Identification of disability status in persons with multiple sclerosis by lower limb neuromuscular function -...

Neurodegeneration is an inevitable consequence of multiple sclerosis (MS) leading to impaired neuromuscular function, especially of the lower extremities. Whilst maximal muscle strength (or force; Fmax) is the most examined feature of neuromuscular function, the ability to rapidly increase muscle force (= rate of force development; RFD) appear to be preferentially sensitive towards neurodegeneration and potentially also of great importance for physical function. The purpose of the present study was to comprehensively examine and compare different outcome measures of neuromuscular function (with specific emphasis given to RFD) across disability status in persons with MS (pwMS), and in comparison, to age- and sex-matched healthy controls (HC).

A total of n=34 HC and n=99 pwMS were enrolled in the study, with the latter being divided into Expanded Disability Status Scale (EDSS) subgroups: MS_mild (EDSS 0-2.5, n=51), MS_moderate (EDSS 3.0-4.5, n=33), and MS_severe (EDSS 5-6.5, n=15). Knee extensor neuromuscular function was assessed by Fmax and RFD (RFD_50ms and RFD_200ms, respectively; calculated in the interval 0-50 ms and 0-200 ms relative to the onset of contraction) with simultaneous electromyography (maximal EMG (EMG_Fmax) and rate of EMG rise (rEMG_50ms and rEMG_200ms, respectively)). Voluntary muscle activation derived from the interpolated twitch technique was also determined during additional Fmax trials. Lastly, physical function was assessed by the 5 x sit-to-stand test (5STS), the timed 25-foot walk test (T25FWT), and the 2-min walking test (2MWT).

Substantial differences (∼deficits) (p<0.05) were observed for all pwMS subgroups compared to HC across all neuromuscular function outcome measures; RFD_50ms (MS_mild -22%, MS_moderate -36%, MS_severe -66%), RFD_200ms (-12%, -21%, -51%), and Fmax (-11%, -14%, -33%). Somewhat comparable differences (∼deficits) (p<0.05) were observed for voluntary muscle activation (rEMG_50ms, rEMG_200ms, EMG_Fmax, and activation) and for physical function (5STS, T25FWT, and 2MT). Deficits in neuromuscular function were strongly associated with EDSS (p<0.05) (RFD_50ms: slope steepness -13% per 1 point increase in EDSS, r²=0.79; RFD_200ms: slope steepness -10%, r²=0.84; Fmax: slope steepness -6%, r²=0.82). Fmax and RFD were associated with physical function outcome measures (p<0.05) to a comparable extent (r²-values ranging from 0.21 to 0.35).

Lower extremity neuromuscular function is impaired in pwMS compared to HC with differences (∼deficits) becoming greater with increasing disability status. RFD was preferentially sensitive in capturing differences (∼deficits) across disability status and by showing strong associations with EDSS. Altogether, knee extensor RFD could serve as a simple objective marker of disability status or even progression in pwMS, that may be helpful to both researchers and clinicians.