title: Fatigue is not associated with raised inflammatory markers in multiple sclerosis.
abstract: BACKGROUND
  The pathogenesis of fatigue in patients with MS is poorly understood.
  
  
  OBJECTIVE
  To test the hypothesis that fatigue in MS is related to inflammatory disease activity as measured by systemic markers of inflammation.
  
  
  METHODS
  Fatigue as assessed by the Fatigue Questionnaire Scale (FQS) and Krupp's Fatigue Severity Scale (KFSS) was correlated with several inflammatory markers in 38 patients with MS (16 relapsing-remitting [RR; 7 of whom had benign MS), 9 secondary progressive [SP], 13 primary progressive [PP]). The markers included daily urinary neopterin excretion, a marker of interferon-gamma-activated macrophage activity, and serum C-reactive protein (CRP) and soluble intercellular adhesion molecule-1 (sICAM-1) levels. Urinary neopterin excretion was measured daily for 2 weeks.
  
  
  RESULTS
  No correlation was found between urinary neopterin excretion, CRP, or sICAM-1 and the fatigue scores. However, patients with a raised serum CRP level had higher KFSS, but not FQS, scores than patients with normal CRP levels (KFSS, 50 +/- 8 vs 41 +/- 14, p = 0.05; FQS, 13 +/- 4 vs 11 +/- 5, p = NS). When assessed using the FQS, patients with RR and SP MS were more fatigued than patients with PP MS (RR = 12.5 [4 to 23] vs SP = 13 [8 to 18] vs PP = 9 [7 to 14], p = 0.02). The patients with benign MS were as fatigued as patients with nonbenign disease.
  
  
  CONCLUSIONS
  The pathogenesis of fatigue in MS is complex and does not appear to be directly related to systemic markers of inflammatory disease activity. Interestingly, patients with PP MS were less fatigued than patients with RR disease.
authors.affiliation: Department of Neurochemistry, Institute of Neurology, London, United Kingdom. G.Giovannoni@ion.ucl.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Giovannoni
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
authors.forename: E J
authors.initials: EJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers; D002097:C-Reactive Protein / Q000096:biosynthesis; D016009:Chi-Square Distribution; D005221:Fatigue / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D019798:Neopterin / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D018799:Intercellular Adhesion Molecule-1; D019798:Neopterin; D002097:C-Reactive Protein