BACKGROUND AND PURPOSE: Atrophy of the brain and the upper cervical cord, which both have major impact on the severity of clinical symptoms in multiple sclerosis (MS), may be interrelated by neuraxonal degeneration. Aiming to identify possible spatially remote effects of neuraxonal brain damage on spinal cord atrophy, we studied regional and global brain volumes and the upper cervical cord area (UCCA) in a large group of MS patients and a healthy control group. METHODS: In a group of 132 MS patients (71 relapsing-remitting MS; 61 secondary progressive MS; median [range] of EDSS: 5 [0-7], respectively 6 [2-8.5] and mean±standard deviation of age/disease duration: 37±11 years/6.7±6.3 years; respectively: 49±8 years/14.5±8.0 years) and 45 healthy subjects UCCA, regional and global brain volumes, and brain lesion load were assessed. Associations between MRI results and clinical parameters in the entire cohort and differentiated according to MS-subtype were investigated using t-tests, partial correlation analyses, voxel-based morphometry and statistical parametric mapping. RESULTS: Exclusively in RRMS, a significant positive correlation of UCCA with cerebellar cortical grey matter (GM) in the vermis and with regional white matter volume in the entire brainstem, corresponding to the corticospinal tracts, was detected. Although SPMS patients were considerably more affected by disability and decrease of UCCA (RRMS:75.2±10.4 mm(2); SPMS: 66.0±11.8 mm(2),controls: 84.5±8.7mm(2)), brain grey matter (RRMS:585.8±53.6 ml; SPMS: 528.2±61.5 ml, controls: 608.7±48.1 ml) and total brain volume (RRMS:1162.9±41.8 ml; SPMS: 1117.9±51.2 ml, controls: 1194.1±19.5 ml) than RRMS patients, significant positive associations in this group were found only between UCCA and a cluster of white matter in the medulla, but not in grey matter. CONCLUSION: Cervical cord and brain atrophy were present in both, RRMS and even more severe in SPMS. Still, spatial associations between cervical cord area and remote cerebellar and brainstem volume, possibly driven by neuraxonal degeneration, were detected mostly in RRMS patients with predominantly short disease durations. Future longitudinal studies may elucidate the interplay between affection of spinal cord and infratentorial structures in MS, and contribute to the understanding of the conversion processes from relapsing-remitting to secondary progressive MS.