BRECKENRIDGE, COLO. — Seizures in many epileptic women exhibit a stereotypic menses-related pattern that may have important treatment implications, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.
How common is this catamenial exacerbation of seizures? In one recent study led by Andrew G. Herzog, M.D., of Harvard Medical School, Boston, 87 women with localization-related epilepsy charted their seizures in three menstrual cycles. Fully 39% showed one of three predefined catamenial patterns of seizure exacerbation during at least two of the three cycles.
The three patterns characteristic of catamenial epilepsy were perimenstrual or periovulatory exacerbations during normal cycles, and exacerbations during the second half of anovular cycles (Ann. Neurol. 2004;56:431-4).
The implication is that for the many women whose seizures follow a catamenial pattern, anticipatory short-term increases in antiepileptic drug dosing may help. Or patients can add an adjunctive anticonvulsant such as acetazolamide or a benzodiazepine for 3-4 days. Several days of clomiphene are another possibility, according to Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.
To date, there have been no large prospective treatment studies in women with catamenial epilepsy. Reported therapeutic successes are strictly anecdotal, and there is no universally accepted therapy, the neurologist added.
The biologic basis of catamenial epilepsy is grounded in two well-established observations: Estrogens are mildly proconvulsant, whereas progesterones have a slight anticonvulsant effect. Animal studies have shown that a drop in serum levels of the endogenous neurosteroid allopregnanolone, a progesterone metabolite, lower the seizure threshold. But attempts to quell catamenial epilepsy via progesterone therapy have generally been thwarted by the finding that effective doses also result in depressive symptoms and other side effects, Dr. Cavazos continued.
Another etiologic factor in catamenial epilepsy is menstrual cycle-related alteration in hepatic metabolism of antiepileptic drugs. The perimenstrual decrease in sex hormones is associated with increased hepatic enzyme activity, which can result in lower serum anticonvulsant levels, he said.