Relapse Phenotype Associated With Accumulation of Disability in MS

Relapses presenting in the bowel/bladder, cerebellar, and pyramidal systems were linked to greater disability.

Analysis of data from the MSBase cohort demonstrated that relapse phenotypes including the bowel/bladder, cerebellar, and pyramidal systems have the greatest association with accumulation of disability and disability change in multiple sclerosis (MS).

The study, published in Multiple Sclerosis Journal, notes that relapse phenotype is an important predictor of patient prognosis, and therefore could influence treatment plans and outcomes.

In order to evaluate the effect of relapse phenotype on disability accumulation, Tomas Kalincik, MD, PhD, of the Department of Neurology at Melbourne Brain Centre in Parkville, Australia, and colleagues conducted a prospective analysis of participants with relapse-onset MS from the MSBase cohort. The participants were followed for a median of 5.9 years with a 0.25 per year median relapse rate. In total, they recorded 34 858 relapses over 136 462 patient-years.

Using multivariate linear regression, the authors observed an association between higher relapse frequency and increased Expanded Disability Status Scale score (β=0.16, 95% CI: 0.13-0.19, P<.001). Other factors associated with an increase in EDSS included male sex, older age, a history of secondary progressivee MS, longer duration of MS, and longer follow-up. Compared to monosymptomatic relapses, polysymptomatic MS relapses were associated with more disability accrual (β=0.06, 95% CI: 0.04-0.09 vs β=0.20, 95% CI: 0.17-0.23). Relapses that necessitated treatment with corticosteroids were also associated with greater accrual of disability (β=0.06, 95% CI: 0.04-0.08).

A multivariable analysis of the 16 052 participants with data on all relapses demonstrated an association between increased EDSS and bowel and bladder (β=0.42, 95% CI: 0.35-0.49), cerebellar (β=0.35, 95% CI: 0.30-0.39), and pyramidal (β=0.27, 95% CI: 0.25-0.29) relapses compared to visual, brainstem, sensory, and cerebral relapses.

The final model assessed changes in Kurtzke Functional System (KFS) scores based on relapse phenotype. The investigators found an association between particular relapse phenotypes and disability accumulation in related anatomical locations. For instance, pyramidal relapses were tied to an increase in KFS scores of the bowel and bladder.

The authors pointed out several potential limitations of the study, including the possibility of recall bias and EDSS assessment interrater variability.

“Using a large, representative MS cohort, this study … has shown that relapse phenotype constitutes an additional prognostic marker readily accessible to clinicians and their patients,” the authors wrote. “Therefore, prevention of relapses, in particular those presenting with pyramidal, cerebellar, and bowel/bladder signs, represents an important therapeutic goal.”


Stewart T, Spelman T, Havrdova E, et al. Contribution of different relapse phenotypes to disability in multiple sclerosis. Mult Scler. 2016; doi: 10.1177/1352458516643392.