Evaluation of muscular activity duration in shoulders with rotator cuff tears using inertial sensors and electromyography.

Shoulder disorders, including rotator cuff tears, affect the shoulder function and result in adapted muscle activation. Although these adaptations have been studied in controlled conditions, free-living activities have not been investigated. Based on the kinematics measured with inertial sensors and portable electromyography, the objectives of this study were to quantify the duration of the muscular activation in the upper trapezius (UT), medial deltoid (MD) and biceps brachii (BB) during motion and to investigate the effect of rotator cuff tear in laboratory settings and daily conditions. The duration of movements and muscular activations were analysed separately and together using the relative time of activation (TEMG/mov). Laboratory measurements showed the parameter's reliability through movement repetitions (ICC > 0.74) and differences in painful shoulders compared with healthy ones (p < 0.05): longer activation for UT; longer activation for MD during abduction and tendency to shorter activation in other movements; shorter activation for BB. In daily conditions, TEMG/mov for UT was longer, whereas it was shorter for MD and BB (p < 0.05). Moreover, significant correlations were observed between these parameters and clinical scores. This study thus provides new insights into the rotator cuff tear effect on duration of muscular activation in daily activity.

Statines et effets indésirables musculaires [Statins and muscular side-effects]

Statins are effective in the treatment of hypercholesterolemia for primary and secondary prevention of cardiovascular disease. While most side effects of statins are mild and transient, muscular symptoms are relatively common (5 to 10% of patients), but rarely serious (myositis, rhabdomyolysis). In cases of myopathy, the severity of symptoms and the determination of CK (creatine kinase) determine whether discontinuation of statin is necessary. Alternative strategies are also suggested. This article reviews suggestions on the management of these complaints that are a challenge in clinical practice.

Défaillances respiratoires aiguës d'origine neuromusculaire [Acute respiratory failure due to neuromuscular disorders].

Numerous acute and chronic neuromuscular disorders may induce an acute ventilatory failure. The latter is sometimes triggered by a complication like a bronchial aspiration, a pneumonia, or an atelectasis. The acute ventilatory failure often develops insidiously and may be missed until the terminal event. Four different clinical presentations are depicted in this review: slowly progressive (Duchenne muscular dystrophy), rapidly progressive (Guillain-Barré syndrome), chronic with exacerbations (myasthenia gravis), and a form consecutive to critical care (critical care polyneuropathy and myopathy). For each type of ventilatory failure, the review discusses the preventive surveillance, the treatment of acute respiratory failure, and the long-term management.

Increased Presence of FOXP3+ Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood.

Juvenile dermatomyositis (JDM) is an immune-mediated inflammatory disease affecting the microvasculature of skin and muscle. CD4+CD25+FOXP3+ regulatory T cells (Tregs) are key regulators of immune homeostasis. A role for Tregs in JDM pathogenesis has not yet been established. Here, we explored Treg presence and function in peripheral blood and muscle of JDM patients. We analyzed number, phenotype and function of Tregs in blood from JDM patients by flow cytometry and in vitro suppression assays, in comparison to healthy controls and disease controls (Duchenne's Muscular Dystrophy). Presence of Tregs in muscle was analyzed by immunohistochemistry. Overall, Treg percentages in peripheral blood of JDM patients were similar compared to both control groups. Muscle biopsies of new onset JDM patients showed increased infiltration of numbers of T cells compared to Duchenne's muscular dystrophy. Both in JDM and Duchenne's muscular dystrophy the proportion of FOXP3+ T cells in muscles were increased compared to JDM peripheral blood. Interestingly, JDM is not a self-remitting disease, suggesting that the high proportion of Tregs in inflamed muscle do not suppress inflammation. In line with this, peripheral blood Tregs of active JDM patients were less capable of suppressing effector T cell activation in vitro, compared to Tregs of JDM in clinical remission. These data show a functional impairment of Tregs in a proportion of patients with active disease, and suggest a regulatory role for Tregs in JDM inflammation.

A PiggyBac-mediated approach for muscle gene transfer or cell therapy.

An emerging therapeutic approach for Duchenne muscular dystrophy is the transplantation of autologous myogenic progenitor cells genetically modified to express dystrophin. The use of this approach is challenged by the difficulty in maintaining these cells ex vivo while keeping their myogenic potential, and ensuring sufficient transgene expression following their transplantation and myogenic differentiation in vivo. We investigated the use of the piggyBac transposon system to achieve stable gene expression when transferred to cultured mesoangioblasts and into murine muscles. Without selection, up to 8% of the mesoangioblasts expressed the transgene from 1 to 2 genomic copies of the piggyBac vector. Integration occurred mostly in intergenic genomic DNA and transgene expression was stable in vitro. Intramuscular transplantation of mouse Tibialis anterior muscles with mesoangioblasts containing the transposon led to sustained myofiber GFP expression in vivo. In contrast, the direct electroporation of the transposon-donor plasmids in the mouse Tibialis muscles in vivo did not lead to sustained transgene expression despite molecular evidence of piggyBac transposition in vivo. Together these findings provide a proof-of-principle that piggyBac transposon may be considered for mesoangioblast cell-based therapies of muscular dystrophies.

Low penetrance in facioscapulohumeral muscular dystrophy type 1 with large pathological D4Z4 alleles: a cross-sectional multicenter study.

BackgroundFacioscapulohumeral muscular dystrophy type 1(FSHD1) is an autosomal dominant disorder associated with the contraction of D4Z4 less than 11 repeat units (RUs) on chromosome 4q35. Penetrance in the range of the largest alleles is poorly known. Our objective was to study the penetrance of FSHD1 in patients carrying alleles ranging between 6 to10 RUs and to evaluate the influence of sex, age, and several environmental factors on clinical expression of the disease. Methods A cross-sectional multicenter study was conducted in six French and one Swiss neuromuscular centers. 65 FSHD1 affected patients carrying a 4qA allele of 6¿10 RUs were identified as index cases (IC) and their 119 at-risk relatives were included. The age of onset was recorded for IC only. Medical history, neurological examination and manual muscle testing were performed for each subject. Genetic testing determined the allele size (number of RUs) and the 4qA/4qB allelic variant. The clinical status of relatives was established blindly to their genetic testing results. The main outcome was the penetrance defined as the ratio between the number of clinically affected carriers and the total number of carriers. Results Among the relatives, 59 carried the D4Z4 contraction. At the clinical level, 34 relatives carriers were clinically affected and 25 unaffected. Therefore, the calculated penetrance was 57% in the range of 6¿10 RUs. Penetrance was estimated at 62% in the range of 6¿8 RUs, and at 47% in the range of 9¿10 RUs. Moreover, penetrance was lower in women than men. There was no effect of drugs, anesthesia, surgery or traumatisms on the penetrance. Conclusions Penetrance of FSHD1 is low for largest alleles in the range of 9¿10 RUs, and lower in women than men. This is of crucial importance for genetic counseling and clinical management of patients and families.