Progressive multiple sclerosis exhibits decreasing glutamate and glutamine over two years

Abstract

Background: Few biomarkers of progressive multiple sclerosis (MS) are sensitive to change within the two-year time frame of a clinical trial. Objective: To identify biomarkers of MS disease progression with magnetic resonance spectroscopy (MRS) in secondary progressive MS (SPMS). Methods: Forty-seven SPMS subjects were scanned at baseline and annually for two years. Concentrations of N-acetylaspartate, total creatine, total choline, myo-inositol, glutamate, glutamine, and the sum glutamate+glutamine were measured in a single white matter voxel. Results: Glutamate and glutamine were the only metabolites to show an effect with time: with annual declines of (95% confidence interval): glutamate −4.2% (−6.2% to −2.2%, p < 10−4), glutamine −7.3% (−11.8% to −2.9%, p = 0.003), and glutamate+glutamine −5.2% (−7.6% to −2.8%, p < 10−4). Metabolite rates of change were more apparent than changes in clinical scores or brain atrophy measures. Conclusions: The high rates of change of both glutamate and glutamine over two years suggest they are promising new biomarkers of MS disease progression.