Muscle & Nerve最新文献

Introduction/aims: A pragmatic evaluation of bulbar function among adults with spinal muscular atrophy (awSMA) is needed, requiring the validation of a low-cost, feasible outcome measure (OM). Maximum phonation time (MPT) and S/Z ratio (S/Z) are potential low-cost OMs for bulbar function. This study aimed to evaluate the psychometric properties of MPT and S/Z among awSMA.

Methods: This single-site prospective observational study followed awSMA over 12 months. Each participant completed MPT, S/Z, and a battery of routinely used OMs at baseline and 12 months. The psychometric properties of intra-rater reliability (IRR), test-retest reliability (TRT), concurrent validity (CV), predictive validity (PV), and sensitivity to change were evaluated.

Results: Fifteen awSMA completed the study, with a mean age of 35.5 (SD: 16.7) and 47% male participants. MPT correlated moderately with forced vital capacity (liters) and peak cough flow, and demonstrated high IRR (0.95, 0.94) and TRT over 12 months (0.80). MPT exhibited poor sensitivity to change over 12 months (0.08, 95% CI: -0.56 to 0.71). The S/Z did not exhibit significant CV, and demonstrated only modest TRT (0.55, 95% CI: 0.06-0.83), and low sensitivity to change (0.25, 95% CI: -0.32 to 0.83).

Discussion: MPT is a low-cost pragmatic tool to measure bulbar function and a surrogate for respiratory function OMs among awSMA. MPT may be helpful for patients with limited access to alternative bulbar or respiratory measures or for telehealth clinical care settings. MPT's low sensitivity to change limits its clinical utility over a 12-month interval. Larger studies are necessary.

Introduction/aims: The availability of reference cross-sectional area (CSA) values for the brachial plexus in healthy Japanese individuals and their relationship with physical characteristics remains limited. This study aimed to determine ultrasonographic reference CSA values of the brachial plexus and to examine their relationship with physical characteristics.

Methods: CSA measurements were performed at the nerve roots (C5-Th1), nerve trunks, and total cord (TC) of 60 healthy Japanese adults. Physical characteristics were measured, and statistical analyses assessed their relationships with the CSA.

Results: The CSA values differed by anatomical level. At the nerve root level, the CSA of C7 was the largest (mean 9.5 ± standard deviation 2.2 mm²), while the CSAs of C5 (4.7 ± 1.3 mm²) and Th1 (5.2 ± 1.3 mm²) were the smallest. At the nerve trunk level, the CSA of the upper trunk (19.9 ± 3.2 mm²) was larger than that of the middle trunk (13.1 ± 2.4 mm²). The CSA of TC was 73.7 ± 12.2 mm². Age, body mass index (BMI), and wrist circumference correlated with several CSAs, but no single characteristic was significantly associated with all the CSAs. The coefficients of variation ranged from approximately 20% to 30%.

Discussion: The site-specific reference values presented in this study may be useful for the clinical interpretation of brachial plexus enlargement. While the BMI and wrist circumference influence the CSAs of the nerve trunk and TC, measurement errors must be carefully considered.

Introduction/aims: The demographic and geographic representation of participants in myasthenia gravis (MG) trials has yet to be systematically reviewed. The goal of this study was to explore potential disparities in MG interventional clinical trial enrollment.

Methods: We included completed interventional clinical trials from January 2002 to December 2021 that enrolled participants with MG within the United States and Canada. Twenty-eight trials meeting these criteria were identified at Clinicaltrials.gov, and 16 trials contributed data. Study sponsors provided data for age, sex/gender, race, ethnicity, and state/province of site enrollment.

Results: Pooled data showed the following participant ethno-racial composition across trials: White = 79.9%, Black = 11.9%, Asian = 3.3%, Native American = 1.2%, "Other" race = 3.7%; 10.5% of participants identified as Hispanic ethnicity. Male participation was approximately 53%. Average participant age was 55.0 ± 17.0 years. The three highest enrolling US states were Texas, California, and Florida, and the highest enrolling Canadian province was Ontario. There was no enrollment in several Upper Midwest, Northern Rocky Mountain, and Southern US states. Total enrollment among White, Black, and Native American participants was proportional to the US population, whereas Hispanic and Asian participants were under-enrolled.

Discussion: The geographic distribution of enrollment suggests a possible concern that many patients do not have convenient access to trial centers. Strategies are needed to facilitate greater clinical trial participation among underrepresented and underserved communities that will improve generalization of study results to the overall MG population.

Introduction/aims: To optimize therapeutic trials involving individuals with myotonic dystrophy type 2 (DM2), it is useful to have a fully validated, regulatory-grade, disease-specific patient-reported outcome (PRO) measure that is capable of detecting clinically relevant changes in response to therapeutic interventions and designed in accordance with U.S. Food and Drug Administration guidelines. The purpose of this research was to develop and validate a DM2-specific instrument that is relevant to the patient population and capable of quantifying multifactorial disease.

Methods: We conducted semi-structured qualitative interviews and a cross-sectional study to identify the most important and prevalent symptoms for individuals with DM2. Symptom items were selected for inclusion in the Myotonic Dystrophy Type 2 Health Index (MD2HI) based on their high prevalence, relative impact, and potential ability to respond to therapeutic intervention. Further validation and optimization of the MD2HI were performed through beta interviews, test-retest reliability assessments, factor analysis, and subgroup analysis.

Results: Seventy-four individuals with DM2 participated in a cross-sectional study to identify the most common and important symptoms to include in the MD2HI. Beta testing with 20 participants with DM2 demonstrated that the MD2HI is highly relevant, easy to use, and comprehensive. During a short longitudinal study of 24 DM2 participants, the MD2HI depicted high reliability (ICC = 0.97) and high internal consistency (Cronbach's α = 0.98), resulting in a 17-subscale instrument.

Discussion: Initial assessment of the MD2HI provides evidence that it is a valid and reliable PRO capable of quantifying a patient's perception of their disease burden to better detect clinically relevant changes in response to therapeutic intervention.

Introduction/aims: The harmonized version of the ALS Functional Rating Scale - Revised (ALSFRS-R) is typically administered according to standard operating procedures (SOPs) to ensure procedural consistency. In contrast, obtaining the self-explanatory (SE) version of the ALSFRS-R does not include the use of SOPs. The aim of this study was to examine the level of agreement between the harmonized and the SE version of the ALSFRS-R in a cohort of ALS patients.

Methods: In a prospective study, the harmonized ALSFRS-R was assessed in 107 ALS patients. In parallel, all patients independently completed the ALSFRS-R-SE, either on a printed form (n = 36) or remotely via the ALS App (n = 71). Agreement between methods was investigated using Spearman's correlation, Lin's concordance correlation coefficient (CCC), Deming regression, Bland-Altman plots and item-level statistics including Kendall's tau-b and the Stuart-Maxwell test.

Results: Total scores from ALSFRS-R and ALSFRS-R-SE showed high correlation (ρ = 0.91-0.95) and concordance (CCC > 0.9). Deming regression (intercept≈0; slope≈1) and Bland-Altman analysis (95% of values within limits of agreement [LoA]) revealed no systematic bias. Item-level agreement was high (76.6% on average), with some variability in items such as handwriting, walking, and dyspnea. ALS progression rates were consistent (differences ≤ 0.02). ALSFRS-R-SE remained robust across remote digital and paper-based assessments.

Discussion: The strong agreement between the harmonized and self-explanatory versions of the ALSFRS-R supports their interchangeable use. The SE format may facilitate remote digital assessment and reduce complexity of ALSFRS-R assessment in research and clinical practice. Further studies are warranted to validate the ALSFRS-R-SE across larger cohorts, multiple languages, and diverse rater groups.

Introduction/aims: Accurate detection of pathophysiology from tissue images is critical for appropriate diagnoses and treatments of muscular dystrophies. The application of machine learning (ML) models offers a promising approach for image assessment. We compared three ML models in their ability to classify mouse skeletal muscle images based on store-operated calcium entry (SOCE) activity, as an indicator of prolonged muscle activity and/or disease.

Methods: Immunofluorescent images were collected from muscle fibers obtained from calpain-3 null mice and wildtype mice at rest or following exercise. Images were categorized with respect to SOCE activity and disease status, then split into training, validation, and testing sets. Data were then utilized by three deep learning models: Convolutional Neural Networks (CNN), EfficientNet, and Support Vector Machines (SVM).

Results: CNN exhibited strongest performance in accuracy (0.91) and F1 score (0.88), and SVM exhibited the highest precision (0.92). Both models achieved similar area under the receiver operating characteristic curves (0.91). Performance differences between CNN and SVM yielded a p-value of 0.19, indicating no significant differences in their ability to classify SOCE activity in muscle images.

Discussion: This study demonstrated that CNN and SVM machine learning models provide a promising approach in classifying SOCE activity in muscle images. These models offer scalable solutions for automating tissue classification, with potential to transform clinical classification in muscle pathologies. Future research can explore using larger datasets and integration of other techniques, such as transformer-based models, to improve performance in more complex muscle conditions.

Introduction/aims: Azathioprine (AZA) is a first-line immunosuppressive agent for myasthenia gravis (MG), yet most toxicity data for AZA are from gastrointestinal literature. The aim of the current study is to add a large MG patient cohort with a comprehensive evaluation of the adverse event profile of AZA and associations between patient demographics and drug reactions.

Methods: Patients were identified from the Duke Electronic Medical Record using EPIC's SlicerDicer tool.

Inclusion criteria: MG diagnosis confirmed by antibody/electrodiagnostic testing, evaluation by a Duke neuromuscular physician, and AZA use between January 1, 2014 and January 7, 2023. Drug reaction was defined as an abnormal lab result or symptomatic side effect after AZA initiation.

Results: Among 145 patients, 96 (66%) developed a drug reaction; 63 (43.5%) required AZA dose reduction or discontinuation, and 23 (16%) had symptomatic side effects. Most reactions improved with dose reduction or observation. Leukopenia, macrocytosis, and hepatotoxicity were the most frequent. For every additional comorbidity, the odds of drug reaction increased by 30% (OR 1.3; 95% CI 1.12-1.51; p < 0.001). Flu-like reactions occurred in 10% of patients. Cancer incidence (4.1%) was rare and there were no cases of Pneumocystis jirovecii pneumonia despite rare use of trimethoprim-sulfamethoxazole prophylaxis.

Discussion: AZA drug reactions were common but infrequently severe or symptomatic. Higher comorbidity burden predicted drug reactions. Most laboratory abnormalities resolved without AZA discontinuation, supporting individualized monitoring and dose adjustment rather than automatic cessation. Lower doses should be considered for balancing efficacy with dose-dependent drug reactions.

Introduction/aims: Amyotrophic lateral sclerosis (ALS) lacks reliable biomarkers to predict disease trajectories or guide therapeutic strategies. Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase implicated in cytoskeletal destabilization and neuroinflammatory pathways in preclinical ALS models, represents a promising yet unvalidated biomarker candidate. We aimed to translate preclinical findings by validating SIRT2's role in ALS.

Methods: A cross-sectional cohort study was conducted, comparing serum SIRT2 levels, measured via enzyme-linked immunosorbent assay (ELISA), between 182 ALS patients and 65 healthy controls. Clinical progression rates were derived from the ALS Functional Rating Scale-Revised (ALSFRS-R), and cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Edinburgh Cognitive and Behavioral ALS Screen (ECAS).

Results: SIRT2 levels were significantly elevated in ALS patients versus controls, though diagnostic accuracy was modest (AUC = 0.620). Furthermore, SIRT2 levels showed a weak but significant positive correlation with disease progression rate (r = 0.182, p = 0.014) and inverse correlations with cognitive scores on both MMSE (r = -0.250, p = 0.032) and ECAS (r = -0.286, p = 0.031). Notably, SIRT2 demonstrated a limited but detectable ability to stratify patients into fast- and slow-progressing subgroups (AUC = 0.635).

Discussion: These findings provide preliminary clinical evidence linking elevated serum SIRT2 to disease progression and cognitive impairment in ALS, thereby supporting its role in disease heterogeneity. This work lends clinical support to preclinical insights, suggesting SIRT2 may aid in prognosis prediction and may represent a potential therapeutic target, necessitating further studies.

Introduction/aims: It has been demonstrated that muscle echo intensity quantification and needle electromyography (EMG) produce disparate results. The aim of this study was to investigate whether a more detailed muscle ultrasound texture analysis is associated with electrophysiological parameters in EMG.

Methods: We retrospectively analyzed muscle ultrasound and EMG data from consecutive subjects > 18 years of age suspected of myopathy or neurogenic disease, and healthy controls. Muscles with inconsistent ultrasound presets or missing EMG data were excluded. Texture parameters encompassed grayscale level histograms, second-order features (contrast, entropy, correlation), and higher-order features (short-run frequency and gray-level distribution, local entropy). EMG data included motor unit size index (SI), polyphasia, recruitment, and the presence of active denervation.

Results: We analyzed 156 muscles from 64 individuals (median age 55 years [IQR 45-69], 51% female). In neurogenic processes the SI correlated moderately and positively with contrast (r = 0.62, p = 0.002), whereas reduced recruitment was associated with a higher frequency of short runs. In non-inflammatory myopathies polyphasia was moderately and negatively correlated with entropy (r = -0.46, p = 0.003), while in inflammatory myopathies brightness correlated weakly and negatively with SI (r = -0.39, p = 0.014) and was increased in muscles that showed active denervation on EMG (p = 0.018).

Discussion: Muscle ultrasound texture parameters correlate with certain EMG findings, possibly reflecting underlying pathology. This study advances the use of ultrasound textural parameters beyond grayscale measurements to potentially bridge the gap between imaging and electrophysiology.