E L MacMillan1, R Tam2, Y Zhao3, I M Vavasour4, D K B Li2, J Oger5, M S Freedman6, S H Kolind5, A L Traboulsee5. 1. Division of Neurology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada erin.macmillan@ubc.ca. 2. Department of Radiology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada/UBC MS/MRI Research Group, The University of British Columbia, Vancouver, Canada. 3. UBC MS/MRI Research Group, The University of British Columbia, Vancouver, Canada. 4. Department of Radiology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada. 5. Division of Neurology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada. 6. Department of Neurology, Faculty of Medicine, The University of Ottawa, Canada.
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.
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.
Authors: Erin L MacMillan; Julia J Schubert; Irene M Vavasour; Roger Tam; Alexander Rauscher; Carolyn Taylor; Rick White; Hideki Garren; David Clayton; Victoria Levesque; David Kb Li; Shannon H Kolind; Anthony L Traboulsee Journal: Mult Scler J Exp Transl Clin Date: 2019-10-15