Fatigue in multiple sclerosis is associated with the disruption of frontal and parietal pathways

Background: Fatigue is one of the most frequent and disturbing symptoms in multiple sclerosis (MS), directly affecting the patient's quality of life. However, many questions remain unclear regarding the anatomic brain correlate of MS-related fatigue. Objective: To assess the relationship between fatigue and white matter lesion location and gray matter atrophy. Methods: In this study, 60 patients with MS were evaluated with the Modified Fatigue Impact Scale and magnetic resonance imaging. Location of white matter lesion was analyzed using a voxel-by-voxel lesion probability mapping approach and gray matter atrophy degree and location using an optimized voxel-based morphometry method. Results: We found a correlation between lesion load and fatigue score (T2 lesion load: r = 0.415, P = 0.001; T1 lesion load r = 0.328, P = 0.011). Moreover, fatigue correlated with lesions in the right parietotemporal (periatrial area, juxtaventricular white matter deep in the parietal lobe and callosal forceps) and left frontal (middle-anterior corpus callosum, anterior cingulum and centrum semiovale of the superior and middle frontal gyri) white matter regions (P < 0.001 in all cases). Finally, fatigue score significantly correlated with gray matter atrophy in frontal regions, specifically, the left superior frontal gyrus and bilateral middle frontal gyri (P < 0.001 in all cases). Conclusion: Our results suggest that the symptom of fatigue is associated with a disruption of brain networks involved in cognitive/ attentional processes.