Reversible pseudoatrophy of the brain and mental deterioration associated with valproate treatment

Renzo Guerrini, Anna Belmonte, Raffaello Canapicchi, Claudia Casalini, Emilio Perucca

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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 (≤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 μg/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.

Original languageEnglish
Pages (from-to)27-32
Number of pages6
JournalEpilepsia
Volume39
Issue number1
DOIs
Publication statusPublished - 1998

Fingerprint

Valproic Acid
Brain
Therapeutics
Magnetic Resonance Imaging
Intelligence
Electroencephalography
Cognitive Dysfunction
Hyperammonemia
Wechsler Scales
Crows
Partial Epilepsy
Parkinsonian Disorders
Drug-Related Side Effects and Adverse Reactions
Neuroimaging
Pharmaceutical Preparations
Atrophy

Keywords

  • Brain pseudoatrophy
  • Mental deterioration
  • MRI
  • Valproate

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Reversible pseudoatrophy of the brain and mental deterioration associated with valproate treatment. / Guerrini, Renzo; Belmonte, Anna; Canapicchi, Raffaello; Casalini, Claudia; Perucca, Emilio.

In: Epilepsia, Vol. 39, No. 1, 1998, p. 27-32.

Research output: Contribution to journalArticle

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