Longitudinal Assessment of Blood-Based Inflammatory, Neuromuscular, and Neurovascular Biomarker Profiles in Intensive Care Unit-Acquired Weakness: A Prospective Single-Center Cohort Study.

BACKGROUND: The diagnosis of intensive care unit (ICU)-acquired weakness (ICUAW) and critical illness neuromyopathy (CINM) is frequently hampered in the clinical routine. We evaluated a novel panel of blood-based inflammatory, neuromuscular, and neurovascular biomarkers as an alternative diagnostic approach for ICUAW and CINM. METHODS: Patients admitted to the ICU with a Sequential Organ Failure Assessment score of ≥ 8 on 3 consecutive days within the first 5 days as well as healthy controls were enrolled. The Medical Research Council Sum Score (MRCSS) was calculated, and motor and sensory electroneurography (ENG) for assessment of peripheral nerve function were performed at days 3 and 10. ICUAW was defined by an MRCSS < 48 and CINM by pathological ENG alterations, both at day 10. Blood samples were taken at days 3, 10, and 17 for quantitative analysis of 18 different biomarkers (white blood cell count, C-reactive protein, procalcitonin, C-terminal agrin filament, fatty-acid-binding protein 3, growth and differentiation factor 15, syndecan 1, troponin I, interferon-γ, tumor necrosis factor-α, interleukin-1α [IL-1α], IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-13, and monocyte chemoattractant protein 1). Results of the biomarker analysis were categorized according to the ICUAW and CINM status. Clinical outcome was assessed after 3 months. RESULTS: Between October 2016 and December 2018, 38 critically ill patients, grouped into ICUAW (18 with and 20 without) and CINM (18 with and 17 without), as well as ten healthy volunteers were included. Biomarkers were significantly elevated in critically ill patients compared to healthy controls and correlated with disease severity and 3-month outcome parameters. However, none of the biomarkers enabled discrimination of patients with and without neuromuscular impairment, irrespective of applied classification. CONCLUSIONS: Blood-based biomarkers are generally elevated in ICU patients but do not identify patients with ICUAW or CINM. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02706314.

Permanent cutaneous vesicostomy: a pragmatic approach to safely manage lower urinary tract dysfunction in pediatric patients with chronic and life-limiting conditions and neuropathic bladders.

Introduction: Lower urinary tract dysfunction (LUTD) in cerebral palsy (CP) and other neuromuscular diseases can present with chronic retention that leads to hydronephrosis, recurrent urinary tract infections (UTI), and stone formation. Whenever the conservative treatment of LUTD fails for any reason, it is considered to be complicated LUTD, in which a surgical approach is warranted. Cutaneous vesicostomy (CV) is a simple, well-tolerated, and potentially reversible procedure that protects the upper tracts. We describe our experience using CV for this complex population. Materials and methods: Children with CP and other neuromuscular diseases admitted to pediatric long-term care units for palliative care between 2015 and 2019 were included in the study. They present multi-system involvement, polypharmacy, and Gross Motor Function Classification System levels of 4 or 5. We retrospectively studied this population's indications and results of CV. Results: Of the 52 admitted patients, 18 presented LUTD with UTI (n:18; 100%), stones (n:5; 28%), progressive hydroureteronephrosis (n:3; 17%), or stones (n:2; 11%). Conservative initial management (catheterizations, prophylaxis antibiotics) was effective in half the cases. The remaining nine were defined as complicated LUTD and underwent CV. After a mean follow-up of 11.3 months, the follow-up showed improved hydronephrosis in all nine (100%) patients. Recurrent UTIs were no longer seen in eight of nine patients, although three patients required bladder irrigations; bladder stones did not recur after CV; the kidney stones needed further intervention. Revision of the CV was required in two (11%) cases at 12 and 24 months postoperatively due to stoma stenosis. Conclusion: CV is a relatively simple and effective procedure representing a pragmatic solution for managing complicated LUTD in complex long-term institutionalized pediatric palliative care patients with neuropathic bladders.

Comparison of spatiotemporal and angular parameters during shallow water walking in different immersion depths by older adults with and without Parkinson's disease.

BACKGROUND: People with Parkinson's Disease (PwPD) have motor symptoms that directly interfere on dry land walking performance. Despite the shallow water walking is a viable and beneficial physical intervention for PwPD, it lacks information on the comparison of the biomechanical responses of the shallow water walking by PwPD and age paired healthy individuals. RESEARCH QUESTION: Are there differences in the spatiotemporal and angular responses of shallow water walking by older adults with and without Parkinson's disease? METHODS: In this cross-sectional study, ten older adults (9 men/1 women) with Parkinson disease (PwPD group) and ten older adults (3 men/7 women) without Parkinson's disease (Older group) walked in shallow water at self-selected comfortable speed on pool floor in the immersion depths of waist and xiphoid levels. The 2D kinematic data from the sagittal plane was collected to calculate the walking speed, stride length, stride frequency, duty factor, walk ratio, lower limb joints' range of motion and peak angular speed RESULTS: Both groups reduced similarly the walking speed with the immersion depth increase. The speed decrease was achieved by a reducing both the stride frequency and stride length only in the PwPD. The PwPD had lower contact phase than Older in the waist depth, probably due to the reduced risk of fall in water immersion and to attenuate drag force effects. The total range of joint motion was similar between groups, while the peak angular speed of ankle and knee reduced in the deeper depth in both groups. SIGNIFICANCE: The present findings can help professionals of aquatic rehabilitation to choose the best depth for exercise programs, according to the treatment objectives. To our knowledge, this was the first study that analyzed spatiotemporal and angular variables during shallow water walking of PwPD at different depths and compared them with older people without Parkinson's disease.

Avoiding the use of long-term parenteral support in patients without intestinal failure: A position paper from the European Society of Clinical Nutrition & Metabolism, the European Society of Neurogastroenterology and Motility and the Rome Foundation for Disorders of Gut-Brain Interaction.

The role of long-term parenteral support in patients with underlying benign conditions who do not have intestinal failure (IF) is contentious, not least since there are clear benefits in utilising the oral or enteral route for nutritional support. Furthermore, the risks of long-term home parenteral nutrition (HPN) are significant, with significant impacts on morbidity and mortality. There has, however, been a recent upsurge of the use of HPN in patients with conditions such as gastro-intestinal neuromuscular disorders, opioid bowel dysfunction, disorders of gut-brain interaction and possibly eating disorders, who do not have IF. As a result, the European Society of Clinical Nutrition and Metabolism (ESPEN), the European Society of Neuro-gastroenterology and Motility (ESNM) and the Rome Foundation for Disorders of Gut Brain Interaction felt that a position statement is required to clarify - and hopefully reduce the potential for harm associated with - the use of long-term parenteral support in patients without IF. Consensus opinion is that HPN should not be prescribed for patients without IF, where the oral and/or enteral route can be utilised. On the rare occasions that PN commencement is required to treat life-threatening malnutrition in conditions such as those listed above, it should only be prescribed for a time-limited period to achieve nutritional safety, while the wider multi-disciplinary team focus on more appropriate biopsychosocial holistic and rehabilitative approaches to manage the patient's primary underlying condition.

Protein biomarker signature in patients with spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is a slowly progressing disease with limited sensitive biomarkers that support clinical research. We analyzed plasma and serum samples from patients with SBMA and matched healthy controls in multiple cohorts, identifying 40 highly reproducible SBMA-associated proteins out of nearly 3,000 measured. These proteins were robustly enriched in gene sets of skeletal muscle expression and processes related to mitochondria and calcium signaling. Many proteins outperformed currently used clinical laboratory tests (e.g., creatine kinase [CK]) in distinguishing patients from controls and in their correlations with clinical and functional traits in patients. Two of the 40 proteins, Ectodysplasin A2 receptor (EDA2R) and Repulsive guidance molecule A (RGMA), were found to be associated with decreased survival and body weight in a mouse model of SBMA. In summary, we identified what we believe to be a robust and novel set of fluid protein biomarkers in SBMA that are linked with relevant disease features in patients and in a mouse model of disease. Changes in these SBMA-associated proteins could be used as an early predictor of treatment effects in clinical trials.

Obesity is associated with muscle atrophy in rotator cuff tear.

Objective: The primary goal of this study is to evaluate the relationship between Body Mass Index (BMI) and muscle atrophy in individuals with rotator cuff tears. Methods: This study consists of patients with rotator cuff tears identified by MRI from two independent cohorts, the Rotator Cuff Outcomes Workgroup (ROW) and the Multicenter Orthopaedic Outcomes Network (MOON). Presence of atrophy (yes/no) and severity of atrophy (as an ordinal variable) were assessed on MRI by expert physicians. We used multivariable regression models to evaluate the relationship between BMI and muscle atrophy while adjusting for age and sex in each study, conducted sensitivity analyses for full-thickness tear and combined results using inverse variance-weighted meta-analysis. Results: A total of 539 patients (MOON=395, ROW=144) from the combined cohorts had MRI data available on muscle atrophy. Among these patients, 246 (46%) had atrophy of at least one of the muscles of the rotator cuff and 282 (52%) had full-thickness tears. In meta-analysis across both cohorts, each 5 kg/m2 increase in BMI was associated with a 21% (aOR=1.21, 95% CI=1.02, 1.43) increased odds of having muscle atrophy among individuals with any tear size, and 36% (aOR=1.36, 95% CI=1.01-1.81) increased odds among individuals with full-thickness tear. Conclusions: Higher BMI was associated with significantly higher odds of muscle atrophy in patiens with rotator cuff tears. More study is needed to unders1tand why and how this relationship exists, as well as whether interventions to reduce BMI may help improve outcomes for these patients. Level of Evidence: III.

Impact of Glycemic Control on Shoulder Proprioception in Type 2 Diabetes Mellitus: Mediating the Connection - Insights from a Cross-Sectional Analysis.

Introduction: Shoulder proprioception is vital and this cross-sectional study investigated the association between glycemic control and shoulder joint proprioception in Type 2 Diabetes Mellitus (T2DM). Methods: A total of 120 participants, including 60 with T2DM and 60 healthy individuals, were assessed for shoulder joint position sense (JPS) using a digital inclinometer. The T2DM group exhibited significantly greater mean shoulder joint position errors in flexion (4.32° vs 2.15°), abduction, medial rotation, and lateral rotation compared to the healthy group (p < 0.001). Results: The study found significantly greater shoulder joint position errors in the T2DM group compared to the healthy group, highlighting notable proprioceptive deficits in individuals with T2DM. Additionally, a significant positive correlation was found between HbA1c levels and shoulder joint position errors in the T2DM group, suggesting a link between long-term glycemic control and proprioceptive accuracy. Discussion: The significant positive correlation between HbA1c levels and shoulder joint position errors suggests that poor glycemic control is associated with impaired proprioception in T2DM patients. This underscores the need for comprehensive management strategies to mitigate proprioceptive deficits and improve the quality of life in individuals with T2DM.

Deformity correction from the convexity of the curve in neuromuscular scoliosis.

Background: "Convex Pedicle Screw Technique" reduces the theoretical risk of neurovascular injury. Our aim is to evaluate the efficacy of this technique in patients with neuromuscular scoliosis (NMS). Methods: Retrospective study of 12 patients who underwent a Convex Pedicle Screw Technique and were diagnosed with NMS. Patients who had undergone previous spinal surgery were excluded. The minimum follow-up required was 24 months. Demographic data, intraoperative data, neurovascular complications and neurophysiological events requiring implant repositioning, as well as pre- and postoperative radiological variables were collected. Results: Twelve patients diagnosed with NMS underwent surgery. The median operative time was 217 minutes. Mean blood loss was 3.8±1.1 g/dL hemoglobin (Hb). The median postoperative stay was 8.8±4 days. A reduction of the Cobb angle in primary curve of 49.1% (from 52.8°±18° to 26.5°±12.6°; P<0.001) and in secondary curve of 25.2% (from 27.8°±18.9° to 18.3°±13.3°; P=0.10) was achieved. Coronal balance improved by 69.4% (7.5±46.2 vs. 2.3±20.9 mm; P=0.72) and sagittal balance by 75% (from -14.1±71.8 vs. -3.5±48.6 mm; P=0.50). There were no neurovascular complications. There were no intraoperative neurophysiological events requiring implant repositioning, nor during reduction maneuvers. No infections were reported. Conclusions: The correction of the deformity from convexity in NMS achieves similar results to other techniques, and a very low complication rate.

Improving Lower Limb Function and Frailty in Frail Older Patients with Acute Myocardial Infarction After Percutaneous Coronary Intervention: A Randomized Controlled Study of Neuromuscular Electrical Stimulation.

Background: A global public health problem, frailty is closely associated with poor prognosis after percutaneous coronary intervention (PCI) in older patients with acute myocardial infarction (AMI). Although exercise intervention is the most commonly used method to reverse and alleviate frailty, its application is restricted in patients with acute myocardial infarction following PCI due to cardiovascular instability and autonomic imbalance. Consequently, there is a need for a new practical intervention to address frailty syndrome in these patients. Purpose: This study aimed to investigate the effect of neuromuscular electrical stimulation in frail older AMI patients post-PCI. Patients and Methods: A single-blind, randomized controlled trial was carried out in the Department of Cardiovascular Medicine from March to October 2023. A total of 100 eligible participants were randomly divided into two groups: experimental (n = 50) and control (n = 50) groups, respectively. Both groups received usual care. The experimental group underwent neuromuscular electrical stimulation (NMES) on bilateral quadriceps and gastrocnemius muscles for 30 minutes daily from day 1 to day 7 after surgery. The primary outcomes measured included the frailty score, lower limb muscle strength, and lower limb muscle quality. Secondary outcomes included the activities of daily living score, inflammatory markers, and length of hospital stay. All participants were included in an intention-to-treat analysis after the study ended. Results: The frailty scores of the two groups exhibited a gradual decrease over time, and the scores of the experimental group were lower than those of the control group at 4 and 7 days after surgery (P<0.001). Concurrently, the lower limb muscle strength showed an increasing trend over the time in the experimental group and a decreasing trend in the control group, and the scores of the experimental group surpassed those of the control group (p<0.001). Moreover, a statistical difference was observed in the lower limb muscle mass across the groups after 7 days postoperatively compared with baseline on both sides (p<0.05). Conclusion: Neuromuscular electrical stimulation has the potential to enhance lower limb function and alleviate frailty in elderly patients with acute myocardial infarction after PCI. These findings introduce a novel intervention approach for frailty management in the elderly population.

Area under the curve and amplitude of the compound motor action potential are clinically interchangeable quantitative measures of neuromuscular block: a method comparison study.

Background: Current guidelines recommend quantitative neuromuscular block monitoring during neuromuscular blocking agent administration. Monitors using surface electromyography (EMG) determine compound motor action potential (cMAP) amplitude or area under the curve (AUC). Rigorous evaluation of the interchangeability of these methods is lacking but necessary for clinical and research assurance that EMG interpretations of the depth of neuromuscular block are not affected by the methodology. Methods: Digitised EMG waveforms were studied from 48 patients given rocuronium during two published studies. The EMG amplitudes and AUCs were calculated pairwise from all cMAPs classified as valid by visual inspection. Ratios of the first twitch (T1) to the control T1 before administration of rocuronium (T1c) and train-of-four ratios (TOFRs) were compared using repeated measures Bland-Altman analysis. Results: Among the 2419 paired T1/T1c differences where the average T1/T1c was ≤0.2, eight (0.33%) were outside prespecified clinical limits of agreement (-0.148 to 0.164). Among the 1781 paired TOFR differences where the average TOFR was ≥0.8, 70 (3.93%) were outside the prespecified clinical limits of agreement ((-0.109 to 0.134). Among all 7286 T1/T1c paired differences, the mean bias was 0.32 (95% confidence interval 0.202-0.043), and among all 5559 paired TOFR differences, the mean bias was 0.011 (95% confidence interval 0.0050-0.017). Among paired T1/T1c and TOFR differences, Lin's concordance correlation coefficients were 0.98 and 0.995, respectively. Repeatability coefficients for T1/T1c and TOFR were <0.08, with no differences between methods. Conclusions: Quantitative assessment neuromuscular block depth is clinically interchangeable when calculated using cMAP amplitude or the AUC.

The association between unilateral and bilateral performance-related measures in elite female soccer players: a multifaceted investigation.

Purpose: The present study aimed to investigate a) the associations between bilateral performance utilizing countermovement jump (CMJ), squat jump (SJ), speed and unilateral CMJ, isokinetic peak torque in knee extension and flexion with angular velocities of 60°/s and 180°/s and tensiomyography (TMG) parameters; b) whether the asymmetries derived from unilateral tests are associated with bilateral CMJ, SJ and speed in elite female soccer players. Methods: Thirty-five elite female soccer players (average age: 20 ± 5 years) completed CMJ, SJ, speed, isokinetic muscle strength and TMG tests. Results: Compared to the non-dominant leg, the dominant leg demonstrated greater peak torque output in both knee flexion (7.4%) and knee extension (5.6%) isokinetic tasks, as well as m. vastus medialis contraction time (7.6%), and soccer-specific agility test (4.1%). Conversely, the hamstring to quadriceps peak torque ratio at 180°/s (8.5%) was significantly greater in the non-dominant leg. The associations between CMJ, SJ and speed performance were positive and ranged from weak (r = 0.350) to high (r = 0.710). For speed and TMG-derived variables, correlations were negative and ranged from weak (r = -0.345, p = 0.042, for vastus medialis contraction time) to moderate (r = -0.530, p = 0.001, for biceps femoris contraction time). Furthermore, both bilateral CMJ and SJ negatively correlated with TMG-derived variables, ranging from weak (r = -0.350, p = 0.039, for vastus lateralis contraction time) to moderate (r = -0.537, p = 0.003, for rectus femoris contraction time). Conclusion: The overall significant, albeit inconsistent, correlations between the diverse performance scores obtained highlight the necessity for a multifaceted and thorough diagnostic strategy in female soccer players.

A comparison of morning priming exercise using traditional-set and cluster-set configurations on afternoon explosive performance.

The impact of two priming exercise protocols using traditional (TS) or cluster-set (CS) arrangements on explosive performance 6 hours later were examined. Sixteen male collegiate athletes performed three testing sessions (one baseline without any prior exercise in the morning and two experimental sessions) separated by 72 hours. Participants completed two morning (9-11 am) priming protocols in a randomized order, either using a TS (no rest between repetitions) or CS (30 seconds of rest between repetitions) configuration. The protocols consisted of 3 sets × 3 repetitions of barbell back squat at 85% of 1 repetition maximum, with 4 minutes of rest between sets. In the afternoon (3-5 pm) of each trial, after a 6-hour rest period, a physical test battery was conducted that replicated baseline testing, including countermovement jump, 20-meter straight-line sprint, and T-test abilities. Across both conditions, participants exhibited increased countermovement jump height, 20-meter sprint time and T-test time compared to baseline (P < 0.05). Improvements in countermovement jump height (+4.4 ± 5.4%; P = 0.008) and 20-meter sprint time (+1.3 ± 1.7%; P = 0.022), but not T-test time (+1.1 ± 3.3%; P = 0.585), were significantly greater for CS than TS. In conclusion, compared to a traditional set arrangement, a morning-based priming protocol using a cluster-set configuration led to superior explosive performance benefits in the afternoon.

Rasch analysis of the modified Fatigue Severity Scale in neuromuscular disorders and comparison between sex, age and diagnoses.

INTRODUCTION/AIMS: Fatigue is a common and debilitating symptom encountered in the neuromuscular clinic. The 7-item Fatigue Severity Scale (FSS-7) is a Rasch-modified assessment validated in inflammatory neuropathies but not across a typical neuromuscular patient population. The aim of this study was to validate this measure in neuromuscular disorders and to compare between patient sex, age and diagnoses. METHODS: The modified FSS-7 was mailed to patients recruited from a specialist neuromuscular clinic at the Walton Centre. Responses were subjected to Rasch analysis and descriptive statistics were performed on the Rasch converted data. RESULTS: The mFSS-7 met the Rasch model expectations with an overall Chi-square probability of 0.4918, a strict unidimensional scale free from differential item functioning (DIF) that satisfied the model with substantial test-retest reliability using Lin's concordance correlation coefficient 0.71 (95% CI 0.63-0.77). A 15.7% ceiling effect was observed in this patient cohort. Post hoc analysis did not show any significant difference in fatigue between sex, age or neuromuscular diagnoses. DISCUSSION: The self-completed Rasch mFSS-7 showed acceptable test-retest reliability across patients with varied disorders under follow-up in a specialist neuromuscular clinic. The ceiling effect constrains its use for those with the most severe fatigue. Future considerations could include assessment of the benefits of clinical interventions, particularly multidisciplinary team input or dedicated fatigue clinics.

A training goal-oriented categorization model of high-intensity interval training.

There are various categorization models of high-intensity interval training (HIIT) in the literature that need to be more consistent in definition, terminology, and concept completeness. In this review, we present a training goal-oriented categorization model of HIIT, aiming to find the best possible consensus among the various defined types of HIIT. This categorization concludes with six different types of HIIT derived from the literature, based on the interaction of interval duration, interval intensity and interval:recovery ratio. We discuss the science behind the defined types of HIIT and shed light on the possible effects of the various types of HIIT on aerobic, anaerobic, and neuromuscular systems and possible transfer effects into competition performance. We highlight various research gaps, discrepancies in findings and not yet proved know-how based on a lack of randomized controlled training studies, especially in well-trained to elite athlete cohorts. Our HIIT "toolbox" approach is designed to guide goal-oriented training. It is intended to lay the groundwork for future systematic reviews and serves as foundation for meta-analyses.

Aberrant evoked calcium signaling and nAChR cluster morphology in a SOD1 D90A hiPSC-derived neuromuscular model.

Familial amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder that is due to mutations in one of several target genes, including SOD1. So far, clinical records, rodent studies, and in vitro models have yielded arguments for either a primary motor neuron disease, or a pleiotropic pathogenesis of ALS. While mouse models lack the human origin, in vitro models using human induced pluripotent stem cells (hiPSC) have been recently developed for addressing ALS pathogenesis. In spite of improvements regarding the generation of muscle cells from hiPSC, the degree of maturation of muscle cells resulting from these protocols has remained limited. To fill these shortcomings, we here present a new protocol for an enhanced myotube differentiation from hiPSC with the option of further maturation upon coculture with hiPSC-derived motor neurons. The described model is the first to yield a combination of key myogenic maturation features that are consistent sarcomeric organization in association with complex nAChR clusters in myotubes derived from control hiPSC. In this model, myotubes derived from hiPSC carrying the SOD1 D90A mutation had reduced expression of myogenic markers, lack of sarcomeres, morphologically different nAChR clusters, and an altered nAChR-dependent Ca2+ response compared to control myotubes. Notably, trophic support provided by control hiPSC-derived motor neurons reduced nAChR cluster differences between control and SOD1 D90A myotubes. In summary, a novel hiPSC-derived neuromuscular model yields evidence for both muscle-intrinsic and nerve-dependent aspects of neuromuscular dysfunction in SOD1-based ALS.

Bickerstaff Brainstem Encephalitis Presenting With Negative Anti-GM1 and Anti-GQ1B Antibodies.

A woman in her 60s initially presented with rapid-onset left-sided hemiparesis with later development of slurred speech and left-sided facial droop. Despite ruling out common causes, her condition rapidly progressed with the development of bilateral proximal weakness, ophthalmoplegia, ataxia, and pyramidal signs eventually leading to a cardiorespiratory arrest. Extensive investigations, including computerised tomography (CT), magnetic resonance imaging (MRI), and lumbar puncture (LP), were negative for infectious or vascular aetiologies. Nerve conduction studies (NCS) revealed severe peripheral nerve damage, and despite a provisional diagnosis of Guillain-Barré Syndrome (GBS), the clinical picture aligned more with Bickerstaff Brainstem Encephalitis (BBE) given the central nervous system (CNS) involvement, despite negative anti-GM1 and anti-GQ1b autoantibodies. Treatment involved ventilatory support, immunoglobulins, and steroids. This case report describes a rare and challenging presentation of BBE and reminds clinicians to have a systematic approach to a patient presenting with rapid onset neurological symptoms and that BBE is a clinical diagnosis.

Nociceptive Pain in Patients with Neuromuscular Disorders - A Cross-Sectional Clinical Study.

Background: Muscle pain is a common symptom in patients with neuromuscular disorders (NMD) and accounts for severely reduced quality of life. OBJECTIVE: This clinical study aimed to observe possible differences in pain prevalence among distinct NMDs and to determine whether the patients' nociceptive pain is influenced by gender, muscle strength and psychological factors and to examine potential pain-associated alterations in muscle properties. Methods: The cross-sectional study on nociceptive pain in various NMDs involved patient-reported outcomes, muscle strength evaluations (dynamometry and quick motor function test (QMFT)), nociceptive pain evaluations (muscular pressure pain threshold (PPT)), and non-invasive measurement of muscle stiffness, frequency, decrement, relaxation, and creep (myotonometry). Results: Involving 81 NMD patients and a control group, the study found high variability in pain prevalence among the subgroups. Patients with DM2 and FSHD had significantly higher levels of pain prevalence compared to other examined NMD subgroups and the control group. Female gender, high fatigue levels (representing factors such as depression, anxiety, stress, and impairment of quality of life), and low QMFT scores (representing reduced muscle strength) showed an association with increased sensitivity to pressure pain in the arm and leg region. As assessed by myotonometry, less pain is experienced in neck muscles with a high muscle tone, high stiffness, and a short relaxation time highlighting the importance of intrinsic muscular tone for their pressure pain sensitivity. Conclusion: Individualized therapeutic concepts including psychological and physical approaches in the pain management of patients with NMDs, especially in women, should be considered. Further research in this field is necessary to gain a more detailed insight into the perception of muscle pain.

Use of computational modeling to examine fingertip force production in children with hemiplegic cerebral palsy.

Most children with hemiplegic cerebral palsy (HCP), one of the most prevalent subtypes of cerebral palsy, struggle with grasping and manipulating objects. This impairment may arise from a diminished capacity to properly direct forces created with the finger pad due to aberrant force application. Children with HCP were asked to create maximal force with the index finger pad in the palmar (normal) direction with both the paretic and non-paretic hands. The resulting forces and finger postures were then applied to a computational musculoskeletal model of the hand to estimate the corresponding muscle activation patterns. Subjects tended to create greater shear force relative to normal force with the paretic hand (p < 0.05). The resultant force was directed 33.6°±10.8° away from the instructed palmar direction in the paretic hand, but only 8.0°±7.3° in the non-paretic hand. Additionally, participants created greater palmar force with the non-paretic hand than with the paretic hand (p < 0.05). These differences in force production are likely due to differences in muscle activation pattern, as our computational models showed differences in which muscles are active and their relative activations when recreating the measured force vectors for the two hands (p < 0.01). The models predicted reduced activation in the extrinsic and greater reductions in activation in the intrinsic finger muscles, potentially due to reduced voluntary activation or muscle atrophy. As the large shear forces could lead to objects slipping from grasp, muscle activation patterns may provide an important target for therapeutic treatment in children with HCP.

Congenital Myasthenic Syndromes in Belgium: Genetic and Clinical Characterization of Pediatric and Adult Patients.

BACKGROUND: Congenital myasthenic syndromes (CMS) are a group of genetic disorders characterized by impaired neuromuscular transmission. CMS typically present at a young age with fatigable muscle weakness, often with an abnormal response after repetitive nerve stimulation (RNS). Pharmacologic treatment can improve symptoms, depending on the underlying defect. Prevalence is likely underestimated. This study reports on patients with CMS followed in Belgium in 2022. METHODS: Data were gathered retrospectively from the medical charts. Only likely pathogenic and pathogenic variants were included in the analysis. RESULTS: We identified 37 patients, resulting in an estimated prevalence of 3.19 per 1,000,000. The patients harbored pathogenic variants in CHRNE, RAPSN, DOK7, PREPL, CHRNB1, CHRNG, COLQ, MUSK, CHRND, GFPT1, and GMPPB. CHRNE was the most commonly affected gene. Most patients showed disease onset at birth, during infancy, or during childhood. Symptom onset was at adult age in seven patients, caused by variants in CHRNE, DOK7, MUSK, CHRND, and GMPPB. Severity and distribution of weakness varied, as did the presence of respiratory involvement, feeding problems, and extraneuromuscular manifestations. RNS was performed in 23 patients of whom 18 demonstrated a pathologic decrement. Most treatment responses were predictable based on the genotype. CONCLUSIONS: This is the first pooled characterization of patients with CMS in Belgium. We broaden the phenotypical spectrum of pathogenic variants in CHRNE with adult-onset CMS. Systematically documenting larger cohorts of patients with CMS can aid in better clinical characterization and earlier recognition of this rare disease. We emphasize the importance of establishing a molecular genetic diagnosis to tailor treatment choices.

Measurement properties of the Inclusion Body Myositis Functional Rating Scale.

OBJECTIVES: To evaluate the validity, reliability, responsiveness and meaningful change threshold of the Inclusion Body Myositis (IBM) Functional Rating Scale (FRS). METHODS: Data from a large 20-month multicentre, randomised, double-blind, placebo-controlled trial in IBM were used. Convergent validity was tested using Spearman correlation with other health outcomes. Discriminant (known groups) validity was assessed using standardised effect sizes (SES). Internal consistency was tested using Cronbach's alpha. Intrarater reliability in stable patients and equivalence of face-to-face and telephone administration were tested using intraclass correlation coefficients (ICCs) and Bland-Altman plots. Responsiveness was assessed using a standardised response mean (SRM). An receiver operator characteristic (ROC) curve anchor-based approach was used to determine clinically meaningful IBMFRS change. RESULTS: Among the 150 patients, mean (SD) IBMFRS total score was 27.4 (4.6). Convergent validity was supported by medium to large correlations (rs modulus: 0.42-0.79) and discriminant validity by moderate to large group differences (SES=0.51-1.59). Internal consistency was adequate (overall Cronbach's alpha: 0.79). Test-retest reliability (ICCs=0.84-0.87) and reliability of telephone versus face-to-face administration (ICCs=0.93-0.95) were excellent, with Bland-Altman plots showing good agreement. Responsiveness in the worsened group defined by various external constructs was large at both 12 (SRM=-0.76 to -1.49) and 20 months (SRM=-1.12 to -1.57). In ROC curve analysis, a drop in two IBMFRS total score points was shown to represent a meaningful decline. CONCLUSIONS: When administered by trained raters, the IBMFRS is a reliable, valid and responsive tool that can be used to evaluate the impact of IBM and its treatment on physical function, with a 2-point reduction representing meaningful decline. TRIAL REGISTRATION NUMBER: NCT02753530.