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Neuromuscular ultrasound is a rapidly evolving technique for diagnosing, monitoring and facilitating treatment of patients with muscle and nerve disorders. It is a portable point-of-care technology that is non-invasive, painless and without ionizing radiation. Ultrasound can visualize muscle texture alterations indicating dystrophy or denervation, changes in size and anatomic continuity of nerve fascicles, and its dynamic imaging capabilities allow capturing of contractions and fasciculations. Ultrasound can also provide real-time guidance for needle placement, and can sometimes make a diagnosis when electromyography is not tolerated or not informative anymore. This review will focus on the technical and practical aspects of ultrasound as an imaging technique for muscles and nerves. It will discuss basic imaging principles, hardware and software setup, and provide examples of ultrasound use for visualizing muscle and nerve abnormalities with accuracy and confidence. The review is intended as a practical “how-to” guide to get started with neuromuscular ultrasound in daily practice. Les examens d’échographie dans le cas de pathologies neuromusculaires : un nouvel outil à votre disposition. Les examens d’échographie destinés aux pathologies neuromusculaires sont en mutation rapide. Ils permettent de diagnostiquer des troubles des muscles et des nerfs, d’assurer le suivi des patients atteints et de faciliter leur traitement. À la fois non-invasive et sans douleur, pouvant être utilisée sur les lieux des soins, cette technologie n’entraîne aucune radiation ionisante. De tels examens permettent ainsi de constater des altérations à la texture des muscles pouvant constituer des indices de dystrophie ou de dénervation mais aussi des modifications concernant la taille et la continuité anatomique des faisceaux nerveux. Ces capacités dynamiques d’imagerie permettent aussi de détecter des signes de contraction et de fasciculation. Ce n’est pas tout : les examens d’échographie peuvent aussi permettre un guidage en temps réel pour le positionnement d’une seringue et parfois faciliter l’établissement d’un diagnostic lorsqu’un examen d’électromyographie n’est pas toléré ou n’est plus en mesure de fournir des données utiles. Cette étude entend donc se pencher sur les aspects techniques et pratiques de ce type d’échographie destinée aux muscles et aux nerfs. Elle abordera les principes de base de l’imagerie, le type d’installation informatique requise ainsi que les logiciels utilisés. Elle fournira des exemples d’examens d’échographie permettant de détecter, avec exactitude et en toute confiance, des anomalies des muscles et des nerfs. En somme, cette étude a été conçue comme un guide pratique permettant, dans le cas de pathologies neuromusculaires, d’utiliser pour la première fois et quotidiennement des examens d’échographie.

Inactivating variants in PIEZO2, which encodes a stretch-gated ion channel, impair touch perception and proprioception. Visual cues partially compensate for these impairments, allowing affected persons to perform complex movements with greater accuracy. The ability to sense force, which is known as mechanosensation, provides humans and other animals with important information about the environment; it is crucial for social interactions, such as comforting or caressing, and is required for motor coordination. A number of anatomical classes of somatosensory neurons with distinct selectivity for mechanical stimuli have been identified, but the way in which these inputs combine to provide the richness of the human sense of touch remains unclear. 1 , 2 Similarly, proprioception is considered to be essential for posture and controlled movement, but little is known about the underlying mechanisms and the precise role . . .

Significance Duchenne muscular dystrophy (DMD) is a rare and devastating muscle disease caused by mutations in the X-linked DMD gene (which encodes the dystrophin protein). Serum biomarkers hold significant potential as objective phenotypic measures of DMD disease state, as well as potential measures of pharmacological effects of and response to therapeutic interventions. Here we describe a proteomics approach to determine serum levels of 1,125 proteins in 93 DMD patients and 45 controls. The study identified 44 biomarkers that differed significantly between patients and controls. These data are being made available to DMD researchers and clinicians to accelerate the search for new diagnostic, prognostic, and therapeutic approaches. Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy–Cincinnati Children’s Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and healthy volunteers at a 1% false-discovery rate, a large number of significant protein changes for such a small study. These biomarkers can be classified by known cellular processes and by age-dependent changes in protein concentration. Our findings demonstrate both the utility of this unbiased biomarker discovery approach and suggest potential new diagnostic and therapeutic avenues for ameliorating the burden of DMD and, we hope, other rare and devastating diseases.

Aims/hypothesisSmall cohort studies raise the hypothesis that corneal nerve abnormalities (including corneal nerve fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large cohort of participants with and without DSP.MethodsNine hundred and ninety-eight participants from five centres (516 with type 1 diabetes and 482 with type 2 diabetes) underwent CNFL quantification and clinical and electrophysiological examination. AUC and diagnostic thresholds were derived and validated in randomly selected samples using receiver operating characteristic analysis. Sensitivity analyses included latent class models to address the issue of imperfect reference standard.ResultsType 1 and type 2 diabetes subcohorts had mean age of 42 ± 19 and 62 ± 10 years, diabetes duration 21 ± 15 and 12 ± 9 years and DSP prevalence of 31% and 53%, respectively. Derivation AUC for CNFL was 0.77 in type 1 diabetes (p < 0.001) and 0.68 in type 2 diabetes (p < 0.001) and was approximately reproduced in validation sets. The optimal threshold for automated CNFL was 12.5 mm/mm2 in type 1 diabetes and 12.3 mm/mm2 in type 2 diabetes. In the total cohort, a lower threshold value below 8.6 mm/mm2 to rule in DSP and an upper value of 15.3 mm/mm2 to rule out DSP were associated with 88% specificity and 88% sensitivity.Conclusions/interpretationWe established the diagnostic validity and common diagnostic thresholds for CNFL in type 1 and type 2 diabetes. Further research must determine to what extent CNFL can be deployed in clinical practice and in clinical trials assessing the efficacy of disease-modifying therapies for DSP.

Background: The muscular dystrophies are a heterogeneous group of genetic muscle diseases with variable distribution of weakness and mode of inheritance. Methods: We previously performed a systematic review of worldwide population-based studies on Duchenne and Becker muscular dystrophies; the current study focused on the epidemiology of other muscular dystrophies using Medline and EMBASE databases. Two reviewers independently reviewed all abstracts, full-text articles, and abstracted data from 1985 to 2011. Pooling of prevalence estimates was performed using random-effect models. Results: A total of 1104 abstracts and 167 full-text articles were reviewed. Thirty-one studies met all eligibility criteria and were included in the final analysis. The overall pooled prevalence of combined muscular dystrophies was 16.14 (confidence interval [CI], 11.21-23.23) per 100,000. The prevalence estimates per 100,000 were 8.26 (CI, 4.99-13.68) for myotonic dystrophy, 3.95 (CI, 2.89-5.40) for facioscapulohumeral dystrophy, 1.63 (CI, 0.94-2.81) for limb girdle muscular dystrophy, and 0.99 (CI, 0.62-1.57) for congenital muscular dystrophies. Conclusions: The studies differed widely in their approaches to case ascertainment, and substantial gaps remain in the global estimates of many other types of muscular dystrophies. Additional epidemiological studies using standardized diagnostic criteria as well as multiple sources of case ascertainment will help address the economic impact and health care burden of muscular dystrophies worldwide. Revue systématique et méta-analyse de l’épidémiologie des dystrophies musculaires. Contexte: Les dystrophies musculaires constituent un groupe hétérogène de maladies musculaires génétiques ayant une distribution de la faiblesse et une hérédité variables. Méthode: Nous avons effectué antérieurement une revue systématique des études populationnelles du monde entier sur la dystrophie musculaire de Duchenne et celle de Becker. Cette étude, effectuée dans les bases de données Medline et EMBASE, cible l’épidémiologie d’autres dystrophies musculaires. Deux examinateurs indépendants ont revu tous les résumés, le texte intégral des articles et les données publiées de 1985 à 2011. Le regroupement des estimés de prévalence a été effectué au moyen de modèles à effets aléatoires. Résultats: En tout, 1104 résumés et 167 articles en texte intégral ont été revus. Trente et une études rencontraient tous les critères d’éligibilité et ont été incluses dans l’analyse finale. La prévalence globale des dystrophies musculaires combinées était de 16,14 (intervalle de confiance [IC] de 11,21 à 23,23) par 100,000 de population. Les estimés de prévalence par 100,000 étaient de 8,26 (IC : 4,99 à 13,68) pour la dystrophie myotonique, 3,95 (IC : 2,89 à 5,40) pour la myopathie facio-scapulo-humérale, 1,63 (IC : 0,94 à 2,81) pour la myopathie scapulo-humérale et 0,99 (IC : 0,62 à 1,57) pour les dystrophies musculaires congénitales. Conclusions: Les études utilisaient des approches sensiblement différentes pour l’identification des cas et il existe des écarts considérables dans les estimés globaux de plusieurs autres types de dystrophies musculaires. D’autres études épidémiologiques utilisant des critères diagnostiques standardisés ainsi que de multiples sources d’identification des cas aideront à faire face à l’impact économique et au fardeau des soins de santé engendrés par les dystrophies musculaires à l’échelle mondiale.

Introduction The North Star Ambulatory Assessment (NSAA) tool is a key instrument for measuring clinical outcomes in patients with Duchenne muscular dystrophy (DMD). To gain a better understanding of the longitudinal utility of the NSAA, we evaluated NSAA data from a phase II trial of 120 patients with DMD treated with domagrozumab or placebo. Methods The NSAA exploratory analyses included assessment of individual skills gained/lost, total skills gained/lost, cumulative loss of function, and the impact of transient loss of function due to a temporary disability on NSAA total score (temporary zero score). Results There was no significant difference in the total number of NSAA skills gained (mean 1.41 and 1.04, respectively; p = 0.3314) or lost (3.90 vs. 5.0; p = 0.0998) between domagrozumab- vs. placebo-treated patients at week 49. However, domagrozumab-treated patients were less likely to lose the ability to perform a NSAA item (hazard ratio 0.80, 95% confidence interval [CI]: 0.65–0.98, p = 0.029) over 48-weeks vs. placebo-treated patients. When temporary zero scores were changed to “not obtainable” (8 values from 7 patients), domagrozumab-treated patients scored higher on the NSAA total score versus placebo-treated patients (difference at week 49: 2.0, 95% CI: 0.1–3.9, p = 0.0359). Conclusions These exploratory analyses reveal additional approaches to interpreting the NSAA data beyond just change in NSAA total score. These observations also highlight the importance of reporting items as “not obtainable” for a patient with a temporary/transient physical disability that impacts their ability to perform the NSAA test. ClinicalTrials.gov identifier NCT02310763.

We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton ( p  = 0.050) and arms ( p  < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation. Trial registration : ClinicalTrials.gov, NCT02310763; registered 8 December 2014.

Serum metabolite profiling in Duchenne muscular dystrophy (DMD) may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS) for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate) in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown compounds at m/z of 357 and 312 while decreased metabolites included creatinine, androgen derivatives and other unknown yet to be identified compounds. Furthermore, the creatine to creatinine ratio is significantly associated with disease progression in DMD patients. This ratio sharply increased with age in DMD patients while it decreased with age in healthy controls. Overall, this study yielded promising metabolic signatures that could prove useful to monitor DMD disease progression and response to therapies in the future.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying mutations using new gene-editing technologies and corticosteroid analogs with better safety profiles offers renewed hope for many individuals with DMD and their families.