Fatigued patients with multiple sclerosis have impaired central muscle activation

Abstract
Background The pathogenesis of fatigue in multiple sclerosis (MS) is poorly understood. Objective To elucidate the role of central motor activation we hypothesized that patients with primary fatigue have impaired central motor function and increased fatigability as compared to secondary fatigued and non-fatigued patients. Methods Sixty patients with relapsing remitting MS and an Expanded Disability Status Scale score ≤ 3.5 were recruited and grouped as fatigued (Fatigue Severity Scale (FSS) ≥ 5.0) or non-fatigued (FSS ≤ 4.0). Nineteen patients were primary fatigued, 20 secondary fatigued and 21 non-fatigued. Maximal voluntary contraction, central activation and peripheral activation were determined by percutaneous twitch interpolation of the right quadriceps muscle. Results Maximal voluntary contraction was similar between groups but did relate to scores of fatigue. Peripheral activation was similar in all groups. Central activation was impaired in both groups of fatigued patients compared to non-fatigued patients being 0.96(0.05) in primary fatigued and 0.96(0.04) in secondary fatigued versus 0.99(0.1) in non-fatigued patients. The impairment of central motor activation was related to degree of fatigue in all patients. During fatiguing exercise there was a similar loss of strength, without any time differences between the three groups. Conclusion We conclude that impaired central motor activation is involved in MS-fatigue.