Paradoxical response to valproic acid in a patient with a hypothalamic hamartoma

OBJECTIVE: To report a patient who developed the paradoxical effect of increasing electrical seizure activity and confusion with initiation of valproic acid therapy. CASE SUMMARY: A 25-year-old African-American woman with a hypothalamic hamartoma had an electroencephalogram (EEG) that demonstrated frequent bursts of generalized spike and wave activity. The prevalence of spike and wave activity increased dramatically and the patient became increasingly somnolent as valproic acid was added to carbamazepine and phenobarbital therapy. Her EEG and mental status changes resolved when the valproic acid was discontinued. There was a strong positive correlation between the prevalence of spike and wave activity and the valproic acid concentration, but not between spike and wave activity and the concentrations of carbamazepine or phenobarbital. DISCUSSION: Although this is a complex case, it is clear that the addition of valproic acid produced an increase in spike and wave activity. Possible mechanisms and pathophysiologic significance of this paradoxical effect are discussed in light of the differences between this epileptic syndrome and the primary generalized epilepsies.