Metabolic alterations associated with epileptic seizures detected by NMR spectroscopy

Epilepsy affects over 50 million individuals worldwide. Despite the availability of anti-seizure medications, approximately 30% of patients remain drug-resistant, emphasizing the pressing need for alternative therapeutic strategies. In recent years, NMR-based metabolomics has emerged as a robust platform to investigate metabolic disturbances in neurological disorders, potentially improving diagnostic precision and explore individualized treatment options.In this study, we analysed serum metabolomics profiles from 32 patients with epilepsy, evaluated both at baseline and shortly after seizure episodes, and 28 healthy controls. Using an untargeted NMR-based metabolomics approach combined with multivariate and statistical analyses, we identified significant metabolic alterations and assessed their diagnostic potential. A total of 14 metabolites differed significantly between patients and controls. Among these, citrate, glutamate, proline, 3-methyl-2-oxovalerate, and glucose showed strong potential as biomarkers. Post-seizure samples revealed alterations in seven metabolites, including hippurate, pyroglutamate, isovalerate, creatinine, threonine, 3-methyl-2-oxovalerate, and 2-oxoisocaproate. Notably, we observed distinct metabolic signatures distinguishing focal from generalized seizures.To our knowledge, this is the first comprehensive serum metabolomics study using NMR to evaluate both basal and post-seizure states in epilepsy. Our findings highlight key alterations in energy metabolism, oxidative stress, and amino acid pathways, offering promising leads for improving clinical assessment and tailoring therapeutic strategies in epilepsy care.