title: The natural history of early versus late disability accumulation in primary progressive MS.
abstract: BACKGROUND
  Primary progressive multiple sclerosis (PPMS) is the least common MS disease course and carries the worst prognosis. In relapsing-remitting multiple sclerosis (RRMS) disability accumulation occurs in two distinct phases, but it is unclear whether this is also true for PPMS. Here we investigate factors associated with early and late disability accumulation in PPMS.
  
  
  METHODS
  We used Kaplan-Meier survival analyses and Cox regression to investigate the influence of sex, age at disease onset and onset symptoms on time to, and age at, Expanded Disability Status Scale (EDSS) 4 and 6, as well as the time from EDSS 4 to 6 in patients with PPMS.
  
  
  RESULTS
  We identified 500 patients with PPMS. The analyses on time to EDSS 4 included 358 patients, and those on time to EDSS 6 included 392 patients. The median times to EDSS 4 and EDSS 6 were 5 and 9 years. The analyses on age at EDSS 4 included 360 patients, and those on age at EDSS 6 included 402 patients. The median ages at EDSS 4 and EDSS 6 were 51 and 55 years. Older age at onset and bilateral motor onset symptoms were independently associated with a shorter time to both EDSS 4 and EDSS 6. Sex and other onset symptoms were not associated with time to, or age at, landmark disability. Only age at onset was significantly associated with the time from EDSS 4 to EDSS 6.
  
  
  CONCLUSIONS
  Age at disease onset is the most important predictor of disability accumulation in PPMS. Bilateral motor onset symptoms were associated with quicker disease progression. In contrast to RRMS, we found no evidence for distinct phases of disability accumulation in PPMS. Disability accumulation in PPMS appears to be affected by the same factors throughout its course.
authors.affiliation: Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Marcus W
authors.initials: MW
authors.lastname: Koch
authors.affiliation: Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jamie
authors.initials: J
authors.lastname: Greenfield
authors.affiliation: Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Omid
authors.initials: O
authors.lastname: Javizian
authors.affiliation: Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Deighton
authors.affiliation: Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Winona
authors.initials: W
authors.lastname: Wall
authors.affiliation: Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Luanne M
authors.initials: LM
authors.lastname: Metz
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009068:Movement; D020528:Multiple Sclerosis, Chronic Progressive / Q000503:physiopathology*; D012307:Risk Factors; D012677:Sensation; D012727:Sex Characteristics; D016019:Survival Analysis
keywords: EPIDEMIOLOGY; MULTIPLE SCLEROSIS