Tract-specific white matter correlates of fatigue and cognitive impairment in benign multiple sclerosis

Background Although benign multiple sclerosis (BMS) is traditionally defined by the presence of mild motor involvement decades after disease onset, symptoms of fatigue and cognitive impairment are very common. Objective To investigate the association between micro-structural damage in the anterior thalamic (AT) tracts and in the corpus callosum (CC), as measured by diffusion tensor imaging (DTI) tractography, and fatigue and cognitive deficits. Methods DTI data were acquired from 26 BMS patients and 24 sex- and age-matched healthy controls. Results General and mental fatigue scores were significantly impaired in patients compared with controls (p ≤ 0.05 for both) and 38% of patients resulted cognitively impaired. Mean diffusivity (MD) of the AT and CC tracts was significantly higher and fractional anisotropy (FA) was lower in patients compared with controls (p < 0.001 for all). Fatigue was associated with increased MD (p = 0.01) of the AT tracts whereas deficit of executive functions and verbal learning were associated with decreased FA in the body (p = 0.004) and genu (p = 0.008) of the CC. Deficits in processing speed and attention were associated with the T2 lesion volume of the AT tracts (p < 0.01 for all). Discussion These findings suggest that fatigue and cognitive impairment are quite frequent in BMS patients and are, at least in part, related to micro-structural damage and T2LV of WM tracts connecting the brain cortical and sub-cortical regions of the two hemispheres.