搜索结果：Journal of neuromuscular diseases

To assess the prevalence of 5q spinal muscular atrophy (SMA) among adult patients with undifferentiated neuromuscular disorders. Prospective study of 50 patients (19-78 years) presenting ≥1 feature of 5q SMA: areflexia, proximal weakness, fasciculations, neurogenic EMG changes, atrophy, calf hypertrophy, or elevated creatine kinase (CK). Molecular testing (MLPA/melting curve analysis of SMN1/SMN2) was performed. 5q SMA was confirmed in one female patient (2% [95% CI 0.05-10.6]), who was found to have a homozygous deletion of exons 7-8 in the SMN1 gene. Her clinical presentation included proximal lower limb weakness and neurogenic EMG changes, but she lacked areflexia and had normal CK levels. For 29 years, she had been misdiagnosed with «unspecified myopathy»(G72.9). The findings highlight the need to include 5q SMA in the differential diagnosis of adult patients with undifferentiated neuromuscular disorders. Optimizing diagnostic algorithms and enhancing epidemiological monitoring in this age group are essential to reduce diagnostic delays. Оценка частоты встречаемости спинально-мышечной атрофии (СМА) 5q у взрослых с недифференцированными нервно-мышечными заболеваниями. В проспективное исследование включены 50 пациентов (19—78 лет) с ≥1 клиническим признаком СМА 5q: арефлексия, проксимальная слабость, фасцикуляции, нейрогенные изменения по результатам электромиографии (ЭМГ), гипотрофии, гипертрофия икроножных мышц или повышение уровня креатинфосфокиназы (КФК). Проведено молекулярно-генетическое тестирование (MLPA/анализ кривой плавления SMN1/SMN2). Диагноз СМА 5q подтвержден у одной пациентки (2% [95% ДИ 0,05—10,6]), у которой выявлена гомозиготная делеция экзонов 7—8 гена SMN1. Клиническая картина включала проксимальную слабость нижних конечностей и нейрогенные изменения по данным ЭМГ при отсутствии арефлексии и нормальном уровне КФК. В течение 29 лет пациентка наблюдалась с ошибочным диагнозом «неуточненная миопатия» (G72.9). Результаты исследования демонстрируют необходимость включения СМА 5q в спектр дифференциальной диагностики у взрослых пациентов с недифференцированными нервно-мышечными заболеваниями. Для сокращения времени диагностики требуются оптимизация алгоритмов обследования и усиление эпидемиологического мониторинга в данной возрастной группе.

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.

Shoulder-related disorders are highly prevalent, with the global incidence being on the rise. Neuromuscular rehabilitation aims to optimize muscle function and motor performance by modulating the neuromuscular system, which comprises the central and peripheral nervous systems. This study aimed to synthesize evidence on neuromuscular rehabilitation for shoulder disorders, evaluating its effects on pain, range of motion, and shoulder function. English-language literature was retrieved from the PubMed, Cochrane, and Embase databases up to June 2025 via search terms such as "Shoulder," "Neuromuscular," and "Rehabilitation". The inclusion criterion was randomized controlled trials that used neuromuscular rehabilitation techniques for shoulder diseases. The primary outcome was pain improvement, and secondary indicators included joint range of motion and function. The effect size was the standardized mean difference (SMD) and 95% confidence interval (CI). Heterogeneity was evaluated via I2. Neuromuscular therapy significantly reduced pain (SMD [95% CI] = -2.82 [-4.79, -0.85]), with greater improvements than did the control (SMD [95% CI] = -0.75 [-1.35, -0.15]). Improvements were observed in shoulder flexion, extension, abduction, and external rotation, with external rotation showing the most significant benefit versus controls. Neuromuscular therapy improved functional scores (SMD [95% CI] = -1.95 [-3.71, -0.19]) and outperformed the control (SMD [95% CI] = -0.65 [-1.25, -0.05]). This study revealed that neuromuscular physical therapy can effectively relieve pain in patients with shoulder disorders, improve joint mobility, and enhance function. These findings support its use as an adjunctive therapy in conventional rehabilitation.

Heart pumping weakness occurs progressively in all patients with Duchenne muscular dystrophy (DMD), but symptoms only occur very late in the process. Regular imaging assessments of heart function are needed to see how the heart is 'doing' and how well it is responding to treatment with heart drugs. Echocardiography (echo) has been the standard type of imaging used for these assessments in the UK. It is widely available but has limitations. Cardiac MRI (CMR), although less readily available and more expensive, is better able to detect tissue changes in the heart before there is any reduction of heart pump function and retains accuracy in all measures even as DMD progresses. An expert panel of cardiologists, muscle specialists and patient representatives was set up to review evidence and provide expert guidance on how to use both echo and CMR best to the benefit of patients with DMD, Becker muscular dystrophy (BMD) and females affected by DMD-gene abnormalities ('female gene carriers').The working group concluded that echo should remain the predominant method used in heart checks for patients with DMD in the UK. However, wider use of CMR, performed at times individualised to key decision points after about the age of 10 years, would allow earlier detection of those heart changes prompting the introduction and changes in heart therapies. Similarly, greater use of CMR could contribute to improving cardiac management of males with BMD and females with DMD-gene variations._______________________ OBJECTIVE: To provide guidance on the use of cardiac MRI (CMR) in the UK in paediatric and adult patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) as well as recommendations for screening and monitoring females with dystrophin-gene variations. Specifically, to examine the 'added value' of CMR over echocardiography at selected time points in the assessment of individuals with or at risk of developing cardiac dystrophinopathy. METHODS: Initiated by an expert working group of UK-based and US-based imaging cardiologists, neuromuscular clinicians and DMD-patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK cardiologists, consensus was reached on the optimal use of CMR in clinical decision-making about therapy. RESULTS AND CONCLUSIONS: Echocardiography should remain the predominant modality for cardiac surveillance and to guide therapy for patients with DMD in the UK. However, when tolerated, wider use of CMR at key stages in patients with DMD, older than age 10 years, and for males with BMD and females with DMD-gene variations would allow earlier detection of those with cardiac involvement and inform the earlier initiation of regimes of cardiac medications. In this way, greater use of CMR could contribute to improving cardiac health in each of these patient groups.

In a previous study we demonstrated that standardized tapering off subcutaneous immunoglobulin (SCIG) is a safe way to identify remission in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, clinical characteristics and dosage of SCIG in patients in remission are unknown. In the present study, we aimed to identify characteristics of patients in remission during tapering off SCIG. Participants received a stable SCIG dosage and followed a standardized tapering off regimen providing 90%, 75%, 50%, 25% and 0% of the initial dose, every 12th week, pending no deterioration occurred. All patients were followed for 164 weeks after inclusion and were evaluated with disability scores, quality of life score (EQ-5D-5L), blood samples and clinical examination. Receiving a dosage of SCIG >25 g/week predicts a higher risk of relapse, OR 6.3 (95CI 1.8-20.2)(p = 0.004), but not when considering body weight (SCIG >0.3 g/kg/week), OR 3.3 (95CI 1.0-9.7)(p = 0.05). Moreover, a higher level of serum NfL OR 8.2 (95CI 1.1-93.3)(p = 0.04) predicts relapse. Low scores on EQ-5D-5L at baseline predicted increased risk of relapse. Serum calprotectin was similar in patients with relapse and in remission. Evaluating measurements from baseline, final visit and the last visit before final visit (LVBF), we found that deterioration in clinical performance could not be predicted at LVBF based on any of the tests performed. Patients experiencing a relapse of CIDP during tapering off SCIG seem to receive a total higher dosage of immunoglobulin and had a higher sNfL prior to tapering off compared to patients without a relapse.

The 2025 MDA Gene Therapy Summit brought together leading researchers, clinicians, and industry representatives to discuss the latest advancements and challenges in the development and clinical translation of genetic therapies for neuromuscular disorders. The meeting featured in-depth presentations on clinical trials, therapeutic developments, and regulatory pathways for AAV-mediated gene therapies, highlighting both successes and challenges in the field.

Anal canal stenosis is a functionally disabling condition that results in impaired continence, constipation, and decreased quality of life. Although most cases arise after anorectal surgery, high-energy blast trauma (HEBT) represents a distinct etiology characterized by extensive tissue loss and neuromuscular injury. Long-term outcomes of anoplasty in this setting remain insufficiently described. This retrospective study evaluated functional and quality-of-life outcomes following flap anoplasty for anal stenosis of both postoperative and trauma-related origins. All patients who underwent anoplasty between 2008 and 2015 with ≥12 months of follow-up were included. Functional status was assessed preoperatively and at 12 months postoperatively using the Modified Wexner Score, Wexner Constipation Scale, and the Fecal Incontinence Quality of Life (FIQL) questionnaire. Sphincter morphology was evaluated using endoanal ultrasonography. Statistical analyses included paired tests, effect size calculations, and multivariable logistic regression to identify independent predictors of good continence (Wexner score ≤5). Thirty-seven patients met the inclusion criteria: 27 with postoperative stenosis and 10 with blast-related trauma. Ano-plasty resulted in overall improvement in continence, constipation, and FIQL scores. However, functional recovery differed significantly by etiology: postoperative patients experienced substantial improvement, whereas blast-injured patients achieved only modest gains, reflecting persistent neuromuscular and fibrotic damage. Trauma cases demonstrated lower FIQL scores (14.7 vs. 16.8), higher constipation scores (8.1 vs. 7.2), and increased rates of fecal incontinence (20% vs. 11.1%). Sphincter integrity and shorter stricture length independently predicted good continence, while blast mechanism and advanced age were associated with reduced improvement. Anoplasty provides meaningful functional benefits in patients with anal stenosis; however, recovery is significantly attenuated in survivors of high-energy trauma. These findings underscore the importance of etiology-based planning, thorough sphinc-ter evaluation, and realistic patient counseling. Anal kanal darlığı, kontinans ve yaşam kalitesini bozan nadir ancak yıkıcı bir durumdur. Postoperatif fibrozis anorektal cerrahi sonrası en sık neden olmaya devam ederken, yüksek enerjili patlama travmaları, yaygın yumuşak doku kaybı, nöromüsküler hasar ve aşamalı yara yönetimiyle karakterize, farklı bir klinik tablo oluşturmaktadır. Anoplasti sonrası uzun dönem fonksiyonel sonuçlara ilişkin veriler, patlama yaralanması geçirmiş hastalarda sınırlıdır. Bu çalışma, hem elektif anorektal cerrahiye bağlı hem de savaşla ilişkili travmaya bağlı anal darlığı olan hastalarda anoplasti sonrası kontinans ve yaşam kalitesi sonuçlarını değerlendirmeyi amaçladı. 2008-2015 yılları arasında anal darlık nedeniyle anoplasti uygulanan ve en az 12 aylık takibi bulunan hastalar çalışmaya dahil edildi. Kontinans ve yaşam kalitesi, ameliyat öncesi ve 12. ayda Modifiye Wexner ve FIQL (Fecal Incontinence Quality of Life) skorları ile değerlendirildi. Sfinkter bütünlüğü endoanal ultrasonografi ile incelendi. İyileşmeyi değerlendirmek için eşleştirilmiş istatistiksel testler ve Cohen’s d etki büyüklüğü analizi uygulandı. İyi kontinans (Wexner ≤5) ve postoperatif fonksiyonun öngördürücüleri, lojistik ve lineer regresyon modelleri ile belirlendi. Otuz yedi hasta dahil edilme kriterlerini karşıladı. 27’sinde postoperatif darlık, 10’unda ise patlamaya bağlı pelvik travma mevcuttu. Her iki grup da kontinans ve FIQL skorlarında anlamlı iyileşme gösterdi, ancak, fonksiyonel iyileşme etiyolojiye göre önemli ölçüde farklılık gösterdi: ameliyat sonrası hastalar önemli kazanımlar elde ederken, patlama sonucu yaralanan hastalar, kalıcı nöromüsküler ve fibrotik hasarı yansıtan, sadece mütevazı bir iyileşme elde etti. Travma vakaları daha düşük FIQL skorları (14.7'ye karşı 16.8), daha yüksek kabızlık skorları (8.1'e karşı 7.2) ve artmış fekal inkontinans (20%'ye karşı 11.1%) gösterdi. Sfinkter bütünlüğü ve daha kısa darlık uzunluğu, bağımsız olarak iyi kontinansı öngörürken, patlama mekanizması ve ileri yaş, iyileşmenin azalmasıyla ilişkiliydi. Anoplasti, anal stenozda anlamlı fonksiyonel fayda sağlar; ancak, yüksek enerjili travma geçirmiş hastalarda iyileşme önemli ölçüde azalır. Bu bulgular, etiyolojiye dayalı planlama, dikkatli sfinkter değerlendirmesi ve gerçekçi hasta danışmanlığı ihtiyacını vurgulamaktadır.

Spinocerebellar ataxia type 27B (SCA27B), caused by an intronic GAA repeat expansion in the FGF14 gene, has recently emerged as a major cause of late-onset cerebellar ataxia (LOCA). Its prevalence and clinical profile in Central and Eastern Europe remain largely unknown. To determine the frequency and phenotypic characteristics of FGF14 GAA·TTC repeat expansions, a large cohort of Polish patients with undiagnosed adult-onset cerebellar ataxia was investigated. We retrospectively analyzed 701 patients (age of onset ≥ 25 years) with adult-onset cerebellar ataxia of unknown etiology, previously tested negative for SCA1, SCA2, SCA3, SCA8, and RFC1 expansions. GAA·TTC repeat lengths were assessed using long-range and repeat-primed PCR. Expansions ≥ 250 repeats were classified as pathogenic. Clinical and MRI data were evaluated where available. A control group of 66 neurologically healthy individuals was also screened. Pathogenic FGF14 expansions (≥ 250 repeats) were identified in 4.4% (31/701) of patients, including 23 with fully penetrant (≥ 300) and 8 with incompletely penetrant (250-299) alleles. No pathogenic expansions were found in controls. The mean age of onset was 49.8 years. Common symptoms included balance and gait disturbances, cerebellar syndrome, and episodic features such as diplopia. Cerebellar atrophy was present in 45% of patients with available MRI. No significant correlation between repeat length and age of onset was observed. Our findings confirm that FGF14 repeat expansions are an underrecognized cause of LOCA in Poland and support their inclusion in standard genetic testing for adult-onset ataxias. Further studies are warranted to better define penetrance and genotype-phenotype correlations.

For youth living with neurodisabilities and rare conditions, transitioning from pediatric to adult care results in significant loss of services and supports. This article examines transition-related health systems, policies and provider roles in the context of Duchenne muscular dystrophy (DMD). DMD is a multi-systemic X-linked disorder mainly characterized by progressive muscle degeneration, with about 30% of patients presenting with neurodevelopmental comorbidities. Due to advances in respiratory and cardiac care, life expectancy has increased significantly, creating a new population of adults living with DMD. This demographic shift has exposed critical gaps in the transition from pediatric to adult health care. To date, there is no systematic review covering existing transition policies and programs. This article utilizes integrated care and continuity of care frameworks to examine transition-related health systems, policies, and provider roles. We conducted a PRISMA-compliant systematic review searching OVID Medline, Embase, PsycINFO, CINAHL, Web of Science, and SCOPUS from January 1, 2000, to August 31, 2025. Studies were included if they reported on health systems, programs, policies or health care providers' roles in DMD. For synthesizing evidence, we utilized Popay's Narrative Synthesis framework to analyze health systems, policies, and provider roles across included studies, allowing for an aggregation of a body of heterogenous data (quantitative, qualitative and mixed-methods). This methodological approach ensured that the review moved beyond a simple aggregation of findings to generate new insights into the structural gaps. 42 studies met the inclusion criteria. The programs described in these studies varied from residential life-skills training to respiratory-focused transition protocols. A significant disconnect was identified between international care guidelines and implementation; most initiatives are project-based rather than policy-driven. While neurology is central in pediatric care, respiratory and sleep medicine often become the de facto "medical home" for adults. Crucially, support for patients with neurodiverse development was only discussed in 4 of the 42 studies. This review underlines a lack of comprehensive care models for DMD transition, specifically within the high-resource settings that dominate the literature. Future policies must bridge the gap between project-based funding and sustainable health systems, specifically addressing neurodiversity and caregiver burden.

The ADAPT phase 3 trial (NCT03669588) showed efgartigimod was well tolerated and efficacious in acetylcholine receptor antibody-positive (AChR-Ab +) 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 + participants who received a stable dose of ≥ 1 (any) treatment for gMG and were randomized 1:1 to efgartigimod (10 mg/kg) or placebo (administered as four once-weekly infusions per cycle) for 26 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 + participants were included (efgartigimod, n = 65; placebo, n = 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).

Myasthenia gravis (MG) is an immune-mediated disease with a bimodal incidence: early-onset (< 50 years, predominantly female) and late-onset (> 50 years, predominantly male). Recently, a subgroup with very late-onset (&#x2265; 65 years) has been described; however, its clinical relevance concerning disease course and prognosis remains uncertain. To evaluate the potential clinical implications of very late presentations of MG. The present is a retrospective cohort study comprising all patients diagnosed with MG currently followed up in the Neuromuscular Disorders Unit of a tertiary center. Clinical and paraclinical parameters including number of hospitalization and current regime were evaluated. A total of 92 patients were included, 51 (55.4%) of whom were female. Concerning the age of onset, 23 (25.6%) patients were classified as very late-onset. In order to better understand the clinical implications of a later onset, we compare the very late-onset subgroup to the late-onset subgroup. Gender distribution and number of patients with minimal manifestation status or better did not statistically differ between these subgroups. Myasthenic crisis and refractoriness were more frequent in the late-onset subgroup compared with very late-onset, but no statistical difference was found (p&#x2009;=&#x2009;0.221 and p&#x2009;=&#x2009;0.650 respectively). We did not find statistically significant differences in acetylcholine receptor antibody titers between the groups. Concomitant autoimmune diseases were found in 14 (15.2%) patients, comprising three patients with late-onset and three patients with very late-onset MG. Our study suggests that the recently established subgroup of very late-onset may not be clinically distinct from late-onset MG, as these patients seem to exhibit a similar clinical trajectory.

Charcot-Marie-tooth disease type 4D (CMT4D) is an early-onset, severe autosomal recessive demyelinating neuropathy, caused by mutations in the N-myc downstream-regulated gene 1 (NDRG1). Because of its rarity and predominance among specific ethnic groups, clinical knowledge remains limited. We report the case of two siblings of Romani ancestry, a 38-year-old man and a 40-year-old woman, with homozygous NM_006096.4:c.442C&#x2009;>&#x2009;T, p.(Arg148*) variant, and provide a review of the current literature.Both patients presented with severe distal-proximal sensorimotor neuropathy, muscle weakness and atrophy, generalized areflexia, and sensorineural deafness typical of CMT4D. Notably, they exhibited previously unreported features including severe dysphagia requiring PEG tube placement, bilateral vocal cord paralysis causing respiratory insufficiency necessitating non-invasive ventilation, and cognitive delay. Visual system involvement was demonstrated through abnormal visual evoked potentials with reduced P100 amplitude and absent responses, expanding the recognized phenotypic spectrum.Our systematic literature review identified 26 articles describing 72 patients with CMT4D. Twenty-two pathogenic NDRG1 variants were documented, with p.(Arg148*) being most frequent (64% of patients), predominantly in Roma populations. The median age of onset was 7 years, 96% of patients presented with lower limb involvement and all presented skeletal deformities were universal, including pes cavus (67%), claw hand (40%), and scoliosis (33%). Hearing impairment affected 61% of patients, while visual system involvement occurred in 17%.This study expands the clinical spectrum of CMT4D by documenting novel manifestations including severe bulbar dysfunction and respiratory involvement. These findings emphasize the importance of comprehensive assessment including swallowing evaluation, vocal cord examination, and pulmonary function testing in CMT4D patients, potentially impacting clinical management and prognosis.

In patients with Duchenne muscular dystrophy (DMD) the effect of continued corticosteroid (CS) use into adulthood on respiratory function remains unclear. We studied if prolongation of CS into adulthood is beneficial for forced vital capacity (FVC), age at start of non-invasive ventilation (NIV), and age at start of continuous (24/24&#x2005;h) ventilation. In this retrospective study, adult (&#x2265;18 years) DMD patients were stratified into 20 'CS-na&#xef;ve' patients (never used CS or only as a child during <1 year) and 37 'continued CS' patients (continued CS until age of 18 years or older). 'Continued CS' patients showed at 18 years a higher FVC%pred (50.3, SD:16.4) compared to 'CS-na&#xef;ve' patients (36.9, SD:13.8) (p&#x2009;=&#x2009;0.007). Patients continuing CS beyond the age of 18 demonstrated a slower annual decline in FVC%pred of 2.9% (SE:0.5) in comparison to 3.8% (SE:0.4) in the 'CS-na&#xef;ve' group, and the difference in relative annual decline in FVC%pred was significant (p&#x2009;=&#x2009;0.012). The annual decline in FVC in absolute value in patients continuing CS was 102&#x2005;ml (SE:28) slower in comparison to 'CS-na&#xef;ve' patients (p&#x2009;<&#x2009;0.001). Moreover, there was a delay in age at initiation of NIV: mean age at start of NIV was 28.3 (95%CI: 25.4-31.2) in 'continued CS' in comparison to 20.3 (95%CI: 19.0-21.6) in 'CS-na&#xef;ve' patients (p&#x2009;<&#x2009;0.001), and at start of continuous NIV 33.3 (95%CI: 31.5-35.2) in comparison to 26.0 (95%CI: 24.7-27.2) years (p&#x2009;<&#x2009;0.001). Our data suggest benefit of continuing CS until age 18 years and beyond on respiratory function including delayed need to start (continuous) NIV.

BackgroundChildren with cerebral palsy (CP) and related neuromuscular conditions often experience barriers to physical activity due to motor and cognitive impairments. Active video games (AVG), with or without adaptive technologies (AT), have demonstrated potential to improve outcomes in these populations.ObjectiveThis scoping review mapped existing research on AVG and AT in pediatric CP and related neuromuscular conditions, summarizing intervention characteristics and effects on physical, cognitive, and quality of life (QoL) outcomes.MethodsThe review followed PRISMA-ScR guidelines. Four databases were searched up to November 2025 (MEDLINE, Embase, Web of Science, and IEEE Xplore), supplemented by a manual citation search using Google Scholar. Eligible studies included participants under 18 years with CP and related neuromuscular conditions, reported physical, cognitive, or QoL outcomes, employed AVG, virtual/augmented reality, or gamified interventions, and were peer-reviewed and published in English.ResultsA total of 192 studies were included, of which 178 examined the impact of AVG and immersive technology on physical outcomes in children with either CP (n&#x2009;=&#x2009;173), muscular dystrophy (n&#x2009;=&#x2009;7), or CP and a mix of related conditions (n&#x2009;=&#x2009;12). Fewer studies included cognitive (n&#x2009;=&#x2009;17) and QoL (n&#x2009;=&#x2009;46) outcome measures. Findings highlighted substantial heterogeneity in study design, outcome measures, gaming devices, and AT implemented, limiting comparability and generalization. Despite this variability, AVG interventions seemed to improve patient outcomes, especially in physical function.ConclusionWe underscore the need for standardized measures to guide the development of gaming interventions that benefit patient outcomes.

Binocular diplopia is a distressing clinical condition that prompts clinicians to investigate underlying etiologies, particularly cranial nerve (CN) III, IV, or VI palsies. These may arise from microvascular ischemia, inflammation, trauma, compression, or neuromuscular junction disorders. This study aims to explore the association factors of these three ocular motor cranial nerve palsies and to compare their respective all-cause mortality rates using the real-world TriNetX Clinical Research Database (TriNetX CRD). TriNetX is a global federated administrative database with real-time updates of electronic medical records (EMRs). We used the US Collaborative Network within the TriNetX platform to establish the patient cohorts. This network contains electronic health record data from more than 100&#xa0;million patients across 68 US healthcare organizations (HCOs). This study utilized TriNetX platform to analyze the demographics and associated factors of ocular motor cranial nerve palsies, including diabetes, hypertension, acute myocardial infarction (AMI), overweight status, blood glucose and lipid profiles, body mass index (BMI), and history of brain aneurysm surgery, through intergroup comparisons using paired t-tests. All-cause mortality was assessed using Cox proportional hazards modeling and Kaplan-Meier survival analysis. The average age at presentation was 63, 57, and 60 years for CN III, IV, and VI palsies, respectively, with a slight male predominance. CN VI palsy was the most common, followed by CN IV and CN III palsies. CN III and CN VI palsy cohorts were more commonly associated with diabetes, hypertension, AMI, overweight, and brain aneurysm surgery, suggesting a microvascular or compressive etiology. In contrast, the CN IV palsy cohort was younger and more similar to the general population in clinical and laboratory characteristics. Regarding all-cause mortality, the CN III palsy cohort had the poorest survival, followed closely by the CN VI group, while the CN IV group exhibited the most favorable survival outcome. This study confirmed that CN VI palsy is the most frequent cause of ocular motor nerve palsy leading to binocular diplopia. Notably, CN III and VI palsies shared similar vascular and compressive association factors, while CN IV palsy appeared to be more frequently linked to congenital or traumatic origins. These differences were reflected in the mortality analysis, where CN III palsy showed the worst prognosis, CN VI a slightly better but comparable pattern, and CN IV the best survival outcome. Using the TriNetX CRD, this study delineated the demographic profiles, associated clinical factors, and survival outcomes of patients with ocular motor cranial nerve palsies. The typical demographic was males in their late 50s to early 60s, with CN VI being the most frequently affected nerve. CN III and VI palsies were more often associated with microvascular and compressive conditions, which correlated with higher mortality. Conversely, CN IV palsy was associated with a younger population and more benign clinical profiles, reflected in better survival outcomes.

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.

Next generation sequencing (NGS) impacted on clinical algorithm of solid tumor patients. A heterogeneous series of NGS platforms have been implemented in clinical practice but challenging handling procedures, high technical costs, and scant affordability on sequencing diagnostic routine specimens can leave behind some patients who could benefit from target drugs. Here, we sought to evaluate technical feasibility of Oxford Nanopore Technologies (ONT) sequencing accurate identification of tumor-associated molecular alterations, in a pilot series of real-world samples. We developed a technical workflow adapting the SiRe&#xae; NGS panel, originally designed for Ion semiconductor sequencing, on MinION platform (Oxford nanopore technologies), a portable, cost effective long read sequencer. The SiRe&#xae; panel enables detection of &#x665;&#x666;&#x668; clinically actionable somatic mutations across six key genes (EGFR, KRAS, NRAS, BRAF, cKIT, PDGFR&#x3b1;) relevant to targeted therapies in several solid tumors. We implemented a multiplexed assay using pooled and barcoded samples, processed on a single MinION flow cell. Performance was benchmarked from a pilot series of nine FFPE samples against Ion Torrent sequencing data. A single liquid biopsy sample was also analyzed testing accuracy of MinION technology. The adapted ONT workflow demonstrated high concordance ratei in detecting clinically relevant molecular alterations on short-read fragments, achieving comparable accuracy with standardized second generation NGS platforms on tissue and liquid biopsy samples. This proof of concept aimed to integrate ONT sequencing into molecular oncology workflows, providing practical, low-cost, and scalable alternative to conventional NGS platforms. The results support the potential of ONT technology to democratize access to precision oncology, particularly in laboratories with limited resources.

Infants with severe neuromuscular disorders, presenting a birth, are often unable to move, communicate, breathe, and feed. Unlike infants with severe birth asphyxia and cerebral palsy, these neuromuscular conditions are often associated with presumed normal cognition. Supporting these very severely affected infants and maintaining life through medical intervention or re-orientating care to palliation is often debated, and decision-making can be extremely challenging. Although guidelines exist to help navigate this process (Nuffield Council of Bioethics and Royal Collage of Paediatrics guidelines) deciding what is in the child's best interest is fraught with difficulties. This article explores some of the unique issues that arise in infants with severe neuromuscular conditions and illustrates the challenges in determining best interest for these patients, using some of the cases in the legal literature and the authors personal experience.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by Survival Motor Neuron 1 (SMN1) gene mutations, leading to reduced SMN protein levels and progressive motor neuron (MN) degeneration. Although current therapies aim to restore SMN expression, limitations highlight the need for alternative strategies. We investigated haloperidol (HALO), a classical antipsychotic, as a potential therapeutic based on its ability to enhance SMN2 splicing and SMN expression. Using the delta 7 SMA mouse model, we assessed effects of HALO on survival, motor function, neuroprotection, and neuroinflammation, by histological, molecular, and RNA-sequencing analyses of spinal cord and muscle samples. Additionally, we examined patient induced pluripotent stem cell-derived MNs and myotube co-cultures for validation in human cells. HALO increased lifespan and motor performance in mice with SMA, upregulated SMN protein in spinal cord and muscles, reduced MN loss, and attenuated neuroinflammation. Moreover, HALO enhanced neuromuscular junction integrity and muscle trophism, suggesting peripheral benefits. RNA-sequencing analysis revealed extensive splicing changes, including SMN target transcripts, supporting enhanced activity. In human models, HALO improved MN survival and SMN expression, supporting dual SMN-dependent and neuroprotective mechanisms. Given its central nervous system penetrance and clinical approval, HALO emerges as a promising SMA therapy candidate, warranting further dose optimization and validation for translational potential.