Valproic acid treatment of learning disorder and severely epileptiform EEG without clinical seizures

Using a single-patient (n = 1) clinical trial, we studied a 7-year-old boy who presented with unsatisfactory progress in school and whose electroencephalogram had very active independent frontal spike discharges. He had not had clinical seizures. The patient was randomized to receive valproic acid, 125 mg twice daily, (four periods) or matching placebo (four periods) over 8 weeks. Primary endpoints were the Wechsler Intelligence Scale for Children-Revised Coding sub-test and a handwriting sample. Behavior was monitored using teacher's and parent's Conners questionnaires. His score on the Wechsler Intelligence Scale for Children-Revised Coding subtest was significantly improved while he was taking valproic acid (P = .03). His electroencephalogram improved from a pretreatment recording of 28 spike discharges per minute to a normal recording while on valproic acid. We conclude that in this patient, valproic acid had a cognitive enhancing effect, probably by reducing epileptiform discharges.