Traumatic Brain Injury a Growing Problem Among Troops Serving in Today’s Wars

Thousands of troops serving in Iraq and Afghanistan have sustained traumatic brain injury (TBI), an invisible wound that is poorly understood and difficult to diagnose and treat.

Soldiers who have experienced TBI during combat are often capable of continued service. But some individuals may experience serious and lingering physical, emotional, and behavioral effects. As a result, the growing number of soldiers and veterans who have sustained TBI has brought new urgency to efforts aimed at developing better ways to diagnose and treat this condition.

Traumatic brain injury accounts for a larger proportion of casualties in the Iraq and Afghanistan wars than in other recent US wars because explosive devices have been the opposition's weapon of choice. Some information about TBI's effects on patients can be gleaned from civilian cases of TBI that often arise from events such as motor vehicle crashes, sports injuries, and falls. But the latter may not mirror the full range of effects of the combat-related TBI that today's soldiers in Operation Enduring Freedom and Operation Iraqi Freedom experience, especially TBI resulting from blast exposures from explosive devices, a common cause of brain injury in these settings (Elder GA et al. Psychiatr Clin North Am. 2010;33[4]:757-781; MacDonald CL et al. N Engl J Med. 2011;364[22]:2091-2100; http://tinyurl.com/5ugudqh).

“There is still more that we do not know about nonimpact blast-induced TBI than what we do know,” said Ibolja Cernak, MD, PhD, of the Department of National Security Technology at the Johns Hopkins University's Applied Physics Laboratory.

Combat settings can present challenges to making a diagnosis of TBI, which can cause a range of physical and psychological symptoms of varying degrees that may appear immediately after the traumatic event or days or weeks later.

“TBI has been referred to as a silent epidemic because the major post-TBI disabilities and neuropsychiatric problems are often not immediately apparent,” said Roy Reeves, DO, PhD, chief of mental health at G. V. (Sonny) Montgomery VA Medical Center in Jackson, Mississippi.

Mild TBI or concussion is the most common type of TBI among troops in Iraq and Afghanistan, and in many cases it is caused by blast exposure. Primary blast injury results from blast wave–induced changes in atmospheric pressure, which can accelerate organs and tissues of different densities at different relative rates, resulting in displacement, stretching, and shearing forces. Researchers are working to understand precisely how primary blast waves damage the brain and whether multiple exposures to low-level blasts can lead to lasting damage (Elder GA et al. Psychiatr Clin North Am. 2010;33[4]:757-781). More is known about secondary blast injury, which results from being struck by objects put in motion by the blast wind, and tertiary blast injury, which results from being blown into objects by the blast wind. These injuries are thought to be similar to those experienced by civilians with TBI (http://tinyurl.com/5t9bsnx).

“Primary blast can cause brain damage by either interacting directly with the head through direct passage of the blast wave through the skull and/or causing acceleration and/or rotation of the head,” said Cernak. “It can also act indirectly, when the kinetic energy from the blast wave is transferred through large blood vessels in the abdomen and chest to the central nervous system,” he added.

At the recent Federal Interagency Conference on Traumatic Brain Injury, held in Washington, DC (http://tinyurl.com/2fdgfux), investigators noted that in mice exposed to a single blast wave, oxidative stress may cause neuronal damage, and immunological effects may lead to chronic systemic and neurological abnormalities. Others at the meeting explained that blasts likely affect the delicate connections of the brain at the level of capillary beds of the gray matter, resulting in a generalized bruising pattern of tissue damage that is not evident on structural imaging.

Although most individuals who experience mild TBI recover quickly from their injuries, studies have shown that 5% to 15% of patients may be burdened with long-term problems. A recent analysis of 907 soldiers in one Army unit who had TBI, mostly mild, found that 33.4% reported 3 or more symptoms after injury and 7.5% reported 3 or more symptoms postdeployment. Headache and dizziness were most frequently reported after injury, with irritability and memory problems presenting and persisting over time (Terrio H et al. J Head Trauma Rehabil. 2009;24[1]:14-23).

Research indicates that many patients with TBI develop depression or other mood disorders that restrict their social contact and increase loneliness. Also complicating TBI in soldiers is a high prevalence of posttraumatic stress disorder (PTSD). A study of veterans from the Iraq and Afghanistan wars found that compared with veterans without mild TBI, those with mild TBI were younger, more likely to have PTSD, and more likely to report fair to poor overall health and unmet medical and psychological needs; they also scored higher on measures of psychosocial difficulties and perceived barriers to mental health care (Pietrzak RH et al. J Nerv Ment Dis. 2009;197[10]:748-753). Neurological deficits associated with TBI may explain the increased susceptibility of brain-injured individuals to PTSD as well as to substance use disorders (Corrigan JD, Cole TB. JAMA. 2008;300[6]:720-721).

Soldiers' risk of TBI remains high despite attempts to prevent or limit such injuries through protective military equipment such as helmets and armored vehicles, as well as the use of technologies to detect improvised explosive devices. “At present, the military medical community can do little to reduce this risk,” said Remington Nevin, MD, MPH, an Army epidemiologist who served in Afghanistan. “But what it can do is enforce stringent policies that sharply restrict the deployment of susceptible or highly at-risk service members, such as those already with a history of symptomatic TBI.”

Evidence indicates that individuals with a history of symptomatic TBI are at a significantly increased risk of morbidity and disability from a subsequent TBI. “Since today's service members routinely deploy multiple times, often with only months between tours, accurately identifying and restricting them from subsequent deployments should be the cornerstone of a TBI policy focused around prevention,” said Nevin. Figures from January 2003 to April 2011 from the Armed Forces Health Surveillance Center indicate that there have been 2858 service members with a predeployment diagnosis of TBI who were deployed to Iraq or Afghanistan (see http://tinyurl.com/3rtq9wj, page 17). Also, military personnel have a disincentive to report TBI if they suspect they would not be allowed to serve overseas. This could interfere with prevalence estimates as well as treatment efforts.

With prevention as a first line of defense against TBI falling short, much effort is focused on providing treatment for affected service members who have been diagnosed as having the condition. For example, 15 TBI programs in the Department of Defense and the Department of Veterans Affairs hospitals and 2 civilian TBI rehabilitation programs make up the Defense and Veterans Brain Injury Center, which is headquartered at the Walter Reed Army Medical Center in Washington, DC. Sites work collaboratively to provide and improve TBI care for active-duty military, veterans, and their eligible beneficiaries. The Department of Veterans Affairs also heads a nationwide program called the Polytrauma/TBI System of Care (http://www.polytrauma.va.gov/), and the military provides additional TBI treatment programs such as those at Brooke Army Medical Center at Fort Sam Houston, San Antonio, Texas (http://tinyurl.com/5rptpr7).

But treatment of patients with TBI can be difficult and complex. Therapy typically involves a multidisciplinary approach using medication, such as antidepressants and psychiatric drugs, and rehabilitative interventions, such as cognitive therapies, behavioral treatments, social skills training, vocational training, and individual, group, and family therapy.

While a safe and effective treatment for TBI has yet to reach clinical practice, preclinical and early clinical research exploring novel treatment strategies for TBI are under way and are generating promising results. Some investigators are probing approaches such as mild to moderate hypothermia immediately following injury. Results have been mixed, and factors such as injury severity, age, and sex may play an important role in determining the efficacy of this strategy. Also, questions remain regarding the therapeutic window of hypothermic treatment, how long cooling should be continued in different patient populations, and how rewarming should be conducted (Dietrich WD, Bramlett HM. Neurotherapeutics. 2010;7[1]:43-50).

Other potentially promising interventions target the inflammatory response in an attempt to provide neuroprotection to the brain. At the Federal Interagency Conference on Traumatic Brain Injury, researchers noted that while inflammation is thought to exacerbate injury after TBI, certain aspects of the brain inflammatory response may also promote neuronal plasticity and brain recovery after injury.

These opposing effects are likely to be temporally discrete, with the injurious aspects of inflammation dominating in the first few days after injury and the beneficial, recovery-promoting aspects becoming important later on. Preclinical study results presented at the meeting suggest that administering an inhibitor of poly(ADP-ribose) polymerase, which acts against inflammation by blocking NF-κB–mediated gene transcription, during the first few days after TBI, can improve long-term outcomes.

Also, recent data suggest that strategies that promote brain repair at the cellular level—by promoting angiogenesis, axonal remodeling, and neurogenesis—show potential rehabilitative effects. For example, there is a substantial increase in vasculogenesis following TBI, and pharmacologic agents such as erythropoietin and statins promote angiogenesis and improve functional recovery in rats after TBI. In addition, axonal sprouting from surviving neurons may be associated with spontaneous motor recovery over time after TBI, and treatments such as bone marrow stromal cells that promote axonal plasticity could provide additional benefits (Xiong Y et al. Curr Opin Investig Drugs. 2010;11[3]:298-308).

Also, because TBI is a complex condition caused by a cascade of changes in the brain and throughout the body that leads to pathological events including neuronal hyperactivity, excessive glutamate release, inflammation, increased blood-brain barrier permeability and cerebral edema, altered gene expression, and neuronal dysfunction, attention is now turning to pleiotropic drugs (agents that have more than one effect) that act on multiple genomic, proteomic, and metabolic pathways to improve outcomes after brain injury.

One such agent, progesterone, which acts through numerous metabolic and physiological pathways that can affect injury responses, is proving to be an effective neuroprotective agent in a variety of central nervous system injury models (Stein DG. Neuroscienc e. doi:10.1016 /j.neuroscience.2011.04.013 [published online ahead of print April 14, 2011]; Junpeng M et al. Cochrane Database Syst Rev. 2011;[1]:CD008409). Valproate, an antiepileptic drug, is also generating promising results in animal studies. This agent has a number of targets including γ-aminobutyric acid (GABA) transaminase, voltage-gated sodium channels, glycogen synthase kinase 3, and histone deacetylases, and therefore may attenuate various TBI-associated pathologies (Dash PK et al. PLoS One. 2010;5[6]:e11383).

It is likely that optimal treatment for TBI will involve tailoring various therapies to the needs of each patient at different stages after injury, said Jennifer Vasterling, PhD, chief of the VA Boston Healthcare System's psychology service.

“Work being done to identify biomarkers and other risk factors that might help predict natural recovery will prove useful in further developing interventions and matching the right patients to the right interventions to optimize their recovery,” said Vasterling.

This article was corrected for errors on August 4, 2011.