Health-Related Quality of Life in Radiologically Isolated Syndrome Resembles Relapsing–Remitting Multiple Sclerosis

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: The FAMS totals were similar in RIS vs. RRMS (median 167.5 vs. 164.0; <i>p</i> = 0.694) and remained non-different after adjustment (β= -2.37, 95% CI -10.18 to 5.44; <i>p</i> = 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 <i>p</i> < 0.001). Psychological distress was associated with lower FAMS (β = -14.53; <i>p</i> < 0.001) but not with EQ-5D outcomes. <b>Conclusions</b>: HRQoL in RIS was comparable to RRMS, and fatigue impact was the most consistent correlate of poorer HRQoL.