TY - JOUR
T1 - Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy
AU - Godoi, Alexandre B.
AU - Canto, Amanda M. do
AU - Donatti, Amanda
AU - Rosa, Douglas C.
AU - Bruno, Danielle C. F.
AU - Alvim, Marina K.
AU - Yasuda, Clarissa L.
AU - Martins, Lucas G.
AU - Quintero, Melissa
AU - Tasic, Ljubica
AU - Cendes, Fernando
AU - Lopes-Cendes, Iscia
N1 - Funding Information:
Funding: This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil (Grant numbers: 2013/07559-3, and 2018/24069-3), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil (Grant number 001). A.B.G. and D.C.R. received scholarships from FAPESP, Grant numbers: 2019/00213-0, and 2019/00048-0. A.M.C., A.D., D.C.F.B., and M.D. received fellowships from FAPESP, Grant numbers, 2019/25948-3, 2021/04441-8, 2017/26167-0, and 2021/04451-3. I.L.-C. is supported by a grant from Conselho Nacional de Pesquisa (CNPq), Brazil (Grant number: 311923/2019-4).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5/17
Y1 - 2022/5/17
N2 - 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), β-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.
AB - 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), β-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.
KW - metabolomics
KW - antiseizure medication
KW - 1H Nuclear Magnetic Resonance
KW - focal epilepsy
KW - response to treatment
KW - H Nuclear Magnetic Resonance
UR - https://doi.org/10.3390/metabo12050446
UR - https://www.mendeley.com/catalogue/2af021d5-8e35-36de-a80a-526df67c7046/
UR - http://www.scopus.com/inward/record.url?scp=85130707425&partnerID=8YFLogxK
U2 - 10.3390/metabo12050446
DO - 10.3390/metabo12050446
M3 - Artículo (Contribución a Revista)
VL - 12
SP - 446
JO - Metabolites
JF - Metabolites
IS - 5
M1 - 446
ER -
