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-III (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 (< or = 26 mg/kg/day) the girl insidiously developed mental deterioration (loss 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 VPA concentrations near 100 microg/ml. 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.
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-III (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 (< or = 26 mg/kg/day) the girl insidiously developed mental deterioration (loss 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 VPA concentrations near 100 microg/ml. 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.
Authors: D G Corrêa; N Ventura; N Zimmermann; T M Doring; G Tukamoto; J Leme; M Pereira; I D'Andrea; C Rêgo; S V Alves-Leon; E L Gasparetto Journal: Neuroradiology Date: 2017-01-12 Impact factor: 2.804
Authors: Pierre N Tariot; Lon S Schneider; Jeffrey Cummings; Ronald G Thomas; Rema Raman; Laura J Jakimovich; Rebekah Loy; Barbara Bartocci; Adam Fleisher; M Saleem Ismail; Anton Porsteinsson; Michael Weiner; Clifford R Jack; Leon Thal; Paul S Aisen Journal: Arch Gen Psychiatry Date: 2011-08
Authors: A S Fleisher; D Truran; J T Mai; J B S Langbaum; P S Aisen; J L Cummings; C R Jack; M W Weiner; R G Thomas; L S Schneider; P N Tariot Journal: Neurology Date: 2011-09-14 Impact factor: 9.910
Authors: Duygu Tosun; Kevin Dabbs; Rochelle Caplan; Prabha Siddarth; Arthur Toga; Michael Seidenberg; Bruce Hermann Journal: Brain Date: 2011-03-11 Impact factor: 13.501