[Dementia and extrapyramidal problems caused by long-term valproic acid].
Among the side-effects attributed to valproic acid (VPA), the occurrence of Parkinsonian syndromes and cognitive impairment is very uncommonly reported. We describe five cases of reversible associated Parkinsonism. These cases were observed in epileptic patients, 57 to 74 years old, two women and three men. Extrapyramidal disorders appeared after various durations of treatment (from 6 months to 10 years). Dementia characterized by an insidious onset was associated in three cases and bradypsychia in one case. Brain pseudoatrophy was present in three patients. In all cases the signs and symptoms improved some weeks or months after discontinuation of VPA. In the literature some cases, usually in young adults or children, have been reported. In a prospective study, Armon et al. found various abnormal symptoms and signs related to motor and cognitive function impairment in patients with long-term VPA therapy. These side-effects may be related to a disturbance in the gabaergic pathways in the basal ganglia system. It is of interest to consider that delta 2-valproic acid, a metabolite of VPA, is especially accumulated in selected areas of the brain: the substantia nigra, superior and inferior colliculus, hippocampus and medulla.
Masmoudi
K
K
Service de Neurologie CHU Nord, 80054 Amiens, France.
Gras-Champel
V
V
Bonnet
I
I
Pannier
M
M
Masson
H
H
Rosa
A
A
Andréjak
M
M
D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001479:Basal Ganglia / Q000378:metabolism; D001480:Basal Ganglia Diseases / Q000139:chemically induced*; D003704:Dementia / Q000139:chemically induced*; D005260:Female; D018755:GABA Agonists / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D014635:Valproic Acid / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D018755:GABA Agonists; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid
Démence et troubles extra-pyramidaux sous acide valproïque au long cours.