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Summary: Purpose:We report the frequency of parkinsonism and cognitive decline (P/CD) in patients treated with valproate (VPA) after 1 year of treatment and at least 1 year of follow-up.Methods: Three hundred sixty-four patients with various epileptic syndromes and seizure types were treated with VPA mono-or polytherapy for more than 1 year.Results: We found five cases of P/CD (1.37%; 95% CI, 0.18-2.56%). Among 140 patients with different adverse effects (AEs) of VPA, P/CD were among the rarest in frequency but significant in terms of drug discontinuation (five of 17).Conclusions: Early identification of this type of AE and discontinuation of the drug led to complete recovery in affected patients. Key Words: Parkinsonism-Cognitive declineValproate-Epilepsy.Valproate (VPA) is considered to have a good safety profile. Sporadic reports and a few case series or clinical studies of reversible syndrome of parkinsonism and cognitive decline (P/CD) have been made in patients treated with VPA (Zaret and Cohen, 1986;Armon et al., 1996;Easterford et al., 2004;Masmoudi et al, 2006). The prevalence of this type of treatment complication has been estimated at 6% in a smaller group of consecutively recruited patients (Easterford et al., 2004). We report the frequency of P/CD in patients treated with VPA after 1 year of treatment and with ≥1 year of follow-up. MATERIALS AND METHODS PatientsIn total, 364 patients (55.2% women) aged between 17 and 73 years were treated with VPA mono-(37.6%) or polytherapy (VPA as comedication with enzyme-inducing anticonvulsants, 26.3%; VPA with lamotrigine, 22.5%; and VPA with other anticonvulsants, 13.4%) for >1 year were prospectively included in this study (Table 1). Of these, 110 patients had generalized and 254 had partial epileptic syndromes. Patients were recruited from the Epilepsy

The majority of patients with epilepsy maintain seizure control during pregnancy. The apparently higher risk of seizures among women treated with oxcarbazepine and the more frequent increases in drug load in the oxcarbazepine and lamotrigine cohorts prompts further studies on relationships with pharmacokinetic changes. Risks associated with status epilepticus appear to be lower than previously reported.

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