Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis

Melih Tutuncu, Junger Tang, Nuhad Abou Zeid, Nilufer Kale, Daniel J. Crusan, Elizabeth J. Atkinson, Aksel Siva, Sean J. Pittock, Istvan Pirko, B. Mark Keegan, Claudia F. Lucchinetti, John H. Noseworthy, Moses Rodriguez, Brian G. Weinshenker, Orhun H. Kantarci

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


Background: It is unclear if all patients with relapsing-remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases. Objective: Our aim is to confirm that onset of progressive disease course is more relevant to the patient's age than the presence or duration of a pre-progression relapsing disease course in MS. Methods: We studied a population-based MS cohort (n=210, RRMS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary (PPMS; n=322), single attack (SAPMS; n=112) and secondary progressive (SPMS; n=421). We studied demographics (chi2 or t-test), age-of-progression- onset (t-test) and time to Expanded Disability Status Scale of 6 (EDSS6) (Kaplan-Meier analyses). Results: Sex ratio (p=0.58), age at progression onset (p=0.37) and time to EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. Conclusions: Patients with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.

Original languageEnglish (US)
Pages (from-to)188-198
Number of pages11
JournalMultiple Sclerosis Journal
Issue number2
StatePublished - Feb 2013


  • EDSS
  • Multiple sclerosis
  • disability
  • outcome measurement
  • progressive
  • relapsing remitting

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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