Objective: To evaluate the pre-progressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive MS (PPMS).
Methods: A multicenter RIS cohort was previously established. Demographic, clinical and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing from onset disease (clinically isolated syndrome (CIS) or relapsing-remitting MS), and were also compared to two other population-based and clinic-based PPMS cohorts.
Results: Of the 453 subjects with RIS, 128 evolved to symptomatic MS during the follow-up (113 developed a first acute clinical event consistent with CIS/MS, 15 evolved to PPMS). PPMS prevalence (11.7%) and onset age (mean ± SD; 49.1 ± 12.1) in the RIS group was comparable to other PPMS populations (p>0.05). Median time to PPMS was 3.5 years (range: 1.6-5.4). RIS evolved to PPMS more commonly in men (p=0.005) and at an older age (p<0.001) when compared to CIS/MS, independent of follow-up duration. Subjects who evolved to PPMS had more spinal cord lesions (100%) before symptomatic evolution then those that developed CIS/MS (64%) and those that remained asymptomatic (23%) within the follow-up period (p=0.005). Other MRI characteristics in the pre-progressive phase of PPMS were indistinguishable from CIS/MS.
Interpretation: Subjects with RIS evolve to PPMS at the same frequency as expected from general MS populations in an age dependent manner. Besides age unequivocal presence of spinal cord lesions and being male predicts evolution to PPMS. Our findings further suggest that RIS is biologically part of the MS spectrum