AAMC Reporter: June 2007

Greater Knowledge Born from Battlefield Tragedies

Col. Geoffrey Ling, M.D., Ph.D., of the Uniformed Services University of the Health Sciences, researches traumatic brain injuries often sustained by soldiers in combat situations.

By Gregg Siegel, special to the Reporter

It happened in the blink of an eye back in January 2006. On a stretch of Iraqi desert just north of Baghdad, television journalist Bob Woodruff, host of ABC's World News Tonight, became the story himself after suffering devastating head injuries from the detonation of an insurgent's improvised explosive device (IED).

"He suffered penetrative wounds, which is what most people think of when they think of a head wound," explained Col. Geoffrey Ling, M.D., Ph.D., a neurosurgeon on the faculty of the Uniformed Services University of the Health Sciences (USUHS), who was serving at the Baghdad Combat Support Hospital where Woodruff was brought after the explosion. "But he also suffered blast injury to the brain, which is an injury not seen or well recognized until recently."

But if there was a silver lining to the event (in addition to the fact that Woodruff survived the blast), it was a new wave of public awareness for the innovative research into the traumatic brain injuries (TBI) sustained on the battlefields of Iraq.

Ling recalled that he and his neurosurgical colleagues were amazed at what they saw in IED blasts during their time in Iraq. Soldiers were saved from possibly fatal torso injuries by their body armor, but they were exhibiting other, previously unknown, physical effects.

"We found that the brain behaved unlike anything we had ever seen before," he said. "The tissue was angry and red and so swollen that we routinely had to remove a piece of skull to allow the brain to expand without damage. Brains often swell, but you don't see that immediate and dramatic swelling in other types of brain injuries, and it really shocked us. And we were seeing this day after day. It wasn't an isolated case."

Injuries like these are characterized as "severe traumatic brain injury," but are just one of many classes of TBIs being identified in Iraq war victims.

"With mild TBIs, victims might not have a scratch on them after being in the vicinity of an explosion," said Henry Lew, M.D., Ph.D., clinical associate professor at Stanford University Medical Center and medical director of the Inpatient Rehabilitation Center at the VA Palo Alto Health Care System.

"It is only perhaps months or years later that victims of these 'closed head' injuries manifest dramatic changes in behavior, and they and their families suspect that a physical injury has occurred, even if it can't be seen with current diagnostic technologies. In fact, it has been hypothesized that what is commonly called 'post traumatic stress disorder' might in many cases ultimately be shown to be a result of quantifiable brain damage," said Lew.

Ling, Lew, and many other medical school researchers are dedicating their talents to studying TBI in its many forms, unlocking the mystery of many TBIs and finding better short- and long-term treatments for their victims. In fact, much of the knowledge and procedures that saved Woodruff—and many brave men and women whose names are not as well known—were developed at the nation's medical schools.

Impact on the Brain

A wounded soldier is transferred to a helicopter in Iraq  Photo credit: U.S. Department of Defense

Ling's observations at the Baghdad Combat Support Hospital made him wonder what caused the brain to react the way it did to the IED blast, and led him to new research avenues when he returned to the United States.

"Blasts throw off a lot of different types of energy," he explained. "Pressure waves, heat, light, sonic boom, electromagnetic pulses. Which ones are impacting the brain, and how are they impacting the brain? No one knows yet."

So far, the work of Ling and his colleagues has led to several discoveries. They have seen that a blast can cause nerve track degeneration patterns they believe are similar to those seen in some known degenerative nerve disorders. They have also found that the impact of pressure waves alone are different than those of a full blast, adding strength to the hypothesis that there is a "force x" in the explosive environment that can cause much of the damage to the brain.

"If we can identify the forces involved and get our data to the helmet designers, the result could be the development of a helmet which protects the brain even more effectively than current technologies," said Ling.

Far from the battlefields of Iraq, Stanford's Lew is helping TBI patients at the Palo Alto VA Medical Center fight a new and very different war.

"A lot of our guys are returning and having problems adjusting because they are forgetful, confused, angry, or unable to carry out a task," he said. "This obviously affects their work and family life."

Most frustrating, Lew noted, is that these veterans are sometimes told their problems are "all in their heads." Lew is out to prove the literal truth of that statement by discovering imaging techniques and diagnostic markers for what cannot yet be detected via X-ray.

In testing TBI victims, Lew has discovered they often respond to certain stimuli differently than non-victims. For example, in a test where patients are asked to identify angry versus neutral faces, TBI victims not only take longer to do so and demonstrate less accuracy, they also display different brainwave patterns while performing the test.

"This is one of the ways we hope to objectively quantify this injury," said Lew.

Lew has also developed a multifaceted approach to helping victims improve their lives. He has been effective in helping them overcome frustrating memory lapses through mental exercises and compensatory strategies. The ability to drive a car, a skill often degraded by the injury, can be regained significantly through practice in a driving simulator. He is also working to educate people and change perceptions about TBIs.

"Patients, spouses, employers, psychiatrists, primary care doctors, and the public at large need to understand that the behavior is a result of injury and that help is available," he said.

Regenerating Brain Tissue

While many people believe that brain cells—unlike, say, skin cells—are unable to regenerate, recent research shows that cells in at least two regions of the human brain do, in fact, regrow themselves in response to injury. One of these regions is the hippocampus, a brain structure that plays a vital role in retaining memories. Memory problems are one of the most prevalent long-term consequences of TBIs of all kinds.

"There is a definite attempt by the injured brain to generate new neurons, but it is very slow and ineffective, with many cells dying before they can become part of a neural network," said Denes Agoston M.D., Ph.D., associate professor of neurosurgery at USUHS. Agoston is working on making this delicate natural biological process more robust.

"The hippocampal area is extremely vulnerable to any kind of trauma, but I believe that the natural tendency of the human brain to generate new neurons and incorporate them into the hippocampal network offers great promise if we can understand the mechanism and optimize it," he said.

Agoston's efforts are centered around two potential interventions. He is studying the efficacy of using existing pharmaceuticals to affect neuron regenesis, and investigating the impact of helping build neurons through memory exercises, akin to building muscle through physical exercises.

"I don't think it is yet understood how truly elastic our brains can be," he said.

Foundational Research at LSU

Bullet and shrapnel injuries are still the leading cause of TBIs on the battlefield, and medical school research has long focused on unique aspects of penetrative wounds, as well as on more generally applicable TBI research. Agoston, for example, is developing a pharmaceutical approach to treating brain edema, common in penetrative and other types of brain injury, as well as a predictive model for its development. Ling was involved with a project that attempted to characterize types of bullet head wounds by predicted clinical outcome as a way of managing triage priorities.

Both men point to a team led by Col. M.E. Carey, M.D., a former neurology professor at Louisiana State University (LSU) Health Sciences Center, as the group that conducted the field's seminal work.

Carey, who served as a combat doctor in Vietnam and the First Persian Gulf War, noted with frustration that "no significant reduction in the neurosurgical mortality associated with (gunshot wounds to the head) has occurred between World War II and the Vietnam conflict."

His work at LSU changed all that, leading to several innovations, with perhaps the most dramatic being changes to the process by which victims are treated in the precious seconds after injury occurs.

"Carey discovered that when one gets a gunshot wound to the brain, breathing stops for a brief period and that this apnea can kill before any actual brain damage does," said Ling.

"So now, even before tending to any obvious wounds, the preclinical management guidelines for brain injury in the field dictate that the victim's breathing be optimized. That's what the medics did for Bob Woodruff and many like him, and the procedure has helped to save the lives of many people that, before, might have died where they fell."

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