The combined deleterious effects of multiple sclerosis and ageing on neuromuscular function.

BACKGROUND: The prevalence of older (>60 years) people with multiple sclerosis (pwMS) is increasing. This introduces numerous challenges, as both MS and ageing independently contribute to the deterioration of neuromuscular function. AIM: The aim was to compare the neuromuscular function in pwMS and healthy controls (HC) across three age groups: young, middle-aged, and old. METHODS: Using a cross-sectional study design, the maximal muscle strength (Fmax) and rate of force development (RFD) of the knee extensors (KE) and plantar flexors (PF) were assessed using an isokinetic dynamometer. In addition, voluntary activation (VA) and resting twitch (RT) were measured using the interpolated twitch technique. RESULTS: The Fmax, RFD, and VA of the KE were reduced in pwMS compared to HC across age groups. In pwMS, reductions were observed in PF Fmax, RFD, and RT, predominantly in the middle-aged and old age groups. Reductions increased with age in KE for both groups (except for VA) but in PF only for pwMS. The "trajectory" differed between pwMS and HC, as pwMS showed reductions from young to middle age, while HC showed reductions from middle to old age in KE. CONCLUSION: The combined negative effects of MS and ageing on neuromuscular function were especially present in the PF but also substantial in the KE. RFD showed large deficits for pwMS compared to HC across age groups. The findings can partly be explained by a reduction in VA and RT, but further investigations of neural regulation are needed to explain large RFD deficits.

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

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: MSmild (EDSS 0-2.5, n=51), MSmoderate (EDSS 3.0-4.5, n=33), and MSsevere (EDSS 5-6.5, n=15). Knee extensor neuromuscular function was assessed by Fmax and RFD (RFD50ms and RFD200ms, respectively; calculated in the interval 0-50 ms and 0-200 ms relative to the onset of contraction) with simultaneous electromyography (maximal EMG (EMGFmax) and rate of EMG rise (rEMG50ms and rEMG200ms, 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; RFD50ms (MSmild -22%, MSmoderate -36%, MSsevere -66%), RFD200ms (-12%, -21%, -51%), and Fmax (-11%, -14%, -33%). Somewhat comparable differences (∼deficits) (p<0.05) were observed for voluntary muscle activation (rEMG50ms, rEMG200ms, EMGFmax, and activation) and for physical function (5STS, T25FWT, and 2MT). Deficits in neuromuscular function were strongly associated with EDSS (p<0.05) (RFD50ms: slope steepness -13% per 1 point increase in EDSS, r2=0.79; RFD200ms: 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). 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.

Physical activity is associated with neuromuscular and physical function in patients with multiple sclerosis independent of disease severity.

PURPOSE: Examine the association between physical activity and neuromuscular and physical function in patients with multiple sclerosis when also considering disease severity. METHODS: 91 patients with multiple sclerosis were enrolled. Assessments included physical activity by 7-day thigh-worn accelerometry, knee extensor neuromuscular function by dynamometry (maximal isometric muscle strength, rate of force development (0-50 ms)), and physical function by 5× sit-to-stand, 2-min walk test, and timed 25 ft walk test. Physical activity tertile comparisons along with simple and multiple regressions (adjusting for age, gender, EDSS, time since diagnosis) were performed. RESULTS: Physical activity tertiles revealed differences (p < 0.05) in maximal muscle strength (1.77 ≈ 1.97 < 2.28 Nm/kg), rate of force development (4.66 < 8.03 ≈ 10.55 Nm/kg/s), 5× sit-to-stand (11.4 ≈ 9.7 > 8.5 s), 2-min walk test (153 < 183 < 207 m), and timed 25 ft walk test (6.3 > 4.4 > 4.3 s). Moreover, physical activity was associated (p < 0.05) with maximal muscle strength and rate of force development (r2 = 0.13-0.15) along with 5× sit-to-stand, 2-min walk test, and timed 25 ft walk test (r2 = 0.18-0.24), also after adjusting for age + gender + EDSS + time since diagnosis (r2 = 0.25-0.37 and 0.24-0.52), with physical activity consistently being a strong predictor. CONCLUSIONS: Higher levels of physical activity are associated with greater neuromuscular and physical function in ambulatory patients with multiple sclerosis independent of disease severity. These findings emphasize the importance of performing regular physical activity at all stages of multiple sclerosis.IMPLICATIONS FOR REHABILITATIONPhysical activity is associated with neuromuscular and physical function, independent of disease severity.Physical activity may be important in improving or preserving neuromuscular and physical function at all stages of ambulatory multiple sclerosis patients, yet longitudinal studies are warranted.Clinicians and rehabilitation professionals should encourage ambulatory patients at all stages of their disease to be as physically active as possible.