In this cross-sectional study, expanded disability status scale (EDSS), timed 25-foot walk (T25FW), six-minute walk test (6MWT), timed up and go (TUG) test, finger tapping (FT), nine-hole peg test (9HPT) and MUCCA measure (derived from 3D T1-weigthed brain images) were collected for 60 MS patients and 36 healthy controls (HC). In MS, the associations between MUCCA and clinical variables were explored. Then focusing on the relation between MUCCA and EDSS, we performed a mediation analysis to understand the potential role of clinical impairment as mediator.

In MS, lower MUCCA was associated with higher EDSS (R=-0.47, p<0.001) and lower values of inverse TUG (R=0.41, p=0.002), inverse T25FW (R=0.38, p=0.003), 6MWT (R=0.38, p=0.004) and FT (R=0.39, p=0.003). Within the mediation model, there was no direct effect of MUCCA on EDSS (β=-0.02, 95%CI [-0.05;0.01]), but there was a significant total indirect effect acting through T25FW, 6MWT, TUG and FT (β=-0.06, 95%CI [-0.10;-0.03]). Singularly, none of the clinical impairment seems to act as mediator.

In MS, in accordance with the ICF system, upper cervical cord atrophy predicts disability, but this relation is indirectly mediated by the overall impact of impairment in walking capacity, balance and manual dexterity domains.