Background and ObjectivesHealth-related quality of life (HR-QoL) is compromised in patients with neuromuscular disorders (NMDs). Disease severity alone does not predict HR-QoL; there are other known predictors including physical, psychological, and social factors. This study aims to provide insight into how mobility, age, and diagnosis may affect HR-QoL in adults with NMD. MethodsThe QoL in Genetic Neuromuscular Disease Questionnaire (QoL-gNMD) was completed by adult patients with NMDs before attending a clinical visit at the John Walton Muscular Dystrophy Research Centre in Newcastle upon Tyne, UK. The Summary of Function Scale was administered during the clinical visit to characterize mobility status. ResultsA total of 580 responses were included in this cross-sectional study. Overall perceived health and HR-QoL were reported poorest by ambulant patients who walked using aids. Items from the QoL-gNMD that were affected the most by NMDs were future planning and the need to rely more on others. A nonlinear trend where patients with "midlevel" mobility (walked with aids or manual wheelchair users) reported the poorest HR-QoL were observed in all 3 HR-QoL domains: Impact of Physical Symptoms (IPSs), Self-Perception (SP), and Activities and Social Participation (ASP). This nonlinear trend between HR-QoL and mobility was observed for younger patients but became more linear in older age groups. In our cohort, patients with "midlevel" mobility were the oldest, and those with the lowest levels of mobility (i.e., powered wheelchair users) were the youngest. Interaction between age and mobility was significant and both affected HR-QoL. There was marked variability in HR-QoL between diagnoses. Diagnosis was a significant factor for IPS (p < 0.01) and SP (p = 0.04) but not for ASP (p = 0.17). DiscussionAge and mobility status affect HR-QoL. Individuals with limited ambulation reported the poorest HR-QoL, which was partially restored in powered wheelchair users, to levels comparable with more ambulant patients. However, the positive effect of wheelchair use became less substantial as patients get older. There was also marked variability in HR-QoL between diagnoses that was unrelated to physical disability. These findings provide evidence to guide care management discussions and highlight the importance of timely introduction of powered mobility.

There is growing evidence on safety and efficacy of exercise in neuromuscular diseases. We sought to establish the levels of exercise exposure for people living with NMD and its association with mobility levels and pain. A standardized questionnaire was used during clinical follow up consultations to categorise exposure to aerobic, strengthening and stretching exercise for 830 patients with 41 different NMD. The level of exercise exposure of people living with NMD in each type of exercise has been found to be limited and the proportion of patient being complying with WHO physical activity guidelines (8 %) was lower than previously reported. Stretching exercise was the most performed type of exercise (37 %), while resistance exercise was the least performed type of exercise (25 %) with aerobic exercise being performed by 33 %. Associations were found between exercise type and diagnosis, mobility status and pain all using chi square testing with significance level of less than 1 %. Patients with greater levels of mobility were more likely to participate in aerobic and resistance exercise and less likely to participate in stretching exercise. The presence of pain was associated with lack of participation in aerobic and resistance exercise but not stretching exercise. Levels of mobility and presence of pain have been identified as significant factors. It is critical to improve supported access and specific exercise guidelines for people living with NMD.

ABSTRACT Background Dysferlin plays a key role in cell membrane repair; its absence or malfunction in patients with dysferlin‐deficient limb girdle muscular dystrophy leads to muscle fibre death. Muscle magnetic resonance (MR) imaging allows non‐invasive and repeatable measurements that can report on pathological changes observed in dysferlinopathy patients (DP). We aimed to demonstrate the feasibility of utilising volume‐localised 23Na spectroscopy as a novel approach to characterise muscle Na+ content and biexponential T2* at rest, and dynamically post‐exercise, in patients with dysferlinopathy and in matched healthy controls. Methods Adult DP and age and sex matched healthy volunteers (HV) were recruited and scanned on a 3 T clinical MR scanner. Following baseline scans, participants performed physiotherapist‐guided isometric dorsiflexion contractions until tibialis anterior (TA) muscle exhaustion. Dynamic volume‐localised sodium‐23 (23Na)‐ and proton (1H)‐MR scans were acquired serially for 35 min post‐exercise. MR data were analysed to determine TA lipid content, change in TA sodium content, biexponential sodium T2* properties and TA water 1H T2. Results Ten DP (mean age ± standard deviation [SD]: 38.0 ± 10.8 years; 80% female) and 10 HV (mean age ± SD: 38.9 ± 11.5 years) were scanned. Baseline muscle water 1H T2 and sodium concentration were significantly higher in DP compared to matched controls (1H T2 DP [SD] = 33.8 [2.7] ms, 1H T2 HV = 29.3 [1.1] ms, p < 0.001; [23Na]DP = 36.2 [11.4] mM, [23Na]HV = 19.6 [3.1] mM, p < 0.001). 1H T2 and sodium content in healthy controls showed significant post‐exercise elevation with a slower time‐to‐peak for sodium content compared to 1H T2. 1H T2 and sodium content change post‐exercise was highly variable in the DP group. Notably, 23Na dynamics in one DP with normal muscle fat fraction were similar to HV. Biexponential 23Na T2* was measured at baseline in HV (T2*slow = 13.4 [2.3] ms, T2*fast = 2.2 [1.3] ms), and DP (T2*slow = 14.0 [1.5] ms and T2*fast = 1.0 [0.5] m). Equivalent measurements post‐exercise revealed an increase in the fraction of the slow‐relaxing component in HV (p < 0.05), consistent with oedematous changes. Conclusions Assessment of TA muscle fat fraction, 1H T2, sodium content and sodium T2* relaxation properties revealed differences at baseline and in post‐exercise dynamics between patients with dysferlinopathy and matched controls. Post‐exercise 23Na recovery dynamics followed a well‐defined time course in HV. Heterogeneous alterations in sodium content and MR relaxation properties in DP may reflect altered ion homeostasis associated with chronic muscle damage.

We investigated the comorbidities, associated factors, and the relationship between anthropometric measures and respiratory function and functional abilities in adults with Duchenne muscular dystrophy (DMD). This was a single-centre cross-sectional study in genetically diagnosed adults with DMD (>16 years old). Univariate and multivariate analyses identified factors associated with dysphagia, constipation, Body Mass Index (BMI), and weight. Regression analysis explored associations between BMI, weight, and respiratory/motor abilities. We included 112 individuals (23.4 ± 5.2 years old), glucocorticoid-treated 66.1 %. The comorbidities frequency was 61.6 % scoliosis (61.0 % of them had spinal surgery), 36.6 % dysphagia, 36.6 % constipation, and 27.8 % urinary conditions. The use of glucocorticoids delayed the time to spinal surgery. The univariate analysis revealed associations between dysphagia and constipation with age, lack of glucocorticoid treatment, and lower respiratory and motor function. In the multivariate analysis, impaired cough ability remained as the factor consistently linked to both conditions. Constipation associated with lower BMI and weight. BMI and weight positively correlated with respiratory parameters, but they did not associate with functional abilities. Glucocorticoids reduce the frequency of comorbidities in adults with DMD. The ability to cough can help identifying dysphagia and constipation. Lower BMI and weight in individuals with DMD with compromised respiratory function may suggest a higher calories requirement.

BACKGROUND AND PURPOSE:The transition to adult services, and subsequent glucocorticoid management, is critical in adults with Duchenne muscular dystrophy. This study aims (1) to describe treatment, functional abilities, respiratory and cardiac status during transition to adulthood and adult stages; and (2) to explore the association between glucocorticoid treatment after loss of ambulation (LOA) and late-stage clinical outcomes. METHODS:This was a retrospective single-centre study on individuals with Duchenne muscular dystrophy (≥16 years old) between 1986 and 2022. Logistic regression, Cox proportional hazards models and survival analyses were conducted utilizing data from clinical records. RESULTS:In all, 112 individuals were included. Mean age was 23.4 ± 5.2 years and mean follow-up was 18.5 ± 5.5 years. At last assessment, 47.2% were on glucocorticoids; the mean dose of prednisone was 0.38 ± 0.13 mg/kg/day and of deflazacort 0.43 ± 0.16 mg/kg/day. At age 16 years, motor function limitations included using a manual wheelchair (89.7%), standing (87.9%), transferring from a wheelchair (86.2%) and turning in bed (53.4%); 77.5% had a peak cough flow <270 L/min, 53.3% a forced vital capacity percentage of predicted <50% and 40.3% a left ventricular ejection fraction <50%. Glucocorticoids after LOA reduced the risk and delayed the time to difficulties balancing in the wheelchair, loss of hand to mouth function, forced vital capacity percentage of predicted <30% and forced vital capacity <1 L and were associated with lower frequency of left ventricular ejection fraction <50%, without differences between prednisone and deflazacort. Glucocorticoid dose did not differ by functional, respiratory or cardiac status. CONCLUSION:Glucocorticoids after LOA preserve late-stage functional abilities, respiratory and cardiac function. It is suggested using functional abilities, respiratory and cardiac status at transition stages for adult services planning.

Background and Objectives The prevalence and progression of respiratory muscle dysfunction in patients with limb girdle muscular dystrophies (LGMDs) has been only partially described to date. Most reports include cross-sectional data on a limited number of patients making it difficult to gain a wider perspective on respiratory involvement throughout the course of the disease and to compare the most prevalent LGMD subtypes. Methods We reviewed the results of spirometry studies collected longitudinally in our cohort of patients in routine clinical visits from 2002 to 2020 along with additional clinical and genetic data. A linear mixed model was used to investigate the factors associated with the progression of respiratory dysfunction. Results We followed up 156 patients with 5 different forms of LGMDs for a median of 8 years (range 1-25 years). Of them, 53 patients had pathogenic variants in the Capn3 gene, 47 patients in the Dysf gene, 24 patients in the Fkrp gene, 19 in the Ano5 gene, and 13 in one of the sarcoglycan genes (SCG). At baseline, 58 patients (37.1%) had a forced vital capacity percentage predicted (FVCpp) below 80%, while 14 patients (8.9%) had peak cough flow (PCF) values below 270 L/min. As a subgroup, FKRP was the group with a higher number of patients having FVC <80% and/or PCF <270 L/min at initial assessment (66%). We observed a progressive decline in FVCpp and PCF measurements over time, being age, use of wheelchair, and LGMD subtype independent factors associated with this decline. Fkrp and sarcoglycan patients had a quicker decline in their FVC (Kaplan-Meier curve, F test, p < 0.001 and p = 0.02, respectively). Only 7 of the 58 patients with low FVCpp values reported symptoms of respiratory dysfunction, which are commonly reported by patients with FVCpp below 50%-60%. The number of patients ventilated increased from 2 to 8 during follow-up. Discussion Respiratory dysfunction is a frequent complication of patients with LGMDs that needs to be carefully studied and has direct implications in the care offered in daily clinics. Respiratory dysfunction is associated with disease progression because it is especially seen in patients who are full-time wheelchair users, being more frequent in patients with mutations in the Fkrp and sarcoglycan genes.

Abstract Objective The North Star Assessment for limb-girdle type muscular dystrophies (NSAD), a clinician-reported outcome measure (ClinRO) of motor performance, was initially developed and validated for use in dysferlinopathy, an autosomal recessive form of limb-girdle muscular dystrophy (LGMD R2/2B). Recent developments in treatments for limb-girdle muscular dystrophies (LGMD) have highlighted the urgent need for disease-specific ClinROs. The purpose of this study was to understand the ability of the NSAD to quantify motor function across the broad spectrum of LGMD phenotypes. Methods Assessments of 130 individuals with LGMD evaluated by the physical therapy teams at Nationwide Children’s Hospital and the John Walton Muscular Dystrophy Research Centre were included in the analysis. NSAD, 100-m timed test (100MTT), and Performance of Upper Limb 2.0 assessment data were collected. Psychometric analysis with Rasch measurement methods was used to examine the NSAD for suitability and robustness by determining the extent to which the observed data “fit” with predictions of those ratings from the Rasch model. The NSAD score was correlated with the 100MTT and Performance of Upper Limb 2.0 assessment scores for external construct validity. Results The NSAD demonstrated a good spread of items covering a continuum of abilities across both individuals who had LGMD and were ambulatory and individuals who had LGMD and were weaker and nonambulatory. Items fit well with the construct measured, validating a summed total score. The NSAD had excellent interrater reliability [intraclass correlation coefficient (ICC) = 0.986, 95% CI = 0.981–0.991] and was highly correlated with the 100MTT walk/run velocity (Spearman rho correlation coefficient of rs(134) = .92). Conclusion Although LGMD subtypes may differ in age of onset, rate of progression, and patterns of muscle weakness, the overall impact of progressive muscle weakness on motor function is similar. The NSAD is a reliable and valid ClinRO of motor performance for individuals with LGMD and is suitable for use in clinical practice and research settings. Impact Recent developments in potential pharmacological treatments for LGMD have highlighted the urgent need for disease-specific outcome measures. Validated and meaningful outcome measures are necessary to capture disease presentation, to inform expected rates of progression, and as endpoints for measuring the response to interventions in clinical trials. The NSAD, a scale of motor performance for both individuals who have LGMD and are ambulatory and those who are nonambulatory, is suitable for use in clinical and research settings.

Our primary aim was to establish the prevalence of pain within limb girdle muscular dystrophy R9 (LGMDR9). As part of the Global FKRP Registry, patients are asked to complete the Short Form McGill Pain Questionnaire (SF-MPQ) annually. We used the results of this questionnaire to determine individuals' maximum pain score and total pain score and examined overall pain intensity and associations between pain intensity and LGMDR9 genotypes, age, and ambulatory status. We also considered the pain descriptors used and pain progression over time. Of the 502 patients, 87% reported current pain and 25% reported severe current pain. We found no associations in pain severity between the different genotypes of LGMDR9. However, we did find statistically significant associations between pain severity and ambulatory status and between our paediatric and adult populations. We found pain descriptors to be more common words that one may associate with non-neural pain, and we found that a significant number of individuals (69%) reported a fluctuating pain pattern over time. We concluded that pain should be considered a significant issue among individuals with LGMDR9 requiring management. Implications regarding assessment of pain for other degenerative diseases are discussed.