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Context: Exercise-induced muscle damage (EIMD) is prevalent especially in sports and rehabilitation. It causes loss in skeletal muscle function and soreness. As there are no firm preventive strategies, we aimed to evaluate the preventive efficacy of nonthermal 448-kHz capacitive resistive monopolar radiofrequency (CRMRF) therapy after eccentric bouts of EIMD response in knee flexors. Design: Twenty-nine healthy males (age: 25.2 [4.6] y) were randomized in control group (CG; n = 15) and experimental group (EG; n = 14) where EG followed 5 daily 448-kHz CRMRF therapies. All assessments were performed at baseline and post EIMD (EIMD + 1, EIMD + 2, EIMD + 5, and EIMD + 9 d). We measured tensiomyography of biceps femoris and semitendinosus to calculate contraction time, the maximal displacement and the radial velocity of contraction, unilateral isometric knee flexors maximal voluntary contraction torque, and rate of torque development in first 100 milliseconds. Results: Maximal voluntary contraction torque and rate of torque development in first 100 milliseconds decreased more in CG than in EG and recovered only in EG. Biceps femoris contraction time increased only in CG (without recovery), whereas in semitendinosus contraction time increased in EG (only at EIMD + 1) and in CG (without recovery). In both muscles, tensiomyographic maximal displacement decreased in EG (in EIMD + 1 and EIMD + 2) and in CG (without recovery). Furthermore, in both muscles, radial velocity of contraction decreased in EG (from EIMD + 1 until EIMD + 5) and in CG (without recovery). Conclusion: The study shows beneficial effect of CRMRF therapy after inducing EIMD in skeletal muscle strength and contractile parameters in knee flexors. [ABSTRACT FROM AUTHOR]

Congenital myopathies (CMs) are a kind of non-progressive or slow-progressive muscle diseases caused by genetic mutations, which are currently defined and categorized mainly according to their clinicopathological features. CMs exhibit pleiotropy and genetic heterogeneity. Currently, supportive treatment and pharmacological remission are the mainstay of treatment, with no cure available. Some adeno-associated viruses show promising prospects in the treatment of MTM1 and BIN1-associated myopathies; however, such gene-level therapeutic interventions target only specific mutation types and are not generalizable. Thus, it is particularly crucial to identify the specific causative genes. Here, we outline the pathogenic mechanisms based on the classification of causative genes: excitation-contraction coupling and triadic assembly (RYR1, MTM1, DNM2, BIN1), actin-myosin interaction and production of myofibril forces (NEB, ACTA1, TNNT1, TPM2, TPM3), as well as other biological processes. Furthermore, we provide a comprehensive overview of recent therapeutic advancements and potential treatment modalities of CMs. Despite ongoing research endeavors, targeted strategies and collaboration are imperative to address diagnostic uncertainties and explore potential treatments. [ABSTRACT FROM AUTHOR]

The epidemiology of idiopathic inflammatory myopathies (IIMs) varies by country. Investigating the epidemiological profile among Thai IIMs could help to inform public health policy, potentially leading to cost-reducing strategies. We aimed to assess the prevalence and incidence of IIM in the Thai population between 2017 and 2020. A descriptive epidemiological study was conducted on patients 18 or older, using data from the Information and Communication Technology Center, Ministry of Public Health, with a primary diagnosis of dermatopolymyositis, as indicated by the ICD-10 codes M33. The prevalence and incidence of IIMs were analyzed with their 95% confidence intervals (CIs) and then categorized by sex and region. In 2017, the IIM cases numbered 9,074 among 65,204,797 Thais, resulting in a prevalence of 13.9 per 100,000 population (95% CI 13.6–14.2). IIMs were slightly more prevalent among women than men (16.8 vs 10.9 per 100,000). Between 2018 and 2020, the incidence of IIMs slightly declined from 5.09 (95% CI 4.92–5.27) in 2017 and 4.92 (95% CI 4.76–5.10) in 2019 to 4.43 (95% CI 4.27–4.60) per 100,000 person-years in 2020. The peak age group was 50–69 years. Between 2018 and 2020, the majority of cases occurred in southern Thailand, with incidence rates of 7.60, 8.34, and 8.74 per 100,000 person-years. IIMs are uncommon among Thais, with a peak incidence in individuals between 60 and 69, especially in southern Thailand. The incidence of IIMs decreased between 2019 and 2020, most likely due to the COVID-19 pandemic, which reduced reports and investigations. [ABSTRACT FROM AUTHOR]

Objective: Rare disease. Background: Statin-induced myopathy can present with symptoms ranging from mild myalgia to significant muscle weakness. Muscle-related adverse effects of statins have been very challenging in clinical practice and they necessitate high clinical suspicion. This case report highlights how statin-induced autoimmune myopathy often goes undiagnosed. Case Report: We present a 69-year-old man with a past medical history of coronary artery disease who presented with myalgia and progressive proximal muscle weakness for 2 months, with a creatinine kinase of 8323 U/L. Atorvastatin was held on admission and the patient received intravenous (IV) fluid as treatment for presumed rhabdomyolysis. Although CK was trending down, he did not show significant improvement in muscle weakness or myalgia. At this point, myositis was suspected, so a myositis panel including anti-HMG Co-A reductase antibody was ordered and he was started on IV steroids. Anti-HMG Co-A reductase antibody was positive, and the rest of myopathy workup was negative. Meanwhile, the patient's muscle weakness significantly improved with IV steroid. He was discharged on methylprednisolone with close outpatient rheumatology follow-up. Conclusions: Muscle-related adverse effects of statins, including rhabdomyolysis and myopathy, can fail to respond to conservative management. It is crucial to identify and manage statin-induced autoimmune myopathy as a possible differential diagnosis in patients with muscle weakness and elevated CK while on statin therapy who do not respond to intravenous fluid alone. [ABSTRACT FROM AUTHOR]

Objective Idiopathic inflammatory myopathies (IIM) are a heterogeneous and life-threatening group of diseases; in particular, anti-melanoma differentiation-associated gene 5 antibody positive DM (MDA5+ DM) is reportedly strongly associated with high mortality rate. Tacrolimus (TAC) provides an excellent therapeutic option, but the trough concentration (Cmin)–outcome relationship remains unexplored. This study was undertaken to identify optimal Cmin and individualized dose based on CYP3A5 genotype for IIM patients. Methods A total of 134 IIM patients with 467 Cmin were enrolled. We examined the relationship between TAC Cmin and relapses. The receiver operating characteristic analysis was used to confirm the optimal Cmin. Analyses of factors influencing Cmin were conducted. The dose requirement based on CYP3A5 genotype was confirmed. Results TAC Cmin is strongly associated with relapses. The optimal cutoff values were 5.30, 5.85, 4.85 and 5.35 ng/ml for acute, subacute, chronic and all-phase IIM patients (P   =  0.001, 0.013, 0.002 and <0.001, respectively), as well as 5.35, 5.85, 5.55 and 5.85 ng/ml for acute, subacute, chronic and all-phase MDA5+ DM patients (P   =  0.007, 0.001, 0.036 and <0.001, respectively). CYP3A5 genotype was one of the significant factors influencing TAC Cmin. CYP3A5 expressers required 0.059 mg/kg/day to attain the target Cmin, while nonexpressers required 0.046 mg/kg/day (P   =  0.019). Conclusion TAC treatment may elicit favorable outcome in patients with IIM and MDA5+ DM when Cmin exceeded 5.35 and 5.85 ng/ml, which is crucial to a lower relapse rate. The individualized dose based on the CYP3A5 genotype provides a reference for TAC personalized therapy in IIM. [ABSTRACT FROM AUTHOR]

Objectives Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort. Methods Serum samples from patients within the MyoCite cohort, a well-characterized retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017–2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patients' serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against immunoprecipitation as the reference standard, measuring sensitivity, specificity and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific myositis-specific autoantibodies. Results Immunoprecipitation identified myositis autoantibodies in 56.5% (n  = 83) of patient samples, with anti-Jo1 (n  = 16; 10.9%) as the most common, followed by anti-MDA5 (n  = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83 and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and immunoprecipitation, and κ values for LIAs for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2 and anti-SAE ranged between 0.21 and 0.60. Conclusion While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5 and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor. [ABSTRACT FROM AUTHOR]

As the most frequent cause of acquired myopathy, toxic myopathies are characterised by clinicopathological features that vary depending on the mode of action of the drugs or toxins involved. Although a large number of substances can induce myotoxicity, the main culprits are statins, alcohol, and corticosteroids. A rigorous, well-organised diagnostic approach is necessary to obtain a rapid diagnosis. For early diagnosis and management, it is important for clinicians to be aware that most toxic myopathies are potentially reversible, and the goal of treatment should be to avoid serious muscle damage. [ABSTRACT FROM AUTHOR]

• TIA1/SQSTM1 myopathy is one of the few digenic myopathies. • All patients carry the TIA1 p.Asn357Ser variant and four different SQSTM1 variants have been reported. • Patients present with asymmetric ankle dorsiflexion and hand finger extensors weakness. • Sensorimotor axonal polyneuropathy may be an additional feature of the disease. • TIA1 p.Asn357Ser is increased in distal myopathy patients and could act as a genetic modifier. TIA1/SQSTM1 myopathy is one of the few digenic myopathies. We describe four new French adult male patients carrying the TIA1 p.Asn357Ser and SQSTM1 p.Pro392Leu variant and review the literature to include 20 additional cases to define the spectrum of the disease. These twenty-four patients (75% males) had late-onset (52,6 ± 10,1 years), mainly asymmetric, distal ankle and hand finger extension weakness (75%), mild CK elevation (82.4%) and myopathic EMG. Two of the four French patients had sensorimotor axonal polyneuropathy and an additional one had neurogenic changes in muscle biopsy. Muscle biopsy showed rimmed vacuoles (44.4%), myofibrillar disorganization (16.7%) or both (38.9%), with P62/TDP43 aggregates. The TIA1 p.Asn357Ser variant was present in all patients and the SQSTM1 p.Pro392Leu was the most frequent (71%) of the four reported SQSTM1 variants. We reviewed the distal myopathy gene panels of Pitié-Salpêtrière's hospital cohort finding a prevalence of 11/414=2.7% of the TIA1 p.Asn357Ser variant, with two patients having an alternative diagnosis (TTN and MYH7) with atypical phenotypes, resembling some of the features seen in TIA1/SQSTM1 myopathy. Overall, TIA1/SQSTM1 myopathy has a homogenous phenotype reinforcing the pathogenicity of its digenic variants. We confirm an increased burden of the TIA1 p.Asn357Ser variant in distal myopathy patients which could act as a genetic modifier. [ABSTRACT FROM AUTHOR]

• Ophthalmoparesis has not been previously described in anti-HMGCR antibody-associated myopathies and two cases are presented. • Other causes of ophthalmoparesis and proximal weakness were extensively ruled out. • Consider anti-HMGCR antibody-associated myopathies in patients with proximal weakness, elevated creatine kinase, and ophthalmoparesis. We describe two anti-3‑hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) antibody-positive patients with treatment-responsive ophthalmoparesis. Patient 1 was a 53-year-old male with progressive proximal limb weakness, dysphagia, ptosis, and diplopia over 6 weeks and creatine kinase (CK) of 3,512 units/L. Patient 2 was a 55-year-old female with progressive proximal weakness, dysarthria, ptosis, diplopia, and dyspnea over 2 weeks with CK of 31,998 units/L. Both patients had normal thyroid studies and repetitive nerve stimulation, myopathic electromyography with fibrillation potentials, magnetic resonance imaging demonstrating abnormal enhancement of extraocular muscles, muscle biopsy showing necrotic myofibers, and positive anti-HMGCR antibodies. Patient 1 also had weakly positive anti-PM/Scl antibodies. Immunomodulatory therapies led to resolution of oculobulbar weakness and normalization of CK levels in both patients, while limb weakness resolved completely in patient 1 and partially in patient 2. These cases expand the phenotypic spectrum of anti-HMGCR antibody-associated myopathies to include subacute ophthalmoparesis with limb-girdle weakness and markedly elevated CK. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disease. Lack of dystrophin in skeletal muscles leads to intrinsic weakness, injury, subsequent degeneration and fibrosis, decreasing contractile function. Dystropathology eventually presents in all inspiratory and expiratory muscles of breathing, severely curtailing their critical function. In people with DMD, premature death is caused by respiratory or cardiac failure. There is an urgent need to develop therapies that improve quality of life and extend life expectancy in DMD. Surprisingly, there is a dearth of information on respiratory control in animal models of DMD, and respiratory outcome measures are often limited or absent in clinical trials. Characterization of respiratory performance in murine and canine models has revealed extensive remodelling of the diaphragm, the major muscle of inspiration. However, significant compensation by extradiaphragmatic muscles of breathing is evident in early disease, contributing to preservation of peak respiratory system performance. Loss of compensation afforded by accessory muscles in advanced disease is ultimately associated with compromised respiratory performance. A new and potentially more translatable murine model of DMD, the D2.mdx mouse, has recently been developed. Respiratory performance in D2.mdx mice is yet to be characterized fully. However, based on histopathological features, D2.mdx mice might serve as useful preclinical models, facilitating the testing of new therapeutics that rescue respiratory function. This review summarizes the pathophysiological mechanisms associated with DMD both in humans and in animal models, with a focus on breathing. We consider the translational value of each model to human DMD and highlight the urgent need for comprehensive characterization of breathing in representative preclinical models to better inform human trials. What is the topic of this review?We review current understanding of the respiratory phenotype in Duchenne muscular dystrophy (DMD), a fatal genetic neuromuscular disease.What advances does it highlight?Diaphragm muscle dystropathology and contractile dysfunction present early in dystrophic disease, yet respiratory system performance is maintained by compensatory mechanisms until late‐stage advanced disease. Loss of compensation afforded by accessory muscles of breathing contributes to respiratory morbidity in canine and murine models of DMD, mirroring the human disease. The D2.mdx mouse appears convenient for the study of the complex respiratory phenotype associated with dystrophin deficiency, and assessments of new therapeutics in this model might be translatable to human DMD. [ABSTRACT FROM AUTHOR]

Background: Although biofeedback with contingent electrical stimulation (CES) has demonstrated the reduction effect on sleep bruxism (SB), the relationship between the actual applied CES intensity and efficacy remains uncertain. Objective: This study aimed to investigate whether the reduction of bruxism events and jaw muscle symptoms could vary according to the intensity of CES and in probable sleep bruxers. Methods: Twenty probable sleep bruxers were initially screened for bruxer confirmation based on a 2‐week recording of SB events with a portable electromyography recorder (BUTLER®GrindCare®, GC4). A 3‐week recording was conducted without CES using a GC4, followed by another 3‐week recording with CES. At baseline and before and after the CES (+) session, clinical muscle symptoms were assessed using a 0–10 numerical rating scale (NRS). The relationships between the actual applied CES intensity and the number of SB events/hour, as well as the NRS of clinical muscle symptoms, were analysed. Results: The actual applied CES intensity was positively correlated with the reduction rate of the number of SB events/hour (R =.643, p =.002), as well as with the reduction rate of NRS for pain, unpleasantness, fatigue, tension and stiffness (R >.500, p <.011). Conclusion: Higher CES elicited a more robust reduction in SB events and clinical muscle symptoms, in probable bruxers. Prior to selecting CES biofeedback as a management option for SB, it would be beneficial to assess the tolerance threshold of CES in each bruxer in order to predict the effectiveness of CES in probable sleep bruxers. [ABSTRACT FROM AUTHOR]

Due to its exceptional sensitivity to soft tissues, MRI has been extensively utilized to assess anatomical muscle parameters such as muscle volume and cross‐sectional area. Quantitative Magnetic Resonance Imaging (qMRI) adds to the capabilities of MRI, by providing information on muscle composition such as fat content, water content, microstructure, hypertrophy, atrophy, as well as muscle architecture. In addition to compositional changes, qMRI can also be used to assess function for example by measuring muscle quality or through characterization of muscle deformation during passive lengthening/shortening and active contractions. The overall aim of this review is to provide an updated overview of qMRI techniques that can quantitatively evaluate muscle structure and composition, provide insights into the underlying biological basis of the qMRI signal, and illustrate how qMRI biomarkers of muscle health relate to function in healthy and diseased/injured muscles. While some applications still require systematic clinical validation, qMRI is now established as a comprehensive technique, that can be used to characterize a wide variety of structural and compositional changes in healthy and diseased skeletal muscle. Taken together, multiparametric muscle MRI holds great potential in the diagnosis and monitoring of muscle conditions in research and clinical applications. Evidence Level: 5 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

SUMMARY: This systematic review scrutinises the literature on white striping and wooden breast phenomena in broiler chickens, with a specific emphasis on identifying nutritional strategies designed to alleviate these myopathies. Additionally, the review sought to ascertain whether avian welfare was compromised when nutritional interventions were employed to address pectoral myopathies. Employing the ProKnow-C methodology, a total of twenty-two research articles were meticulously selected based on pre-established inclusion and exclusion criteria, following the Knowledge Development Process – Constructivist approach. Inclusion criteria encompassed studies featuring the application of nutritional strategies, specifically evaluating their impacts on the incidence of myopathies and their broader ramifications on animal welfare. Collated data facilitated to identify various nutritional strategies, evaluating their influence on the occurrence of pectoral myopathies, with researchers predominantly focusing on either white striping or wooden breast, or concurrently investigating both conditions. Upon a comprehensive analysis of the scientific content, the selected articles were categorised according to the applied nutritional strategies, namely: levels of crude protein, amino acids, and/or energy; antioxidants and various mineral sources; quantitative dietary restriction; and food additives. Our findings revealed a multitude of strategies deployed by the industry to mitigate the incidence of pectoral myopathies. Predominantly, these strategies fell into two broad categories: those associated with growth rate alterations, involving manipulation or retardation of the birds' growth curve throughout the production phase; and those utilising dietary antioxidants, whether natural or synthetic. Approaches related to the growth curve aimed at mitigating myopathy severity by controlling or slowing down avian growth. It is noteworthy that the scarcity of studies examining the impact of pectoral myopathies on animal welfare raises concerns that necessitate urgent attention from the scientific community. [ABSTRACT FROM AUTHOR]

Key points Nemaline myopathy (NM) is a genetic muscle disease, primarily caused by mutations in the NEB gene (NEB‐NM) and with muscle myosin dysfunction as a major molecular pathogenic mechanism. Recently, we have observed that the myosin biochemical super‐relaxed state was significantly impaired in NEB‐NM, inducing an aberrant increase in ATP consumption and remodelling of the energy proteome in diseased muscle fibres. Because the small‐molecule Mavacamten is known to promote the myosin super‐relaxed state and reduce the ATP demand, we tested its potency in the context of NEB‐NM. We first conducted in vitro experiments in isolated single myofibres from patients and found that Mavacamten successfully reversed the myosin ATP overconsumption. Following this, we assessed its short‐term in vivo effects using the conditional nebulin knockout (cNeb KO) mouse model and subsequently performing global proteomics profiling in dissected soleus myofibres. After a 4 week treatment period, we observed a remodelling of a large number of proteins in both cNeb KO mice and their wild‐type siblings. Nevertheless, these changes were not related to the energy proteome, indicating that short‐term Mavacamten treatment is not sufficient to properly counterbalance the metabolically dysregulated proteome of cNeb KO mice. Taken together, our findings emphasize Mavacamten potency in vitro but challenge its short‐term efficacy in vivo. No cure exists for nemaline myopathy, a type of genetic skeletal muscle disease mainly derived from mutations in genes encoding myofilament proteins. Applying Mavacamten, a small molecule directly targeting the myofilaments, to isolated membrane‐permeabilized muscle fibres from human patients restored myosin energetic disturbances. Treating a mouse model of nemaline myopathy in vivo with Mavacamten for 4 weeks, remodelled the skeletal muscle fibre proteome without any noticeable effects on energetic proteins. Short‐term Mavacamten treatment may not be sufficient to reverse the muscle phenotype in nemaline myopathy. [ABSTRACT FROM AUTHOR]

Recent research has sparked a discussion on the spectrum of diseases linked to the MATR3 gene associated with amyotrophic lateral sclerosis and distal myopathy with vocal cord and pharyngeal weakness (VCPDM). To date, fewer than 50 cases of VCPDM have been reported in the literature. We aim to build upon the work of previous researchers by gathering additional information about VCPDM. In this study, we present six patients from four unrelated families affected by VCPDM. Our observations include patients exhibiting both the typical phenotype associated with MATR3-related distal myopathy and rare symptomatic manifestations of the disease. Notably, two cases presented with an asymmetric scapuloperoneal phenotype, leading in one case to an initial misdiagnosis of facioscapulohumeral muscular dystrophy. [ABSTRACT FROM AUTHOR]

A growing body of research has provided evidence that de novo expression of connexin hemichannels and upregulation of pannexin hemichannels (Cx HCs and Panx HCs, respectively) in the cytoplasmic membrane of skeletal muscle (sarcolemma) are critical steps in the pathogenesis of muscle dysfunction of many genetic and acquired muscle diseases. This review provides an overview of the current understanding of the molecular mechanisms regulating the expression of Cx and Panx HCs in skeletal muscle, as well as their roles in both muscle physiology and pathologies. Additionally, it addresses existing gaps in knowledge and outlines future challenges in the field. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is a heart muscle disease associated with an increased risk for sudden cardiac death (SCD). Cytokeratin 18-based proteins, such as M30 and M65 antigens, are known cell-death biomarkers. M30 antigen is released from cells during apoptosis, and M65 antigen is released during cell death from any cause, such as apoptosis or necrosis. We aimed to study the expression of M30 and M65 antigens in peripheral blood obtained by 46 HCM patients and compare with 27 age- and sex-matched patients without HCM. We also investigated the CK18 expression in myocardium from postmortem HCM hearts. M30 and M65 antigens were significantly increased in the HCM vs. non-HCM group (Μ30: 338 ± 197 U/uL vs. 206 ± 166 U/uL, p = 0.003; M65: 428 ± 224 U/uL vs. 246 ± 214 U/uL, p = 0.001), and HCM patients with a higher expression of these markers (M30: 417 ± 208 vs. 271 ± 162 U/uL, p = 0.011; M65: 518 ± 242 vs. 351 ± 178 U/uL, p = 0.011) had a higher risk for SCD. In HCM, both apoptosis and necrosis are increased, but particularly necrosis (M30/M65 ratio: 0.75 ± 0.09 vs. 0.85 ± 0.02, p < 0.001). CK18 is expressed in the HCM myocardium (1.767 ± 0.412 vs. 0.537 ± 0.383, % of area, p = 0.0058). Therefore, M30 and M65 antigens may be novel biomarkers in HCM. [ABSTRACT FROM AUTHOR]

Increasing evidence has shown that gut microbiota (GM) was involved in the pathophysiology of musculoskeletal disorders through multiple pathways such as protein anabolism, chronic inflammation and immunity, and imbalanced metabolism. We performed a systematic review and meta-analysis of human studies to evaluate GM diversity differences between individuals with and without sarcopenia, and explore bacteria with potential to become biomarkers. PubMed, Embase and Cochrane library were systematically searched from inception to February 16, 2024. Studies were included if they (1) sampled adults with sarcopenia, and (2) performed GM analysis and reported α-diversity, β-diversity or relative abundance. The methodological quality of included studies and the certainty of evidence were assessed through the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system, respectively. Weighted standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs) were estimated for α-diversity indices using a fixed-effects and a random-effects model. Beta diversity and the relative abundance of GM were summarized qualitatively. A total of 19 studies involving 6,565 participants were included in this study. Compared with controls, significantly moderate decrease in microbial richness in participants with sarcopenia were found (Chao1: SMD = -0.44; 95%CI, -0.64 to -0.23, I2 = 57.23%, 13 studies; observed species: SMD = -0.68; 95%CI, -1.00 to -0.37, I2 = 66.07%, 5 studies; ACE index: SMD = -0.30; 95%CI, -0.56 to -0.04, I2 = 8.12%, 4 studies), with very low certainty of evidence. Differences in β-diversity were consistently observed in 84.6% of studies and 97.3% of participants. The detailed analysis of the gut microbial differential abundance identified a loss of Prevotellaceae, Prevotella, and Megamonas in sarcopenia compared with non-sarcopenia. In conclusion, sarcopenia was found to be associated with reduced richness of GM, and supplementing intestinal bacteria described above may contribute to preventing and treating this muscle disease. The research protocol was registered and approved in PROSPERO (CRD42023412849). [ABSTRACT FROM AUTHOR]

• Multiple myeloma (MM) and AL amyloidosis are two closely related conditions that can occur concurrently in some patients. • Amyloid myopathy is a rare manifestation of AL amyloidosis. It is characterized by muscle weakness that can be difficult to distinguish from the muscle weakness associated with other myopathies, including inflammatory myopathies. • For all unexplained myopathies in the adult age, it is suggested to perform a muscle biopsy and use routine Congo red staining to improve diagnostic accuracy of this rare disease. We present the case of a 79-year-old man with rapidly progressive myopathy as the initial manifestation of light chain amyloidosis associated with multiple myeloma. The patient experienced progressive lower limb weakness resulting in difficulty climbing stairs. Ancillary tests revealed slightly elevated serum creatine kinase levels. The electromyogram revealed a diffuse myogenic pattern while muscle MRI indicated fatty replacement of the quadriceps muscles. Muscle biopsy revealed the presence of amyloid deposits in the vessel walls. An elevated level of lambda (246 mg/L) light chain was detected. The bone marrow aspiration results were consistent with the diagnosis of multiple myeloma. In conclusion, even if amyloid myopathy is a rare condition, routine screening for amyloid deposits in muscle biopsy is crucial and should be performed systematically. In the present case, it enabled a rapid diagnosis and the beginning of treatment. [ABSTRACT FROM AUTHOR]

• A critical literature review of case reports on statins-induced side effects in various hereditary myopathies. • Setting criteria to assess case reports of statin myotoxicity in hereditary myopathies. • Identification of myopathies with high risk for statin usage (MELAS and other mitochondrial disorders, myotonic dystrophy type 2, McArdle disease). • Suggesting practical management of hyperlipidemia in hereditary myopathies. Hyperlipidemia is not uncommon in patients with hereditary myopathies who get older and also in several conditions in which it is frequently observed. Thus, using the common cholesterol reducing medications of the stains group could be considered. However, the side effects of these drugs include myalgia, myopathy and rhabdomyolysis typically associated with high serum creatine kinase (CK). Because high CK levels are very frequently found in hereditary myopathies, physicians are reluctant to use statins in such patients. Reviewing the literature about statin side effects in hereditary myopathies does not provide a clear evidence about the true risk of these drugs. This review critically describes the reported cases of statin side effects in several genetic myopathies and suggests some guidelines for conditions that are contra indicated for statin usage (particularly in mitochondrial disorders, metabolic myopathies, myotonic dystrophy type 2). Possible solutions to the dilemma of whether to use statins in hereditary myopathies are discussed (prescribing other cholesterol lowering agents and a carefully monitored treatment initiation of statins). [ABSTRACT FROM AUTHOR]

Patients with Coronavirus Disease 2019 (COVID-19) who required mechanical ventilation and had prolonged hospital stay present with medical instability and functional impairments after the acute hospitalization. To present the rehabilitation outcome of three patients with COVID-19 admitted to an inpatient rehabilitation unit using a case series method. Subjects included three consecutive male patients admitted to the rehabilitation unit with a diagnosis of deconditioning and critical illness myopathy. On admission, patients were evaluated by a multidisciplinary team using outcome measures such as 6-min walk test (6 MWT), 10-m walk test (10 MWT), berg balance scale (BBS), and dynamometry. Each patient received daily therapy with a minimum of 900 min per week during their rehabilitation stay. Treatment strategies included fatigue management, training of mobility and activities for daily living tasks, muscle strengthening, and cognitive retraining. All patients showed significant improvements across all the outcome measures, specifically, the 6MWT (minimal clinically identifiable difference (MCID) range: 14–30.5 m) and the 10MWT (MCID range: 0.10–0.20 m/s) which exceeded the MCID for all three patients. The BBS also demonstrated significant improvement, surpassing the minimum detectable change of 5–7 points. Of the three patients, two were able to be discharged at an independent level, while one required supervision for safety. Patients with COVID-19, who experienced prolonged hospital stay present with severe impairments in muscle strength, functional mobility, and participation in daily living tasks. Inpatient rehabilitation may have the potential to reduce impairments and accelerate the recovery process while managing ongoing medical issues. [ABSTRACT FROM AUTHOR]

This study investigates the association between inflammatory myopathies (IM), and their correlation with cancer. There are several potential causes behind the association of cancer and inflammatory myopathies. The positivity of specific antibodies for myositis plays a significant role. Our objective is to describe cancer and inflammatory myopathies in Colombia, focusing on demographics, clinical characteristics, and laboratory data. We retrospectively analyzed 112 IM patients diagnosed at Fundación Valle del Lili in Cali, Colombia, the cases met the EULAR/ACR criteria. Data included demographics, clinical signs, laboratory findings, and malignancy. Malignancy associations were explored using logistic regression. The survival analysis was assessed using Kaplan–Meier curves and the Log-Rank test. Dermatomyositis was the most common subtype (45.5%), with a female predominance (66.1%). Cancer diagnosis occurred in 11.6% of cases, predominantly thyroid cancer. The median time from myopathy onset to cancer diagnosis was 11 months, with 75% of cases within the first year. Bivariate analysis indicated associations between cancer and age, Gottron's papules, digital ulcers, and heliotrope rash. However, multivariate analysis identified age as the only significant malignancy risk factor. Survival analysis showed better rates in younger patients. This study provides into the link between IM and cancer in the Colombian population. Thyroid cancer predominated, with a slightly higher proportion of female cancer diagnoses. Age emerged as a significant risk factor for malignancy. Understanding this association is crucial for early detection and improving patient outcomes related to IM-associated malignancies. [ABSTRACT FROM AUTHOR]

Atraumatic muscle disorders comprise a very wide range of skeletal muscle diseases, including metabolic, inflammatory, autoimmune, infectious, ischemic, and neoplastic involvement of the muscles. Therefore, one must take clinical and laboratory data into consideration to elucidate the differential diagnoses, as well as the distribution of the muscle compromise along the body—whether isolated or distributed along the body in a symmetric or asymmetrical fashion. Assessment of muscular disorders often requires imaging investigation before image-guided biopsy or more invasive procedures; therefore, radiologists should understand the advantages and limitations of imaging methods for proper lesion evaluation and be aware of the imaging features of such disorders, thus contributing to proper decision-making and good patient outcomes. In this review, we propose a systematic approach for the assessment of muscle disorders based on their main imaging presentation, dividing them into patterns that can be easily recognized. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcopenia in cancer patients, understood as the progressive loss of muscle mass and function, reduces physical function, quality of life, and survival, and increases surgical complications and disease progression. Myosteatosis is an excess of fat mass infiltrated into the muscle, which causes a reduction in its functionality. Given the current scientific evidence on its reversibility, it is important to know the implications that its prevention, diagnosis, and early treatment could entail in the evolutionary course of the disease. Therefore, this study aims to make an early diagnosis and evaluate the incidence of sarcopenia and myosteatosis in patients diagnosed with esophageal, stomach, or pancreatic cancer and analyze their clinical evolution. In our sample, 22.2% of the patients had sarcopenia, and 60% had myosteatosis. At 6 months, 60% of the patients with sarcopenia died, compared with 14.3% of the patients who did not have sarcopenia. Therefore, it is important to make a correct early diagnosis to carry out a comprehensive approach that can reverse the patient's situation. Likewise, prevention and care campaigns for muscle health could be carried out at all stages of life. The increase in the global incidence of cancer highlights the need to continue advancing in the techniques of diagnosis and nutritional assessment of cancer patients, given the prognostic and therapeutic impact of nutritional status. In this study, sarcopenia was evaluated as an independent predictor of morbidity and mortality. Data from 45 patients diagnosed with esophagogastric or pancreatic cancer were analyzed. Body composition was determined using computed tomography images, and functionality tests were performed. Sarcopenia was present in 22.2% of the patients, while only 31.1% had correct musculature. A reduction in muscle mass or function was observed in 46.7% of the patients. Likewise, the prevalence of myosteatosis reached 60% of the patients. No significant differences were found with regard to the presence of sarcopenia according to BMI classifications, so it is necessary to evaluate the patient with body composition techniques that include the evaluation of the different muscle and fat compartments. In conclusion, a comprehensive intervention is necessary to improve the detection of sarcopenia/myosteatosis and, in the future, to be able to carry out an approach that improves the quality of life and survival rates of patients. [ABSTRACT FROM AUTHOR]

Background: Preventing severe arthrogenic muscle inhibition (AMI) after knee injury is critical for better prognosis. The novel Sonnery-Cottet classification of AMI enables the evaluation of AMI severity but requires validation. This study aimed to investigate the electromyography (EMG) patterns of leg muscles in the examination position from the classification during isometric contraction to confirm its validity. We hypothesised that the AMI pattern, which is characterised by quadriceps inhibition and hamstring hypercontraction, would be detectable in the supine position during isometric contraction. Methods: Patients with meniscal or knee ligament injuries were enrolled between August 2023 and May 2024. Surface EMG was assessed during submaximal voluntary isometric contractions (sMVIC) at 0° extension in the supine position for the vastus medialis (VM) and vastus lateralis (VL) muscles and at 20° flexion in the prone position for the semitendinosus (ST) and biceps femoris (BF) muscles. Reference values for normalisation were obtained from the EMG activity during the gait of the uninjured leg. The Kruskal–Wallis test was used to compare the activation patterns of the muscle groups within the same leg, and the post-hoc tests were conducted using the Mann–Whitney U test and Bonferroni correction. Results: Electromyographic data of 40 patients with knee injuries were analyzed. During sMVIC, the extensor and flexor muscles of the injured leg showed distinct behaviours (P < 0.001), whereas the uninjured side did not (P = 0.144). In the injured leg, the VM differed significantly from the ST (P = 0.018), and the VL differed significantly from the ST and BF (P = 0.001 and P = 0.026, respectively). However, there were no statistically significant differences within the extensor muscle groups (VM and VL, P = 0.487) or flexor muscle groups (ST and BF, P = 0.377). Conclusion: AMI was detectable in the examination position suggested by the Sonnery-Cottet classification. The flexor and extensor muscles of the injured leg exhibited distinct activation behaviours, with inhibition predominantly occurring in the quadriceps muscles, whereas the hamstrings showed excitation. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis‐like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1.Two individuals with unsolved juvenile‐onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole‐exome sequencing (WES).The two probands (MNOT002‐01 and K1440‐01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440‐01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002‐01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440‐01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002‐01 displayed rimmed vacuoles. Monoallelic stop‐loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440‐01) and c.1118A>C p.*373Serext*6 (MNOT002‐01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon.Both stop‐loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile‐onset myopathy. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies (IIMs) are rare disorders characterized by inflammation of skeletal muscle, which can result in fatty replacement of muscle, muscle atrophy, and subsequent weakness. Therapeutic advancements have improved clinical outcomes but impose an economic impact on healthcare systems. We aimed to summarize the direct and indirect costs associated with IIMs in a systematic review (PROSPERO Registration #CRD42023443143). Electronic databases (MEDLINE, Embase, CINAHL, and Scopus) were systematically searched for full-length articles (excluding case reports) reporting costs specific to patients diagnosed with an IIM, published between database inception and April 19, 2023. Direct cost categories included inpatient, outpatient, medication, home/long-term care, and durable medical equipment such as mobility and respiratory aids. Indirect costs included lost productivity. Eligibility criteria were met by 21 of the 3,193 unique titles identified. Costs are expressed in 2023 United States of America dollars, with adjustments for differences in purchasing power applied to currency conversions. As no study reported on all cost categories, annualized cost of IIM per patient was estimated by calculating the mean cost per category, and then adding the means of the different cost categories. By this method, IIM was estimated to cost $52,210 per patient per year. Proportional contributions by category were lost productivity (0.278), outpatient care (0.214), medications (0.171), inpatient care (0.161), home/long-term care (0.122), and durable medical equipment (0.053). Newer findings with intravenous immunoglobulin considered first line therapy for IIM demonstrated markedly higher annual medication costs per patient, upwards of $33,900 compared to an average of $3,908 ± $1,042 in older studies. Future cost-effectiveness studies require updated cost-of-illness studies reflecting the evolving sub-classification and treatment options for IIM, and should consider the impact of IIM on patients and their families. [ABSTRACT FROM AUTHOR]

Oculopharyngodistal myopathy (OPDM) is an inherited myopathy manifesting with ptosis, dysphagia and distal weakness. Pathologically it is characterised by rimmed vacuoles and intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified in OPDM individuals in Asian populations. None of these have been found in affected individuals of non-Asian ancestry. In this study we describe the identification of CCG expansions in ABCD3, ranging from 118 to 694 repeats, in 35 affected individuals across eight unrelated OPDM families of European ancestry. ABCD3 transcript appears upregulated in fibroblasts and skeletal muscle from OPDM individuals, suggesting a potential role of over-expression of CCG repeat containing ABCD3 transcript in progressive skeletal muscle degeneration. The study provides further evidence of the role of non-coding repeat expansions in unsolved neuromuscular diseases and strengthens the association between the CGG • CCG repeat motif and a specific pattern of muscle weakness. A significant proportion of individuals with inherited neuromuscular disease do not receive a genetic diagnosis. Here, the authors establish CCG expansions in the 5' untranslated region of ABCD3 as a cause of oculopharyngodistal myopathy (OPDM) in individuals of European ancestry and identify increased expression of expansion-containing ABCD3 transcripts as a possible disease mechanism underlying muscle degeneration. [ABSTRACT FROM AUTHOR]

Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progressive degeneration of muscle fibers, resulting in inflammation and fibrosis that ultimately affect the overall muscle biomechanics. At the opposite end of the spectrum of muscle diseases, age‐related sarcopenia is a common condition that affects an increasing proportion of the elderly. Although characterized by different pathological mechanisms, DMD and sarcopenia share the development of progressive muscle weakness and tissue inflammation. Here, the therapeutic effects of Cyclo Histidine‐Proline (CHP) against DMD and sarcopenia are evaluated. In the mdx mouse model of DMD, it is shown that CHP restored muscle contractility and force production, accompanied by the reduction of fibrosis and inflammation in skeletal muscle. CHP furthermore prevented the development of cardiomyopathy and fibrosis in the diaphragm, the two leading causes of death for DMD patients. CHP also attenuated muscle atrophy and functional deterioration in a mouse model of age‐related sarcopenia. These findings from two different models of muscle dysfunction hence warrant further investigation into the effects of CHP on muscle pathologies in animal models and eventually in patients. [ABSTRACT FROM AUTHOR]

Brachio-cervical inflammatory myopathy (BCIM) is a rare inflammatory myopathy characterized by dysphagia, bilateral upper limb atrophy, limb-girdle muscle weakness, and myositis-specific antibody (MSA) negativity. BCIM has a low incidence and is commonly associated with autoimmune diseases. We present a case report of a 55-year-old man with progressive upper limb weakness and atrophy, diagnosed with flail arm syndrome (FAS). The initial electromyography revealed extensive spontaneous muscle activity and increased duration of motor unit potentials (MUPs). During follow-up, evidence of myogenic damage was observed, as indicated by a decreased duration of MUPs in the right biceps muscle. Laboratory and genetic testing ruled out hereditary or acquired diseases. Negative serological antibodies for myasthenia gravis. Hereditary or acquired diseases were ruled out through laboratory and genetic testing. Whole-body muscle magnetic resonance imaging (MRI) showed extensive edema and fat replacement in the bilateral upper limbs, scapular, and central axis muscles, while the lower extremities were relatively mildly affected. Muscle biopsy revealed numerous foci of inflammatory cells distributed throughout the muscle bundle, with predominant CD20, CD138, and CD68 expression, accompanied by a light infiltration of CD3 and CD4 expression. The muscle weakness improved with the combination of oral prednisone (initially 60 mg/day, tapered) and methotrexate (5 mg/week) treatment. [ABSTRACT FROM AUTHOR]

Myositis with anti-Ku-autoantibodies is a rare inflammatory myopathy associated with various connective tissue diseases. Histopathological studies have identified inflammatory and necrotizing aspects, but a precise morphological analysis and pathomechanistic disease model are lacking. We therefore aimed to carry out an in-depth morpho-molecular analysis to uncover possible pathomechanisms. Muscle biopsy specimens from 26 patients with anti-Ku-antibodies and unequivocal myositis were analyzed by immunohistochemistry, immunofluorescence, transcriptomics, and proteomics and compared to biopsy specimens of non-disease controls, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Clinical findings and laboratory parameters were evaluated retrospectively and correlated with morphological and molecular features. Patients were mainly female (92%) with a median age of 56.5 years. Isolated myositis and overlap with systemic sclerosis were reported in 31%, respectively. Isolated myositis presented with higher creatine kinase levels and cardiac involvement (83%), whereas systemic sclerosis-overlap patients often had interstitial lung disease (57%). Histopathology showed a wide spectrum from mild to pronounced myositis with diffuse sarcolemmal MHC-class I (100%) and -II (69%) immunoreactivity, myofiber necrosis (88%), endomysial inflammation (85%), thickened capillaries (84%), and vacuoles (60%). Conspicuous sarcoplasmic protein aggregates were p62, BAG3, myotilin, or immunoproteasomal beta5i-positive. Proteomic and transcriptomic analysis identified prominent up-regulation of autophagy, proteasome, and hnRNP-related cell stress. To conclude, Ku + myositis is morphologically characterized by myofiber necrosis, MHC-class I and II positivity, variable endomysial inflammation, and distinct protein aggregation varying from IBM and IMNM, and it can be placed in the spectrum of scleromyositis and overlap myositis. It features characteristic sarcoplasmic protein aggregation on an acquired basis being functionally associated with altered chaperone, proteasome, and autophagy function indicating that Ku + myositis exhibit aspects of an acquired inflammatory protein-aggregate myopathy. [ABSTRACT FROM AUTHOR]

Truncation of the protein-protein interaction SH3 domain of the membrane remodeling Bridging Integrator 1 (BIN1, Amphiphysin 2) protein leads to centronuclear myopathy. Here, we assessed the impact of a set of naturally observed, previously uncharacterized BIN1 SH3 domain variants using conventional in vitro and cell-based assays monitoring the BIN1 interaction with dynamin 2 (DNM2) and identified potentially harmful ones that can be also tentatively connected to neuromuscular disorders. However, SH3 domains are typically promiscuous and it is expected that other, so far unknown partners of BIN1 exist besides DNM2, that also participate in the development of centronuclear myopathy. In order to shed light on these other relevant interaction partners and to get a holistic picture of the pathomechanism behind BIN1 SH3 domain variants, we used affinity interactomics. We identified hundreds of new BIN1 interaction partners proteome-wide, among which many appear to participate in cell division, suggesting a critical role of BIN1 in the regulation of mitosis. Finally, we show that the identified BIN1 mutations indeed cause proteome-wide affinity perturbation, signifying the importance of employing unbiased affinity interactomic approaches. [ABSTRACT FROM AUTHOR]

Cramp–fasciculation syndrome (CFS) is a rare and benign neuromuscular disorder that may initially masquerade as motor neuron disease/amyotrophic lateral sclerosis. While CFS may have a familial disposition, we report on cases associated with high consumption of popular food items. One set of patients reversibly experienced acute onset of headache, flushing, muscle stiffness and fasciculations following the consumption of umami-flavored food containing a large concentration of monosodium glutamate. A second group of patients consuming food derived from lupin seed developed acute cholinergic toxicity, CFS, and, with chronic intake, significant, self-limiting, but incompletely reversible upper and lower motor neuron deficits. While these cases may improve our knowledge about the possible causes of CFS, our series also demonstrates that excessive consumption of some popular foods is not harmless. This warrants further research on their safety at all stages of human development from a neurological point of view. [ABSTRACT FROM AUTHOR]

Background: Congenital myopathies are severe genetic diseases with a strong impact on patient autonomy and often on survival. A large number of patients do not have a genetic diagnosis, precluding genetic counseling and appropriate clinical management. Our objective was to find novel pathogenic variants and genes associated with congenital myopathies and to decrease diagnostic odysseys and dead-end. Methods: To identify pathogenic variants and genes implicated in congenital myopathies, we established and conducted the MYOCAPTURE project from 2009 to 2018 to perform exome sequencing in a large cohort of 310 families partially excluded for the main known genes. Results: Pathogenic variants were identified in 156 families (50%), among which 123 families (40%) had a conclusive diagnosis. Only 44 (36%) of the resolved cases were linked to a known myopathy gene with the corresponding phenotype, while 55 (44%) were linked to pathogenic variants in a known myopathy gene with atypical signs, highlighting that most genetic diagnosis could not be anticipated based on clinical–histological assessments in this cohort. An important phenotypic and genetic heterogeneity was observed for the different genes and for the different congenital myopathy subtypes, respectively. In addition, we identified 14 new myopathy genes not previously associated with muscle diseases (20% of all diagnosed cases) that we previously reported in the literature, revealing novel pathomechanisms and potential therapeutic targets. Conclusions: Overall, this approach illustrates the importance of massive parallel gene sequencing as a comprehensive tool for establishing a molecular diagnosis for families with congenital myopathies. It also emphasizes the contribution of clinical data, histological findings on muscle biopsies, and the availability of DNA samples from additional family members to the diagnostic success rate. This study facilitated and accelerated the genetic diagnosis of congenital myopathies, improved health care for several patients, and opened novel perspectives for either repurposing of existing molecules or the development of novel treatments. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an autosomal recessive disease associated with alterations in mitochondrial DNA (mtDNA). The typical age of onset of MNGIE is between the first and second decade of life. Diagnosis requires the presence of several key clinical features: sensorimotor neuropathy, external ophthalmoplegia, ocular ptosis, leukoencephalopathy, and gastrointestinal (GI) dysmotility. Unfortunately, MNGIE diagnosis is very challenging, and patients often undergo multiple diagnostic and surgical operations that are unnecessary. Case presentation: This case is of a 51-year-old male presenting with a 2-year history of limb weakness, GI problems and cachexia. There was also a 1-year history of progressive ptosis and ophthalmoplegia. The patient's uncle and brother had both died from GI-related issues prior to the age of 40. On physical examination, ocular motility was impaired in all directions and there was atrophy and reduction in power in both lower and upper extremities. FLAIR and T2-weighted sequences of brain MRI demonstrated diffuse cerebral white matter hyperintensity (leukoencephalopathy). On discharge, the patient was referred for genetic consultation for bone marrow transplantation and had regular follow-up with a gastroenterology specialist. Conclusion: In patients presenting with chronic progressive ophthalmoplegia, severe gastrointestinal complications, sensorimotor neuropathy and white matter lesions on MRI, it is important to consider investigating for MNGIE. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cells (VSMCs) are integral to the pathophysiology of cardiovascular diseases (CVDs). Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, plays a crucial role in epigenetic regulation of VSMCs gene expression. Emerging researches suggest that EZH2 has a dual role in VSMCs, contingent on the pathological context of specific CVDs. This mini-review synthesizes the current knowledge on the mechanisms by which EZH2 regulates VSMC proliferation, migration and survival in the context of CVDs. The goal is to underscore the potential of EZH2 as a therapeutic target for CVDs treatment. Modulating EZH2 and its associated epigenetic pathways in VSMCs could potentially ameliorate vascular remodeling, a key factor in the progression of many CVDs. Despite the promising outlook, further investigation is warranted to elucidate the epigenetic mechanisms mediated by EZH2 in VSMCs, which may pave the way for novel epigenetic therapies for conditions such as atherosclerosis and hypertension. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to perform a long-term evaluation of the efficacy and safety of treatment with botulinum toxin A (BoNT-A) in patients with blepharospasm (BS) and hemifacial spasm (HFS) from January 2007 to December 2019. Methods: In each application of BoNT-A, the date of treatment, number of units applied, and time elapsed since the previous application were recorded. Outcome data was: mean latency of the clinical effect, mean duration of the clinical effect, mean improvement on Jankovic rating scale, side effects were self-reported, and evaluated 2 weeks after injection, including non-responding patients to BoNT-A for two consecutive sessions. The comparison between the first and last dose of BoNT-A was analyzed by Student's t-test, for which a value of p < 0.05 was considered statistically significant. Results: A total of 136 patients were analyzed; 60 had BS, 76 had HFS, and 75% were female. The duration between onset and referral for BoNT-A treatment was 18 ± 3 months, and the mean age at the time of the first therapeutic injection was 50 ± 12 years. The mean dose per session was 16 ± 4 for BS and 36 ± 12 for HFS. The therapeutic interval for injections was 4.4 ± 1 month. The mean latency of the clinical effect was 8 ± 3 days, the mean duration of the clinical effect was 112 ± 9 days, and the mean improvement on the Jankovic scale was 2 ± 1 points. Side effects were observed in 9 patients (6.6%), that is, ptosis (7 patients) and hematoma (2 patients). Conclusions: BoNT-A is a safe and effective long-term treatment for BS and HFS. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 81-year-old woman successfully treated with reduced oral steroid dosage for statin-induced anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) immune-mediated necrotizing myopathy. Topics discussed include the management strategies, clinical outcomes, and therapeutic adjustments in elderly patients experiencing rare immune-mediated muscle disorders associated with statin use.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85–24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62–25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12–9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06–0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies. [ABSTRACT FROM AUTHOR]

This article summarizes a study that explores the role of the PACSIN3 gene in a rare muscle disorder. The study focuses on two families with children who experience exercise intolerance and early fatigue. Genetic testing reveals that the children have loss-of-function variants in the PACSIN3 gene, which is involved in cytoskeleton organization and intracellular trafficking. The study suggests that PACSIN3 deficiency can cause a myopathy with elevated creatine kinase levels in children. Further research is needed to fully understand the mechanisms and implications of PACSIN3 deficiency in muscle function. [Extracted from the article]

Purpose: We aim to propose a visual quantitative score for muscle edema in lower limb MRI to contribute to the diagnosis of idiopathic inflammatory myopathy (IIM). Material and methods: We retrospectively evaluated 85 consecutive patients (mean age 57.4 ± 13.9 years; 56.5% female) with suspected IIM (muscle weakness and/or persistent hyper-CPK-emia with/without myalgia) who underwent MRI of lower limbs using T2-weighted fast recovery-fast spin echo images and fat-sat T2 echo planar images. Muscle inflammation was evaluated bilaterally in 11 muscles of the thigh and eight muscles of the leg. Edema in each muscle was graded according to a four-point Likert-type scale adding up to 114 points ([11 + 8)] × 3 × 2). Diagnostic accuracy of the total edema score was explored by assessing sensitivity and specificity using the area under the ROC curve. Final diagnoses were made by a multidisciplinary Expert Consensus Panel applying the Bohan and Peter diagnostic criteria whenever possible. Results: Of the 85 included patients, 34 (40%) received a final diagnosis of IIM (IIM group) while 51 (60%) received an alternative diagnosis (non-IIM group). A cutoff score ≥ 18 was able to correctly classify patients having an IIM with an area under the curve of 0.85, specificity of 96%, and sensitivity of 52.9%. Conclusion: Our study demonstrates that a quantitative MRI score for muscle edema in the lower limbs (thighs and legs) aids in distinguishing IIM from conditions that mimic it. [ABSTRACT FROM AUTHOR]

Introduction: There is an increasing need for a reproducible and sensitive outcome measure in patients with hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy (PN) due to the emergence of disease modifying therapies. In the current study, we aimed to investigate the role of quantitative muscle ultrasound (QMUS) as a disease biomarker in ATTRv-PN. Methods: Twenty genetically confirmed ATTRv amyloidosis patients (nine symptomatic, 11 pre-symptomatic) were enrolled prospectively between January to March 2023. Muscle ultrasound was performed on six muscles at standardized locations. QMUS parameters included muscle thickness (MT) and muscle echo intensity (EI). Twenty-five age- and sex-matched healthy controls were recruited for comparison. Significant QMUS parameters were correlated with clinical outcome measures. Results: Muscle volume of first dorsal interosseus (FDI) muscle [measured as cross-sectional area (CSA)] was significantly lower in symptomatic patients compared to healthy controls and pre-symptomatic carriers (98.3 ± 58.0 vs. 184.4 ± 42.5 vs. 198.3 ± 56.8, p < 0.001). EI of biceps and FDI for symptomatic ATTRv-PN patients were significantly higher compared to the other two groups (biceps: 76.4 ± 10.8 vs. 63.2 ± 11.5 vs. 59.2 ± 9.0, p = 0.002; FDI: 48.2 ± 7.5 vs. 38.8 ± 7.5 vs. 33.0 ± 5.3, p < 0.001). CSA of FDI and EI of biceps and FDI correlated with previous validated outcome measures [polyneuropathy disability score, neuropathy impairment score, Karnofsky performance scale, Rasch-built overall disability scale, European quality of life (QoL)-5 dimensions and Norfolk QoL questionnaire—diabetic neuropathy]. Conclusion: QMUS revealed significant difference between ATTRv amyloidosis patients and healthy controls and showed strong correlation with clinical outcome measures. QMUS serves as a sensitive and reliable biomarker of disease severity in ATTRv-PN. [ABSTRACT FROM AUTHOR]

Statins represent the primary therapy for combatting hypercholesterolemia and reducing mortality from cardiovascular events. Despite their pleiotropic effects in lowering cholesterol synthesis, circulating cholesterol, as well as reducing the risk of other systemic diseases, statins have adverse events in a small, but significant, population of treated patients. The most prominent of these adverse effects is statin-induced myopathy, which lacks precise definition but is characterised by elevations in the muscle enzyme creatine kinase alongside musculoskeletal complaints, including pain, weakness and fatigue. The exact aetiology of statin-induced myopathy remains to be elucidated, although impaired mitochondrial function is thought to be an important underlying cause. This may result from or be the consequence of several factors including statin-induced inhibition of coenzyme Q10 (CoQ10) biosynthesis, impaired Ca2+ signalling and modified reactive oxygen species (ROS) generation. The purpose of this review article is to provide an update on the information available linking statin therapy with mitochondrial dysfunction and to outline any mechanistic insights, which may be beneficial in the future treatment of myopathic adverse events. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive analysis of the clinical characteristics of cardiac involvement in idiopathic inflammatory myopathies (IIM). The study found that 39% of patients with IIM had cardiac involvement, with arrhythmia being the most common symptom. The presence of autoantibodies was similar across different subtypes of IIM, but the prevalence of abnormal cardiac findings varied. Risk factors for symptomatic cardiac involvement included Raynaud's syndrome and an elevated neutrophil/lymphocyte ratio. Further research is needed to confirm these findings and understand the pathophysiology of cardiac damage in IIM. [Extracted from the article]

Background: GNE myopathy is an ultra-rare autosomal recessive distal myopathy caused by pathogenic variants of the GNE gene, which encodes a key enzyme in sialic acid biosynthesis. The present study aimed to examine the long-term progression of GNE myopathy, genotype–phenotype correlations, and complications to provide useful information for predicting patient progression and designing clinical trials using a large collection of registry data over a 10-year period. Methods: We analyzed 220 Japanese patients with GNE myopathy from a national registry in Japan. Diagnoses were confirmed by genetic curators based on genetic analysis reports. We analyzed registration sheets and annually updated items completed by attending physicians. Results: In total, 197 of 220 participants (89.5%) carried p.D207V or p.V603L in at least one allele. The median disease duration to loss of ambulation was estimated to be 10 years in p.V603L homozygotes (n = 48), whereas more than 90% of p.D207V/p.V603L compound heterozygotes were estimated to be ambulatory even 20 years after disease onset according to Kaplan–Meier analysis (p < 0.001). Moreover, participants with a younger age of onset lost ambulation earlier regardless of genotype. A decline in respiratory function was observed as the disease progressed, particularly in p.V603L homozygotes, whereas none of the p.D207V/p.V603L compound heterozygotes showed a decline. Conclusions: The present study demonstrated large differences in disease progression and respiratory function between genotypes. Moreover, age of onset was found to be an indicator of disease severity regardless of genotype in GNE myopathy patients. These results may help stratify patients in clinical trials and predict disease progression. [ABSTRACT FROM AUTHOR]

Objective: X-linked myopathy with excessive autophagy (XMEA) linked to the VMA21 gene leads to autophagy failure with progressive vacuolation and atrophy of skeletal muscles. Current knowledge of this rare disease is limited. Our objective was to define the clinical, radiological, and natural history of XMEA. Methods: We conducted a retrospective study collecting clinical, genetic, muscle imaging, and biopsy data of XMEA patients followed in France and reviewed the literature for additional cases. Results: Eighteen males had genetically confirmed XMEA in France, carrying four different VMA21 variants. Mean age at disease onset was 9.4 ± 9.9 (range 1–40) years. In 14/18 patients (77.8%), onset occurred during childhood (< 15 years); however in four patients, the disease started in adulthood. Patients had anterior and medial compartment thigh muscle weakness, distal contractures (56.3%), elevated CK levels (1287.9 ± 757.8 U/l) and autophagic vacuoles with sarcolemmal features on muscle histopathology. Muscle MRI (n = 10) showed a characteristic pattern of lower limb muscle involvement. In 11 patients, outcome measures were available for an average follow-up period of 10.6 ± 9.8 years and six of them show disease progression. Mean change of functional outcomes was 0.5 ± 1.2 points for Brooke and 2.2 ± 2.5 points for Vignos score, 7/16 patients (43.8%) needed a walking aid and 3/16 (18.8%) were wheelchair-bound (median age of 40 years old, range 39–48). The variant c.164-7 T > G was associated with a later onset of symptoms. Respiratory insufficiency was common (57.1%) but cardiac involvement rare (12.5%). Interpretation: XMEA has variable age of onset, but a characteristic clinical, histopathological, and muscle imaging presentation, guiding the diagnosis. Although slowly, motor disability progresses with time, and relevant genotype–phenotype correlations will help design future clinical trials. [ABSTRACT FROM AUTHOR]

The commonality between various muscle diseases is the loss of muscle mass, function, and regeneration, which severely restricts mobility and impairs the quality of life. With muscle stem cells (MuSCs) playing a key role in facilitating muscle repair, targeting regulators of muscle regeneration has been shown to be a promising therapeutic approach to repair muscles. However, the underlying molecular mechanisms driving muscle regeneration are complex and poorly understood. Here, we identified a new regulator of muscle regeneration, Deaf1 (Deformed epidermal autoregulatory factor-1) – a transcriptional factor downstream of foxo signaling. We showed that Deaf1 is transcriptionally repressed by FOXOs and that DEAF1 targets to Pik3c3 and Atg16l1 promoter regions and suppresses their expression. Deaf1 depletion therefore induces macroautophagy/autophagy, which in turn blocks MuSC survival and differentiation. In contrast, Deaf1 overexpression inactivates autophagy in MuSCs, leading to increased protein aggregation and cell death. The fact that Deaf1 depletion and its overexpression both lead to defects in muscle regeneration highlights the importance of fine tuning DEAF1-regulated autophagy during muscle regeneration. We further showed that Deaf1 expression is altered in aging and cachectic MuSCs. Manipulation of Deaf1 expression can attenuate muscle atrophy and restore muscle regeneration in aged mice or mice with cachectic cancers. Together, our findings unveil an evolutionarily conserved role for DEAF1 in muscle regeneration, providing insights into the development of new therapeutic strategies against muscle atrophy.Abbreviations: DEAF1: Deformed epidermal autoregulatory factor-1; FOXO: Forkhead box O; MuSC: Muscle Stem Cell; PAX7: Paired box 7; PIK3C3: Phosphatidylinositol 3-kinase catalytic subunit type 3. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double-negative subsets, as well as an expansion of the naive compartment relative to healthy controls, that contribute to defining disease-associated B-cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathy onset or development. [ABSTRACT FROM AUTHOR]

Objective : To determine the sensitivity and specificity of velar notching seen on nasopharyngoscopy for levator veli palatini (LVP) muscle discontinuity and anterior positioning. Design : Nasopharyngoscopy and MRI of the velopharynx were performed on patients with VPI as part of their routine clinical care. Two speech-language pathologists independently evaluated nasopharyngoscopy studies for the presence or absence of velar notching. MRI was used to evaluate LVP muscle cohesiveness and position relative to the posterior hard palate. To determine the accuracy of velar notching for detecting LVP muscle discontinuity, sensitivity, specificity, and positive predictive value (PPV) were calculated. Setting : A craniofacial clinic at a large metropolitan hospital. Participants: Thirty-seven patients who presented with hypernasality and/or audible nasal emission on speech evaluation and completed nasopharyngoscopy and velopharyngeal MRI study as part of their preoperative clinical evaluation. Results : Among patients with partial or total LVP dehiscence on MRI, presence of a notch accurately identified discontinuity in the LVP 43% (95% CI 22-66%) of the time. In contrast, the absence of a notch accurately indicated LVP continuity 81% (95% CI 54-96%) of the time. The PPV for the presence of notching to identify a discontinuous LVP was 78% (95% CI 49-91%). The distance from the posterior edge of the hard palate to the LVP, known as effective velar length, was similar in patients with and without notching (median 9.8 mm vs 10.5 mm, P = 1.00). Conclusion : The observation of a velar notch on nasopharyngoscopy is not an accurate predictor of LVP muscle dehiscence or anterior positioning. [ABSTRACT FROM AUTHOR]