Weinshenker, Brian G.

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 (chi 2 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.