Since 2001, better body armor and innovations in battlefield medicine have made troops in Iraq and Afghanistan more likely than ever to survive modern warfare’s multiple, complex injuries. Partly as a result of these breakthroughs, the characteristic weapons of enemy combatants in these conflicts – improvised explosive devices (IEDs), rocket-propelled grenades (RPGs), and other explosive weapons – have, instead of killing service members, left many with one of the war’s signature wounds: traumatic brain injury, or TBI.

According to the Armed Forces Health Surveillance Center, 266,810 cases of TBI were recorded among service members from 2000 to 2012, more than 80 percent of them non-combat-related. Because the use of Kevlar helmets and body armor have reduced the number of penetrating wounds, the vast majority of combat-related TBI cases are closed-head injuries caused by blast-related concussion.

Because several of TBI’s physical and psychological symptoms – which can include headaches, dizziness, nausea, mood swings, fatigue, sleep disorders, and problems with memory or concentration – are indicative of other conditions as well, TBI (especially mild TBI, also known as concussion or mTBI) often goes unrecognized. The Department of Veterans Affairs (VA) has confirmed that 11.8 percent of the 760,250 veterans who were deployed to Iraq and Afghanistan and have sought service at VA facilities have suffered some degree of TBI. MTBI may persist as post-concussive syndrome (PCS), a chronic condition that may have physical, cognitive, emotional, and behavioral effects.

The Department of Veterans Affairs (VA) has confirmed that 11.8 percent of the 760,250 veterans who were deployed to Iraq and Afghanistan and have sought service at VA facilities have suffered some degree of TBI.

The Department of Defense (DoD) and the VA collaborate closely on both healthcare and research related to TBI. For obvious reasons, DoD research focuses on the development of battlefield screening tools, combat casualty care, and rehabilitation efforts aimed at returning a service member to duty. Once a service member separates from active-duty service, it’s the job of VA clinicians to both screen for and diagnose chronic TBI-related conditions and to administer therapies, treatments, and coping strategies that can help veterans and their families.

VA’s research program, led by its Rehabilitation Research and Development (RR&D) Service, is focused on better understanding the brain changes that occur in TBI, refining screening and diagnostic tools, and developing and evaluating treatments and strategies for coping with chronic mTBI symptoms.

 

TBI and the Brain

TBI is often difficult to diagnose because its indicators are cognitive, behavioral, vary widely among patients, and have overlapping co-occurring conditions. Researchers are challenged by imprecise diagnostic tools, as well as the criteria used to classify TBI by severity and type.

Another challenge associated with TBI research is that the effects of an injury are so diffuse: Most people are aware of the cognitive, emotional, and behavioral problems associated with TBI, but a brain injury can also have lingering effects on sensory issues; it can damage not only the sensory organs and nerves used to see, hear, and smell, but also the brain processing of the sensory information that leads to a person’s perception of these sensations. VA researchers at facilities across the country are examining TBI’s effects on auditory and visual processing, as well as balance: The vestibular organ, located in the inner ear, is especially vulnerable to blast injury.

These TBI-related changes are often challenging to quantify, but continued research points to the possibility of using hearing, smell, and vision tests, including binocular function tests, that may detect subtle TBI-related impairments that might be missed by standard exams.

VA researchers are contributing to a large and growing body of work examining TBI-specific changes in the brain that can be detected and measured. If proven reliable, these “biomarkers” can indicate either the existence of a chronic degenerative condition or its opposite: the brain healing or regeneration or recovery of function – in clinical terms, neuroplasticity.

“The injured brain looks and functions differently from a normal brain,” said Dr. Stuart Hoffman, scientific program manager for VA’s TBI research. “Even the older technologies, like EEG, show there’s different activity.” What exactly these differences are, however – especially in a chronic post-concussive state – are difficult to detect with conventional X-ray imaging technologies. So far, nobody knows for sure what TBI – especially in the chronic post-concussive state sometimes associated with mTBI – looks and acts like in the brain. But according to Hoffman, investigators are getting closer.

In Houston, Texas, researchers at the Traumatic Brain Injury Center of Excellence at the Michael E. DeBakey VA Medical Center have been using functional magnetic resonance imaging (fMRI), a technology that measures brain activity by detecting associated changes in blood flow, to study brain activity in TBI patients. A number of fMRI studies have shown alterations in blood flow, in specific regions of the brain, among subjects who have suffered blast injuries.

In the spring of 2012, a team of researchers from VA and the University of California, San Diego reported that magnetoencephalograpy (MEG), which records magnetic fields to map brain activity, is useful for detecting the subtle abnormalities in brain waves caused by TBI – even mTBI.

This same team is combining MEG with another type of imaging, a form of MRI known as diffusion tensor imaging, to offer a more complete picture of the injured brain. This work, said Hoffman, may be bringing VA researchers to the brink of a breakthrough: the discovery of a reliable diagnostic tool for mTBI. Diffusion imaging, Hoffman explained, works by reading the directionality of water molecules through brain tissues, i.e., water in white-matter fiber tracts is more constrained than water in grey matter. It is rapidly becoming the technology of choice for revealing abnormalities in the brain’s white-matter tracts – nerve fibers that carry nerve impulses between neurons – because it is sensitive enough to detect when these tracts have been torn or otherwise damaged. “In white matter,” explained Hoffman, “the water is constrained and typically goes in two directions, instead of all four. So you can visualize white-matter tracts.” Some diffusion imaging studies have indicated a correlation between white-matter damage and neurocognition.

Not all TBI-specific biomarkers are detected through imaging; many – such as higher- or lower-than-expected levels of proteins or other compounds – can be detected in samples of brain tissue, blood, or cerebrospinal fluid. Such markers have typically been more relevant to DoD researchers in detecting acute TBI shortly after a blast injury, and one of the most serious markers – an abnormal buildup of proteins associated with the progressive degenerative disease chronic traumatic encephalopathy, which can result from multiple concussions or head injuries – can only be definitively diagnosed after death.

In the summer of 2013, a joint University of Washington/VA Puget Sound team, in a study of 35 veterans with blast injuries, reported irregular pituitary hormone levels in blood samples from 42 percent of the subjects. The study, led by Dr. Charles Wilkinson, affirms past studies suggesting that up to half of TBI sufferers later experience a drop in the concentrations in at least one of the eight hormones produced by the pituitary, the pea-sized gland at the base of the brain.

“I would say we’re fairly close to having biomarkers for chronic conditions after brain injury,” Hoffman said. “It’s still probably three or four years out, but we’re fairly close.” VA researchers are confident enough in the effectiveness of MEG and diffusion imaging in detecting mTBI that they are helping lead the effort to establish a diagnostic standard, among image device manufacturers, for measuring and monitoring neural degeneration.

“Right now we have no way of monitoring these patients over time,” Hoffman said. “So having this standard imaging technique, along with biomarkers, we can not only detect whether veterans have this condition; we can monitor the progress of the condition – and that becomes very important when you talk about developing some possible treatment, or evaluating whether a certain treatment is working.”