Muscle & Nerve最新文献

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.

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: Segmental zoster paresis (SZP) of the upper limb is a complication of herpes zoster (HZ), but the risk factors for onset and prognosis of SZP are still unknown. The aims of this study were to analyze the correlations between neural foraminal stenosis (NFS) and the incidence and prognosis of upper-limb SZP.

Methods: In this retrospective case-control study, 87 HZ inpatients with C5-T1 spinal nerves affected were reviewed and divided into a case group (n = 21) and a control group (n = 66) based on whether they had SZP. Logistic regression analysis was used to assess correlation between NFS and the incidence of upper-limb SZP. Within the case group, Cox regression analyses were used to evaluate the correlation between NFS and complete muscle strength recovery at 24 months.

Results: Univariate and multifactor logistic analysis revealed that the grade of NFS was an independent risk factor for the incidence of upper extremity SZP [mild NFS (aOR = 18, p < 0.05); moderate NFS (aOR = 30, p < 0.05); severe NFS (aOR = 90, p < 0.05)]. Univariate and multifactorial Cox regression analyses confirmed the grade of NFS (HR = 0.186, p < 0.05) and baseline muscle strength (HR = 23.015, p < 0.05) as independent prognostic factors affecting complete muscle strength recovery of upper-limb SZP.

Discussion: The grade of NFS is an independent risk factor for the occurrence and poor prognosis of SZP in patients with upper extremity HZ. The evaluation of NFS should be incorporated into the prognosis assessment and individualized treatment strategy development for patients with upper limb SZP. Prospective cohort studies with larger sample sizes are needed.

Introduction/aims: Nerve ultrasound is becoming increasingly important for diagnosing and monitoring peripheral nerve disorders in children. This research seeks to determine reference values for ultrasound cross-sectional area (CSA) and elastography of peripheral nerves in healthy children from northern China.

Methods: A total of 150 healthy children aged 2-16 years were recruited. To make the results more intuitive and applicable, the CSA data were divided into five age groups and the elastography data into two. The CSA measurements included nerves of the cervical region (C5, C6, vagus), upper limb (median, ulnar, radial), and lower limb (sciatic, tibial, common peroneal, sural). Shear wave velocity (SWV) measurements were performed solely on the median nerve in the right forearm. t Tests and analysis of variance (ANOVA) were used to compare the data.

Results: The average CSA of all nerves increased with age, particularly in the sciatic, tibial, and common peroneal nerves. No sex-based differences were observed in nerve CSA, which increased with weight and height. Among groups categorized by weight and height, significant differences were noted in the larger nerves, with the exception of the vagus and sural nerves. The mean median nerve SWV in this cohort was 3.48 ± 0.62 m/s, with no significant variations attributable to sex, age, height, weight, or CSA.

Discussion: In children, nerve CSA as measured by ultrasound changes with age, height, and weight, while median nerve SWV values remain consistent despite these variations.

Introduction/aims: Previous ultrasound (US)-based assessments of median nerve (MN) displacement within the carpal tunnel have shown inconsistent results due to methodological variability. Quantitative data on how different upper-limb movements affect MN displacement and shear strain at the wrist remain scarce. This study aimed to quantify MN longitudinal displacement and shear strain during finger, wrist, and elbow movements in healthy individuals to establish normative patterns of nerve gliding and deformation.

Methods: Twenty healthy subjects (13 females; mean age: 31.9 years, range: 27-36 years) were prospectively recruited. US videos captured MN motion during middle finger, wrist, and elbow movements. A custom robotic device ensured consistent wrist motion and forearm stability. Speckle-tracking software was used to analyze MN absolute longitudinal displacement, relative displacement to adjacent deep and superficial tissues, and normalized shear strain at both interfaces.

Results: Elbow motion resulted in significantly greater MN absolute displacement (3.8 ± 1.2 mm) and displacement relative to deep tissue (3.6 ± 1.2 mm), compared to finger or wrist motion. No significant differences were observed in MN displacement relative to superficial tissue across motions. Normalized shear strain at the deep interface was lowest during elbow motion (41.8 ± 16.6 mm^-1). Significant differences were found for wrist-to-elbow and finger-to-elbow motions, but not for finger-to-wrist motions.

Discussion: Presented findings highlight the importance of joint-specific contributions to MN motion and suggest that proximal joint movements, such as at the elbow, may promote more effective nerve excursion while minimizing shear strain. This knowledge may help refine nerve current mobilization approaches.

Introduction/aims: Accurate needle electromyography (EMG) of the short head of the biceps femoris (SHBF) is often important to localize nerve damage when proximal to the fibular head. Techniques have been proposed for accurate SHBF EMG; however, needle placement accuracy is low and with the risk of inadvertent needle placement into the long head (LHBF) potentially resulting in false localization and inappropriate operative management. This study aimed to define the optimal window for accurate SHBF needle EMG placement through ultrasound (US) investigation of the anatomical relationships of the SHBF, LHBF, and common fibular nerve (CFN) in the distal posterolateral thigh.

Methods: Forty lower limbs from 20 healthy adults were evaluated using US. Distances from the popliteal crease (PC) to the SHBF and LHBF myotendinous junctions and position of the CFN in the popliteal fossa were recorded. The "SHBF window" was defined as the region where the SHBF muscle body is present in the absence of the LHBF.

Results: The SHBF was located anterolateral to the LHBF tendon/muscle and the CFN medial to the SHBF in all limbs. The average distances from the PC to SHBF and LHBF muscles were 0.6 and 6.4 cm, respectively. The optimal "SHBF window" was identified to be 3-4 cm (2-3 fingerbreadths) proximal to the PC, anterolateral to the LHBF tendon in the distal thigh.

Discussion: SHBF examination within this optimized window results in increased accuracy of needle placement, aiding in the electrodiagnostic localization of fibular nerve lesions.

Introduction/aims: While neurofilament light chain is a promising biomarker in spinal muscular atrophy (SMA), its dynamics in presymptomatic patients have not yet been determined. This study aimed to analyze the plasma neurofilament light chain (pNfL) as a treatment response biomarker in patients with presymptomatic spinal muscular atrophy (SMA) undergoing nusinersen treatment.

Methods: Eight 5q-SMA patients with three SMN2 copies (four presymptomatic patients from newborn screening and four symptomatic patients) were prospectively enrolled from August 2022 to June 2023. All patients received nusinersen treatment and were followed up for 660 days. pNfL levels were measured at baseline and throughout the treatment, analyzing their temporal changes and correlation with motor function outcomes.

Results: At baseline, presymptomatic patients exhibited higher pNfL levels than symptomatic patients (388.74 ng/L vs. 113.60 ng/L). During the loading phase, pNfL levels decreased markedly in both groups, with greater reductions in presymptomatic patients (94.64% vs. 79.50%). All presymptomatic patients achieved age-appropriate motor milestones. Decreased pNfL levels correlated moderately with motor function improvements, as measured by CHOP INTEND (r = -0.548, p < 0.01) and HINE-2 scores (r = -0.635, p < 0.01).

Discussion: pNfL is a promising biomarker for monitoring treatment response in patients with presymptomatic SMA, highlighting the importance of early diagnosis and treatment through newborn screening.

Introduction/aims: An On/Off dosing regimen of intravenous (IV) edaravone and edaravone oral suspension is currently approved in the US for treatment of amyotrophic lateral sclerosis (ALS). Placebo-controlled clinical trials showed that IV edaravone slows physical functional decline. Study MT-1186-A04 continued to examine the efficacy and safety of investigational once daily and approved on/off dosing of edaravone oral suspension in patients with ALS.

Methods: Study MT-1186-A04 (NCT05151471) was a phase 3b, multicenter, randomized, double-blind, parallel group extension study for up to an additional 48 weeks following 48-week Study MT-1186-A02 that randomized patients to investigational once daily or approved 105-mg on/off dosing of edaravone oral suspension. Patients who met Study MT-1186-A04 eligibility criteria, including Study MT-1186-A02 completion, continued in the same treatment regimen as Study MT-1186-A02. The primary efficacy endpoint for MT-1186-A04 was time from randomization in Study MT-1186-A02 to a ≥ 12-point decrease in ALS Functional Rating Scale-Revised (ALSFRS-R) or death, whichever happened first.

Results: Over 96 weeks, including Study MT-1186-A02, daily dosing did not show a statistically significant difference vs. approved on/off dosing for the primary endpoint (p = 0.78). Edaravone oral suspension was well tolerated, and no new safety concerns were identified in either group.

Discussion: Similar to Study MT-1186-A02, once daily edaravone oral suspension in extension Study MT-1186-A04 did not show superiority in terms of the primary efficacy endpoint, but had equivalent efficacy, safety, and tolerability, compared with the approved On/Off regimen. The results reinforce the appropriateness of the approved dosing regimen.

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.