Multiple sclerosis (MS (is a disease of the central nervous system that adversely impacts functional performance and activities of daily living (Compston and Coles, 2008). The most prevalent and disabling symptom experienced by persons with MS (PwMS) is fatigue, which is reported by more than 80 % of PwMS as their most debilitating symptom (Wood et al., 2013). Fatigue is commonly defined as a subjective feeling of tiredness or exhaustion that interferes with one's performance of physical or mental voluntary tasks (Norheim et al., 2011). Fatigue can be classified using several methods. Depending on its origin, fatigue can be described using central and peripheral components based on the motor pathways of the involved muscles. Central fatigue may occur due to deficits in the activation signals to a muscle from the central nervous system (Norheim et al., 2011). In contrast, peripheral fatigue includes failure to complete both motor and cognitive tasks due to the depletion of the neuromuscular junction of the skeletal muscle (Norheim et al., 2011). Fatigue is acute when its duration is short and relieved by rest, and fatigue is chronic when it persists for months and is not mitigated by rest (Wan et al., 2017). Fatigue can also be categorized as mental fatigue, which refers to the inability to perform mental tasks due to a lack of self-motivation, and physical fatigue, which refers to a decrease in maximal muscle strength during physical activity (Norheim et al., 2011). Additionally, fatigue can arise from secondary associated conditions such as depression and sleep disorders (Braley et al., 2012; Sparasci et al., 2022).

Indeed, owing to the multiple dimensions of fatigue, it may not be surprising that there is a great deal of confusion across studies regarding the best way to measure fatigue. Much of the clinical research on MS-related fatigue focuses on the rate of change in perceptions of fatigue, which can be assessed using self-report scales (Braley and Chervin, 2010). However, such scales can be influenced by the homeostatic and psychological state of the individual (Enoka and Duchateau, 2016). Furthermore, “objective” measures of fatiguability are poorly defined and ambiguous, as decrements in motor performance during functional tasks can be primarily related to changes in neuromuscular performance (Seamon and Harris-Love, 2016). To remedy this situation and better understand this subject, Kluger et al. have proposed a unified taxonomy in neurologic diseases to distinguish between fatigue (what a patient subjectively feels about the presence and severity of fatigue) and fatigability (objectively diminished strength that a patient develops through sustained movements during given tasks) (Kluger et al., 2013).

Fatigability is the most reliable outcome measure in clinical trials for understanding the activity context in which the fatigue occurs, both physically and cognitively. Fatigability is often studied in terms of two entities: perceived and performance fatigability. Perceived fatigability relies on the overall subjective sensation of the level of fatigue on self-reported questionnaires while performance fatigability depends on a more objective approach that measures declines in the performance of the involved muscles during defined activities (Loy et al., 2017; Severijns et al., 2017). Attempts have been made to assess motor fatigability by applying different protocols and outcomes of repeated and sustained muscle contractions in PwMS (Kalron et al., 2011; Severijns et al., 2016; Skurvydas et al., 2011; Steens et al., 2012). However, particular attention has been paid and growing emphasis has been placed on several objective outcome measures during prolonged walking tests, such as the 25-Foot Walk Test (25 WT), the 6-min Walk Test (6 MWT), and the 12-min Walk Test (12 MWT), to monitor all aspects of walking in PwMS that may occur as a consequence of fatigue (Burschka et al., 2012; Cohen et al., 2014; Engelhard et al., 2016; Leone et al., 2016; McLoughlin et al., 2014). A growing body of evidence indicates that PwMS exhibit significant walking-related deficits as reflected by lower mean walking speed and total distance covered compared to healthy controls (Burschka et al., 2012; Leone et al., 2016). Hence, examining dynamic walking patterns and identifying walking limitations in PwMS are crucial components to provide a complete picture of patients' global wellbeing.

Due to the apparent significance of the construct of fatigability, further exploration of methods to quantify fatigability in MS seems warranted. While the traditional methods of measuring fatigue using self-reported questionnaires remain an important outcome measure, using fatigue-inducing tasks during sustained or repeated contractions may reflect the functional status of PwMS. Specifically, a 10-min walk test (10 MWT) has been proposed by Schnelle et al. to independently measure the severity of fatigability (Schnelle et al., 2012). The 10 MWT quantifies perceived fatigability by computing a subject's rated change in tiredness over the distance walked in meters and performance fatigability by calculating the ratio of change in walking speed over the total distance at a self-selected pace. This test is preferred over the other walking performance tests due to its unique and perhaps more sensitive information that fully captures the subjective and objective measures of a walking task that mimics the functional task requirements of normal daily living and does not depend exclusively on subjective self-report ratings.

To date, no published studies quantify fatigability severity measures using the standardized 10 MWT in the MS population. Therefore, greater knowledge of fatigability from this study would provide important clinically meaningful information for patient assessment and inspire more rigorous designs and implementations of exercise training interventions to increase the physical activity of PwMS. The objective of this study was, therefore, to compare fatigability severity measures using the 10 MWT for ambulatory PwMS against healthy controls (HCs). It was hypothesized that the MS group would demonstrate greater perceived fatigability and performance fatigability from the 10 MWT from age- and gender-matched healthy control subjects.