Spinal muscular atrophy (SMA) causes progressive muscle weakness. Respiratory muscle weakness results in progressive lung function decline, scoliosis, and chest wall deformities that predispose to respiratory failure. The efficacy of survival motor neuron protein-augmenting therapies on motor function in patients with SMA has been reported extensively, but how respiratory function changes under treatment remains underexplored. The aim of this study was to evaluate longitudinal changes in lung function and respiratory muscle strength during nusinersen treatment. We conducted a national retrospective observational cohort study at the University Medical Center Utrecht. We included children and adults with SMA types 1, 2, and 3a, who symptomatically started treatment with nusinersen between May 2017 and July 2025 as part of the Dutch reimbursement arrangements. We retrieved all available data on lung function and respiratory muscle strength collected during routine care. We analyzed the differences in the annual rates of change of lung function and respiratory muscle strength before and after nusinersen treatment initiation, using linear mixed-effects models. We included 120 patients (60 female individuals, 50%), of whom 78 were children (median age 7.3 years, range 0.7, 17.7) and 42 adults (median age 34.4 years, range 18.1, 76.1) at nusinersen initiation. In children, we observed a slower decline in lung function and a higher expiratory muscle strength after starting nusinersen. The absolute mean slope differences were 4.1% (95% CI 2.2-6.0) for forced vital capacity, 3.8% (95% CI 1.4-6.2) for forced expiratory volume in 1 second (FEV1), 4.2% (95% CI 0.3-8.0) for peak expiratory flow, and 5.1% (95% CI 0.7-7.6) for maximal expiratory pressure after initiation of nusinersen. In adults, we only observed a change in FEV1 after starting nusinersen. At treatment initiation, 30 patients required ventilatory support. None were able to discontinue ventilation, and 6 patients started noninvasive ventilation during treatment. This large retrospective cohort study found slower deterioration of lung function in symptomatic children during nusinersen treatment and improvements in respiratory muscle strength. In adult patients treated with nusinersen, we only observed a change in FEV1. This study provides Class IV evidence that nusinersen slows deterioration of lung function and improves respiratory muscle strength in symptomatic children with SMA.

Respiratory muscle weakness after stroke: An exploratory mediation analysis of associated factors.

Facioscapulohumeral dystrophy (FSHD) causes progressive muscle weakness, limits function and may lead to altered muscle co-contraction patterns to accomplish task performance and joint stability. In this study we examined time-changes in co-contraction of scapular and humeral muscles in persons with FSHD vs. healthy controls during reaching. Participants with FSHD (N=12, 56.0±14.5 yrs) and age-matched healthy controls (N=12, 55.8±13.1 yrs) performed ipsilateral and contralateral reaching to target. Surface electromyograms, kinematics and maximum voluntary force data were recorded. The co-contraction index CI1 was calculated as mean over the whole movement and further compared over time using statistical parametric mapping. During contralateral reaching, mean co-contraction of the trapezius ascendens-serratus anterior (TA-SA) muscle pair was higher in persons with FSHD vs. healthy controls (P=0.007, Delta CI1: +16, Hg: 1.15) and increased in the last phase of reaching (P<0.008, Delta CIi1: +30 to+48, normalized time: 75-100%), consistent with a pattern of high excitation of the TA muscle in FSHD participants. The increase in TA-SA co-contraction in FSHD during contralateral reaching is required to accomplish scapular stability and mobility, in the presence of muscle weakness when approaching the target. A higher co-contraction has implications for higher energy expenditure and affects joint loads.

Children and adolescents with chronic kidney disease (CKD) often exhibit reduced physical fitness due to physical inactivity, fatigue, and muscle weakness. Despite the exercise benefits, participation remains limited due to barriers such as limited access, inadequate resources, and poor motivation. The m-Health platform may provide an adaptable strategy to address these challenges. Hence, this study aimed to assess the feasibility of the m-Health-based exercise program among the pediatric CKD population. Thirty children and adolescents with CKD stages 3-5, aged 6-18years, were enrolled in a 4-week m-Health-based exercise program. Feasibility was evaluated through adherence, usability, satisfaction, and semi-structured telephonic interviews with participants and caregivers. Functional outcomes included the 6-min walk test (6-MWT) and hand grip strength (HGS). Adherence, usability, and satisfaction data were summarized using descriptive statistics. Thematic analysis was used to represent the qualitative data. Pre- and post-intervention 6-MWT and HGS values were compared using paired t-tests. Twenty-seven participants completed the study. Adherence to the m-Health exercise program was low, with 18.5% meeting the criteria. However, 51.8% reported excellent usability, and satisfaction was reported by 70.3% of parents and 62.9% of participants. Qualitative data highlighted three key aspects-alternative exercise practices, perceived exercise benefits, and multifaceted barriers. Participants demonstrated significant improvements in their functional outcomes post-intervention (6-MWT, 48.8m, p < 0.001; HGS, 0.7kg, p = 0.021). Despite low adherence, the m-Health-based exercise program served as a motivating stimulus for promoting physical activity and facilitating positive behavior change among children and adolescents with CKD. This study was registered with the Clinical Trials Registry of India (CTRI) on 20-11-2024 under registration number CTRI/2024/11/077131.

We applied an advanced diffusion model of Neurite Orientation Dispersion and Density Imaging (NODDI) to patients with acute traumatic cervical spinal cord injury and investigated the correlation of NODDI metrics with clinical symptoms and neurological prognosis. We enrolled 13 patients (mean age, 66.6 [48-80] years) who were admitted to our hospital with acute traumatic cervical spinal cord injury. Magnetic resonance imaging (MRI) diffusion-weighted images were acquired for 13 patients 6.4±1.7days post-injury and 10 healthy volunteers (mean age, 67.0 [53-79] years). Fractional anisotropy (FA), intracellular volume fraction (ICVF), isotropic volume fraction (ISO), and orientation dispersion index (ODI) were calculated at the level of the injury in patients and at C3/4, C4/5, and C5/6 in healthy volunteers. We assessed the American Spinal Injury Association International Standards Neurological Classification of Spinal Cord Injury (ASIA) motor score at injury onset and at 6months and 1year post-injury. Patients had significantly lower FA and higher ODI values than healthy volunteers. FA and ODI values were significantly correlated with the ASIA motor scores at onset and at 1year post-injury. ODI demonstrated the highest correlation with the ASIA motor score at 1year post-injury. Complete recovery of muscle weakness occurred in all six cases with ODI values <0.12, while muscle weakness persisted in six of seven cases with ODI values >0.12. ODI is a relevant predictor of motor function at 1year post-injury.

Biallelic intronic repeat expansions in the replication factor C subunit 1 (RFC1) gene are a common cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome and other late-onset ataxias. Recent evidence suggests a broader phenotypic spectrum. This systematic review and meta-analysis evaluated the prevalence and features of motor neuron, extrapyramidal, and cognitive involvement in RFC1 disease. We systematically searched PubMed, Scopus, and Web of Science for studies reporting motor neuron, extrapyramidal, or cognitive involvement in RFC1 disease from inception to March 2025. Eligible sources comprised research articles and case reports/series on genetically confirmed cases. Extracted data included publication details, study design, location, and individual participant data (IPD) covering demographics, signs, and symptoms. When needed, IPD were obtained from corresponding authors. Random-effects models were used to estimate pooled prevalences (95% CIs). Univariable mixed-effects logistic regression accounted for clustering within studies, with multivariable models including variables with p < 0.10 in univariate analyses. Of 729 articles, 37 were included in the systematic review and 36 (874 patients) in the proportion meta-analyses. For IPD meta-analysis, 30 cohorts provided data on 312 patients (mean age 66.91 ± 10.76 years; median disease duration 12 [interquartile range 7-18] years; 51.5% male). Upper and lower motor neuron signs were present in 18% (95% CI 6%-34%) and 11% (95% CI 2%-24%). Patients with the ACAGG pentanucleotide repeat expansion (biallelic or compound heterozygous with an AAGGG expansion) had higher odds of muscle atrophy (OR 17.90, p 0.001) and weakness (OR 11.69, p 0.001); men had an increased likelihood of muscle atrophy (OR 2.71, p = 0.038). The pooled prevalence of parkinsonism and cognitive impairment was 8% (95% CI 1%-18%) and 31% (95% CI 13%-53%), with prominent executive-attention deficits. Cognitive decline was more likely with longer disease duration (OR 1.04, p = 0.047) and in biallelic AAGGG carriers vs ACAGG (ACAGGexp: OR 0.13, p = 0.041). Motor neuron, extrapyramidal, and cognitive involvement may extend the phenotypic spectrum of RFC1 disease. Still, their true prevalence remains uncertain due to heterogeneity across studies, with potential overestimation from publication bias favoring atypical cases and underestimation when subtle signs are not systematically investigated. Larger multicenter cohorts with standardized assessments are needed to clarify their clinical relevance.

Novel LIPC-related recessive form of postural proprioceptive deficits in Brown Swiss cattle.

Which factors correlate with muscle strength capacity in people with patellofemoral pain? A systematic review with meta-analysis.

ABSTRACTIntroduction:Sarcopenia has been associated with an increased risk of falls in diversepopulations. Patients with end-stage renal disease (ESRD) undergoinghemodialysis (HD) have an increased prevalence of muscle weakness andwasting. The aim of this study was to investigate the association betweenparameters of sarcopenia and a history of falls in ESRD patients on HD.Methods:A cross-sectional study was utilized to assess 111 participants with ESRD onHD (54 ± 15.6 years; 59.5% men). Sarcopenia was defined by low musclestrength (handgrip dynamometry) and low muscle mass (bioelectricalimpedance). History of falls was self-reported. Bivariate analyses wereperformed, and a multivariate logistic regression model was used to assessthe association between sarcopenia and falls while adjusting forconfounders.Results:In the multivariate analysis, sarcopenia was not independently associatedwith a history of falls (OR = 1.73; p = 0.40). However,advanced age (OR = 1.04 per year; p = 0.03) and a historyof stroke (OR = 6.07; p = 0.05) were identified assignificant independent predictors of falls.Conclusion:History of falls was not independently associated with muscle strength ormass in ESRD patients on HD. Future longitudinal studies are needed toinvestigate other factors associated with this outcome.

Sarcopenia has been associated with an increased risk of falls in diverse populations. Patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) have an increased prevalence of muscle weakness and wasting. The aim of this study was to investigate the association between parameters of sarcopenia and a history of falls in ESRD patients on HD. A cross-sectional study was utilized to assess 111 participants with ESRD on HD (54 ± 15.6 years; 59.5% men). Sarcopenia was defined by low muscle strength (handgrip dynamometry) and low muscle mass (bioelectrical impedance). History of falls was self-reported. Bivariate analyses were performed, and a multivariate logistic regression model was used to assess the association between sarcopenia and falls while adjusting for confounders. In the multivariate analysis, sarcopenia was not independently associated with a history of falls (OR = 1.73; p = 0.40). However, advanced age (OR = 1.04 per year; p = 0.03) and a history of stroke (OR = 6.07; p = 0.05) were identified as significant independent predictors of falls. History of falls was not independently associated with muscle strength or mass in ESRD patients on HD. Future longitudinal studies are needed to investigate other factors associated with this outcome.

Patients undergoing hemodialysis often exhibit inspiratory muscle weakness, which has been associated with a reduced health-related quality of life (HRQoL). However, the extent to which this relationship is mediated by cardiorespiratory fitness remains unclear. To evaluate the mediating effect of cardiorespiratory fitness on the association between inspiratory muscle strength and HRQoL in hemodialysis patients. Cross-sectional study in which hemodialysis patients underwent assessment of inspiratory muscle strength by measuring Maximum Inspiratory Pressure (MIP), cardiorespiratory fitness by the Incremental Shuttle Walk Test (ISWT), and HRQoL by measuring the physical, mental, and general health component summary scores of the Kidney Disease Quality of Life questionnaire (KDQOL-SF). Simple mediation analyses were performed using the PROCESS macro (version 3.5) for SPSS, with HRQoL as the dependent variable, MIP as the independent variable, and cardiorespiratory fitness as the mediating variable. 64 individuals, 67.2% male, with a mean age of 48.1 years (95%CI 44.3-51.9), were evaluated. Cardiorespiratory fitness exerted a partial mediating effect on the association between MIP and PCS (β = 0.14; 95%CI: 0.02-0.27), resulting in a 6% reduction in PCS variance explained by MIP (6% of R2). The mediating proportion was 32.5%. There was no association between MIP and the mental component, and cardiorespiratory fitness did not mediate the relationship between MIP and the general component of HRQoL (β = 0.13; p = 0.350). In the sample studied, the association between inspiratory muscle strength and the physical aspects of HRQoL is partially mediated by cardiorespiratory fitness. However, this mediating effect was not observed for the mental or general aspects of HRQoL.

Incomplete recovery with persistent muscle weakness is frequently observed following Achilles tendon rupture. The mechanisms for this weakness remain unclear, but tendon elongation has been suggested as a contributing factor. The aim of this study was to compare tendon and muscle morphology in high- and low-functioning patients more than 2 years after non-surgical treatment of a total Achilles tendon rupture. Forty-six patients underwent screening, including a standardized heel-rise work test on both legs. Based on this test, a heel-rise index (HRI) for total muscle work, categorized 29 patients into a low- (HRI < 33%) or high-functioning (HRI > 67%) group. Both groups underwent bilateral magnetic resonance imaging to assess tendon and muscle morphology, and the main variable was tendon elongation. High-functioning patients were on average 13 years younger than the low-functioning patients (p < 0.001). Free tendon length was longer on the injured side in both groups, 3.59 and 5.19 cm in the high- and low-functioning group (p = 0.053). Tendon cross-sectional area was significantly larger in the high-functioning group compared to the low-functioning group (383% vs. 256% after normalization to the uninjured side, p = 0.005). The soleus muscle had notable differences between the groups, as low-functioning patients had a smaller mediolateral diameter (p = 0.002), a more pronounced muscle length difference (p = 0.009) and a higher atrophy grading. Additionally, there were significant correlations between age, HRI and tendon size. Free tendon length after rupture may play a role in muscle weakness. However, tendon elongation does not necessarily lead to low function, as it was also evident in the high-functioning group. These findings may be important, as they suggest that tendon elongation is not the sole determinant of functional outcome and that other factors may contribute to muscle performance after rupture. Further research is needed on the role of age in muscle function following Achilles tendon ruptures. Level III.

BACKGROUND Legionella pneumophila is a common and often severe cause of community-acquired pneumonia. Infection with this organism is also known to be associated with a wide range of extrapulmonary manifestations, such as neurologic deficits, hyponatremia, acute kidney injury, and elevated liver enzymes. Other complications, such as rhabdomyolysis and hypertriglyceridemia, are rare. CASE REPORT A rare presentation of Legionella infection was observed in a 34-year-old man, characterized by severe rhabdomyolysis, acute kidney injury (AKI), and hypertriglyceridemia. The patient presented with severe muscle cramps, weakness, dark urine, diarrhea, fever, and chills. Initial laboratory evaluations revealed significantly elevated creatine kinase (163 600 U/L), creatinine (7.79 mg/dL), and transaminases (AST 1179 U/L, ALT 184 U/L), in conjunction with hyponatremia. A chest X-ray and computed tomography (CT) showed left basilar pneumonia, and a positive Legionella urine antigen test confirmed the diagnosis. A fasting lipid panel also revealed profound hypertriglyceridemia (1173 mg/dL). The patient's only identified risk factor for Legionella infection was vaping. Despite aggressive therapeutic interventions, including intravenous fluids and azithromycin, AKI progressed, necessitating hemodialysis. The patient also received treatment for alcohol withdrawal and severe hypertension. While creatine kinase, AST, and ALT levels gradually decreased, BUN and creatinine remained elevated at discharge, with ongoing plans for outpatient hemodialysis. CONCLUSIONS Legionella pneumonia can present with a diverse array of extrapulmonary manifestations. This case illustrates the diverse and potentially life-threatening systemic complications associated with Legionella infection.

Amyotrophic lateral sclerosis (ALS) is characterised by progressive degeneration of motor neurons, resulting in muscle weakness and atrophy. This neuronal loss is partially compensated for by the collateral sprouting of surviving motor neurons, leading to the formation of enlarged motor units (MUs). These MU adaptations, together with hyperexcitability and altered descending messages from the brain, lead to altered characteristics of the MU action potential shape and discharge pattern, that can be captured using high-density surface electromyography (HDsEMG). The aim of this review is to survey all available literature, investigating how HDsEMG has been used in ALS, and highlight differences in methods and outcomes to allow comparison between studies. A systematic literature search was conducted using four databases (PubMed, Scopus, IEEE Xplore, and Academic Search Ultimate) to identify studies employing HDsEMG in individuals diagnosed with ALS. Eligible studies were reviewed to examine experimental protocols, hardware and software configurations and reported outcome measures. Out of 168 identified articles, 26 were included in this review. High heterogeneity was observed in recording methods, analysis, and reporting strategies. Based on measurable features of MU behaviour and morphology, the outcomes reported in the studies were grouped into five main categories: fasciculations, MU properties, MU discharge characteristics, multiple discharges and number of MUs. HDsEMG represents a promising non-invasive technique that allows for repeated, longitudinal measurements as well as the detection of multiple MUs and their individual analysis, the potential of which has not been fully explored. HDsEMG has a strong potential for clinical use in ALS, but its application should first be based on a clear understanding of disease pathophysiology. The findings of this review highlight the urgent need for a consensus on standardised protocols and reporting practices for the application of HDsEMG in ALS research, along with the development of methods that can sensitively indicate disease-specific physiological changes to improve comparability, reproducibility. This understanding will improve how HDsEMG findings are interpreted and support the translation of HDsEMG into a diagnostic tool.

Idiopathic inflammatory myopathies (IIM) have historically been considered to cause painless muscle weakness. However, recent studies suggest that pain can be an important symptom for patients with IIM. This study aims to examine the discussions related to myositis and pain on Reddit to understand its frequency and impact. Reddit posts from Academic Torrents were searched for myositis-related terms using the Pushshift archive. A two-step cleaning process was used, including a large language model-based classification, to retain posts describing suspected or confirmed IIM. Posts were analyzed for pain descriptors and anatomical regions. A semantic network of the top 500 pain posts was built to map connections between descriptors, body regions and experiences. The dataset included 1,529 IIM-related Reddit posts written by 968 unique authors. Pain-related terms were present in 63.0% of the posts. Pain was described using qualifiers reflecting chronicity and severity, including "chronic", "constant" and "severe" pain. Muscle was the most frequently mentioned body region (18.5%) in pain-related posts. Semantic network analysis showed nine distinct communities, showing that pain-related discussions were closely integrated with core disease concepts such as myositis, muscle involvement, and weakness. Additional clusters reflected dermatomyositis-related skin features, sensory and neuropathic pain experiences, and comorbid autoimmune conditions. Pain is a common topic among people discussing myositis on Reddit. Results suggest pain as a prevalent symptom and highlight the need for more research to understand the pain to help provide more effective strategies for management.

Doxorubicin (DOX) is a highly effective and widely used chemotherapeutic agent employed to treat various types of cancer. Unfortunately, DOX also has some undesirable and off-target effects, particularly debilitating muscle weakness and fatigue. The mechanism behind this DOX-induced skeletal myotoxicity (DISM) remains unclear. Here, we show that acute DOX exposure, at clinically relevant concentrations, impairs isometric force production and accelerates fatigue in ex vivo murine flexor digitorum brevis (FDB) muscles. Mechanistically, we found that DOX increases the open probability of single RyR1 and disrupts calcium (Ca2+)-dependent inactivation (CDI). This results in a persistent sarcoplasmic reticulum (SR) Ca2+ leak, elevated basal cytosolic Ca2+, and abnormal Ca2+ release during action potentials. This abnormal intracellular Ca2+ handling ultimately leads to increased cellular reactive oxygen species (ROS) production, which, in turn, exacerbates the functional instability of RyR1. Interestingly, the cytosolic basal Ca2+ elevation precedes ROS generation, suggesting that it initiates a destructive cross-talk between Ca2+ dysregulation and oxidative stress. Further, our study suggests that DOX disrupts the interaction between RyR1 and FKBP12 and that pharmacological stabilization of this complex with the novel triazole compounds MP-001 and MP-034 normalizes RyR1 function, Ca2+ and ROS homeostasis, as well as muscle force and fatigue resistance. Our findings indicate that DISM is initiated by DOX destabilization of the RyR1-FKBP12 complex (abnormal SR Ca2+ leak) and then exacerbated by the Ca-ROS vicious cycle. Limiting RyR1-mediated Ca2+ leak with MP compounds represents a promising therapeutic strategy for anti-DISM, aiming to normalize muscle function in patients undergoing DOX chemotherapy.

Hyperthyroidism is a prevalent endocrine disorder that can lead to severe multisystem complications, including atrial fibrillation (AF), thyrotoxic periodic paralysis (TPP), and thyroid storm (TS). This review discusses the pathophysiology, clinical presentation, and management challenges of these complications through illustrative clinical cases. AF is the most common cardiovascular manifestation, with restoration of euthyroidism and rate control being central to treatment. TPP presents with transient muscle weakness due to hypokalemia from intracellular potassium shift, requiring cautious potassium supplementation and hyperthyroidism control. TS is a life-threatening endocrine emergency characterized by multisystem decompensation, necessitating prompt multimodal therapy including antithyroid drugs, beta-blockers, corticosteroids, and supportive care. Thus, early recognition and tailored management remain the cornerstones of successful treatment for these severe complications of hyperthyroidism.

The pericapsular nerve group (PENG) block is increasingly used for analgesia in hip-related procedures. However, the optimal local anesthetic volume remains unclear. This randomized non-inferiority trial aimed to compare the analgesic efficacy of 10 mL versus 20 mL PENG block after total hip arthroplasty, hypothesizing that the lower volume would provide non-inferior analgesia. In this single-center randomized controlled non-inferiority trial, 50 patients undergoing hip replacement surgery received an ultrasound-guided PENG block with 0.25% bupivacaine, either 20 mL (n = 25) or 10 mL (n = 25). Postoperative analgesia was provided using morphine patient-controlled analgesia. Pain scores at rest and during movement were assessed at predefined time points up to 24h postoperatively. The primary outcome was the NRS pain score at rest 1h after surgery. Secondary outcomes included opioid consumption, quadriceps muscle strength, postoperative nausea and vomiting, and patient satisfaction. There were no significant differences between groups in opioid-related side effects, quadriceps muscle weakness, patient satisfaction, or length of hospital stay. Non-inferiority analysis demonstrated that the median differences in NRS scores between groups remained within the predefined non-inferiority margin of 1 NRS point at all assessment time points. Non-inferiority of the 10 mL PENG block was confirmed for the primary outcome. A 10 mL PENG block provides postoperative analgesia non-inferior to a 20 mL volume without increasing opioid consumption or motor weakness, suggesting that lower volumes may be sufficient and potentially safer after total hip arthroplasty. ClinicalTrials.gov, NCT06166602. Registered on December 04, 2023. Retrospectively registered (study start date July 30, 2023).

Duchenne Muscular Dystrophy (DMD) is a progressive neuromuscular disease leading to muscle weakness and impaired quality of life. Standard clinical methods for assessing motor-functional changes have limitations, such as poor sensitivity in detecting early alterations. This study proposes the use of wearable inertial sensors for the objective monitoring of trunk and pelvic biomechanics. Wearable inertial sensors were used to record accelerations and angular velocities during the Six-Minute Walk Test (6MWT) in a pediatric patient with DMD. Spatio-temporal gait parameters, trunk and pelvis harmonic ratios, and 3D angular range of motion were analyzed. Preliminary results demonstrate the feasibility of the proposed method. The objective quantification of spatio-temporal gait parameters and trunk and pelvic biomechanics was possible. The patient showed an increased range of motion of the trunk (total average sagittal ROM = 12.27°, total average frontal ROM = 10.80°, total average transverse ROM = 11.38°) and pelvis (total average sagittal ROM = 9.36°, total average frontal ROM = 18.17°, total average transverse ROM = 22.27°) compared to normative literature values. This preliminary study indicates that wearable inertial sensors offer objective insights into trunk and pelvic biomechanics in DMD patients during the 6MWT. This approach may enhance disease monitoring and aid in developing more effective therapies.

Exercise-induced muscle injury in Duchenne muscular dystrophy: impaired mitophagy and altered PINK1-PARKIN pathway in mdx mice.