title: 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.
authors.affiliation: Division of Neurology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada erin.macmillan@ubc.ca.
authors.forename: E L
authors.initials: EL
authors.lastname: MacMillan
authors.affiliation: 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.
authors.forename: R
authors.initials: R
authors.lastname: Tam
authors.affiliation: UBC MS/MRI Research Group, The University of British Columbia, Vancouver, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Radiology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
authors.forename: I M
authors.initials: IM
authors.lastname: Vavasour
authors.affiliation: 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.
authors.forename: D K B
authors.initials: DK
authors.lastname: Li
authors.affiliation: Division of Neurology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Oger
authors.affiliation: Department of Neurology, Faculty of Medicine, The University of Ottawa, Canada.
authors.forename: M S
authors.initials: MS
authors.lastname: Freedman
authors.affiliation: Division of Neurology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
authors.forename: S H
authors.initials: SH
authors.lastname: Kolind
authors.affiliation: Division of Neurology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
authors.forename: A L
authors.initials: AL
authors.lastname: Traboulsee
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D005973:Glutamine; D018698:Glutamic Acid
keywords: Secondary progressive multiple sclerosis; biomarkers; magnetic resonance imaging