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

Neuroradiology. 2024 Mar;66(3):389-398. doi: 10.1007/s00234-023-03263-1. Epub 2023 Dec 19.

Abstract

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 (1H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare 1H-MRS of MELAS patients with controls, the 1H-MRS after glutamine supplementation in the MELAS group, and investigate the association between 1H-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 1H-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.

Keywords: Glutamate; Glutamine supplementation; MELAS syndrome; MRI spectroscopy; Mitochondrial disease.

Publication types

  • Observational Study

MeSH terms

  • Case-Control Studies
  • Cohort Studies
  • Creatine / metabolism
  • Dietary Supplements
  • Glutamic Acid / metabolism
  • Glutamine* / metabolism
  • Humans
  • Lactates
  • MELAS Syndrome* / diagnostic imaging
  • MELAS Syndrome* / drug therapy
  • MELAS Syndrome* / metabolism
  • Magnetic Resonance Spectroscopy / methods
  • Proton Magnetic Resonance Spectroscopy / methods

Substances

  • Glutamine
  • Creatine
  • Glutamic Acid
  • Lactates

Associated data

  • ClinicalTrials.gov/NCT04948138