Journal
MULTIPLE SCLEROSIS JOURNAL
Volume 19, Issue 2, Pages 188-198Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458512451510
Keywords
Multiple sclerosis; outcome measurement; progressive; relapsing remitting; EDSS; disability
Categories
Funding
- Mayo Clinic Rochester Department of Neurology
- National Multiple Sclerosis Society
- Hilton Foundation
- NINDS [U01 NS 45719, R01 NS 49577-6, 2P50NS038667-11, R01 NS058698-01A2, R01 NS 58698, R01 NS 60881, R01 NS060881-01A209, R01 NS 65829]
- Biogen Idec. [101JC402]
- NIH [UL1 RR 24150-2, R01 GM092993, R01 NS024180, R01 NS032129, R01 NS048357, R21 NS073684]
- Guthy-Jackson Charitable Foundation
- Alexion Pharmaceuticals, Inc.
- NIH CTSA (Center for Translational Science Activities - HIPFA) from the National Center for Research Resources (NCRR) [UL1 RR024150]
- National Multiple Sclerosis Society [CA 1060A11]
- Applebaum Foundation
- Hilton and Peterson Foundation
- Minnesota Partnership Award for Biotechnology and Medical Genomics
- European Regional Development Fund - Project FNUSA-ICRC [CZ.1.05/1.1.00/02.0123]
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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.
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