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[Dementia and extrapyramidal problems caused by long-term valproic acid].

K Masmoudi1, V Gras-Champel, I Bonnet

  • 1Service de Neurologie CHU Nord, 80054 Amiens, France.

Therapie
|February 24, 2001
PubMed
Summary

Valproic acid (VPA) can rarely cause reversible Parkinsonism and cognitive issues in adults. Discontinuing VPA treatment led to symptom improvement in all reported cases.

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Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Valproic acid (VPA) is an anticonvulsant medication.
  • Parkinsonian syndromes and cognitive impairment are rare side effects of VPA.

Observation:

  • Five adult epileptic patients (57-74 years) developed reversible Parkinsonism after 6 months to 10 years of VPA treatment.
  • Three patients experienced dementia, and one had bradypsychia.
  • Brain pseudoatrophy was noted in three patients.

Findings:

  • All patients' symptoms improved within weeks or months after VPA discontinuation.
  • Literature review indicates similar, though typically younger, patient cases.
  • Abnormal motor and cognitive signs were observed in a prospective study of long-term VPA therapy.

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Implications:

  • VPA-induced Parkinsonism and cognitive impairment may stem from GABAergic pathway disturbances in the basal ganglia.
  • A VPA metabolite, delta 2-valproic acid, accumulates in brain regions like the substantia nigra and hippocampus, potentially contributing to these side effects.