Neuromuscular Disorders Research Articles

Acute Respiratory Failure in Children: A Clinical Update on Diagnosis.

Acute respiratory failure (ARF) is a sudden failure of the respiratory system to ensure adequate gas exchanges. Numerous clinical conditions may cause ARF, including pneumonia, obstructive lung diseases (e.g., asthma), restrictive diseases such as neuromuscular diseases (e.g., spinal muscular atrophy and muscular dystrophy), and albeit rarely, interstitial lung diseases. Children, especially infants, may be more vulnerable to ARF than adults due to anatomical and physiological features of the respiratory system. Assessing respiratory impairment in the pediatric population is particularly challenging as children frequently present difficulties in reporting symptoms and due to compliance and cooperation in diagnostic tests. The evaluation of clinical and anamnestic aspects represents the cornerstone of ARF diagnosis: first level exams (e.g., arterial blood gas analysis) confirm and evaluate the severity of the ARF and second level exams help to uncover the underlying cause. Prompt management is critical, with supplemental oxygen, mechanical ventilation, and the treatment of the underlying problem. The aim of this review is to provide a comprehensive summary of the current state of the art in diagnosing pediatric ARF, with a focus on pathophysiology, novel imaging applications, and new perspectives, such as biomarkers and artificial intelligence.

Predictive Value of Diaphragm and Lung Ultrasonography for Weaning Failure in Critically Ill Patients with Acute Respiratory Failure Due to COVID-19 Pneumonia.

This study analyzed weaning characteristics and assessed the association of clinical and ultrasonographic indices-maximum inspiratory pressure (MIP), rapid shallow breathing index (RSBI), peak flow expiratory (PFE), diaphragm-thickening fraction (DTF), diaphragm thickness (DT), diaphragm excursion (DE), diaphragm-RSBI (D-RSBI), and lung ultrasound (LUS) patterns-with weaning failure. This retrospective cohort study included critically ill COVID-19 patients aged 18 and older who had been on invasive mechanical ventilation for at least 48 h and undergoing weaning. Exclusion criteria included absence of ultrasound assessments, neuromuscular diseases, and chronic cardio-respiratory dysfunction. Among 61 patients, 44.3% experienced weaning failure, 27.9% failed the spontaneous breathing trial (SBT), 16.4% were re-intubated within 48 h, and 28% required tracheostomy. Weaning failure was associated with prolonged ventilation (29 vs. 7 days, p < 0.001), extended oxygen therapy, longer ICU stays, and higher ICU mortality. These patients had higher pressure support, lower oxygenation levels, a higher RSBI, and a lower MIP. While PEF, DTF, DE, and D-RSBI showed no significant differences, both right and left diaphragm thicknesses and the inspiratory thickness of the left diaphragm were reduced in failure cases. LUS scores were significantly higher before and after SBT in the failure group. Bivariate analysis identified RSBI [OR = 1.04 (95% CI = 1.01-1.07), p = 0.010], MIP [OR = 0.92 (95% CI = 0.86-0.99), p = 0.018], and LUS [OR = 1.15 (95% CI = 0.98-1.35), p = 0.025] as predictors of weaning failure; however, these associations were not confirmed in multivariate analysis. Ultrasound provides supplementary information during weaning, but no definitive association between ultrasound indices and weaning failure was confirmed in this study.

Myopathy in glycogen storage disease type IV: case report of a family

Aim. To study the clinical presentation and differential diagnosis of a rare hereditary disease glycogen storage disease type IV with progressive skeletal myopathy in a case report of a family.Materials and methods. Two patients were followed up in the specialized neurology unit of the regional clinical hospital and in the outpatient setting.Results. Long-term follow-up and examination in two clinically similar cases of myopathy in siblings allowed us to diagnose a hereditary metabolic disease. The congenital muscular form of glycogen storage disease type IV was manifested by myopathy and peripheral tetraparesis with the development of bone deformities. Difficulty in the diagnosis was due to isolated myopathy progression with no signs of liver involvement. The diagnosis was established with account of clinical manifestations, the progressive course of the disease, electromyography findings, and the results of molecular genetic testing for pathogenic mutations associated with hereditary neuromuscular diseases.Conclusion. Glycogen storage disease type IV can clinically manifest itself by progressive myopathy without liver involvement and changes in blood biochemistry. The presented clinical cases in siblings are identical. Myopathy does not have clinical features that are significant for the differential diagnosis with other hereditary neuromuscular diseases. Genetic testing identified a mutation in the GBE1 gene and is considered as the main diagnostic criterion of the disease.

The quality of the electrodiagnostic referral system and the electrodiagnostic patterns in a sample of Egyptian patients

BackgroundElectrodiagnosis is a localizing, diagnostic, and prognostic tool for individuals with suspected neuromuscular diseases. In addition to detailed history taking and thorough clinical examination, correct execution and interpretation of these tests can provide vital insights into the underlying neuromuscular disorders and frequently guide the need for proper management decision. The request for an electrodiagnosis examination should include brief clinical information and a provisional clinical diagnosis; this enhances the efficient easy performance of the test. The current study aims to detect the pattern of neuromuscular diseases in the Alexandria Main University Hospital, Egypt, and to evaluate the quality of the referral system to the electrodiagnosis unit.ResultsThe study included 371 patients, out of which, 65% were referred from the Governmental Specialized Medical Councils and the Neurosurgery department. Although sensory complaints were the main reason for referral, yet 28.8% of patients did not show any electrodiagnosis abnormality. A compatible referral note led to shorter test times and fewer electromyography needle insertions.ConclusionDisorders of the peripheral nerves are the most frequent neuromuscular diseases referred to the electrodiagnosis unit with carpal tunnel syndrome being the most common disorder. A compatible referral letter is necessary when requesting an electrodiagnosis test, to save the physician time and focus on targeted procedures.

Acetylcholine receptor-β inhibition by interleukin-6 in skeletal muscles contributes to modulating neuromuscular junction during aging

BackgroundAging-related strength decline contributes to physiological deterioration and is a good predictor of poor prognosis. However, the mechanisms underlying neuromuscular junction disorders affecting contraction in aging are not well described. We hypothesized that the autocrine effect of interleukin (IL)-6 secreted by skeletal muscle inhibits acetylcholine receptor (AChR) expression, potentially causing aging-related strength decline. Therefore, we investigated IL-6 and AChR β-subunit (AChR-β) expression in the muscles and sera of aging C57BL/6J mice and verified the effect of IL-6 on AChR-β expression.MethodsAnimal experiments, in vitro studies, bioinformatics, gene manipulation, dual luciferase reporter gene assays, and chromatin immunoprecipitation experiments were used to explore the role of the transcription cofactor peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) and its interacting transcription factors in the IL-6-mediated regulation of AChR-β expression.ResultsIL-6 expression gradually increased during aging, inhibiting AChR-β expression, which was reversed by tocilizumab. Both tocilizumab and the PGC1α agonist reversed the inhibiting effect of IL-6 expression on AChR-β. Compared to inhibition of signal transducer and activator of transcription 3, extracellular signal-regulated kinases 1/2 (ERK1/2) inhibition suppressed the effects of IL-6 on AChR-β and PGC1α. In aging mouse muscles and myotubes, myocyte enhancer factor 2 C (MEF2C) was recruited by PGC1α, which directly binds to the AChR-β promoter to regulate its expression.ConclusionsThis study verifies AChR-β regulation by the IL-6/IL-6R-ERK1/2-PGC1α/MEF2C pathway. Hence, evaluating muscle secretion, myokines, and AChRs at an earlier stage to determine pathological progression is important. Moreover, developing intervention strategies for monitoring, maintaining, and improving muscle structure and function is necessary.

AML-DECODER: Advanced Machine Learning for HD-sEMG Signal Classification-Decoding Lateral Epicondylitis in Forearm Muscles.

Innovative algorithms for wearable devices and garments are critical for diagnosing and monitoring disease (such as lateral epicondylitis (LE)) progression. LE affects individuals across various professions and causes daily problems. We analyzed signals from the forearm muscles of 14 healthy controls and 14 LE patients using high-density surface electromyography. We discerned significant differences between groups by employing phase-amplitude coupling (PAC) features. Our study leveraged PAC, Daubechies wavelet with four vanishing moments (db4), and state-of-the-art techniques to train a neural network for the subject's label prediction. Remarkably, PAC features achieved 100% specificity and sensitivity in predicting unseen subjects, while state-of-the-art features lagged with only 35.71% sensitivity and 28.57% specificity, and db4 with 78.57% sensitivity and 85.71 specificity. PAC significantly outperformed the state-of-the-art features (adj. p-value < 0.001) with a large effect size. However, no significant difference was found between PAC and db4 (adj. p-value = 0.147). Also, the Jeffries-Matusita (JM) distance of the PAC was significantly higher than other features (adj. p-value < 0.001), with a large effect size, suggesting PAC features as robust predictors of neuromuscular diseases, offering a profound understanding of disease pathology and new avenues for interpretation. We evaluated the generalization ability of the PAC model using 99.9% confidence intervals and Bayesian credible intervals to quantify prediction uncertainty across subjects. Both methods demonstrated high reliability, with an expected accuracy of 89% in larger, more diverse populations. This study's implications might extend beyond LE, paving the way for enhanced diagnostic tools and deeper insights into the complexities of neuromuscular disorders.

Type 1 spinal muscular atrophy treated with nusinersen in Norway, a five-year follow-up

BackgroundNew treatments for 5q spinal muscular atrophy (SMA) have led to changes in the disease phenotype. Questions about long-term efficacy, however, persist. We present the results from five-year follow-up of the first ten Norwegian patients with SMA type1 treated with nusinersen. Methods– Ten patients referred to the expanded access program were included. Standardized assessments with Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), the Hammersmith Infant Neurological Examination (HINE-2), compound muscle action potential (CMAP) examination and cerebrospinal fluid analysis of neurofilament light chain (cNfL) were performed. ResultAge at baseline ranged from three months to 11 years and eight months. Nine patients were alive and continued to receive treatment at 62 months of follow-up. CHOP INTEND scores increased significantly up to 38 months. Any further increase from 38 to 50 months was not statistically significant, and scores remained almost unchanged from 50 to 62 months. HINE-2 scores increased but the difference from baseline never reached statistical significance.The youngest patients showed the best motor outcome. The changes in CMAP scores were not statistically significant. cNfL values were significantly reduced after 18 months compared with baseline; the largest difference occurred between baseline and 6 months. There was a significant negative correlation between log cNfL and CHOP INTEND (p = 0.042). Bulbar and respiratory function did not improve during the observation period. ConclusionOur findings support previously reported results on efficacy and safety of nusinersen. All patients have shown improvement in motor function. The need of respiratory and nutritional support did not improve.

Challenges Faced By Families of SMA Patients

SMA, a genetic neuromuscular disease that affects the control of muscle movement and results in severe motor disorders, is among the rare diseases. Due to the low prevalence of rare diseases and serious problems with correct diagnosis, there may be delays in diagnosis. When the studies on SMA are examined, it is known that the issues related to diagnosis are mostly emphasised, but a limited number of studies have been conducted on the current issues of patients with SMA or their caregivers. In addition to studies on treatment, it would be useful to consider the patient and his/her environment together in studies on the quality of life of patients and caregivers. Examining the concept of quality of life in SMA disease will form the basis for studies on quality of life, and at the same time, the continuity of studies on the subject will be ensured. In this sense, current issues the treatment of patients diagnosed with SMA was addressed in this study. The fact that these patients experience significant deficiencies such as respiratory impairment, malnutrition and skeletal deformity causes them to face difficulties in meeting their basic needs, especially in nutrition and toileting. These problems reduce the quality of life of patients and their relatives. Therefore, early diagnosis and providing medical, psychological, and social support to patients and their relatives will be effective in their quality of life. In this review, recommendations were made to address the current issues of SMA patients and their relatives.

Analysis of muscle synergies and muscle network in sling exercise rehabilitation technique

The study assessed motor control strategies across the four sling exercises of supine sling exercise (SSE), prone sling exercise (PSE), left side-lying sling exercise (LLSE), and right side-lying sling exercise (RLSE) positions base on the muscle synergies and muscle network analyses. Muscle activities of bilateral transversus abdominis (TA), rectus abdominis, multifidus (MF), and erector spinae (ES) were captured via surface electromyography. Muscle synergies were extracted through principal components analysis (PCA) and non-negative matrix factorization (NNMF). Muscle synergies number, muscle synergies complexity, muscle synergies sparseness, muscle synergies clusters and muscle networks were calculated. PCA results indicated that SSE and PSE decomposed into 2.88 ± 0.20 and 2.82 ± 0.15 synergies respectively, while the LLSE and RLSE positions decomposed into 3.76 ± 0.14 and 3.71 ± 0.11 muscle synergies, respectively, which were more complex (P = 0.00) but less sparse (P = 0.01). Muscle synergies clusters analysis indicated common muscle synergies among different sling exercises. SSE position demonstrated specific muscle synergies with a strong contribution of the bilateral TA. LLSE-specific synergy has a strong contribution of the left erector spinae (ES). The RLSE-specific synergy has significant contributions from the right ES and multifidus. Muscle networks were functionally organized, with clustering coefficient (F(1.5, 24) = 6.041, P = 0.01) and global efficiency of the undirected network (F(1.5, 24) = 6.041, P = 0.01), and betweenness-centrality of the directed network (F(2.7, 44) = 6.453, P = 0.00). Our research highlights the importance of evaluating muscle synergies and network adaptation strategies in individuals with neuromuscular disorders and developing targeted therapeutic interventions accordingly.

The 9 bp Deletion between the Mitochondrial COII and Lysine tRNA Genes in a Caucasian Population with Cognitive Disorders: An Observational Study.

The loss of one of the two copies of the 9 bp tandem repeat sequence (CCCCCTCTA) located in the small non-coding region between the cytochrome oxidase II (COII) and the lysine tRNA genes in human mtDNA has been reported to be polymorphic in Asian, Oceanian and Sub-Saharan African populations, but it has rarely been observed in Europe. In this study, we will evaluate the possible association between the MIC9D polymorphism and cognitive disorders. A genetic analysis of unrelated Sicilian patients with cognitive deficits was performed to identify the 9 bp deletion MIC9D polymorphism. The MIC9D polymorphism was found in six patients, whereas this variant was absent in control individuals without cognitive deficits. The patients with the MIC9D polymorphism exhibited more complex clinical presentations; in particular, all had neuromuscular disorders and five also presented with behavioral disorders. The present study suggests a potential association between the MIC9D polymorphism and cognitive impairment with concurrent neuromuscular and behavioral involvement.

AAV gene therapy for Duchenne muscular dystrophy: the EMBARK phase 3 randomized trial.

Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disease caused by pathogenic variants in the DMD gene that result in the absence of functional dystrophin, beginning at birth and leading to progressive impaired motor function, loss of ambulation and life-threatening cardiorespiratory complications. Delandistrogene moxeparvovec, an adeno-associated rh74-viral vector-based gene therapy, addresses absent functional dystrophin in DMD. Here the phase 3 EMBARK study aimed to assess the efficacy and safety of delandistrogene moxeparvovec in patients with DMD. Ambulatory males with DMD, ≥4 years to <8 years of age, were randomized and stratified by age group and North Star Ambulatory Assessment (NSAA) score to single-administration intravenous delandistrogene moxeparvovec (1.33 × 1014 vector genomes per kilogram; n = 63) or placebo (n = 62). At week 52, the primary endpoint, change from baseline in NSAA score, was not met (least squares mean 2.57 (delandistrogene moxeparvovec) versus 1.92 (placebo) points; between-group difference, 0.65; 95% confidence interval (CI), -0.45, 1.74; P = 0.2441). Secondary efficacy endpoints included mean micro-dystrophin expression at week 12: 34.29% (treated) versus 0.00% (placebo). Other secondary efficacy endpoints at week 52 (between-group differences (95% CI)) included: Time to Rise (-0.64 (-1.06, -0.23)), 10-meter Walk/Run (-0.42 (-0.71, -0.13)), stride velocity 95th centile (0.10 (0.00, 0.19)), 100-meter Walk/Run (-3.29 (-8.28, 1.70)), time to ascend 4 steps (-0.36 (-0.71, -0.01)), PROMIS Mobility and Upper Extremity (0.05 (-0.08, 0.19); -0.04 (-0.24, 0.17)) and number of NSAA skills gained/improved (0.19 (-0.67, 1.06)). In total, 674 adverse events were recorded with delandistrogene moxeparvovec and 514 with placebo. There were no deaths, discontinuations or clinically significant complement-mediated adverse events; 7 patients (11.1%) experienced 10 treatment-related serious adverse events. Delandistrogene moxeparvovec did not lead to a significant improvement in NSAA score at week 52. Some of the secondary endpoints numerically favored treatment, although no statistical significance can be claimed. Safety was manageable and consistent with previous delandistrogene moxeparvovec trials. ClinicalTrials.gov: NCT05096221.

Differences between women and men in prolonged weaning

BackgroundIn recent years, the importance of sex as a factor influencing medical care has received increasing attention in the field of intensive care medicine. The objective of this study was to examine the influence of sex in prolonged weaning.MethodsA retrospective analysis of patients undergoing prolonged weaning at Thoraxklinik, University Hospital Heidelberg between 12/08 and 12/23 was conducted. Patients with neuromuscular diseases were excluded from the analyses. The risk factors for weaning failure in men and women were identified through stepwise cox-regression analyses.ResultsA total of 785 patients were included, of whom 313 (39.9%) were women. 77.9% of the women and 75.4% of the men were successfully weaned from invasive ventilation. In group comparisons and multivariable analyses, sex was not found to be a risk factor for weaning failure. Cox regression analyses were performed separately for both sexes on the outcome of weaning failure, adjusting for relevant covariates. The results indicated that age ≥ 65 years (HR 2.38, p < 0.001) and the duration of IMV before transfer to the weaning centre (HR 1.01/day, p < 0.001) were independent risk factors in men. In women, however, the duration of IMV before transfer (HR 1.01, p < 0.001), previous non-invasive ventilation (HR 2.9, p 0.005), the presence of critical illness polyneuropathy (HR 1.82; p = 0.040) and delirium (HR 2.50, p = 0.017) were identified as relevant risk factors. In contrast delirium was associated with a favourable weaning outcome in men (HR 0.38, p = 0.020) and nosocomial pneumonia as a reason for prolonged weaning in women (HR 0.43; p = 0.032).ConclusionThe analyses indicate that there are sex-based differences in the risk factors associated with weaning failure. Further studies, ideally prospective, should confirm these findings to assess whether sex is a factor that should be taken into account to improve weaning outcomes.

A Comprehensive Review of Electromyography in Rehabilitation: Detecting Interrupted Wrist and Hand Movements with a Robotic Arm Approach

Electromyography (EMG) is a diagnostic technique that measures the electrical activity generated by skeletal muscles. Utilizing electrodes placed either on the skin (surface EMG) or inserted directly into the muscle(intramuscular EMG), it detects electrical signals produced during muscle contractions. EMG is widely employed in clinical and research settings to assess muscle function, diagnose neuromuscular disorders,and guide rehabilitation therapy. Over the years, EMG has evolved from a basic measurement tool into an essential technology within clinical and research environments, propelled by advances in recording techniques and digital innovations. The integration of wearable technology and artificial intelligence (AI) has significantly expanded its applications, particularly in rehabilitation and sports science. By capturing muscle electrical activity through surface or intramuscular electrodes, EMG benefits from enhanced signal processing that improves accuracy and data analysis. Despite challenges such as signal interference and the complexities of movement patterns—especially in wrist and hand rehabilitation—EMG combined with robotic systems offers real-time feedback for precise and personalized therapy. However, obstacles like cost, complexity, and variability among patients still remain. Future advancements aim to make EMG more accessible and to integrate AI for tailored rehabilitation strategies, alongside improvements in sensors and wireless communication to enhance reliability and performance. This review explores various facets of EMG,from its fundamental principles to its application in detecting disrupted wrist and hand movements through robotic approaches. It provides a comprehensive analysis of EMG’s historical and technological evolution, recent innovations like AI and wearable devices, and its extensive applications in rehabilitation and sports science. Detailed case studies illustrate its effectiveness in areas such as stroke recovery and spinal cord injury rehabilitation. Additionally, the review addresses challenges like technical limitations and patient variability while emphasizing the integration of EMG with robotic systems for personalized therapy. It also discusses the significance of real-time feedback, future enhancements in AI and sensor technology, and the pressing need for more affordable, user-friendly solutions to improve therapeutic outcomes.

Unusual presentation of PYGM gene mutation as late-onset McArdle disease with camptocormia: a case report

BackgroundGlycogen storage disease type 5 (McArdle disease) leads to a deficiency in the activity of myophosphorylase resulting in an impaired glucose utilization. The disease can be caused by a variety of mutations in the PYGM gene, and its typical clinical manifestation is muscles weakness within the first three decades of life.Case presentationIn this case report we present the diagnostic work-up of a physically active 78-year-old Caucasian patient suffering from a 2-year history of progressive camptocormia including clinical, radiologic, histological, and genetic tests. There was no history of neuro-muscular diseases in the family. Serum CK levels were moderately increased while other blood/urine parameters were normal. Magnetic resonance imaging showed fatty remodeling of the muscles of the back. Histochemical examination of a muscle biopsy revealed the absence of myophosphorylase activity, while gene analysis identified a known early-onset McArdle mutation in the PYGM gene.ConclusionThis case highlights that the clinical spectrum of PYGM gene mutation typically manifest during adolescence, but it is also a differential diagnosis in late onset muscle disorders and emphases the investigation of the role of ACE inhibitors in this disease.

Management of Chronic Neuromuscular Respiratory Failure in the Intensive Care Unit.

In this seminar we describe the critical care management of patients with chronic neuromuscular diseases (cNMD). Determination of the acuity of the critical illness and trajectory of illness in the setting of cNMD is necessary to guide decision making. Systemic complications of critical illness, cardiac support needs, and peri-intubation considerations may be affected by underlying diagnosis. Mechanical ventilatory support, whether noninvasive or invasive, requires redefinition of the goals of ventilation on a patient-by-patient basis. Mode and approach to invasive ventilation and liberation to noninvasive ventilation versus tracheostomy have limited evidence, but potential clinical approaches are reviewed.

Longitudinal monitoring of hypertonia through a multimodal sensing glove

As clinical evaluations of neuromuscular disorders such as hypertonia mostly rely on perception-based scales, the imprecise subjective ratings make it difficult to accurately monitor treatment progress. To promote objective evaluation, this work used a multi-modal sensing glove in a double-blind study to enable sensitive monitoring of medication effects across 19 participants. The biomechanical measurements from the sensing glove effectively distinguished patient cohorts receiving a baclofen treatment or a placebo with 95% confidence. Consistent monitoring over a two-month period was demonstrated, closely tracking variations in individual responses to treatment. The biomechanical changes were correlated to neural activities as recorded by electromyography, verifying the medication effects. The sensing glove is shown to be a reliable tool for point-of-care settings to facilitate precise evaluation of hypertonia, essential for tailoring individual treatment choices and timely management of chronic symptoms.

Long-term course of gastrostomy nutritional management in patients with Duchenne muscular dystrophy: A retrospective cohort study

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease that commonly requires gastrostomy due to dysphagia. This study aimed to investigate the proportion of patients with DMD requiring gastrostomy and to assess the timing and outcomes of gastrostomy in patients with DMD to optimize perioperative care and improve long-term management. We conducted a retrospective cohort study by reviewing the medical records of patients with DMD treated between March 1991 and November 2023 at Kobe University Hospital. To identify risk factors for gastrostomy, Fisher’s two-tailed test and logistic analysis were used to compare the gastrostomy (group G) and comparison group without gastrostomy (group C) groups. We identified patients >18 years with DMD. We excluded those without medical records from the last decade and those on nasogastric tube feeding. Among the 135 eligible patients, five (median age, 23 years) underwent percutaneous endoscopic gastrostomy (PEG; uptake rate, 3.7 %), and their data were analyzed for perioperative outcomes. Complications included ventilatory disturbances, aspiration pneumonia, and hemorrhagic shock. Two patients experienced significant postoperative complications, underscoring the high-risk nature of PEG in this population. Participants’ postoperative weight changes varied significantly. The presence or absence of ventilatory management, cardiomyopathy treatment, scoliosis, and steroid treatment were examined as risk factors between groups G and C, but no significant differences were observed. This study highlights low gastrostomy usage among patients with DMD, with varying outcomes. Meticulous planning and early consideration of gastrostomy are crucial to enhance the quality of life and nutritional outcomes in these patients.

Exploring novel natural compound-based therapies for Duchenne muscular dystrophy management: insights from network pharmacology, QSAR modeling, molecular dynamics, and free energy calculations.

Muscular dystrophies encompass a heterogeneous group of rare neuromuscular diseases characterized by progressive muscle degeneration and weakness. Among these, Duchenne muscular dystrophy (DMD) stands out as one of the most severe forms. The present study employs an integrative approach combining network pharmacology, quantitative structure-activity relationship (QSAR) modeling, molecular dynamics (MD) simulations, and free energy calculations to identify potential therapeutic targets and natural compounds for DMD. Upon analyzing the GSE38417 dataset, it was found that individuals with DMD exhibited 290 upregulated differentially expressed genes (DEGs) compared to healthy controls. By utilizing gene ontology (GO) and protein-protein interaction (PPI) network analysis, this study provides insights into the functional roles of the identified DEGs, identifying ten hub genes that play a critical role in the pathology of DMD. These key genes include DMD, TTN, PLEC, DTNA, PKP2, SLC24A, FBXO32, SNTA1, SMAD3, and NOS1. Furthermore, through the use of ligand-based pharmacophore modeling and virtual screening, three natural compounds were identified as potential inhibitors. Among these, compounds 3874518 and 12314417 have demonstrated significant promise as an inhibitor of the SMAD3 protein, a crucial factor in the fibrotic and inflammatory mechanisms associated with DMD. The therapeutic potential of the compounds was further supported by molecular dynamics simulation and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis. These findings suggest that the compounds are viable candidates for experimental validation against DMD.

233VP Review of inpatient care of children affected by neuromuscular disorders or complex neurodisability from the carer perspective

233VP Review of inpatient care of children affected by neuromuscular disorders or complex neurodisability from the carer perspective

260P NEUROMYODredger – 3 billion megaproject: expanding the accessibility of exome sequencing for the diagnosis of neurodevelopmental and neuromuscular disorders in nine countries

260P NEUROMYODredger – 3 billion megaproject: expanding the accessibility of exome sequencing for the diagnosis of neurodevelopmental and neuromuscular disorders in nine countries