title: The natural history of secondary progressive multiple sclerosis.
abstract: BACKGROUND
  The onset of secondary progression is a pivotal event in the course of relapsing-remitting (RR) multiple sclerosis (MS). Patients with secondary progressive MS (SPMS) experience continuous worsening of symptoms independent of the occurrence of relapses. Possible risk factors associated with the onset of SPMS remain under investigated in natural history studies of MS disease course.
  
  
  METHODS
  We used Kaplan-Meier survival analyses and Cox regression models to investigate the influence of gender, onset age and onset symptoms on time to and age at SPMS in British Columbia (BC) MS patients with a RR disease onset who were not exposed to immunomodulatory drugs.
  
  
  RESULTS
  Of 5778 patients in the BCMS database with definite MS, 5207 (90%) had an RR onset. Median time to SPMS was 21.4 years (95% CI 20.6 to 22.2), reached at a median age of 53.7 years (95% CI 53.1 to 54.3). Male gender and motor onset symptoms were associated with a shorter time to and a younger age at SPMS. A younger age at disease onset was associated with a longer time to SPMS but also with a younger age at secondary progression. Other onset symptoms were not associated with time to, or age at, SPMS.
  
  
  CONCLUSIONS
  We identified three factors influencing the onset of SPMS in untreated patients with RRMS: motor onset symptoms and male gender were associated with both a shorter time to and a younger age at SPMS. A younger age at disease onset should not be viewed as indicating a better prognosis.
authors.affiliation: Department of Neurology, University Medical Centre Groningen, GZ Groningen, The Netherlands. m.w.koch@neuro.umcg.nl
authors.forename: Marcus
authors.initials: M
authors.lastname: Koch
authors.forename: Elaine
authors.initials: E
authors.lastname: Kingwell
authors.forename: Peter
authors.initials: P
authors.lastname: Rieckmann
authors.forename: Helen
authors.initials: H
authors.lastname: Tremlett
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009048:Motor Skills; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis* / Q000453:epidemiology; D012737:Sex Factors; D013997:Time Factors