title: Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review.
abstract: OBJECTIVE
  To identify clinical and demographic factors associated with long-term disability in patients with relapsing-remitting multiple sclerosis.
  
  
  METHODS
  We searched the MEDLINE (1966-May 2005), EMBASE, CINAHL, Cochrane, and PsycINFO computerized databases, and reviewed reference lists of retrieved articles.
  
  
  METHODS
  We included studies that examined predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. We excluded studies that did not distinguish relapsing-remitting multiple sclerosis from primary progressive multiple sclerosis, enrolled fewer than 40 subjects, observed subjects for less than 5 years, or collected follow-up information in less than 80% of the inception cohort.
  
  
  METHODS
  Two reviewers assessed study quality in 4 domains: cohort assembly, definitions and assessments of prognostic factors and outcomes, and statistical methods. One reviewer extracted data on the direction, magnitude, precision, and statistical significance of the effect of each predictor on prognosis.
  
  
  RESULTS
  Heterogeneity of study designs precluded us from pooling the results of 27 eligible studies. Study quality was limited by cross-sectional design, enrollment of prevalent cases from referral centers, and lack of multivariate adjustment. Sphincter symptoms at onset (hazard ratio, 1.1-3.1), incomplete recovery from the first attack (hazard ratio, 1.3-3.3), and a short interval between the first and second attack (hazard ratio, 1.6-1.9) were most strongly and consistently associated with poor prognosis. Other factors widely believed to be of prognostic importance, including sex and age at onset, demonstrated inconsistent or weak effects on prognosis.
  
  
  CONCLUSIONS
  The most robust predictors of long-term physical disability in relapsing-remitting multiple sclerosis are sphincter symptoms at onset and early disease course outcomes. These factors can be used to guide treatment decisions for drugs with significant toxicities.
authors.affiliation: Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA. annette1@stanford.edu
authors.forename: Annette
authors.initials: A
authors.lastname: Langer-Gould
authors.forename: Rita A
authors.initials: RA
authors.lastname: Popat
authors.forename: Stella M
authors.initials: SM
authors.lastname: Huang
authors.forename: Kristin
authors.initials: K
authors.lastname: Cobb
authors.forename: Paulo
authors.initials: P
authors.lastname: Fontoura
authors.forename: Michael K
authors.initials: MK
authors.lastname: Gould
authors.forename: Lorene M
authors.initials: LM
authors.lastname: Nelson
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001003:Anal Canal / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000453:epidemiology* / Q000503:physiopathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D012107:Research Design; D012737:Sex Factors; D016896:Treatment Outcome