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).