Distinguishing between Fatigue and Fatigability in Multiple Sclerosis

Abstract

Fatigue is one of the most common debilitating symptoms reported by persons with multiple sclerosis (MS). It reflects feelings of tiredness, lack of energy, low motivation, and difficulty in concentrating. It can be measured at a specific instant in time as a perception that arises from interoceptive networks involved in the regulation of homeostasis. Such ratings indicate the state level of fatigue and likely reflect an inability to correct deviations from a balanced homeostatic state. In contrast, the trait level of fatigue is quantified in terms of work capacity (fatigability), which can be either estimated (perceived fatigability) or measured (objective fatigability). Clinically, fatigue is most often quantified with questionnaires that require respondents to estimate their past capacity to perform several cognitive, physical, and psychosocial tasks. These retrospective estimates provide a measure of perceived fatigability. In contrast, the change in an outcome variable during the actual performance of a task provides an objective measure of fatigability. Perceived and objective fatigability do not assess the same underlying construct. Persons with MS who report elevated trait levels of fatigue exhibit deficits in interoceptive networks (insula and dorsal anterior cingulate cortex), including increased functional connectivity during challenging tasks. The state and trait levels of fatigue reported by an individual can be modulated by reward and pain pathways. Understanding the distinction between fatigue and fatigability is critical for the development of effective strategies to reduce the burden of the symptom for individuals with MS.

Fatigability and the Role of Neuromuscular Impairments in Chronic Kidney Disease

“…Recent efforts have been made to further clarify distinctions between fatigue and fatigability [8,12,[25][26][27][28][29][30][31]. These efforts are influenced, in part, by the lack of significant associations between measures of fatigue and performance fatigability in the medical literature, suggesting potential differences in biological underpinnings [25,[65][66][67][68][69][70][71][72].…”

“…There has been extensive clinical and scientific interest in the problem of fatigue in CKD and ESKD patients, whereas less attention has been directed to understanding fatigability. Although fatigue is a major challenge to everyday life, fatigue is not synonymous with fatigability [8,12,13,[25][26][27][28][29][30][31]. Accordingly, the primary purposes of this review are to (1) discuss fatigue and fatigability and their potential interactions in patients with CKD and ESKD, (2) provide evidence for increased fatigability in CKD and ESKD patients, (3) examine how commonly experienced neuromuscular impairments in CKD and ESKD patients may contribute to the severity of performance fatigability, and (4) highlight preliminary evidence of the effects of exercise as a potential clinical treatment for targeting fatigability in this population.…”

The Role of Remote Monitoring in Evaluating Fatigue in Multiple Sclerosis: A Review

“…Considering the inherent limitations of self-report measures, efforts to measure fatigue more objectively have involved several physical and cognitive performance-based measures. In these tests, compared to healthy controls, patients with MS demonstrate a decline in physical (e.g., sustained muscle contraction) and cognitive function (e.g., visual and verbal memory) after an effortful continuous performance task ( 14 ). These declines can happen even if baseline muscle strength and cognitive performance are normal.…”

Brain Under Fatigue – Can Perceived Fatigability in Multiple Sclerosis Be Seen on the Level of Functional Brain Network Architecture?

“…Fatigue Severity Scale is a method widely used in studies on MS and is characterized with good psychometric properties with Cronbach’s alpha of 0.93 ( Amtmann et al, 2012 ). According to Enoka et al (2021) it allows to quantify perceived fatigability.…”

“…The phenomenon of fatigue in MS can be understood on the level of state fatigue, which relates to psychological state in the specific moment of time or fatigue as a trait. Enoka et al (2021) divide trait fatigue into perceived fatigability and objective fatigability. The former can be operationalized from capacity to perform past, present, and future activities, while the latter refers to limits of current actions, manifested in voluntary activations and contractile function.…”