Assessing the Correlation between Grey and White Matter Damage with Motor and Cognitive Impairment in Multiple Sclerosis Patients

Background: Multiple sclerosis (MS) is characterized by demyelinating and degenerative processes within the central nervous system. Unlike conventional MRI, new advanced imaging techniques improve pathological specificity and better highlight the relationship between anatomical damage and clinical impairment. Objective: To investigate the relationship between clinical disability and both grey (GM) and white matter (WM) regional damage in MS patients. Methods: Thirty-six relapsing remitting-MS patients and 25 sex- and age-matched controls were enrolled. All patients were clinically evaluated by the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite (MSFC) scale, which includes the 9-hole peg test (9HPT), the timed 25-feet walking test (T25FW) and the paced auditory serial addition test (PASAT). All subjects were imaged by a 3.0 T scanner: dual-echo fast spin-echo, 3DT1-weighted and diffusion-tensor imaging (DTI) sequences were acquired. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses were run for regional GM and WM assessment, respectively. T2 lesion volumes were also calculated, by using a semi-automated technique. Results: Brain volumetric assessment of GM and DTI measures revealed significant differences between patients and controls. In patients, different measures of WM damage correlated each-other (p<0.0001), whereas none of them correlated with GM volume. In patients, focal GM atrophy and widespread WM damage significantly correlated with clinical measures. In particular, VBM analysis revealed a significant correlation (p<0.05) between GM volume and 9HPT in cerebellum and between GM volume and PASAT in orbito-frontal cortex. TBSS showed significant correlations between DTI metrics with 9HPT and PASAT scores in many WM bundles (p<0.05), including corpus callosum, internal capsule, posterior thalamic radiations, cerebral peduncles. Conclusions: Selective GM atrophy and widespread WM tracts damage are associated with functional impairment of upper-limb motion and cognition. The combined analysis of volumetric and DTI data may help to better understand structural alterations underlying physical and cognitive dysfunction in MS.