Multimodal assessment of normal-appearing corpus callosum is a useful marker of disability in relapsing–remitting multiple sclerosis: an MRI cluster analysis study

Background and purpose Corpus callosum (CC) is frequently involved in relapsing–remitting multiple sclerosis (RRMS). Magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) allow to study CC macrostructural and microstructural tissue integrity. Here, we applied a data-driven approach to MRI and DTI data of normal-appearing CC in RRMS subjects, and subsequently evaluated if differences in tissue integrity corresponded to different levels of physical disability and cognitive impairment. Methods 74 RRMS patients and 20 healthy controls (HC) underwent 3 T MRI and DTI. Thickness and fractional anisotropy (FA) along midsagittal CC were extracted, and values from RRMS patients were fed to a hierarchical clustering algorithm. We then used ANOVA to test for differences in clinical and cognitive variables across the imaging-based clusters and HC. Results We found three distinct MRI-based subgroups of RRMS patients with increasing severity of CC damage. The first subgroup showed callosal integrity similar to HC (Cluster 1); Cluster 2 had milder callosal damage; a third subgroup showed the most severe callosal damage (Cluster 3). Cluster 3 included patients with longer disease duration and worst scores in Expanded Disability Status Scale. Cognitive domains of verbal memory, executive functions and processing speed were impaired in Cluster 3 and Cluster 2 compared to Cluster 1 and HC. Conclusions Within the same homogeneous cohort of patients, we could identify three neuroimaging RRMS clusters characterized by different involvement of normal-appearing CC. Interestingly, these corresponded to three distinct levels of clinical and cognitive disability.