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.

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.

Investigating the potential disease-modifying and neuroprotective efficacy of exercise therapy early in the disease course of multiple sclerosis: The Early Multiple Sclerosis Exercise Study (EMSES).

BACKGROUND: Potential supplemental disease-modifying and neuroprotective treatment strategies are warranted in multiple sclerosis (MS). Exercise is a promising non-pharmacological approach, and an uninvestigated 'window of opportunity' exists early in the disease course. OBJECTIVE: To investigate the effect of early exercise on relapse rate, global brain atrophy and secondary magnetic resonance imaging (MRI) outcomes. METHODS: This randomized controlled trial (n = 84, disease duration <2 years) included 48 weeks of supervised aerobic exercise or control condition. Population-based control data (Danish MS Registry) was included (n = 850, disease duration <2 years). Relapse rates were obtained from medical records, and patients underwent structural and diffusion-kurtosis MRI at baseline, 24 and 48 weeks. RESULTS: No between-group differences were observed for primary outcomes, relapse rate (incidence-rate-ratio exercise relative to control: (0.49 (0.15; 1.66), p = 0.25) and global brain atrophy rate (-0.04 (-0.48; 0.40)%, p = 0.87), or secondary measures of lesion load. Aerobic fitness increased in favour of the exercise group. Microstructural integrity was higher in four of eight a priori defined motor-related tracts and nuclei in the exercise group compared with the control (thalamus, corticospinal tract, globus pallidus, cingulate gyrus) at 48 weeks. CONCLUSION: Early supervised aerobic exercise did not reduce relapse rate or global brain atrophy, but does positively affect the microstructural integrity of important motor-related tracts and nuclei.

Parkinson's disease and intensive exercise therapy - An updated systematic review and meta-analysis.

In 2015, Uhrbrand et al. published the first review on Parkinson´s disease (PD) and exercise entirely based on randomized controlled trials (RCT) applying strict exercise definitions. The present review aimed to update the PD literature by assessing the effects of different intensive exercise modalities: resistance training (RT), endurance training (ET), and other intensive exercise modalities (OITM). An updated systematic literature search identified 33 new RCTs. Qualitative and quantitative analyses were performed. A total of 18 RT, 14 ET, and 1 OITM studies were identified (adding to the 8 RT, 6 ET, and 4 OITM studies identified by Uhrbrand et al. in 2015). RT, ET, and OITM were feasible, safe, and did not worsen PD symptoms. Furthermore, RT, ET, and OITM may positively affect functional outcomes (e.g., balance) and depressive symptoms in PD but inconsistencies across these findings warrant cautious conclusions. Meta-analyses showed that RT had a positive impact on muscle strength (standardized mean difference (SMD) = 0.83 [95% CI;0.54, 1.12]), functional capacity (Timed Up and Go Test (TUG): SMD = -0.62 [-1.01, -0.24]), and quality of life (SMD = -0.41 [-0.72, -0.09]), while ET had a positive impact on cardiorespiratory fitness (SMD = 0.27 [0.07, 0.47]) and functional capacity (TUG: SMD = -0.21 [-0.46, 0.04], 6-Min Walk Test: SMD = 0.89 [0.17, 1.62]), and a potentially positive impact on "on-medication" UPDRS-III (SMD = -0.15 [-0.38, 0.09]) and "off-medication" UPDRS-III (SMD = -0.19 [-0.41, 0.04]). In conclusion, RT, ET, and OITM all represent safe, feasible, and beneficial adjunct rehabilitation strategies in PD, with particularly RT and ET showing solid effects.

Vitamin D supplementation and increased dairy protein intake do not affect muscle strength or physical function in healthy 6-8-year-old children: the D-pro randomized trial.

PURPOSE: To investigate separate and combined effects of vitamin D supplementation during the extended winter and increased dairy protein intake on muscle strength and physical function in children, and furthermore to explore potential sex differences. METHODS: In a 2 × 2-factorial, randomized winter trial, 183 healthy, 6-8-year-old children received blinded tablets with 20 µg/day vitamin D3 or placebo, and substituted 260 g/day dairy with yogurts with high (HP, 10 g protein/100 g) or normal protein content (NP, 3.5 g protein/100 g) for 24 weeks during winter at 55° N. We measured maximal isometric handgrip and leg press strength, and physical function by jump tests and a 30 s sit-to-stand test. Physical activity was measured by 7-day accelerometry. RESULTS: Baseline (mean ± SD) serum 25-hydroxyvitamin D was 80.8 ± 17.2 nmol/L, which increased to 88.7 ± 17.6 nmol/L with vitamin D supplementation and decreased to 48.4 ± 19.2 nmol/L with placebo. Baseline protein intake was 15.5 ± 2.4 E%, which increased to 18.4 ± 3.4 E% with HP and was unchanged with NP. We found no separate or combined effects of vitamin D supplementation and/or increased dairy protein intake on muscle strength or physical function (all P > 0.20). There was an interaction on the sit-to-stand test (Pvitamin×yogurt = 0.02), which however disappeared after adjusting for physical activity (P = 0.16). Further, vitamin D supplementation increased leg press strength relatively more in girls compared to boys (mean [95% CI] 158 [17, 299] N; Pvitamin×sex = 0.047). CONCLUSION: Overall, vitamin D and dairy protein supplementation during the extended winter did not affect muscle strength or physical function in healthy children. Potential sex differences of vitamin D supplementation should be investigated further. REGISTERED AT CLINICALTRIALS.GOV: NCT0395673.

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.

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.

Effects of blood-flow restricted resistance training on mechanical muscle function and thigh lean mass in sIBM patients.

Sporadic inclusion body myositis (sIBM) is an idiopathic inflammatory muscle disease associated with skeletal muscle inflammation and a parallel progressive decline in muscle strength and physical function. Eventually, most sIBM patients require use of wheelchair after about 10 years of diagnosis and assistance to perform activities of daily living. This study presents data from a randomized controlled intervention trial (NCT02317094) that examined the effect of 12 weeks low-load blood-flow restricted (BFR) resistance training on maximal muscle strength, power, rate of force development (RFD), thigh lean mass (TLM), and voluntary muscle activation (VA) in sIBM patients. A time-by-group interaction in knee extensor strength was observed in the stronger leg (p ≤ 0.033) but not the weaker leg. Within-group changes were observed with BFR training (BFR) manifested by increased knee extensor strength in the strongest leg (+13.7%, p = 0.049), whereas non-exercising patients (CON) showed reduced knee extensor strength (-7.7%, p = 0.018). Maximal leg extensor power obtained for the stronger leg remained unchanged following BFR training (+9.5%, p = 0.37) while decreasing in CON (-11.1%, p = 0.05). No changes in TLM were observed. VA declined post-training (p = 0.037) in both BFR (-6.3% points) and CON (-7.5% points). The present data indicate that BFR resistance training can attenuate the rate of decline in mechanical muscle function typically experienced by sIBM patients. The preservation of muscle mass and mechanical muscle function with BFR resistance training may be considered of high clinical importance in sIBM patients to countermeasure the disease-related decline in physical function.

The expression of HSP70 in skeletal muscle is not associated with glycogen availability during recovery following prolonged exercise in elite endurance athletes.

The 70-kDa heat shock protein (HSP70) is a ubiquitous molecular chaperone which is highly inducible by cellular stress such as exercise. To investigate the role of muscle glycogen content on the HSP70 expression, muscle glycogen was manipulated by consumption of either water (H2O) or a carbohydrate-enriched diet (CHO) during recovery from 4 h of glycogen-depleting cycling exercise in fourteen elite endurance athletes. Muscle biopsies were obtained pre- and post-exercise, and after 4 and 24 h of recovery, and analyzed for HSP70 mRNA expression, as well as HSP70 protein expression and muscle glycogen within the same skeletal muscle fibers using immunohistochemistry. Exercise reduced glycogen by 59 ± 10% (P < 0.0001). After 4 h of recovery, glycogen approached resting levels in the CHO group (86% of pre, P = 0.28) but remained suppressed in the H2O group (41% of pre, P < 0.001) (group × time interaction: P = 0.002). Importantly, both the HSP70 mRNA (+ 1.6-fold (+ 0.28/- 0.24), P = 0.02) and protein expression (+ 147 ± 99%, P < 0.0001) was substantially increased after exercise and remained elevated in both groups after 4 h of recovery, despite clear differences in muscle glycogen content. Thus, muscle glycogen content was not related to the variation in single fiber HSP70 expression at the 4-h time-point (r2 = 0.004). In conclusion, muscle HSP70 expression remained elevated during recovery from prolonged exercise in highly trained skeletal muscle, irrespective of muscle glycogen availability.

Effects of Resistance Training Cessation on Cycling Performance in Well-Trained Cyclists: An Exploratory Study.

ABSTRACT: Bláfoss, R, Rikardo, J, Andersen, AØ, Hvid, LG, Andersen, LL, Jensen, K, Christensen, PM, Kvorning, T, and Aagaard, P. Effects of resistance training cessation on cycling performance in well-trained cyclists: an exploratory study. J Strength Cond Res 36(3): 796-804, 2022-Supplementary (i.e., concurrent) resistance training can enhance cycling performance among competitive cyclists. However, a lack of knowledge exists about the retention (decay profile) in mechanical muscle function and cycling performance after concurrent resistance and endurance training. The present exploratory intervention study investigated the effect of 6 weeks of resistance training cessation when preceded by 8 weeks of concurrent resistance and endurance training on mechanical muscle function and cycling performance in 9 male well-trained competitive cyclists (V̇o2max = 66 ± 7 ml·min-1·kg-1). Cyclists performed periodized resistance training targeting leg and core muscles for 8 weeks as a supplement to their normal endurance (cycling) training. This was followed by 6 weeks of endurance training only (retention period) leading up to the start of the competitive season. Maximal leg extensor power, isometric leg extensor strength (maximal voluntary contraction [MVC]), rate of force development (RFD), and long-term cycling performance (2-hour submaximal cycling at 55% of Wmax), followed by 5-minute max cycling were evaluated. After 8 weeks of concurrent resistance and endurance training, leg extensor power, MVC, and RFD increased by 12, 15, and 17%, respectively while mean power output (W) during 5-minute max cycling increased by 7% (p < 0.05). Training-induced gains in MVC and 5-minute max cycling power were retained after 6-week cessation of resistance training (p < 0.05). These findings indicate that competitive cyclists can focus on cycling training alone for at least 6 weeks leading up to competition without losing attained gains in maximal muscle strength and cycling performance achieved by preceding periods of concurrent resistance training.

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.

Associations between objectively measured physical activity, sedentary behaviour and time in bed among 75+ community-dwelling Danish older adults.

BACKGROUND: Older adults are recommended to sleep 7-8 h/day. Time in bed (TIB) differs from sleep duration and includes also the time of lying in bed without sleeping. Long TIB (≥9 h) are associated with self-reported sedentary behavior, but the association between objectively measured physical activity, sedentary behavior and TIB is unknown. METHODS: This study was based on cross-sectional analysis of the Healthy Ageing Network of Competence (HANC Study). Physical activity and sedentary behaviour were measured by a tri-axial accelerometer (ActiGraph) placed on the dominant wrist for 7 days. Sedentary behavior was classified as < 2303 counts per minute (cpm) in vector magnitude and physical activity intensities were categorized, as 2303-4999 and ≥ 5000 cpm in vector magnitude. TIB was recorded in self-reported diaries. Participants were categorized as UTIB (usually having TIB 7-9 h/night: ≥80% of measurement days), STIB (sometimes having TIB 7-9 h/night: 20-79% of measurement days), and RTIB (rarely having TIB 7-9 h/night: < 20% of measurement days). Multinominal regression models were used to calculate the relative risk ratios (RRR) of being RTIB and STIB by daily levels of physical activity and SB, with UTIB as the reference group. The models were adjusted for age, sex, average daily nap length and physical function. RESULTS: Three hundred and fourty-one older adults (median age 81 (IQR 5), 62% women) were included with median TIB of 8 h 21 min (1 h 10 min)/day, physical activity level of 2054 (864) CPM with 64 (15) % of waking hours in sedentary behavior. Those with average CPM within the highest tertile had a lower RRR (0.33 (0.15-0.71), p = 0.005) for being RTIB compared to those within the lowest tertile of average CPM. Accumulating physical activity in intensities 2303-4999 and ≥ 5000 cpm/day did not affect the RRR of being RTIB. RRR of being RTIB among highly sedentary participants (≥10 h/day of sedentary behavior) more than tripled compared to those who were less sedentary (3.21 (1.50-6.88), p = 0.003). CONCLUSIONS: For older adults, being physically active and less sedentary was associated with being in bed for 7-9 h/night for most nights (≥80%). Future longitudinal studies are warranted to explore the causal relationship sbetween physical activity and sleep duration.

Does physical performance and muscle strength predict future personal and nursing care services in community-dwelling older adults aged 75+?

AIM: The objective of this study was to investigate if grip strength or the short physical performance battery could predict the rate of receiving two different types of home care services: (a) personal care and (b) home nursing care for community-dwelling older adults aged 75+ years. METHODS: A secondary data analysis of a prospective cohort study including 323 community-dwelling older adults. Measures of grip strength and the short physical performance battery were incorporated in a nationally regulated preventive home visit programme. Referral to personal and home nursing care were obtained from an administrative database with an average follow-up of 4.1 years. The rate of receiving the individual home care services and the study measures were determined using multivariable Cox proportional hazards models controlling for a priori selected covariates (age, sex, living status, obesity, smoking and prior use of home care). RESULTS: The mean age was 81.7 years with 58.8% being women. The rate of receiving personal care differed between the short physical performance battery groups but not between the grip strength groups after adjusting for all covariates with hazard ratios (95% confidence intervals) of 1.90 (1.29-2.81) and 1.41 (0.95-2.08), respectively. The rate of receiving home nursing care differed between both the short physical performance battery and grip strength groups after adjusting for all covariates with hazard ratios of 2.03 (1.41-2.94) and 1.48 (1.01-2.16), respectively. CONCLUSIONS: The short physical performance battery was associated with the rate of receiving both personal care and home nursing care. The short physical performance battery can be used to predict home care needs of community-dwelling older adults aged 75+ years.

Moving exercise research in multiple sclerosis forward (the MoXFo initiative): Developing consensus statements for research.

Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleotropic effects. There is an exponential increase in the quantity of research on exercise in MS, yet a number of barriers associated with study content and quality hamper rapid progress in the field. To address these barriers and accelerate discovery, a new international partnership of MS-related experts in exercise has emerged with the goal of advancing the research agenda. As a first step, the expert panel met in May 2018 and identified the most urgent areas for moving the field forward, and discussed the framework for such a process. This led to identification of five themes, namely "Definitions and terminology," "Study methodology," "Reporting and outcomes," "Adherence to exercise," and "Mechanisms of action." Based on the identified themes, five expert groups have been formed, that will further (a) outline the challenges per theme and (b) provide recommendations for moving forward. We aim to involve and collaborate with people with MS/MS organizations (e.g. Multiple Sclerosis International Federation (MSIF) and European Multiple Sclerosis Platform (EMSP)) in all of these five themes. The generation of this thematic framework with multi-expert perspectives can bolster the quality and scope of exercise studies in MS that may ultimately improve the daily lives of people with MS.

Neurophysiological impairments in multiple sclerosis-Central and peripheral motor pathways.

A systematic review of the literature was conducted comparing neurophysiological outcomes in persons with multiple sclerosis (PwMS) to healthy controls (HC), in studies of the central nervous system (CNS) function comprising motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) and in studies of the peripheral nervous system (PNS) function comprising electroneuronography (ENG) outcomes elicited by peripheral nerve stimulation. Studies comparing neuromuscular function, assessed during maximal voluntary contraction (MVC) of muscle, were included if they reported muscle strength along with muscle activation by use of electromyography (EMG) and/or interpolated twitch technique (ITT). Studies investigating CNS function showed prolonged central motor conduction times, asymmetry of nerve conduction motor pathways, and prolonged latencies in PwMS when compared to HC. Resting motor threshold, amplitude, and cortical silent periods showed conflicting results. CNS findings generally correlated with disabilities. Studies of PNS function showed near significant prolongation in motor latency of the median nerve, reduced nerve conduction velocities in the tibial and peroneal nerves, and decreased compound muscle action potential amplitudes of the tibial nerve in PwMS. ENG findings did not correlate with clinical severity of disabilities. Studies of neuromuscular function showed lower voluntary muscle activation and increased central fatigue in PwMS, whereas EMG showed divergent muscle activation (ie, EMG amplitude) during MVC. When comparing the existing literature on neurophysiological motor examinations in PwMS and HC, consistent and substantial impairments of CNS function were seen in PwMS, whereas impairments of the PNS were less pronounced and inconsistent. In addition, impairments in muscle activation were observed in PwMS.

Exercise as Medicine in Multiple Sclerosis-Time for a Paradigm Shift: Preventive, Symptomatic, and Disease-Modifying Aspects and Perspectives.

PURPOSE OF REVIEW: For many years, exercise was controversial in multiple sclerosis (MS) and thought to exacerbate symptoms and fatigue. However, having been found to be safe and effective, exercise has become a cornerstone of MS rehabilitation and may have even more fundamental benefits in MS, with the potential to change clinical practice again. The aim of this review is to summarize the existing knowledge of the effects of exercise as primary, secondary, and tertiary prevention in MS. RECENT FINDINGS: Initial studies established exercise as an effective symptomatic treatment (i.e., tertiary prevention), but recent studies have evaluated the disease-modifying effects (i.e., secondary prevention) of exercise as well as the impact on the risk of developing MS (i.e., primary prevention). Based on recent evidence, a new paradigm shift is proposed, in which exercise at an early stage should be individually prescribed and tailored as "medicine" to persons with MS, alongside conventional medical treatment.

Effects of plyometric training on jumping, sprint performance, and lower body muscle strength in healthy adults: A systematic review and meta-analyses.

OBJECTIVE: To determine the effect of lower body plyometric training (PLY) on jumping, sprint performance, and lower body muscle strength in healthy adults. METHODS: A systematic literature search (PubMed, Embase) was performed. Studies were included if they (a) described a lower body PLY intervention lasting ≥4 weeks; (b) included measures of jumping, sprint, and/or lower body muscle strength; (c) included healthy individuals ≥18 years; (d) included a training or non-training control group; and (e) were written in English. Meta-analyses identifying the effects of PLY on jumping, sprint, and lower body muscle strength were conducted providing the standardized mean difference (SMD). RESULTS: A total of 826 records were identified of which 25 fulfilled the inclusion criteria, yielding 19, 11, and seven data points for the meta-analyses of jumping, sprint performance, and lower body muscle strength, respectively. The data showed improvements for all three performance variables after 4-12 weeks of PLY. The SMD (CI95%) across studies for jump height, sprint time, and muscle strength were 0.45 (0.16: 0.75), -0.59 (-1.01: -0.17), and 0.33 (0.03: 0.63), respectively, where the latter two showed within-sample heterogeneity. CONCLUSION: The systematic review and meta-analyses showed that PLY elicits a small-to-moderate positive effect on jumping, sprint performance, and lower body muscle strength in healthy adults being recreationally active or athletes.

SPARC Interacts with Actin in Skeletal Muscle in Vitro and in Vivo.

The cytoskeleton is an integral part of skeletal muscle structure, and reorganization of the cytoskeleton occurs during various modes of remodeling. We previously found that the extracellular matrix protein secreted protein acidic and rich in cysteine (SPARC) is up-regulated and expressed intracellularly in developing muscle, during regeneration and in myopathies, which together suggests that SPARC might serve a specific role within muscle cells. Using co-immunoprecipitation combined with mass spectrometry and verified by staining for direct protein-protein interaction, we find that SPARC binds to actin. This interaction is present in regenerating myofibers of patients with Duchenne muscular dystrophy, polymyositis, and compartment syndrome. Analysis of the α-, ß-, and γ-actin isoforms in SPARC knockout myoblasts reveals a changed expression pattern with dominance of γ-actin. In SPARC knockout mice, we performed an injury study to investigate whether lack of SPARC would compromise the ability to repair muscle. We report that these mice develop normal skeletal muscle with retained ability to regenerate. However, when we subject muscle from SPARC-deficient mice to an in vitro fatigue stimulation protocol, we find a defective force recovery. Therefore, SPARC appears to be an important modulator of the actin cytoskeleton, implicating maintenance of muscular function. This direct interaction with actin suggests a new role of SPARC during tissue remodeling.

Is there an overlooked "window of opportunity" in MS exercise therapy? Perspectives for early MS rehabilitation.

While early medical treatment has proven effective in MS, early-phase MS rehabilitation has not gained much attention in MS research and clinical practice. Exercise therapy is one of the most promising treatment strategies in MS rehabilitation. Here, we provide a topical review investigating when exercise therapy is initiated in existing MS studies, showing that exercise is initiated at a rather late disease stage, where it predominantly serves as a symptomatic treatment. Recent findings in MS suggest that exercise may have neuroprotective and disease-modifying effects. Such findings along with the findings from medical trials that an early-stage "window of opportunity" exists leads to the proposal that early exercise therapy should be an increased focus in research and clinical practice for persons with MS. A further perspective relates to other rehabilitation interventions that are also initiated at a later disease stage, as these may also take advantage of an early-phase approach.

Impact of musculoskeletal pain on balance and concerns of falling in mobility-limited, community-dwelling Danes over 75 years of age: a cross-sectional study.

BACKGROUND: In older adults, musculoskeletal pain is associated with increased concerns of falling, reduced balance and increased occurrence of falls. In younger adults, the intensity of neck pain and low back pain is associated with increased postural sway. It is not known if pain further impairs balance and concerns of falling in mobility-limited older adults, and if so, whether this is associated with different intensities of pain. OBJECTIVE: This study examined whether mobility-limited older adults with mild or intense neck pain and/or low back pain have significantly increased postural sway as measured by centre of pressure (COP) changes and concerns of falling compared to those without pain. METHODS: 48 older adults with a gait speed of < 0.9 m/s from Odense, Denmark were recruited through the public health service. Self-reported neck pain, low back pain, and concerns of falling were recorded on questionnaires. Sway range, velocity and area were recorded on a force plate in a comfortable standing stance. Pain intensity was rated on an 11 point numerical rating scale (0-10). Participants were sub-grouped into mild (0-4) and intense (> 5) neck pain or low back pain. RESULTS: Intense neck pain was associated with increased anterior-posterior sway range and area of sway. Intense low back pain was associated with increased concerns of falling. CONCLUSION: Intense neck pain in mobility-limited older adults is associated with significant changes in postural balance, and intense low back pain is associated with significantly higher concerns of falling.