Treadmill running and mechanical overloading improved the strength of the plantaris muscle in the dystrophin-desmin double knockout (DKO) mouse.

Limited knowledge exists regarding the chronic effect of muscular exercise on muscle function in a murine model of severe Duchenne muscular dystrophy (DMD). Here we determined the effects of 1 month of voluntary wheel running (WR), 1 month of enforced treadmill running (TR) and 1 month of mechanical overloading resulting from the removal of the synergic muscles (OVL) in mice lacking both dystrophin and desmin (DKO). Additionally, we examined the effect of activin receptor administration (AR). DKO mice, displaying severe muscle weakness, atrophy and greater susceptibility to contraction-induced functional loss, were exercised or treated with AR at 1 month of age and in situ force production of lower leg muscle was measured at the age of 2 months. We found that TR and OVL increased absolute maximal force and the rate of force development of the plantaris muscle in DKO mice. In contrast, those of the tibialis anterior (TA) muscle remained unaffected by TR and WR. Furthermore, the effects of TR and OVL on plantaris muscle function in DKO mice closely resembled those in mdx mice, a less severe murine DMD model. AR also improved absolute maximal force and the rate of force development of the TA muscle in DKO mice. In conclusion, exercise training improved plantaris muscle weakness in severely affected dystrophic mice. Consequently, these preclinical results may contribute to fostering further investigations aimed at assessing the potential benefits of exercise for DMD patients, particularly resistance training involving a low number of intense muscle contractions. KEY POINTS: Very little is known about the effects of exercise training in a murine model of severe Duchenne muscular dystrophy (DMD). One reason is that it is feared that chronic muscular exercise, particularly that involving intense muscle contractions, could exacerbate the disease. In DKO mice lacking both dystrophin and desmin, characterized by severe lower leg muscle weakness, atrophy and fragility in comparison to the less severe DMD mdx model, we found that enforced treadmill running improved absolute maximal force of the plantaris muscle, while that of tibialis anterior muscle remained unaffected by both enforced treadmill and voluntary wheel running. Furthermore, mechanical overloading, a non-physiological model of chronic resistance exercise, reversed plantaris muscle weakness. Consequently, our findings may have the potential to alleviate concerns and pave the way for exploring the prescription of endurance and resistance training as a viable therapeutic approach for the treatment of dystrophic patients. Additionally, such interventions may serve in mitigating the pathophysiological mechanisms induced by physical inactivity.

Effect of sirolimus on muscle in inclusion body myositis observed with magnetic resonance imaging and spectroscopy.

BACKGROUND: Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1-year longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31P MRS) in a placebo-controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles. METHODS: Quantitative MRI and 31P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year-1, and 21 healthy controls. Assessments included fat fraction (FF), contractile cross-sectional area (cCSA), and water T2 in global leg and thigh segments, muscle groups, individual muscles, as well as 31P MRS indices in quadriceps or triceps surae. Analyses covered patient-control comparisons, annual change assessments via standard t-tests and linear mixed models, calculation of standardized response means (SRM), and exploration of correlations between MRI, 31P MRS, functional, strength, and clinical parameters. RESULTS: The quadriceps and gastrocnemius medialis muscles had the highest FF values, displaying notable heterogeneity and asymmetry, particularly in the quadriceps. In the placebo group, the median 1-year FF increase in the quadriceps was 3.2% (P < 0.001), whereas in the sirolimus group, it was 0.7% (P = 0.033). Both groups experienced a significant decrease in cCSA in the quadriceps after 1 year (P < 0.001), with median changes of 12.6% for the placebo group and 5.5% for the sirolimus group. Differences in FF and cCSA changes between the two groups were significant (P < 0.001). SRM values for FF and cCSA were 1.3 and 1.4 in the placebo group and 0.5 and 0.8 in the sirolimus group, respectively. Water T2 values were highest in the quadriceps muscles of both groups, significantly exceeding control values in both groups (P < 0.001) and were higher in the placebo group than in the sirolimus group. After treatment, water T2 increased significantly only in the sirolimus group's quadriceps (P < 0.01). Multiple 31P MRS indices were abnormal in patients compared to controls and remained unchanged after treatment. Significant correlations were identified between baseline water T2 and FF at baseline and the change in FF (P < 0.001). Additionally, significant correlations were observed between FF, cCSA, water T2, and functional and strength outcome measures. CONCLUSIONS: This study has demonstrated that quantitative MRI/31P MRS can discern measurable differences between placebo and sirolimus-treated IBM patients, offering promise for future therapeutic trials in idiopathic inflammatory myopathies such as IBM.

Poor Correlation between Diaphragm Thickening Fraction and Transdiaphragmatic Pressure in Mechanically Ventilated Patients and Healthy Subjects.

BACKGROUND: The relationship between the diaphragm thickening fraction and the transdiaphragmatic pressure, the reference method to evaluate the diaphragm function, has not been clearly established. This study investigated the global and intraindividual relationship between the thickening fraction of the diaphragm and the transdiaphragmatic pressure. The authors hypothesized that the diaphragm thickening fraction would be positively and significantly correlated to the transdiaphragmatic pressure, in both healthy participants and ventilated patients. METHODS: Fourteen healthy individuals and 25 mechanically ventilated patients (enrolled in two previous physiologic investigations) participated in the current study. The zone of apposition of the right hemidiaphragm was imaged simultaneously to transdiaphragmatic pressure recording within different breathing conditions, i.e., external inspiratory threshold loading in healthy individuals and various pressure support settings in patients. A blinded offline breath-by-breath analysis synchronously computed the changes in transdiaphragmatic pressure, the diaphragm pressure-time product, and diaphragm thickening fraction. Global and intraindividual relationships between variables were assessed. RESULTS: In healthy subjects, both changes in transdiaphragmatic pressure and diaphragm pressure-time product were moderately correlated to diaphragm thickening fraction (repeated measures correlation = 0.40, P < 0.0001; and repeated measures correlation = 0.38, P < 0.0001, respectively). In mechanically ventilated patients, changes in transdiaphragmatic pressure and thickening fraction were weakly correlated (repeated measures correlation = 0.11, P = 0.008), while diaphragm pressure-time product and thickening fraction were not (repeated measures correlation = 0.04, P = 0.396). Individually, changes in transdiaphragmatic pressure and thickening fraction were significantly correlated in 8 of 14 healthy subjects (ρ = 0.30 to 0.85, all P < 0.05) and in 2 of 25 mechanically ventilated patients (ρ = 0.47 to 0.64, all P < 0.05). Diaphragm pressure-time product and thickening fraction correlated in 8 of 14 healthy subjects (ρ = 0.41 to 0.82, all P < 0.02) and in 2 of 25 mechanically ventilated patients (ρ = 0.63 to 0.66, all P < 0.01). CONCLUSIONS: Overall, diaphragm function as assessed with transdiaphragmatic pressure was weakly related to diaphragm thickening fraction. The diaphragm thickening fraction should not be used in healthy subjects or ventilated patients when changes in diaphragm function are evaluated.

MRI and muscle imaging for idiopathic inflammatory myopathies.

Although idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases nearly all patients display muscle inflammation. Originally, muscle biopsy was considered as the gold standard for IIM diagnosis. The development of muscle imaging led to revisiting not only the IIM diagnosis strategy but also the patients' follow-up. Different techniques have been tested or are in development for IIM including positron emission tomography, ultrasound imaging, ultrasound shear wave elastography, though magnetic resonance imaging (MRI) remains the most widely used technique in routine. Whereas guidelines on muscle imaging in myositis are lacking here we reviewed the relevance of muscle imaging for both diagnosis and myositis patients' follow-up. We propose recommendations about when and how to perform MRI on myositis patients, and we describe new techniques that are under development.

Free-Living Physical Activity and Sedentary Behaviour in Autoimmune Myasthenia Gravis: A Cross-Sectional Study.

BACKGROUND: Muscle weakness and fatigability, the prominent symptoms of autoimmune myasthenia gravis (MG), negatively impact daily function and quality of life (QoL). It is currently unclear as to what extent symptoms limit activity and whether physical activity (PA) behaviours are associated with reduced QoL. OBJECTIVES: This study aimed to describe habitual PA patterns and explore relationships between PA metrics, clinical MG characteristics, and health-related QoL (HRQoL). METHODS: PA data from a tri-axial trunk accelerometer worn for seven days, was collected from females with generalized, stable MG and compared to control subjects. MG-specific evaluations, the six-minute walk test and knee extension strength were assessed in individuals with MG (IwMG). Mann-Whitney tests were used to study between-group differences. Spearman rank correlation coefficient was performed to explore relationships between variables. RESULTS: Thirty-three IwMG (mean (SD) age 45 (11) years) and 66 control subjects were included. IwMG perform less vigorous-intensity PA than control subjects (p = 0.001), spend more time sedentary (p = 0.02) and engage in less and shorter durations of moderate-vigorous-intensity PA (MVPA). For IwMG, habitual PA correlated positively with 6 min walking distance (rho = 0.387, p = 0.029) and negatively with body mass index (rho = -0.407, p = 0.019). We did not find any association between PA or sedentary behaviour and; HRQoL, symptom severity nor lower limb strength. CONCLUSIONS: Individuals with stable MG perform less PA, at lower intensities, and are more inactive than control individuals. Further research is warranted to understand factors influencing PA patterns in MG and whether interventions could be successful in increasing PA quantity and intensity in IwMG.

Non-invasive assessment of skeletal muscle fibrosis in mice using nuclear magnetic resonance imaging and ultrasound shear wave elastography.

Fibrosis is a key pathological feature in muscle disorders, but its quantification mainly relies on histological and biochemical assays. Muscle fibrosis most frequently is entangled with other pathological processes, as cell membrane lesions, inflammation, necrosis, regeneration, or fatty infiltration, making in vivo assessment difficult. Here, we (1) describe a novel mouse model with variable levels of induced skeletal muscle fibrosis displaying minimal inflammation and no fat infiltration, and (2) report how fibrosis affects non-invasive metrics derived from nuclear magnetic resonance (NMR) and ultrasound shear-wave elastography (SWE) associated with a passive biomechanical assay. Our findings show that collagen fraction correlates with multiple non-invasive metrics. Among them, muscle stiffness as measured by SWE, T2, and extracellular volume (ECV) as measured by NMR have the strongest correlations with histology. We also report that combining metrics in a multi-modality index allowed better discrimination between fibrotic and normal skeletal muscles. This study demonstrates that skeletal muscle fibrosis leads to alterations that can be assessed in vivo with multiple imaging parameters. Furthermore, combining NMR and SWE passive biomechanical assay improves the non-invasive evaluation of skeletal muscle fibrosis and may allow disentangling it from co-occurring pathological alterations in more complex scenarios, such as muscular dystrophies.

Lean regional muscle volume estimates using explanatory bioelectrical models in healthy subjects and patients with muscle wasting.

BACKGROUND: The availability of non-invasive, accessible, and reliable methods for estimating regional skeletal muscle volume is paramount in conditions involving primary and/or secondary muscle wasting. This work aimed at (i) optimizing serial bioelectrical impedance analysis (SBIA ) by computing a conductivity constant based on quantitative magnetic resonance imaging (MRI) data and (ii) investigating the potential of SBIA for estimating lean regional thigh muscle volume in patients with severe muscle disorders. METHODS: Twenty healthy participants with variable body mass index and 20 patients with idiopathic inflammatory myopathies underwent quantitative MRI. Anatomical images and fat fraction maps were acquired in thighs. After manual muscle segmentation, lean thigh muscle volume (lVMRI ) was computed. Subsequently, multifrequency (50 to 350 kHz) serial resistance profiles were acquired between current skin electrodes (i.e. ankle and hand) and voltage electrodes placed on the anterior thigh. In vivo values of the muscle electrical conductivity constant were computed using data from SBIA and MRI gathered in the right thigh of 10 healthy participants. Lean muscle volume (lVBIA ) was derived from SBIA measurements using this newly computed constant. Between-day reproducibility of lVBIA was studied in six healthy participants. RESULTS: Electrical conductivity constant values ranged from 0.82 S/m at 50 kHz to 1.16 S/m at 350 kHz. The absolute percentage difference between lVBIA and lVMRI was greater at frequencies >270 kHz (P < 0.0001). The standard error of measurement and the intra-class correlation coefficient for lVBIA computed from measurements performed at 155 kHz (i.e. frequency with minimal difference) against lVMRI were 6.1% and 0.95 in healthy participants and 9.4% and 0.93 in patients, respectively. Between-day reproducibility of lVBIA was as follows: standard error of measurement = 4.6% (95% confidence interval [3.2, 7.8] %), intra-class correlation coefficient = 0.98 (95% confidence interval [0.95, 0.99]). CONCLUSIONS: These findings demonstrate a strong agreement of lean muscle volume estimated using SBIA against quantitative MRI in humans, including in patients with severe muscle wasting and fatty degeneration. SBIA shows promises for non-invasive, fast, and accessible estimation and follow-up of lean regional skeletal muscle volume for transversal and longitudinal studies.

Effects of Repetitive Transcranial Magnetic Stimulation and Multicomponent Therapy in Patients With Fibromyalgia: A Randomized Controlled Trial.

OBJECTIVE: Fibromyalgia (FM) is a chronic painful condition partly due to alterations in pain modulation by the central nervous system. Multicomponent therapy (MT) and repetitive transcranial magnetic stimulation (rTMS) have both been reported as pain modulators in patients with FM. The aim of this study was to compare the effects of rTMS on pain with a combination of MT and rTMS versus MT alone. METHODS: Thirty-nine FM patients with visual analog scale (VAS) results for pain of ≥40 mm were randomized to active or sham rTMS (high-frequency, primary motor cortex M1) plus 12 weeks of MT (3 sessions per week combining aerobic training, pool-based exercises, and relaxation). Repetitive TMS was started 2 weeks prior to MT and maintained until the end of the program (week 14). Assessments were achieved at baseline, at week 14, and at 6 months (week 40) after completion of the program. The main criterion was pain reduction, as assessed by the weekly mean self-reported level of pain (reported daily). Secondary outcomes were cardiorespiratory fitness (graded maximal exercise test), cardiac autonomic adaptations, and FM impact (using scales for FM impact, depression, sleep efficiency, and pain catastrophizing). RESULTS: The reduction of the weekly mean of pain reported daily did not differ significantly between groups (using repeated measures of analysis of variance [ANOVA]). Two-way ANOVAs showed that pain VAS results, as well as cardiorespiratory fitness, quality of life, depression, and catastrophizing, improved significantly at week 14 and remained stable until week 40. Neither cardiac autonomic adaptations nor sleep efficiency changed significantly. CONCLUSION: Repetitive TMS did not reduce pain in patients with FM who followed the MT program.

Sirolimus for treatment of patients with inclusion body myositis: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2b trial.

BACKGROUND: Inclusion body myositis is the most frequent myositis in patients older than 50 years. Classical immunosuppressants are ineffective in treating inclusion body myositis, and to date there are no recommendations for pharmacological approaches to treatment. When used after organ transplantation, sirolimus can block the proliferation of effector T cells, while preserving T regulatory cells, and induce autophagy, all of which are processes that are impaired in inclusion body myositis. In this pilot study, we aimed to test the efficacy of sirolimus in patients with inclusion body myositis. METHODS: This randomised, double-blind, placebo-controlled, proof-of-concept, phase 2b trial was done at a single hospital in Paris, France. The study included men and women (aged 45-80 years) who had a defined diagnosis of inclusion body myositis according to established criteria. Eligible participants were randomly assigned (1:1) to receive once-daily oral sirolimus 2 mg or placebo. Centralised balanced block randomisation (blocks of four) was computer generated without stratification. The study comprised a 15-day screening period (days -15 to 0) and a 52-week treatment period (day 0 to month 12). The primary endpoint was the relative percentage change from baseline to month 12 in maximal voluntary isometric knee extension strength. Secondary endpoints included the following assessments at months 6 and 12: 6-min walking distance, isometric muscle strength for hand grip (finger flexors), knee flexion and elbow flexion and extension, forced vital capacity, muscle replacement with fat measured by quantitative nuclear MRI, Inclusion Body Myositis Weakness Composite Index (IBMWCI), Inclusion Body Myositis Functional Rating Scale (IBMFRS), Health Assessment Questionnaire without Disability Index (HAQ-DI), and analyses of T-cell subpopulations by mass cytometry. The primary analysis was done on the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT02481453. FINDINGS: Between July 15, 2015, and May 13, 2016, we screened 285 patients, 44 of whom were randomly allocated to sirolimus (22 patients) or placebo (22 patients). We observed no difference in the primary outcome of relative percentage change from baseline to month 12 of the maximal voluntary isometric knee extension strength (median difference 3·78, 95% CI -10·61 to 17·31; p=0·85). For secondary outcomes, differences between the groups were not significant for changes in strength of other muscle groups (grip, elbow flexion and extension, or knee flexion), IBMWCI, IBMFRS, and lower limb muscle fat fraction. However, we observed significant differences in favour of sirolimus between the study groups for HAQ-DI, forced vital capacity, thigh fat fraction, and 6-min walking distance. Ten (45%) of 22 patients in the sirolimus group had a serious adverse event compared with six (27%) of 22 patients in the placebo group. Four (18%) patients in the sirolimus group stopped their treatment because of adverse events (severe mouth ulcers, aseptic pneumonia, renal insufficiency, and peripheral lower limb oedema), which resolved after treatment discontinuation. Canker sores were the most frequent side-effect and were mainly mild or moderate in ten patients. INTERPRETATION: We found no evidence for efficacy of sirolimus for treating inclusion body myositis based on maximal voluntary isometric knee extension strength and other muscle strength measures, and the side-effects of treatment were substantial for some patients. However, we believe there was enough evidence of benefit in certain secondary outcomes to pursue a multicentre phase 3 trial to further assess the safety and efficacy of sirolimus. FUNDING: Institut national de la santé et de la recherche médicale, Direction générale de l'offre de soins, and Association Française contre les Myopathies.

Ultrasound shear wave elastography for assessing diaphragm function in mechanically ventilated patients: a breath-by-breath analysis.

BACKGROUND: Diaphragm dysfunction is highly prevalent in mechanically ventilated patients. Recent work showed that changes in diaphragm shear modulus (ΔSMdi) assessed using ultrasound shear wave elastography (SWE) are strongly related to changes in Pdi (ΔPdi) in healthy subjects. The aims of this study were to investigate the relationship between ΔSMdi and ΔPdi in mechanically ventilated patients, and whether ΔSMdi is responsive to change in respiratory load when varying the ventilator settings. METHODS: A prospective, monocentric study was conducted in a 15-bed ICU. Patients were included if they met the readiness-to-wean criteria. Pdi was continuously monitored using a double-balloon feeding catheter orally introduced. The zone of apposition of the right hemidiaphragm was imaged using a linear transducer (SL10-2, Aixplorer, Supersonic Imagine, France). Ultrasound recordings were performed under various pressure support settings and during a spontaneous breathing trial (SBT). A breath-by-breath analysis was performed, allowing the direct comparison between ΔPdi and ΔSMdi. Pearson's correlation coefficients (r) were used to investigate within-individual relationships between variables, and repeated measure correlations (R) were used for determining overall relationships between variables. Linear mixed models were used to compare breathing indices across the conditions of ventilation. RESULTS: Thirty patients were included and 930 respiratory cycles were analyzed. Twenty-five were considered for the analysis. A significant correlation was found between ΔPdi and ΔSMdi (R = 0.45, 95% CIs [0.35 0.54], p < 0.001). Individual correlation displays a significant correlation in 8 patients out of 25 (r = 0.55-0.86, all p < 0.05, versus r = - 0.43-0.52, all p > 0.06). Changing the condition of ventilation similarly affected ΔPdi and ΔSMdi. Patients in which ΔPdi-ΔSMdi correlation was non-significant had a faster respiratory rate as compared to that of patient with a significant ΔPdi-ΔSMdi relationship (median (Q1-Q3), 25 (18-33) vs. 21 (15-26) breaths.min-1, respectively). CONCLUSIONS: We demonstrate that ultrasound SWE may be a promising surrogate to Pdi in mechanically ventilated patients. Respiratory rate appears to negatively impact SMdi measurement. Technological developments are needed to generalize this method in tachypneic patients. TRIAL REGISTRATION: NCT03832231 .

Ultrafast ultrasound coupled with cervical magnetic stimulation for non-invasive and non-volitional assessment of diaphragm contractility.

KEY POINTS: Twitch transdiaphragmatic pressure elicited by cervical magnetic stimulation of the phrenic nerves is a fully non-volitional method for assessing diaphragm contractility in humans, yet it requires invasive procedures such as oesophageal and gastric catheter balloons.  Ultrafast ultrasound enables a very high frame rate allowing the capture of transient events, such as muscle contraction elicited by nerve stimulation (twitch). Whether indices derived from ultrafast ultrasound can be used as an alternative to the invasive measurement of twitch transdiaphragmatic pressure is unknown.  Our findings demonstrate that maximal diaphragm tissue velocity assessed using ultrafast ultrasound following cervical magnetic stimulation is reliable, sensitive to change in cervical magnetic stimulation intensity, and correlates to twitch transdiaphragmatic pressure.  This approach provides a novel fully non-invasive and non-volitional tool for the assessment of diaphragm contractility in humans. ABSTRACT: Measuring twitch transdiaphragmatic pressure (Pdi,tw ) elicited by cervical magnetic stimulation (CMS) is considered as a reference method for the standardized evaluation of diaphragm function. Yet, the measurement of Pdi requires invasive oesophageal and gastric catheter-balloons. Ultrafast ultrasound is a non-invasive imaging technique enabling frame rates high enough to capture transient events such as evoked muscle contractions. This study investigated relationships between indices derived from ultrafast ultrasound and Pdi,tw , and how these indices might be used to estimate Pdi,tw . CMS was performed in 13 healthy volunteers from 30% to 100% of maximal stimulator intensity in units of 10% in a randomized order. Pdi,tw was measured and the right hemidiaphragm was imaged using a custom ultrafast ultrasound sequence with 1 kHz framerate. Maximal diaphragm axial velocity (Vdi ,max ) and diaphragm thickening fraction (TFdi,tw ) were computed. Intra-session reliability was assessed. Repeated-measures correlation (R) and Spearman correlation coefficients (ρ) were used to assess relationships between variables. Intra-session reliability was strong for Pdi,tw and Vdi,max and moderate for TFdi,tw . Vdi,max correlated with Pdi,tw in all subjects (0.64 < ρ < 1.00, R = 0.75; all P < 0.05). TFdi,tw correlated with Pdi,tw in eight subjects only (0.85 < ρ < 0.93, R = 0.69; all P < 0.05). Coupling ultrafast ultrasound and CMS shows promise for the non-invasive and fully non-volitional assessment of diaphragm contractility. This approach opens up the prospect of both diagnosis and follow-up of diaphragm contractility in clinical populations.

Relationship between change in physical activity and in clinical status in patients with idiopathic inflammatory myopathy: A prospective cohort study.

OBJECTIVE: This study aimed to investigate the relationship between changes in clinical status on daily life physical activity (PA) in patients with idiopathic inflammatory myopathy (IIM). METHODS: Patients with dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) or overlap myositis (OM) who presented either a new-onset or relapsing IIM, stable disease on maintenance therapy or were undergoing immunosuppressant tapering were included. Patients were evaluated at inclusion (V0), and at two follow-up visits (V1, 94±12 days from V0; V2, 96±17 days from V1). The American College of Rheumatology/European League against Rheumatism (ACR/EULAR) response criteria was recorded. PA assessed using 14-days raw accelerometry data gathered using a wrist-worn accelerometer after each visit (mean daily Euclidean norm minus 1 g (ENMO) was computed). RESULTS: Fifty-five patients (16 OM, 27 IMNM and 12 DM) were included. At baseline, 67% of patients had an ENMO Z-score less than 1. At inclusion, ENMO mainly correlated with health assessment questionnaire score (HAQ, ρ=-0.51, p<0.01), manual muscle testing 8 (MMT8, ρ=0.42, p<0.01), creatinine level (ρ=0.41, p<0.01), and SF-36 physical functioning score (ρ=0.38, p<0.002). At follow-up, ENMO changes mainly correlated with changes in MMT8, HAQ, SF-36 fatigue, and depression score (all ρ>0.43, all p<0.001). Level of agreement between ACR/EULAR response criteria and changes in PA was 15, 45, and 90% for minimal (n = 13), moderate (n = 20), and major (n = 10) improvements, respectively. CONCLUSION: Baseline PA levels and change in PA correlated with muscle strength and function, yet changes in PA were also influenced by psychological status. Only patients with major improvements on the ACR/EULAR criteria had significant increase in PA. Accelerometer may serve as an objective tool to define a clinically relevant real-life outcome.

Routine monitoring of isometric knee extension strength in patients with muscle impairments using a new portable device: cross-validation against a standard isokinetic dynamometer.

OBJECTIVE: Muscle strength is a critical clinical hallmark in both health and disease. The current study introduces a novel portable device prototype (MyoQuad) for assessing and monitoring maximal voluntary isometric knee extension torque (MVIT). APPROACH: Fifty-six patients with inclusion body myositis were studied. Knee extension weakness is a key feature in this inflammatory muscle disease. Cross-validation with an isokinetic dynamometer (Biodex System 3 Pro) was performed. Between-day reproducibility and ability to monitor changes in muscle strength over time compared to the gold standard method as a reference, were also investigated. MAIN RESULTS: The measurement was feasible even in the weakest patients. Agreement between methods was excellent (standard error of measurement (SEM) was 3.8 Nm and intra-class correlation coefficient (ICC) was 0.973). Least significant difference (LSD) was 4.9 and 5.3 Nm for the MyoQuad and the Biodex, respectively Measurements using the MyoQuad exhibited excellent between-day reproducibility (SEM was 2.4 Nm and ICC was 0.989 versus 2.6 Nm and 0.988 using the Biodex). Changes in MVIT at 6 and 12 months were similar between methods (timepoint × method interaction was not significant; all p  > 0.19); strength changes classified according to LSD at 6 and 12 months were consistent between methods (>70% consistent classification)). SIGNIFICANCE: The measurement of MVIT using the MyoQuad offers a cost-effective, portable and immediate alternative for the routine measurement of maximal voluntary isometric strength of the quadriceps. The MyoQuad offers a comfort and stability that cannot be provided by standard hand-held dynamometers. These results support quantitative muscle strength assessment using fixed yet flexible dynamometry within clinical routine and multicenter trials.

Diaphragm shear modulus reflects transdiaphragmatic pressure during isovolumetric inspiratory efforts and ventilation against inspiratory loading.

The reference method for the assessment of diaphragm function relies on the measurement of transdiaphragmatic pressure (Pdi). Local muscle stiffness measured using ultrafast shear wave elastography (SWE) provides reliable estimates of muscle force in locomotor muscles. This study aimed at investigating whether SWE could be used as a surrogate of Pdi to evaluate diaphragm function. Fifteen healthy volunteers underwent a randomized stepwise inspiratory loading protocol of 0-60% of maximal isovolumetric inspiratory pressure during closed-airways maneuvers and 0-50% during ventilation against an external inspiratory threshold load. During all tasks, Pdi was measured and SWE was used to assess shear modulus of the right hemidiaphragm (SMdi) at the zone of apposition. Pearson correlation coefficients ( r) and repeated-measures correlation coefficients ( R) were computed to determine within-individual and overall relationships between Pdi and SMdi, respectively. During closed-airways maneuvers, mean Pdi correlated to mean SMdi in all participants [ r ranged from 0.77 to 0.96, all P < 0.01; R = 0.82, 95% confidence intervals (0.76, 0.86), P < 0.01]. During ventilation against inspiratory threshold loading, Pdi swing correlated to maximal SMdi in all participants [ r ranged from 0.40 to 0.90, all P < 0.01; R = 0.70, 95% confidence intervals (0.66, 0.73), P < 0.001]. Changes in diaphragm stiffness as assessed by SWE reflect changes in transdiaphragmatic pressure. SWE provides a new opportunity for direct and noninvasive assessment of diaphragm function. NEW & NOTEWORTHY Accurate and specific estimation of diaphragm effort is critical for evaluating and monitoring diaphragm dysfunction. The measurement of transdiaphragmatic pressure requires the use of invasive gastric and esophageal probes. In the present work, we demonstrate that changes in diaphragm stiffness assessed with ultrasound shear wave elastography reflect changes in transdiaphragmatic pressure, therefore offering a new noninvasive method for gauging diaphragm effort.

Muscle Shear Wave Elastography in Inclusion Body Myositis: Feasibility, Reliability and Relationships with Muscle Impairments.

Degenerative muscle changes may be associated with changes in muscle mechanical properties. Shear wave elastography (SWE) allows direct quantification of muscle shear modulus (MSM). The aim of this study was to evaluate the feasibility and reliability of SWE in the severely disordered muscle as observed in inclusion body myositis. To explore the clinical relevance of SWE, potential relationships between MSM values and level muscle impairments (weakness and ultrasound-derived muscle thickness and echo intensity) were investigated. SWE was performed in the biceps brachii at 100°, 90°, 70° and 10° elbow flexion in 34 patients with inclusion body myositis. MSM was assessed before and after five passive stretch-shortening cycles at 4°/s from 70° to 10° elbow angle and after three maximal voluntary contractions to evaluate potential effects of muscle pre-conditioning. Intra-class correlation coefficients and standard errors of measurements were >0.83 and <1.74 kPa and >0.64 and <1.89 kPa for within- and between-day values, respectively. No significant effect of passive loading-unloading and maximal voluntary contractions was found (all p values >0.18). MSM correlated to predicted muscle strength (all Spearman correlation coefficients (ρ) > 0.36; all p values < 0.05). A significant correlation was found between muscle echo intensity and muscle shear modulus at 70° only (ρ = 0.38, p <0.05). No correlation was found between muscle thickness and MSM (all ρ values > 0.23 and all p values > 0.25, respectively). Within- and between-day reliability of muscle SWE was satisfactory and moderate, respectively. SWE shows promise for assessing changes in mechanical properties of the severely disordered muscle. Further investigations are required to clarify these findings and to refine their clinical value.

Local Texture Anisotropy as an Estimate of Muscle Quality in Ultrasound Imaging.

This study introduces local pattern texture anisotropy as a novel parameter to differentiate healthy and disordered muscle and to gauge the severity of muscle impairments based on B-mode ultrasound images. Preliminary human results are also presented. A local pattern texture anisotropy index (TAI) was computed in one region of interest in the short head of the biceps brachii. The effects of gain settings and box sizes required for TAI computation were investigated. Between-day reliability was studied in patients with sporadic inclusion body myositis (n = 26). The ability of the TAI to discriminate dystrophic from healthy muscle was evaluated in patients with Duchenne muscular dystrophy and healthy controls (n = 16). TAI values were compared with a gray-scale index (GSI). TAI values were less influenced by gain settings than were GSI values. TAI had lower between-day variability (typical error = 2.3%) compared with GSI (typical error = 2.3% vs. 8.3%, respectively). Patients with Duchenne muscular dystrophy had lower TAIs than controls (0.76 ± 0.06 vs. 0.87 ± 0.03, respectively, p <0.05). At 40% gain, TAI values correlated with percentage predicted elbow flexor strength in inclusion body myositis (R = 0.63, p <0.001). The TAI may be a promising addition to other texture-based approaches for quantitative muscle ultrasound imaging.

Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy: A randomized controlled trial.

BACKGROUND: Previous randomized controlled trials investigating exercise training programs in facioscapulohumeral muscular dystrophy (FSHD) patients are scarce and of short duration only. This study assessed the safety and efficacy of a 6-month home-based exercise training program on fitness, muscle, and motor function in FSHD patients. METHODS: Sixteen FSHD patients were randomly assigned to training (TG) and control (CG) groups (both n = 8) in a home-based exercise intervention. Training consisted of cycling 3 times weekly for 35 minutes (combination of strength, high-intensity interval, and low-intensity aerobic) at home for 24 weeks. Patients in CG also performed an identical training program (CTG) after 24 weeks. The primary outcome was change in peak oxygen uptake (VO2 peak) measured every 6 weeks. The principal secondary outcomes were maximal quadriceps strength (MVC) and local quadriceps endurance every 12 weeks. Other outcome measures included maximal aerobic power (MAP) and experienced fatigue every 6 weeks, 6-minute walking distance every 12 weeks, and muscle characteristics from vastus lateralis biopsies taken pre- and postintervention. RESULTS: The compliance rate was 91% in TG. Significant improvements with training were observed in the VO2 peak (+19%, P = 0.002) and MAP by week 6 and further to week 24. Muscle endurance, MVC, and 6-minute walking distance increased and experienced fatigue decreased. Muscle fiber cross-sectional area and citrate synthase activity increased by 34% (P = 0.008) and 46% (P = 0.003), respectively. Dystrophic pathophysiologic patterns were not exacerbated. Similar improvements were experienced by TG and CTG. CONCLUSIONS: A combined strength and interval cycling exercise-training program compatible with patients' daily professional and social activities leads to significant functional benefits without compromising muscle tissue.