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Traumatic Brain Injury: New Insight, But Treatment Remains Elusive

He was a veteran professional football player, in his mid-60s when he died, and a paper-thin cross section of his brain tissue taken at the autopsy appears visibly shrunken and atrophied. Perhaps that’s no surprise in an older man who played in an era of more primitive equipment. But neuropathologist Ann McKee has other samples that show similar damage in soldiers and athletes who died far younger. One, a football player, was just 18.

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Credit: Paul Kitagaki Jr

Head injuries among soldiers and athletes are hardly a new discovery, but for decades they were a blind spot. A bullet hole would get you a ticket home; a broken arm or torn ligaments would force you from the game. But until recently, a warrior who sustained a concussion—who’d had his bell rung—would shake it off and then return quickly to the battlefield or the playing field.

Today, there’s a growing alarm about the long-term dangers of traumatic brain injury (TBI). And in a discussion at AAAS, researchers described how injuries that show little abnormality on an MRI or CT scan can, years later, have debilitating effects ranging from irritability to rage and dementia. While scientists are learning much about the nature of these injuries, they said, therapies to protect or repair the brain are proving elusive.

The 23 October event, cosponsored by the Dana Foundation and AAAS, came at a critical time: Blast injuries, not bullets, are the dominant risk for soldiers deployed to Iraq and Afghanistan. The National Football League is facing lawsuits from nearly 4000 ex-players, and several current or former players have committed suicide in recent years; safety concerns now extend to community pee-wee football programs. Taken together, those streams represent a seeming TBI epidemic.

Chronic traumatic encephalopathy (CTE) is neuron degeneration that occurs after mild but repetitive traumatic brain injury, more commonly called concussions and subconcussions. James L. Hancock endured three concussions playing football and rugby. Then, while he was a Navy doctor deployed with the Marines at an advance base in Afghanistan’s Helmand province, his vehicle hit an improvised explosive device. The blast knocked him unconscious.

Captain Hancock told the AAAS audience that as he recovered, his sense of balance was compromised. He started to have migraines. “My emotions were absolutely flat,” he added. “Sleep became a problem.”

McKee, who is also a neurologist and director of the Neuropathology Service for the New England Veterans Administration Medical Centers, used images of stained brain tissue to illustrate features of CTE, including unusual deposits of the protein p-tau. Even "without the aid of a microscope…you can immediately see the abnormalities because they are so profound," she said. There is shrinkage and atrophy in the prefrontal cortex, the hippocampus, the amygdala, and other areas associated with learning, memory, judgment, and emotional control.

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 colonel and program manager at the Defense Advanced Research Projects Agency. Ling played a leading role in developing standard concussion treatment guidelines for the military and the Military Acute Concussion Evaluation tool, which enables frontline medics and junior officers to evaluate TBI.
 

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Visible damage. Mild but repetitive brain injury can transform healthy brain tissue (left) into the atrophied and deteriorated tissue associated with chronic traumatic encephalopathy (right).
Credit: Ann McKee

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, he explained, "it leads to an exaggerated response and has a 50% mortality rate."

Because so much remains unknown about the brain and the complex effects of TBI, "for us to try to grapple with all of the variables is impossible," McKee said. She believes that 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.

Authors

Bob Roehr

Edward W. Lempinen

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