Researchers Try to Predict Epilepsy

Survivors of traumatic brain injuries - from car-crash victims to soldiers wounded in Iraq - face an extra hurdle as they recover: Thousands of them will develop epilepsy months or years later. The risk is especially high for certain kinds of war injuries. Studies of Vietnam veterans suggest up to 50 percent, says Dr. Nancy Temkin of the University of Washington.

Major new research is beginning into ways to predict exactly who is most at risk and how to protect their vulnerable brains.

Among the efforts: pilot studies to see if the newer seizure-treating drugs Topamax or Keppra might actually prevent epilepsy if they're taken immediately after a serious brain injury.

"It is among the most frustrating things in medicine to know that someone's at risk ... and be unable to do anything about it," says Dr. Marc Dichter of the University of Pennsylvania, who is leading the Topamax study and pushing for better recognition of such patients.

Adding to their struggle: Epilepsy may not begin with the classic jerking seizures, but instead with memory loss, attention problems or other more subtle symptoms that doctors can mistakenly attribute to the original brain injury, post-traumatic stress or some other factor.

Almost 3 million Americans have epilepsy, a condition in which the brain essentially suffers periodic electrical storms. When its circuits misfire fast enough, a seizure results.

Epilepsy has multiple causes. Some people are born with it.

But about 5 percent of the nation's epilepsy was caused by traumatic brain injury, or TBI. What's the risk? Roughly 25 percent of survivors of moderate to severe brain injury will develop epilepsy. Even more, perhaps, for certain types of war injuries.

Injuries that cause bleeding inside the brain are the riskiest.

The population at risk is huge: Some 1.4 million children and adults suffer serious brain injuries every year from car or bike crashes, falls, gunshot wounds and other trauma.

After the initial injury, inflammation and treatment comes a "silent period" during which survivors work to recover. It can last months or even years before epilepsy appears.

"This silent period is not really silent," Dr. Shlomo Shinnar of the Albert Einstein College of Medicine told a meeting of epilepsy specialists at the National Institutes of Health last week.

Instead, as the damaged brain tries to rewire itself - a crucial process called plasticity - misfiring circuitry can form. Injured neurons can make new connections in wrong places, or overly excitable connections. Even the brain's genes change the way they work after head injury.

"You need the plasticity for recovery. You don't want to stop it. You just want to structure it in a way that it aids recovery without causing seizures," Temkin explains.

It's not clear yet how to do that, so scientists instead are testing what's available - seizure-controlling drugs - as possible epilepsy preventers. Three old medications have failed. New pilot studies funded by the NIH and Defense Department are checking Topamax and Keppra, which work differently from older competitors.

"It's a bit of a shot in the dark," acknowledges Dr. Pavel Klein, who is running the Keppra study at Washington Hospital Center and Children's National Medical Center in the nation's capitol.

But there are some hints that these newer drugs might work, perhaps by inhibiting cell-harming chemicals wrought by post-injury inflammation, he says.

Each study is enrolling about 90 patients, a first step to ensure the drugs won't harm overall recovery before larger trials begin. Participants get the drug within hours of arriving at the emergency room, and take it for one to three months. Klein has treated 60 patients so far with no serious side effects; Dichter's study at Penn begins enrolling soon.

Until some protection is found, Dichter wants a bigger effort at warning about the epilepsy risk so that patients can recognize subtle symptoms. At his urging, the American Epilepsy Society is creating a task force to target brain-injured soldiers, work that Dichter says may eventually translate to the far bigger population of injured civilians.

Consider Denise Pease, an assistant comptroller for New York City. Months after what was initially deemed a minor head injury in a 1995 taxi crash, she began experiencing lost periods of time, increasing confusion and cognitive problems.

"This woman who dealt with the titans of industry ... was unable to make change at the corner store," Pease told the NIH meeting.

Only when a nephew witnessed a muscle-jerking seizure well over a year later did she get the right diagnosis and begin her recovery. Today, after years of trying different medications, she has good epilepsy control, and warns that "my experience ... is not unique."

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Lauran Neergaard covers health and medical issues for The Associated Press in Washington.

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On the Net:

Patient epilepsy info: https://www.epilepsyfoundation.org

Brain Injury Association of America: https://www.biausa.org

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