Biochemical Correlations with Fatigue in Multiple Sclerosis Detected by MR 2D Localized Correlated Spectroscopy

J Neuroimaging. 2021 May;31(3):508-516. doi: 10.1111/jon.12836. Epub 2021 Feb 22.

Abstract

Background and purpose: Fatigue is the common symptom in patients with multiple sclerosis (MS), yet its pathophysiological mechanism is poorly understood. We investigated the metabolic changes in fatigue in a group of relapsing-remitting MS (RRMS) patients using MR two-dimensional localized correlated spectroscopy (2D L-COSY).

Methods: Sixteen RRMS and 16 healthy controls were included in the study. Fatigue impact was assessed with the Modified Fatigue Impact Scale (MFIS). MR 2D L-COSY data were collected from the posterior cingulate cortex. Nonparametric statistical analysis was used to calculate the changes in creatine scaled metabolic ratios and their correlations with fatigue scores.

Results: Compared to healthy controls, the RRMS group showed significantly higher fatigue and lower metabolic ratios for tyrosine, glutathione, homocarnosine (GSH+Hca), fucose-3, glutamine+glutamate (Glx), glycerophosphocholine (GPC), total choline, and N-acetylaspartate (NAA-2), while increased levels for isoleucine and glucose (P ≤ .05). Only GPC showed positive correlation with all fatigue domains (r = .537, P ≤ .05). On the other hand, Glx-upper, NAA-2, GSH+Hca, and fucose-3 showed negative correlations with all fatigue domains (r = -.345 to -.580, P ≤ .05). While tyrosine showed positive correlation with MFIS (r = .499, P ≤ .05), cognitive fatigue was negatively correlated with total GSH (r = -.530, P ≤ .05). No correlations were found between lesion load or brain volumes with fatigue score.

Conclusions: Our results suggest that fatigue in MS is strongly correlated with an imbalance in neurometabolites but not structural brain measurements.

Keywords: 2D L-COSY; MS fatigue; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Carnosine / analogs & derivatives
  • Carnosine / metabolism
  • Choline / metabolism
  • Creatine / metabolism
  • Fatigue / pathology*
  • Female
  • Glutathione / metabolism
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / pathology*
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging*
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Young Adult

Substances

  • Aspartic Acid
  • homocarnosine
  • Carnosine
  • N-acetylaspartate
  • Glutathione
  • Creatine
  • Choline