Functional intermuscular reduction in spasticity for people with multiple sclerosis

Background Eighty-five percent of people with multiple sclerosis (MS) incur gait impairments debilitating enough to significantly impact their function. Objectives The aim of this study was to determine if a novel combination of intermuscular electrical stimulation, followed by functional electrical stimulation combined with supported bodyweight treadmill training, would improve gait, decrease spasticity and fatigue, and improve muscle strength. Methods Using a pre-post experimental design, we implemented this combination six-week protocol in 16 individuals with MS. We completed summary statistics and longitudinal pre-post results using Wilcoxon sign rank tests with Bonferroni adjustment. Results Participants responded with median increases of 29.4 feet ( p < 0.0001) during the Six Minute Walk Test, median decreases of 0.7 s ( p = 0.0011) in the 25-Foot Walk Test, median increases of 3.8 toe taps to fatigue ( p = 0.0306) and median increases of 5.0 heel raises ( p = 0.0093). Significant changes were noted in the Modified Ashworth Scale, both after intermuscular electrical stimulation (median change = −0.5 p = 0.0039) and after treadmill walking (median change = −0.5, p < 0.0005). Conclusions Results of this novel protocol suggest this intervention combination has the potential to decrease spasticity, and improve gait speed and endurance in individuals with MS. Observed changes in mobility occurred without accompanying increases in fatigue.

Analysis of Fractal Correlation Properties of Heart Rate Variability during an Initial Session of Eccentric Cycling

Eccentric cycling (ECC) has attracted attention as a method to improve muscle strength and aerobic fitness in populations unable to tolerate conventional methods. However, agreement on exercise prescription targets have been problematic. The current report is an initial exploration of a potentially useful tool, a nonlinear heart rate (HR) variability (HRV) index based on the short-term scaling exponent alpha1 of detrended fluctuation analysis (DFA a1), which has been previously shown to correspond to exercise intensity. Eleven male volunteers performed 45 min of concentric (CON) cycling and ECC separated by 1 month. Work rates were matched for HR (~50% of the maximal HR) during the first 5 min and remained stable thereafter. HRV, HR, oxygen consumption (VO2), and cycling power were monitored and evaluated at elapsed times of 10 (T10) and 45 (T45) minutes duration. HR significantly increased between ECC T10 and ECC T45 (p = 0.003, d = 1.485), while DFA a1 significantly decreased (p = 0.004, d = 1.087). During CON, HR significantly increased (p < 0.001 d = 1.570) without significant DFA a1 change (p = 0.48, d = 0.22). Significantly higher HR was observed at T45 in ECC than in CON (p = 0.047, d = 1.059). A session of unaccustomed ECC lead to decreased values of DFA a1 at T45 in comparison to that seen with CON at similar VO2. ECC lead to altered autonomic nervous system balance as reflected by the loss of correlation properties compared to CON.

Exercise interventions can improve muscle strength, endurance, and electrical activity of lumbar extensors in individuals with non-specific low back pain: a systematic review with meta-analysis

Exercise interventions have been recommended for people with non-specific low back pain. The literature is scarce regarding the effects of exercise on muscle strength, endurance, and electrical activity of lumbar extensor muscles. Electronic searches were carried out from May 2020 until August 2020 in the following databases: PUBMED, CENTRAL, EMBASE, PEDro, SPORTDiscus, Scielo, and LILACS. Only randomized controlled trials with passive and active control groups were included. The methodological quality of the included studies was performed using the Physiotherapy Evidence Database Scale. Eight studies, involving 508 participants, were included in metanalytical procedures. Exercise interventions demonstrated superior effects on muscle activity (Electromyography) when compared with active controls (p < 0.0001). Exercise interventions demonstrated superior effects on muscle endurance (Sorensen Test) when compared with passive (p = 0.0340) and active controls (p = 0.0276). Exercise interventions demonstrated superior effects on muscle strength (Machine) when compared with passive controls (p = 0.0092). Exercise interventions can improve muscle strength, endurance, and electrical activity in people with non-specific low back pain.

Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use

L-Citrulline is a non-essential but still important amino acid that is released from enterocytes. Because plasma levels are reduced in case of impaired intestinal function, it has become a biomarker to monitor intestinal integrity. Moreover, oxidative stress induces protein citrullination, and antibodies against anti-citrullinated proteins are useful to monitor rheumatoid diseases. Citrullinated histones, however, may even predict a worse outcome in cancer patients. Supplementation of citrulline is better tolerated compared to arginine and might be useful to slightly improve muscle strength or protein balance. The following article shall provide an overview of L-citrulline properties and functions, as well as the current evidence for its use as a biomarker or as a therapeutic supplement.

OP0247 IN MYOSITIS MUSCLE FIBRE PLAYS A DIRECT AND CRITICAL ROLE IN THERAPEUTIC RESPONSE TO GLUCOCORTICOIDS

Background:Myositis are rare autoimmune diseases, affecting more women than men, characterized by chronic inflammation of skeletal muscle causing muscle weakness, decreased quality of life and increased mortality.Glucocorticoids (GC) are potent anti-inflammatory drugs, and are the first line treatment of myositis. They improve muscle strength of myositis patients (therapeutic effect), yet muscle recovery is generally only partial. Moreover, GC have an iatrogenic effect on skeletal muscle fibre leading to steroid myopathy. Thus myositis care has to be improved. Despite the autoimmune terrain of myositis, our team has recently shown that muscle fibres themselves develop immuno-metabolic modifications that participate to muscle weakness and perpetuation of the disease1. GC effects are mediated by the glucocorticoid receptor (GR), which is expressed in various cell types including immune cells and myofibres, but the cells mediating therapeutic responses remain to be determined.Objectives:Unravel the mechanisms underlying the therapeutic effect of GC in myositis, particularly elucidate the role of skeletal muscle fibres.Methods:Experimental myositis was induced in eight to ten week-old C57BL/6J female mice by a single intradermal injection of part of skeletal muscle fast-type C protein along with Freund’s adjuvant and an intraperitoneal (IP) injection of pertussis toxin, as previously described2. Prednisone (PDN) was administered 14 days (D) after the immunization at 1 mg/kg/day for 7 days by gavage. Mice were euthanized 21 days after myositis induction. Muscle strength was assessed by grip test at D 0, before the 1st PDN administration (D 14) and the day before sacrifice (D 20). To investigate whether the PDN effects are mediated by myofibre, we generated transgenic mice carrying two LoxP sites within the GR gene in muscle, expressing the tamoxifen-inducible Cre-ERT2 recombinase selectively in skeletal muscle fibre (HSA-CreERT2/GR L2/L2). Tamoxifen (1 mg/day for 5 days by IP injection) was administered 9 days after immunization to induce GR ablation selectively in skeletal muscle fibres (GR(i)skm-/- mice). Similar treatments were applied to GR L2/L2 that do not express Cre-ER(T2), and served as controls.We compared 4 groups of myositis mice, GR L2/L2 treated by PDN (n=9) or vehicle (n=9) and GR(i)skm-/- treated by PDN (n=10) or vehicle (n=10), by grip test and at the histological level (hematoxylin-eosin (HE) and Gomori trichrome (GT) staining). Moreover, LC3 expression was studied by RTqPCR and western blot.Results:Muscle strength was decreased in both GR L2/L2 and GR(i)skm-/- myositis mice from D 14 to D 20. GR L2/L2 myositis mice recovered muscle strength after PDN treatment; no significant difference compared to D 0 was detected. In contrast, PDN did not improve muscle strength in GR(i)skm-/- myositis mice (Figure 1).HE and GT staining did not reveal quantitative differences in inflammatory infiltrate. Necrotic and degenerative fibres were detected in the 4 groups. At RTqPCR, LC3, an autophagy marker, was upregulated in PDN-treated GR L2/L2 myositis mice compared to untreated GR L2/L2 myositis mice; moreover it was 2-fold more expressed in PDN-treated GR L2/L2 myositis mice compared to PDN-treated GR(i)skm-/- mice.Conclusion:GR in skeletal muscle fibre is crucial to mediate the therapeutic response to GC in a murine model of myositis. Autophagy is one of the candidate pathways controlled by myofibre GR underlying this effect.References:[1]Meyer A et al. IFN-β-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis. Acta Neuropathol. 2017 Oct;134(4):655-666.[2]Sugihara T et al. A new murine model to define the critical pathologic and therapeutic mediators of polymyositis. Arthritis Rheum. 2007 Apr;56(4):1304-14.Disclosure of Interests:None declared

Novel myostatin-specific antibody enhances muscle strength in muscle disease models

Myostatin, a member of the transforming growth factor-β superfamily, is an attractive target for muscle disease therapy because of its role as a negative regulator of muscle growth and strength. Here, we describe a novel antibody therapeutic approach that maximizes the potential of myostatin-targeted therapy. We generated an antibody, GYM329, that specifically binds the latent form of myostatin and inhibits its activation. Additionally, via “sweeping antibody technology”, GYM329 reduces or “sweeps” myostatin in the muscle and plasma. Compared with conventional anti-myostatin agents, GYM329 and its surrogate antibody exhibit superior muscle strength-improvement effects in three different mouse disease models. We also demonstrate that the superior efficacy of GYM329 is due to its myostatin specificity and sweeping capability. Furthermore, we show that a GYM329 surrogate increases muscle mass in normal cynomolgus monkeys without any obvious toxicity. Our findings indicate the potential of GYM329 to improve muscle strength in patients with muscular disorders.

ROM Therapy on Muscle Strength in Post Stroke Patients: Scoping Review

Hemiparesis and hemiplegia are motor deficits found mostly in stroke patients. If the deterioration in muscle strength that occurs is not handled properly, it will cause permanent disability. ROM therapy is a therapy to increase muscle strength which has undergone various developments according to the research that has been done. The aim of this article was to identify interventions using ROM therapy to improve muscle strength in post-stroke patients. The databases used were JCS, PMC, Science Direct, and PubMed. The search was limited to articles published in 2014 to 2019. The study criteria was for adult, quantitative comparisons between before and after intervention ROM therapy and full text article, published in peer-reviewed journal and written in English and Indonesian. This article used the methodological framework by Arksey and O'Malley for the scoping review. The research has conducted a study of 4 articles, in which all of the items discussed the application of ROM therapy to increase muscle strength in post-stroke patients. The results from each articles showed that ROM therapy has helped improve muscle strength in post-stroke patients.

Novel Myostatin-Specific Antibody Enhances Muscle Strength in Muscle Disease Models

Myostatin, a member of the transforming growth factor-b superfamily, is an attractive target for muscle disease therapy because of its role as a negative regulator of muscle growth and strength. Here, we describe a novel antibody therapeutic approach that maximizes the potential of myostatin-targeted therapy. We generated an antibody, GYM329, that specifically binds the latent form of myostatin and inhibits its activation. Additionally, via “sweeping antibody technology”, GYM329 reduces or “sweeps” myostatin in the muscle and plasma. Compared with conventional anti-myostatin agents, GYM329 and its surrogate antibody exhibit superior muscle strength-improvement effects in three different mouse disease models. We also demonstrate that the superior efficacy of GYM329 is due to its myostatin specificity and sweeping capability. Furthermore, we show that a GYM329 surrogate increases muscle mass in normal cynomolgus monkeys without any obvious toxicity. Our findings indicate the potential of GYM329 to improve muscle strength in patients with muscular disorders.

The effect of rehabilitative exercises accompanied by aids to improve muscle strength and range of motion for people with dislocated shoulder joint

The research aims to: Preparing rehabilitative exercises with accompanying tools to rehabilitate those with shoulder dislocation. Knowing the effect of rehabilitative exercises and accompanying aids in improving the muscular strength and motor range of those with dislocations in the shoulder joint. The two researchers used the experimental design with the same experimental group with the pre and post tests, so the researcher chose a sample appropriate to the nature of his research problem, its goals and its hypotheses, as a sample of the injured was chosen to remove the shoulder joint, who completed the treatment, who were not practicing sports, and those who went to the Physiotherapy Center at Al-Wasiti Hospital, as their number reached (10) were injured. A group of rehabilitative exercises was prepared and accompanied by auxiliary tools presented to experts and specialists in the field of sports medicine. Pre-test tests were conducted and then rehabilitative exercises were implemented to achieve the desired goal of the research. The number of rehabilitative units was 3 rehabilitative units per week and for days Sunday, Tuesday, Thursday. For a period of eight weeks, i.e. at the rate of 24 rehabilitative units and then conducting post-test. The researchers concluded the following: _ Rehabilitation exercises prepared by the two researchers with a clear positive effect on improving muscle strength and motor range among the individuals in the research sample. _ The auxiliary tools used by the two researchers have a positive effect in stimulating and provoking motivation and suspense among the injured to perform rehabilitative exercises. The researchers recommended: - To conduct similar research on other injuries and different samples and to adopt the rehabilitation approach by the two researchers in other physiotherapy centers.