Pathophysiology and Differentiation from Other Symptoms and Diseasess

Abstract

Fatigue is considered the most common symptom, reported by up to 90% of people with multiple sclerosis, which can have a significant negative impact on quality of life, regardless of age, gender, disease duration, and extent of neurological impairment (Paul and Veauthier 2012; von Bismarck et al. 2018) and is also one of the main risk factors for reduced employment and early retirement. In addition, quite a few sufferers name fatigue as the most distressing symptom of MS. In contrast to the high prevalence and the considerable socio-medical relevance, the pathophysiology of fatigue in MS is at best only rudimentarily understood, which therefore makes causal therapeutic approaches difficult (Penner and Paul 2017). This is further complicated by the fact that fatigue is ultimately a subjectively experienced symptom that is difficult to objectify and quantify. Therefore, stricter definitional discrimination between fatigue as a subjective perception and objectively measurable performance in motor or cognitively demanding tasks (“load-dependent fatigability”) (Kluger et al. 2013) has been proposed, especially since “fatigue” and “fatigability” are not necessarily closely associated. Recently, an even more differentiated taxonomy has been proposed and also used in a fatiguing motor paradigm in MS fatigue. According to Drebinger, Kluger, Wolff, Enoka et al. (Drebinger et al. 2020; Wolff et al. 2019; Enoka and Duchateau 2016) different constructs can be distinguished: “state fatigue” (“perception of exertion in situations of effort-demanding activities that is physiologically transient and recovers with rest”) from “trait fatigue” (“pathological fatigue as frequent, prolonged, or constant disabling sensation of weariness and exhaustion over longer time frames, interfering with usual/desired activities”) and from “performance fatigability” (“reduced capacity to maintain activity which can be observed as a decline in performance measures with effort-demanding activities”). To what extent these constructs will contribute to a more precise classification of patient-reported fatigue remains to be seen.