Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Circulating Metabolites as Biomarkers of Disease and Pharmacoresistance in Patients with Mesial Temporal Lobe Epilepsy

Version 1 : Received: 20 March 2022 / Approved: 23 March 2022 / Online: 23 March 2022 (09:11:52 CET)

A peer-reviewed article of this Preprint also exists.

Godoi, A.B.; do Canto, A.M.; Donatti, A.; Rosa, D.C.; Bruno, D.C.F.; Alvim, M.K.; Yasuda, C.L.; Martins, L.G.; Quintero, M.; Tasic, L.; Cendes, F.; Lopes-Cendes, I. Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy. Metabolites 2022, 12, 446. Godoi, A.B.; do Canto, A.M.; Donatti, A.; Rosa, D.C.; Bruno, D.C.F.; Alvim, M.K.; Yasuda, C.L.; Martins, L.G.; Quintero, M.; Tasic, L.; Cendes, F.; Lopes-Cendes, I. Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy. Metabolites 2022, 12, 446.

Journal reference: Metabolites 2022, 12, 446
DOI: 10.3390/metabo12050446

Abstract

A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments, such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of pharmacoresistance in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We compared the group of patients with controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, lipoproteins (p = 0.05), lactate (p = 0.05), glucose (p = 0.05), unsaturated lipids (p = 0.05), isoleucine (p = 0.05), and proline (p = 0.05), could discriminate between the two groups of patients classified according to response to ASM. The identified metabolites were linked to different biological pathways related to cell energy metabolism, and pathways linked to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In contrast, we found that pyruvate metabolism may be linked to resistance to ASM. In conclusion, in addition to insights into the mechanisms underlying MTLE and the response to treatment with ASM, our results suggest that plasma metabolites may be used as biomarkers of disease and response to ASM in patients with MTLE. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE.

Keywords

metabolomics; antiseizure medication; ¹H Nuclear Magnetic Resonance; focal epilepsy; response to treatment

Subject

MEDICINE & PHARMACOLOGY, Clinical Neurology

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