Researchers Gain New Insight on Traumatic Brain Injury, but Treatment Remains Elusive

The first concussion came playing football in high school, the second playing the game at Annapolis, and a third playing rugby. It meant the end of contact sports for U.S. Navy Captain and doctor James L. Hancock, but not the end of his risk for traumatic brain injury.

While he was deployed with the Marines at an advance base in Afghanistan’s Helmand province, his vehicle hit an IED. The blast threw him against the radio tower on the vehicle and knocked him out. “I have no recollection of what happened that day,” Hancock told a AAAS audience. “I lost about eight hours of my life.”

The battlefield corpsmen stitched up the obvious wounds, but it would be several days before he could be evacuated to a larger base. With clinical precision, Hancock noted how his sense of balance was no longer the same: “I was stumbling over things that I wouldn’t ordinarily have done.”

He started to have migraines and activity made them worse. “My emotions were absolutely flat,” he added. “Sleep became a problem.” Back pain became a problem too, though it took him two years to link it to damage to four vertebrae.

 

James L. Hancock [All photos by Bob Roehr]

James L. Hancock
[All photos by Bob Roehr]

Hancock shared his personal experience at a forum, “The Science and Impact of Traumatic Brain Injury” that packed the AAAS auditorium on 23 October. It was co-sponsored by AAAS and the Dana Foundation, a leading funder of brain research.

 

“This is an extremely interesting and timely discussion,” said AAAS CEO Alan I. Leshner at the start of the forum. Leshner, a neuroscientist and also executive publisher of Science, praised the speakers “for both substantive expertise and experience on the ground dealing with these kinds of issues.” He noted the growing public concern with brain injury incurred through sports and warfare.

Chronic traumatic encephalopathy (CTE) is neurodegeneration that occurs after repetitive but mild traumatic brain injury (TBI), more commonly called a concussion, explained Ann McKee, associate professor of neurology and pathology at the Boston University School of Medicine.

“If you look at a CT scan or MRI you don’t see any abnormality,” she said. “You really have to look deep inside the brain to see the subtle alternations that occur after the traumatic injury,” she said. Some of the insults appear to have little or no short-term effect, but often become serious years or decades later.

Alan I. Leshner

Alan I. Leshner

Using images of paper-thin cross-sections of brain tissue from autopsy of boxers, football players, and soldiers, McKee pointed out features that distinguish CTE from other brain diseases. One is deposits of the protein p-Tau that in the early stages are “perivascular, around small blood vessels,” she explained. “That is entirely unique.” The greatest abnormality is seen at the bottom of the crevices that characterize the brain.

“When you look at the brain after it has been sectioned and stained for Tau, even looking at the brain sections without the aid of a microscope, with your naked eye, you can immediately see the abnormalities because they are so profound,” she said. There is shrinkage in volume in parts that control judgment, impulsiveness, emotion, and memory “in a way that no other disorder affects the brain.”

There was little surprise to see these changes in the brain of a 73-year-old ex-boxer, but the same patterns were repeated in a variety of men as young as an 18 year-old high school football and rugby player who died from complications of a concussion. “Usually the traumatic brain trauma occurs early in life,” McKee said, “and there is a lag period before they develop symptoms of neurodegeneration.”

The first treatment guidelines for TBI were developed in the 1990s and were simply “to maintain the general physiology to support the brain,” said Geoffrey Ling, a retired Army Colonel, program manager at the Defense Advanced Research Projects Agency (DARPA) and professor in the department of neurology at the Uniformed Services University of the Health Sciences. While some drugs have shown neuroprotection in animals, none have proven useful in humans.

Ann McKee

Ann McKee

He played a leading role in developing standard concussion treatment guidelines for the military and the Military Acute Concussion Evaluation tool, which enables front line medics and junior officers to evaluate TBI.

“It is our firm belief that a brain-injured patient may not know that he or she is injured—that is the nature of the injury,” said Ling. That denial of injury is further reinforced by a culture of the military (and sports teams) to not let their buddies down. This is why “we moved medicine to the patient” rather than wait for the soldier to acknowledge symptoms and seek help, he added.

The key medical reason to quickly identify TBI is second-impact syndrome. Ling said when a patient sustains a second head injury before fully recovered from the first, “it leads to an exaggerated response and has a 50% mortality rate.”

“We put the burden of responsibility on the leadership” to make sure that soldiers under their command are properly evaluated for exposure to concussion, and are properly referred for medical help, he explained.

Ling said that Jeffrey Rogers, in DARPA’s Microsystems Technology Office, also developed a small, $45 personal pressure gauge that measures exposure to blast. Push the button and if the light is green, then the level of the blast was insufficient to cause damage, but yellow or red indicates greater risk of exposure and the need for evaluation.

Geoffrey Ling

Geoffrey Ling

After experiencing concussion on the gridiron and in an explosion, Hancock believes that they are different, with the later tending to be more severe. It also is more likely to be accompanied by back injury and PTSD.

He also suspects that consistently elevated adrenal levels as a response to the stress and hypervigilance of deployment in combat and hypoxia from the high altitudes of Afghanistan might contribute to a different neural state and affect capacity to recover.

The standard of care for TBI today consists of letting the brain rest and providing symptom relief, primarily for pain, Hancock said, even though there is little evidence to back that practice.

“In order to make good therapies we have to understand the basic mechanisms of the disease,” McKee argued. While acknowledging that blast might cause more severe or extreme brain injury than other forms of TBI, she believes that structurally and physiologically the injuries are similar.

“For us to try to grapple with all of the variables is impossible,” she said. McKee believes improved treatment will come through understanding the physical changes in the brain that occur at the microscopic and molecular levels when the brain is subject to trauma. And that understanding is only beginning to emerge.

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