Valproate-induced reversible cognitive decline presenting as dementia and associated clinical features: A literature review

Background/Aim: Valproate (VPA) is an effective broad-spectrum anti-seizure medication. Both VPA induced encephalopathy and reversible cognitive decline (VIRCD) have been reported as rare side effects. While the former is well-described in terms of risk factors, mechanism and management, the latter is less recognised and can be easily mistaken for neurodegenerative dementia. In this paper, we present a literature review of VIRCD, describe its clinical features and compare our findings to those in VPA-induced encephalopathy.Methods: We used PubMed search for valproate induced (dementia OR cognitive impairment OR cognitive decline OR cognitive dysfunction). Patients included were those with normal or well-defined cognitive baseline who presented with dementia after valproate therapy, in whom cognitive decline reversed after VPA dose reduction or discontinuation. Clinical features were compared to published descriptions of VPA-induced encephalopathy.Results: A total of 33 cases in 11 publications were included. Mean age was 51.2 years. Most were being treated for epilepsy on VPA with good seizure control and no encephalopathic features. VPA levels were within the usual quoted range. Mean latency after VPA initiation and symptoms was 6.87 years. Most had parkinsonian features. The most commonly reported cognitive deficits were in short-term memory and processing speed. All recovered fully on VPA discontinuation.Conclusion: VIRCD mimics neurodegenerative dementia but is reversible on VPA discontinuation. The absence of encephalopathic features and good seizure control in addition to the prolonged latency make it easy to miss. VIRCD should be considered in relevant patient groups, especially in the presence of extrapyramidal signs.