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Fatigue can be a very disabling symptom in MS and its pathogenesis is still poorly understood. The authors studied a group of people with MS with moderate levels of physical disability. They found that the people who suffered from fatigue had brain volume loss in specific areas of the cortical grey matter and the white matter nearby. No differences in the other MRI parameters were observed between fatigued and non-fatigued individuals. The findings of this study strongly suggest that the pathological substrate of primary fatigue (i.e. the fatigue not related to physical disability but to MS itself) in MS could be the interruption of the cortico-subcortical circuit. Neuroimage. 2010 Jan 5
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