Age-dependent motor unit remodelling in human limb muscles.

Voluntary control of skeletal muscle enables humans to interact with and manipulate the environment. Lower muscle mass, weakness and poor coordination are common complaints in older age and reduce physical capabilities. Attention has focused on ways of maintaining muscle size and strength by exercise, diet or hormone replacement. Without appropriate neural innervation, however, muscle cannot function. Emerging evidence points to a neural basis of muscle loss. Motor unit number estimates indicate that by age around 71 years, healthy older people have around 40 % fewer motor units. The surviving low- and moderate-threshold motor units recruited for moderate intensity contractions are enlarged by around 50 % and show increased fibre density, presumably due to collateral reinnervation of denervated fibres. Motor unit potentials show increased complexity and the stability of neuromuscular junction transmissions is decreased. The available evidence is limited by a lack of longitudinal studies, relatively small sample sizes, a tendency to examine the small peripheral muscles and relatively few investigations into the consequences of motor unit remodelling for muscle size and control of movements in older age. Loss of motor neurons and remodelling of surviving motor units constitutes the major change in ageing muscles and probably contributes to muscle loss and functional impairments. The deterioration and remodelling of motor units likely imposes constraints on the way in which the central nervous system controls movements

Home-based exercise in autoimmune myasthenia gravis: A randomized controlled trial

International audienceThe tolerance of exercise and its effects on quality of life in myasthenia gravis are not currently backed up by strong evidence. The aim of this study was to determine whether exercise as an adjunct therapy is well tolerated and can improve health-related quality of life (HRQoL) in stabilized, generalized autoimmune myasthenia gravis (gMG). We conducted a parallel-group, multi-center prospective RCT using computer-generated block randomization. Adults with stabilized, gMG, and no contra-indication to exercise, were eligible. Participants received usual care alone or usual care and exercise. The exercise intervention consisted of 3-weekly 40 min sessions of an unsupervised, moderate-intensity home rowing program over 3 months. The primary endpoint was the change in HRQoL from randomization to postintervention. Assessor-blinded secondary endpoints were exercise tolerance and effects on clinical, psychological and immunological status. Of 138 patients screened between October 2014 and July 2017, 45 were randomly assigned to exercise (n = 23) or usual care (n = 20). Although exercise was well tolerated, the intention-to-treat analysis revealed no evidence of improved HRQoL compared to usual care (MGQOL-15-F; mean adjusted between-groups difference of-0.8 points, 95%CI-5.4 to 3.7). Two patients hospitalized for MG exacerbation were from the usual care group

The benefits and tolerance of exercise in myasthenia gravis (MGEX): study protocol for a randomised controlled trial

the MGEX Study GroupInternational audienceBackground: Research exploring the effects of physical exercise in auto-immune myasthenia gravis (MG) is scarce. The few existing studies present methodological shortcomings limiting the conclusions and generalisability of results. It is hypothesised that exercise could have positive physical, psychological as well as immunomodulatory effects and may be a beneficial addition to current pharmacological management of this chronic disease. The aim of this study is to evaluate the benefits on perceived quality of life (QOL) and physical fitness of a home-based physical exercise program compared to usual care, for patients with stabilised, generalised auto-immune MG.Methods: MGEX is a multi-centre, interventional, randomised, single-blind, two-arm parallel group, controlled trial. Forty-two patients will be recruited, aged 18–70 years. Following a three-month observation period, patients will be randomised into a control or experimental group. The experimental group will undertake a 40-min home-based physical exercise program using a rowing machine, three times a week for three months, as an add-on to usual care. The control group will receive usual care with no additional treatment. All patients will be followed up for a further three months. The primary outcome is the mean change in MGQOL-15-F score between three and six months (i.e. pre-intervention and immediately post-intervention periods). The MGQOL-15-F is an MG-specific patient-reported QOL questionnaire. Secondary outcomes include the evaluation of deficits and functional limitations via MG-specific clinical scores (Myasthenia Muscle Score and MG-Activities of Daily Living scale), muscle force and fatigue, respiratory function, free-living physical activity as well as evaluations of anxiety, depression, self-esteem and overall QOL with the WHO-QOL BREF questionnaire. Exercise workload will be assessed as well as multiple safety measures (ECG, biological markers, medication type and dosage and any disease exacerbation or crisis).Discussion: This is the largest randomised controlled trial to date evaluating the benefits and tolerance of physical exercise in this patient population. The comprehensive evaluations using standardised outcome measures should provide much awaited information for both patients and the scientific community. This study is ongoing

Detection of Multiple Innervation Zones from Multi-Channel Surface EMG Recordings with Low Signal-to-Noise Ratio Using Graph-Cut Segmentation

Knowledge of the location of muscle Innervation Zones (IZs) is important in many applications, e.g. for minimizing the quantity of injected botulinum toxin for the treatment of spasticity or for deciding on the type of episiotomy during child delivery. Surface EMG (sEMG) can be noninvasively recorded to assess physiological and morphological characteristics of contracting muscles. However, it is not often possible to record signals of high quality. Moreover, muscles could have multiple IZs, which should all be identified. We designed a fully-automatic algorithm based on the enhanced image Graph-Cut segmentation and morphological image processing methods to identify up to five IZs in 60-ms intervals of very-low to moderate quality sEMG signal detected with multi-channel electrodes (20 bipolar channels with Inter Electrode Distance (IED) of 5 mm). An anisotropic multilayered cylinder model was used to simulate 750 sEMG signals with signal-to-noise ratio ranging from -5 to 15 dB (using Gaussian noise) and in each 60-ms signal frame, 1 to 5 IZs were included. The micro- and macro- averaged performance indices were then reported for the proposed IZ detection algorithm. In the micro-averaging procedure, the number of True Positives, False Positives and False Negatives in each frame were summed up to generate cumulative measures. In the macro-averaging, on the other hand, precision and recall were calculated for each frame and their averages are used to determine F1-score. Overall, the micro (macro)-averaged sensitivity, precision and F1-score of the algorithm for IZ channel identification were 82.7% (87.5%), 92.9% (94.0%) and 87.5% (90.6%), respectively. For the correctly identified IZ locations, the average bias error was of 0.02±0.10 IED ratio. Also, the average absolute conduction velocity estimation error was 0.41±0.40 m/s for such frames. The sensitivity analysis including increasing IED and reducing interpolation coefficient for time samples was performed. Meanwhile, the effect of adding power-line interference and using other image interpolation methods on the deterioration of the performance of the proposed algorithm was investigated. The average running time of the proposed algorithm on each 60-ms sEMG frame was 25.5±8.9 (s) on an Intel dual-core 1.83 GHz CPU with 2 GB of RAM. The proposed algorithm correctly and precisely identified multiple IZs in each signal epoch in a wide range of signal quality and is thus a promising new offline tool for electrophysiological studies.peerReviewe

Update on outcome assessment in myositis

The adult and juvenile myositis syndromes, commonly referred to collectively as idiopathic inflammatory myopathies (IIMs), are systemic autoimmune diseases with the hallmarks of muscle weakness and inflammation. Validated, well-standardized measures to assess disease activity, known as core set measures, were developed by international networks of myositis researchers for use in clinical trials. Composite response criteria using weighted changes in the core set measures of disease activity were developed and validated for adult and juvenile patients with dermatomyositis and adult patients with polymyositis, with different thresholds for minimal, moderate and major improvement in adults and juveniles. Additional measures of muscle strength and function are being validated to improve content validity and sensitivity to change. A health-related quality of life measure, which incorporates patient input, is being developed for adult patients with IIM. Disease state criteria, including criteria for inactive disease and remission, are being used as secondary end points in clinical trials. MRI of muscle and immunological biomarkers are promising approaches to discriminate between disease activity and damage and might provide much-needed objective outcome measures. These advances in the assessment of outcomes for myositis treatment, along with collaborations between international networks, should facilitate further development of new therapies for patients with IIM