Correlation between fatigue and brain atrophy and lesion load in multiple sclerosis patients independent of disability.

Abstract Background Fatigue is a major problem in multiple sclerosis (MS), and its association with MRI features is debated. Objective To study the correlation between fatigue and lesion load, white matter (WM), and grey matter (GM), in MS patients independent of disability. Methods We studied 222 relapsing remitting MS patients with low disability (scores ≤ 2 at the Kurtzke Expanded Disability Status Scale). Lesion load, WM and GM were measured by fully automated, operator-independent, multi-parametric segmentation method. T1 and T2 lesion volume were also measured by a semi-automated method. Fatigue was assessed by the Fatigue Severity Scale (FSS), and patients divided in high-fatigue (FSS ≥ 5; n  = 197) and low-fatigue groups (FSS ≤ 4; n  = 25). Results High-fatigue patients showed significantly higher abnormal white matter fraction (AWM-f), T1 and T2 lesion loads, and significant lower WM-f, and GM-f. Multivariate analysis showed that high FSS was significantly associated with lower WM-f, and GM-f. Females and highly educated patients were significantly less fatigued. Conclusion These results suggest that among MS patients with low disability those with high-fatigue show higher WM and GM atrophy and higher lesion load, and that female sex and higher levels of education may play a protective role towards fatigue. Furthermore, they suggest that in MS, independent of disability, WM and GM atrophy is a risk factor to have fatigue.