnormalities but no readily apparent neurological deficit. In this study, a research team at Duke University sought to evaluate the utility of three biomarkers in predicting intracranial pathology. Plasma levels of biomarkers are measured to determine the presence or absence of a particular condition or disease. This research could propel development of a diagnostic tool that could possibly reduce the need for unnecessary testing or observation.

In a study of 119 prospectively enrolled patients with mTBI, two biomarkers -- brain natriuretic peptide (BNP) and D-Dimer -- were significantly predictive of intracranial abnormalities on a diagnostic head CT scan. Interestingly, the biomarker S100B, which has been a focus of TBI biomarker research, demonstrated the least predictive value. A logistical model combining all three of these biomarkers, BNP, D-Dimer, and S100B, demonstrated a high degree of sensitivity (92 percent) and a high negative predictive value (92 percent).

"A rapid diagnostic point-of-care test with a high negative predictive value for intracranial pathology would be a beneficial tool for physicians in emergency departments and for medics in the field, both civilian and military, when triaging patients who have sustained a mild traumatic brain injury," said Principal Investigator Gerald Grant, M.D., a Pediatric Neurosurgeon at Duke and former Lieutenant Colonel in the United States Air Force.

Source: US Department of Defense Congressionally Directed Medical Research Programs