Journal of neuromuscular diseases最新文献

Background: There is currently no reliable epidemiological data in the Russian Federation nor data on patient routing and evaluation of the efficacy and feasibility of diagnostic and therapeutic approaches to patients with suspected Duchenne/Becker muscular dystrophy (DMD/BMD).

Objective: To record and monitor all patients with DMD/BMD in Russia.

Methods: Observational multicenter prospective & retrospective Registry of patients with DMD/BMD.

Results: Almost half of the 626 included patients live in the Central and Volga Federal Districts. The most common cause of the disease was large deletions of one or more exons (328 patients, 52.4%). Large duplications were identified in 92 patients (14.7%). Point mutations were identified in 206 patients, 32.9%. Among 448 patients with a known family history, 20% had a first-line relative diagnosed with DMD/BMD. The mean delay in diagnosis (the time from onset to clinically confirmed diagnosis) was 24.3 months.

Conclusions: These data demonstrate the preliminary results of the Registry and indicate a considerable delay in diagnosis in Russia.

Purpose: To investigate how parents of children with SMA who are treated with disease modifying therapies cope with hopes and worries related to disease progression, and to investigate their needs for counseling and rehabilitation initiatives.

Methods: The design of this study was qualitative using the Interpretive Description methodology and Joyce Travelbee's theory of interpersonal aspects. The method was semi-structured interviews conducted in Denmark at the homes of the parents or through the online platform Teams between February 29 and May 3, 2024.

Findings: Seventy-five parents representing 41 children were invited. Twenty-six parents of 20 children participated in the study. Twenty-four parents were interviewed at home and two were interviewed online. The key element of the parents' narratives was the reality of the diagnosis: the trajectory toward the diagnosis, getting the diagnosis, and the hope related to the effect af disease modifying therapies. At the same time, they experienced grief related to the uncertainty of the disease progression while hoping for normalcy in the future: a 'normal' child and a 'normal' life. Finally, they struggled with balancing professional counseling to maintain hope.

Conclusions: The families need coordinated, multidisciplinary care and information on disease modifying therapies, including what they can actively do to increase the effectiveness of the treatment. Counseling should include facilitated peer-support and acknowledge differences in children in terms of development, how they respond to the disease modifying therapy, and its long-term effects. Health professionals must tailor their support to the families' needs and sustain their hopes for the future.

ObjectiveTo describe the disease burden in patients with Pompe disease treated with enzyme replacement therapy (ERT) in the US as defined by comorbid conditions, supportive services, and treatment patterns.MethodsA retrospective cohort study (01/01/2012-09/30/2022) was conducted using the Merative™ MarketScan Research Databases. Inclusion criteria were: ≥ 2 outpatient or ≥1 inpatient claims of Pompe disease, ≥ 1 claim of ERT, and continuous enrollment in medical/prescription coverage for ≥90 days before diagnosis date for patients ≥2 years and ≥1-month post-index date. Patients were stratified into infantile-onset Pompe disease (IOPD) or late-onset Pompe disease (LOPD) cohorts based on age at diagnosis and clinical presentation. Key comorbidities, supportive services, and treatment modifications were presented as cumulative incidence.ResultsA total of 105 patients were included (IOPD: n = 50; LOPD: n = 55). For IOPD and LOPD groups, the 12-month cumulative incidence was 84.5% and 79.4% for respiratory, 57.4% and 54.3% for ambulatory, 67.8% and 33.4% for gastrointestinal, and 16.9% and 28.7% for cardiovascular comorbidities, respectively; 12-month cumulative incidence was 66.9% and 31.8% for physical therapy, 59.5% and 3.9% for speech therapy, 48.6% and 1.8% for immune tolerance induction or intravenous immunoglobulin, 47.3% and 11.2% for nutritional therapy, 15.1% and 17.0% for respiratory support, 27.8% and 3.7% for occupational therapy, and 8.3% and 11.1% for ambulatory support, respectively. Fourteen (IOPD: n = 2; LOPD: n = 12) patients switched ERT therapy, and 21 (IOPD: n = 14; LOPD: n = 7) had ≥1 dose modification.ConclusionsPatients with Pompe disease demonstrate substantial comorbidity burden and utilization of supportive services despite ERT treatment.

Nusinersen is a designer drug for spinal muscular atrophy (SMA) and was the first approved treatment for this once deadly disease. It is an antisense oligonucleotide that pairs with a specific locus of the Survival Motor Neuron 2 (SMN2) gene, to modify splicing and generate an increase in full-length SMN2 transcript. This in turn increases expression of survival motor neuron protein, deficiency of which results in motor neuron dysfunction and reduced cellular survival, the principal cause of SMA. Pre-clinical studies of nusinersen in animal models of SMA demonstrated substantial clinical responses and proof-of-concept, leading to successful clinical trials in symptomatic children and then in infants. Nusinersen's favorable safety profile after repeated lumbar intrathecal delivery as well as improvement in motor function and survival resulted in US regulatory approval for SMA in 2016. Other countries have followed with variable coverage policies depending upon age, weight, genotype and/or clinical severity. In the current treatment era, two populations of individuals with SMA exist: symptomatic patients identified in the clinic and pre-symptomatic patients (having no or few early clinical features of disease) largely identified by newborn screening. Real-world experience with nusinersen, the topic of this focused review, presents post-approval data in a broad range of patients beyond those studied in clinical trials. The favorable clinical response and safety profile are discussed, as well as the emerging new phenotypes of disease. Nusinersen, one of three FDA-approved drugs for SMA (as of 2025) remains an important therapeutic consideration for infants, children and adults with SMA.

Idiopathic inflammatory myopathies (IIM), also known as myositis, are a group of heterogeneous autoimmune diseases characterized by muscle inflammation and frequent involvement of extramuscular organs. Autoantibodies are present in approximately 70% of the patients. Despite treatment advances, management of IIM largely relies on empirical approaches and current treatment options lack robust evidence, with the exception of intravenous immunoglobulin (IVIg). Even with immunosuppressive therapy, up to 80% of the patients continue to experience ongoing disease activity, functional impairment and a significant reduced quality of life. Several challenges complicate the management of IIM, including rare occurrence, heterogeneity of the disease, systemic manifestations, higher prevalence of malignancies and the complexity of conducting large-scale clinical trials in rare diseases. Along with this, therapeutic development has long been hindered by an incomplete understanding of the disease pathogenesis. However, recent insights into the molecular and cellular mechanisms of IIM have revealed novel therapeutic targets. In this review, we will discuss the underlying immunopathogenesis of IIM, including the role of potentially pathogenic autoantibodies, B and T cells, the interferon (IFN) pathway and the complement system. We will also review current treatment strategies and provide an overview of emerging and promising new treatments tested in recently published clinical trials or ongoing clinical trials, including chimeric antigen receptor (CAR) T-cell therapy, T-cell engagers, T-cell targeting therapies, neonatal Fc receptor (FcRn) inhibitors, and small-molecule inhibitors targeting intracellular signaling molecules such as Janus kinases (JAKs), IFNs, and complement.

Introduction: Spinal muscular atrophy (SMA) is a neuromuscular disease that affects patients and caregivers worldwide, including in India, with a significant economic burden.

Methods: A comprehensive literature review was conducted to evaluate SMA, patient journeys, healthcare access, and treatment barriers in India, forming the basis for an expert panel discussion.

Results: The experts highlighted that early detection of SMA through newborn, carrier, or prenatal screening, and diagnosis through genetic testing enable timely interventions including disease-modifying therapies (DMTs) and multidisciplinary care. Currently, in India, Risdiplam is the only Drugs Controller General of India (DCGI) approved DMT for SMA. It is administered orally and approved for use in SMA type 1, 2, 3, and 4 among pediatric and adult patients. The management of SMA often revolves around the management of its complications, which requires respiratory, nutritional, and orthopedic care, both while awaiting and after receiving DMTs. Therefore, the gold standard for SMA care requires the availability of multidisciplinary care involving specialists from various fields. Despite the availability of DMTs, challenges such as affordability and timely access to these therapies remain major hurdles faced by SMA patients in India. Additionally, a lack of awareness among healthcare professionals, contributed to underdiagnosis and undiagnosed cases, further exacerbating the situation.

Conclusion: This review provides insights from the expert opinions of Indian pediatricians, neurologists, geneticists, pediatric neurologists, and pediatric pulmonologists on the burden of SMA, diagnosis and management practices, importance of a multidisciplinary approach, challenges faced in SMA care in India, and strategies to overcome these challenges.

Slowly progressive proximal muscle weakness in an otherwise healthy male posed particular challenges for the treating physicians, considering the wide range of possible differentials. Here we present a case of a 52-year-old male with paraparesis, elevated creatine kinase-levels, antibodies against the Mi-2 antigen and subtle skin lesions, leading to subsequent treatment for dermatomyositis. Beyond that, exome sequencing revealed biallelic variants in the gene encoding acid alpha-glucosidase with concordant reduced enzymatic activity in fibroblasts, indicating late onset Pompe disease. Subsequently performed magnetic resonance imaging revealed a pattern of involvement typical for LOPD, but histological workup from the vastus lateralis muscle was more indicative of an immune-mediated myopathy. After treatment for dermatomyositis and Pompe disease the patient showed an improvement in skin changes and a halt in muscular weakness. In conclusion, both entities could be seen in the patient. However, early and prolonged subclinical hyper-CK-emia hinted at Pompe disease as the primary entity.

The Western Canadian Neuromuscular Conference (WCNMC) is a conference focused on neuromuscular medicine that was held in Calgary, Alberta from September 27-29, 2024. Although WCNMC has a history going back to 2010 as a regional event, the most recent iteration of the conference aimed to expand this as a national meeting. A collaboration with Muscular Dystrophy Canada and the Neuromuscular Network for Canada (NMD4C) helped to achieve this goal and encourage participation from across Canada. Other goals for this event were to increase the opportunities for trainees, showcase new research, and integrate new topics into the program. The sessions included a clinicopathologic case series for the first time, which was led by neuromuscular fellows from across Canada. Sessions covering topics in neuromuscular disease focused on challenging diagnostic situations, and therapeutic developments for diseases including spinal muscular atrophy, Pompe disease, and TTR amyloidosis. A separate session covered genetic neuromuscular diseases, with a focus on conditions with genetic founder effects in western Canada. Finally, a transdisciplinary session was included, which discussed patient-focused issues in neuromuscular care, as well as preliminary results from the Burden of Inherited Neuromuscular Disease (BIND) study, on the indirect costs of living with a neuromuscular disorder. A research symposium at the conclusion of the event focused on trainee-led research but also included lectures regarding antisense therapies in neuromuscular disease and updates in research on amyotrophic lateral sclerosis.

BackgroundWeakness associated with facioscapulohumeral muscular dystrophy (FSHD) impacts daily activities. Impact is often measured using standardized clinical assessments, documenting activity capacity, and only captures a snapshot of function. Wearable sensors may enable assessments of real-world activity performance.ObjectiveTo examine activity performance (actigraphy) and its relationship with capacity (clinical measures of strength and function) in adults with FSHD.MethodsRemote assessments were piloted in a subgroup from Motor Outcomes to Validate Evaluations in FSHD. Participants wore waist-worn activity monitors for 7 days. Activity metrics included moderate-to-vigorous intensity physical activity (MVPA), time in activity levels, and step counts. Descriptive statistics summarized activity, Mann Whitney U tests compared groups, and correlation analyses examined relationships between activity performance and capacity.ResultsThirteen subjects wore the device for a median of 7 days. Most time was sedentary, with minimal vigorous activity. Participants spent a median of 23.1 min daily (IQR: 23.8) and 161.7 min weekly (IQR: 157.9) in MVPA. Median daily step count was 4245 (IQR: 2892), with a median maximum step count of 20 (IQR: 7) within a 10-second epoch. Correlations were found between total MVPA and 10mw/r (ρ=-0.720, p = 0.006) and TUG-comfortable (ρ=-0.720, p = 0.006), and between maximum step count and several functional measures.ConclusionThis pilot study provides insights into activity performance and its relationship with capacity in a small cohort of adults with FSHD. Total MVPA and maximum step count appear most informative for evaluating activity performance; larger studies are needed to confirm findings and assess psychometric properties of these metrics.

IntroductionMyotonic dystrophy type 1 (DM1) is characterized by a lifelong progressive muscular weakness associated with life-threatening events such as chronic respiratory failure (CRF). Early identification of patients at risk remains challenging.ObjectiveTo identify clinical and biological markers predictive of CRF onset and survival in a large DM1 cohort.MethodsWe conducted a retrospective cohort study of 126 DM1 adult patients followed from 2000 to 2024 at Rouen University Hospital. The primary outcome was the first forced vital capacity (FVC) ≤ 70% of predicted value. Prognostic factors were analyzed using Cox proportional hazards models with the start of follow-up at the time of diagnosis of DM1 and were followed until the outcome occurred, or death (censorship according to Kalbfleisch & Prentice approach to competing risks).ResultsDuring a median follow-up of 12.5 years, 45 patients developed FVC ≤ 70%. Muscular impairment rating scale (MIRS) (HR: 1.85, 95%CI:1.30-2.63) and conduction/rhythm disorders (HR: 3.13, 95%CI: 1.37-7.31) at diagnosis were independent predictors of FVC ≤ 70% adjusted on age, female sex (HR: 1.54, 95%CI: 0.82-2.91) and cataract at diagnosis (HR: 0.50, 95%CI: 0.22-1.16). CTG repeats ≥400 was associated with a doubled risk of respiratory decline but did not reach statistical significance. The 20-year mortality rate was 32%. MIRS (HR: 2.34, 95%CI:1.22- 4.51), male sex and older age at diagnosis significantly predicted death.ConclusionsMuscular impairment and cardiac rhythm/conduction disorders at diagnosis were strong predictors of respiratory complications. MIRS, male sex and older age at diagnosis were predictors of mortality in DM1. These prognostic markers should inform clinical management strategies to improve survival in DM1 patients.