Many people with epilepsy find that their seizures come on all of a sudden, arriving and subsiding without warning. For others, prediction is as simple as looking at a calendar—some women with epilepsy discover that seizures rise and fall in step with their menstrual cycles.
"About 30 percent of women of childbearing age with epilepsy report this pattern," says neurologist Edward Faught, M.D., director of the UAB Epilepsy Center. "It's an increase that is independent of their usual seizure activity."
Seizures that occur during the menstrual cycle, known as catamenial seizures, are linked to fluctuating hormone levels—especially the hormone estrogen, Faught says. Higher estrogen levels tend to increase seizures, while higher levels of another hormone, progesterone, tend to lower the incidence. As a result, women often have these seizures either right before their periods or at ovulation.
"When the ratio between estrogen and progesterone is highest, that is when there is the highest chance of a seizure," Faught says.
UAB has been a leader in developing anti-epileptic drugs for decades, participating in trials for 12 of the 15 new medications introduced since 1993. So it was natural that the university's epilepsy center would play a significant role in testing a potential new treatment for catamenial seizures.
The current standard treatment involves adjusting a patient's existing epilepsy medication in order to provide a measure of safety during the menstrual cycle. "A mild diuretic can help, and dosage increases during the month are sometimes tried," Faught says. "Some women have received extra progesterone to counteract the estrogen, but that approach has side effects that aren't satisfactory."
The new drug under study, ganaxolone, works in much the same way as progesterone. But because it isn't a hormone, "it doesn't cause the body swelling, headaches, and other premenstrual symptoms that progesterone can," Faught says. Ganaxolone is part of a new class of anticonvulsants that modulate so-called GABAA receptors in the brain. Side effects are mild and include dizziness and sleepiness, reactions that are common to other antiseizure medications and that wear off as the body adjusts to the drug.
Patterns in the Storm
Surprisingly, UAB's ganaxolone trials are not restricted to women. "We are most interested in women with epilepsy who have a pattern of catamenial seizures, but we can work with other women or even men with epilepsy for this medication," Faught says. While men with epilepsy do not have catamenial seizures, he explains, the drug may be effective against other forms of seizures. Current medications leave up to 30 percent of patients without full control of their seizures.
"Our center has one of the largest clinical trial programs in the United States," says Faught. "If these trials are successful, there will be larger trials, and ganaxolone could be available within two to three years."