Muscle Weakness Research Articles

Comparative Analysis of Respiratory and Functional Outcomes in Children Post-Fontan Procedure Versus Healthy Peers.

Studies have shown that respiratory muscle training enhances functional capacity and pulmonary function in Fontan patients. However, diaphragm muscle characteristics in Fontan children have not been fully elucidated. The aim of this study was to compare respiratory function, maximal and submaximal functional capacities, and quality of life, as well as to assess diaphragm mobility and thickness, between Fontan patients aged 8 to 12years and healthy individuals. This cross-sectional study included 45 children-27 Fontan patients, Fontan Group (FG) and 18 healthy control Group (CG) subjects. Different examinations were performed: spirometry was used to analyze pulmonary volume and capacity; manovacuometry was used to determine respiratory muscle strength; chest ultrasound was used to determine diaphragm muscle characteristics; cardiopulmonary exercise and the six-minute walk test (6MWT) wereused to determine functional capacity; the AUQEI questionnaire was used to determine quality of life. Descriptive analysis and intergroup comparisons were performed for all the data. Compared with the CG, the FG exhibited impaired pulmonary function and reduced functional capacity. Significant differences in median values were noted for forced expiratory volume in one second (FEV1): 2.39L/min, p = 0.002; forced vital capacity (FVC): 1.73 vs. 3.06L/min, p = 0.002; maximal inspiratory pressure: - 73 vs. - 117cmH2O, p = 0.007; absolute peak VO2: 1.09 vs. 1.51L/min, p < 0.001; relative peak VO2: 31.9 vs. 42.5mL/kg/min, p = 0.003; and 6MWT distance: 420 vs. 586m, p < 0.001. Diaphragmatic thickness, mobility and quality of life were similar between the groups. Despite the reduced functional capacity, impaired pulmonary volume and capacity, and respiratory muscle weakness of the FG compared to those of the CG, the diaphragm characteristics and quality of life were similar between the groups.

Musculoskeletal, Pulmonary, and Cardiovascular COVID-19 Sequelae in the Context of Firefighter Occupational Health: A Narrative Review.

For most individuals infected with SARS-CoV-2, the acute illness resolves completely. However, for millions of people, symptoms or sequelae from COVID-19 recur or persist for months to years after infection. Post-COVID-19 sequelae are wide-ranging, often affecting the musculoskeletal, pulmonary, and cardiovascular systems. All who experience post-COVID-19 sequelae face significant challenges navigating home and work life. Occupations such as firefighting, however, are of particular concern given the strenuous nature of a job that relies on a healthy musculoskeletal, pulmonary, and cardiovascular system. Research has documented significant musculoskeletal impairment (including muscle weakness, pain, and fatigue), respiratory dysfunction (including reduced lung function, interstitial disease, and diffusion abnormalities), cardiovascular conditions (including cardiac events, ischemic disease, dysrhythmias, and infectious diseases), and diminished cardiorespiratory fitness that continues for months to years in some individuals. These persistent post-COVID-19 conditions may affect a firefighter's ability to return to work, function at full capacity while at work, and potentially compromise firefighter health and public safety. This review, therefore, explores musculoskeletal, pulmonary, and cardiovascular sequelae post-COVID-19 and the impact of these sequelae on firefighter health and occupational readiness.

Hand dynamometer and clinical tests to evaluate the recovery of neuromuscular conductance in atracurium versus rocuronium in patients undergoing laparoscopic surgery

Background. Postoperative muscle weakness is not unusual and may be related to postoperative complications in patients after general anesthesia. However, the clinical practice of neuromuscular conductance monitoring is uncommon among anesthesiologists.The objective was to evaluate the rate of neuromuscular recovery after atracurium and rocuronium and to determine the numerical value of grip strength using a hand dynamometer, indicating the safety of transferring a patient from the postoperative ward.study design. A prospective, observational, clinical comparison study.Materials and Methods. Upon proper authorization and approval from the local ethics committee, patients referred for laparoscopic surgery, 120 patients of the American Society of Anesthesiology (ASA) physical status I &amp;II between ages 20–49 years were randomly assigned into 2 groups of 60 each. Group I received a single atracurium dose of 0.5mg/kg of ideal body weight and Group II patients received a single rocuronium dose of 0.6mg/kg of ideal body weight. Parameters such as modified Alderete score (MAS), grip strength, and sustained head and leg lift for five seconds were compared in both groups 50 minutes after giving the reversal agent at 10-minute intervals.Results. Postoperative muscle recovery (grip strength) was faster in the atracurium group than the rocuronium group, with a p-value of 0.042 at 20 minutes, and 0.0000 for 30, 40, and 50 minutes after giving the reversal agent. The time to obtain a modified Alderete score (MAS) &gt; 8 scores was statistically insignificant with a p-value of 0.335. Positive clinical test for sustained head lift for 5 seconds was statistically insignificant within a majority of the time, except in the 20 minutes, most of the cases in the atracurium group were able to sustain head elevation for 5 seconds with a p-value of 0.021. In the 10 &amp;20 minutes, most cases in the atracurium group could sustain leg elevation for 5 seconds with a p-value of 0.015 and 0.014 respectively. However, most cases in both groups could sustain head and leg elevation for 5 seconds in the 30 minutes after giving a reversal agent.Conclusion. Compared to rocuronium, atracurium has been associated with faster muscle recovery after a single tracheal intubation dose for a short surgery. This was determined by utilizing an electronic hand dynamometer to measure grip strength. 42% grip strength from baseline might be applicable for safe discharge from the recovery room. A hand dynamometer assessment revealed more post-operative muscle weakening than a clinical evaluation.

Role of Magnesium in Skeletal Muscle Health and Neuromuscular Diseases: A Scoping Review

Magnesium (Mg) is a vital element for various metabolic and physiological functions in the human body, including its crucial role in skeletal muscle health. Hypomagnesaemia is frequently reported in many muscle diseases, and it also seems to contribute to the pathogenesis of skeletal muscle impairment in patients with neuromuscular diseases. The aim of this scoping review is to analyze the role of Mg in skeletal muscle, particularly its biological effects on muscle tissue in neuromuscular diseases (NMDs) in terms of biological effects and clinical implications. This scoping review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. From the 305 studies identified, 20 studies were included: 4 preclinical and 16 clinical studies. Preclinical research has demonstrated that Mg plays a critical role in modulating pathways affecting skeletal muscle homeostasis and oxidative stress in muscles. Clinical studies have shown that Mg supplementation can improve muscle mass, respiratory muscle strength, and exercise recovery and reduce muscle soreness and inflammation in athletes and patients with various conditions. Despite the significant role of Mg in muscle health, there is a lack of research on Mg supplementation in NMDs. Given the potential similarities in pathogenic mechanisms between NMDs and Mg deficiency, further studies on the effects of Mg supplementation in NMDs are warranted. Overall, maintaining optimal Mg levels through dietary intake or supplementation may have important implications for improving muscle health and function, particularly in conditions associated with muscle weakness and atrophy.

Tractography analysis results of the trigeminus nerve, which contains fibers responsible for proprioception sensation and motor control in Adolescent Idiopathic Scoliosis.

Cross-sectional Study. It is not yet clear whether the loss of proprioceptive sensation and muscle weakness seen in adolescent idiopathic scoliosis (AIS) is the result of central nervous system dysfunction or secondary to spinal deformity. In our study, in order to find an answer to this question, we examined the microarchitecture of the nervus trigeminus, which is least affected by spinal deformity and contains both proprioceptive sensory and motor fibers. In this single-center, cross-sectional cohort study, 40 Lenke Type 3 (27 female, 13 male) AIS patients and 40 (25 female, 15 male) healthy individuals between the ages of 10-18 years. Tractography of the nervus trigenimus was performed using the "DSI Studio" program. The volumes of the targeted musculus pterygoideus lateralis and musculus pterygoideus medialis were measured using the Insight Segmentation and Registration Tool Kit (ITK -SNAP) program. The data were evaluated using the Statistical Package for the Social Sciences 22.0 program for Windows. There was no significant difference between the two groups in terms of baseline characteristics (p˃0.05). Left nervus trigeminus fiber number and fiber ratio were significantly higher in the control group compared to the scoliosis group p < 0.05. Right and left lateral pterygoid muscle showed lower volume and volume percentage in the scoliosis group compared to the control group (p < 0.05). According to the study data, proprioceptive sensory and motor control dysfunction in AIS is predicted to develop independently of spinal deformity.

A qualitative exploratory study into medical, nursing and allied health professional experiences of elective withdrawal of non-invasive ventilation in a motor neurone disease cohort.

With absence of a cure, the mainstay of management for patients with motor neurone disease (MND) is holistic supportive care and symptom control. Non-invasive ventilation (NIV) can provide relief from distressing dyspnoea which often accompanies progressive respiratory muscle weakness. Some patients using NIV will become dependent on it, with a small proportion of these patients going on to request withdrawal. Despite being legal in the UK, elective withdrawal of NIV can be emotionally and ethically challenging for the staff involved. To guide the process of symptom-controlled withdrawal, in 2015 the Association for Palliative Medicine (APM) released clinical guidance. The aim of this study is to explore the experiences of the multi-disciplinary team (MDT) involved in elective withdrawal of NIV in an MND cohort following the publication of this guidance. A qualitative, semi-structured interview study of eight NHS qualified staff members (three Doctors, four Nurses, one Allied Health Professional). Clinicians were asked questions relating to their experiences of the withdrawals. After full transcription, data was analysed thematically. Four main themes were identified, offering insight into how the withdrawals affected staff's well-being and summarised via an 'enablers and barriers' model. The setting was important, as was the depth and longevity of the clinician's investment in the patient. Positive influences on staff's well-being arose from the sense of fulfilling the patient's wishes, good teamwork, presence of an experienced clinician and awareness of the APM (2015) Guidance. Conversely, barriers to well-being were expressed through the unpredictability of each scenario, moral and ethical uncertainties, external pressures on time, mismatched expectations, poor communication and the emotional intensity of the act. Elective withdrawal is highly emotive, simultaneously positively and negatively influencing staff well-being. By addressing the potential mitigating factors, the overall impact on staff's mental health and well-being maybe improved and thus, subsequently, patient care.

Lower limb acute onset muscle pain: what do we have to look for? A case of isolated rupture of the rectus femoris.

Acute muscle pain is muscle soreness that occurs during or within 24 hours of strenuous activity. Possible causes of acute muscle pain include localized muscle trauma, muscle tear, contusion with acute hemorrhage, or acute compartment syndrome. Isolated ruptures of the rectus femoris muscle are rare clinical conditions that result from excessive muscle strain following an abrupt contraction, incorrect movement, or sudden snap that exceeds the physiological limit of strain that the muscle can withstand. To date, there are few published reports evaluating the results of non-invasive treatment of such injuries. Herein, we report an unusual case of isolated distal rectus femoris tear in a 46-year-old female patient with no risk factors, who initially presented with extensor muscle weakness and pain and was treated conservatively with functional rest, physiotherapy, and cryotherapy.

Evaluation of the Role of Tanshinone I in an In Vitro System of Charcot-Marie-Tooth Disease Type 2N.

Charcot-Marie-Tooth disease type 2N (CMT2N) is an inherited nerve disorder caused by mutations in the alanyl-tRNA synthetase (AlaRS) gene, resulting in muscle weakness and sensory issues. Currently, there is no cure for CMT2N. Here, we found that all five AlaRS mutations in the aminoacylation domain can interact with neuropilin-1 (Nrp1), which is consistent with our previous findings. Interestingly, three of these mutations did not affect alanine activation activity. We then performed a high-throughput screen of 2000 small molecules targeting the prevalent R329H mutant. Using thermal stability assays (TSA), biolayer interferometry (BLI), ATP consumption, and proteolysis assays, we identified Tanshinone I as a compound that binds to and modifies the conformation of the R329H mutant and other CMT-related AlaRS mutants interacting with Nrp1. Molecular docking and dynamic simulation studies further clarified Tanshinone I's binding mode, indicating its potential against various AlaRS mutants. Furthermore, co-immunoprecipitation (Co-IP) and pull-down assays showed that Tanshinone I significantly reduces the binding of AlaRS mutants to Nrp1. Collectively, these findings suggest that Tanshinone I, by altering the conformation of mutant proteins, disrupts the pathological interaction between AlaRS CMT mutants and Nrp1, potentially restoring normal Nrp1 function. This makes Tanshinone I a promising therapeutic candidate for CMT2N.

An Orai1 gain-of-function tubular aggregate myopathy mouse model phenocopies key features of the human disease.

Tubular aggregate myopathy (TAM) is a heritable myopathy primarily characterized by progressive muscle weakness, elevated levels of creatine kinase (CK), hypocalcemia, exercise intolerance, and the presence of tubular aggregates (TAs). Here, we generated a knock-in mouse model based on a human gain-of-function mutation which results in a severe, early-onset form of TAM, by inducing a glycine-to-serine point mutation in the ORAI1 pore (Orai1G100S/+ or GS mice). By 8 months of age, GS mice exhibited significant muscle weakness, exercise intolerance, elevated CK levels, hypocalcemia, and robust TA presence. Unexpectedly, constitutive Ca2+ entry in mutant mice was observed in muscle only during early development and was abolished in adult skeletal muscle, partly due to reduced ORAI1 expression. Consistent with proteomic results, significant mitochondrial damage and dysfunction was observed in skeletal muscle of GS mice. Thus, GS mice represent a powerful model for investigation of the pathophysiological mechanisms that underlie key TAM symptoms, as well as those compensatory responses that limit the damaging effects of uncontrolled ORAI1-mediated Ca2+ influx.

Persistent Fatigue, Weakness, and Aberrant Muscle Mitochondria in Survivors of Critical COVID-19.

Persistent skeletal muscle dysfunction in survivors of critical illness due to acute respiratory failure is common, but biological data elucidating underlying mechanisms are limited. The objective of this study was to elucidate the prevalence of skeletal muscle weakness and fatigue in survivors of critical illness due to COVID-19 and determine if cellular changes associate with persistent skeletal muscle dysfunction. A prospective observational study in two phases: 1) survivors of critical COVID-19 participating in physical outcome measures while attending an ICU Recovery Clinic at short-term follow-up and 2) a nested cohort of patients performed comprehensive muscle and physical function assessments with a muscle biopsy; data were compared with non-COVID controls. ICU Recovery Clinic and clinical laboratory. Survivors of critical COVID-19 and non-COVID controls. None. One hundred twenty patients with a median of 56 years old (interquartile range [IQR], 42-65 yr old), 43% female, and 33% individuals of underrepresented race attended follow-up 44 ± 17 days after discharge. Patients had a median Acute Physiology and Chronic Health Evaluation-II score of 24.0 (IQR, 16-29) and 98 patients (82%) required mechanical ventilation with a median duration of 14 days (IQR, 9-21 d). At short-term follow-up significant physical dysfunction was observed with 93% of patients reporting generalized fatigue and performing mean 218 ± 151 meters on 6-minute walk test (45% ± 30% of predicted). Eleven patients from this group agreed to participate in long-term assessment and muscle biopsy occurring a mean 267 ± 98 days after discharge. Muscle tissue from COVID exhibited a greater abundance of M2-like macrophages and satellite cells and lower activity of mitochondrial complex II and complex IV compared with controls. Our findings suggest that aberrant repair and altered mitochondrial activity in skeletal muscle associates with long-term impairments in patients surviving an ICU admission for COVID-19.

Preservation of masseter muscle until the end stage in the SOD1G93A mouse model for ALS

Amyotrophic lateral sclerosis (ALS) progressively impairs motor neurons, leading to muscle weakness and loss of voluntary muscle control. This study compared the effects of SOD1 mutation on masticatory and limb muscles from disease onset to death in ALS model mice. Notably, limb muscles begin to atrophy soon after ALS-like phenotype appear, whereas masticatory muscles maintain their volume and function in later stages. Our analysis showed that, unlike limb muscles, masticatory muscles retain their normal structure and cell makeup throughout most of the disease course. We found an increase in the number of muscle satellite cells (SCs), which are essential for muscle repair, in masticatory muscles. In addition, we observed no reduction in the number of muscle nuclei and no muscle fibre-type switching in masticatory muscles. This indicates that masticatory muscles have a higher resistance to ALS-related damage than limb muscles, likely because of differences in cell composition and repair mechanisms. Understanding why masticatory muscles are less affected by ALS could lead to the development of new treatments. This study highlights the importance of studying different muscle groups in ALS to clarify disease aetiology and mechanisms.

Dysphagia and Muscle Weakness Secondary to Botulinum Toxin Type A Treatment of Cervical Dystonia: A Drug Class Analysis of Prescribing Information.

The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R2) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R2 = 0.74; muscle weakness = 0.096, R2 = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY®, Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia.

Biomechanical significance of intervertebral discs on growthplate stresses in scoliotic trunks following unilateral muscle weakening: A hybrid approach of finite element and musculoskeletal modeling.

This study aimed to ascertain the relevance of intervertebral discs (IVD) in the stress distribution on growthplates (GPs) of a trunk model with adolescent idiopathic scoliosis (AIS) following a unilateral weakening of muscles. A thoracolumbar spine finite element (FE) model of a young female healthy and an AIS spine comprising GPs linked to the T12 through sacrum vertebrae. Two scenarios of including (FEI) and excluding (FEE) IVDs were considered. Then, using optimization-driven musculoskeletal models of the AIS and healthy trunks, the FE models were examined under subject-specific muscle forces and gravity loads. Results of this study demonstrate that when IVDs included in the FE model, an increase, ranging from 0.2 to 1.7 MPa, with the highest value occurring at the apex of the AIS model, in the von Mises stresses in the GPs. The ratio of 1.5 was found for the maximum von-Mises stress value on the most tilted GP in the FEI over the FEE model. Unilateral paralysis of muscles caused a reduction of 50% and 63% in the von Mises stress ratio of the concave-over-convex side of the most tilted GP in the FEI and FEE models of the AIS spine with healthy muscles, respectively. The intradiscal pressures, found for FEE and FEI models, assented to recent in-vivo investigations. Nonetheless, employing IVDs in the simulations provides an indispensable tool to anticipate the effects of neuromuscular disorders on GP stresses in an AIS spine and predict deformity progression during growth.

Modified tai chi movement training based on sEMG and movement analysis on improving upper extremities motor function: a protocol for a clinical randomised controlled trial

IntroductionStroke survivors often face motor dysfunction, increasing fall risk. Lower extremity muscle weakness is a key factor affecting walking ability. Tai chi (TC) has been shown to improve muscle strength...

Video head impulse gain is impaired in myotonic dystrophy types 1 and 2.

This study was undertaken to examine vestibulo-ocular reflex (VOR) characteristics in myotonic dystrophy type 1 (DM1) and type 2 (DM2) using video head impulse testing (vHIT). VOR gain, refixation saccade prevalence, first saccade amplitude, onset latency, peak velocity, and duration were compared in DM1, DM2, age-matched normal controls, and patients with peripheral and central vestibulopathies. Fifty percent of DM1 and 37.5% of DM2 patients demonstrated reduced VOR gain. Refixation saccade prevalence for horizontal canal (HC) and posterior canal (PC) was significantly higher in DM1 (101 ± 42%, 82 ± 47%) and DM2 (70 ± 45%, 61 ± 38%) compared to controls (40 ± 28% and 43 ± 33%, p < 0.05). The first saccade amplitudes and peak velocities were higher in HC and PC planes in DM1 and DM2 compared to controls (p < 0.05). HC slow phase eye velocity profiles in DM1 showed delayed peaks. The asymmetry ratio, which represents the percentage difference between the first and second halves of the slow phase eye velocity response, was therefore negative (-22.5 ± 17%, -2.3 ± 16%, and - 4.7 ± 8% in DM1, DM2, and controls). HC VOR gains were lower and gain asymmetry ratio was larger and negative in patients with DM1 with moderate to severe ptosis and a history of imbalance and falls compared to the remaining DM1 patients (p < 0.05). In peripheral vestibulopathies, saccade amplitude was larger, peak velocity was higher, and onset latency was shorter (p < 0.05) than in DM1. In central vestibulopathy (posterior circulation strokes), saccade peak velocity was higher, but amplitude and onset latency were not significantly different from DM1. VOR impairment is common in DM1 and DM2. In DM1, refixation saccade characteristics are closer to central than peripheral vestibulopathies. Delayed peaks in the vHIT eye velocity profile observed in patients with DM1 may reflect extraocular muscle weakness. VOR impairment and VOR asymmetry in DM1 are associated with imbalance and falls.

Genotype-phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. All affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype-phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J-domain may predict a more severe phenotype.

Paraspinal muscle fibre structural and contractile characteristics demonstrate distinct irregularities in patients with spinal degeneration and deformity.

Paraspinal and spinopelvic muscular dysfunction are hypothesized to be a causative factor for spinal degeneration and deformity; however, our fundamental understanding of paraspinal muscle (dys)function remains limited. Twelve surgical patients with spinal degeneration were recruited and categorized into group DEG (four patients) with no sagittal imbalance and no usage of compensatory mechanisms; group DEG-COMP (four patients) with no sagittal imbalance through use of compensatory mechanisms; and group DEG-COMP-UNBAL (four patients) with sagittal imbalance despite use of compensatory mechanisms. From each patient, four biopsies were collected from right and left multifidus (MULT) and longissimus (LONG) for single fibre contractile and structural measurements. Eight of 48 (17%) biopsies did not exhibit any contractile properties. Specific force was not different between groups for the MULT (p = 0.47) but was greater in group DEG compared to group DEG-COMP-UNBAL for the LONG (p = 0.02). Force sarcomere-length properties were unusually variable both within and amongst patients in all groups. Thin filament (actin) lengths were in general shorter and more variable than published norms for human muscle. This study is the first to show a heightened intrinsic contractile muscle disorder (i.e. impaired specific force generation)in patients with spinal degeneration who are sagittally imbalanced (compared to patients without deformity). Additionally, there are clear indications that patients with spinal degeneration (all groups) have intrinsic force sarcomere-length properties that are dysregulated. This provides important insight into the pathophysiology of muscle weakness in this patient group.

Immune repertoire profiling in myasthenia gravis.

Myasthenia gravis (MG) is the most frequent immune-mediated neurological disorder, characterized by fluctuating muscle weakness. Specific recognition of self-antigens by T-cell receptors (TCRs) and B-cell receptors (BCRs), coupled with T-B cell interactions, activates B cells to produce autoantibodies, which are critical for the initiation and perpetuation of MG. The immune repertoire comprises all functionally diverse T and B cells at a specific time point in an individual, reflecting the essence of immune selectivity. By sequencing the nucleotide sequences of TCRs and BCRs, it is possible to track individual T- and B-cell clones. This review delves into the generation of autoreactive TCRs and BCRs in MG and comprehensively examines the applications of immune repertoire sequencing in understanding disease pathogenesis, developing diagnostic and prognostic markers and informing targeted therapies. We also discuss the current limitations and future potential of this approach.

Clinical characteristics and impairment of activities of daily living among patients with myasthenia gravis with differing degrees of muscle weakness: a real-world study of patients in the US and five European countries

BackgroundReal-world data were employed to determine clinical characteristics of patients with myasthenia gravis (MG) with differing degrees of muscle weakness, as defined using the Myasthenia Gravis Foundation of America (MGFA) classification system.MethodsData were drawn from the Adelphi MG Disease Specific Programme (DSP)™, a multinational (United States, France, Germany, Italy, Spain, United Kingdom) survey completed by physicians and their patients with MG in 2020. The association between MGFA class and impairment in activities of daily living (ADL) was tested using linear regression adjusting for sex and Charlson Comorbidity Index. Bivariate comparisons were performed for each individual item. A range of other clinical characteristics were also explored according to MGFA class.ResultsAmong 1232 patients, those in MGFA class I had significantly lower ADL impairment versus class II or III/IV (adjusted for sex and Charlson Comorbidity Index) (p < 0.01). However, heterogeneity occurred within each MGFA class. Bulbar symptoms (impaired speech, difficulty swallowing, and/or difficulty chewing/choking on food) were reported in some class I patients (mild in 1.1–1.9% and moderate in 0.3–1.1% of patients) and class II patients (mild in 8.5–16.4%, moderate in 4.7–7.4%, and severe in 0.3–0.9% of patients), and shortness of breath was reported in some class I (mild in 0.5% of patients) and class II patients (mild in 9.8%, moderate in 4.8%, and severe in 0.3% of patients). Conversely, in 11.2–19.2% of class III/IV patients, bulbar symptoms and shortness of breath reported were only mild in severity. In line with this finding, despite significant correlations between MGFA class and several clinical characteristics, patients across every class were at risk of experiencing myasthenic crisis or hospitalization, experiencing comorbidities including anxiety and depression, and not being in remission.ConclusionsAlthough MGFA class correlates with greater ADL impairment and presence of other clinical characteristics, there is variability between patients in each class in terms of symptoms experienced, overall disease burden, and the precise nature of ADL impairment.

Biochemical changes in the aetiology of floppy kid syndrome in goat kids

AbstractIn the herd, 20 of 75 goat kids born became progressively ill. Twelve affected kids, aged 4–9 days, exhibited muscle weakness, pain without fever, diarrhoea and dehydration. Their health deteriorated rapidly, and within a few hours, one kid died. The results of the blood test revealed severe metabolic acidosis, hypokalaemia and changes in urea concentrations. Floppy kid syndrome was diagnosed. Treatment was initiated to correct the acid–base balance, and all affected kids were temporarily separated from their mothers. All the treated kids recovered. Before the onset of clinical signs, elevated urea concentrations and differences in maternal blood potassium levels were observed. This is the first report on changes in potassium concentrations in periparturient dams of goat kids with and without floppy kid syndrome, as well as the first report on changes in urea concentrations in kids before the onset of clinical signs.