Relapse-associated worsening in a real-life multiple sclerosis cohort: The role of age and pyramidal phenotype

Background: The overall disability in patients with relapsing-remitting multiple sclerosis (RRMS) is likely to be partly rather than entirely attributed to relapse. Materials and methods: We aimed to investigate the determinants of recovery from first relapse and relapse associated worsening (RAW) in RRMS patients from the Italian MS registry during a five-years epoch from the beginning of first-line disease modifying therapy. To determine recovery, the functional system score (FSS) was used to calculate the difference between the score on the date of maximum improvement and the score before the onset of relapse. Incomplete recovery was defined as a combination of partial (1 point in one FS), and poor recovery (two points in one FS or one point in two FSs or any other higher combination). RAW was indicated by a confirmed disability accumulation measured by the Expanded Disability status scale score confirmed 6 months after the first relapse. Results: A total of 767 patients had at least one relapse within 5-years of therapy. Of these patients, 57.8% experienced incomplete recovery. Age (OR= 1.02, 95% Confidence interval-CI 1.01-1.04; p = 0.007) and pyramidal phenotype were associated to incomplete recovery (OR= 2.1, 95% CI 1.41-3.14; p < 0.001). RAW was recorded in 179 (23.3%) patients. Age (OR= 1.02, 95% CI 1.01-1.04; p=0.029) and pyramidal phenotype (OR= 1.84, 95% CI 1.18-2.88; p = 0.007) were the strongest predictors in the multivariable model. Conclusions: Age and pyramidal phenotype were the strongest determinants of relapse-associated worsening in early disease epochs.