Background: Radiologically isolated syndrome (RIS) is defined by MRI findings that are suggestive of multiple sclerosis (MS) in the absence of prior clinical demyelinating events. We aimed to compare the health-related quality of life (HRQoL) between RIS and relapsing–remitting MS (RRMS) after adjusting for fatigue, cognition, and psychological distress, and to contextualize generic HRQoL, relative to healthy controls. Methods: In this cross-sectional analysis of the baseline data, 30 RIS, 29 RRMS, and 30 healthy controls were analyzed. MS-specific HRQoL (patients only) was assessed with the Functional Assessment of Multiple Sclerosis (FAMS), and generic HRQoL (all participants) was assessed with the EuroQol-5D (EQ-5D) visual analogue scale and utility index. Multi-variable linear regression models with robust (HC3) standard errors were used, adjusting for demographics, fatigue impact, cognitive performance, and psychological distress. Results: The FAMS totals were similar in RIS vs. RRMS (median 167.5 vs. 164.0; p = 0.694) and remained non-different after adjustment (β= −2.37, 95% CI −10.18 to 5.44; p = 0.544). EQ-5D outcomes showed an unadjusted gradient across groups, but adjusted differences relative to RIS were not statistically significant. Greater fatigue impact was associated with poorer HRQoL across all models (all p < 0.001). Psychological distress was associated with lower FAMS (β = −14.53; p < 0.001) but not with EQ-5D outcomes. Conclusions: HRQoL in RIS was comparable to RRMS, and fatigue impact was the most consistent correlate of poorer HRQoL.
Benito-León et al. (2026) studied this question.