Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy
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 meta...
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| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/5/446 |
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| author | Alexandre B. Godoi Amanda M. do Canto Amanda Donatti Douglas C. Rosa Danielle C. F. Bruno Marina K. Alvim Clarissa L. Yasuda Lucas G. Martins Melissa Quintero Ljubica Tasic Fernando Cendes Iscia Lopes-Cendes |
| author_facet | Alexandre B. Godoi Amanda M. do Canto Amanda Donatti Douglas C. Rosa Danielle C. F. Bruno Marina K. Alvim Clarissa L. Yasuda Lucas G. Martins Melissa Quintero Ljubica Tasic Fernando Cendes Iscia Lopes-Cendes |
| author_sort | Alexandre B. Godoi |
| collection | DOAJ |
| description | 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 (<i>p</i> = 0.01), saturated lipids (<i>p</i> = 0.0002), isoleucine (<i>p</i> = 0.0001), β-hydroxybutyrate (<i>p</i> = 0.0003), and proline (<i>p</i> = 0.02) were different in patients compared to controls (<i>p</i> < 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. |
| first_indexed | 2024-03-10T03:25:48Z |
| format | Article |
| id | doaj.art-29ae5a156def4565875d676804ff9707 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T03:25:48Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-29ae5a156def4565875d676804ff97072023-11-23T12:07:35ZengMDPI AGMetabolites2218-19892022-05-0112544610.3390/metabo12050446Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe EpilepsyAlexandre B. Godoi0Amanda M. do Canto1Amanda Donatti2Douglas C. Rosa3Danielle C. F. Bruno4Marina K. Alvim5Clarissa L. Yasuda6Lucas G. Martins7Melissa Quintero8Ljubica Tasic9Fernando Cendes10Iscia Lopes-Cendes11Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, BrazilBrazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, BrazilBrazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, BrazilDepartment of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas 13083-888, BrazilDepartment of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas 13083-888, BrazilDepartment of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas 13083-888, BrazilBrazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, BrazilA 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 (<i>p</i> = 0.01), saturated lipids (<i>p</i> = 0.0002), isoleucine (<i>p</i> = 0.0001), β-hydroxybutyrate (<i>p</i> = 0.0003), and proline (<i>p</i> = 0.02) were different in patients compared to controls (<i>p</i> < 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.https://www.mdpi.com/2218-1989/12/5/446metabolomicsantiseizure medication<sup>1</sup>H Nuclear Magnetic Resonancefocal epilepsyresponse to treatment |
| spellingShingle | Alexandre B. Godoi Amanda M. do Canto Amanda Donatti Douglas C. Rosa Danielle C. F. Bruno Marina K. Alvim Clarissa L. Yasuda Lucas G. Martins Melissa Quintero Ljubica Tasic Fernando Cendes Iscia Lopes-Cendes Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy Metabolites metabolomics antiseizure medication <sup>1</sup>H Nuclear Magnetic Resonance focal epilepsy response to treatment |
| title | Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy |
| title_full | Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy |
| title_fullStr | Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy |
| title_full_unstemmed | Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy |
| title_short | Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy |
| title_sort | circulating metabolites as biomarkers of disease in patients with mesial temporal lobe epilepsy |
| topic | metabolomics antiseizure medication <sup>1</sup>H Nuclear Magnetic Resonance focal epilepsy response to treatment |
| url | https://www.mdpi.com/2218-1989/12/5/446 |
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