Effects of power training in older patients with multiple sclerosis on neurodegeneration, neuromuscular function, and physical function. A study protocol for the "power training in older multiple sclerosis patients (PoTOMS) randomized control trial.

Introduction: Approximately one-third of all persons with multiple sclerosis (pwMS) are older, i.e., having an age ≥60 years. Whilst ageing and MS separately elicit deteriorating effects on brain morphology, neuromuscular function, and physical function, the combination of ageing and MS may pose a particular challenge. To counteract such detrimental changes, power training (i.e., a type of resistance exercise focusing on moderate-to-high loading at maximal intended movement velocity) presents itself as a viable and highly effective solution. Power training is known to positively impact physical function, neuromuscular function, as well as brain morphology. Existing evidence is promising but limited to young and middle-aged pwMS, with the effects of power training remaining to be elucidated in older pwMS. Methods: The presented 'Power Training in Older MS patients (PoTOMS)' trial is a national, multi-center, parallel-group, randomized controlled trial. The trial compares 24 weeks of usual care(n = 30) to 24 weeks of usual care and power training (n = 30). The primary outcome is whole brain atrophy rate. The secondary outcomes include changes in brain micro and macro structures, neuromuscular function, physical function, cognitive function, bone health, and patient-reported outcomes. Ethics and dissemination: The presented study is approved by The Regional Ethics Committee (reference number 1-10-72-222-20) and registered at the Danish Data Protection Agency (reference number 2016-051-000001). All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences independent of the results. The www.clinicaltrials.gov identifier is NCT04762342.

Effects of walking interventions in persons with multiple sclerosis-A systematic review.

OBJECTIVE: The aim of the present systematic review was to investigate the effects of voluntary walking interventions in persons with multiple sclerosis (pwMS). For this purpose, we developed a framework to describe the components of walking interventions. DATA SOURCES: Two databases (MEDLINE/PubMed and EMBASE) were searched in January 2023. STUDY SELECTION: Included studies enrolled pwMS and evaluated walking interventions with a duration of 2 weeks or longer. Further, they evaluated at least one walking-related outcome. Both RCTs and non-controlled studies were enrolled. DATA EXTRACTION: Data were extracted using a customized spreadsheet, which included detailed information on patient characteristics, interventions, outcomes, and results. Based on the extracted results, the effect sizes (ES, Hedge's g) of the walking interventions were calculated if possible. The methodological quality of the included studies and their reporting was determined using the TESTEX evaluation tool. DATA SYNTHESIS: Data from a total of n = 200 pwMS was included from N = 7 RCT´s (from 3 we used within-group data) and N = 5 single-group studies. On average 91.7 ± 9.9 % of the planned walking sessions were attended, 8.7 ± 10.5 % of the participants dropped out, and very few adverse events occurred. Walking interventions improved walking performance during short distance walk tests (ES ranging from -0.21 to -0.72, "walking time") and long distance walk tests (ES ranging from 0.27 to 0.72, "walking distance"). CONCLUSIONS: Voluntary walking interventions appear to be safe and effective at improving walking performance in pwMS. However, well-powered walking intervention studies are needed to confirm these promising effects. The simplicity of walking interventions makes them highly relevant for ambulatory pwMS.

The role of sensory systems in the association between balance and walking in people with multiple sclerosis.

BACKGROUND: In Multiple Sclerosis, it has been demonstrated that balance is related to performances in walking tasks at different levels of complexity. However, it is unknown how the different sensory systems involved in balance control contribute to walking. This observational study investigates the associations between somatosensory, vestibular, and visual systems and measures of self-reported walking and walking capacity at different complexity levels (i.e. low, medium, and high). METHODS: People with MS with EDSS<6 were assessed through the Sensory Organization Test (SOT), 12-Item MS Walking Scale (MSWS-12), Timed 25-Foot Walk (T25FW), Timed Up-and-Go Test (TUG), and Six-Spot-Step-Test (SSST). T25FW, TUG and SSST are measures of low, medium and high walking capacity, respectively. RESULTS: Forty-five PwMS were enrolled (EDSS: 3.4 ± 1.3). Capacity/ability walking measures were moderate-to-highly significantly associated (p < 0.01). Balance measures from SOT showed significant correlation (p < 0.05) between vestibular system and all the walking measures; between visual system and T25FW, SSST and MSWS-12; between the degree to which the patient relies on the visual system to maintain balance with conflicting visual surroundings information (VIS PREF) and T25FW and TUG. In the multivariate analyses, only VIS PREF significantly correlated (p < 0.05) with T25FW (std. Beta=0.42) and TUG (std. Beta=0.38). CONCLUSIONS: Vestibular and visual systems are associated with walking capacity. However, tasks with higher complexity levels require more visual attention towards ground obstacles, as often seen in real-life activities, whereas simpler walking tasks seem to require visual attention towards the surroundings.

Cardiorespiratory fitness (V̇O2peak) across the adult lifespan in persons with multiple sclerosis and matched healthy controls.

OBJECTIVES: Cardiorespiratory fitness (measured as peak oxygen uptake; V̇O2peak) is a well-established health predictor in the general population and in persons with multiple sclerosis (pwMS). We aimed to investigate differences in V̇O2peak between age groups and the prevalence of V̇O2peak impairments across the adult lifespan in pwMS compared to age- and sex-matched healthy controls (HC). DESIGN: Cross-sectional study. METHODS: Data from 469 pwMS (EDSS range 1.0-7.0), who carried out graded cardiopulmonary exercise testing during their rehabilitation stay at the Valens clinic from 07/2010 to 10/2022, were retrospectively analyzed. Data from 21,063 HC were extracted from previously published studies containing normative reference values. RESULTS: With advanced age (i.e., across age groups), a continuous deterioration of V̇O2peak was observed in both pwMS and HC. Within all age groups, V̇O2peak was reduced in pwMS compared to HC with deficits ranging from 29 % to 40 % for females (p < .05), and from 30 % to 41 % for males (p < .05). However, no age ∗ group interaction was observed in neither males (p = .626) nor females (p = .557). With V̇O2peak impairments defined as values below the 5th percentile of HC, a high prevalence was observed in pwMS, with values ranging from 48 % to 100 % across age groups. CONCLUSIONS: The present data provide evidence for a parallel deterioration of V̇O2peak in pwMS and matched controls with advancing age, coinciding with a high prevalence of impairments in V̇O2peak already present in young adulthood in pwMS. Understanding the extent of impairments as well as the age trajectories of cardiorespiratory fitness in pwMS is crucial for designing optimal rehabilitative and preventive interventions.

The six spot step test is superior in detecting walking capacity impairments compared to short- and long-distance walk tests in persons with multiple sclerosis.

Background: Walking capacity is important not only to persons with multiple sclerosis but also to clinical practice and research. The present study aims to compare the extent of impairments (relative to healthy controls) across three commonly used walking capacity outcomes in persons with multiple sclerosis. Methods: In a two-hospital cross-sectional study, walking capacity was assessed using the timed-25-footwalk-test (timed 25-ft walk test; 'walking speed'), the six-minute-walk-test ('walking endurance') and the six-spot-step-test ('walking balance and coordination'). Data were compared to normative reference data in healthy controls. Results: A total of 228 persons with multiple sclerosis (68% females) were involved in the study: age 53.7 ± 11.6 y (range 26-81 y); patient-determined-disease-steps 3 [IQR; 1; 4] (range 0-7); time since diagnosis 12.6 ± 9.9 y (range 0-49 y); MS-phenotype (relapse remitting MS, secondary progressive MS, primary progressive MS) 146/39/41; and co-morbidity n = 80 (35%). Compared to healthy controls, deficits were observed across all walking capacity outcomes (p < 0.001): timed 25-foot walk test -26 [-30; -23]%, 6 minute-walk-test -36 [-39; -32]% and six-spot-step-test -44 [-47; -40]%. Deficits differed across walking capacity outcomes (p < 0.001). Conclusion: Altogether, persons with multiple sclerosis performed substantially worse than healthy controls across all three walking capacity outcomes. The results showed that the six-spot-step-test was superior to the timed 25-foot walk test and the 6 minute-walk-test in detecting walking capacity impairments in persons with multiple sclerosis.

The effect of low-frequency fatigue on the torque-velocity relationship in human quadriceps.

Low-frequency fatigue (LFF) is usually defined as the decline in low:high-frequency force of electrically evoked isometric muscle contractions. The influence of LFF on dynamic muscle function is not well studied. Our aim was to assess the effect of LFF on the electrically evoked torque-velocity relationship in humans. Sixteen participants underwent a series of electrically evoked knee extensions in an isokinetic dynamometer to establish torque-velocity relationships at 15 and 50 Hz using isokinetic contractions. Hereafter, fatigue was induced by five sets of 10 repetitions of maximal voluntary dynamic knee extensions. After 30 min of rest, torque-velocity tests were repeated. Maximal torque (Fmax) was measured, whereas maximal contraction velocity (Vmax) and maximal power (Pmax) were estimated using Hill's force-velocity equation, 15:50 Hz ratios were calculated for Fmax, Vmax, and Pmax as markers of LFF. Fmax decreased by 40% at 15 Hz (P = 0.001) and by 15% at 50 Hz (P = 0.001) in the fatigued state. No significant change was detected for Vmax at 15 Hz [-2%, (P = 0.349)] or 50 Hz [+3% (P = 0.763)], whereas 15 and 50 Hz Pmax decreased by 30% (P = 0.004) and 10% (P = 0.008), respectively. Following the fatigue protocol, the 15:50 Hz Fmax ratio decreased by 31% (P < 0.001), indicating LFF. The 15:50 Hz Pmax ratio also decreased by 23% (P = 0.002), whereas the 15:50 Hz Vmax ratio was unchanged (P = 0.313). In conclusion, fatiguing contractions decreased Fmax and Pmax at both high and low stimulation frequencies, whereas Vmax appeared unaffected. Nevertheless, LFF influences power production during human dynamic contractions at a range of submaximal velocities.NEW & NOTEWORTHY Force-velocity relationships were established using either low- or high-frequency electrical stimulation before and after fatiguing voluntary eccentric/concentric contractions of the knee extensors. Low-frequency fatigue was assessed by the relative decrease in low- and high-frequency maximal torque, maximal shortening velocity, and maximal power estimated by the force-velocity relationship. Low-frequency fatigue manifests itself as a large decrease in low-frequency maximal force and power with a modest decrease in high-frequency maximal force and power. Contraction velocity does not seem to decrease in the same manner.

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.

The MoxFo initiative-Mechanisms of action: Biomarkers in multiple sclerosis exercise studies.

BACKGROUND: As exercise exerts neurobiological and immunomodulatory effects, it might also act as a disease-modifying intervention in MS. However, a clear mechanistic link between exercise and disease-modifying effects in MS has yet to be established. OBJECTIVE: Establish recommendations for future mechanistic exercise studies in MS. METHODS: In regular meetings, members of the mechanisms of action group within the MoXFo (Moving eXercise research Forward in MS) initiative evaluated gaps of knowledge and discussed unmet needs in mechanistic MS research. RESULTS: We concluded that biomarkers assessed in translational studies in humans and animals are essential to decipher the underlying mechanisms of exercise in MS. Consequently, we defined clear definitions of different types of biomarkers examined in MS exercise studies and operationalized their use to align with the research question and optimal testing time points. Furthermore, we provide key considerations to improve the rigor of translational studies and defined minimal reporting criteria for animal studies. CONCLUSION: The resulting recommendations are intended to improve the quality of future mechanistic exercise studies in MS and consequently lead to a better understanding of therapeutic approaches.

Applicability of the Load-Velocity Relationship to Predict 1-Repetition Maximum in the Half-Squat in High-Level Sprinters.

PURPOSE: To investigate the indirect measurement of 1-repetition-maximum (1RM) free-weight half-squat in high-level sprinters using the load-velocity relationship. METHODS: Half-squat load and velocity data from 11 elite sprinters were collected in 2 separate testing sessions. Approximately 24 hours prior to the first testing session, sprinters completed a fatiguing high-intensity training session consisting of running intervals, staircase exercises, and body-weight exercises. Prior to the second testing session, sprinters had rested at least 48 hours. Two different prediction models (multiple-point method, 2-point method) were used to estimate 1RM based on the load and either mean or peak concentric velocity data of submaximal lifts (40%-90% 1RM). The criterion validity of all methods was examined through intraclass correlation coefficients, coefficient of variation (CV%), Bland-Altman plots, and the SEM. RESULTS: None of the estimations were significantly different from the actual 1RM. The multiple-point method showed higher intraclass correlation coefficients (.91 to .97), with CVs from 3.6% to 11.7% and SEMs from 5.4% to 10.6%. The 2-point method showed slightly lower intraclass correlation coefficients (.76 to .95), with CVs 1.4% to 17.5% and SEMs from 9.8% to 26.1%. Bland-Altman plots revealed a mean random bias in estimation of 1RM for both methods (mean and peak velocity) ranging from 1.06 to 13.79 kg. CONCLUSION: Velocity-based methods can be used to roughly estimate 1RM in elite sprinters in the rested and fatigued conditions. However, all methods showed variations that limit their applicability for accurate load prescription for individual athletes.

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.

Exploring the peripheral mechanisms of lower limb immobilisation on muscle function using novel electrophysiological methods.

OBJECTIVE: To explore the effects of short-term immobilisation and subsequent retraining on peripheral nervous system (PNS) measures using two novel electrophysiological methods, muscle velocity recovery cycles (MVRC) and MScanFit motor unit number estimation (MUNE) alongside lower limb muscle strength, muscle imaging and walking capacity. METHODS: Twelve healthy participants underwent 1-week of ankle immobilisation and 2-weeks of retraining. Assessments before and after immobilisation, and after retraining, included MVRC [muscle membrane properties; muscle relative refractory period (MRRP), early and late supernormality], MScanFit, MRI-scans [muscle contractile cross-sectional area (cCSA)], isokinetic dynamometry [dorsal and plantar flexor muscle strength], and 2-minute maximal walk test [physical function]. RESULTS: After immobilisation, compound muscle action potential (CMAP) amplitude reduced (-1.35[-2.00;-0.69]mV); mean change [95%CI]) alongside reductions in plantar (but not dorsal) flexor muscle cCSA (-124[-246;3]mm2), dorsal flexor muscle strength (isometric -0.06[-0.10;-0.02]Nm/kg, dynamicslow -0.08[-0.11;-0.04]Nm/kg, dynamicfast no changes), plantar flexor muscle strength (isometric -0.20[-0.30;-0.10]Nm/kg, dynamicslow -0.19[-0.28;-0.09]Nm/kg, dynamicfast -0.12[-0.19;-0.05]Nm/kg) and walking capacity (-31[-39;-23]m). After retraining, all immobilisation-affected parameters returned to baseline levels. In contrast, neither MScanFit nor MVRC were affected apart from slightly prolonged MRRP in gastrocnemius. CONCLUSIONS: PNS do not contribute to the changes observed in muscle strength and walking capacity. SIGNIFICANCE: Further studies should include both corticospinal and peripheral mechanisms.

Exercise Therapy in Early Multiple Sclerosis Improves Physical Function But Not Cognition: Secondary Analyses From a Randomized Controlled Trial.

BACKGROUND: Exercise positively affects multiple sclerosis (MS) symptoms, physiological systems, and potentially cognition. However, an uninvestigated "window of opportunity" exists for exercise therapy early in the disease. OBJECTIVE: This study presents secondary analyses from the Early Multiple Sclerosis Exercise Study, and aims to investigate the efficacy of exercise on physical function, cognition, and patient-reported measures of disease and fatigue impact early in the disease course of MS. METHODS: This randomized controlled trial (n = 84, time since diagnosis <2 years) included 48 weeks of aerobic exercise or an active control condition (health education) and between-group changes are based on repeated measurement mixed regression models. Physical function tests included measures of aerobic fitness, walking (6-minute walk, Timed 25-foot walk, Six-spot step test), and upper-limb dexterity. Tests of processing speed and memory evaluated cognition. The questionnaires Multiple Sclerosis Impact Scale and Modified Fatigue Impact Scale assessed perception of disease and fatigue impact. RESULTS: Following early exercise aerobic fitness showed superior between-group physiological adaptations (4.0 [1.7; 6.3] ml O2/min/kg; large effect size [ES = 0.90]). No other outcomes showed significant between-group differences, yet all measures of walking and upper-limb function showed small-to-medium effect sizes in favor of exercise (ES = 0.19-0.58). Overall disability status as well as cognition were unaffected by exercise, whereas perception of disease and fatigue impact were reduced in both groups. CONCLUSION: In early MS, 48 weeks of supervised aerobic exercise seem to positively modify physical function, but not cognitive function. Perception of disease and fatigue impact may be modifiable by exercise in early MS. TRIAL REGISTRATION: Clinicaltrials.gov (identifier: NCT03322761).

Aerobic capacity in persons with Parkinson's disease: a systematic review.

PURPOSE: To systematically review studies assessing (1) psychometric properties of the maximal oxygen uptake (VO2max) test in PD, (2) VO2max levels in persons with PD (pwPD) compared to healthy controls (HCs), and (3) reported VO2max associations in PD. MATERIALS AND METHODS: Six databases were searched. Descriptive data synthesis was used to summarize psychometric properties and reported VO2max associations. The VO2max means and test end-criteria were calculated using linear mixed models. Simple linear regression was used for associations. RESULTS: The review included 25 studies. Psychometric properties of the VO2max test, reported in one study, showed intraclass correlations of 0.90-0.94 for VO2max. Thirteen studies reported test end-criteria, with only mean respiratory exchange ratio (on medication) and percentage of predicted maximal heart rate (off medication) fulfilling standardized minimum values for the VO2max test. The VO2max was comparable between pwPD and HC as well as between different PD-medication states. Associations between VO2max and age, sex, and fatigue were reported. CONCLUSIONS: In mildly to moderately affected pwPD, limited evidence exists on the psychometric properties of the VO2max test and end-criteria were sparsely reported. Surprisingly, VO2max was comparable between pwPD and HC as well as between different PD-medication states, and only age, sex, and fatigue were associated with VO2max. Implications for rehabilitationIn mildly to moderately affected persons with PD (pwPD), only one study has examined psychometric properties of the VO2max test, reporting excellent test-retest reliability.A general lack of consistency on how to measure and report VO2max end-criteria was observed, but when reported, the end-criteria were most often not met.No difference was found in VO2max between mildly to moderately affected pwPD and HC, or between pwPD across different medication states.The identified negative association between VO2max and fatigue suggests aerobic exercise as a potential symptomatic treatment of fatigue when rehabilitation professionals are treating pwPD.

Torque and Discomfort During Electrically Evoked Muscle Contractions in Healthy Young Adults: Influence of Stimulation Current and Pulse Frequency.

OBJECTIVE: To investigate (1) how current and pulse frequency of electrical stimulation (ES) as well as contraction mode (isometric, concentric, and eccentric) influence torque output and discomfort and (2) how familiarization by repeated ES sessions influences ratings of perceived discomfort. DESIGN: An experimental study, 3 sessions. SETTING: A university laboratory. PARTICIPANTS: Eight healthy participants (5 men, 3 women; mean age 25.2 years; N=8). INTERVENTIONS: Participants completed 3 trial days, each including 17 electrically evoked thigh muscle contractions. On each trial day, the first 6 contractions consisted of 2 isometric, 2 concentric, and 2 eccentric muscle contractions randomly ordered with a fixed stimulation current and pulse frequency (200 mA, 20 Hz), while the remaining 11 muscle contractions were all isometric with randomly ordered combinations of current (100-250 mA) and pulse frequency (20-100 Hz). MAIN OUTCOME MEASURES: Torque and perceived discomfort were measured for each ES-evoked contraction. RESULTS: Overall, the findings revealed that a higher stimulation frequency was associated with an increased torque without increased discomfort, while higher currents were associated with increases of both torque and discomfort. Contraction type did not influence level of discomfort, despite eccentric contractions eliciting higher torque compared with concentric and isometric contractions (P<.001). Finally, a significant familiarization to ES (P<.001) was observed after just 1 of 3 identical stimulation sessions. CONCLUSIONS: The outlined data suggest that to elicit high torque levels while minimizing levels of discomfort in young subjects, eccentric muscle contractions evoked with a low stimulation current, and a high pulse frequency are preferable. Furthermore, a single familiarization session significantly lowers rating of perceived discomfort during ES.

Effects of age on muscle power, postural control and functional capacity after short-term immobilization and retraining.

OBJECTIVES: This study investigated the effect of lower limb immobilization and retraining on postural control and muscle power in healthy old and young men. METHODS: Twenty men, nine old (OM:67.3±4.4 years) and eleven young (YM:24.4±1.6 years) underwent 2 weeks of unilateral whole-leg casting, followed by 4 weeks of retraining. Measures included center of pressure (CoP) sway length and area during single- and double-leg stance, maximal leg extensor muscle power, habitual and maximal 10-m gait speed, sit-to-stand performance, and 2-min step test. RESULTS: After immobilization, leg extension muscle power decreased by 15% in OM (from 2.68±0.60 to 2.29±0.63 W/kg, p<0.05) and 17% in YM (4.37±0.76 to 3.63±0.69 W/kg, p<0.05). Double-leg CoP sway area increased by 45% in OM (218±82 to 317±145 mm2; p<0.05), with no change in YM (p=0.43). Physical function did not change after immobilization but sit-to-stand performance (+20%, p<0.05) and 2-min step test (+28%, p<0.05) increased in OM following retraining. In both groups, all parameters returned to baseline levels after retraining. CONCLUSION: Two weeks of lower limb immobilization led to decreases in maximal muscle power in both young and old, whereas postural control was impaired selectively in old men. All parameters were restored in both groups after 4 weeks of resistance-based retraining.

The importance of neuromuscular rate of force development for physical function in aging and common neurodegenerative disorders - a systematic review.

We systematically reviewed existing literature regarding lower extremity neuromuscular rate of force development (RFD), maximal muscle strength (Fmax), and physical function in neurodegenerative populations, and to what extent these outcomes are affected and/or associated. Following PRISMA guidelines, 4 databases (Pubmed, Embase, SPORTDiscus, Web of Science) were searched. Across aging, Parkinson Disease (PD), Alzheimer's Disease (AD), Multiple Sclerosis (MS), or Stroke, included studies should report (Part 1) deficits in lower extremity RFD, Fmax, and physical function (~ individuals having inferior vs. superior physical function), and/or (Part 2) associations between RFD (or Fmax) and physical function. A total of N=32 studies (n=1087 participants) were included. Part 1: deficits in RFD (-31%, mean; N=22) were comparable to deficits in physical function (-26%; N=7), yet both deficits exceeded that of Fmax (-21%; N=20). Part 2: associations between RFD and physical function (r2=0.13, mean; N=16) were comparable to associations between Fmax and physical function ((r2=0.15; N=12). Lower extremity RFD is (1) particularly sensitive (i.e. adapts earlier and/or more extensively) towards neurodegeneration, and more so than Fmax, and (2) of importance for physical function but apparently not superior to Fmax. RFD could serve as a useful indicator/biomarker of changes in neuromuscular function elicited by neurodegeneration.

Participant characteristics of existing exercise studies in persons with multiple sclerosis - A systematic review identifying literature gaps.

BACKGROUND: Exercise is a cornerstone in rehabilitation of persons with multiple sclerosis (pwMS), which is known to elicit beneficial effects on various symptoms and to have a potential disease-modifying effect. However, it remains to be elucidated if the existing MS exercise literature covers the full age and disability span of pwMS. OBJECTIVE: To systematically review MS exercise studies and provide a detailed mapping of the demographic and clinical characteristics of the included pwMS. METHODS: A systematic review of MS exercise studies were performed using MEDLINE and EMBASE. From the resulting MS exercise studies, mean sample characteristics were extracted. RESULTS: 4576 records were identified, from which 202 studies were included. Of these, 166 studies (82.2%) enrolled pwMS aged 35-54 years, 10.9% enrolled pwMS <35 years, and 6.9% enrolled pwMS ≥55 years (only 1.5% enrolled pwMS ≥60 years). A total of 118 studies (58.4%) reported Expanded Disability Status Scale (EDSS), with 88.1% of included pwMS having an EDSS between 2.0 and 6.5, while only one study enrolled pwMS with an EDSS ≥7.0. Finally, 80% of the studies included pwMS having a disease duration of 5-14.5 years. CONCLUSION: Exercise studies in pwMS included primarily middle-aged (35-54 years) pwMS having an EDSS of 2.0-6.5 and a disease duration of 5-14.5 years. Few exercise studies were identified in young and older pwMS, in pwMS with mild disability and severe disability, and in pwMS having shorter or longer disease durations. These findings highlight the need for further investigation of exercise in these specific subgroups of pwMS as benefits of exercise might not generalize across subpopulations.

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.