Tony Coelho is having déjà vu. The former congressman and author of the Americans with Disabilities Act recalls a commencement address he gave a quarter-century ago, in the wake of the Vietnam war, in which he warned of the potential for seizure disorders in returning troops who had suffered head injuries and called for more research on the link between traumatic brain injury (TBI) and epilepsy. Today, as he watches the storm build amid reports of alarmingly high TBI rates among soldiers returning from Iraq – and the military’s apparent inability to care for them properly – Coelho is struck by the parallels. “Here I am, 25 years later, talking about the same thing,” says Coelho, who has epilepsy as a result of a head injury and is the immediate past chair of the Epilepsy Foundation. “What have we learned?

Growing Chorus of Concern

Coelho is not alone in his concern for the long-term effects of the head injuries that have become the signature injury of the Iraq conflict. A chorus of concern is rising among veterans’ advocates and medical experts across the USA who understand the heightened risk America’s returning war heroes have for a range of posttraumatic europsychological problems. Epilepsy is prominent among them.

The risk is very real, even if the precise numbers are impossible to predict. Trauma to the brain, whether mild or severe, is a clearly defined risk factor for epilepsy. Studies suggest that about 20 to 25 percent of individuals with “closed-head” brain injuries will go on to develop what is termed post-traumatic epilepsy (PTE). PTE accounts for 5 percent of epilepsy overall. The only study that has investigated the prevalence of PTE in the military, reported in 1985, found that as many as 50 percent of Vietnam veterans who had suffered penetrating brain injuries during combat developed seizure disorders months or years later.

Penetrating injuries – when a foreign object or piece of fractured skull enters the brain – are the most severe form of TBI. They are relatively uncommon in civilians and are distinct from the types of head injuries most commonly seen in U.S. troops serving in Iraq. There, most head trauma seems to be a result of the “shock wave” of high pressure that reverberates out from the point of an explosion. Improvised Explosive Devices, or IED’s, have notoriously become the weapon of choice against U.S. troops; the Department of Veterans Affairs (VA) estimates that IED’s account for two-thirds of combat injuries. These “blast injuries” can – and apparently often do – cause brain trauma, even in the absence of obvious wounds.

There is little hard data on the incidence of blast-related head injuries among U.S. soldiers in Iraq, at least that is available to the public. 2003 data from the Walter Reed Army Medical Center found evidence of brain injury in 61 percent of returning soldiers who had been exposed to blasts, according to the Defense and Veterans Brain Injury Center, a partnership between the VA and the Department of Defense (DoD).

No one knows how many of those troops with brain injuries will eventually develop epilepsy.

But with an estimated 1.4 million troops who have served or are currently serving in Iraq, even the most conservative statistics portend a looming crisis of post-TBI neurologic problems that will haunt these soldier heroes, and society at large, for generations to come.

Preventing PTE: New Priority?

The specter of a coming wave of combat-related TBI has refocused attention on the critical need to better predict whom among the head-injured are likely to develop epilepsy, and how to prevent it. It also underscores how little we yet know about preventing epilepsy.

“For many years – even decades – epilepsy research has been focused primarily on the seizures themselves: what they are, how they are generated in the brain, how they spread and what drugs might control them,” says Marc Dichter, M.D., Ph.D., professor of neurology and pharmacology at the University of Pennsylvania. “Basically, we’ve been waiting for epilepsy to happen and then seeing if we can tag heuer replica treat it.”

This approach is in stark contrast, Dichter says, to how we as a society deal with other public health problems, such as cancer or heart disease, where we identify risk factors and try to prevent disease from occurring.

“Why aren’t we paying attention to the development of epilepsy, as we do for every other medical disease?” he asks.

Dichter is leading a DoD-funded pilot study in civilians to determine if the anti-seizure drug topiramate (Topamax®)might decrease the risk of post-traumatic epilepsy if given within 12 hours or so of a head injury. Recruitment for the trial is just beginning.

Health and led by Pavel Klein, M.D., a neurologist with Washington Hospital Center in Washington D.C., is further along. The study is designed to evaluate the safety and tolerability of levetiracetam (Keppra®) in people who have suffered a head injury. (Keppra is approved as add-on therapy for partial seizures in adults.) Klein says about 50 adults and children with TBI had been enrolled as of late April, with an eventual goal of 90. If Keppra is found to be safe for use in this population – and so far Klein says it appears to be – the goal is to initiate a much larger study to investigate the drug’s efficacy in preventing PTE.

At least three well-designed clinical studies have previously investigated other anti-seizure medications for preventing injury-induced epilepsy. All have failed to show a benefit. The trials are exceedingly difficult to do, say Dichter and Klein, because they are labor intensive, costly, and take a long time to recruit enough subjects to have meaningful statistical power. Yet it’s critical that they be done. “If you don’t study the question, you’ll never get an answer,” says Dichter.

“Epilepsy is a chronic condition, and a proportion of people will develop refractory epilepsy, which requires life-long, extensive medical treatment and management,” says Klein. “It’s a complicated recovery, in many ways. Prevention is better than treatment.”

'Strike While the Iron is Hot'

Coelho is particularly concerned that troops who develop seizures long after their active duty is finished may be denied disability benefits. “It has been a huge fight to get the VA and DoD to understand that epilepsy can be a delayed effect of war trauma,” he says.

Still, he points out, the current situation, dire though it is, presents an opportunity to act.

“Congress right now is very conscious of the need to take care of our military men and women,” Coelho says. “It is critically important that we take advantage of the heightened sensitivity to this situation to uncover the facts, identify the problems and go to Congress to get the appropriate funding to get the job done right. We need to strike while the iron is hot.”

Brenda Patoine is a freelance science writer who has been covering neuroscience for more than 15 years. She can be reached at bpatoine@aol.com.

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