Spatial distribution of multiple sclerosis lesions in the cervical spinal cord

Background: Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success however, suggesting that lesion location may be a contributor. Purpose: To explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. Material and methods: We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2 * -weighted axial and sagittal MRI scans acquired at 3 or 7 Tesla. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterised by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalised lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. Results: The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (p<0.001), which was further confirmed by absolute and normalised lesion volumes (p<0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (p<0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (p<0.001), however when normalising by each region, normalised lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (p<0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than a long disease duration. Conclusion: Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the the distribution of spinal cord lesions in various patient groups.