The progressive muscle disease inclusion body myositis (IBM) is characterized, amongst others, by inflammatory features and protein accumulation in skeletal muscle fibers. One of the proteins that accumulates in perinuclear and peripheral regions of muscle fibers is cytosolic 5'-nucleotidase 1A (cN1A), the target of anti-cN1A autoantibodies, which are found in many IBM patients. To shed more light on potential pathogenic aspects of IBM, we identified post-translational modifications of cN1A in human skeletal muscle. Immunoaffinity-purification followed by mass spectrometry resulted in the identification of three monomethylation sites, K178, R223, and K243. Single amino acid substitutions of each of these methylation sites did not detectably affect the accumulation of cN1A in perinuclear regions of cultured human cell lines. Two of these monomethylation sites, R223 and K243, are located within one of the previously identified major linear epitope regions of cN1A. Synthetic peptides, corresponding to aa 219 - aa 247, were used to investigate the effect of monomethylation on the antigenicity of this epitope by ELISA. The results showed that the simultaneous monomethylation of R223 and K243 may enhance its recognition by IgG autoantibodies. We conclude that cN1A contains at least three amino acids that can be monomethylated and that monomethylation may affect its autoantigenicity.
BackgroundMyasthenia gravis (MG) is commonly associated with thymic tumors and may be triggered or worsened by immune checkpoint inhibitors (ICIs). Although pembrolizumab (PEM) has shown efficacy in relapsed/refractory thymic tumors, its relationship with MG in thymic tumor patients is unclear.MethodsWe retrospectively reviewed patients with thymic tumors treated with PEM at a tertiary center (2016-2021) to assess the prevalence, timing, and clinical features of new-onset or exacerbated MG, along with immune-related adverse events (irAEs). Outcomes were compared with 714 thymic tumor patients not treated with ICIs (1993-2021), stratified by tumor type.ResultsAmong 60 PEM-treated patients (mean age 50.4 years; 33% female), six (10%) developed new-onset (3/60) or relapsed (3/60) generalized MG which worsened after PEM administration. MG occurred in 42% of thymoma (5/12) versus 2% of thymic carcinoma patients (1/43; p = 0.001). All MG cases had other irAEs, most frequently myositis (n = 5) and myocarditis/cardiomyopathy (n = 3). Despite improvement of MG with immunotherapy, three patients died from tumor progression or irAEs. Compared with non-PEM-treated thymoma patients, MG incidence was numerically higher but not statistically significant.ConclusionPEM-treated thymic tumor patients may develop or experience worsening MG, typically with severe symptoms and concurrent irAEs that affect prognosis. While a direct causal link between PEM and MG remains uncertain, careful monitoring is warranted.
ObjectivePLOD1-related kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by generalized joint laxity, severe congenital hypotonia, progressive kyphoscoliosis, hyperextensible and easily bruised skin, ocular abnormalities, and significant vascular complications.MethodsWe report on nine patients from seven families, eight of them carrying the common homozygous duplication of exons 10-16 in PLOD1. Longitudinal clinical assessments included muscle ultrasound (n=6) and vascular ultrasound (n=4). Genetic diagnostics varied, with most patients ultimately undergoing trio exome or genome sequencing. Urine pyridinoline analysis was performed in seven of nine patients. A literature review and age-stratified recalculation of vascular incidence, including our cohort, were conducted.ResultsDiagnosis was challenging in five families, as the exon 10-16 duplication often escaped detection due to its high allele frequency. Seven patients were initially diagnosed with congenital myopathy. Muscle ultrasound revealed abnormalities in five of six sonographically examined cases. Severe vascular events included neonatal intracranial hemorrhage, fatal aortic aneurysm rupture at the age of 13 years, multiple aneurysms/dissections (ages 14-19 years), and mesenteric dissection at the age of 10 years. Four younger patients (aged 3-9 years have had no vascular complications to date. Urine pyridinoline analysis was abnormal in all tested cases.DiscussionPLOD1-related kEDS often presents with a phenotype of congenital myopathy, complicating genetic diagnosis and potentially leading to underdiagnosis - especially in cases where the common PLOD1 duplication may be missed by strict frequency filters in exome or genome sequencing data. Literature and our data indicate a vascular event incidence from childhood age of ∼25%.
Objectives Anti-signal recognition particle (SRP) myositis is a rare subset of immune-mediated necrotizing myopathy (IMNM). It is characterized by proximal muscle weakness, markedly elevated serum creatine kinase (CK) levels, and poor response to conventional therapies. Evidence for optimal management remains limited, particularly regarding the long-term outcomes of rituximab treatment. Method We retrospectively reviewed anti-SRP myositis patients who received rituximab at Seoul National University Hospital. Diagnosis was based on clinical features, elevated CK levels, and positivity for anti-SRP antibodies. Demographic, clinical, laboratory, radiological, histopathological, and treatment data were collected. Results Five patients, aged between 4 and 71 years, exhibited proximal muscle weakness, elevated CK levels, and variable disease severity. Rituximab induction followed by maintenance therapy led to a significant improvement in muscle strength and normalization of CK and aldolase levels. In patients with mild or subclinical phenotypes, aldolase elevations often preceded clinical relapses. Relapses during follow-up were managed with rituximab re-administration, which restored muscle strength and biochemical markers. MRI, EMG, and muscle biopsy findings were consistent with myopathic changes. Conclusions This case series highlights the heterogeneity in age, disease severity, and clinical course of anti-SRP myositis and the efficacy of rituximab in refractory and relapsing cases. Multimodal monitoring, including CK, aldolase, CD19+ B-cell counts, and clinical assessment, is essential for the early detection of relapses. Our findings support rituximab as a valuable component of individualized treatment strategies for anti-SRP myositis, though larger studies are warranted to establish standardized protocols and clarify long-term outcomes.
Background The classification of idiopathic inflammatory myopathies (IIMs) has evolved substantially with the identification of myositis-specific autoantibodies (MSAs). However, how contemporary classification frameworks are applied in routine clinical practice remains variable. This study provides a clinicopathological and serological characterization of IIMs from a national neuromuscular referral center in Cyprus. Methods We conducted a retrospective, single-center cohort study of adult patients diagnosed with IIM between 2007 and 2025. Patients were classified using a clinicopathological and serological approach into dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASyS), overlap myositis (OM), inclusion body myositis (IBM), and polymyositis (PM), with the 2017 EULAR/ACR criteria used as a reference framework and historical diagnoses re-evaluated. Results 36 patients were included. Final subtype distribution: IMNM in 14 patients (39%), DM in 7 (19%), IBM in 4 (11%), OM in 5 (14%), ASyS in 3 (8%), PM in 2 (6%). Only one patient remained non-classifiable. Autoantibody testing was performed in 26/36 patients; MSAs were detected in 19/26 tested (73%; 53% of the total cohort), most commonly anti-HMGCR, while anti-NT5C1A antibodies were detected in three additional patients. Muscle biopsy was performed in the majority of patients, reflecting historical diagnostic practices. Conclusion This study demonstrates real-world application of contemporary IIM classification, enabling accurate disease subtyping with direct implications for malignancy surveillance and interstitial lung disease monitoring, as well as reclassification of cases, most notably those previously labelled as PM. The findings further underscore the role of muscle biopsy, particularly when serology is negative, discordant, or unavailable.
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder characterized by muscle weakness and autonomic dysfunction. While amifampridine is the established first-line symptomatic treatment, longitudinal data regarding the evolution of therapeutic regimens over time and the use of immunosuppressive therapies remain limited. This retrospective study analyzed 70 LEMS patients treated at the Leiden University Medical Center (LUMC) between 1992 and 2023. Treatment was evaluated and a four-point “leg score” was developed and used to retrospectively quantify functional impairment and response to amifampridine. Sixty-six percent of the cohort was female, the median age of diagnosis was 54 years and non-tumor LEMS was more prevalent (77%). All patients used amifampridine at some point, and 91% initiated it within six months of diagnosis. Amifampridine improved leg scores in 57% of patients. Although 58% of patients reported side effects (mostly paresthesia), discontinuation was rare (7%). Pyridostigmine was used in 81% of patients. Immunosuppressive drug use—predominantly prednisolone and azathioprine —increased over time, reaching 44% after five years. Conversely, azathioprine, prednisolone and pyridostigmine were discontinued by 50%, 38% and 32% of patients, respectively, often due to adverse effects. In conclusion, amifampridine provides significant clinical benefits and remains the cornerstone of LEMS therapy. Immunomodulatory therapies were introduced gradually and their use increased over time. Compared with autoimmune myasthenia gravis, immunomodulatory therapy was used less frequently during the early disease course of LEMS.
BackgroundX-linked myotubular myopathy (XLMTM) and autosomal dominant centronuclear myopathy (ADCNM) are rare neuromuscular disorders characterized by severe weakness and respiratory impairment and have recently been the focus of therapeutic development. Robust baseline data are essential to understand disease trajectories and enable trial readiness. We present baseline clinical, functional, and biomarker findings from the terminated Unite-CNM trial (NCT04033159), a basket study of the antisense oligonucleotide DYN101, designed to modulate DNM2 expression in adolescents and adults with XLMTM or ADCNM.MethodsScreening and baseline evaluations included medical history, patient-reported outcomes, quantitative muscle strength and motor function, respiratory testing, muscle ultrasound and histology, and biomarker analyses (DNM2 protein, creatinine, creatine kinase, cystatin C, myostatin, and microRNAs) in plasma and muscle.ResultsTwenty-six patients were screened (15 DNM2, 11 MTM1); 14 entered the study. Patient-reported measures highlighted swallowing challenges and variable personal goals. Baseline respiratory impairment was variable in DNM2 and female MTM1 patients but consistently reduced in males with MTM1 (FVC% and FEV1% stable over follow-up to 78 weeks). MFM32 scores were similar across genotypes and sexes, while Myogrip strength was reduced versus age norms yet stable longitudinally. Muscle pathology was comparable across groups. Biomarker analyses showed altered DNM2 protein, reduced myostatin, and specific abnormalities in creatinine, creatine kinase, cystatin C, and microRNAs.ConclusionThis dataset provides valuable phenotypic, functional, and biomarker characterization of adult XLMTM and ADCNM, emphasizes the importance of baseline data for ultrarare disease trials, and highlights the need for protocol flexibility in response to safety signals and disruptions (e.g. COVID-19).
Background and objectivesTo evaluate the safety and clinical efficacy of efgartigimod in adults with severe generalized myasthenia gravis (MG) exacerbations requiring ventilatory or enteral support.MethodsProspective, single-arm, open-label study conducted between November 2024 and April 2025. Sixteen consecutive adults with AChR- or MuSK-antibody-positive generalized MG requiring invasive or non-invasive ventilatory support or enteral feeding were enrolled; all met 2016 MG Guidelines criteria for impending myasthenic crisis. MGFA classification included Class IIIb (n=14), IIIa (n=1), and IVb (n=1). The primary endpoint was clinically meaningful improvement (CMI) in MG Activities of Daily Living (MG-ADL), defined as ≥2-point reduction from baseline at weeks 4 and 8.ResultsAll 16 participants (mean age 58.5±17.4 years; 8 women) completed eight weeks of follow-up. At week 8, 12 patients (75%; 95% CI 47-91%) achieved the primary endpoint. Median MG-ADL decreased from 11 (IQR 9-13) to 7 (IQR 6-9) (median change -5 points; p=0.003). Median QMG decreased from 21 (IQR 19-23) to 13 (IQR 11-16) (median change -7.5 points; p<0.001), with 56% meeting QMG-CMI by week 1. Among 12 participants receiving corticosteroids (mean starting dose 21.2 mg/day), 50% reduced or discontinued by week 8. No treatment-related serious adverse events occurred.DiscussionEfgartigimod produced rapid, clinically meaningful improvement in severe MG exacerbations without safety concerns. FcRn blockade may represent a practical alternative to plasma exchange or IVIG in acute care settings. Findings are limited by the absence of a control arm, which precludes definitive attribution of clinical improvement to efgartigimod alone.Clinical trials registrationNCT06688253.
BackgroundWheelchair users with muscular dystrophy face health challenges from their condition, sedentary lifestyle, and wheelchair use. While exercise benefits are well-documented in healthy individuals, its effects in wheelchair users with muscular dystrophy are underexplored: low muscle mass might limit exercise benefits. This study investigates benefits and adverse events of assisted leg cycling to improve fatigue, pain, constipation, and quality of life in wheelchair users with muscular dystrophy.MethodsWheelchair users with muscular dystrophy were tested at baseline, after a 10-week control period, and after 10 weeks of assisted leg cycling (20 minutes, 3 times/week). Efficacy outcomes were changes in fatigue, lower back/leg pain, constipation, and quality of life. Secondary outcomes included changes in exercise performance, cardiovascular response, and metabolic health. A 1.5-year follow-up of voluntary training evaluated long-term effects.ResultsNineteen participants enrolled; two dropped out. Lower back pain and fatigue decreased and physical quality of life improved. Constipation did not change overall but improved in more than half of participants. HbA1c decreased by 2 mmol/mol, mainly in two participants with diabetes. Blood lipids, leg pain, cycling time, and power output showed no changes. Benefits persisted or improved over 1.5 years in participants with a high adherence.DiscussionAssisted cycling may reduce lower back pain, improve quality of life, and possibly decrease fatigue and constipation in wheelchair users with muscular dystrophy. Furthermore, exercise likely lowers HbA1c, particularly in individuals with diabetes. These findings suggest that assisted cycling is a feasible health intervention for wheelchair users with muscular dystrophy.
Background & AimsMyotonic dystrophy type 1 (DM1) is frequently associated with metabolic abnormalities and altered body composition, yet energy metabolism under free-living conditions remains incompletely characterized. This study aimed to characterize total energy expenditure (TEE) using the doubly labeled water (DLW) method and to examine its associations with body composition and functional status. Estimated energy balance was also explored as a secondary variable.MethodsTwelve patients with genetically confirmed DM1 were included. TEE was assessed using the DLW method. Body composition was evaluated using multifrequency bioelectrical impedance analysis. Energy intake was estimated from dietary records, and energy balance was calculated as energy intake minus TEE. Associations were examined using correlation analyses.ResultsThe mean TEE was 990 ± 169 kcal/day. TEE showed moderate positive associations with skeletal muscle mass and fat-free mass, and functional status was moderately associated with body weight-adjusted TEE. The mean energy intake was 1,355 ± 229 kcal/day, resulting in a positive energy balance of 366 ± 282 kcal/day; however, energy balance was not associated with body fat percentage or fat mass.ConclusionsDLW-measured free-living TEE was markedly low in DM1 patients with severe mobility limitation and reduced lean body mass despite largely normal BMI values. Estimated energy balance was not associated with adiposity. These findings suggest that functional severity and body composition should be considered when interpreting energy expenditure in DM1.
BackgroundMyotonic dystrophy type 1 (DM1) is associated with reduced physical activity, overweight and cardiovascular morbidity. Nutritional management requires accurate estimation of total daily energy expenditure (TEE), based on basal metabolic rate (BMR) and physical activity level (PAL). However, DM1-related changes in body composition may reduce the accuracy of commonly used BMR equations. This study evaluated BMR equation accuracy in DM1 versus controls, and assessed PAL and substrate oxidation.MethodsIn this secondary analysis of a prospective case-control study, 15 DM1 patients were compared with 15 age-, sex-, and BMI-matched controls. Body composition was measured using dual-energy X-ray absorptiometry. Overnight metabolic rate (OMR) was assessed by room calorimetry and compared with standard predictive equations (Harris-Benedict, WHO, Mifflin-St Jeor). Additionally, OMR was compared to body composition-based equations (Wang, Nelson, Sabounchi structures 4, 5, and 11). TEE was measured over 15 days using doubly labeled water. PAL was calculated as TEE/OMR, and substrate oxidation was assessed using the respiratory exchange ratio (RER).ResultsStandard predictive equations significantly overestimated metabolic rate in DM1, with median biases of +100 to +165 kcal/day (+7% to +12%, p<0.01), with no significant bias in controls. Structure 11 performed best in DM1 (+0.0%, p=1.000). PAL was lower in DM1 than in controls (1.42 vs. 1.69, p<0.001), whereas RER did not differ.ConclusionCommon predictive equations overestimate energy requirements in DM1. Body composition-based approaches or correction factors may improve estimation, while low PAL should be considered when estimating TEE. These findings have direct implications for nutritional management in DM1.
Objective To investigate the association of cardiac autonomic dysfunction with clinical staging and disease progression rate upon diagnosis of amyotrophic lateral sclerosis (ALS), and its impact on survival. Methods 24-hour Holter was performed in 95 ALS patients at diagnosis and 39 controls. Patients were grouped by King’s Clinical Staging and progression rate (ΔFS, median cut-off 0.67). Heart rate variability parameters were compared across groups. A survival-based cut-point optimization approach was used to determine the cut-off value of standard deviation of all normal-to-normal intervals (SDNN). Kaplan-Meier estimator and multivariable Cox regression analysis were used to evaluate of the effect of SDNN on survival during a median follow-up of 21.5 months. Results ΔFS in ALS patients in King’s Stage 4 upon diagnosis was faster ( P =0.007) compared to that of those diagnosed in earlier stages, featuring a higher incidence of respiratory ( P <0.001) and bulbar symptoms ( P <0.001). In addition, ALS patients in King’s Stage 4 exhibited elevated HR-min ( P =0.007) and decreased RR intervals (RRI) ( P =0.032), SDNN ( P =0.004), and standard deviation of the averages of NN intervals in all 5-min segments (SDANN) values ( P =0.020) compared to controls. Patients in the ΔFS-fast group had a higher HR-min than those in the ΔFS-slow group ( P =0.013) and controls ( P =0.003) and lower SDNN ( P =0.018) than controls. Both Kaplan-Meier estimator ( P =0.03) and multivariable Cox regression analysis ( P =0.019) showed that lower SDNN (cut-off value: 111 ms) was associated with poor survival in ALS patients. Conclusion Upon diagnosis, ALS patients in King’s Stage 4 and with faster disease progression demonstrated significantly diminished cardiac autonomic control. Lower SDNN was associated with poor survival in ALS.
MEGF10 biallelic variants cause early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD), congenital myopathies with cores, and later-onset myopathies with respiratory failure. As MEGF10 plays a key role in satellite cells proliferation and differentiation, these disorders are considered primary Satellite Cell-opathies. We present clinical, genetic, and laboratory findings from three patients with MEGF10-related myopathy from two families: a 6-year-old boy with EMARDD, and two siblings with a milder myopathy with respiratory involvement. Patient 1, male, showed decreased fetal movements and profound neonatal hypotonia with respiratory failure, requiring tracheostomy soon after birth. At 6 years, he had lack of head and trunk control, scoliosis, and upper limbs antigravity movements. Muscle MRI revealed mild-to-moderate, symmetrical fibro-fatty replacement affecting scapular, paravertebral, gluteal and adductor muscles, with bilateral absence of the semimembranosus. Muscle biopsy revealed a reduction of Pax7-positive satellite cells. Genetic studies disclosed the novel homozygous MEGF10 c.337T>C, p.(Cys113Arg) variant. Patient 2 is a 24-year-old woman with myopathic facies, progressive axial and generalized weakness, and thoracolumbar scoliosis at 11 years, leading to progressive respiratory involvement necessitating tracheostomy at 14 years. Her 17-year-old brother, patient 3, experienced a threatened abortion and perinatal complications consisting of neonatal hypoxia, right arm monoplegia, and clavicle fracture, followed by motor delay, scoliosis and progressive respiratory dysfunction, requiring non-invasive ventilation at 16 years. P2 and P3 harbour the novel homozygous c.917G>C, p. (Arg306Pro) MEGF10 pathogenic variant. We describe three new patients with MEGF10-related myopathy, showing severe but variable clinical expression, associated with two novel variants.
Introduction Spinal involvement is common in Duchenne muscular dystrophy (DMD), specifically scoliosis and vertebral fractures. Treatment with corticosteroids (CS) delays scoliosis onset, but also induces low bone mineral density, increasing fracture risk. Objective Assess long-term effects of intermittent CS on scoliosis development, bone mineral density and vertebral fractures in DMD. Method We retrospectively analysed real-world data from a single national reference center in the Netherlands. Spinal imaging was obtained by yearly anteroposterior radiographs. Scoliosis was defined as lateral spinal curvature with a Cobb angle of >10°. Yearly lumbar spine bone mineral density (LSBMD) Z-scores were measured with dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine. Vertebral fractures were evaluated using yearly vertebral fractures assessments (VFA). Results We included 86 individuals with DMD who visited the outpatient clinic between 2002 and 2022, aged 4-18 years. Seventy-five patients (87.2%) developed scoliosis (median age 11.0 years), mostly after loss of ambulation. Scoliosis progressed to >20° in 40 (46.5%) and to >30° in 29 (33.7%) of all patients. Spinal fusion was performed in 20 (23.3%) of all patients (median age 18.5 years). Cobb angles significantly increased after loss of ambulation (LoA) (p<0.001). Mean height SDS was -0.8. LSBMD Z-score declined below -2.0 in 27 (31.4%) patients and was significantly lower after LoA (p<0.001). Of 86 patients, 64 underwent VFAs, with 16 (25%) developing vertebral fractures during follow-up, mostly asymptomatic (87.5%). Conclusion Individuals with DMD on intermittent CS experience a higher incidence of scoliosis, fewer vertebral fractures, and generally maintain higher LSBMD Z-scores compared to published data on patients receiving daily CS.
Background/Objective Pathogenic variants in the dystrophin gene ( DMD ) cause dystrophinopathies. These variants can cause skeletal and cardiac involvement. Disease progression in skeletal muscle is characterized by fatty replacement, but whether similar processes occur in the myocardium remain unclear. Dixon cardiovascular magnetic resonance (CMR) can quantify myocardial fat fraction (FF). This study used Dixon CMR to quantify myocardial FF in patients with BMD and women carrying DMD gene variants, and to explore associations with cardiac function, assessed by left ventricular ejection fraction (LVEF), age, and skeletal muscle FF. Methods This cross-sectional study included 20 patients with BMD, 27 women carrying DMD gene variants, and 40 healthy controls who underwent three-point Dixon CMR to quantify myocardial FF. Muscle MRI was performed to assess lower-limb muscle FF. Results Myocardial FF did not differ significantly among the three groups ( p = 0.11); mean values were 10.0% in patients with BMD, 11.2% in women carrying DMD gene variants, and 10.4% in healthy controls. Subgroup analyses showed no significant differences between patients with BMD and healthy men or between women carrying DMD gene variants and healthy women. Myocardial FF was not associated with LVEF, age, or skeletal muscle FF. Conclusions Dixon CMR revealed no increase in myocardial FF in patients with BMD or women carrying DMD gene variants compared with healthy controls. Unlike skeletal muscle, myocardial remodeling in dystrophinopathies does not appear to be adipogenic and is likely predominantly fibrotic. Dixon CMR is useful for skeletal muscle imaging but has limited clinical use for myocardial assessment.
Rare neuromuscular and neurological diseases (NMDs and RNDs) present diagnostic challenges due to their clinical heterogeneity and genetic complexity. Despite the advancements in next-generation sequencing (NGS) and other high-throughput genomic technologies, a significant proportion of patients with NMDs and RNDs remain undiagnosed. This is primarily due to genetic heterogeneity, the presence of novel or private variants, and incomplete variant detection by short-read sequencing platforms. The Solve-RD project, a pan-European initiative funded by the Horizon 2020 programme, established a robust interdisciplinary framework integrating expert clinical and bioinformatics teams through Data Interpretation Task Forces (DITFs) and Data Analysis Task Force (DATF). Focusing on previously undiagnosed NMD and RND patients, Solve-RD implemented a systematic reanalysis of exome/genome data. For specific cohorts, various omics approaches were added, including long-read genome sequencing, RNA sequencing, and optical genome mapping. This collaborative framework significantly improved diagnostic yield in RND and NMD cohorts and led to the identification of novel pathogenic variants and mechanisms. The Solve-RD model exemplifies how structured expert collaboration, data sharing and harmonisation, and cutting-edge multi-omics technologies can overcome current diagnostic limitations in rare disease research.
BackgroundDuchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder causing progressive muscle loss and early death. Despite global evidence on its burden, data from Sweden remain limited.ObjectiveThis study described the natural history of DMD, treatment patterns, healthcare resource utilization, and direct medical and non-medical costs among patients with DMD and their caregivers in Sweden.MethodsA retrospective, observational matched cohort study was conducted using data from the Swedish National Registry for Neuromuscular Disorders linked to national health and social registers. Patients diagnosed with DMD and their caregivers were compared to matched population controls. Disease progression was classified into four stages based on the HERCULES model.ResultsA total of 211 DMD patients (mean age at diagnosis: 4.9 years) and 877 comparators were included. Patients experienced progressive loss of function, spending on average 3.8, 4.8, 4.8, and 7.4 years in stages 1-4, respectively. Glucocorticoid use was high (84% on either prednisolone or deflazacort). Annual direct medical costs were significantly higher for DMD patients (€14,590 vs. €660). Direct non-medical costs, predominantly for personal assistance, increased substantially with disease stage, representing 89% of total DMD-related costs (€135,671 annually).ConclusionsDMD is a severe disorder marked by prolonged time in the later stages of the disease and increasing need for support. DMD imposes a significant economic burden in Sweden, with direct non-medical costs far exceeding direct medical costs. These findings highlight the need for and value of early and effective interventions to delay disease progression and alleviate societal burden.
ObjectiveCharcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and usually manifests in the first two decades of life. However, prospective data on the natural course during childhood remain scarce.MethodsThis two-year, prospective, observational cohort study was conducted at two German pediatric neuromuscular centers. Annual standardized clinical assessments were performed. Sixty-eight pediatric patients with CMT (age range: 4-18 years; 35 females) were included. The primary outcome was the CMTPedS score, assessed at baseline and after a mean interval of 2.03 ± 0.23 years. Changes in the 11 individual CMTPedS subitems were also analyzed.ResultsThe mean baseline CMTPedS score for the total cohort (n=68) was 20.5 ± 8.8. Stratified by genotype, mean scores were: CMT1A (n=31), 16.5 ± 7.6; CMT1B (n=6), 21.5 ± 9.4; CMT2A (n=4), 35.8 ± 10.0; CMT4C (n=4), 27.0 ± 3.7; CMTX (n=4), 24.3 ± 10.1); others (n=13), 24.6 ± 7.7; genetically unsolved (n=6), 19.8 ± 8.6. Over a two-year observation period, the mean change in CMTPedS was 0.0 ± 2.7, indicating overall no significant progression.ConclusionIn this well-characterized cohort, overall disease course was non-progressive over two years-most notably in CMT1A, the most prevalent subtype. CMT2A and CMT1B showed numerically greater changes, yet none reached statistical significance. These results emphasize the slow-progressive nature of pediatric CMT and highlight the limitations of using short-term clinical progression as an outcome measure in therapeutic trials.
Introduction Knowledge about facilitators and barriers to exercise among individuals with MG is limited. Objective The aim of this study was to identify factors that influence exercise participation for adults with MG and to explore beliefs and perceptions with respect to exercise. Methods This was a cross-sectional observational study via an online questionnaire. Adults with MG residing in France were eligible. Results Responses from 455 participants were analysed. The majority were between 50 and 69 years, 71% were female, 80% had generalised MG, and half had early-onset MG. Participants reported reduced MG-specific QoL (MGQOL-15F-r), a moderate-to-high impact of MG on activities of daily living (MG-ADL), and mild-to-moderate fatigue levels (NeuroQoL fatigue). Overall, 54% of respondents reported engaging in exercise (“exercisers”), while 47% did not (“non-exercisers”). Exercisers had a lower BMI, reported less fatigue, better HRQoL and a lower impact of MG on ADLs compared to non-exercisers. Fear of exercising was reported by one-third of participants, including half of non-exercisers versus 19% of exercisers (p < 0.001). Non-exercisers reported significantly more barriers to exercise (mean 3.5 (1.8)) than exercisers (mean 2.6 (1.9), p < 0.001). Health/symptoms was the most frequently reported barrier in both groups (59% of non-exercisers, 39% of exercisers). Non-exercisers also reported fewer facilitators (mean 2.1 (1.4)) than for exercisers (mean 2.5 (1.3), p=0.004). The most frequently cited facilitator for non-exercisers was specialised supervision/coaching (59%), while exercisers most frequently cited health/symptom improvement (57%). Conclusion Several barriers and facilitators influencing exercise participation for individuals with MG could be addressed with tailored programmes.
Background Distal myopathies (DMs) comprise a heterogeneous group of hereditary muscle diseases characterized by predominant distal muscle weakness and atrophy overlapping with hereditary neuropathies, leading to diagnostic delays or misclassification. Results We conducted a retrospective analysis of 125 patients from 103 families with DMs revealed at a federal genetics referral center in Russia from 2010 to 2025, representing the largest Russian DM cohort. Causative variants were identified in 20 genes, most commonly in the GNE (30.1%), DYSF (13.6%), and TTN (9.7%) genes. Although distal muscle involvement predominated, lower limb muscle magnetic resonance imaging (MRI) showed proximal involvement in 93.4% (71/76) of cases regardless of disease stage. Across the cohort, gracilis, rectus femoris, and tibialis posterior were relatively spared. Referral misdiagnosis as hereditary neuropathy occurred in 32.8% (41/125) of cases. To characterize diagnostic pitfalls, we compared patients initially referred with neuropathy to those referred with DM. We demonstrated that group differences were evident solely in the needle electromyography (EMG) reports, while clinical features and lower limb muscle MRI data were broadly comparable. We analyzed the probable causes of EMG misinterpretations, which most commonly included severe spontaneous activity being mistaken for active denervation, high-amplitude motor unit potentials being misclassified as neurogenic, and, in some cases, the wrong choice of muscle for the study. Conclusion According to our data, one-third of patients with DM were initially referred for suspected neuropathy. In many cases, misclassification was likely due to pitfalls in EMG interpretation, highlighting the need for careful EMG analysis in patients with myopathies.
