Journal of neuromuscular diseases最新文献

Objective: The objective of this scoping review was to map the body of existing literature regarding muscle strength, balance and mobility limitations in oculopharyngeal muscular dystrophy (OPMD).

Methods: The Joanna Briggs Institute's methodology was followed. All original research including participants with OPMD 18 years or older and describing muscle strength, balance and/or mobility limitations using clinical outcome assessments retrieved from the PubMed, MEDLINE, PEDro, Cochrane Database of Systematic Reviews, and CINHAL Plus databases (searched before January 30^th, 2023) were included.

Results: Titles and abstracts from 416 studies were screened, and 54 articles were fully reviewed. Proximal upper and lower limb muscle strength were assessed in majority (92.6% of studies). Lack of common methodology made conclusions on their prevalence and severity difficult. Regarding balance, no performance outcome measures was retrieved. 29.6 to 63.0% of studies addressed mobility limitations; only two prospective longitudinal studies were retrieved, and two studies used reference values to assess impairments/limitations severity.

Conclusion: This scoping review highlights the current knowledge on muscle strength, balance and mobility limitations in OPMD. A lack of balance and complete mobility assessments, and OPMD-specific questionnaire for motor impairments or mobility limitations are noted. Future studies should focus on using standardized clinical outcome assessments to better document these impairments/limitations.

Numerous potential treatments are being developed for facioscapulohumeral muscular dystrophy (FSHD). Project Mercury was initiated to overcome challenges that could slow or prevent effective therapies from widespread availability to patients. It is important that upcoming trials include trial sites from different countries. We share our lessons learnt in clinical trials to assist inexperienced sites to become eligible for upcoming clinical trials. To become an eligible site, several key elements need to be in place such as personnel, facilities, and accessible patient populations. Clinical trial networks, patient advocacy groups and patient registries can support new sites in establishing these elements. As the preparation, execution and close-out of clinical trials generally involve the same steps every time, it is recommended to create and follow a trial roadmap. Most clinical trials are sponsor-initiated and involve working closely with the sponsor and vendors. It is therefore important to understand each other perspectives and goals for each trial. Once a drug receives regulatory approval and becomes available for market use new challenges arise such as patient reimbursement and phase 4 surveillance of the patients. In summary, we are at a pivotal time for FSHD and other rare neuromuscular disorders with the development of new disease modifying therapies. It is vital that as many sites as possible can participate in upcoming trials.

Charcot Marie Tooth disease (CMT) is a neurological condition characterised by fatigue alongside motor and sensory impairments. CMT also has a high prevalence of lifestyle dependent co-morbidities, despite which there are limited dietary guidelines for those with CMT. The present study aimed to determine whether diet quality and nutrient intake differed between CMT and control, and whether this may be associated with fatigue and mobility. Age matched participants [n = 25 CMT aged 53.6(15.3) years, n = 27 controls aged 51.5(12.0) years] completed 3-day food diaries, and online surveys. Food diaries were assessed using daily nutrient targets (Recommended daily intake, RDI), micronutrient-based scoring (MyNutritionIndex, MNI), food group-based scoring (healthy eating index, HEI-2020) and ultraprocessed food (UPF) intake. Survey outcomes included fatigue, quality of life (QoL), and mobility. CMT participants met none of the RDI targets of 32 nutrients, with 16 sufficiency nutrients lower than controls based on RDI and MNI (P < 0.05). MNI and HEI-2020 were not different between CMT and control. Minimally processed food intake was 27% lower in the CMT group, with UPF contributing double the caloric intake in CMT than controls (P < 0.05). In CMT, QoL domains were 36% lower than control (P < 0.05), fatigue severity and mobility were 56% and 11% worse than controls, respectively (P < 0.05). Fatigue severity was negatively associated with HEI-2020 in CMT and controls (P < 0.05). In the present study, diet quality using RDI was lower in CMT compared to controls. In both CMT and controls, fatigue severity was associated with worse diet quality based on micronutrient and food group analysis.

Myasthenia Gravis (MG) is a chronic autoimmune neuromuscular condition that significantly impacts patients' lives. Whilst psychosocial challenges are increasingly recognised as important in understanding the lived experience of patients, insight into these experiences during periods of clinical stability remains underexplored. This qualitative study explores the psychological and social aspects of living with MG through thematic analysis of semi-structured interviews with eight adults from a specialist MG care clinic in London, all considered clinically stable for at least three months. Data were derived from participants initially interviewed about their day-to-day experience of physical symptoms to inform development of a symptom monitoring tool. As psychosocial themes emerged strongly but remained unanalysed, this paper presents a secondary analysis focusing on psychosocial themes. Three overarching themes emerged: (1) coping with adaptation - including the burden of planning, struggles to accept diagnosis, therapeutic challenges and fear of the future; (2) social and identity disruption - involving changes in self-image, social withdrawal, and occupational challenges; and (3) emotional and psychological impact - highlighting negative emotions and cognitive fatigue. Uncertainty emerged as a meta-theme underpinning all other themes, reflecting, driving, and being created by MG's fluctuating symptoms. Findings suggest that psychological and social challenges underscored by uncertainty persist independently of symptom stability, highlighting the importance of uncertainty-focused interventions and integrated psychosocial support in MG care.

Purpose: Skeletal muscle constitutes 30-40% of total body mass and is now considered an endocrine organ, given its secretion of a variety proteins, metabolites, and cytokines. We have previously shown that the absence of dystrophin in skeletal muscle contributes to lethal systemic stress pathology in the mdx mouse model of Duchenne muscular dystrophy through a mechanism that remains to be identified. Here we searched for secreted protein signaling factors, or myokines, released from dystrophin-deficient skeletal muscle that influence the organism-wide integrated stress response. We performed skeletal muscle extracellular fluid extraction and discovery proteomics for wild-type, mdx, and transgenic mdx mice rescued by expression of a dystrophin construct, all analyzed under basal conditions and following brief scruff restraint stress that causes inactivity in mdx mice.

Major findings: Our analysis demonstrated that skeletal muscle dystrophinopathy is associated with increased expression of numerous proteins in both intact mdx skeletal muscle and extracellular fluid compared to healthy mice. Brief scruff restraint revealed protein candidates with differential abundance in mdx extracellular fluid. Specifically, altered follistatin-like 1 protein and adiponectin secretion in response to scruff stress was shown to be dependent on skeletal muscle dystrophinopathy. The diverse signaling roles of follistatin-like 1 in the cardiovascular, musculoskeletal, and nervous system implicate it as a particularly intriguing myokine candidate regulating the mdx stress response.

Conclusions: Our current study informs on the skeletal muscle secretory profile in mdx following a stressful stimulus and provides new leads to elucidate the mechanism by which mdx skeletal muscle orchestrates inter-organ stress signaling.

The Neuromuscular Disease Network for Canada aims to accelerate research and improve care for individuals living with neuromuscular disorders by connecting basic scientists, clinicians, and trainees nationwide. As part of this mission, the network held its second Basic Research Summer School (May 7-8, 2025, York University, Toronto), integrating patient and caregiver perspectives with advanced scientific sessions and full-day methodological workshops. The program emphasized experimental rigor, reproducibility, and collaboration across research pillars, while launching the Basic Science Trainee Committee and Canada's first national, publicly accessible database of standard operating procedures for muscle research. This trainee-led, reproducibility-focused model of Summer School provides a transferable framework for building standardized preclinical capacity across international neuromuscular disorders research networks.

The GNE gene encodes the UDP-GlcNAc-2-epimerase/ManNAc kinase, a bifunctional enzyme required for the synthesis of sialic acid. The mouse Gne gene is essential for embryonic development, but humans with recessive partial loss of function GNE mutations can develop infantile thrombocytopenia, juvenile amyotrophic lateral sclerosis, or adult-onset myopathy (GNE myopathy). We have created inducible Gne^lox/lox gene deletion mice to study how loss of Gne in adult mice relates to these disease states. Systemic Gne gene deletion in tamoxifen-treated Rosa-CreER^T2/Rosa-CreER^T2Gne^lox/lox mice caused uniform fatality within 30 days of gene deletion with spontaneous bleeding, thrombocytopenia, and anemia. Skeletal myofiber-specific Gne deletion in tamoxifen-treated HSA-CreER^T2/+Gne^lox/lox mice had no bleeding and no muscle pathology at 60 or 270 days post-treatment. Intramuscular injection of AAV.MCK.GFP-Cre in Gne^lox/lox mice also showed little to no evidence of muscle pathology, while AAV.CMV.GFP-Cre caused extensive muscle damage, reduced muscle force, and changed expression of markers for muscle regeneration, muscle cell senescence, muscle denervation, and muscle atrophy. These data demonstrate that Gne is an essential gene in adult mice that can mimic aspects of human hematologic and muscle diseases caused by GNE mutations, but suggests induction of muscle disease requires loss of gene GNE expression in cell types beyond skeletal myofibers.

Introduction: Temperature-induced aggravation of weakness is a well-known characteristic of demyelinating and motor neuron disorders. We investigated prevalence, frequency, and severity of symptoms during heat and cold exposure in patients with 5q-spinal muscular atrophy (SMA).

Methods: We conducted a longitudinal cohort study systematically assessing temperature-induced symptoms by means of a standardized questionnaire at baseline and after one year in adolescents and adults with SMA types 1-4 and age-matched healthy and disease controls. All patients were treatment-naïve for SMN-augmenting therapies at baseline.

Results: We included 103 patients with SMA types 1-4 (median age 39 years, range 13-67 years), 25 healthy controls and 46 disease controls. Eighty-four (82%) patients with SMA and 24 (52%) disease controls were non-ambulatory. Ninety patients with SMA (87%) reported cold-induced symptoms, primarily as aggravation of weakness (85%, n = 88), i.e., cold paresis. Cold paresis was more prevalent in non-ambulatory patients with SMA (94% vs. 47%) and associated with lower Revised Upper Limb Module (RULM) scores in these patients. Healthy controls did not report cold-induced symptoms, in contrast to the 30 (65%) disease controls who did experience cold paresis. Cold paresis was more prevalent in non-ambulatory patients with SMA compared to disease controls. The prevalence of cold paresis was unchanged after one year of disease-modifying treatment.

Conclusions: Cold paresis is commonly experienced by patients with SMA, particularly those with more severe weakness based on SMA type, ambulatory status, and RULM score. Better understanding of the underlying mechanisms of cold paresis might lead to new symptomatic treatment to preserve motor functionality.Trial registration information: NL72562.041.20 (registered at www.toetsingonline.nl; 26-03-2020).

BackgroundThis study aimed to investigate sleep quality, restless legs syndrome (RLS), and excessive daytime sleepiness in adults with spinal muscular atrophy (SMA) and their relationships with motor function, quality of life (QoL), fatigue, and depression.MethodsWe included 43 adults with SMA (31 non-ambulatory; 11 using non-invasive ventilation) and 43 age- and sex-matched healthy controls (HC). Subjective sleep quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). RLS was diagnosed using the International RLS Study Group diagnostic criteria. Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE) and respiratory function, as well as, 36-Item Short Form Health Survey (SF-36), Beck Depression Inventory (BDI) and Fatigue Severity Scale (FSS) were recorded.ResultsSMA patients had significantly worse scores in sleep efficiency domain of the PSQI (0.7 ± 1.0 vs. 0.3 ± 0.6, p = 0.04) as well as in global PSQI score compared to HC (5.5 ± 3.5 vs. 4.0 ± 2.6, p = 0.029). Patients classified as poor sleepers (PSQI > 5) had a higher body mass index (BMI), greater BDI, and ESS scores. No association between global PSQI score and HFMSE or RULM score was observed. Patients classified as poor sleepers had lower total SF-36 score in comparison to good sleepers (53.2 ± 15.4 vs. 69.6 ± 12.3, p < 0.001). RLS was present in five SMA patients (11.6%).ConclusionPoor sleep quality is common in adults with SMA. It contributes to a lower QoL and should be addressed as a part of the standard of care in adults with SMA.

Patient-oriented research is increasingly recognized as an important methodology in health sciences. Benefits of patient engagement include aligning research priorities to those living with health conditions, developing better recruitment strategies and protocols, and integrating findings more meaningfully. However, for research teams to work well with patient-partners, training for all stakeholders is needed. While training exists, none consider the uniqueness of the neuromuscular disease experience. To address this gap, our team of researchers, clinicians, and patient-partners collaborated to increase the capacity for patient-engagement in neuromuscular disease research. Our methods included: 1) conducting a landscape of available resources, and 2) using adult education principles and a backwards design process to develop unique training modules. The result is an online platform with three modules focusing on the neuromuscular disease context, addressing the inclusion, diversity, equity, and accessibility needs of those with neuromuscular diseases, and building teamwork skills. Early evaluation of the first two modules indicates high satisfaction and knowledge gain. Through this process, we have learned about the barriers of patient-oriented research, how to support the required system culture shift, and how to plan for long-term sustainability.