Clinical Assessment of Fatigability in Multiple Sclerosis: A Shift from Perception to Performance

Multiple sclerosis (MS) is a neurodegenerative disorder characterized by an inflammatory autoimmune disease process in the central nervous system (CNS) (1). MS presents with clinical impairments based on location and severity of CNS lesions. Fatigue is the most common reported symptom of people with MS (PwMS) (2), and 80–85% of individuals describe it as the most disabling feature of the disease (3, 4). Decreased quality of life (5), limited physical activity (6, 7), and increased rates of depression and anxiety (8, 9) are associated with higher levels of reported fatigue among PwMS. The specific etiology of fatigue in MS is unknown, and it is likely the product of multiple factors rather than a single cause (1). There is a need for development of a unified taxonomy to help define what people experience when they report fatigue (10, 11). An early attempt to define fatigue was published from the 1981 CIBA Foundation Symposium in “Human Muscle Fatigue: Physiological Mechanisms” by Edwards (12) as “a failure to maintain the required or expected force. ” While Edwards provided a simple and direct operational definition, it failed to convey subjective feelings described by PwMS. Enoka and Stuart (13) expanded Edwards’ definition to include perception, stating that fatigue is “an acute impairment of performance that includes both an increase in the perceived effort necessary to exert a desired force and the eventual inability to produce this force. ” This definition features Mosso’s dichotomy and is now a commonly used framework within the realm of fatigue research (13). Within this taxonomy, force decrements are considered distinct from sensations that arise from prolonged muscular activity. However, as investigators began to uncover multiple mechanistic causes for fatigue, they began to label fatigue with descriptors consisting of the independent variables studied. Examples of this trend include cognitive fatigue, peripheral fatigue, and central fatigue among others. Beyond cohesive operational definitions, the limited ability to isolate components of Enoka and Stuart’s expanded definition explains, in part, why so little progress has been made in addressing clinically reported fatigue symptoms (14). Kluger et al. (10) presented a taxonomy that attempts to reunite the developing silos of fatigue work by returning to Enoka and Stuart’s definition. He calls for the common language of fatigue to be divided into two well-defined categories, distinguishing between the perception of fatigue and fatigability. “Perception of fatigue” defines subjective sensations related to an individual’s symptom complaint and is the result of homeostatic and psychological factors. “Fatigability” relates to task performance and is defined by a change in performance relative to an objective criterion. Enoka and Duchateau (11) presented additional framework for viewing fatigue as a symptom that has a trait characteristic and can be influenced by state variables. This view of fatigue allows researchers to measure the effects of short-term and modifiable state variables on the long-term trait characteristic of fatigue (i.e., the perception of fatigue or fatigability). The approach of Enoka and Duchateau (11) encourages investigators to emphasize their assessment methodology and the task dependency of fatigue, while minimizing use of obtuse modifiers or descriptors that lack clarity and yield little insight into causative factors. Developing and conceptualizing unified operational definitions of fatigue holds ramifications for clinical practice. It is our view that a combination of poorly defined taxonomies, unknown etiology, and vague clinical descriptions have made fatigue difficult to quantify during clinical assessment. Therefore, it is not surprising that current treatments are non-specific and yield unsatisfactory outcomes. The purpose of this paper is to convey the limitations of current fatigue assessments for evaluating task performance fatigability in rehabilitative settings for PwMS. Additionally, we call for the development of clinical tests which can measure the influence of state variables on the trait characteristic of performance fatigability as it relates to function and quality of life.