Muscle & Nerve最新文献

The pivotal phase 3 trial MCI186-19 (Study 19) demonstrated the efficacy of intravenous edaravone in slowing functional decline in patients with amyotrophic lateral sclerosis (ALS), leading to United States Food and Drug Administration approval. Study 19 utilized a targeted enrollment enrichment strategy based on post hoc analyses from earlier trials, selecting patients with higher baseline function, more rapid disease progression, and better respiratory status. To evaluate the generalizability of Study 19 results, subsequent post hoc analyses assessed the efficacy of edaravone in broader ALS populations. One machine learning-based analysis retrospectively applied a validated model to Study 16 data, stratifying patients by predicted risk of respiratory decline. This detectable effect cluster analysis suggested that up to 70% of Study 16 participants may have benefited from edaravone. A second analysis investigated edaravone efficacy in patients from Study 19 with forced vital capacity (FVC) < 80% predicted (%p) at the start of treatment, since FVC ≥ 80%p was one of the Study 19 inclusion criteria. Both high- and low-FVC subgroups demonstrated reduced ALS functional rating scale-revised decline at 48 weeks when treated continuously with edaravone. These findings support the potential benefit of edaravone in a wider range of patients with ALS than those enrolled in Study 19, providing important insights into how clinical trial enrichment strategies may influence perceived efficacy, and underscoring the need for future prospective studies in more diverse ALS populations.

Introduction/aims: Local corticosteroid injection (LCI) improves symptoms in the injected hand of carpal tunnel syndrome (CTS). Whether it affects the non-injected hand is unknown. This study assesses the effect of unilateral LCI on the non-injected hand in mild to moderate bilateral CTS.

Methods: Sixty patients with bilateral CTS were recruited from December 2021 to August 2024 and received a unilateral injection of 1 mL (40 mg) depo-methylprednisolone with 0.5 mL (10 mg) lidocaine in the more severely affected or dominant hand if symptoms were comparable. The primary outcome was the change in Symptom Severity Scale (SSS) score of the non-injected hand at 1 and 3 months. Secondary outcomes were the comparison of response rates and the change in the median nerve electrophysiology at 3 months in both hands. A significant response was defined as ≥ 0.8 reduction in SSS.

Results: The median age of patients was 45 (range 20-81) years. Seven patients were lost to follow-up at 1 month and 15 at 3 months. Mean SSS change was significantly greater in the injected than in the non-injected hands at 1 month (-1.25 ± 0.64 vs. -0.89 ± 0.67; p < 0.01) and 3 months (-1.23 ± 0.72 vs. -0.77 ± 0.64; p < 0.01). Taking patients lost to follow-up as treatment failures, response rates at 3 months were 65% in injected hands and 57% in non-injected hands (p = 0.45). Median nerve conduction improved bilaterally at 3 months.

Discussion: Unilateral LCI in bilateral mild to moderate CTS results in significant symptomatic improvement in the contralateral hand, underscoring the need to routinely assess the non-injected hand in treatment assessment.

Introduction/aims: Azathioprine (AZA) and mycophenolate mofetil (MMF) are generally used for long periods when treating myasthenia gravis. In well-controlled patients, discontinuation of AZA/MMF may be a cause for concern because of the possibility of relapse. We aimed to evaluate relapse and relapse-related parameters after discontinuation of AZA/MMF.

Method: Patients who had discontinued AZA or MMF monotherapy were retrospectively reviewed. We reviewed relapse, whether in pharmacological remission (PR) or exhibiting minimal manifestations (MM 1), disease duration, duration of AZA/MMF use, and other clinical parameters.

Results: A total of 32 patients were included who either discontinued AZA (n = 28) or MMF (n = 4) treatments. Relapse was detected in 11 (34%). Patients in PR had fewer relapses than those with MM 1 (p = 0.023). Intravenous immunoglobulin was required in four. All patients who relapsed were stabilized with AZA/MMF. No significant association was found between relapse and age of disease onset, duration of disease, duration of AZA/MMF use, thymectomy status, or maximum Myasthenia Gravis Foundation of America score during active disease.

Discussion: The results of this study suggest that patients in PR are less likely to relapse compared to those in MM 1. In well-controlled MG patients, AZA/MMF may be discontinued.

Introduction/aims: Diagnosis of degenerative cervical myelopathy (DCM) is frequently delayed. A lack of awareness and standardized screening criteria have been identified as major contributors. The objective of this study was to conduct a survey of international experts to determine the value of various signs and symptoms in diagnosing patients with DCM. This study forms part of a three-step initiative that aims to develop pragmatic screening criteria for DCM.

Methods: An open voluntary English-language Likert scale survey was disseminated among international networks of experts in DCM. Respondents were asked to rank each sign or symptom on a scale of 0 (not important at all) to 10 (extremely important); a mean value of ≥ 6.5 was set a priori as the threshold to consider a feature as having significant diagnostic value.

Results: Fifteen symptoms and 12 signs were ranked as having significant diagnostic value. The most highly ranked symptoms are primarily related to abnormalities of the upper limb, hand function, and gait. The top-rated signs included pathological reflexes as well as impairment of motor function, gait, and coordination. Features ranked as significant were largely consistent across professions, levels of experience, and continental regions.

Discussion: The integration of expert stakeholder opinion with evidence from existing literature strengthens the clinical framework for identifying key clinical features of DCM. These 27 features will be discussed at an international consensus meeting to establish a standardized clinical screening toolkit that can be used by frontline healthcare professionals to detect patients with DCM.

Introduction/aims: To study the association of risk factors with axonal degeneration, based on below-threshold sural nerve amplitudes, as a proxy for distal symmetric polyneuropathy (DSP). In particular, to assess the differential contribution of risk factors in diabetes status subgroups.

Methods: In 7242 participants of The Maastricht Study, a population-based cohort (aged 40 to 75 years, southern part of the Netherlands) focusing on type 2 diabetes (T2DM), associations between below-threshold sural nerve amplitudes (< 2.3 μV) and risk factors (diabetes status, demographics, anthropometrics, office systolic blood pressure, lifestyle, medication intake, and lipid profiles) were determined using logistic regression analysis in the total population and after stratification for no diabetes, prediabetes, and T2DM. Analyses were adjusted for age, sex, height, and body mass index (BMI).

Results: Below-threshold sural nerve responses were observed in 741 participants (10.2%). Crude analysis showed increased odds of having below-threshold sural nerve responses for most factors; after adjustments, this association remained significant only for T2DM, female sex, older age, taller height, and a higher BMI. After stratification, individuals who were older, taller and had a higher BMI showed significantly increased odds of having below-threshold sural nerve responses in all subgroups. Notably, the increased odds for height and BMI were stronger in those with T2DM and prediabetes respectively. Higher odds for women were significant in the non-T2DM group only.

Discussion: This study emphasizes the importance of preventive lifestyle measures targeting BMI in those with prediabetes, as other independent risk factors for axonal degeneration are nonmodifiable.

Introduction/aims: Artificial intelligence (AI) has shown potential in analyzing electromyography (EMG) signals, but clinical applicability remains limited by studies based on small, curated datasets, and variable accuracy. This study evaluated AI performance in classifying needle electromyography (EMG) signals as muscle activity versus background/noise/artifact, and then in distinguishing three clinical categories: amyotrophic lateral sclerosis (ALS), myopathy, and non-disease controls.

Methods: Data from the Cleveland Clinic Foundation EMG Database (CCFDB), a large clinically acquired EMG dataset was utilized for this study. A two-step classification approach was used: a convolutional neural network (CNN) to separate muscle activity from background/noise/artifact, followed by a random forest algorithm and CNNs for clinical category classification. Feature extraction techniques included Short-Time Fourier Transform (STFT), Discrete Wavelet Transform (DWT), Continuous Wavelet Transform (CWT), and Wavelet Packet Decomposition (WPD).

Results: EMG data from 608 participants (266 ALS, 89 myopathy, 253 non-disease controls), totaling 11,456 muscle recordings, and 15,613 segments of muscle activity were included. The muscle activity detection model achieved 85.4% accuracy. For clinical category classification, CWT with a two-layer CNN performed best on the CCFDB (62% accuracy). Deeper CNN architectures did not consistently improve performance. On the publicly available curated EMGlab dataset, the best accuracy using the same AI models was higher (91%).

Discussion: AI can assist in EMG analysis, but the performance gap between curated and clinically-acquired datasets underscores the need for robust models capable of handling signal variability and complexity in authentic clinical contexts. Future efforts should focus on clinically-oriented AI development to improve translational applicability.

Introduction/aims: Denervation-induced muscle atrophy lacks effective therapies. Adipose-derived stem cells (ADSCs) show promise for tissue repair. This study aimed to evaluate the effect of local ADSC delivery on denervated muscle, investigate underlying mechanisms, and track ADSC distribution and migration in vivo.

Methods: In a mouse model of sciatic nerve transection and immediate reverse autograft repair, ADSCs or phosphate-buffered saline (PBS) were injected into the right gastrocnemius following nerve injury. Magnetic resonance imaging (MRI) and in vivo imaging system (IVIS) tracked ADSC migration. Muscle strength and gastrocnemius mass were measured. Histology (H&E, Masson), immunostaining (MyoD, CD163), and the real-time reverse transcription polymerase chain reaction (RT-PCR) assessed fiber size, fibrosis, muscle regeneration, M2 macrophage infiltration, and inflammatory gene expression. Endpoints were measured 1 week after the final injection (4 weeks post-injury).

Results: IVIS showed that injected ADSCs were visualized for 3-5 days in vivo while MRI localized cells predominantly to the quadriceps and knee regions. ADSC treatment increased normalized muscle strength (p < 0.05), normalized gastrocnemius muscle weight (p < 0.001) and fiber diameter (p < 0.05); downregulated MMP2 expression (p < 0.001), enhanced MyoD+ cell count (p < 0.001), and promoted M2 macrophage infiltration (CD163+ cells, p < 0.05; ARG1 mRNA, p < 0.05). RT-PCR revealed reduced pro-inflammatory transcripts (IL-6, IL-1b; p < 0.05).

Discussion: ADSCs ameliorate denervation-induced muscle atrophy by improving muscle function and structure via M2 macrophage infiltration, MyoD upregulation, MMP2 inhibition, and reduced inflammation. These findings underscore the therapeutic potential of ADSCs for mitigating muscle atrophy following nerve injury, although the acute injury model used may not fully represent chronic clinical denervation.

The rise in popularity of nerve transfer surgery in individuals with peripheral nerve and spinal cord injuries has elevated the importance of the preoperative electrodiagnostic examination. Needle electromyography (EMG) provides peripheral nerve surgeons with precise information about donor and recipient muscle health, aiding in decisions regarding surgical options, donor muscle viability, and timing of intervention. However, traditional anatomical landmarks for typical donor and recipient nerve-muscle combinations in nerve transfer surgery are either not well described in the literature or become less dependable in the presence of contracture, spasticity, or muscle atrophy and fibrosis. Ultrasound (US) can be a valuable tool to augment the needle EMG examination. Herein, we describe US approaches to improve the precision of the needle EMG examination for 10 muscles in the upper extremity and two muscles in the lower extremity that are routinely involved as either donors or recipients in nerve transfer surgery. The purpose is to provide a reference guide for the electrodiagnostic medicine specialist in the complex nerve injury setting. This includes information on surrounding anatomical structures for localization and those that should be avoided. Relevant US principles for EMG are discussed including: (1) the advantages and disadvantages of short-axis and long-axis views of the target muscle, emphasizing the predominant use of short-axis for adequate visualization of all surrounding structures and enhancing patient safety, (2) in-plane versus out-of-plane approaches, and (3) enhancing confidence in the precision of the needle EMG via the dynamic capability of US.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with marked phenotypic and clinical heterogeneity. Three active pharmaceutical agents are currently approved by the United States Food and Drug Administration (FDA) for ALS: riluzole, edaravone (including intravenous [IV] and oral suspension formulations), and tofersen. Study MCI186-19 (Study 19) was a pivotal, phase 3 randomized controlled trial that demonstrated a significant reduction in physical functional decline vs. placebo in Japanese patients with ALS and contributed to FDA approval of IV edaravone in 2017. Edaravone oral suspension was FDA-approved in May 2022 following the results of Study MT-1186-A01, which showed it was well tolerated with a safety profile consistent with IV edaravone. Following Study 19, the clinical benefit of edaravone has remained an active area of investigation. This supplement presents data from clinical trials, post hoc analyses, and clinical studies that expand understanding of the use of edaravone in broader ALS populations. Topics include safety in clinical practice, generalizability of efficacy, clinical treatment outcomes, and health economics and outcomes research studies. Together, these findings aim to inform clinicians, researchers, and stakeholders regarding the evolving evidence base for edaravone in the management of ALS.

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.