Feasibility and Reproducibility of Isokinetic Dynamometry in Children with Neuromuscular Diseases.

High-precision measurement tools are needed to measure relevant changes in strength and power in children with neuromuscular diseases. The aim of this study was to determine the feasibility (i), reproducibility (ii), and validity (iii) of isokinetic dynamometry in this population. Isometric and isokinetic knee and elbow flexion and extension were measured twice on the same day.

Exploring functional strength changes during nusinersen treatment in symptomatic children with SMA types 2 and 3.

The Hammersmith Functional Motor Scale-Expanded (HFMSE) is a validated outcome measure for monitoring changes in functional strength in patients with spinal muscular atrophy (SMA). The objective of this study was to explore changes in HFMSE item-scores in children with SMA types 2 and 3a treated with nusinersen over a period of six to twenty months. We stratified patients according to motor ability (sitting and walking), and calculated numbers and percentages for each specific improvement (positive score change) or decrease (negative score change) for the total group and each subgroup and calculated frequency distributions of specific score changes.

Monitoring Nusinersen Treatment Effects in Children with Spinal Muscular Atrophy with Quantitative Muscle MRI.

Background: Spinal muscular atrophy (SMA) is caused by deficiency of survival motor neuron (SMN) protein. Intrathecal nusinersen treatment increases SMN protein in motor neurons and has been shown to improve motor function in symptomatic children with SMA.

Objective: We used quantitative MRI to gain insight in microstructure and fat content of muscle during treatment and to explore its use as biomarker for treatment effect.

Electrophysiological and Imaging Biomarkers to Evaluate Exercise Training in Patients with Neuromuscular Disease: A Systematic Review.

Exercise therapy as part of the clinical management of patients with neuromuscular diseases (NMDs) is complicated by the limited insights into its efficacy. There is an urgent need for sensitive and non-invasive quantitative muscle biomarkers to monitor the effects of exercise training. Therefore, the objective of this systematic review was to critically appraise and summarize the current evidence for the sensitivity of quantitative, non-invasive biomarkers, based on imaging and electrophysiological techniques, for measuring the effects of physical exercise training.

Enhanced low-threshold motor unit capacity during endurance tasks in patients with spinal muscular atrophy using pyridostigmine.

Objective: To investigate the electrophysiological basis of pyridostigmine enhancement of endurance performance documented earlier in patients with spinal muscular atrophy (SMA).

Methods: We recorded surface electromyography (sEMG) in four upper extremity muscles of 31 patients with SMA types 2 and 3 performing endurance shuttle tests (EST) and maximal voluntary contraction (MVC) measurements during a randomized, double blind, cross-over, phase II trial. Linear mixed effect models (LMM) were used to assess the effect of pyridostigmine on (i) time courses of median frequencies and of root mean square (RMS) amplitudes of sEMG signals and (ii) maximal RMS amplitudes during MVC measurements.

Longitudinal prospective cohort study to assess peripheral motor function with extensive electrophysiological techniques in patients with Spinal Muscular Atrophy (SMA): the SMA Motor Map protocol.

Background: Hereditary spinal muscular atrophy (SMA) is a motor neuron disorder with a wide range in severity in children and adults. Two therapies that alter splicing of the Survival Motor Neuron 2 (SMN2) gene, i.e.

The RESISTANT study (Respiratory Muscle Training in Patients with Spinal Muscular Atrophy): study protocol for a randomized controlled trial.

Background: Spinal Muscular Atrophy (SMA) is characterized by progressive and predominantly proximal and axial muscle atrophy and weakness. Respiratory muscle weakness results in impaired cough with recurrent respiratory tract infections, nocturnal hypoventilation, and may ultimately lead to fatal respiratory failure in the most severely affected patients. Treatment strategies to either slow down the decline or improve respiratory muscle function are wanting.

Lung function decline preceding chronic respiratory failure in spinal muscular atrophy: a national prospective cohort study.

Background: Progressive lung function decline, resulting in respiratory failure, is an important complication of spinal muscular atrophy (SMA). The ability to predict the need for mechanical ventilation is important. We assessed longitudinal patterns of lung function prior to chronic respiratory failure in a national cohort of treatment-naïve children and adults with SMA, hypothesizing an accelerated decline prior to chronic respiratory failure.

Randomized double-blind placebo-controlled crossover trial with pyridostigmine in spinal muscular atrophy types 2-4.

Hereditary proximal spinal muscular atrophy causes weakness and increased fatigability of repetitive motor functions. The neuromuscular junction is anatomically and functionally abnormal in patients with spinal muscular atrophy. Pharmacological improvement of neuromuscular transmission may therefore represent a promising additional treatment strategy.

Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study.

Nusinersen (Spinraza®) improves survival of infants with hereditary proximal spinal muscular atrophy and motor function in children up to 12 years. Population-based assessments of treatment efficacy are limited and confined to select cohorts of patients. We performed a nationwide, population-based, single-centre cohort study in children with spinal muscular atrophy younger than 9.

Respiratory muscle fatigability in patients with spinal muscular atrophy.

Background: Respiratory failure is a major cause of morbidity and mortality in patients with Spinal Muscular Atrophy (SMA). Lack of endurance, or "fatigability," is an important symptom of SMA. In addition to respiratory muscle weakness, respiratory function in SMA may be affected by Respiratory Muscle Fatigability (RMF).

Reliability of Muscle Strength and Muscle Power Assessments Using Isokinetic Dynamometry in Neuromuscular Diseases: A Systematic Review.

Objective: The purpose of this study was to critically appraise and summarize the evidence for reliability of muscle strength and muscle power assessment in patients with neuromuscular diseases (NMDs) using isokinetic dynamometry.

Methods: PubMed, CINAHL, and Embase electronic databases were searched from inception to March 8, 2022. Studies designed to evaluate reliability of muscle strength and power measurements using isokinetic dynamometry were included in this review.

Motor Unit and Capillary Recruitment During Fatiguing Arm-Cycling Exercise in Spinal Muscular Atrophy Types 3 and 4.

Background: Exercise intolerance is an important impairment in patients with SMA, but little is known about the mechanisms underlying this symptom.

Objective: To investigate if reduced motor unit and capillary recruitment capacity in patients with SMA contribute to exercise intolerance.

Methods: Adolescent and adult patients with SMA types 3 and 4 (n = 15) and age- and gender matched controls (n = 15) performed a maximal upper body exercise test.

Short-term effect of air stacking and mechanical insufflation-exsufflation on lung function in patients with neuromuscular diseases.

Air stacking (AS) and mechanical insufflation-exsufflation (MI-E) aim to increase cough efficacy by augmenting inspiratory lung volumes in patients with neuromuscular diseases (NMDs). We studied the short-term effect of AS and MI-E on lung function. We prospectively included NMD patients familiar with daily AS or MI-E use.

Natural history of respiratory muscle strength in spinal muscular atrophy: a prospective national cohort study.

Background: Respiratory complications are the most important cause of morbidity and mortality in spinal muscular atrophy (SMA). Respiratory muscle weakness results in impaired cough, recurrent respiratory tract infections and eventually can cause respiratory failure. We assessed longitudinal patterns of respiratory muscle strength in a national cohort of treatment-naïve children and adults with SMA, hypothesizing a continued decline throughout life.

Multi-parametric quantitative magnetic resonance imaging of the upper arm muscles of patients with spinal muscular atrophy.

Quantitative magnetic resonance imaging (qMRI) is frequently used to map the disease state and disease progression in the lower extremity muscles of patients with spinal muscular atrophy (SMA). This is in stark contrast to the almost complete lack of data on the upper extremity muscles, which are essential for carrying out daily activities. The aim of this study was therefore to assess the disease state in the upper arm muscles of patients with SMA in comparison with healthy controls by quantitative assessment of fat fraction, diffusion indices, and water T2 relaxation times, and to relate these measures to muscle force.

Cardiopulmonary exercise testing in neuromuscular disease: a systematic review.

Introduction: Cardiopulmonary exercise testing (CPET) is increasingly used to determine aerobic fitness in health and disability conditions. Patients with neuromuscular diseases (NMDs) often present with symptoms of cardiac and/or skeletal muscle dysfunction and fatigue that might impede the ability to deliver maximal cardiopulmonary effort. Although an increasing number of studies report on NMDs' physical fitness, the applicability of CPET remains largely unknown.

Magnetic resonance reveals mitochondrial dysfunction and muscle remodelling in spinal muscular atrophy.

Genetic therapy has changed the prognosis of hereditary proximal spinal muscular atrophy, although treatment efficacy has been variable. There is a clear need for deeper understanding of underlying causes of muscle weakness and exercise intolerance in patients with this disease to further optimize treatment strategies. Animal models suggest that in addition to motor neuron and associated musculature degeneration, intrinsic abnormalities of muscle itself including mitochondrial dysfunction contribute to the disease aetiology.

Motor unit reserve capacity in spinal muscular atrophy during fatiguing endurance performance.

Objective: To investigate the availability of any motor unit reserve capacity during fatiguing endurance testing in patients with spinal muscular atrophy (SMA).

Methods: We recorded surface electromyography (sEMG) of various muscles of upper- and lower extremities of 70 patients with SMA types 2-4 and 19 healthy controls performing endurance shuttle tests (ESTs) of arm and legs. We quantitatively evaluated the development of fatigability and motor unit recruitment using time courses of median frequencies and amplitudes of sEMG signals.

Correlates of Fatigability in Patients With Spinal Muscular Atrophy.

Objective: To determine the associations between fatigability and muscle strength, motor function, neuromuscular junction (NMJ) function, and perceived fatigue in spinal muscular atrophy (SMA), we assessed 61 patients with SMA.

Methods: Fatigability was defined as the inability to continue a 20-minute submaximal repetitive task of either walking or proximal or distal arm function and expressed as drop-out on the Endurance Shuttle Test Combined Score (ESTCS). We assessed muscle strength with the Medical Research Council (MRC) sum score, motor function with the Hammersmith Functional Motor Scale Expanded (HFMSE) and Motor Function Measure (MFM), NMJ function with repetitive nerve stimulation of the accessory and ulnar nerve, and perceived fatigue with the PROMIS Fatigue Short Form questionnaire in 61 children and adults with SMA types 2-4.

Muscle strength and motor function in adolescents and adults with spinal muscular atrophy.

Objective: To assess longitudinal patterns of muscle strength, motor function, and maximal compound muscle action potential amplitudes (CMAP) in older patients with spinal muscular atrophy (SMA), hypothesizing a continued decline of motor function parameters throughout life.

Methods: We measured muscle strength (Medical Research Council), motor function (Hammersmith Functional Motor Scale Expanded [HFMSE] and Motor Function Measure), and CMAP in treatment-naive patients. We used both longitudinal and cross-sectional data in mixed models to analyze natural history patterns.

Quantitative MRI of skeletal muscle in a cross-sectional cohort of patients with spinal muscular atrophy types 2 and 3.

The aim of this study was to document upper leg involvement in spinal muscular atrophy (SMA) with quantitative MRI (qMRI) in a cross-sectional cohort of patients of varying type, disease severity and age. Thirty-one patients with SMA types 2 and 3 (aged 29.6 [7.

Fatigability in spinal muscular atrophy: validity and reliability of endurance shuttle tests.

Background: To determine construct validity and test-retest reliability of Endurance Shuttle Tests as outcome measures for fatigability of remaining motor functions in children and adults with Spinal Muscular Atrophy (SMA) across the severity spectrum.

Results: We assessed the Endurance Shuttle - Nine Hole Peg Test (ESNHPT), - Box and Block Test (ESBBT) and - Walk Test (ESWT) in 61 patients with SMA types 2-4, 25 healthy controls (HC) and 15 disease controls (DC). Convergent validity, discriminative validity and test-retest reliability were investigated.

Natural history of lung function in spinal muscular atrophy.

Background: Respiratory muscle weakness is an important feature of spinal muscular atrophy (SMA). Progressive lung function decline is the most important cause of mortality and morbidity in patients. The natural history of lung function in SMA has, however, not been studied in much detail.

Natural course of scoliosis and lifetime risk of scoliosis surgery in spinal muscular atrophy.

Objective: To investigate the natural course of scoliosis and to estimate lifetime probability of scoliosis surgery in spinal muscular atrophy (SMA).

Methods: We analyzed cross-sectional data from 283 patients from our population-based cohort study. Additional longitudinal data on scoliosis progression and spinal surgery were collected from 36 consecutive patients who received scoliosis surgery at our center.