Positivity of oligoclonal bands in the cerebrospinal fluid predisposed to metabolic changes and rearrangement of inhibitory/excitatory neurotransmitters in subcortical brain structures in multiple sclerosis

Abstract

Background: The latest diagnostic criteria for multiple sclerosis (MS) have revitalized the role of oligoclonal bands synthesis in the cerebrospinal fluid (CSF-OCB). This study identifies predictors of CSF-OCB-positivity among in vivo metabolic markers in the subcortical gray/white matter in MS patients after their first episode (CIS) and in patients with relapsing-remitting course (RRMS). Methods: The study enrolled 13 CIS and 23 RRMS patients. Metabolism was evaluated using Mescher-Garwoodedited proton-magnetic resonance spectroscopy on a 3T MR scanner. In addition to N-acetyl-aspartate (tNAA), myoinositol (mIns), and choline-and creatine compounds (tCho, tCr) were also evaluated γ-aminobutyric acid (GABA) and glutamate-glutamine (Glx) ratios. Results: CSF-OCB-positivity was found in 76.9% of CIS and 78.2% of RRMS patients. GABA and Glx ratios in putamen and corpus callosum strongly determined CSF-OCB-positive CIS patients. Other essential predictors of CSF-OCB-positive CIS were mIns and Glx ratios in the putamen, and tCho/tNAA in the corpus callosum. In RRMS, GABA ratios in the right thalamus and Glx ratios in the left hippocampus strongly predicted CSF-OCB-positive patients. tCho/tNAA and tNAA/tCr in the left hippocampus were also identified as essential predictors of CSF-OCB-positive RRMS patients. Conclusion: This is the first in vivo evidence of GABA-Glx rearrangement in CSF-OCB-positive patients since its early stages of MS.

Untargeted Pixel-by-Pixel Imaging of Metabolite Ratio Pairs as a Novel Tool for Biomedical Discovery in Mass Spectrometry Imaging

“…Glutamine is synthesized from glutamate and ammonia by the catalytic action of glutamine synthetase (GS) in glial cells of the brain, while it is also taken into neurons and generates glutamate and ammonia by the catalytic action of glutaminase. The glutamate-glutamine cycle is closely linked to cellular energy metabolism 56 , and ratios between neurotransmitters (GABA, glutamine and glutamate) have been used in MRS studies to probe neurological disease mechanisms and progression 59,60 . Specifically, ratios among glutamine, glutamate and aspartate have been implicated in memory function 61 , schizophrenia, depression, alcoholism and motivated performance via NAc 62 .…”