Magnetic resonance spectroscopy in MELAS syndrome: correlation with CSF and plasma metabolite levels and change after glutamine supplementation.

Autor: Guerrero-Molina MP; Neurology Department, Neuromuscular Disorders Unit, University Hospital, 12 de Octubre Avda. de Córdoba, S/N 28041, Madrid, Spain. maripazguerrero@gmail.com., Bernabeu-Sanz Á; Magnetic Resonance Department, Inscanner SL, Alicant, Spain., Ramos-González A; Department of Neuroradiology, University Hospital, 12 de Octubre, Madrid, Spain., Morales-Conejo M; Department of Internal Medicine, University Hospital, 12 de Octubre, Madrid, Spain.; National Reference Center for Congenital Errors of Metabolism (CSUR) an European Reference Center for Inherited Metabolic Disease (MetabERN), University Hospital, 12 de Octubre, Madrid, Spain.; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Madrid, Spain., Delmiro A; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Madrid, Spain.; Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigación Sanitaria Hospital, 12 de Octubre' ('imas12'), Madrid, Spain.; Research Institute ('imas12'), University Hospital, 12 de Octubre, Madrid, Spain., Domínguez-González C; Neurology Department, Neuromuscular Disorders Unit, University Hospital, 12 de Octubre Avda. de Córdoba, S/N 28041, Madrid, Spain.; National Reference Center for Congenital Errors of Metabolism (CSUR) an European Reference Center for Inherited Metabolic Disease (MetabERN), University Hospital, 12 de Octubre, Madrid, Spain.; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Madrid, Spain.; Research Institute ('imas12'), University Hospital, 12 de Octubre, Madrid, Spain., Arenas J; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Madrid, Spain.; Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigación Sanitaria Hospital, 12 de Octubre' ('imas12'), Madrid, Spain.; Research Institute ('imas12'), University Hospital, 12 de Octubre, Madrid, Spain., Martín MA; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Madrid, Spain.; Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigación Sanitaria Hospital, 12 de Octubre' ('imas12'), Madrid, Spain.; Research Institute ('imas12'), University Hospital, 12 de Octubre, Madrid, Spain., González de la Aleja J; National Reference Center for Congenital Errors of Metabolism (CSUR) an European Reference Center for Inherited Metabolic Disease (MetabERN), University Hospital, 12 de Octubre, Madrid, Spain.; Neurology Department, Epilepsy Unit, University Hospital, 12 de Octubre, Madrid, Spain.
Jazyk: angličtina
Zdroj: Neuroradiology [Neuroradiology] 2024 Mar; Vol. 66 (3), pp. 389-398. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1007/s00234-023-03263-1
Abstrakt: Purpose: MELAS syndrome is a genetic disorder caused by mitochondrial DNA mutations. We previously described that MELAS patients had increased CSF glutamate and decreased CSF glutamine levels and that oral glutamine supplementation restores these values. Proton magnetic resonance spectroscopy ( 1 H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare 1 H-MRS of MELAS patients with controls, the 1 H-MRS after glutamine supplementation in the MELAS group, and investigate the association between 1 H-MRS and CSF lactate, glutamate, and glutamine levels.
Methods: We conducted an observational case-control study and an open-label, single-cohort study with single-voxel MRS (TE 144/35 ms). We assessed the brain metabolism changes in the prefrontal (PFC) and parieto-occipital) cortex (POC) after oral glutamine supplementation in MELAS patients. MR spectra were analyzed with jMRUI software.
Results: Nine patients with MELAS syndrome (35.8 ± 3.2 years) and nine sex- and age-matched controls were recruited. Lactate/creatine levels were increased in MELAS patients in both PFC and POC (0.40 ± 0.05 vs. 0, p < 0.001; 0.32 ± 0.03 vs. 0, p < 0.001, respectively). No differences were observed between groups in glutamate and glutamine (Glx/creatine), either in PFC (p = 0.930) or POC (p = 0.310). No differences were observed after glutamine supplementation. A positive correlation was found between CSF lactate and lactate/creatine only in POC (0.85, p = 0.003).
Conclusion: No significant metabolite changes were observed in the brains of MELAS patients after glutamine supplementation. While we found a positive correlation between lactate levels in CSF and 1 H-MRS in MELAS patients, we could not monitor treatment response over short periods with this tool.
Trial Registration: ClinicalTrials.gov Identifier: NCT04948138; initial release 24/06/2021; first patient enrolled on 1/07/2021. https://clinicaltrials.gov/ct2/show/NCT04948138.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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