The relationship between regional microstructural abnormalities of the corpus callosum and physical and cognitive disability in relapsing–remitting multiple sclerosis

• We assess corpus callosum damage in relapsing–remitting multiple sclerosis.
• We used no a priori subdivisions to model the bundle in a continuous fashion.
• Imaging–clinical relationship was explored by correlation and regression analyses.
• Damage of large, heavily myelinated axons was mainly linked to physical disability.
• Damage of small-diameter axons was mainly linked to cognitive impairment.

Significant corpus callosum (CC) involvement has been found in relapsing–remitting multiple sclerosis (RRMS), even if conventional magnetic resonance imaging measures have shown poor correlation with clinical disability measures. In this work, we tested the potential of multimodal imaging of the entire CC to explain physical and cognitive disability in 47 patients with RRMS. Values of thickness, fractional anisotropy (FA) and mean diffusivity (MD) were extracted from 50 regions of interest (ROIs) sampled along the bundle. The relationships between clinical, neuropsychological and imaging variables were assessed by using Spearman's correlation. Multiple linear regression analysis was employed in order to identify the relative importance of imaging metrics in modeling different clinical variables. Regional fiber composition of the CC differentially explained the response variables (Expanded Disability Status Scale [EDSS], cognitive impairment). Increases in EDSS were explained by reductions in CC thickness and MD. Cognitive impairment was mainly explained by FA reductions in the genu and splenium. Regional CC imaging properties differentially explained disability within RRMS patients revealing strong, distinct patterns of correlation with clinical and cognitive status of patients affected by this specific clinical phenotype.