title: Fatigue in Multiple Sclerosis: Assessing Pontine Involvement Using Proton MR Spectroscopic Imaging.
abstract: OBJECTIVE
  The underlying mechanism of fatigue in multiple sclerosis (MS) remains poorly understood. Our study investigates the involvement of the ascending reticular activating system (ARAS), originating in the pontine brainstem, in MS patients with symptoms of fatigue.
  
  
  METHODS
  Female relapsing-remitting MS patients (n = 17) and controls (n = 15) underwent a magnetic resonance spectroscopic imaging protocol at 1.5T. Fatigue was assessed in every subject using the Fatigue Severity Scale (FSS). Using an FSS cut-off of 36, patients were categorized into a low (n = 9, 22 ± 10) or high (n = 10, 52 ± 6) fatigue group. The brain metabolites N-acetylaspartate (NAA) and total creatine (tCr) were measured from sixteen 5x5x10 mm3 spectroscopic imaging voxels in the rostral pons.
  
  
  RESULTS
  MS patients with high fatigue had lower NAA/tCr concentration in the tegmental pons compared to control subjects. By using NAA and Cr values in the cerebellum for comparison, these NAA/tCr changes in the pons were driven by higher tCr concentration, and that these changes were focused in the WM regions.
  
  
  CONCLUSIONS
  Since there were no changes in NAA concentration, the increase in tCr may be suggestive of gliosis, or an imbalanced equilibrium of the creatine and phosphocreatine ratio in the pons of relapsing-remitting MS patients with fatigue.
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Wan Hazlin
authors.initials: WH
authors.lastname: Zaini
authors.affiliation: Department of Medicine, Division of Neurology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giuliani
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Beaulieu
authors.affiliation: Department of Medicine, Division of Neurology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kalra
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hanstock
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005221:Fatigue; D005260:Female; D006801:Humans; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011149:Pons / Q000378:metabolism* / Q000473:pathology; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine