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

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Godoi, Alexandre B. ; do Canto, Amanda M. ; Donatti, Amanda ; Rosa, Douglas C. ; Bruno, Danielle C. F. ; Alvim, Marina K. ; Yasuda, Clarissa L. ; Martins, Lucas G. ; Quintero, Melissa ; Tasic, Ljubica ; Cendes, Fernando ; Lopes-Cendes, Iscia

• Document type: Journal article
• Source: METABOLITES; v. 12, n. 5, p. 16-pg., 2022-05-01.

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 disease 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 for a supplementary and preliminary comparison: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We analyzed the group of patients and controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), beta-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, we found some suggestive metabolites (without enough predictability) by multivariate analysis (VIP scores > 2), such as lipoproteins, lactate, glucose, unsaturated lipids, isoleucine, and proline, that might be relevant to the process of pharmacoresistance in the comparison between patients with refractory and responsive MTLE. The identified metabolites for the comparison between MTLE patients and controls were linked to different biological pathways related to cell-energy metabolism and pathways related to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In conclusion, in addition to insights into the mechanisms underlying MTLE, our results suggest that plasma metabolites may be used as disease biomarkers. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE. (AU)

• FAPESP's process: 21/04451-3 - Technical training in metabolomic analysis: searching for biomarkers in neurological diseases
• Grantee: Melissa Quintero Escobar
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/00213-0 - Metabolomic analysis from plasma of patients with mesial temporal lobe epilepsy: searching for drug resistant biomarkers
• Grantee: Alexandre Barcia de Godoi
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/24069-3 - ReSEARCH: Recognizing Signatures of the Exposome to Anticipate the Risks for a Continuous Health
• Grantee: Fernando Barbosa Júnior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/04441-8 - Analysis of molecular biomarkers in patients with stroke.
• Grantee: Amanda Donatti
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 19/00048-0 - Metabolic profile of patients with ischemic strokes: research for biomarkers
• Grantee: Douglas Cescon da Rosa
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/25948-3 - Analysis of synaptosomes isolated from hippocampus tissue of patients with Mesial Temporal Lobe Epilepsy using proteomics and metabolomics
• Grantee: Amanda Morato Do Canto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/26167-0 - Detection of methylated circulating DNA as a non-invasive biomarker for the identification of patients with mesial temporal lobe epilepsy and ischemic stroke
• Grantee: Danielle do Carmo Ferreira Bruno
• Support Opportunities: Scholarships in Brazil - Post-Doctoral