Grey and white matter atrophy in a large cohort of multiple sclerosis patients: Relation to MRI parameters and impact on clinical disability

Th e abundance of grey matter damage in multiple sclerosis and its clinical relevance is currently fully recognized. Although previous studies have provided information regarding determinants of grey matter atrophy and its relationship with disability in multiple sclerosis, the majority of these studies were limited by their sample size. Th e objectives of the current study were therefore to: 1) measure grey matter and white matter atrophy across diff erent disease phenotypes in a large cohort (N=927) of multiple sclerosis patients; 2) identify magnetic resonance imaging parameters that determine grey matter atrophy; 3) study grey matter and white matter atrophy as explanatory variables for clinical impairment. Magnetic resonance imaging data of 95 clinically isolated syndrome, 657 relapsing remitting, 125 secondary progressive and 50 primary progressive multiple sclerosis patients from three centres (GeneMSA consortium) were acquired. Grey and white matter volumes, normalized for head size, were determined, together with T2 hyperintense and T1 hypointense lesion volumes. Physical disability was assessed with the Expanded Disability Status Scale (EDSS), cognitive impairment with the Paced Auditory Serial Addition Task (PASAT). Data were analyzed using analysis of covariance and multiple regression. Grey matter atrophy, corrected for age, sex and centre eff ects, was more prominent in relapsing remitting patients (0.80 ± 0.05L) than in clinically isolated syndrome patients (0.82 ± 0.05L). Greater relative atrophy was found in secondary progressive patients (0.77 ± 0.05L). In contrast, white matter atrophy in secondary progressive patients was comparable to that in relapsing remitting patients. T2 lesion volume was an independent predictor of grey matter atrophy (beta=-0.27; p<0.001). Grey matter atrophy was the strongest independent predictor of physical disability and cognitive impairment. Our fi ndings in a large cohort confi rm that grey matter atrophy is greater in the secondary progressive phase than in relapsing remitting disease, whereas white matter atrophy is similar between these groups. Grey matter atrophy explained both physical and cognitive impairment better than white matter atrophy, and is itself partly predicted by T2 lesion volume. GM and WM atrophy in a large cohort of MS patients | 123