Contribution of Global and Regional Damage of the Gray and White Matter to Fatigue in MS (P6.127)

OBJECTIVE: We combined atrophy and diffusion tensor (DT) MRI measures to investigate the role of damage to lesions, normal-appearing white matter (NAWM) and gray matter (GM) to the pathogenesis of fatigue in patients with multiple sclerosis (MS). BACKGROUND: Fatigue has been reported as one of the most frequent and disabling symptom in MS but its physiopathology is not well elucidated yet. DESIGN/METHODS: Brain dual-echo, double inversion recovery (DIR), high-resolution T1-weighted and DT MRI scans were acquired from 63 MS patients and 35 sex- and age-matched healthy controls. Patients were classified in fatigued (F-MS) and non-fatigued (nF-MS) based on Fatigue Severity Scale (FSS) scores. Patients with depression were excluded. Between-group differences of GM and WM regional volumes were assessed using voxel-based morphometry (p<0.05 FWE corrected). Diffusivity values of cortical lesions (CLs), skeletonized cortex, WM lesions and NAWM were assessed. Tract-based spatial statistics was used to define the regional distribution of DT MRI abnormalities in the T2-lesions. RESULTS: Thirty-one patients were classified as F-MS. Diffusivity values of CLs, skeletonized cortex, WM lesions and NAWM and regional WM atrophy did not differ significantly between F-MS and nF-MS patients. Compared to nF-MS, F-MS patients showed atrophy of the right accumbens and inferior temporal gyrus (ITG). ITG atrophy was correlated with FSS (r=-0.42) and EDSS (r=-0.48). Compared to nF-MS, F-MS patients had lower fractional anisotropy of the forceps major, left inferior fronto-occipital fasciculus and right anterior thalamic radiation (ATR), and a higher frequency of T2 lesions at the level of the right ATR (p<0.01). CONCLUSIONS: The analysis at regional level of measures derived from different MR modalities, specific towards different substrates of MS pathology, is a promising approach to improve the understanding of the pathophysiology of fatigue in MS. Study Supported by: Partially supported by a grant from Italian Ministry of Health (GR-2008-1138784).