A study has identified distinct metabolic profiles in the blood serum of people with epilepsy, both at rest and within an hour of seizure events, using untargeted nuclear magnetic resonance (NMR) spectroscopy. The findings, published in Scientific Reports, offer potential biomarkers for seizure detection and seizure type classification, while shedding light on disrupted biochemical pathways in the disorder.
Researchers at the Italian Hospital of Buenos Aires collected serum samples from 32 patients with epilepsy and 28 healthy controls, analyzing them using ¹H-NMR at 600 MHz. Samples from patients were taken both during interictal periods (at least 24 hours without seizures) and within 60 minutes of seizure onset. After spectral processing and quantification of 44 metabolites, multivariate statistical analysis – including PCA, PLS-DA, and ROC curve evaluation – revealed a series of metabolite alterations with diagnostic potential.
Fourteen metabolites significantly differed between epilepsy patients and healthy controls. Among them, glutamate, proline, glucose, 3-methyl-2-oxovalerate, and tyrosine were elevated, while citric acid, 3-hydroxybutyrate, acetylcarnitine, and glycerol were reduced. These changes pointed to disruptions in energy metabolism, amino acid degradation, and redox balance – notably implicating the TCA cycle, branched-chain amino acid catabolism, and glutathione metabolism. A panel of five metabolites (citrate, glutamate, glucose, proline, 3-methyl-2-oxovalerate) achieved a combined AUC of 0.93, suggesting strong discriminatory power for epilepsy diagnosis.
Analysis of the post-seizure state revealed further shifts in seven metabolites. Levels of pyroglutamate, creatinine, hippurate, isovalerate, and threonine were significantly reduced, while 2-oxoisocaproate was elevated. These changes are consistent with acute energy demand, oxidative stress, and increased amino acid catabolism triggered by seizure activity.
Importantly, the study also identified metabolic distinctions between seizure types. Patients experiencing focal to bilateral tonic-clonic seizures had significantly higher levels of lactic acid and hypoxanthine than those with focal seizures alone, reflecting increased anaerobic metabolism and purine degradation.
This is the first study to use untargeted NMR-based metabolomics to compare basal and immediate postictal states in epilepsy. While limited by cohort size and uncontrolled dietary factors in post-seizure sampling, the approach highlights the potential of high-resolution NMR for identifying biomarkers relevant to diagnosis, seizure monitoring, and treatment personalization.
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