A Comprehensive Evaluation of Multiple Sclerosis-Related Fatigue with a Special Focus on Fatigability

Fatigue is the most common and disabling symptom in multiple sclerosis (MS), being reported by 55% to 78% of patients with MS (PwMS). Etiology of MS-related fatigue remains poorly understood, but an increased neuromuscular fatigability (i.e., greater loss of torque during exercise) could contribute to this phenomenon. This study aimed to characterize the correlates of MS-related fatigue in PwMS using a comprehensive group of physiological and psychosocial measures, with a particular focus on fatigability.

Forty-two relapsing-remitting PwMS and 20 healthy subjects were recruited. PwMS were assigned in two groups (high (HF) and low (LF) fatigue) based on two fatigue questionnaires (Fatigue Severity Scale and Modified Fatigue Impact Scale). The main outcomes of this study are derived from incremental cycling completed to task failure (i.e., inability to pedal around 60 rpm). Maximal voluntary contraction (MVC), rating of perceived exertion, and central and peripheral parameters measured using transcranial magnetic and peripheral nerve stimulation were assessed in the knee extensor muscles before, during, and after the fatiguing task. Other potential correlates of fatigue were also tested.

MVC torque decreased to a greater extent for the HF group than LF group after the third common stage of the incremental fatiguing exercise (-15.7% ± 6.6% vs -5.9% ± 13.0%, P < 0.05), and this occurred concurrently with a higher rating of perceived exertion for HF (11.8 ± 2.5 vs 9.3 ± 2.6, P < 0.05). Subjective parameters (depression, quality of life) were worse for HF compared with LF and healthy subjects ( P < 0.001). Moreover, MVC torque loss at the final common stage and maximal heart rate explained 29% of the variance of the Modified Fatigue Impact Scale.

These results provide novel insight into the relationship between MS-related fatigue and fatigability among PwMS. The HF group exhibited greater performance fatigability, likely contributing to a higher perceived exertion than the LF group when measured during a dynamic task.