The impairment of the functional system and fatigue at the onset of the disease predict reaching disability milestones in relapsing-remitting multiple sclerosis differently in female and male patients.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with variable types of disability progression (DP). Previous studies, defining different disability milestones (DMs), have reported symptoms at MS onset to be the predictors of DP and sex as a risk factor. Meanwhile, accounting for sex differences in MS, predictors in female and male patients might differ. To investigate whether the symptoms at MS onset predict reaching DMs in patients with relapsing-remitting (RR) MS and whether the predictors vary between different DMs and female and male patients. Data from 128 RR MS patients (84 females, 44 males) was retrospectively studied. EDSS scores 4 and 6 (associated with impaired ambulation) were taken as DMs. Association between symptoms at MS onset and time to reach DMs was assessed with Cox multiple regression model. Pyramidal symptoms and fatigue at MS onset predicted the progression to EDSS 4 in the whole study population (HR 1.84, 95% CI 1.07-3.2, p = 0.028 and HR 2.01, 95% CI 1.12-3.4, p = 0.011, correspondingly). The same symptoms predicted reaching DM in female, but not male patients. Bowel/bladder symptoms predicted reaching EDSS 6 in the whole study population (HR 4.31, 95% CI 1.47-12.6, p = 0.008) and female patients only (HR 3.93, 95% CI 1.04-14.8, p = 0.043). In female patients, fatigue was also the predictor of reaching EDSS 6 (HR 3.54, 95% CI 1.16-10.8, p = 0.026). Impairment of functional symptoms at MS onset can predict reaching DMs in patients with RR-MS, but the predictors for EDSS 4 and EDSS 6 differ in female and male patients.