Valproic acid-induced parkinsonism: levodopa responsiveness with dyskinesia

Background: Valproic acid is a drug used for the treatment of a variety of psychiatric and neurological disorders. While it is well known to cause postural tremor, hyperammonemia, slowness, and sedation, it has also been described to occasionally cause a reversible form of parkinsonism.

Materials and methods: A series of five cases is reported.

Results: All patients were taking the drug for at least several months before onset of their parkinsonian symptoms. Parkinsonism was defined by the presence of bradykinesia, rigidity, postural instability, and resting tremor, but not postural or action tremor. After discontinuing their valproic acid, improvement was seen by all patients. The course of improvement took days to months after discontinuance. Two of these patients responded to dopaminergic therapy, with drug-induced dyskinesia observed in one. In another patient, valproic acid was thought to unmask underlying Parkinson's Disease; this patient benefited from levodopa as well.

Conclusion: Valproic acid-induced parkinsonism can look identical to idiopathic parkinsonism. In all five cases, the relationship between the valproic acid use and parkinsonism was initially unclear because of the delayed and insidious onset. Our finding of levodopa responsiveness and dyskinesia added to the diagnostic confusion. This treatment responsiveness also set it apart from neuroleptic-induced parkinsonism. In all cases improvement of symptoms occurred after discontinuation of the offending medication.