Editorial: Fatigue in Multiple Sclerosis

Fatigue in Multiple Sclerosis (MS) is one of the most debilitating symptoms in patients with Multiple Sclerosis (pwMS). It interferes significantly with career as well as participation in everyday life activities. It is an enormous burden to the pwMS, his/her family and friends. Direct and indirect costs are extraordinary, both financial and psychosocial. Ongoing scientific studies struggle to understand the pathophysiology of fatigue in the hope of improving options for treatment. The past decade has seen much progress with important developments emerging to understand different phenomena related to fatigue. Most helpful and essential when discussing fatigue is the distinction between subjective sensations and objective changes in performance (1) and between trait and state fatigue (2). This Research Topic brings together ten novel and exciting perspectives written by leading authorities in this area from around the world from both clinical and scientific perspectives to understand the multidimensional nature of fatigue. The first two chapters propose some new and unique concepts in trying to explain fatigue. Dobryakova, Genova, DeLuca, and Wylie summarize various lines of evidence suggesting that dopa-mine imbalance plays a major role in developing fatigue (Dobryakova et al.). The model builds upon an earlier framework for studying fatigue suggested by Chaudhuri and Behan (3, 4), who suspected that central fatigue was a " failure of the non-motor functions of the basal ganglia. " The current manuscript reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest the critical role that dopamine plays in fatigue. Hanken, Eling, and Hildebrandt focus on different aspects in their model (Hanken et al.). They suggest that the subjective feeling of fatigue is related to inflammation and increased levels of cytokines such as interleukin-1 (IL-1), IL-6, TNF-alpha. These inflammatory substances cause a sickness behavior – described as a highly organized strategy of an organism to cope with the infection. These authors refer to the original description of the sickness behavior by Maes et al. (5). From their structural imaging study, the authors concluded that structural alterations of the brain related to fatigue may be found in the insula, anterior cingulate cortex, and the hypothalamus. These structures are related to homeostasis and representation of internal bodily states. Intuitively one might expect that the cognitive load has a significant impact on fatigue. Interestingly, Sandry, Genova, Dobryakova, DeLuca, and Wylie describe that it is not the cognitive load, but rather the length of the task …