搜索结果：Journal of clinical neuromuscular disease

Neuromuscular disorders (NMDs) are a heterogeneous group of conditions characterised by progressive muscle weakness, motor impairment, and risk of malnutrition, affecting the quality of life (QoL) of patients. While pharmacological treatments are essential for the management of symptoms, the role of diet, nutrition, and other lifestyle factors remains underexplored. This narrative systematic review, performed on PubMed, Web of Science, and Scopus following PRISMA guidelines, aimed to investigate the relationship between lifestyle, the progression of NMDs, and the QoL. A total of 30 studies (n = 5055 patients) met inclusion criteria. According to our search strategy, the most representative lifestyle factors were diet (70%), physical activity (53.3%), and emotional perception and care (36.7%); seven papers (23.3%) evaluated three or more lifestyle aspects. Overall, both quantitative and qualitative deficiencies emerged: calories, proteins, lipids, and fibres, as well as vitamin C, vitamin E, zinc, selenium, and calcium, were lower than recommended. A reduced consumption of fruits, vegetables, legumes, nuts, and seeds, replaced by ultra-processed foods, was detected. Diets optimised for calorie and nutrients intake, rich in anti-inflammatory foods, have shown benefits both in mitigating oxidative stress and muscle degeneration. Regarding other aspects of lifestyle, although physical activity was associated with improved motor performance and QoL, adherence was low, particularly among females. Negative emotional status emerged as a critical factor influencing patients’ overall well-being. Even in the most complex neuromuscular disease settings, addressing nutrition and dietary habits, in the context of lifestyle, could support patients and their families throughout the disease course and improve their QoL.

ADSS1 myopathy (previously referred to as ADSSL1 myopathy) is a rare autosomal recessive muscle disease caused by mutations in the ADSS1 gene, which encodes an enzyme critical for purine nucleotide synthesis. First characterized in Korean patients in 2016, the disease exhibits phenotypic variability in its clinical presentation. We conducted a retrospective cohort study of 30 patients with genetically confirmed ADSS1 myopathy (18 males and 12 females) at Gangnam Severance Hospital from 2002 to 2024. The patients were classified into proximal-onset (n = 9) and distal-onset (n = 20) groups based on the location of initial muscle weakness, with one patient presenting with isolated hyperCKemia. Clinical assessments, genetic analyses, and muscle MRI were performed on 10 patients to evaluate clinical-radiological correlations. The median age at symptom onset was 8.0 years [Interquartile range (IQR): 7.0-14.0] with a median disease duration of 24.0 years [IQR: 17.0-34.0]. The most common initial symptoms were slow running (66.7%), early fatigue (16.7%), and gait disturbances (10.0%). Facial involvement was observed in 80.0% of the patients and oropharyngeal dysfunction in 56.7%. The median serum creatine kinase level was 214.0 IU/L [IQR: 125.0-394.0]. Genetic analysis revealed five pathogenic ADSS1 variants, with c.781G > A (51.7% of alleles) and c.919del (40.0% of alleles) being the most prevalent. Most patients (73.3%) were compound heterozygous for the two variants. Despite the clinical heterogeneity between the proximal- and distal-onset groups, none of the clinical differences were statistically significant. Muscle MRI revealed a remarkably consistent pattern of preferential involvement of the distal lower limb muscles, particularly the gastrocnemius and soleus muscles, regardless of the initial clinical presentation. This study, which represents the largest Korean ADSS1 myopathy cohort to date, highlights the striking discordance between clinical phenotypes and radiological findings. Although the clinical presentations varied considerably, MRI revealed consistent distal dominant muscle involvement patterns across all patients. This suggests that the underlying pathological process follows a predictable anatomical distribution independent of the initial symptomatic muscle groups. Our findings support the utility of muscle MRI as a valuable diagnostic tool for ADSS1 myopathy and suggest its conceptualization as a unified disease entity with a common pathophysiological mechanism involving selective muscle vulnerability based on metabolic requirements.

Patients with cervical dystonia (CD) often believe that disease severity would have progressed beyond the pre-treatment level if botulinum neurotoxin (BoNT) therapy had not been initiated. The aim of the present study was to assess the perceptions of long-term BoNT-treated patients with CD regarding the expected course of disease severity over the next 10 years under the hypothetical assumption that BoNT therapy is discontinued. Fifty patients with idiopathic CD receiving long-term BoNT therapy were screened, and 43 patients were included. Disease severity at the day of recruitment was assessed as a percentage of CD severity at the onset of BoNT therapy (PAS-%). Patients also generated, in a standardized manner, a graph illustrating the development of CD severity since initiation of BoNT therapy. Subsequently, patients estimated the expected severity of CD after 10 years, expressed as a percentage of severity at BoNT therapy onset (PAS-STD), under the hypothetical assumption that BoNT therapy was discontinued at the time of recruitment. They additionally drew a graph depicting the anticipated progression of CD severity over the subsequent 10 years under this assumption. Furthermore, 33 of these 43 patients had previously assessed the expected development of CD severity under the assumption that no BoNT therapy had ever been performed (PAS-NO%) in an earlier study. Mean PAS-STD was significantly higher than mean PAS-% (p < 0.001). Comparison of mean PAS-STD with mean PAS-NO% in the 33 patients who participated in both studies demonstrated that mean PAS-STD was significantly lower than mean PAS-NO% (p < 0.001). Long-term BoNT-treated patients with CD believe that disease severity would worsen again if BoNT therapy were discontinued. However, they do not expect CD severity to deteriorate to the level that they believe would have been reached if no BoNT therapy had been administered. We interpret this finding as suggesting that patients perceive a preventive effect of long-term BoNT therapy.

The ADAPT phase 3 trial (NCT03669588) showed efgartigimod was well tolerated and efficacious in acetylcholine receptor antibody-positive (AChR-Ab&#x2009;+) patients with generalized myasthenia gravis (gMG). This analysis utilized data from the ADAPT trial to investigate the efficacy and safety of efgartigimod in different patient subgroups. ADAPT included a broad population of AChR-Ab&#x2009;+&#x2009;participants who received a stable dose of&#x2009;&#x2265;&#x2009;1 (any) treatment for gMG and were randomized 1:1 to efgartigimod (10&#xa0;mg/kg) or placebo (administered as four once-weekly infusions per cycle) for 26&#xa0;weeks. Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) responder rates in cycles 1 and 2, and rates of treatment-emergent adverse events (TEAEs) were analyzed in the following patient subgroups: history of nonsteroidal immunosuppressive treatment (NSIST), concomitant use of gMG treatments throughout the study, and baseline patient and disease characteristics, including time since diagnosis, age, baseline MG-ADL score, body mass index (BMI), sex, and prior thymectomy. In total, 129 AChR-Ab&#x2009;+&#x2009;participants were included (efgartigimod, n&#x2009;=&#x2009;65; placebo, n&#x2009;=&#x2009;64). Across all subgroups, higher MG-ADL and QMG responder rates were observed in participants treated with efgartigimod versus placebo during cycles 1 and 2. Rates of TEAEs were similar between participants treated with efgartigimod and placebo, regardless of concomitant gMG treatment type. Similar to outcomes observed in the ADAPT overall population, efgartigimod was well tolerated and efficacious across a broad range of patients, regardless of NSIST treatment history, concomitant use of gMG treatments, or baseline patient and disease characteristics. ClinicalTrials.gov: NCT03669588 (registered September 13, 2018).

Monoclonal gammopathy of undetermined significance (MGUS) occurs in some patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but its impact on clinical phenotype and treatment response remains unclear. We assessed the prevalence of paraproteinemia in CIDP and compared disease features between CIDP patients with and without MGUS. We used data from the International CIDP Outcome Study (ICOS), a prospective cohort study. We compared the prevalence and causes of paraproteinemia in CIDP to matched disease controls (axonal polyneuropathy or motor neuron disease) and compared disease features and treatment responses between CIDP patients with and without MGUS. Treatment response, defined as a &#x2265;&#x2009;1-point improvement on the modified Rankin scale, was retrospectively assessed. IgG paraproteinemia was more common in CIDP than in controls (9%, 17/193 vs. 3%, 6/192; p&#x2009;=&#x2009;0.03). IgM and IgA paraprotein prevalences did not differ. One CIDP patient had Waldenstr&#xf6;m macroglobulinemia; others had MGUS. Patients with IgG MGUS less often had an acute clinical presentation (6% vs. 33%; p&#x2009;=&#x2009;0.02), more often had sensory deficits (94% vs. 67%; p&#x2009;=&#x2009;0.02), and prolonged distal CMAP duration (64% vs. 31%; p&#x2009;=&#x2009;0.02), compared to patients without MGUS. First-line treatment response rates were comparable (80% [IgG MGUS] vs. 67% [no MGUS]; p&#x2009;=&#x2009;0.39). IgG MGUS is more prevalent in CIDP than in controls. Presence of IgG MGUS is weakly associated with some CIDP disease features, but not treatment response. These findings indicate that, although IgG MGUS is associated with CIDP, the presence of IgG MGUS does not constitute a distinct subgroup with unique clinical features or treatment implications.

Objective study was the quantification of controlled/inadequately controlled generalized myasthenia gravis (gMG) disease burden, health care resource utilization and costs in MG patients, followed-up at a reference center for MG in Italy. The study is a 2010 to 2020 retrospective analysis of gMG patients. Clinical and health economics variables were those observed during routine clinical care. Data were anonymized and treated in aggregated forms in compliance with GDPR. Only patients with gMG were included in the study. Out of 237 patients, 55.3% were males and 44.7% females with a median follow up duration of 4.7 years. Males were older, with a median age at onset of 58.3 years versus 45.7 years for females; an increased representation of late and very late onset patients was recorded. A shorter time from onset to diagnosis was observed in males. The incidence rate per year of exacerbations changed from 0.76 in the first year to 0.23 at the sixth year, with a similar trend for MG crisis; both exacerbations and crisis incidence were higher in inadequately controlled patients. Disease burden and health care resources utilizations were particularly evident in inadequately controlled patients, which showed a 138% increase of costs. Our data confirmed the observed epidemiological changes occurring in MG population and the high use of health care system resources in uncontrolled patients. The estimates obtained will provide a useful basis for assessing the impact of recently introduced targeted therapies on healthcare expenditure for MG.

To investigate soluble circulating sialic acid-binding Ig-like lectin 1 (scSIGLEC1), a surrogate biomarker for type I IFN, as a novel biomarker for idiopathic inflammatory myopathies (IIM) disease activity. Patients enrolled in a Canadian multicentre cohort of IIM patients with biobanked serum samples and clinical data at baseline and 1-year follow-up were included. Serum scSIGLEC1 levels at baseline were tested using a capture immunoassay and evaluated in relation to disease activity, defined using patients' Physician Global Activity (PGA) scores, Total Improvement Scores (TIS) and visual analogue scale scores for the six organ systems included in the Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT): constitutional, cutaneous, skeletal, gastrointestinal, pulmonary and cardiovascular. Performance of scSIGLEC1, MYOACT and creatine kinase to assess disease activity were compared [area under the receiver operating characteristic curve (ROC AUC)]. A total of 87 IIM patients (67.8% female, mean age 54.4&#x2009;&#xb1;&#x2009;14.3&#x2009;years) were included. Higher scSIGLEC1 levels differentiated between active and inactive disease on the PGA (difference 2.7&#x2009;ng/ml; 95% CI 0.7-4.8). Higher scSIGLEC1 levels were found among patients with cutaneous (difference 1.7&#x2009;ng/ml; 95% CI 0.1-3.4), skeletal (difference 2.0&#x2009;ng/ml; 95% CI 0.1-3.9) and gastrointestinal (difference 2.2&#x2009;ng/ml; 95% CI 0.5-3.9) disease activity compared with patients without disease activity in these extramuscular organs, and were associated with lower TIS scores at 1-year follow-up. scSIGLEC1 levels (ROC AUC 0.74; 95% CI 0.61-0.86) matched MYOACT performance and outperformed creatine kinase in assessing disease activity. scSIGLEC1 levels are a promising biomarker for monitoring overall IIM disease activity, as well as activity involving the cutaneous, musculoskeletal and gastrointestinal systems.

Respiratory muscle weakness (RMW) significantly contributes to ventilatory failure and commonly arises from obstructive airway diseases, thoracic restrictive conditions, and neuromuscular disorders. This narrative review aims to synthesize current literature on the anatomy and physiology of the respiratory musculature, causes of respiratory muscle weakness across disease states, and diagnostic and therapeutic strategies. This narrative review was conducted through a search of PubMed, Scopus, and Web of Science databases. Priority was given to clinical trials, systematic reviews, and landmark studies focusing on the etiology, diagnostic approaches, and therapeutic interventions for RMW. RMW results from increased respiratory workload, altered lung mechanics, or primary muscular dysfunction. In obstructive and thoracic restrictive diseases, dynamic hyperinflation and reduced compliance worsen muscle fatigue. Neuromuscular disorders lead to progressive muscle degeneration, impaired ventilation, and restrictive patterns. Assessment includes spirometry, inspiratory pressure measurements, electromyography, and imaging. Treatment involves mechanical ventilation, respiratory muscle training, and lung volume reduction. Respiratory muscle training and non-invasive ventilation improve strength, endurance, gas exchange, and quality of life. Respiratory muscle weakness requires early recognition and targeted management. Individualized, evidence-based strategies preventive, therapeutic, or rescue are essential to improve outcomes and reduce the burden of respiratory failure.

Cardiopulmonary Exercise Test (CPET) serves as an integrative assessment tool to evaluate cardiac function, respiratory responses, and neuromuscular capacity in patients with chronic obstructive pulmonary disease (COPD) during incremental cycling exercise. VE-VCO2 slope during CPET was not fully understood in predicting acute exacerbations of COPD (AECOPD). This study aims to establish a predictive model for AECOPD based on the VE-VCO2 slope. In total, 79 patients with COPD were recruited between 2013 and 2019. All participants underwent baseline pulmonary function tests and CPET and were followed up for 5 years thereafter. Independent two-sample t-tests and Chi-square tests were used to compare AECOPD and Non-AECOPD groups. Univariate and multivariate Cox regression analyses were utilized to identify predictive factors for AECOPD. The diagnostic performance of these variables was evaluated by receiver operating characteristic (ROC) curve analysis. The optimal cutoff values calculated by Youden's index. Kaplan-Meier survival analysis between subgroups was based on the optimal cutoff values. Generating Forest plots to visualize Cox regression analysis results. The AECOPD group contains 62 participants and the Non-AECOPD group contains 17 participants. Groups comparisons revealed significant differences in VE-VCO2 slope, age, BMI, FEV1%predicted, FEV1/FVC ratio, and EqCO2. Multivariate Cox regression analysis identified VE-VCO2 slope (OR = 1.19, 95% CI: 1.09-1.29, p < 0.001), age (OR = 1.05, 95% CI: 1.02-1.09, p = 0.005), and FEV1%predicted (OR = 0.96, 95% CI : 0.94-0.99, p = 0.015) as significant predictors of AECOPD. The ROC curve analysis results about the above predictors found that the AUC of VE-VCO2 slope is highest independently in 1 year, 3 years and 5 years, with the optimal cutoff values = 28.42 in 5 years (hazard ratio = 3.18, 95% CI: 1.639-6.2, p < 0.001). The stratification of VE-VCO2 slope &#x2265;28.42 was an independent predictor of AECOPD. Our study established VE-VCO2 slope as a novel stratified clinical biomarker for predicting AECOPD.

Assessing respiratory function in spinal muscular atrophy (SMA) is challenging due to the effort-dependent nature of traditional spirometry. While respiratory oscillometry offers a passive alternative, its clinical utility in predicting clinical status remains underexplored. This study evaluates the efficacy of integrating spirometric and respiratory oscillometric indices through machine learning (ML) to predict ambulatory status and the requirement for bilevel positive airway pressure (BiPAP) in SMA patients. We retrospectively analyzed forty-five patients with a genetically confirmed diagnosis of SMA. To address data imbalance, we utilized the SMOTETomek technique and validated Random Forest models through leave-one-out cross-validation. SHAP (SHapley Additive exPlanations) analysis was used to interpret the contribution of individual physiological markers. In univariate logistic regression, forced vital capacity (FVC), peak expiratory flow (PEF), and forced expiratory flow at 75% of vital capacity (FEF75) were significant predictors for walking support. FEF25, FEF50, FEF75, and FEF 25-75 were associated with the requirement for BiPAP use. None of the respiratory oscillometric parameters reached statistical significance in regression models. However, ML models achieved high predictive accuracy, with SMOTETomek improving BiPAP requirement recall from 0.00 to 1.00. SHAP analysis revealed that respiratory oscillometry gained significant predictive weight that traditional models overlooked. R20Hz emerged as a key predictor for ambulatory status, while R5-20&#xa0;Hz was identified as a decisive feature for predicting the BiPAP use. &#xa0;The integration of effort-independent respiratory oscillometry with traditional spirometry via ML has the potential to enhance risk stratification in SMA. &#x2022; SMA requires lung function monitoring, but traditional spirometry is challenging due to the need for forceful expiratory maneuvers. &#x2022; Respiratory oscillometry provides an effort-independent assessment of respiratory mechanics through tidal breathing. &#x2022; Machine learning successfully integrates effort-independent respiratory oscillometry with spirometry to significantly enhance clinical predictions in SMA. &#x2022; It identifies R20Hz and R5-20&#xa0;Hz as critical physiological markers for predicting ambulatory status and the requirement for respiratory support, respectively.

Meningitis remains the leading infectious cause of neurological disabilities globally, disproportionately affecting children younger than 5 years and populations in the African meningitis belt. Whereas previous global estimates focused on ten pathogen categories, this study presents the most comprehensive analysis to date, assessing the meningitis burden attributable to 17 causative pathogens based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework. GBD is a systematic, scientific effort aimed at quantifying the comparative magnitude of health loss caused by diseases, injuries, and risk factors across age groups, sexes, and geographical locations over time. We estimated meningitis mortality using the Cause of Death Ensemble model (CODEm) and morbidity using DisMod-MR 2.1, incorporating data from vital registration, verbal autopsy, surveillance, hospital data, and systematic reviews. Aetiology-specific estimates were generated with pathogen-linked case-fatality ratios and splined binomial regression models. Risk factor attribution was based on established risk-outcome pairs and population attributable fractions. In 2023, there were 259&#x2009;000 (95% uncertainty interval 202&#x2009;000-335&#x2009;000) global deaths and 2&#xb7;54 million (2&#xb7;20-2&#xb7;93) incident cases of meningitis. Children younger than 5 years accounted for more than a third of deaths (86&#x2009;600 [53&#x2009;300-149&#x2009;000]). Streptococcus pneumoniae, Neisseria meningitidis, non-polio enteroviruses, and other viruses were the leading causes of death, while non-polio enteroviruses caused the most cases. The four WHO-defined preventable meningitis pathogens of interest (S pneumoniae, N meningitidis, Haemophilus influenzae, and Group B streptococcus) contributed to 98&#x2009;700 deaths (77&#x2009;000-127&#x2009;000) and 594&#x2009;000 cases (514&#x2009;000-686&#x2009;000). Low birthweight, short gestation, and household air pollution were the top risk factors for meningitis-related mortality. Although mortality and incidence have declined significantly since 1990, progress is insufficient to meet WHO 2030 targets. Despite marked progress in reducing bacterial meningitis via global vaccination campaigns, a substantial meningitis burden persists, attributable both to common pathogens such as S pneumoniae and N meningitidis and to emerging non-bacterial pathogens such as Candida spp and drug-resistant fungi. Achieving WHO goals will require sustained investment in surveillance, vaccination, maternal screening, and health-system strengthening, especially in high-burden settings. Gates Foundation, Wellcome Trust, and UK Department of Health and Social Care.

Patients presenting with musculoskeletal symptoms are fairly common in any neurologist practice, their presentation raises concern of underlying radiculopathy as a cause of their symptoms. The role of electrodiagnostic study has been variable in such patients. Creating a diagnostic tool will be of most help to provide physicians of predictive value of such tests before ordering and help guide them in finding the most appropriate test. Retrospective chart review study of 444 patients older than 18 years. The patients were referred to the electrodiagnostic laboratory with musculoskeletal symptoms such as neck, back, or limb pain; extremity numbness; or to rule out radiculopathy. A total of 308 patients met predefined inclusion criteria. Variables such as age, extremity numbness, back pain, and other symptoms were identified as significant predictors for abnormal results. A diagnostic tool was developed using these variables, scoring each as normal (0) or abnormal (1), with age as the only numerical input. For nerve conduction study (NCS) prediction, significant factors included age [P < 0.01, odds ratio (OR) 0.95], extremity numbness (P = 0.03, OR 0.42), other symptoms (P = 0.04, OR 0.29), and normal magnetic resonance imaging (P = 0.02, OR 2.99). For electromyography (EMG) prediction, age (P < 0.01, OR 0.95), back pain (P = 0.02, OR 0.43), and other symptoms (P = 0.03, OR 0.29) were significant. The logistic regression models for predicting abnormal NCS and EMG exhibited areas under the receiver operating curves of 0.807 and 0.777, respectively. With 95% specificity, the NCS model had a sensitivity of 24.10%, positive predictive value of 68.97%, and negative predictive value of 72.84%, while the EMG model had a sensitivity of 32.14%, positive predictive value of 75%, and negative predictive value of 74.67%. This study highlights the potential for using a scoring system to predict NCS and EMG outcomes based on key clinical variables.

X-linked myotubular myopathy (XLMTM) is a severe, rare, familial neuromuscular disease caused by mutations in the MTM1 gene. XLMTM presents a wide spectrum of clinical manifestations, including neuromuscular symptoms such as hypotonia and severe generalised muscle weakness, which lead to respiratory and orthopaedic complications; and extramuscular manifestations such as hepatobiliary and gastrointestinal involvement. As there is no curative treatment for XLMTM, and given the complications associated with the disease and its high morbidity and mortality, survival and quality of life in these patients rely on a comprehensive, multidisciplinary approach. A group of paediatric neurologists, one pulmonologist, one hepatologist, one intensivist, and rehabilitation specialists from Spain and Portugal with in-depth understanding and experience in XLMTM management present a multicentre series of 24 patients with XLMTM and problems and experience on its clinical management. Severe phenotypes showed significant neuromuscular and non-neuromuscular involvement. Multidisciplinary management, including respiratory support, nutritional interventions, and rehabilitation, is essential. Unmet needs include better neurocognitive assessment tools, improved access to multidisciplinary care, and resources for physical therapy. Communication aids are crucial for patient development. Multidisciplinary management of XLMTM is essential for improving outcomes, with significant unmet needs in several areas of clinical care.

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by a mutation in the SMN1 gene, located on chromosome 5q13. It is characterized primarily by neuronal degeneration due to a deficiency in producing full-length survival motor neuron protein (FL-SMN), which results in progressive muscle weakness with complications such as scoliosis, paralysis, and even death. This article reviews the clinical and genetic aspects of the disease, its diagnosis and classification, as well as therapeutic alternatives. In this context, it highlights the role of the molecular determination of the causal genetic variant and the copy number of the homologous SMN2 gene as the primary modifiers of the course of the disease, both for diagnosis and classification, as well as for therapeutic decision making. Recently, therapies focused on modifying the natural history of SMA by increasing FL-SMN protein production have been developed. Currently, 3 treatments are available: Spinraza (nusinersen), Zolgensma (onasemnogene abeparvovec), and Evrysdi (risdiplam). Studies performed with these drugs to confirm their safety and efficacy show favorable results; however, early diagnosis is decisive for the success of any of these therapeutic alternatives. La atrofia muscular espinal (AME) es un trastorno neuromuscular causado por una mutaci&#xf3;n en el gen SMN1, localizado en el cromosoma 5q13. Se caracteriza fundamentalmente por una degeneraci&#xf3;n neuronal por deficiencia en la producci&#xf3;n de la prote&#xed;na de supervivencia de las neuronas motoras de longitud completa (FL-SMN), lo que ocasiona debilidad muscular progresiva con complicaciones como escoliosis, par&#xe1;lisis e incluso la muerte. En este art&#xed;culo se revisan los aspectos cl&#xed;nicos y gen&#xe9;ticos de la enfermedad, su diagn&#xf3;stico y clasificaci&#xf3;n, as&#xed; como las alternativas terap&#xe9;uticas. En este contexto, resalta el papel que tiene la determinaci&#xf3;n molecular de la variante gen&#xe9;tica causal, as&#xed; como del n&#xfa;mero de copias del gen hom&#xf3;logo SMN2 como principal modificador del curso de la enfermedad, tanto para el diagn&#xf3;stico y la clasificaci&#xf3;n, como para la toma de decisiones terap&#xe9;uticas. Recientemente, se han desarrollado terapias enfocadas en modificar la historia natural de la AME mediante el aumento de la producci&#xf3;n de la prote&#xed;na FL-SMN. Actualmente se encuentran disponibles 3 tratamientos: Spinraza (nusinersen), Zolgensma (onasemnog&#xe9;n abeparvovec) y Evrysdi (risdiplam). Los estudios realizados con estos f&#xe1;rmacos para confirmar su seguridad y eficacia muestran resultados favorables; no obstante, un diagn&#xf3;stico temprano es decisivo para el &#xe9;xito de cualquiera de estas alternativas terap&#xe9;uticas.

Costs associated with in-person outpatient services in childhood neuromuscular disorders represent a major economic burden, and it is often difficult to bring children with these progressive disorders to health care facilities owing to their impaired ambulation. Follow-up of specialists by telephonic consultations after the initial assessment and treatment plan may reduce the costs related to outpatient in-person visits in children with Duchenne muscular dystrophy (DMD). The present study was conducted to evaluate the diagnostic accuracy of telephone consultation to identify critical clinical events related to disease progression, development of new comorbidities, non-compliance with treatment, and medication-related adverse events in children with DMD. Children aged &#x2265;&#x2009;5&#x2009;years with DMD visiting a tertiary care pediatric center were enrolled in the study. Parents of these children were contacted telephonically by a physician 48-72&#x2009;h prior to the child's scheduled outpatient appointment at the hospital. Subsequently, all children were assessed during the scheduled visit at the out-patient facility by another specialist who was blinded to the telephone consultation. The diagnostic accuracy of telephone consultation was determined by comparison with face-to-face consultation. A total of 58 consecutive eligible children were enrolled and 30 were included for final analysis. Telephone consultation demonstrated a sensitivity of 95.2%, specificity of 81.1%, and positive and negative predictive values of 91.9% and 88.2%, respectively, for identifying critical clinical events. The physician-initiated telephone consultation has acceptable diagnostic accuracy to identify critical events that need face-to-face consultation among children with DMD.

Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder associated with respiratory complications and reduced quality of life (QOL). Although disease-modifying therapies have altered the clinical course of SMA, the role of home-based respiratory physiotherapy as an adjunct to pharmacologic treatment remains underexplored. The aim of this study is to evaluate the impact of a 1-year home-based respiratory physiotherapy program on QOL and pulmonary function in nusinersen-treated patients with SMA types 2 and 3. This mixed prospective interventional and retrospective analytical study assessed the impact of weekly home-based, personally tailored respiratory physiotherapy sessions in addition to standard multidisciplinary care. Group allocation was determined by patient or parental willingness to participate and geographical feasibility for weekly home visits. Pulmonary function tests (PFTs) were performed at baseline and after 12 months. QOL was assessed with the SF-36 questionnaire and the Global Rating of Change (GROC) scale. Twenty-nine patients with spinal muscular atrophy (SMA) types 2 and 3 receiving nusinersen were included. The intervention group (n&#x2009;=&#x2009;15) and the control group (n&#x2009;=&#x2009;14) were comparable at baseline. Objective respiratory parameters remained stable in both groups with no significant differences at the end of the intervention (forced vital capacity % predicted: 72.7&#x2009;&#xb1;&#x2009;25.1 in the intervention group vs. 69.4&#x2009;&#xb1;&#x2009;26.5 in the control group, p&#x2009;=&#x2009;0.7). In contrast, the intervention group demonstrated significantly higher scores in multiple SF-36 domains, including physical functioning and energy/fatigue (41.3&#x2009;&#xb1;&#x2009;43.7 vs. 2.1&#x2009;&#xb1;&#x2009;3.7 and 71.7&#x2009;&#xb1;&#x2009;16.9 vs. 51.4&#x2009;&#xb1;&#x2009;14.5, respectively; p&#x2009;<&#x2009;0.05). The median GROC score in the intervention group was 3.0, indicating a clinically meaningful perceived benefit in QOL by exceeding the minimal clinically important difference threshold. Home-based respiratory physiotherapy was associated with stable pulmonary indices as well as significant improvements in perceived health status and QOL in patients with SMA treated with nusinersen.

Objective.Muscle fatigue affects individuals with neuromuscular disease and elite athletes alike. Muscle fatigue is difficult to reliably assess using non-invasive, real-time measures such as surface electromyography (sEMG) due to the coupling of fatigue and contraction level. The objective of this study was to explore the use of topological data analysis (TDA) with sEMG data as a method to assess muscle function.Approach.sEMG data was recorded from the first dorsal interosseous muscle across two experiments: 1) a sustained contraction experiment (n= 57) and 2) a discrete contraction level experiment (n= 18). We performed TDA on raw sEMG data and analyzed the same data with a traditional Fourier transform analysis towards the estimation of muscle fatigue and muscle contraction level. We analyzed the ability of these two approaches to 1) correlate to contraction time during the sustained contraction experiment, and 2) classify muscle contraction level from the discrete contraction experiment.Main Results.Vector TDA measures strongly correlated with contraction time during the sustained experiment on an individual trial level (up toR2= 0.95). TDA leveraged the topological aspects of sEMG time series from this experiment to improve estimations of muscle contraction time using a deep network regression approach (meanR2= 0.51). From a discrete contraction experiment at different contraction levels of measured maximum voluntary contractile force (20%-80%), implementation of KNN classification with frequency-based measures yielded 68% accuracy, while classification with TDA measures yielded 85% accuracy.Significance.These results suggest TDA could be used as a robust analysis approach to estimate muscle contraction level and muscle fatigue from sEMG data, although future work is needed for clinical implementation.

Pompe disease is a rare, progressively debilitating lysosomal disorder. Enzyme replacement therapy (ERT) is an established treatment targeting the underlying enzyme deficiency. Alglucosidase alfa has shown benefits in survival, ambulation, and respiratory function and was approved in China for both infantile-onset (IOPD)and late-onset Pompe disease (LOPD) in 2015.To assess the effectiveness and safety of 52-week Alglucosidase alfa treatment among Chinese patients with LOPD in a multicenter, single arm, open-label, prospective clinical study. Forty-one eligible LOPD patients received Alglucosidase alfa infusions at 20&#xa0;mg/kg every 2&#xa0;weeks for 52&#xa0;weeks. Primary endpoints included the six-minute walk test (6MWT), percentage of predicted forced vital capacity (FVC), and safety profile. Secondary endpoints encompassed manual muscle test (MMT), maximal inspiratory and expiratory pressure (MIP and MEP), Quick motor function test (QMFT) scores, and health-related quality of life (SF-12). After 52&#xa0;weeks, the mean 6MWT distance significantly improved by 43.6&#xa0;m (P&#xa0;=&#xa0;0.0017). Although the mean percentage of predicted FVC improved by 2.4%, the difference was not statistically significant (P&#xa0;=&#xa0;0.1424). MIP and MEP percentages improved, reaching maximal improvement at 38&#xa0;weeks. Both MMT and QMFT scores demonstrated significant improvements, with increases of 2.5 points (P&#xa0;<&#xa0;0.0001) and 5.6 points (P&#xa0;<&#xa0;0.0001), respectively. PCS significantly improved by 3.8 points (P&#xa0;=&#xa0;0.0039), while MCS improvement was not statistically significant. A total of 32 participants (78.0%) experienced 137 treatment-emergent adverse events (TEAEs). Most of these TEAEs were mild to moderate in severity and resolved without sequelae. Alglucosidase alfa demonstrated a positive benefit-risk profile in Chinese LOPD patients, confirming its safety and effectiveness.

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