Fatigue is associated with metabolic and density alterations of cortical and deep gray matter in Relapsing-Remitting-Multiple Sclerosis patients at the earlier stage of the disease: A PET/MR study

Background: Fatigue is a common but complex symptom of multiple sclerosis. A central origin is now suggested as a key feature of its pathophysiology and gray matter (GM) structure seems to be (particularly) involved in the neurobiological basis of fatigue in multiple sclerosis (MS) patients.

Methods: We investigated, in a cohort of 17 Relapsing-Remitting-MS patients recruited within three years of disease diagnosis, the link between fatigue severity evaluated by the EMIF-SEP (a validated self-report questionnaire in French), and metabolic and density alterations of GM using positron emission tomography (PET) and magnetic resonance (MR) imaging using SPM5 (statistical parametric morphometry) analysis and voxel-based-morphometry.

Results: Compared to patients without fatigue-MS (NF-MS) group, patients with fatigue-MS (F-MS) had significant reduction (with correctedp<0.05) of GM density in clusters located in the bilateral middle, superior and inferior frontal cortex and in left temporal and parietal cortex. In addition, the total score for fatigue was negatively correlated with GM density in the same regional areas for the whole group. Total fatigue score was negatively correlated with GM density in bilateral thalamus (correctedp=0.04) and with rest cerebral metabolic rate of glucose (rCMRglu) in the basal ganglia (correctedp<0.05). Juxtacortical and/or overlapping corticosubcortical lesion volume in frontal and temporal areas were significantly higher in the F-MS group compared to NF-MS patients.

Conclusions: These results add new data suggesting that fatigue is associated with functional and structural changes of cerebral gray matter especially in frontal cortex and basal ganglia.