TY - JOUR

T1 - Identification of disability status in persons with multiple sclerosis by lower limb neuromuscular function – Emphasis on rate of force development

AU - Taul-Madsen, Laurits

AU - Riemenschneider, Morten

AU - Jørgensen, Marie Louise K.

AU - Dalgas, Ulrik

AU - Hvid, Lars G.

N1 - Publisher Copyright: © 2022 The Author(s)

PY - 2022/11

Y1 - 2022/11

N2 - BACKGROUND: 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).METHODS: 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). RESULTS: 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, r 2=0.79; RFD 200ms: slope steepness -10%, r 2=0.84; Fmax: slope steepness -6%, r 2=0.82). Fmax and RFD were associated with physical function outcome measures (p<0.05) to a comparable extent (r 2-values ranging from 0.21 to 0.35). CONCLUSION: 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.

AB - BACKGROUND: 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).METHODS: 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). RESULTS: 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, r 2=0.79; RFD 200ms: slope steepness -10%, r 2=0.84; Fmax: slope steepness -6%, r 2=0.82). Fmax and RFD were associated with physical function outcome measures (p<0.05) to a comparable extent (r 2-values ranging from 0.21 to 0.35). CONCLUSION: 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.

KW - Explosive muscle strength

KW - Multiple sclerosis

KW - Neuromuscular function

KW - Knee

KW - Multiple Sclerosis/complications

KW - Humans

KW - Muscle Strength/physiology

KW - Electromyography

KW - Muscle, Skeletal

U2 - 10.1016/j.msard.2022.104082

DO - 10.1016/j.msard.2022.104082

M3 - Journal article

C2 - 35933754

AN - SCOPUS:85135510013

VL - 67

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

SN - 2211-0348

M1 - 104082

ER -