Pittock, S J

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.

As physicians how do we counsel our patients with clinically isolated syndrome (CIS) when they ask, ‘what is the benefit of injecting disease-modifying agents (DMAs) over many years? What disability will they prevent in my future?’ In this debate, we will provide three core points supporting the concept that a watchful waiting approach (annual neurological evaluation and magnetic resonance imaging of the head (with gadolinium) at least for the first few years after diagnosis) for most patients with CIS represents appropriate medical care.