The basal ganglia: a substrate for fatigue in multiple sclerosis

Introduction The origin of fatigue in multiple sclerosis (MS) remains uncertain. However, the use of nonconventional magnetic resonance techniques has increased our understanding of this problem. We aimed to study the relationship between fatigue in MS and the presence of focal dysfunction in the basal ganglia and frontal white matter. Methods Included in the study were 41 patients with relapsing-remitting MS with mild disability and 20 healthy controls. Fatigue was assessed by the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Patients were classified as fatigued when they expressed a subjective feeling of fatigue, and the FSS score was >= 5.0 and/or the MFIS score was > 38. Patients with no subjective fatigue were classified as nonfatigued when the FSS score was < 4.0. Proton magnetic resonance spectra were obtained from two different regions: the frontal white matter and the lentiform nucleus. The relationships between fatigue and NAA/Cr, NAA/Cho and Cho/Cr ratios were analysed. Results A significant decrease in NAA/Cr in the lentiform nucleus region in patients with fatigue was observed. No differences between the groups were found in the frontal white matter. Conclusion Although confirmatory studies are needed, our results would support the idea that a specific dysfunction or involvement of the basal ganglia might partly contribute to the development of MS-related fatigue.