Reversible Pseudoatrophy of the Brain and Mental Deterioration Associated with Valproate Treatment

Abstract

Summary:Purpose: To describe an 11-year-old girl with symptomatic localization-related epilepsy and normal intelligence who developed reversible mental deterioration and pseudoatrophic brain changes while receiving valproate (VPA).Methods; Assessment of mental function using Wechsler Intelligence Scale for Children-I11 (WISC) and Raven's Progressive Matrices (PM), EEG recordings while awake and asleep, and brain magnetic resonance imaging (MRI), were performed at the beginning of VPA therapy, after 2 years and 8 months of treatment and following VPA discontinuation.Results: After 2 years and 6 months on VPA (G26 mg/kg/ day) the girl insidiously developed mental deterioration (loss of I8 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 VPA concentrations near 100 pglml. There were no other manifestations of drug toxicity or hyperammonemia. Background EEG activity was normal. Reduction of VPA dosage and subsequent discontinuation 4 months later resulted in disappearance of clinical symptoms with a 20-point improvement at IQ testing and recovery of previous PM score. Repeat MRI showed disappearance of pseudoatrophic changes.Conclusions: The striking cognitive improvement and reversal of pseudoatrophic brain changes following VPA discontinuation strongly suggest a drug-induced condition. Based on this and previous reports, the syndrome of VPA-associated mental deterioration and pseudoatrophy of the brain appears to encompass different but possibly related clinical entities, which include parkinsonism with cognitive deterioration, mental deterioration with signs of VPA-toxicity, and isolated mental deterioration, as seen in our patient. A drug-induced effect should be considered whenever cognitive deterioration and imaging findings of brain atrophy occur in VPA-treated patients. Key Words: Valproate-MRI-Brain pseudoatrophy-Mental deterioration.Valproate (VPA) is associated with fewer adverse neurological effects than other antiepileptic drugs ( 1). Severe neurological side effects such as VPA-induced encephalopathy with or without hyperammonemia (2,3), extrapyramidal disorders ( 4 3 , and reversible dementia (6-9) are rare. We report on an 1 I-year-old girl with nonsevere epilepsy, in whom mental deterioration with pseudoatrophy of the brain developed insidiously after 2 years on VPA. The condition was not associated with other signs of toxicity or hyperammonemia and was rapidly reversible upon VPA discontinuation. CASE REPORTThis I I-year-old girl was born with mild perinatal suffering (Apgar score 5-9) after a normal pregnancy. Developmental milestones were normal. At age 6 years Accepted June 6, 1997. Address correspondence and reprint requests to Dr. R. Guerrini at Institute of Child Neurology and Psychiatry, University of Pisa, Via dei Giacinti 2, 56018 Calambrone, Pisa, Italy.she experienced her first, sleep related, brief generalized clonic seizure. The electroen...

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