Genetic link to epilepsy after brain injury

Nutrition Health Review, Summer, 2003

People who inherit a particular gene involved in lipid metabolism in the brain appear to be at higher risk of experiencing seizures after traumatic brain injury, according to researchers at University of Texas-Southwestern Medical Center at Dallas.

A study published in Archives of Neurology (June 2003) found that patients with moderate to severe brain injuries who had inherited the epsilon 4 variation of the apolipoprotein E (apoE) gene were 2.41 times more likely to have seizures than patients without the gene.

The finding sheds new light on the pathophysiology of post-traumatic epilepsy and may lead to new therapies to prevent seizures in brain-injured patients, said Dr. Ramon Diaz-Arrastia, Associate Professor of neurology at the University and lead author.

"Post-traumatic epilepsy is a common and frequently disabling complication of traumatic brain injury, for which there is no effective prophylactic therapy," he said. "What this finding indicates is that if we learn to manipulate aspects of lipid or lipoprotein metabolism in the brain we may be able to develop therapies to prevent post-traumatic epilepsy."

Epilepsy develops in approximately 20 to 25 percent of patients with moderate to severe brain injury, such as that sustained in a car crash.

After the injury, there is rewiring and sprouting of the nerve cells," Dr. Diaz-Arrastia said. "That is often a good thing, because it allows recovery. It can also be bad if that rewiring results in a circuit that is, in a sense, misfiring."

Researchers obtained information on 106 patients with diagnoses of moderate or severe brain injury who were admitted to Parkland Memorial Hospital. The patients were evaluated six months after admittance to determine the outcome of their injuries. Scientists also obtained deoxyribonucleic acid (DNA) samples to determine which variation of the apoE gene was present in each patient.

Of the 106 patients, 29 had the epsilon 4 variation of apoE, and 77 did not. Of the apoE carriers, 34 percent had post-traumatic seizures, whereas only 14 percent of those without the gene had seizures.

ApoE first came to the attention of neurologists in 1993, when it was found to be associated with an increased risk for development of Alzheimer's disease. Since then, the gene, which is the major lipid-carrying protein in the central nervous system, has been linked to dementia in boxers following chronic concussive injury, faster progression to disability in multiple sclerosis patients, and a poor outcome after traumatic brain injury.

"We were interested in a complication of brain injury that had not been explored in previous studies--the development of post-traumatic epilepsy," Dr. Diaz-Arrastia said.