Ammonia levels in patients with generalised epilepsy that are on sodium valproate monotherapy

Abstract

Background: Epilepsy is a prevalent neurological disease frequently managed in outpatient clinics at tertiary hospitals. Sodium valproate is widely utilized within the public healthcare sector in South Africa for epilepsy management due to its affordability and accessibility, despite its limitations, particularly in patients of childbearing age. Extensive research published in international literature has demonstrated that sodium valproate can induce hyperammonemia, which may contribute to cognitive dysfunction and a higher frequency of seizures. This study aimed to evaluate the proportion of patients on sodium valproate monotherapy who display elevated serum ammonia levels. Methods: Patients were interviewed at neurology clinics at Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital during their follow-up visits between December 2021 and December 2022. They were not recruited based on new symptoms. Blood samples were collected to measure ammonia levels, sodium valproate levels, and liver function tests. A data collection sheet was completed, detailing the dose of sodium valproate, duration of treatment, chronic medication used, changes in seizure frequency, changes in cognition, and neurological examination since the initiation of the drug. Descriptive statistics were performed for all variables, and the cohort was further categorized into primary and secondary epilepsy. Results: This cross-sectional study evaluated 64 adult epileptic patients on sodium valproate (VPA) monotherapy. After excluding twenty-seven patients, the final cohort consisted of 37 patients. Elevated ammonia levels were observed in 30% of the entire cohort (n=37), with a higher prevalence of 40% among those with primary generalized epilepsy (n=20). The reference range for normal serum ammonia levels in this study was 11-35 μmol/L, with elevated levels defined as those exceeding 35 μmol/L. Among the patients with raised ammonia levels (n=11), one exhibited altered cognition and the other had a higher frequency of seizures. The majority was asymptomatic. Conclusion: From this research study, it can be concluded that 30%-40% of the outpatients on VPA monotherapy had raised ammonia levels and most of them were asymptomatic.