Respiratory features of centronuclear myopathy in the Netherlands.

Centronuclear myopathy (CNM) is a heterogeneous group of muscle disorders primarily characterized by muscle weakness and variable degrees of respiratory dysfunction caused by mutations in MTM1, DNM2, RYR1, TTN and BIN1. X-linked myotubular myopathy has been the focus of recent natural history studies and clinical trials. Data on respiratory function for other genotypes is limited. To better understand the respiratory properties of the CNM spectrum, we performed a retrospective study in a non-selective Dutch CNM cohort. Respiratory dysfunction was defined as an FVC below 70% of predicted and/or a daytime pCO2 higher than 6 kPa. We collected results of other pulmonary function values (FEV1/FVC ratio) and treatment data from the home mechanical ventilation centres. Sixty-one CNM patients were included. Symptoms of respiratory weakness were reported by 15/47 (32%) patients. Thirty-three individuals (54%) with different genotypes except autosomal dominant (AD)-BIN1-related CNM showed respiratory dysfunction. Spirometry showed decreased FVC, FEV1 & PEF values in all but two patients. Sixteen patients were using HMV (26%), thirteen of them only during night-time. In conclusion, this study provides insight into the prevalence of respiratory symptoms in four genetic forms of CNM in the Netherlands and offers the basis for future natural history studies.

Therapeutic Effect of a Soft Robotic Glove for Activities of Daily Living In People With Impaired Hand Strength: Protocol for a Multicenter Clinical Trial (iHand).

BACKGROUND: Decline of hand function, especially reduced hand strength, is a common problem that can be caused by many disorders and results in difficulties performing activities of daily living. A wearable soft robotic glove may be a solution, enabling use of the affected arm and hand repeatedly during functional daily activities and providing intensive and task-specific training simultaneously with assistance of hand function. OBJECTIVE: We aim to investigate the therapeutic effect of an assistive soft robotic glove (Carbonhand). METHODS: This multicenter uncontrolled intervention study consists of 3 preassessments (T0, T1, and T2), a postassessment (T3), and a follow-up assessment (T4). Participants are patients who experience hand function limitations. For the intervention, participants will use the glove during activities of daily living at home for 6 weeks, with a recommended use of at least 180 minutes per week. The primary outcome measure is handgrip strength, and secondary outcome measures are related to functional arm and hand abilities, amount of glove use, and quality of life. RESULTS: The first participant was included on June 25, 2019. Currently, the study has been extended due to the COVID-19 pandemic; data collection and analysis are expected to be completed in 2022. CONCLUSIONS: The Carbonhand system is a wearable assistive device, allowing performance of functional activities to be enhanced directly during functional daily activities. At the same time, active movement of the user is encouraged as much as possible, which has potential to provide highly intensive and task-specific training. As such, it is one of the first assistive devices to incorporate assist-as-needed principles. This is the first powered clinical trial that investigates the unique application of an assistive grip-supporting soft robotic glove outside of clinical settings with the aim to have a therapeutic effect. TRIAL REGISTRATION: Netherlands Trial Register NTR NL7561; https://www.trialregister.nl/trial/7561. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34200.

Strength training and aerobic exercise training for muscle disease.

BACKGROUND: Strength training or aerobic exercise programmes, or both, might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people with a muscle disease. This is an update of a review first published in 2004 and last updated in 2013. We undertook an update to incorporate new evidence in this active area of research. OBJECTIVES: To assess the effects (benefits and harms) of strength training and aerobic exercise training in people with a muscle disease. SEARCH METHODS: We searched Cochrane Neuromuscular's Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL in November 2018 and clinical trials registries in December 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs or cross-over RCTs comparing strength or aerobic exercise training, or both lasting at least six weeks, to no training in people with a well-described muscle disease diagnosis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 14 trials of aerobic exercise, strength training, or both, with an exercise duration of eight to 52 weeks, which included 428 participants with facioscapulohumeral muscular dystrophy (FSHD), dermatomyositis, polymyositis, mitochondrial myopathy, Duchenne muscular dystrophy (DMD), or myotonic dystrophy. Risk of bias was variable, as blinding of participants was not possible, some trials did not blind outcome assessors, and some did not use an intention-to-treat analysis. Strength training compared to no training (3 trials) For participants with FSHD (35 participants), there was low-certainty evidence of little or no effect on dynamic strength of elbow flexors (MD 1.2 kgF, 95% CI -0.2 to 2.6), on isometric strength of elbow flexors (MD 0.5 kgF, 95% CI -0.7 to 1.8), and ankle dorsiflexors (MD 0.4 kgF, 95% CI -2.4 to 3.2), and on dynamic strength of ankle dorsiflexors (MD -0.4 kgF, 95% CI -2.3 to 1.4). For participants with myotonic dystrophy type 1 (35 participants), there was very low-certainty evidence of a slight improvement in isometric wrist extensor strength (MD 8.0 N, 95% CI 0.7 to 15.3) and of little or no effect on hand grip force (MD 6.0 N, 95% CI -6.7 to 18.7), pinch grip force (MD 1.0 N, 95% CI -3.3 to 5.3) and isometric wrist flexor force (MD 7.0 N, 95% CI -3.4 to 17.4). Aerobic exercise training compared to no training (5 trials) For participants with DMD there was very low-certainty evidence regarding the number of leg revolutions (MD 14.0, 95% CI -89.0 to 117.0; 23 participants) or arm revolutions (MD 34.8, 95% CI -68.2 to 137.8; 23 participants), during an assisted six-minute cycle test, and very low-certainty evidence regarding muscle strength (MD 1.7, 95% CI -1.9 to 5.3; 15 participants). For participants with FSHD, there was low-certainty evidence of improvement in aerobic capacity (MD 1.1 L/min, 95% CI 0.4 to 1.8, 38 participants) and of little or no effect on knee extension strength (MD 0.1 kg, 95% CI -0.7 to 0.9, 52 participants). For participants with dermatomyositis and polymyositis (14 participants), there was very low-certainty evidence regarding aerobic capacity (MD 14.6, 95% CI -1.0 to 30.2). Combined aerobic exercise and strength training compared to no training (6 trials) For participants with juvenile dermatomyositis (26 participants) there was low-certainty evidence of an improvement in knee extensor strength on the right (MD 36.0 N, 95% CI 25.0 to 47.1) and left (MD 17 N 95% CI 0.5 to 33.5), but low-certainty evidence of little or no effect on maximum force of hip flexors on the right (MD -9.0 N, 95% CI -22.4 to 4.4) or left (MD 6.0 N, 95% CI -6.6 to 18.6). This trial also provided low-certainty evidence of a slight decrease of aerobic capacity (MD -1.2 min, 95% CI -1.6 to 0.9). For participants with dermatomyositis and polymyositis (21 participants), we found very low-certainty evidence for slight increases in muscle strength as measured by dynamic strength of knee extensors on the right (MD 2.5 kg, 95% CI 1.8 to 3.3) and on the left (MD 2.7 kg, 95% CI 2.0 to 3.4) and no clear effect in isometric muscle strength of eight different muscles (MD 1.0, 95% CI -1.1 to 3.1). There was very low-certainty evidence that there may be an increase in aerobic capacity, as measured with time to exhaustion in an incremental cycle test (17.5 min, 95% CI 8.0 to 27.0) and power performed at VO2 max (maximal oxygen uptake) (18 W, 95% CI 15.0 to 21.0). For participants with mitochondrial myopathy (18 participants), we found very low-certainty evidence regarding shoulder muscle (MD -5.0 kg, 95% CI -14.7 to 4.7), pectoralis major muscle (MD 6.4 kg, 95% CI -2.9 to 15.7), and anterior arm muscle strength (MD 7.3 kg, 95% CI -2.9 to 17.5). We found very low-certainty evidence regarding aerobic capacity, as measured with mean time cycled (MD 23.7 min, 95% CI 2.6 to 44.8) and mean distance cycled until exhaustion (MD 9.7 km, 95% CI 1.5 to 17.9). One trial in myotonic dystrophy type 1 (35 participants) did not provide data on muscle strength or aerobic capacity following combined training. In this trial, muscle strength deteriorated in one person and one person had worse daytime sleepiness (very low-certainty evidence). For participants with FSHD (16 participants), we found very low-certainty evidence regarding muscle strength, aerobic capacity and VO2 peak; the results were very imprecise. Most trials reported no adverse events other than muscle soreness or joint complaints (low- to very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence regarding strength training and aerobic exercise interventions remains uncertain. Evidence suggests that strength training alone may have little or no effect, and that aerobic exercise training alone may lead to a possible improvement in aerobic capacity, but only for participants with FSHD. For combined aerobic exercise and strength training, there may be slight increases in muscle strength and aerobic capacity for people with dermatomyositis and polymyositis, and a slight decrease in aerobic capacity and increase in muscle strength for people with juvenile dermatomyositis. More research with robust methodology and greater numbers of participants is still required.

Strength training and aerobic exercise training for muscle disease.

BACKGROUND: Strength training or aerobic exercise programmes might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people with a muscle disease. OBJECTIVES: To examine the safety and efficacy of strength training and aerobic exercise training in people with a muscle disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Specialized Register (July 2009), the Cochrane Rehabilitation and Related Therapies Field Register (October 2002, August 2008 and July 2009), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2009) MEDLINE (January 1966 to July 2009), EMBASE (January 1974 to July 2009), EMBASE Classic (1947 to 1973) and CINAHL (January 1982 to July 2009). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing strength training or aerobic exercise programmes, or both, to no training, and lasting at least 10 weeks.For strength training Primary outcome: static or dynamic muscle strength. Secondary: muscle endurance or muscle fatigue, functional assessments, quality of life, muscle membrane permeability, pain and experienced fatigue.For aerobic exercise training Primary outcome: aerobic capacity expressed as work capacity. Secondary: aerobic capacity (oxygen consumption, parameters of cardiac or respiratory function), functional assessments, quality of life, muscle membrane permeability, pain and experienced fatigue. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted the data. MAIN RESULTS: We included three trials (121 participants). The first compared the effect of strength training versus no training in 36 people with myotonic dystrophy. The second trial compared strength training versus no training, both combined with albuterol or placebo, in 65 people with facioscapulohumeral muscular dystrophy. The third trial compared combined strength training and aerobic exercise versus no training in 18 people with mitochondrial myopathy. In the myotonic dystrophy trial there were no significant differences between training and non-training groups for primary and secondary outcome measures. In the facioscapulohumeral muscular dystrophy trial only a +1.17 kg difference (95% confidence interval 0.18 to 2.16) in dynamic strength of elbow flexors in favour of the training group reached statistical significance. In the mitochondrial myopathy trial there were no significant differences in dynamic strength measures between training and non-training groups. Exercise duration and distance cycled in a submaximal endurance test increased significantly in the training group compared to the control group. AUTHORS' CONCLUSIONS: In myotonic dystrophy and facioscapulohumeral muscular dystrophy, moderate-intensity strength training appears not to do harm but there is insufficient evidence to conclude that it offers benefit. In mitochondrial myopathy, aerobic exercise combined with strength training appears to be safe and may be effective in increasing submaximal endurance capacity. Limitations in the design of studies in other muscle diseases prevent more general conclusions in these disorders.