REVERSIBLE PSEUDOATROPHY OF THE BRAIN AND MENTAL DETERIORATION ASSOCIATED WITH VALPROATE TREATMENT

Purpose: To describe an 11-year-old girl with symptomatic localization -related epilepsy and normal intelligence who developed reversible men tal deterioration and pseudoatrophic brain changes while receiving val proate (VPA). Methods: Assessment of mental function using Wechsler In telligence Scale for Children-III (WISC) and Raven's Progressive Matri ces (PM), EEG recordings while awake and asleep, and brain magnetic re sonance imaging (MRI), were performed at the beginning of VPA therapy, after 2 years and 8 months of treatment and following VPA discontinua tion. Results: After 2 years and 6 months on VPA (less than or equal t o 26 mg/kg/day) the girl insidiously developed mental deterioration (l oss of 18 IQ points and drop in age-adjusted PM score from the 95th to the 50th percentile) associated with MRI-documented pseudoatrophy of the brain. Onset of severe cognitive impairment coincided with serum V PA concentrations near 100 mu g/ml. There were no other manifestations of drug toxicity or hyperammonemia. Background EEG activity was norma l. Reduction of VPA dosage and subsequent discontinuation 4 months lat er resulted in disappearance of clinical symptoms with a 20-point impr ovement at IQ testing and recovery of previous PM score, Repeat MRI sh owed disappearance of pseudoatrophic changes. Conclusions: The strikin g cognitive improvement and reversal of pseudoatrophic brain changes f ollowing VPA discontinuation strongly suggest a drug-induced condition . Based on this and previous reports, the syndrome of VPA-associated m ental deterioration and pseudoatrophy of the brain appears to encompas s different but possibly related clinical entities, which include park insonism with cognitive deterioration, mental deterioration with signs of VPA-toxicity, and isolated mental deterioration, as seen in our pa tient. A drug-induced effect should be considered whenever cognitive d eterioration and imaging findings of brain atrophy occur in VPA-treate d patients.