Out of the Darkness: Revolutionizing Epilepsy Treatment
Tracy Glauser, MD, Director, Comprehensive Epilepsy Center
Epilepsy Facts
- 200,000 new cases of epilepsy are diagnosed each year.
- 45,000 of these are children
under the age of 15.
- Incidence is highest under the age of 2 and over 65.
- Males are slightly more likely
to develop epilepsy than females.
- Incidence is greater in African- American and socially disadvantaged populations.
- In 70 percent of new cases,
no cause is apparent.
Source: Epilepsy Foundation
It took a long time for epilepsy treatment to get where it is today — nearly 4,000 years, in fact. The first account of seizures dates back to Babylonia, circa 2000 BC. Although seizures were described in terms much like those used today, they were believed to be a spiritual affliction — and an evil one, at that.
Hippocrates was the first to write that epilepsy was caused not by evil spirits, but by a disorder of the brain. It took until nearly the 19th century, however, for this enlightened view to take hold. Until then, people with epilepsy were feared, punished and treated as outcasts.
Today, science has proven that epilepsy is not only a physical disorder, but it is also highly treatable and even curable.
Leading much of this science are the doctors and researchers of the Comprehensive Epilepsy Centerat Cincinnati Children’s. Under the leadership of Tracy Glauser, MD, of the Division of Neurology, the program is focusing on pharmacologic and surgical advances that are changing the course of this mysterious disorder, and the lives of children who have it.
A First-Ever Study
Glauser has a particular interest in the pharmacogenetics and pharmacokinetics of epilepsy treatment. He recently led and completed the largest NIH-funded study of epilepsy ever done — a clinical trial focused on childhood absence epilepsy, the most common form of childhood epilepsy that affects 10 to 15 percent of all kids with epilepsy.
“In the 65 years in which randomized controlled trials have been conducted in adults and children with epilepsy, there have only been four trials that reach the highest level of scientific rigor (class 1 evidence) and only one of those is with children,” Glauser says. “So the scientific evidence we have been using to treat pediatric epilepsy is very poor (class 3 evidence or worse). There was a clear need for a clinical trial such as the one we conducted to provide better evidence to guide therapy.”
The $17 million National Institute for Neurologic Disorders and Stroke (NINDS) grant involved 32 centers and 453 patients between the ages of 2 and 13, including 50 enrolled from Cincinnati Children’s. The randomized, controlled, double-blind comparative trial looked at the efficacy and tolerability of the three most commonly used medications for childhood absence epilepsy: ethosuximide (Zarontin®), valproic acid (Depakote®), and lamotrigine (Lamictal®).
Although all three drugs are FDA-approved, only the first two had been approved for absence epilepsy. But Glauser says recent studies have shown that lamotrigine (Lamictal) can also be effective. So he developed a competitive trial among the three medications to help identify “what should be the proper standard
of care.”
Guidelines Where None Existed
Glauser points out that having a standard of care is particularly important because despite the advances in understanding epilepsy, there is little to guide the physicians who care for those who have it, particularly when the patients are children.
The goal of the NINDS study was to identify the optimal initial therapy for childhood absence epilepsy. Additionally, researchers wanted to understand the effects of the three medications on cognition — specifically attention, which can be a problem for children with seizures. Finally, they wanted to identify the genetic determinants of why some kids respond to drugs and others don’t.
Challenging the Norm
The study is the first to apply the discipline of clinical trial research to long-held assumptions made about medications and dosing when treating children with absence epilepsy.
Glauser couldn’t discuss what the study revealed at the time of this writing; the findings were presented at a national meeting in December and the study team has submitted the results for publication in a major medical journal.
He does say the information will provide answers to many of the questions pediatric neurologists are grappling with about how to treat childhood absence epilepsy.
“While we conducted this double-blind clinical trial, we conducted an international survey on current treatment, and got responses from more than 700 clinicians about how they treat childhood absence epilepsy,” he says. “Our results will change how they go about caring for these kids.”
Medications and Seizures
Can medications “fix” seizure disorders? Tracy Glauser, MD, says in many cases, yes.
He explains that the medicines don’t “cure” the epilepsy; they simply stop the seizures longenough to allow the brain to heal itself, much like putting a cast on a broken arm.
“The cast never touches the bone and yet it “fixes” the broken bone by immobilizing itlong enough to allow the body to heal itself,” says Glauser. Likewise, he says, if a child cango two years without seizures while on medication, there is a good likelihood that the brainwill have “outgrown” its tendency for seizures, the child can be weaned from medication andcan grow and develop without medication and free of seizures.
“For the vast majority of kids we treat, if we can get their seizures under control and theygo two years seizure-free, they have a great chance of outgrowing it,” he says.
About Childhood Absence Epilepsy
The most common form of childhood epilepsy, childhood absence epilepsy (CAE) is associatedwith frequent “absence” seizures where a child “blanks out” of consciousness briefly, staringblankly ahead, and is unaware or unresponsive for up to 20 seconds at a time. Such seizures canoccur as many as several hundred times daily while a child is in a classroom or trying to enjoylife playing baseball, taking ballet lessons or riding a bike.
