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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
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.
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.
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.