Is Aerobic or Resistance Training the Most Effective Exercise Modality for Improving Lower Extremity Physical Function and Perceived Fatigue in People With Multiple Sclerosis? A Systematic Review and Meta-analysis.

OBJECTIVE: The purpose of this systematic review was to investigate whether aerobic training (AT) or resistance training (RT) is most effective in terms of improving lower limb physical function and perceived fatigue in persons with multiple sclerosis (PwMS). DATA SOURCES: Nine databases (MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health, Allied and Complementary Medicine Database, Physiotherapy Evidence Database, SPORTDiscus, PsycINFO, Web of Science, and Scopus) were electronically searched in April 2020. STUDY SELECTION: Included studies were randomized controlled trials (RCTs) involving PwMS attending 1 of 2 exercise interventions: AT or RT. Studies had to include at least 1 objective or self-reported outcome of lower extremity physical function and/or perceived fatigue. DATA EXTRACTION: Data were extracted using a customized spreadsheet, which included detailed information on patient characteristics, interventions, and outcomes. The methodological quality of the included studies was independently assessed by 2 reviewers using the Tool for Assessment of Study Quality for Reporting on Exercise rating scale. DATA SYNTHESIS: Twenty-seven articles reporting data from 22 RCTS (AT=14, RT=8) including 966 PwMS. The 2 modalities were found to be equally effective in terms of improving short walk test (AT: effect size [ES]=0.33 [95% confidence interval (CI), -1.49 to 2.06]; RT: ES=0.27 [95% CI, 0.07-0.47]) and long walk test performance (AT: ES=0.37 [95% CI, -0.04 to 0.78]; RT: ES=0.36 [95% CI, -0.35 to 1.08]), as well as in reducing perceived fatigue (AT: ES=-0.61 [95% CI, -1.10 to -0.11]; RT: ES=-0.41 [95% CI, -0.80 to -0.02]). Findings on other functional mobility tests along with self-reported walking performance were sparse and inconclusive. CONCLUSIONS: AT and RT appear equally highly effective in terms of improving lower extremity physical function and perceived fatigue in PwMS. Clinicians can thus use either modality to target impairments in these outcomes. In a future perspective, head-to-head exercise modality studies are warranted. Future MS exercise studies are further encouraged to adapt a consensus "core battery" of physical function tests to facilitate a detailed comparison of results across modalities.

Study protocol: effects of exercise booster sessions on preservation of exercise-induced adaptations in persons with multiple sclerosis, a multicentre randomised controlled trial-the MS BOOSTER trial.

INTRODUCTION: Multiple sclerosis (MS) causes a broad range of symptoms, with physical function being one of the most disabling consequences according to patients themselves. Exercise effectively improves lower extremity physical function. Nonetheless, it is unknown which exercise modality is most effective and it remains challenging to keep persons with MS adhering to exercise over a longer period. Therefore, the present study aims to investigate how exercise booster sessions (EBS) influence the sustainability of exercise-induced effects on physical function, and furthermore, to investigate which exercise modality (aerobic training or resistance training) is most effective in terms of improving physical function. MATERIALS AND METHODS: This study is a multi-arm, parallel-group, open-label multicentre randomised controlled trial investigating the effects of EBS. Participants (n=150) are initially randomised to 12 weeks of either resistance training+usual care, aerobic training+usual care or usual care. After 12 weeks of intervention, participants in the exercise groups will again be randomised to either EBS+usual care or usual care during a 40-week follow-up period. The primary outcome is physical function (composite score based on 6-min walk test and five-time sit to stand), and the secondary outcomes are fatigue, cognition, physical activity, symptoms of depression and quality of life. ETHICS AND DISSEMINATION: The study is approved by the Central Denmark Region Committees on Health Research Ethics (1-10-72-237-21) and is registered at the Danish Data Protection Agency (2016-051-000001) and at Clinicaltrials.gov (NCT04913012). All study findings will be published in scientific peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04913012.

Neuromuscular rate of force development discriminates fallers in ambulatory persons with multiple sclerosis - an exploratory study.

BACKGROUND: Falls as well as fall-related injuries (e.g., bone fractures) are common in persons with multiple sclerosis (pwMS). Whilst some studies have identified lower extremity maximal muscle strength (Fmax) as one among several risk factors, no previous studies have investigated the association between rate of force development (RFD; ability to generate a rapid rise in muscle force) and falls in pwMS. Not only is RFD substantially compromised (and more so than Fmax) in pwMS, studies involving other neurodegenerative populations have shown that RFD - to a greater extent than Fmax - is crucial for counteracting unexpected perturbations and avoiding falling. OBJECTIVE: To explore whether knee extensor RFD (and Fmax) can discriminate fallers from non-fallers in pwMS. METHODS: Knee extensor neuromuscular function (comprising RFD50ms and RFD200ms (force developed in the interval 0-50 ms and 0-200 ms, respectively) as well as Fmax) of the weaker leg was assessed by isokinetic dynamometry. Falls were determined by 1-year patient recall, with pwMS subsequently being classified as non-fallers (0 falls), fallers (1-2 falls), or recurrent fallers (≥3 falls). RESULTS: A total of n=53 pwMS were enrolled in the study, with n=24 classified as non-fallers (63% females, 48 years, EDSS 2.2), n=16 as fallers (88% females, 57 years, EDSS 3.3), and n=13 as recurrent fallers (46% females, 60 years, EDSS 4.2). Compared with non-fallers, neuromuscular function was reduced in both fallers (RFD50 -4.42 [-7.47;-1.37] Nm.s-1.kg-1, -48%; RFD200 -1.45 [-2.98;0.07] Nm.s-1.kg-1, -24%; Fmax -0.42 [-0.81;-0.03] Nm.kg-1, -21%) and recurrent fallers (RFD50 -5.69 [-8.94;-2.43] Nm.s-1.kg-1, -62%; RFD200 -2.26 [-3.89;-0.63] Nm.s-1.kg-1, -38%; Fmax -0.38 [-0.80;0.03] Nm.kg-1, -19%). Across all participants, associations were observed between RFD50ms and falls (rs = -0.46 [-0.67;-0.24], between RFD200ms and falls (rs = -0.34 [-0.59;-0.09]), and between Fmax and falls (rs = -0.24 [-0.48;0.01]). CONCLUSION: In this exploratory study, knee extensor neuromuscular function was able to discriminate fallers from non-fallers in pwMS, with RFD being superior to Fmax. Routine assessment of lower extremity neuromuscular function (RFD50ms in particular) may be a helpful tool in identifying pwMS at future risk of falling.

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.

A Head-to-Head Comparison of an Isometric and a Concentric Fatigability Protocol and the Association With Fatigue and Walking in Persons With Multiple Sclerosis.

Background. Fatigue is one of the most frequent symptoms in persons with multiple sclerosis (MS). Distinction is made between subjective perceptions of fatigue and objective measures of fatigability. Fatigability can be measured by different protocols. Yet no studies have compared isometric and concentric contraction protocols of the lower extremities head-to-head. Therefore, the purpose of the present study was to (1) compare 2 such protocols head-to-head and (2) to investigate the association between fatigability evoked by the 2 protocols and measures of fatigue and walking. Methods. A total of 45 patients with MS had their walking capacity measured objectively by the 6-minute walk test (6MWT) and subjectively by the 12-item Multiple Sclerosis Walking Scale (MSWS-12). Fatigue was measured by the Modified Fatigue Impact Scale (MFIS) and fatigability by 2 knee extension protocols: sustained isometric and concentric. Results. The sustained isometric protocol induced a higher degree of fatigability than the concentric protocol (P < .01). Regression analyses revealed that sustained isometric fatigability was not associated with either measures of fatigue or walking (all r2 = 0.00; P = .85-.99), whereas the concentric protocol was significantly associated with fatigue (r2 = 0.20; P < .01), 6MWT (r2 = 0.09; P < .05), and MSWS-12 (r2 = 0.16; P < .01). Furthermore, after adjusting for maximal strength and sex, concentric fatigability remained a strong and significant predictor of fatigue (ß = 0.49) and walking (6MWT: ß = -0.26; MSWS: ß = 0.37). Conclusion. This study provides the first evidence that a lower-extremity concentric fatigability protocol provides superior reflection of both fatigue and walking when compared with a sustained isometric protocol. We suggest that concentric protocols should be the focus of future studies investigating fatigability.