Search Results (737)

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder that frequently affects bulbar function, including feeding and swallowing. Although disease-modifying therapies have improved motor outcomes, little is known about the persistence of oromotor difficulties, particularly with regard to solid food intake. Objective: This study aimed to evaluate mastication and swallowing performance in children with SMA undergoing treatment, and to investigate the association between tongue strength and feeding efficiency. Methods: Twenty-two children with SMA types 1–3 were assessed using the Test of Masticating and Swallowing Solids in Children (TOMASS-C) and the Iowa Oral Performance Instrument (IOPI). Key TOMASS-C outcomes included the number of bites, chewing cycles, swallows, and total eating time. Tongue strength was measured in kilopascals. Results: Most participants showed deviations from age-specific normative values in at least one TOMASS-C parameter. Tongue strength was significantly lower than reference values in 86% of participants and correlated negatively with all TOMASS-C outcomes (p < 0.001). Children with weaker tongue pressure required more swallows, more chewing cycles, and longer eating times. Conclusions: Despite pharmacological treatment, children with SMA experience persistent difficulties in eating solid foods. Tongue strength may serve as a non-invasive biomarker for bulbar dysfunction and support dietary decision-making and therapeutic planning. Full article

Skeletal muscle aging and related diseases are characterized by progressive loss of muscle mass, strength, and metabolic function. Central to these processes is mitochondrial dysfunction, which impairs energy metabolism, redox homeostasis, and proteostasis. In addition, non-mitochondrial factors such as muscle stem cell exhaustion, neuromuscular junction remodeling, and chronic inflammation also contribute significantly to muscle degeneration. This review integrates recent advances in understanding mitochondrial and non-mitochondrial mechanisms underlying muscle aging and disease. Additionally, we discuss emerging therapeutic approaches targeting these pathways to preserve muscle health and promote healthy aging. Full article

Background: Nemaline myopathy is a rare congenital neuromuscular disease associated with progressive weakness and frequent respiratory complications. In emergency situations, families often serve as the first and only responders. The aim of this study is to explore how parents in Spain care for children with nemaline myopathy during emergency situations, focusing on the clinical responses performed at home and the organizational challenges encountered when interacting with healthcare systems. Methods: A qualitative phenomenological study was conducted with 17 parents from 10 families belonging to the Asociación Yo Nemalínica. Semi-structured interviews were performed via video calls, transcribed verbatim, and analyzed using Giorgi’s descriptive method and ATLAS.ti software (version 24). Methodological rigor was ensured through triangulation, reflexivity, and member validation. Results: Four themes were identified. First, families were described as acting under extreme pressure and in isolation during acute home emergencies, often providing cardiopulmonary resuscitation and respiratory support without professional backup. Second, families managed ambiguous signs of deterioration using clinical judgment and home monitoring tools, often preventing fatal outcomes. Third, parents frequently assumed guiding roles in emergency departments due to a lack of clinician familiarity with the disease, leading to delays or errors. Finally, the transition to the Pediatric Intensive Care Unit was marked by emotional distress and rapid decision-making, with families often participating in critical choices about invasive procedures. These findings underscore the complex, multidisciplinary nature of caregiving. Conclusions: Parents play an active clinical role during emergencies and episodes of deterioration. Their lived experience should be formally integrated into emergency protocols and the continuity of care strategies to improve safety and outcomes. Full article

Pompe disease is a rare autosomal-recessive neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to the pathological accumulation of glycogen and impaired autophagy. Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) has been available since 2006, but may lead to the formation of anti-drug antibodies (ADAs) against the recombinant human enzyme, which, in turn, may adversely affect the response to ERT. Knowledge of the antigenic determinants of rhGAA involved in interaction with ADAs may facilitate the development of strategies to attenuate the anti-drug immune response in patients. Here, we determined the rhGAA ADA epitopes in the plasma of Pompe disease patients using a series of affinity purifications combined with epitope extraction and label free quantitation LC-MS. Full article

Background: Spinal muscular atrophy type 1 (SMA1) is a severe neuromuscular disorder characterized by progressive muscle weakness and atrophy, including the muscles of the oral cavity and esophagus. Eosinophilic esophagitis (EoE), a chronic, allergic disease, presents with eosinophilic infiltration of the esophagus, leading to esophageal dysmotility. Feeding difficulties may occur in both conditions. So far, the coexistence of EoE and SMA1 has not been described; we present the first such case. Case presentation: The patient was a girl with SMA1 diagnosed shortly after birth, treated with nusinersen and onasemnogene abeparvovec, and fed a standard industrial diet through a gastrostomy. In her second year of life, she developed increasing symptoms: distress during feeding, regurgitation, vomiting, and weight loss. She was treated with proton pump inhibitors without clinical improvement. Gastroscopy was performed, revealing superficial epithelial damage with bleeding in the proximal esophagus. Histopathology showed chronic inflammation with up to 150 eosinophils per high-power field, microabscesses, spongiosis, and basal layer hypertrophy. The girl was diagnosed with EoE. Her diet was switched from a standard industrial formula to an amino acid-based formula, which led to marked clinical improvement, the resolution of symptoms, and appropriate weight gain. Conclusions: This case report highlights the challenges of diagnosing EoE in SMA1 patients and emphasizes the need for multidisciplinary approaches and further investigation of allergic manifestations in SMA1 patients. Full article

Background: Magnesium (Mg) is an essential mineral that plays a vital role in various physiological processes, including enzyme regulation, neuromuscular function, and cardiovascular health. Dysmagnesemia has been associated with arrhythmias, neuromuscular dysfunction, and poor outcomes in intensive care unit (ICU) settings, representing diagnostic and therapeutic challenges. However, the relationship between dysmagnesemia and health outcomes in the ICU remains inadequately defined. Aim/Objective: This study aimed to assess the prevalence of dysmagnesemia and evaluate the correlation between total (tMg) and ionized magnesium (iMg) levels in a cohort of ICU and high dependency unit (HDU) patients. It also sought to evaluate patient characteristics and relevant health outcomes by comparing both concentrations of iMg and tMg. Methods: This prospective study was conducted among adult patients admitted to the ICU and the high dependency unit (HDU). Results: Among the 134 included patients, the median age was 63.5 years (IQR: 52.0–77.0). The majority, 91.0%, required mechanical ventilation. Additionally, 50.0% were diagnosed with diabetes, 28.4% had chronic kidney disease, and proton pump inhibitors (PPIs) were administered to 67.2% of the patients. The prevalence of hypomagnesemia, as measured by iMg, was 6.7%, while hypermagnesemia was at 39.6%. When measured by tMg, hypomagnesemia and hypermagnesemia were observed at rates of 14.9% and 22.4%, respectively. The iMg measurements showed an association between the incidence of atrial fibrillation and hypomagnesemia (p = 0.015), whereas tMg measurements linked hypomagnesemia with longer hospital stays. Notably, only a few patients identified with iMg-measured hypomagnesemia received magnesium replacement during their ICU stay. Conclusions: Dysmagnesemia is prevalent among critically ill patients, with discordance between iMg and tMg measurements. iMg appears more sensitive in detecting arrhythmia risk, while tMg correlates with length of stay. These findings support the need for larger studies and suggest considering iMg in magnesium monitoring and replacement strategies. Full article

Spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disorder and a leading genetic cause of infant mortality. Advances in disease-modifying therapies have significantly improved outcomes when treatment is initiated early, underscoring the importance of timely diagnosis. With the growing availability of prenatal genetic screening and high-resolution molecular diagnostics, opportunities for early detection, and potentially in utero intervention, are rapidly expanding. This narrative review synthesizes current evidence on the prenatal management of SMA, focusing on diagnostic strategies, the clinical application of fetal genetic testing, and the emerging potential of fetal therapy. We explore both invasive and non-invasive diagnostic approaches and evaluate experimental prenatal treatment modalities, while critically addressing the associated ethical, regulatory, and economic considerations. As the field progresses, integrating in utero strategies into clinical care may reshape perinatal medicine and offer transformative potential for genetic neurodegenerative disorders diagnosed before birth. The convergence of early diagnosis, fetal intervention, and personalized genetic counseling will be central to optimizing care pathways and outcomes in the era of precision medicine. Although significant challenges remain, the translation of fetal therapy into routine clinical practice is approaching feasibility. Future clinical trials, anchored in definitive prenatal diagnosis, will be essential, with benefits potentially outweighing the inherent procedural risks. Full article

Whether pattern or amount of daily activity determines neuromuscular properties is the focus of this review. The fast-to-slow conversion of many properties of fast-twitch muscles, by stimulating their nerves electrically with the continuous low-frequency pattern typical of slow motoneurons, argued that muscle properties are determined by their pattern of activity. However, the composition of the motor units (MUs) in almost all muscles is heterogeneous, with the MUs grouped into slow, fast-fatigue-resistant and fast-fatigable types that match corresponding histochemical fiber types. Nonetheless, their contractile forces lie on a continuum, with MUs recruited into activity in order of their size. This ‘size principle’ of MU organization and function applies in normally innervated and reinnervated muscles and, importantly, begs the question of whether it is the amount rather than the pattern of the MU activation that determines their properties. Experimental evidence that uniform daily amounts of ~<0.5, 5%, and 50% ES, converted motoneuron, nerve, and muscle properties to one physiological and histochemical type, argued in favor of the amount of activity determining MU properties. Yet, that the properties were not confined to the expected narrow range argued that factors other than the pattern and/or amount of neuromuscular activity must be considered. These include the progressive increase in the synaptic inputs onto motoneurons. The range of the effects of endurance and intermittent exercise programs on healthy subjects and those suffering nerve injuries and disease is also consistent with the argument that factors other than pattern or amount of neuromuscular activity should be investigated. Full article

Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neuron failure and poor prognosis. This study performed a meta-analysis of gene expression datasets that compared bulk-processed post-mortem spinal cord from ALS and control (CTL) patients. The analysis included 569 samples (454 ALS, 115 CTL) from 348 individuals (262 ALS, 86 CTL). Patterns of differential expression bias, related to mRNA abundance, gene length and GC content, were discernable from individual studies but attenuated by meta-analysis. A total of 213 differentially expressed genes (DEGs) were identified (144 ALS-increased, 69 ALS-decreased). ALS-increased DEGs were most highly expressed by microglia and associated with MHC class II, immune response and leukocyte activation. ALS-decreased DEGs were abundantly expressed by mature oligodendrocytes (e.g., the MOL5 phenotype) and associated with myelin production, plasma membrane and sterol metabolism. Comparison to spatial transcriptomics data showed that DEGs were prominently expressed in white matter, with increased DEG expression strongest in the ventral/lateral white matter. These results highlight white matter as the spinal cord region most strongly associated with the shifts in mRNA abundance observed in bulk-processed tissues. These shifts can be explained by attrition of mature oligodendrocytes and an ALS-emergent microglia phenotype that is partly shared among neurodegenerative conditions. Full article

Engaging in sports, particularly at a competitive level, requires sustained muscle contractions before the onset of physical fatigue. Fatigue is highly prevalent in neuromuscular diseases, especially those affecting neuromuscular transmission (e.g., myasthenia gravis) or muscle membrane excitability (e.g., myotonia, certain metabolic myopathies). A decremental response in repetitive nerve stimulation (RNS) represents the neurophysiological analogue of exercise-induced muscle weakness. Patients with such responses exhibit abnormal suppression of muscle activity during repetitive or prolonged effort. Consequently, it is often assumed they should avoid strenuous physical activity. To assess the safety of sports participation in individuals with fatigability-related neuromuscular disorders, we examined the literature and report a new case of a patient with myotonia congenita who engaged in competitive sports without adverse events. The review identified only a few cases involving patients with myasthenia gravis or muscular dystrophies who also participated in competitive sports safely and with favorable outcomes. No adverse events were reported. While these findings suggest that sports participation may be feasible for selected patients, they cannot be generalized. Large-scale studies involving athletes with neuromuscular conditions are needed to evaluate the safety and long-term impact of exercise in these populations. Full article

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder primarily affecting motor neurons. Emerging evidence suggests it also involves multiple organs, including potential cardiac manifestations. This study aimed to evaluate cardiac abnormalities in pediatric SMA patients compared to age-matched healthy controls, providing insight into underlying cardiomyopathy in this population. A total of 126 children were included in the study, with 63 SMA patients and 63 age-matched controls. We conducted clinical examinations, standard electrocardiography (ECG), and cardiac ultrasound (CUS) in all patients. Electrocardiographic analysis revealed a higher prevalence of sinus tachycardia in the SMA group and significantly deeper Q waves, indicating possible myocardial involvement. Echocardiographic findings demonstrated a significant reduction in left ventricular mass and left ventricular mass index in SMA patients compared to controls, despite normal systolic function. Statistical analysis confirmed that SMA diagnosis was an independent predictor of reduced myocardial mass, suggesting a distinct cardiac phenotype in SMA patients. This study provides new evidence of subclinical cardiac involvement in SMA, characterized by reduced myocardial mass, altered electrocardiographic parameters, and increased sinus tachycardia. These findings suggest a previously unrecognized form of cardiomyopathy in SMA that differs from cardiac manifestations typically seen in other neuromuscular disorders. Full article

Background: Charcot-Marie-Tooth (CMT) disease is a hereditary motor and sensory neuropathy that affects foot morphology and gait patterns, potentially leading to abnormal plantar pressure distribution. This systematic review synthesizes the existing literature examining plantar pressure characteristics in CMT patients. Methods: A comprehensive search was conducted across PubMed, Scopus, and Web of Science databases. Risk of bias was assessed using the Newcastle–Ottawa Scale. Results: Six studies comprising 146 patients were included. Four studies employed dynamic baropodometry, and two used in-shoe pressure sensors to evaluate the main plantar pressure parameters. The findings were consistent across different populations and devices, with a characteristic plantar-pressure profile of marked midfoot off-loading with peripheral overload at the forefoot and rearfoot, often accompanied by a lateralized center-of-pressure path and a prolonged pressure–time exposure. These alterations reflect both structural deformities and impaired neuromuscular control. Interventional studies demonstrated a load redistribution of pressure after corrective surgery, though residual lateral overload often persists. Conclusions: Plantar pressure mapping seems to be a valuable tool to identify high-pressure zones of the foot in order to personalize orthotic treatment planning, to objectively monitor disease progression, and to evaluate therapeutic efficacy. Further longitudinal studies with standardized protocols are needed to confirm these results. Full article

The complexity of RNA metabolism has become crucial in neuromuscular diseases, especially for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Our goal was to search for possible pathways that differ between the two diseases, in which DMD develops a severe phenotype compared to BMD. In this work, we aimed to evaluate the transcriptomic profile in skeletal muscle biopsies derived from patients with either DMD or BMD. We collected RNA obtained from pediatric patients with DMD (n = 12) and with BMD (n = 6). Compared to patients with BMD, patients with DMD showed a particular activation of genes involved in collagen synthesis, extracellular matrix organization, and Oncostatin M-dependent pathways, important for fibrotic processes. This suggests that a more severe phenotype in patients with DMD compared to those with BMD may be due to greater deregulation of these pathways, reflecting the clinical picture of patients observed. Our results allowed us to highlight the molecular differences between the two phenotypic groups, shedding light on the pathways that make Duchenne dystrophy more severe than its counterpart does. This study provides preliminary insights into the difference in gene expression between the two groups and lays the basis for the identification of possible mechanisms that differentiate between the two diseases. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive disease that degeneratively damages both upper and lower motor neurons, eventually resulting in muscular paralysis and death. Although ALS is broad in scope and commonly thought of as a motor neuron disease, more active research sheds light on the that role skeletal muscle plays in the development and progression of the disease. Muscle tissue in ALS patients and in animal models demonstrates severe regenerative deficits, including impaired myogenesis and impaired myoblast fusion. In ALS, muscle stem cells, known as satellite cells, show poor performance in activation, proliferation, and differentiation and thus contribute to ALS muscle wasting. Moreover, the pathological tissue environment that inhibits myoblast fusion is made up of proinflammatory cytokines, oxidative stress, and a lack of trophic signals from the neuromuscular junction, which greatly disrupts homeostatic regulation. It is likely that skeletal muscle is instead a dynamic player, fueling neuromuscular degeneration as opposed to a passive responder to denervation. One must appreciate the cellular and molecular changes that complicate muscle regeneration in ALS for effective treatment to be developed, permitting simultaneous interventions with both muscle and neurons. Full article

Background/Objectives: Systemic lupus erythematosus is an autoimmune disease. The musculoskeletal system is affected in 90% of patients. The most common symptoms are myalgia, arthralgia, and arthritis. The objective was to analyze the efficacy of an intervention using myofascial techniques and proprioceptive neuromuscular facilitation in patients with systemic lupus erythematosus. Methods: A randomized, single-blind, crossover clinical trial. Seventeen patients with systemic lupus erythematosus were randomly assigned to two sequences: Sequence A–B (intervention phase first, then control phase) and Sequence B–A (control phase first, then intervention phase). The intervention lasted for four weeks, with two weekly sessions lasting 50 min each. The intervention consisted of myofascial and proprioceptive neuromuscular facilitation techniques. The variables were: pain intensity (Visual Analog Scale), functional capacity of lower limbs (2-Minute Walk Test), physical function (Timed Up and Go Test), and fatigue (Fatigue Assessment Scale). After a 2-week follow-up and a 2-week washout period, the patients switched groups, and the methodology was replicated. Results: None of the patients developed injury or adverse effects as a direct consequence of the intervention. There were statistically significant differences between groups (p < 0.001) in the intensity of ankle (η²_p = 0.38) and knee (η² = 0.37) pain, functional capacity (η² = 0.33), and physical function (η² = 0.56). There were also intergroup changes in fatigue (η² = 0.52), and the relevant mental (η² = 0.26) and physical (η² = 0.45) components. Conclusions: Proprioceptive myofascial and neuromuscular facilitation techniques are safe in patients with systemic lupus erythematosus. This physical therapy protocol can improve the intensity of knee and ankle joint pain in these patients. This intervention can improve functional capacity, physical function, and fatigue in people with systemic lupus erythematosus. Full article