Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis.
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.
Mayo Clinic Center for Multiple Sclerosis and CNS Demyelinating Diseases, Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Melih
M
Tutuncu
Junger
J
Tang
Nuhad Abou
NA
Zeid
Nilufer
N
Kale
Daniel J
DJ
Crusan
Elizabeth J
EJ
Atkinson
Aksel
A
Siva
Sean J
SJ
Pittock
Istvan
I
Pirko
B Mark
BM
Keegan
Claudia F
CF
Lucchinetti
John H
JH
Noseworthy
Moses
M
Rodriguez
Brian G
BG
Weinshenker
Orhun H
OH
Kantarci
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000375:Aging / Q000473:pathology*; D001921:Brain / Q000473:pathology; D001933:Brain Stem / Q000473:pathology; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology; D011153:Population; D012744:Sex Ratio; D013116:Spinal Cord / Q000473:pathology; D016896:Treatment Outcome