The relationship between neurodegeneration and other pathology in multiple sclerosis

Purpose To identify the focal and diffuse white matter (WM) pathology measures that are related to respectively whole brain, deep and cortical gray matter (GM) atrophy in long-standing multiple sclerosis (MS). Materials and methods The institutional review board approved the study; all subjects gave written informed consent. MRI was performed at 3T in 208 MS patients with long-standing disease (disease duration ≥ 10 years) and 60 healthy controls. Normalized gray and white matter volumes (NGMV and NWMV, respectively), normalized deep GM volumes (NDGMV), cortical thickness (CTh) and normalized lesion volumes (NLV) were quantified. Tissue integrity of normal-appearing WM (NAWM) and lesions was measured using diffusion tensor imaging. Multivariate associations between measures of GM atrophy and WM pathology were assessed in the patient group using multiple linear regression. Results NGMV, NDGMV and CTh were reduced in patients (all p < 0.001). The final model for NGMV consisted of NWMV, NLV, age and sex (adjusted R2 = 0.58; p < 0.001). NWMV, NLV and sex were the explanatory variables for NDGMV (adjusted R2 = 0.75; p < 0.001). The model for CTh consisted of fractional anisotropy of NAWM, NLV, age and sex (adjusted R2 = 0.32; p < 0.001). The relationship between GM atrophy and WM pathology was weaker in primary and secondary-progressive compared to relapsing-remitting patients. Conclusion Whole brain and deep GM atrophy were particularly explained by WM atrophy and lesion volume, while cortical atrophy was associated with NAWM integrity loss. The weaker relationship between GM atrophy and WM pathology in progressive patients might indicate a more independent neurodegenerative disease process in these patients.