Muscle & Nerve最新文献

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: Traditional methods of sampling skeletal muscle tissue are invasive. This study aimed to evaluate a sub-millimeter core-biopsy (microbiopsy) as a potentially more tolerable method, with further regard to tissue yield and analyzability of RNA expression.

Methods: Children (9-13 years, n = 11) and adults (18-50 years, n = 16) were recruited. Microbiopsy and venipuncture were performed, with prior application of local anesthesia cream. Additionally, adults underwent a Bergström muscle biopsy, with infiltrative local anesthesia. Pain was rated using the visual analog scale (VAS), reported as medians (95% CI). Microbiopsy samples were freeze-dried and weighed. To evaluate RNA sequencing performance at low tissue sample weights, a six-step incremental tissue ladder (10-500 μg) was analyzed.

Results: Children rated venipunctures and microbiopsies low, at VAS = 0.1 (0.0-0.6) and 1.6 (0.9-3.9), respectively. Microbiopsy pain ratings were slightly higher than venipuncture, p < 0.001. Pain ratings in adults were 0.0 (0.0-0.5), 1.8 (1.3-2.4), 2.9 (2.4-3.8), and 2.7 (2.2-3.8) for venipuncture, microbiopsy, Bergström biopsy, and infiltrative local anesthesia, respectively. Microbiopsy was rated less painful than Bergström biopsy and local anesthesia (p < 0.05). Children did not rate microbiopsy more painful than adults (p = 0.82). Microbiopsies yielded on average 303 (SD 121.8) μg. RNA sequencing detected similar transcriptomic signatures across the tissue ladder.

Discussion: The generally low pain ratings for the microbiopsy procedure support its use as a tolerable method of acquiring skeletal muscle samples in both children and adults. It represents a less painful alternative to Bergström biopsies while still rendering adequate material for RNA sequencing.

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: 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: 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.

Introduction/aims: Guidelines for the management of chronic inflammatory demyelinating polyneuropathy (CIDP) recommend corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange for first-line therapies and subcutaneous immunoglobulin (SCIg) as a maintenance option. Literature on clinical experience with SCIg in CIDP maintenance therapy is limited. This study outlines practical approaches to SCIg transition and management optimization, considering the varying dosing recommendations in prescribing information and clinical guidelines.

Methods: This retrospective, multicenter study analyzed anonymized patient medical records from eight US centers. Patients with CIDP who transitioned to SCIg were included, and clinical practices regarding SCIg therapy management were analyzed.

Results: These 20 cases presented practical and clinical considerations for successful SCIg transition and maintenance. Switching decisions were guided by patient-physician assessment of treatment goals, benefits, and risks. The most common reason for switching (70%) was preference for site of care. Eight patients (40%) transitioned to a dose equivalent to their baseline IVIg dose. Overall, 12/19 patients (63%) remained stable following transition. Relapse-free rates were higher in patients who transitioned to a higher (67%) or lower (75%) than baseline dose versus those who received an equivalent dose (50%). All relapsed patients restabilized after increasing their SCIg dose. The final mean (SD) SCIg dose was 0.32 (0.15) g/kg/week. SCIg was well tolerated; 11 patients (55%) reported better tolerance versus IVIg.

Discussion: These patient cases provide practical guidance for SCIg therapy in CIDP maintenance, emphasizing individualized dosing strategies, ongoing monitoring, and patient-centered engagement. The findings help inform clinical decision-making to optimize long-term therapeutic outcomes.

Introduction/aims: A previous publication reported that the number of months of training and the number of patient studies independently influenced examination scores for the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) self assessment examination (AANEM-SAE). The purpose of this study was to explore additional questions regarding how electrodiagnostic (EDx) training impacts AANEM-SAE score.

Methods: This was a retrospective review of the 2024 and 2025 AANEM-SAE results. Participants were asked the number of: patient studies performed, months of training completed, hours of didactic training received, and hours they studied to prepare for the AANEM-SAE. There were also questions regarding neuromuscular ultrasound training.

Results: A total of 1530 participants completed the proctored examinations. Scores steadily improved with additional months of training but leveled off after 300-400 patient studies. Regression analysis indicated that higher numbers of patient studies and higher numbers of didactic training hours and study hours were correlated with higher examination scores even after accounting for the number of months of training. Of the 2025 participants, 56% received training in neuromuscular ultrasound, but most completed no more than 30 patient studies. No association was found between ultrasound training and performance on ultrasound questions, but the number of questions was small.

Discussion: EDx training program directors should continue to emphasize core elements of EDx training and design their curricula with attention to providing sufficient numbers of studies and hours of didactic instruction for trainees.

Introduction/aims: Although classically characterized as a motor neuron disease, spinal muscular atrophy (SMA) is increasingly recognized as a multisystem disorder. We previously showed hepatocyte-intrinsic steatosis in SMA, raising the question of whether SMA carriers, who are typically asymptomatic, may also exhibit subclinical hepatic abnormalities.

Methods: We generated induced hepatocyte-like cells (iHeps) from induced pluripotent stem cells (iPSCs) derived from an SMA Type 2 proband, his isogenic wild-type (Iso-WT) line, and both carrier parents, comprised of three carrier lines from the father and one from the mother. Steatosis was assessed by Oil Red O staining and image analysis. Survival motor neuron (SMN) expression was evaluated by immunoblotting. Proteotranscriptomic profiling and mitochondrial respiration assays were performed. Risdiplam, an SMN2 splicing modulator, was used to assess reversibility of observed phenotypes.

Results: SMA and carrier iHeps demonstrated increased lipid accumulation compared to Iso-WT. Risdiplam reduced steatosis by 65.9% in SMA patient-derived iHeps and by 43.6% and 56.9% in father- and mother carrier-derived iHeps, respectively. Carrier and SMA iHeps exhibited downregulation of genes involved in lipid metabolism and liver function, along with altered expression of lipid-related proteins. Mitochondrial dysfunction was present only in SMA iHeps. Carrier-derived induced motor neurons showed normal viability under oxidative stress, consistent with preserved neuromuscular function clinically.

Discussion: Our data reveal hepatocyte-intrinsic lipid metabolic defects in SMA carriers, partially reversible with risdiplam. These findings suggest subclinical hepatic involvement in carriers and support further investigation into the systemic impact of SMN deficiency.